Method for protecting seedlings or plants grown from them against insects, composition for insects control

FIELD: organic chemistry, insecticides, agriculture.

SUBSTANCE: invention describes a method for protection of seedlings or plants grown from them against insects. Method involves contacting seeds with compound of the formula (I)

or its salt taken in the effective amount and acceptable for agriculture wherein A and B represent oxygen atom (O); R1 represents hydrogen atom (H); R2 represents H; R3 represents (C1-C6)-alkyl; R4 represents (C1-C6)-alkyl or -CN; R5 represents H or halogen atom; R6 represents (C1-C6)-halogenalkyl or halogen atom; R7 represents pyridinyl substituted with from one to three substitutes chosen independently from R9; R8 represents H; each R9 represents independently halogen atom; Also, invention describes a composition covering seedling that comprises compound of the formula (I) by cl. 1 or its salt as a biologically active agent and taken in the effective amount, film-forming agent or adhesive agent. Invention provides effective treatment of seedlings for protection against insects being not only seedlings but also plants at later stages of their growth.

EFFECT: valuable properties of composition, improved method of treatment.

16 cl, 39 tbl, 31 ex

 

The scope to which the invention relates

This invention relates to controlling invertebrates herbivorous pests such as arthropods pests by contacting planting material (seedlings) plants or parts of planting material (seedlings) with defined anthranilamide, and containing anthranilamide compositions that are applied to the crop.

Background of invention

To achieve high yields extremely important controlling invertebrate pests such as arthropods. Damage to invertebrate pests of growing and stored crops can cause significant reduction in productivity and, consequently, result in increased cost to the consumer. Also important controlling invertebrate pests in forestry, greenhouse crops, ornamental plants and plants in nurseries.

Plants damaged invertebrate pests at all stages of growth, starting with seeds or other seedlings, such as bulbs, tubers, rhizomes, globalwave, stem and leaf cuttings, and ending with Mature plants. In addition to the cost of materials, effort and time required for application of substances to control the demon is osvoenie pests, make unwanted re-processing. Ideally, a single processing plants at seedling stage would protect the plant from invertebrate pests throughout his life.

Known various methods for processing seed substances for plant protection. They include soaking seedlings arthropodicides-containing solutions, covering their films, the drageeing material and the like, containing arthropodicides composition and application arthropodicides substances for the growth environment of the seedlings. While some substances can effectively protect the seedlings from certain phytophagous invertebrate pests, new substances that are more effective or have a wider spectrum of activity, less costly, less toxic, safer for the environment or with different mechanisms of action.

A special need exists in the regulatory treatment of invertebrate pests, which can protect the plant not only at the stage of seedling and later in its development. To achieve this goal requires compounds that are active against invertebrate pests and can effectively move from the locus of the seedling up to the growing stems, leaves and other parts of the plant who I am. In addition, these compounds should have high activity against invertebrate pests to compensate for the dilution caused by the increasing weight of the plants. Also, these compounds should not rapidly deteriorate and lose its biological effect in the environment surrounding the vascular tissue of plants. The combination of such properties are rare. Here explains how to handle seedlings, effective for protection against phytophagous invertebrate pests not only germs, but also plants at later stages of growth.

Summary of the invention

The invention includes compounds of Formula I, theirNoxides and their salts suitable for use in agriculture.

where A and B are independently O or S;

R1represents H, C1-C6alkyl, C2-C6alkoxycarbonyl or2-C6alkylsulphonyl;

R2represents H or C1-C6alkyl;

R3represents H; C1-C6alkyl, C2-C6alkenyl,2-C6quinil or3-C6cycloalkyl, each optionally substituted by one or more substituents selected from the group consisting of: halogen, CN, NO2, hydroxy, C1-C4of alkyl, C1-C 4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C2-C6alkoxycarbonyl, C2-C6alkylcarboxylic,3-C6trialkylsilyl, phenyl, phenoxy, 5-membered heteroaromatic rings, and 6-membered heteroaromatic ring; each phenyl, phenoxy, 5-membered heteroaromatic ring, and a 6-membered heteroaromatic ring optionally substituted with one to three substituents, independently selected from the group consisting of C1-C4of alkyl, C2-C4alkenyl,2-C4the quinil,3-C6cycloalkyl, C1-C4halogenoalkane,2-C4halogenoalkane,2-C4halogenoalkane,3-C6halogennitroalkane, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4alkylamino, C2-C8dialkylamino, C3-C6cyclooctylamino, C4-C8(alkyl)(cycloalkyl)amino, C2-C4alkylcarboxylic,2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, C3-C8dialkylaminoalkyl and C3-C6Tria is Kinsella; C1-C4alkoxy, C1-C4alkylamino; C2-C8dialkylamino; C3-C6cyclooctylamino; C2-C6alkoxycarbonyl or2-C6alkylcarboxylic;

R4represents H, C1-C6alkyl, C2-C6alkenyl, C2-C6quinil, C3-C6cycloalkyl, C1-C6halogenated, CN, halogen, C1-C4alkoxy, C1-C4halogenoalkane or NO2;

R5represents H, C1-C6alkyl, C1-C6halogenated, C1-C4alkoxyalkyl, C1-C4hydroxyalkyl, C(O)R10, CO2R10C(O)NR10R11, halogen, C1-C4alkoxy, C1-C4halogenoalkane, NR10R11N(R11)C(O)R10N(R11)CO2R10or S(O)nR12;

R6represents H, C1-C6alkyl, C1-C6halogenated, halogen, CN, C1-C4alkoxy or C1-C4halogenoalkane;

R7represents a C1-C6alkyl, C2-C6alkenyl, C2-C6quinil, C3-C6cycloalkyl, C1-C6halogenated, C2-C6halogenoalkanes, C2-C6halogenoalkanes or C3-C6halogenosilanes; or R7represents a phenyl to which ICO, benzyl ring, a 5 - or 6-membered heteroaromatic ring, naftalina ring system or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring or ring system substituted by one to three substituents, independently selected from R9;

R8represents H, C1-C6alkyl, C1-C6halogenated, halogen, C1-C4alkoxy or C1-C4halogenoalkane;

each R9represents independently C1-C4alkyl, C2-C4alkenyl,2-C4quinil,3-C6cycloalkyl, C1-C4halogenated,2-C4halogenoalkanes,2-C4halogenoalkanes,3-C6halogenosilanes, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4alkylamino, C2-C8dialkylamino, C3-C6cyclooctylamino, C4-C8(alkyl)(cycloalkyl)amino, C2-C4alkylsulphonyl, C2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, C3-C8dialkylaminoalkyl or3-C6trialkylsilyl;

R10represents H, C1-C4lkyl or C 1-C4halogenated;

R11represents H or C1-C4alkyl;

R12represents a C1-C4alkyl or C1-C4halogenated; and

n is 0, 1 or 2.

This invention provides a method of protecting seedling or grown from plants from invertebrate pests. This method includes contacting seedling or locus seedling with a biologically effective amount of the compounds of Formula I, its N-oxide or its salts, suitable for use in agriculture.

This invention also offers the seedling containing biologically effective amount of compound I, its N-oxide or its salts, suitable for use in agriculture.

This invention also provides a seedling that came into contact with a biologically effective amount of compound I, its N-oxide or its salts, suitable for use in agriculture.

This invention further provides a composition for controlling invertebrate pests to cover the seedling containing biologically effective amount of the compounds of Formula I, its N-oxide or its salts, suitable for use in agriculture and the film former or adhesive agent.

Detailed description of the invention

Specified in this izobreteny and in the claims, the term "seed" or "seedling" means a seed, or plant part, able to regenerate. The term "plant part, capable of regeneration" means the part of plants, other than seeds, from which may grow a whole plant, or to regenerate, when this part of the plant is placed in a horticultural or agricultural growth medium such as moist soil, peat moss, sand, vermiculite, perlite, mineral wool, glass fibre, coconut shell fiber, tree fern and the like, or even a liquid, such as water. Parts of the plant, able to regenerate, usually include rhizomes, tubers, bulbs and globalwave such geophytic species of plants, such as potatoes, sweet potatoes, yams, onions, Dahlia, Tulip, Narcissus, etc. are Able to regenerate parts of the plant include parts of plants that share (e.g., cut) to preserve their ability to grow into a new plant. Thus, parts of the plant, able to regenerate include a viable part of rhizomes, tubers, bulbs and corms, which remain meristematic tissues, such as eyes. Able to regenerate parts of the plant can also include other parts of plants, such as cut or split stems and leaves, which can be grown some plants with horticultural use or rural the economic growth environment. Specified in the present description and the claims, unless otherwise specified, the term "seeds" includes both naproxene seeds and germinated seeds that seed peel (coated seed) still surrounds part protestuyuschego sprout and root.

In the above enumeration, the term "alkyl", used either alone, or in words, such as "alkylthio" or "halogenated"includes alkyl straight chain or branched alkyl, such as methyl, ethyl, n-propyl, ISO-propyl, or the different butyl isomers, pentile or exile. "Alkenyl includes alkenes with a straight chain or branched alkenes such as 1-propenyl, 2-propenyl, various isomers butenyl, pentenyl and hexenyl. "Alkenyl" also includes a polyene, such as 1,2-PROPADIENE and 2,4-hexadienyl. "Quinil" includes alkinyl straight chain or branched alkinyl, such as 1-PROPYNYL, 2-PROPYNYL and the different isomers of butenyl, pentenyl and hexenyl. "Quinil" may also include components containing a repeating triple bond, such as 2,5-hexadienyl. "Alkoxy" includes for example methoxy, ethoxy, n-propyloxy, isopropoxy and various butoxy, pentox, hexyloxy isomers. "Alkoxyalkyl" means alkoxy substitution on the alkyl. Examples of "alkoxyalkyl" include CH3OCH2C 3OCH2CH2,CH3CH2OCH2,CH3CH2CH2CH2OCH2and CH3CH2OCH2CH2."Alkylthio" includes part of alkylthio branched, or straight chain, such as methylthio, ethylthio, and various propylthio, butylthio, pentylthio and hexylthio isomers. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

The term "heterocyclic ring" or "heterocyclic ring system" denotes a ring or rings, in which at least one atom of the ring is carbon and containing from 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that each heterocyclic ring contains no more than 4 Izotov, no more than 2 oxygens and no more than 2 sulfur atoms. The heterocyclic ring can be attached through any available carbon or nitrogen by replacement of a hydrogen on the specified carbon or nitrogen. The term "aromatic ring system" denotes fully unsaturated carbocycles and heterocycles in which at least one ring of a polycyclic ring system is aromatic (where aromaticity indicates that satisfies hückel rule for ring system). The term "heteroaromatic ring" means a fully ar is automatic ring in which at least one atom of the ring is carbon and containing from 1 to 4 heteroatoms, independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that each heterocyclic ring contains no more than 4 Izotov, no more than 2 oxygens and no more than 2 sulfur atoms (where the aromaticity indicates that you hückel rule). The heterocyclic ring can be attached through any available carbon or nitrogen by replacement of a hydrogen on the specified carbon or nitrogen. The term "aromatic heterocyclic ring system" includes fully aromatic heterocycles and heterocycles in which at least one ring of a polycyclic ring system is aromatic (where the term "aromatic" indicates that the hückel rule). The term "condensed heterobicyclic ring system" includes a ring system consisting of two condensed rings, in which at least one atom of the ring is carbon and can be aromatic or non-aromatic, as defined above.

The term "halogen", either alone or in words, such as "halogenated"includes fluorine, chlorine, bromine or iodine. Further, when used in the composition of words, such as "halogenated"specified alkyl may be partially or p. the color substituted by halogen atoms, which may be the same or different. Examples of "halogenoalkane" include F3C, ClCH2,CF3CH2and CF3CCl2. The terms "halogenoalkanes", "halogenoalkanes", "halogenoalkane" and the like are defined analogously to the term "halogenated". Examples of "halogenoalkane" include (Cl)2C=CHCH2and CF3CH2CH=CHCH2. Examples of "halogenoalkane" include HC≡CCHCl, CF3C≡C, CCl3C≡C and FCH2With≡CCH2. Examples of "halogenoalkane" include CF3Oh, CCl3CH2O, HCF2CH2CH2O and CF3CH2O.

The total number of carbon atoms in the replacement group is indicated by the prefix "Ci-Cj"where i and j are numbers from 1 to 8. For example, C1-C4alkylsulfonyl means methylsulphonyl on butylsulfonyl; C2alkoxyalkyl means CH3Och2;3alkoxyalkyl means, for example, CH3CH(OCH3), CH3OCH2CH2or CH3CH2OCH2; and (C4alkoxyalkyl refers to the various isomers of an alkyl group, a substituted alkoxy group containing all four carbon atoms, examples include CH3CH2CH2OCH2and CH3CH2OCH2CH2. In described above, when the compound of Formula I contains geterotsiklicheskikh number of the TSO, all deputies are associated with this ring through any available carbon atom or nitrogen by replacement of a hydrogen on the designated atom is carbon or nitrogen.

In the case when the group has a Deputy, who may be hydrogen, for example, R3then, in the case when this Deputy is considered as hydrogen, it is recognized equivalent to the specified unsubstituted group.

The compounds of Formula I are as one or more stereoisomers. Different stereoisomers include enantiomers, diastereoisomers, atropisomers and geometric isomers. The person skilled in the art will understand that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomers (stereoisomer) or when separated from the other stereoisomer (stereoisomer). In addition, the person skilled in the art knows how to separate, enrich, and/or to selectively prepare these stereoisomers. Accordingly, the compounds of this invention can be represented as a mixture of stereoisomers, individual stereoisomers or in the form of optically active forms.

Salts of compounds of Formula I include acid additive salt (salt accession of the acids with inorganic or organic acids such as Hydrobromic, chlorestol the portly, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluensulfonate or valeric acid.

Ways seedlings and compositions of this invention preferred for reasons of cost, simple chemical synthesis or application and/or biological effectiveness include the following preferred compounds:

Preference 1. The compound of formula I where A and B both represent O;

R7is a phenyl ring or a 5 - or 6-membered heteroaromatic ring selected from the group consisting of

each ring optionally substituted with one to three substituents, independently selected from R9;

Q represents O, S, NH or NR9; and

W, X, Y and Z independently represent N, CH or CR9provided that in J-3 and J-4 at least one of W, X, Y or Z represents N.

Preference 2. Connection Preferences 1, where

R1, R2and R8all represent H;

R3represents a C1-C4alkyl optionally substituted with halogen, CN, OCH3or S(O)pCH3;

the group R4attached in position 2;

R4represents CH3, CF3, OCF3, OCHF2CN or halogen;

R5represents H, CH3or halogen;

R6represents CH3, CF3or halogen;

R7represents phenyl or 2-pyridinyl, each optionally substituted; and

p is 0, 1 or 2.

Preference 3. Connection Preferences 2, where R3represents a C1-C4alkyl, and R6is a CF3.

Preference 4. Connection Preferences 2, where R3represents a C1-C4alkyl, and R6represents Cl or Br.

As noted above, R7represents (among other things) phenyl, benzyl, 5 - or 6-membered heteroaromatic ring, naftalina ring system or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring or ring system optionally substituted with one to three substituents, independently selected from R9. The term "optionally substituted" in connection with these R7groups refers to groups that are unsubstituted or have at least one non-hydrogen Deputy, which does not extinguish the regulatory activity against invertebrate pests possessed by the unsubstituted analog. It should be noted that with the J-1 through J-4 below mean 5 - or 6-membered heteroaromatic ring. An example of a phenyl ring, optionally samemanner is from 1 to 3. R9is the ring illustrated as J-5 in View 1, where r is an integer from 0 to 3. An example of a benzyl ring, optionally substituted from 1 to 3. R9is the ring illustrated as the J-6 in View 1, where r is an integer from 0 to 3. Example naftilos ring system optionally substituted from 1 to 3. R9shown in the form of J-59 in View 1, where r is an integer from 0 to 3. Examples of 5 - or 6-membered heteroaromatic ring optionally substituted from 1 to 3. R9include rings with J-7 and J-58 shown in View 1, where r is an integer from 0 to 3. It should be noted that with the J-7 to J-26 are examples of J-1, J-27 J-41 are examples of J-2 and J-46 J-58 are examples of J-3 and J-4. The nitrogen atoms that require substitution to fill their valence, replaced with H, or R9. It should be noted that some of the J groups can be substituted only less than 3. R9groups (for example, J-19, J-20, J-23 J-26 J-37 J-40 can be replaced by only one R9). Examples of aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring systems, optionally substituted from 1 to 3. R9include J-60 J-90, shown in View 1, where r is an integer from 0 to 3. Although R9groups is shown in the structures of the J-5 J-90, it is noted that their presence is not necessary, since they are optional substituents. It should be noted that in the case when the place of connection between (R9)rand J group is shown floating, (R9)rcan be attached to any available carbon atom J of the group. It should be noted that in the case when the place of connection to the J group is shown floating, this J group can be attached to the remainder of the compounds of Formula I via any available carbon atom J group by replacement of a hydrogen atom.

View 1

To obtain the compounds of Formula I can be used one or more of the following methods and variations as described in Schemes 1-22. Definitions for A, B, and R1for R9in the compounds of Formula 2-40 below given earlier in the section "Summary of the invention", unless otherwise specified. Compounds of Formulas Ia-d, 2a-d, 3a, 4a-d, 5a-b, 17a-c, 18a and 32a-b represent different subgroups of compounds of Formula I, 2, 3, 4, 5, 17, 18 and 32. In these schemes, Het represents a portion of the molecule, which is azan below:

A typical way to obtain the compounds of Formula Ia described in Scheme 1.

Scheme 1

The method of Scheme 1 involves the interaction of the amine of Formula 2 with an acid chloride of the acid of Formula 3 in the presence of an acid acceptor to obtain the compounds of Formula Ia. Typical acid acceptors include amine bases such as triethylamine,N,N-diisopropylethylamine and pyridine; other acceptors include hydroxides such as sodium hydroxide and potassium carbonates, such as sodium carbonate and potassium carbonate. In some cases it is useful to use acceptors acid on the polymer carrier, such as polymer-bound N,N-diisopropylethylamine and polymer-bound 4-(dimethylamino)pyridine. The interaction may be carried out in a suitable inert solvent such as tetrahydrofuran, dioxane, diethyl ether or dichloromethane getting anilide Formula Ia.

Tioned Formula Ib can be obtained at a later stage from the corresponding amide of the Formula Ia by treatment of one of the various standard reagents, carrying tigroup that includes the phosphor pentasulfide and reagent Lawesson (Lawesson's) (2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphate-2,4-disulfide).

As shown in Scheme 2, an alternative method of obtaining from the dynany Formula Ia includes the interaction of the amine of Formula 2 with an acid of Formula 4 in the presence of a dehydrating agent, such as dicyclohexylcarbodiimide (DCC), 1,1'-carbonyl-diimidazole, bis(2-oxo-3-oxazolidinyl)phosphinic chloride or benzotriazol-1-yloxytris-(dimethylamino)phosphonium hexaflurophosphate.

Scheme 2

There is also a useful reagent to the polymer carrier, such as polymer-bound cyclohexylcarbodiimide. This interaction can be carried out in a suitable inert solvent such as dichloromethane or N,N-dimethylformamide. Methods of synthesis schemes 1 and 2 are only representative examples of a wide variety of communication methods used to obtain compounds of the Formula I; in the literature on the synthesis of many reactions of this type of interaction.

The person skilled in the art will also be understood that the anhydrides of the acids of Formula 3 can be obtained from the acids of Formula 4 with the help of numerous well-known methods. For example, the anhydrides of the acids of Formula 3 is easily derived from carboxylic acids of Formula 4 by reacting carboxylic acid 4 with thionyl chloride or oxalylamino in an inert solvent, such as toluene or dichloromethane in the presence of catalytic amounts of N,N-dimethylformamide.

As shown in Scheme 3, amines of Formula 2a can usually be obtained from the corresponding 2-nitrobenzamide Formulas 5 through catalytics the second hydrogenation of the nitro group.

Scheme 3

Typical techniques include the reduction with hydrogen in the presence of a metal catalyst such as palladium on coal or platinum oxide and hydroxyl solvents, such as ethanol and isopropanol. Amines of Formula 2a can also be obtained by reduction with zinc in acetic acid. These techniques are well described in the chemical literature. R1substituents, such as C1-C6the alkyl can be introduced at this stage by using well-known techniques, including either direct alkylation or by usually the preferred method of rehabilitation amine alkylation. As shown in figure 3, the most commonly used technique is a combination of amine 2A with an aldehyde in the presence of a reducing agent, such as cyanoborohydride sodium obtaining compounds of Formula 2b, where R1represents a C1-C6alkyl.

Figure 4 shows that the compounds of Formula Ic can be alkylated or etilirovany suitable alkylating or allermuir agent such as alkyl halide, alkylchloride or acylchlorides in the presence of a base such as sodium hydride or n-utility in an inert solvent, such as tetrahydrofuran or N,N-dimethylformamide to obtain anilides is ormula Id, where R1other than hydrogen.

Scheme 4

Intermediate amides of Formula 5a are easily prepared from commercially available 2-nitrobenzoic acids. Can be used typical methods of formation of the amide. As shown in figure 5, these methods include direct dehydrative the interaction of the acids of Formula 6 with amines of Formula 7 using, for example, DCC, and the conversion of acids in activated form, such as the anhydrides of the acids or anhydrides and subsequent interaction with amines to form amides of Formula 5a.

Scheme 5

The alkyl chloroformate, such as ethylchloride or isopropylcarbamate are especially used reagents for this type reactions, including activation of this acid. In the chemical literature, there are many ways of forming amides. Amides of Formula 5a can easily turn into thioamides of Formula 5b using commercially available reagents for transfer tigroup, such as phosphoric pentasulfide and reagent Lawesson.

Intermediate anthranilate amides of Formula 2c or 2d can also be derived from anhydrides Stanovoy acid of Formula 8 or 9, respectively, as shown in figure 6.

Scheme 6

Typical methods include the connection of equimolar amounts of amine 7 with anhydride Stanovoy acid in polar aprotic solvents such as pyridine and N,N-dimethylformamide at a temperature in the range from room temperature to 100°C. R1the substituents, such as alkyl and substituted alkyl, can be introduced by alkylation catalyzed by base, anhydride Stanovoy acid 8 known alkylating agents R1-Lg (where Lg represents a nucleophilic substitutable leaving group such as halide, alkyl or arylsulfonate or alkyl sulphates) to give the alkyl substituted intermediate compound 9. Anhydrides Stanovoy acid of Formula 8 may be obtained by methods described in Coppola,Synthesis1980, 505-36.

As shown in Scheme 7, an alternative method of obtaining the characteristic compounds of Formula Ic include the interaction of amine 7 with benzoxazinones Formula 10.

Scheme 7

Reaction Scheme 7 can be carried out neat or in a variety of suitable solvents including tetrahydrofuran, diethyl ether, pyridine, dichloromethane or chloroform with optimum temperatures in the range from room temperature to the boiling temperature under reflux of this solvent. The overall reaction of benzoxazine the s with amines to form anthranilamide well described in the chemical literature. To view chemistry benzoxazinones see Jakobsen et al.,Biorganic and Medicinal Chemistry2000,8,2095-2103 and references cited therein. Cm. also, Coppola, J.Heterocyclic Chemistry1999,36,563-588.

Benzoxazinone Formula 10 can be obtained by using different methods. Two methods are primarily used, as detailed in the Diagrams 8-9. In Scheme 8, benzoxazine Formula 10 get directly through interaction pyrazolylborate acid of Formula 4a with Anthranilic acid of Formula 11.

Scheme 8

This involves the sequential addition of methanesulfonanilide in the presence of a tertiary amine such as triethylamine or pyridine to pyrazolylborate acid of Formula 4a, followed by the addition of Anthranilic acid of Formula 11, followed by re-addition of tertiary amine and methanesulfonanilide. This method generally produces good output benzoxazinone and shown in more detail in Examples 6 and 8.

Scheme 9 describes an alternative getting benzoxazinones Formula 10, which includes interaction pyrazol the carboxylic acid of Formula 3a with the anhydride Stanovoy acid of Formula 8 with direct obtaining benzoxazinone Formula 10.

Scheme 9

For this reaction, suitable solvents, such as pyridine or the feast of the Dean/acetonitrile. The anhydrides of the acids of Formula 3a can be obtained from the corresponding acids of Formula 4a different synthesis methods, such as chlorination with thionyl chloride or oxalylamino.

Anhydrides Stanovoy acid of Formula 8 may be obtained from satinov Formula 13, as depicted in Scheme 10.

Scheme 10

Satiny Formula 13 is obtained from aniline derivatives of Formula 12 using methods known from the literature. Oxidation of isatin 13 hydrogen peroxide will usually produce good outputs corresponding anhydride Stanovoy acid 8(Angew. Chem. Int. Ed. Engl.1980, 19, 222-223). Anhydrides Stanovoy acid can also be obtained from Anthranilic acids 11 using various known techniques, including the interaction of the compound (11) with phosgene or an equivalent of phosgene.

The synthesis of typical acids of Formula 4 are depicted on figures 11-16. Syntheses of pyrazoles of Formula 4a is shown in Scheme 11.

Scheme 11

The synthesis of compounds of Formula 4a figure 11 as a main stage involves the introduction of substituent R7by alkylation or arilirovaniya of pyrazole of Formula 14 with compounds of Formula 15 (where Lg is a leaving group, as defined above). Oxidation of the methyl group gives pyrazol carboxylic acid. Some of the more p is impactfully R 6groups include halogenated.

Synthesis of pyrazoles of Formula 4a is also shown in figure 12.

Scheme 12

These acids can be obtained by metallation and carboxylation of compounds of Formula 18, as the main stage. R7the group is administered the same way as shown in Scheme 11, i.e. through alkylation or atilirovanie compound of Formula 15. Typical R6groups include, for example, cyano, halogenated and halogen.

This technique in particular is used to produce 1-(2-pyridinyl)pyrazolylborate acids of Formula 4b, as shown in figure 13.

Scheme 13

The interaction of the pyrazole of Formula 17 with 2,3-deglomeration Formula 15a gives a good outputs 1-pildiportaal Formula 18a with good properties for the required regioniii. Metallation of compounds 18a-diisopropylamide lithium (LDA) followed by quenching lithium salt with carbon dioxide gives 1-(2-pyridinyl)pyrazolylborate acid of Formula 4b. Additional details of these methods is presented in Examples 1, 3, 6, 8 and 10.

Synthesis of pyrazoles of Formula 4c described in Scheme 14.

Scheme 14

The circuit 14 includes interaction optionally substituted phenylhydrazine of Formula 19 with getoperator Formula 20 with a yield of esters of pyrazole Forms the crystals 21. The hydrolysis of these esters gives pyrazol acid of Formula 4c. This technique is particularly used for producing compounds in which R7represents optionally substituted phenyl, and R6is halogenated.

Alternative synthesis of pyrazol acids of Formula 4c is shown in figure 15.

Scheme 15

The method according to the Circuit 15 includes a 3+2 cycloaddition respectively substituted imidocloprid 22 or substituted propiolate Formula 23 or acrylates of Formula 25. Cycloaddition to the acrylate require additional oxidation of the intermediate pyrazoline in the pyrazole. The hydrolysis of these esters gives pyrazol acid of Formula 4c. Preferred aminoglucoside for this reaction include the trifluoromethyl imidocloprid Formulas 26 and kinodynamic Formula 27. Compounds such as 26, is known for(J. Heterocycl. Chem.1985, 22(2), 565-8). Compounds such as 27, may be obtained by known methods(Tetrahedron Letters1999,40,2605). These techniques are specifically used to produce the compounds where R7represents optionally substituted phenyl, and R6is halogenated or bromine.

Source pyrazoles of Formula 17 are known compounds or can be obtained by known methods. The pyrazole of Formula 17a (Conn the General Formula 17, where R6is a CF3and R8represents H) can be obtained according to the methods of the literature(J. Fluorine Chem.1991,53(1),61-70). The pyrazoles of Formula 17c (compounds of Formula 17, where R6represents Cl or Br, and R8represents H) can also be obtained by methods known from the literature(Chem. Ber.1966, 99(10), 3350-7). A useful alternative method for obtaining compounds 17c presented in figure 16.

Scheme 16

In the method according to Scheme 16 metallation of sulphamerazine Formula 28 n-butyllithium with subsequent direct halogenoalkanes anion or hexachlorethane (R6which Cl), or 1,2-dibromotetrachloroethane (R6which Br), gives a halogenated derivative of Formula 29. Remove allfamilies group triperoxonane acid (TFA) at room temperature proceeds cleanly and in good yield with getting pyrazoles of Formula 17c. The person skilled in the art will understand that the Formula 17c is tautomer Formula 17b. Additional details of the experiments on these methods described in Examples 8 and 10.

Pyrazolylborate acid of Formula 4d, where R6represents H, C1-C6alkyl or C1-C6halogenated can be obtained using the method presented in figure 17.

<> Scheme 17

The interaction of the compounds of Formula 30, where R13represents a C1-C4alkyl, with a suitable base in a suitable organic solvent gives cyklinowanie product Formula 31 after neutralization of the acid, such as acetic acid. A suitable base may be for example, but without limitation, sodium hydride, t-piperonyl potassium, damsel sodium (CH3S(O)CH2-Na+), carbonates of alkali metal (such as lithium, sodium or potassium), or hydroxides, tetraalkyl (such as methyl, ethyl or butyl)ammonium fluoride or hydroxide, or 2-tert-Butylimino-2-diethylamino-1,3-dimethylpyridine-1,3,2-datafactory. Suitable organic solvent may be, for example, but without limitation, acetone, acetonitrile, tetrahydrofuran, dichloromethane, dimethyl sulfoxide or N,N-dimethylformamide. This cyclization reaction is usually conducted at a temperature in the range from approximately 0 to 120°C. the Effect of solvent, base, temperature and time add depend on each other and the choice of reaction conditions is important for minimizing the formation of by-products. The preferred base is tetrabutylammonium fluoride.

The dehydration of compounds of Formula 31 with obtaining the compounds of Formula 32 with the subsequent conversion of the ester is arbonboy acid in the carboxylic acid gives compound of Formula 4d. Dehydration is carried out by treatment with a catalytic amount of a suitable acid. Such catalytic acid may be, for example, but without limitation, sulfuric acid. This reaction is carried out mainly by using organic solvent. The person skilled in the art will understand that the dehydration reaction can be conducted in a wide range of solvents in the temperature range mostly from approximately 0 to 200°C, more preferably from about 0 to 100°C. For dehydration by way of Scheme 17, it is preferable that the solvent contained acetic acid and the temperature was about 65°C. Compounds of ether carboxylic acids can be converted into compounds of carboxylic acids in a variety of ways, including nucleophilic cleavage in anhydrous conditions or hydrolytic methods, including the use of either acids or bases (to view options, see T. W. Greene and P. G. M. Wuts,Protective Groups in Organic Synthesis,2nd ed., John Wiley & Sons, Inc., New York, 1991, pp. 224-269). For the method of Scheme 17 preferred hydrolytic methods, catalyzed by base. Suitable bases include alkali metal hydroxides (such as lithium, sodium or potassium). For example, the ester can be dissolved in a mixture of water and alcohol, such as ethanol. When handling sodium hydroxide sludge is potassium hydroxide, this aired its shades with the formation of sodium or potassium salt of carboxylic acid. Acidification with a strong acid, such as hydrochloric acid or sulfuric acid, yields the carboxylic acid of Formula 4d. This carboxylic acid can be isolated by methods known to experts in this field, including crystallization, extraction and distillation.

The compounds of Formula 30 can be obtained using the method presented in figure 18.

Scheme 18

where R6represents H, C1-C6alkyl or C1-C6halogenated, and R13represents a C1-C4alkyl

Processing hydrazine powered the compounds of Formula 33 ketone of Formula 34 in a solvent such as water, methanol or acetic acid, gives the hydrazone of Formula 35. The person skilled in the art it will be clear that for this reaction can be catalyzed by an arbitrary acid and may require elevated temperature-dependent molecular substitution patterns of the hydrazone of Formula 35. The interaction of the hydrazone of Formula 35 with a compound of Formula 36 in a suitable organic solvent, such as, for example, but without limitation, dichloromethane or tetrahydrofuran in the presence of an acid acceptor, such as triethylamine, gives the compound of Formula 30. This reaction usually is carried out at a temperature from about 0 to 100° C. Further details of the experiment for the method according to the Circuit 18 shown in Example 17. Hydrazine powered the compounds of Formula 33 can be obtained by standard methods, as, for example, the contacting of the corresponding halogen compounds of Formula 15a with hydrazine.

Pyrazolylborate acid of Formula 4d, where R6is a halogen, can be obtained using the method presented in Scheme 19.

Scheme 19

where R13represents a C1-C4alkyl.

Oxidation of compounds of Formula 37 is optional in the presence of acid gives compound of Formula 32, with subsequent transformation group of the ether carboxylic acid to carboxylic acid to obtain the compounds of Formula 4d. The oxidizing agent may be hydrogen peroxide, organic peroxides, potassium persulfate, sodium persulfate, ammonium persulfate, monopersulfate potassium (e.g., Oxone®) or potassium permanganate. For complete conversion you should use at least one equivalent of oxidizing agent in respect of compounds of Formula 37 is preferably from about one to two equivalents. This oxidation is usually carried out in the presence of a solvent. This solvent may be a simple ether, such as tetrahydrofuran, p-dioxane and the like, organic complex is th ether, such as ethyl acetate, dimethylcarbonate and the like, or a polar aprotic organic solvent, such as N,N-dimethylformamide, acetonitrile and the like. Acids suitable for use at this stage of the oxidation, include inorganic acids such as sulfuric acid, phosphoric acid and the like and organic acids such as acetic acid, benzoic acid and the like. When using acids should be used more than 0.1 equivalents relative to the compound of Formula 37. For a complete transformation can be used from one to five equivalents of acid. The preferred oxidizing agent is potassium persulfate and this oxidation is preferably performed in the presence of sulfuric acid. This reaction may be carried out by mixing the compounds of Formula 37 in a predetermined solvent, and acid, if used. Can then be added to the oxidizing agent in a suitable ratio. The reaction temperature usually ranges already from approximately 0°C to the boiling point of the solvent, to obtain an acceptable response time for completing the reaction, preferably, less than 8 hours. The desired product, compound of Formula 32 can be separated by methods known to experts in this field, including crystallization, extraction and distillation. The ways in which walking for the conversion of ester of Formula 32 to carboxylic acid of Formula 4d, already described for Scheme 17. Additional details of the experiment for the method according to figure 19 presents in Examples 12 and 13.

The compounds of Formula 37 can be obtained from corresponding compounds of Formula 38, as shown in figure 20.

Scheme 20

Treatment of compounds of Formula 38 halogenation reagent is typically in the presence of the solvent gives the corresponding halogen compound of the Formula 37. Halogenation reagents that can be used include oxychloride phosphorus, trihalogen phosphorus, pentachloride phosphorus, thionyl chloride, diplocaulobium, digestivesystem, oxalicacid and phosgene. Preferred are oxychloride and pentavalent phosphorus. For complete conversion you should use at least 0.33 equivalents of oxychloride phosphorus in relation to the compound of Formula 38 (i.e. the molar ratio of oxychloride phosphorus to the compound of Formula 18 is at least 0,33), preferably from about 0.33 to 1.2 equivalents. For complete conversion you should use at least 0.20 equivalents of pentavalent phosphorus in relation to the compound of Formula 38, preferably from about 0.20 to 1.0 equivalents. For this reaction, the preferred are the compounds of Formula 38, the de R 13represents a C1-C4alkyl. Typical solvents for the halogenation include halogenated alkanes such as dichloromethane, chloroform, chlorobutane and the like, aromatic solvents such as benzene, xylan, chlorobenzene and the like, ethers such as tetrahydrofuran, p-dioxane, diethyl ether and the like, and polar aprotic solvents such as acetonitrile, N,N-dimethylformamide and the like. Optional can be added an organic base, such as triethylamine, pyridine, N,N-dimethylaniline or the like. The addition of a catalyst, such as N,N-dimethylformamide, optionally. Preferred is a process in which the solvent is acetonitrile, and the base is missing. Usually when you use a solvent of acetonitrile is no need for a base or a catalyst. The preferred process is carried out by mixing the compounds of Formula 38 in acetonitrile. Then after a suitable time add halogenation reagent, and the mixture is then kept at a desired temperature until completion of the reaction. The reaction temperature is usually from 20°C and up to the boiling point of acetonitrile, and the reaction time is usually less than 2 hours. The reaction mass is then neutralized with inorganic base, such as sodium bicarbonate, hydroxide Natrii such, or organic base, such as sodium acetate. The desired product, compound of Formula 37 can be isolated by methods known to experts in this field, including crystallization, extraction and distillation.

Alternatively, the compounds of Formula 37 wherein R6is a halogen, can be obtained by treating the corresponding compounds of Formula 37 wherein R6is another halogen (such as Cl to obtain the compounds of Formula 37 wherein R3represents Br or sulphonate group such as p-toluensulfonate, mesasurement and methanesulfonate, appropriate hydrogen halide. Through this method, R6halogen or sulphonate Deputy of starting compound of the Formula 37 is replaced, for example, Br or Cl from hydrogen bromide or hydrogen chloride, respectively. This reaction is carried out in a suitable solvent, such as dibromomethane, dichloromethane or acetonitrile. This reaction can be conducted at atmospheric pressure or approximately atmospheric pressure in the autoclave. In the case when R6in the initial compound of Formula 37 is a halogen, such as Cl, the reaction is preferably carried out so that the hydrogen halide formed as a result of this reaction, was removed by ozonation or other appropriate SPO is Obama. This reaction can be from about 0 to 100°C, most suitably at about ambient temperature (e.g., about 10 to 40°C), and more preferably from about 20 to 30°C. the Addition of the catalyst of the Lewis acid (such as tribromide aluminum to obtain the compounds of Formula 37 wherein R6represents Br) can facilitate the reaction. The product of Formula 37 emit conventional methods known to experts in this field, including extraction, distillation and crystallization. Additional details of this process are presented in Example 14.

The initial compounds of Formula 37 wherein R6represents Cl or Br, can be obtained from corresponding compounds of Formula 38, as already described. The initial compounds of Formula 37 wherein R6represents a sulphonate group, can be obtained in the same manner from the corresponding compounds of Formula 38 by standard methods such as treatment with sulphonylchloride (for example, p-toluensulfonate) and a base such as tertiary amine (e.g. triethylamine) in a suitable solvent such as dichloromethane; additional details of this process are presented in Example 15.

Pyrazolylborate acid of Formula 4d, where R6represents a C1-C4alkoxy or C1-C4 halogenoalkane can also be obtained by the method presented in Scheme 21.

Scheme 21

where R13represents a C1-C4alkyl, and X is a leaving group.

In this way, instead of halogenation, as shown in figure 20, the compound of Formula 38 oxidized to compounds of Formula 32a. The reaction conditions for the oxidation already described for the conversion of compounds of Formula 37 in the compound of Formula 32 in figure 19.

The compound of Formula 32a then alkylate to produce the compounds of Formula 32b by contact with an alkylating agent CF3CH2X (39) in the presence of a base. In the alkylating agent 39 X represents a leaving group in nucleophilic reactions, such as halogen (such as Br, I), OS(O)2CH3(methanesulfonate), OS(O)2CF3, OS(O)2Ph-p-CH3(p-toluensulfonate), and the like; good methanesulfonate. This reaction is carried out in the presence of at least one equivalent of base. Suitable bases include inorganic bases such as carbonates and hydroxides of alkali metals (such as lithium, sodium or potassium) and organic bases such as triethylamine, diisopropylethylamine and 1,8-diazabicyclo[5,4,0]undec-7-ene. This reaction is mainly carried out in a solvent, which can containing the ü alcohols, such as methanol and ethanol, halogenated alkanes, such as dichloromethane, aromatic solvents such as benzene, toluene and chlorobenzene, ethers, such as tetrahydrofuran, and polar aprotic solvents such as acetonitrile, N,N-dimethylformamide and the like. With inorganic bases, it is preferable to use alcohols and polar aprotic solvents. Preferred are potassium carbonate as base and acetonitrile as solvent. This reaction is mainly carried out from about 0 to 150°C, most typically from ambient temperature to 100°C. the Product of Formula 32b may be separated by conventional techniques such as extraction. Ester of the Formula 32b may then be converted to carboxylic acid of Formula 4d using the methods already described for the conversion of compounds of Formula 32 in the compound of Formula 4d figure 17. Additional experimental details for this method according to the Circuit 21 shown in Example 16.

The compounds of Formula 38 can be obtained from compounds of Formula 33, as shown in figure 22.

Scheme 22

where R13represents a C1-C4alkyl.

In this way hydrazine powered compound of Formula 33 is brought into contact with a compound of Formula 40 (can be used for the van ether fumarata or maleate, or a mixture thereof) in the presence of base and solvent. The basis is usually the salt of the metal alkoxide such as sodium methoxide, potassium methoxide, ethoxide sodium, atoxic potassium tert-piperonyl potassium tert-piperonyl lithium, and the like. You should use more than 0.5 equivalents of base in comparison with the compound of the Formula 33, preferably from 0.9 to 1.3 equivalents. You should use more than 1.0 equivalent of compound of Formula 40, preferably from 1.0 to 1.3 equivalents. Can be used proton polar and polar aprotic organic solvents, such as alcohols, acetonitrile, tetrahydrofuran, N,N-dimethylformamide, dimethylsulfoxide and the like. Preferred solvents are alcohols, such as methanol and ethanol. Particularly preferably, the alcohol was the same as that of fumaric or maleic ester, and alkoxide basis. This reaction is usually carried out by mixing the compounds of Formula 33 and the base in the solvent. This mixture can be heated or cooled to the desired temperature and the compound of Formula 40 add for a certain period of time. The usual reaction temperature ranges from 0°C to the boiling point of the used solvent. These reactions can be conducted under pressure greater than atmospheric pressure to increase the boiling point of the solvent. Mainly preferred temperature from30 to 90° C. the Time of addition can be as fast as possible heat transfer. The usual time added is from 1 minute to 2 hours. The optimum reaction temperature and time add, vary with characteristics of the compounds of Formula 33 and Formula 40. After the addition, the reaction mixture can be kept for some time at the reaction temperature. Depending on the reaction temperature is the required time may be from 0 to 2 hours. Typically, the retention time is from 10 to 60 minutes. The reaction mass may then be acidified by the addition of organic acids such as acetic acid and the like, or inorganic acids such as hydrochloric acid, sulfuric acid and the like. Depending on the reaction conditions and methods of isolation, functional group-CO2R13the compounds of Formula 38 can be hydrolyzed to CO2H; for example, such hydrolysis may contribute to the presence of water in the reaction mixture. In the case of formation of carboxylic acid (-CO2N), it can be converted back into-CO2R13where R13represents a C1-C4alkyl, using methods of esterification are well known in this field. The desired product, compound of Formula 38 can be selected using methods known to experts in the Noi area, such as crystallization, extraction or distillation.

It is obvious that some reagents and reaction conditions described above for preparing compounds of Formula I, may not be combined with some functional features in the intermediate compounds. In these cases, to obtain the desired product will help enable the synthesis of sequences of protect/unprotect functional groups or interconversions. The use and choice of protecting groups will be apparent to the expert in the field of chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M.Protective Groups in Organic Synthesis,2nd ed.; Wiley: New York, 1991). The person skilled in the art will understand that in some cases, after the introduction of a given reagent as shown in any individual scheme, to complete the synthesis of compounds of Formula I may be required to perform additional standard operations that are not described in detail. The person skilled in the art will also understand that it may be necessary to perform a certain sequence of stages, as shown in the above schemes in an order other than individual sequences shown to produce compounds of Formula I.

It is considered that specialist in this field, using the steps can prepare the compounds of Formula I of the present invention in sa who ohms full. The following Examples, therefore, are intended only to illustrate and not to limit the disclosure in any direction. The percentages are given by weight, except for mixtures of solvents for chromatography or where otherwise noted. Parts and percentages for mixtures of solvents for chromatography are by volume unless otherwise stated. Spectra1H NMR are given in ppm relative to tetramethylsilane; means singlet, d means doublet, t means triplet, kV means Quartet, m means multiplet, DD means doublet of doublets, dt means doublet of triplets, with Shir means broad singlet.

EXAMPLE 1

Getting 2-[1-ethyl-3-cryptomaterial-5-yl-carbarnoyl]-3-methyl-N-(1-methylethyl)benzamide

Stage a: 3-Methyl-N-(1-methylethyl)-2-nitrobenzamide

A solution of 3-methyl-2-nitrobenzoic acid (2.00 g, 11.0 mmol) and triethylamine (1.22 g, 12.1 mmol) in 25 ml of methylene chloride was cooled to 10°C. was Carefully added ethyl chloroformate and formed a solid residue. After stirring for 30 minutes was added Isopropylamine (0,94 g, 16.0 mmol) and as a result received the homogeneous solution. The reaction mixture was stirred for an additional hour, poured into water and was extracted with ethyl acetate. The organic extracts were washed with water, dried over magnesium sulfate, evaporated under reduced is the making of obtaining a 1.96 g of the desired intermediate as a white solid, melting at 126-128°C.

1H NMR (CDCl3)δ to 1.24 (d, 6H), of 2.38 (s, 3H), 4,22 (m, 1H), 5,80 (wide s, 1H), and 7.4 (m, 3H).

Stage B: Obtaining 2-amino-3-methyl-N-(1-methylethyl)benzamide

2-nitrobenzamide with Stage A (1.70 g, 7.6 mmol) was hydrogenosomal over 5% Pd/C in 40 ml of ethanol at 50 f/DM2(psi). Upon cessation of hydrogen absorption, the reaction mixture was filtered through Celite® diatom layer for filtering and Celite® washed simple ether. The filtrate is evaporated under reduced pressure obtaining of 1.41 g of the above compound in the form of a solid, melting at 149-151°C.

1H NMR (CDCl3) δ 1,24 (DD, 6H), of 2.16 (s, 3H), 4,25 (m, 1H), 5,54 (wide s, 2H), 5,85 (wide s, 1H), 6,59 (t, 1H), 7,13 (d, 1H), 7,17 (d, 1H).

Stage C: Obtain 1-ethyl-3-cryptomaterial-5-yl carboxylic acid

To a mixture of 3-cryptomaterial (5 g, 37 mmol) and powdered potassium carbonate (10 g, 72 mmol), stirred in 30 ml of N,N-dimethylformamide, was added dropwise Iodate (8 g, 51 mmol). After a moderate selection of heat, the reaction mixture was stirred over night at room temperature. The reaction mixture was distributed between 100 ml of diethyl ether and 100 ml of water. The ether layer was separated, washed with water (3X) and brine and was dried over magnesium sulfate. Evaporation of the solvent in vacuo gave 4 g of oil.

To 3.8 g of this oil mixed in 40 ml of tetr is hydrofuran in the atmosphere of nitrogen in a bath of dry ice/acetone, was added dropwise 17 ml of 2.5 M solution of n-utility in tetrahydrofuran (43 mmol) and the solution was stirred for 20 minutes at -78°C. the mixed solution was barbotirovany excess of carbon dioxide gas at a moderate speed for 10 minutes. After the addition of carbon dioxide, the reaction mixture was left to slowly reach room temperature and was stirred overnight. The reaction mixture was distributed between diethyl ether (100 ml) and 0.5 N. aqueous sodium hydroxide (100 ml). Separated the main layer was acidified with concentrated hydrochloric acid to pH 2-3. This aqueous mixture was extracted with ethyl acetate (100 ml) and the organic extract was washed with water and brine and dried over magnesium sulfate. The oily residue remaining after evaporation of the solvent in vacuo,rubbed until dry matter of a small number of 1-chlorobutane. After filtration and drying was given a sample of 1-ethyl-3-trifluoromethyl-pyrazole-5-yl carboxylic acid (1.4 g) with minor impurities in the form of a consumable in a wide temperature range solid.

1H NMR (CDCl3) δ is 1.51 (t, 3H), and 4.68 (q, 2H), 7.23 percent (s, 1H), 9,85 (wide s, 1H).

Stage D: Obtain 2-[1-ethyl-3-cryptomaterial-5-yl carbarnoyl]-3-methyl-N-(1-methylethyl)benzamide

To a solution of 1-ethyl-3-trifluoromethyl-pyrazole-yl carboxylic acid (i.e. the product from step C) (0.5 g, 2.4 mmol), stirred in 20 ml of methylene chloride, was added oxalicacid (1.2 ml, 14 mmol). Adding 2 drops of N,N-dimethylformamide was foaming and gas. The reaction mixture is in the form of a yellow solution was heated in a flask under reflux for 1 hour. After cooling, the solvent was removed in vacuo and the resulting residue was dissolved in 20 ml of tetrahydrofuran. To the stirred solution was added 2-amino-3-methyl-N-(1-methylethyl)benzamide (i.e. the product from stage B) (0.7 g, 3.6 mmol), followed by adding dropwise N,N-diisopropylethylamine (3 ml, 17 mmol). After stirring at room temperature overnight the reaction mixture was distributed between ethyl acetate (100 ml) and 1 N. aqueous hydrochloric acid (75 ml). The separated organic layer was washed with water and brine and dried over magnesium sulfate. Evaporation in vacuum gave a white solid residue, which upon purification using flash chromatography on a column of silica gel (2:1 hexane/ethyl acetate) gave 0.5 g of the above compounds, the compounds of the present invention, melting at 223-226°C.

1H NMR (DMSO-d6) δ of 1.06 (d, 6H), of 1.36 (t, 3H), of 2.45 (s, 3H), of 3.97 (m, 1H), 4,58 (kV, 2H), 7,43-7,25 (m, 3H), 7,45 (s, 1H), with 8.05 (d, 1H), 10,15 (s, 1H).

EXAMPLE 2

Obtaining N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-phenyl-3-(t is iformity)-1H-pyrazole-5-carboxamide

Stage A: Getting 2-Methyl-1-phenyl-4-(trifluoromethyl)-1H-pyrazole

A solution of 1,1,1-triterpene-2,4-dione (20,0 g, 0,130 mol) in glacial acetic acid (60 ml) was cooled to 7°C using a bath of ice/water. Phenylhydrazine (14.1 g, 0,130 mol) was added dropwise over 60 minutes. During the addition the temperature of the reaction mass was raised to 15°C. the resulting orange solution was kept at ambient conditions for 60 minutes. The amount of acetic acid was removed by evaporation on a rotary evaporator with a bath temperature of 65°C. the Residue was dissolved in methylene chloride (150 ml). The solution is washed with aqueous sodium bicarbonate (3 g in 50 ml water). Purple-red organic layer was separated, treated with activated charcoal (2 g) and MgSO4, then filtered. Volatile components were removed on a rotary evaporator. The crude product contained 28,0 g butter pink, containing ˜89% of the desired product, and 11% of 1-phenyl-5-(trifluoromethyl)-3-methylpyrazole.

1H NMR (DMSO-d6) δ to 2.35 (s, 3H), 6,76 (s, 1H), and 7.6-7.5 (m, 5H).

Stage B: Obtain 1-phenyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

A sample of crude 2-methyl-1-phenyl-4-(trifluoromethyl)-1H-pyrazole (i.e. the product from step A) (˜89%, 50.0 g, 0,221 mol) was mixed with water (400 ml) and chloride of cetyltrimethylammonium (4,00 g to 0.011 mol). This is mesh was heated to 95° C. was Added potassium permanganate 10 equal portions, at intervals ˜8 minutes. During this period, the reaction mass was maintained at 95-100°C. After adding the last portion of this mixture (kept) stood for ˜15 minutes at 95-100°C, after which it discoloured purple color of the permanganate. The reaction mass was filtered hot (˜75°C) through a 1-cm layer of Celite® diatom layer for filtering in 150-ml funnel with steklovata. The filter cake was washed with warm (˜50° (C) water (3×100 ml). The combined filtrate and washings were extracted by a simple ether (2×100 ml) to remove small amounts of yellow water-insoluble substances. The aqueous layer was purged with nitrogen to remove residual ether. Transparent colorless alkaline solution was acidified by adding concentrated hydrochloric acid dropwise to achieve pH ˜1,3 (28 g, 0.28 mol). While adding the first two thirds was intense emission of gas. This product was collected by filtration, washed with water (3×40 ml), then dried overnight at 55°C in vacuum.This product consisted of 11.7 g of white crystalline powder, which was essentially pure from1H NMR.

1H NMR (CDCl3) δ 7,33 (s, 1H), and 7.4-7.5 (m, 5H).

Stage C: Obtain 1-phenyl-3-(trifluoromethyl)-1H-pyrazole-5-carbonyl who lorida

A sample of crude 1-phenyl-3-(trifluoromethyl)pyrazole-5-carboxylic acid (i.e. the product from step B) (4,13 g, 16,1 mmol) was dissolved in methylene chloride (45 ml). This solution was treated with oxalylamino (1.80 ml of 20.6 mmol), then N,N-dimethylformamide (0,010 ml, 0.13 mmol). Gas production began soon after adding the catalyst N,N-dimethylformamide. The reaction mixture was stirred for ˜20 minutes at ambient conditions, and then were heated to the boiling temperature under reflux for 35 minutes. Volatile components were removed by evaporation of the reaction mixture on a rotary evaporator at a bath temperature of 55°C. the product consisted of 4,43 g light yellow oil. The only impurity registered on1H NMR, was N,N-dimethylformamide.

1H NMR (CDCl3) δ 7,40 (m, 1H), 7,42 (s, 1H), 7,50-7,53 (m, 4H).

Stage D: Obtaining N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-phenyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

Sample 3-metalanguage Stanovoy acid (0,30 g, 1.7 mmol)partially dissolved in pyridine (4.0 ml)was treated with 1-phenyl-3-(cryptomaterial)-5-carboxylicacid (i.e. the product from step C) (0.55 g, 1.9 mmol). The mixture was heated up to ˜95°C for 2 hours. The resulting orange solution was cooled to 29°C, then treated with Isopropylamine (1,00 g, 16.9 m is ol). Reaction mass is exothermically heated up to 39°C. in Addition, it was heated to 55°C for 30 minutes, after which formed a large residue. The reaction mass was dissolved in dichloromethane (150 ml). This solution is washed with aqueous acid (5 ml conc. HCl in 45 ml of water), then water (2 g of sodium carbonate in 50 ml of water). The organic layer was dried over MgSO4, filtered, then concentrated on a rotary evaporator. During reduction to ˜4 ml of formed crystals of the product. The suspension was diluted ˜10 ml simple ether, and then was crystallized more product. This product was isolated by filtration, washed with simple ether (2×10 ml), then washed with water (2×50 ml). The wet precipitate was dried for 30 minutes at 70°Cin a vacuum.This product, the compound of the present invention, consisted of 0.52 g not quite white powder, melting at 260-262°C.

1H NMR (DMSO-d6) δ of 1.07 (d, 6H), of 2.21 (s, 3H), was 4.02 (octet, 1H), 7,2-7,4 (m, 3H), 7,45-to 7.6 (m, 6H), 8,10 (d, 1H), 10,31 (s, 1H).

EXAMPLE 3

Obtaining N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-3-(trifluoromethyl)-1-[3-(trifluoromethyl)-2-pyridinyl]-1H-pyrazole-5-carboxamide

Stage a: 3-trifluoromethyl-2-[3-(trifluoromethyl)-1H-pyrazole-1-yl]pyridine

A mixture of 2-chloro-3-triptoreline (3,62 g, 21 mmol), 3-cryptomaterial (2.7 g, 20 mm is l) and potassium carbonate (6.0 g, 43 mmol) was heated at 100°C for 18 h the Cooled reaction mixture was added to ice water (100 ml). The mixture was twice extracted with simple ether (100 ml) and the combined ether extracts washed twice with water (100 ml). The organic layer was dried with magnesium sulfate and concentrated to oil. Chromatography on silica gel with hexane/ethyl acetate 8:1 to 4:1 as eluent gave the titled compound (3.5 g) as oil.

1H NMR (CDCl3) δ to 6.75 (m, 1H), 7.5 (m, 1H), and 8.2 (m, 2H), and 8.7 (m, 1H).

Stage B: 3-(trifluoromethyl)-1-[3-(trifluoromethyl)-2-pyridinyl]-1H-pyrazole-5-carboxylic acid

The mixture of the compounds mentioned in EXAMPLE 3, Stage A (3.4 g, 13 mmol) was dissolved in tetrahydrofuran (30 ml) and cooled to -70°C. was Added diisopropylamide lithium (2 N. in heptane/tetrahydrofuran (THF) (Aldrich) and 9.5 ml, 19 mmol) and the resulting dark mixture was stirred for 10 minutes. Dry carbon dioxide was barbotirovany through the mixture for 15 minutes. The mixture was left to warm to 23°C and treated with water (50 ml) and 1 N. sodium hydroxide (10 ml). This aqueous mixture was extracted with simple ether (100 ml)and then ethyl acetate (100 ml). The aqueous layer was acidified using 6 N. hydrochloric acid to pH 1-2 and extracted twice with dichloromethane. The organic layer was dried with magnesium sulfate and concentrated to obtain the named connection is in (1.5 g).

1H NMR (CDCl3) δ to 7.6 (m, 1H), 7,95 (m, 1H), 8,56 (m, 1H), 8,9 (m, 1H), 14,2 (W, 1H).

Stage C: Obtaining N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-3-(trifluoromethyl)-1-[3-(trifluoromethyl)-2-pyridinyl]-1H-pyrazole-5-carboxamide

The mixture of these compounds of EXAMPLE 3, step B (0.54 g, 1.1 mmol), the title compound from EXAMPLE 1, stage B (of 0.44 g, 2.4 mmol) and BOP chloride (bis(2-oxo-oxazolidinyl)hasfinished, 0.54 g, 2.1 mmol) in acetonitrile (13 ml)was treated with triethylamine (0.9 ml). The mixture was shaken in a closed scintillation vial for 18 h the Reaction mixture was distributed between ethyl acetate (100 ml) and 1 N. hydrochloric acid. The ethyl acetate layer was washed successively 1 N. hydrochloric acid (50 ml), 1 N. sodium hydroxide (50 ml) and saturated sodium chloride solution (50 ml). The organic layer was dried over magnesium sulfate and concentrated. The residue was subjected to flash chromatography on a column of silica gel with hexane/ethyl acetate (5:1 to 3:1) as eluent. A named connection (0,43 g), the compound of the present invention, was isolated as a white solid, TPL 227-230°C.

1H NMR (CDCl3) δ 1,2 (m, 6H), to 4.15 (m, 1H), 5,9 (width d, 1H), and 7.1 (m, 1H), 7,2 (m, 2H), and 7.4 (s, 1H), 7,6 (m, 1H), 8,15 (m, 1H), total of 8.74 (m, 1H), 10,4 (W, 1H).

EXAMPLE 4

Obtain 1-(3-chloro-2-pyridinyl)-N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]-phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carbox the IDA

Stage a: 3-chloro-2-[3-(trifluoromethyl)-1H-pyrazole-1-yl]pyridine

To a mixture of 2,3-dichloropyridine (99,0 g, 0.67 mol) and 3-(trifluoromethyl)pyrazole (83 g, 0.61 mol) in dry N,N-dimethylformamide (300 ml) was added potassium carbonate (166,0 g, 1.2 mol) and then the reaction mixture was heated to 110-125°C for 48 hours. The reaction mixture was cooled to 100°C and filtered through Celite® diatom layer for filtering to remove solid impurities. N,N-Dimethylformamide and excess dichloropyridine was removed by distillation at atmospheric pressure. Distillation of this product under reduced pressure (because 139-141°C, 7 mm) gave the desired intermediate compound as a pale yellow oil (to 113.4 g).

1H NMR (CDCl3) δ is 6.78 (s, 1H), was 7.36 (t, 1H), to 7.93 (d, 1H), 8,15 (s, 1H), 8,45 (d, 1H).

Stage B: Obtain 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

To a solution of 3-chloro-2-[3-(trifluoromethyl)-1H-pyrazole-1-yl]pyridine (i.e. the product of Stage A) (105,0 g, 425 mmol) in dry tetrahydrofuran (700 ml) at -75°C was added via cannula -30°C solution diisopropylamide lithium (425 mmol) in dry tetrahydrofuran (300 ml). Dark red solution was stirred for 15 minutes, after this time has barbotirovany carbon dioxide when -63°C to until the solution became pale yellow and continued heat. The reaction is mesh was stirred for an additional 20 minutes and rapidly cooled with water (20 ml). The solvent was removed under reduced pressure, and the reaction mixture was distributed between the simple ether and 0.5 N. aqueous sodium hydroxide solution. Water extracts were washed with simple ether (3x), filtered through Celite® diatom layer for filtering to remove residual solids, and then acidified to approximately pH 4, at this point was formed orange oil. The aqueous mixture was intensively mixed and added an additional amount of acid to lower the pH to 2.5-3. Orange oil froze in granular solid, which was filtered, washed successively with water and 1 N. hydrochloric acid and dried under vacuum at 50°C with getting this product in the form of not-quite-white solid (130 g). (Product from another faction, obtained by a similar methodology, melted at 175-176°C)

1H NMR (DMSO-d6) δ to 7.61 (s, 1H), 7,76 (DD, 1H), 8,31 (d, 1H), at 8.60 (d, 1H).

Stage C: Getting 8-methyl-2H-3,1-benzoxazin-2,4(1H)dione

To a solution of 2-amino-3-methylbenzoic acid (6 g) in dry 1,4-dioxane (50 ml) was added dropwise a solution of trichlorochloroform (8 ml) in dry 1,4-dioxane (25 ml) with cooling with ice water to keep the reaction temperature below 25°C. while adding began to form a white precipitate. The reaction mixture was stirred at room temperature throughout the night. The precipitated solids were removed by filtration and washed with 1,4-dioxane (2×20 ml) and hexane (2×15 ml), and dried in the air with the release of 6,51 g not quite white solid.

1H NMR (DMSO-d6) δ of 2.33 (s, 3H), 7,18 (t, 1H), to 7.59 (d, 1H), 7,78 (d, 1H), 11,0 (wide s, 1H).

Stage D: Obtain 2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it

To a suspension of the product carboxylic acid, obtained as in Stage B (146 g, 500 mmol) in dichloromethane (about 2 l)was added N,N-dimethylformamide (20 drops) and oxacillin (67 ml, 750 mmol) in portions of approximately 5 ml after approximately 2 hours while adding intense gas evolution. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to obtain the crude carboxylic acid in the form of opaque orange mixture. This substance was placed in dichloromethane, filtered to remove some solids and then concentrated and used without further purification. The crude acid chloride acid was dissolved in acetonitrile (250 ml) was added to a suspension of product from step C in acetonitrile (400 ml). Added pyridine (250 ml), the mixture was stirred for 15 min at room temperature, then was heated to the temperature of the pile is ia under reflux for 3 hours The resulting mixture was cooled to room temperature and was stirred overnight to obtain a solid mass. Added additional amount of acetonitrile and the mixture was stirred for formation of a thick slurry. Solids were collected and washed with cold acetonitrile. Solids were air-dried and dried in vacuum at 90°C for 5 h with output 144,8 g fluffy solid product.

1H NMR (CDCl3) δ of 1.84 (s, 3H), and 7.4 (t, 1H), 7,6 (m, 3H), and 8.0 (DD, 1H)and 8.1 (s, 1H), and 8.6 (d, 1H).

Stage E: Obtain 1-(3-chloro-2-pyridinyl)-N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To a suspension of the product of benzoxazinone Stage D (124 g, 300 mmol) in dichloromethane (500 ml) was added dropwise Isopropylamine (76 ml, 900 mmol) at room temperature. During the addition the temperature of the reaction mixture increased and the suspension was radigales. Then the reaction mixture was heated to boiling point under reflux for 1.5 hours Formed a new suspension. The reaction mixture was cooled to room temperature and was added diethyl ether (1.3 l) and the mixture was stirred at room temperature overnight. The solids were collected and washed simple ether. The solids were air-dried and then dried in vacuum at 90°C for 5 h with output 122 is named connection, the compound of the present invention in the form of a fluffy solid product, melting at 194-196°C.

1H NMR (CDCl3) δ of 1.23 (d, 6H), of 2.21 (s, 3H), 4,2 (m, 1H)and 5.9 (d, 1H), 7,2 (t, 1H), and 7.3 (m, 2H), 7,31 (s, 1H), and 7.4 (m, 1H), and 7.8 (d, 1H), and 8.5 (d, 1H), 10,4 (s, 1H).

EXAMPLE 5

Alternative obtain 1-(3-chloro-2-pyridinyl)-N-[2-methyl-6-[[(1-methylethyl)amino]-carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To a solution of the product carboxylic acid, obtained as in EXAMPLE 4, step B (28 g, 96 mmol) in dichloromethane (240 ml) was added N,N-dimethylformamide (12 drops) and oxacillin (15,8 g, 124 mmol). The reaction mixture was stirred at room temperature until gas evolution stops (approximately 1.5 hours). The reaction mixture was concentrated in vacuo to obtain the crude carboxylic acid in the form of oil, used without further purification. The crude acid chloride acid was dissolved in acetonitrile (95 ml) was added to a solution of benzoxazin-2,4-dione, prepared according to the method of EXAMPLE 4, Stage C, in acetonitrile (95 ml). The resulting mixture was stirred at room temperature (approximately 30 minutes). Added pyridine (95 ml) and the mixture was heated to about 90°C (approximately 1 hour). The reaction mixture was cooled to about 35°C and was added Isopropylamine (25 ml). During the addition the reaction mixture was heated esoterics and, and then kept at about 50°C (approximately 1 hour). The reaction mixture was then poured into ice-cold water and stirred. The resulting precipitate was collected by filtration, washed with water and dried in vacuumduring the night with the receipt of 37.5 g of the above compounds, the compounds of the present invention in the form of a yellowish-brown solid.

1H NMR (CDCl3) δ of 1.23 (d, 6H), of 2.21 (s, 3H), 4,2 (m, 1H)and 5.9 (d, 1H), 7,2 (t, 1H), and 7.3 (m, 2H), 7,31 (s, 1H), and 7.4 (m, 1H), and 7.8 (d, 1H), and 8.5 (d, 1H), 10,4 (s, 1H).

EXAMPLE 6

Obtaining N-[4-[chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide.

Stage A: Obtaining 2-amino-3-methyl-5-chlorbenzoyl acid

To a solution of 2-amino-3-methylbenzoic acid (Aldrich, 15.0 g, to 99.2 mmol) in N,N-dimethylformamide (50 ml) was added N-chlorosuccinimide (13.3 g, and 99.2 mmol) and the reaction mixture was heated to 100°C for 30 minutes. Heat was removed, the reaction mixture was cooled to room temperature and left over night. The reaction mixture was then slowly poured into ice water (250 ml) to precipitate a white solid. The solid was filtered and washed four times with water and then placed in ethyl acetate (900 ml). The ethyl acetate solution was dried over magnesium sulfate, evaporated under reduced pressure, the residual solid was washed about the th ether to give the desired intermediate as a white solid (13,9 g).

1H NMR (DMSO-d6) δ 2,11 (s, 3H), 7,22 (s, 1H), 7,55 (s, 1H).

Stage b: 3-chloro-2-[3-(trifluoromethyl)-1H-pyrazole-1-yl]pyridine

To a mixture of 2,3-dichloropyridine (99,0 g, 0.67 mol) and 3-trifluoromethyl-of-pyrazole (83 g, 0.61 mol) in dry N,N-dimethylformamide (300 ml) was added potassium carbonate (166,0 g, 1.2 mol) and then the reaction was heated to 110-125°C for 48 hours. The reaction was cooled to 100°C, filtered through Celite® diatom layer to remove solid particles. N,N-dimethylformamide and excess dichloropyridine was removed by distillation at atmospheric pressure. Distillation of this product under reduced pressure (because 139-141°C, 7 mm) gave the titled compound as a pale yellow oil (to 113.4 g).1H NMR(CDCl3) δ is 6.78 (s, 1H), was 7.36 (t, 1H), to 7.93 (d, 1H), 8,15 (s, 1H), 8,45 (d, 1H).

Stage C: Obtain 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid.

To a solution of the pyrazole nucleus of the product from step B (105,0 g, 425 mmol) in dry tetrahydrofuran (700 ml) at -75°C was added via cannula -30°C solution diisopropylamide lithium (425 mmol) in dry tetrahydrofuran (300 ml). Intense red solution was stirred for 15 minutes, after this time via the solution was barbotirovany carbon dioxide when -63°C, until then, until the solution became pale yellow and did not stop the heat. The reaction mixture p is remedial for an additional 20 minutes, and then abruptly cooled water (20 ml). The solvent was removed under reduced pressure, and the reaction mixture was distributed between the simple ether and 0.5 N. aqueous sodium hydroxide solution. Water extracts were washed with simple ether (3x), filtered through Celite® diatom layer for filtering to remove residual solids and then acidified to approximately pH 4, at this point was formed orange oil. The aqueous mixture was intensively stirred, was added an additional amount of acid to reduce the pH to 2.5-3. The orange oil was hardened in a granular solid, which was filtered, then washed with water and 1 N. hydrochloric acid and dried under vacuum at 50°C with getting this product in the form of not-quite-white solid (130 g). (Product from another faction on a similar methodology melted at 175-176°C).

1H NMR (DMSO-d6) δ to 7.61 (s, 1H), 7,76 (DD, 1H), 8,31 (d, 1H), at 8.60 (d, 1H).

Stage D: Obtain 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it.

To a solution of methanesulfonamide (2.2 ml, 28.3 mmol) in acetonitrile (75 ml) was added dropwise a mixture of the product carboxylic acid from step C (7.5 g, of 27.0 mmol) and triethylamine (3.75 ml, of 27.0 mmol) in acetonitrile (75 ml) at 0-5°C. Then the reaction temperature was maintained at 0°C for the of just adding reagents. After stirring for 20 minutes was added 2-amino-3-methyl-5-chlorobenzoyl acid from step A (5,1 g of 27.0 mmol) and stirring continued for an additional 5 minutes. Then was added dropwise a solution of triethylamine (7.5 ml, 54,0 mmol) in acetonitrile (15 ml) and the reaction mixture was stirred for 45 minutes followed by the addition of methanesulfonanilide (2.2 ml, 28.3 mmol). The reaction mixture then was heated to room temperature and was stirred overnight. Then add about 75 ml of water to precipitate 5.8 g of a yellow solid. An additional 1 g of the product was isolated by extraction of the filtrate with the receipt in the amount of 6.8 g of the named compound as a yellow solid.

1H NMR (CDCl3) δ to 1.83 (s, 3H), 7,50 (s, 1H), 7,53 (m, 2H), 7,99 (m, 2H), 8,58 (d, 1H).

Stage E: Obtaining N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To a solution of the product of benzoxazinone with Stage D (5.0 g, 11.3 mmol) in tetrahydrofuran (35 ml) was added dropwise Isopropylamine (2,9 ml, 34,0 mmol) in tetrahydrofuran (10 ml) at room temperature. The reaction mixture was heated to dissolve all solids and stirred an additional five minutes, during this time the completion of the reaction was confirmed by thin layer chromatography on silica gel. Then it is carbonated is returnby the solvent evaporated under reduced pressure, and the remaining solids were purified by chromatography on silica gel, followed by kneading the powder with ether/hexane to obtain these compounds, the compounds of the present invention, in the form of a solid (4.6 g), melting at 195-196°C.

1H NMR (CDCl3) δ to 1.21 (d, 6H), 2,17 (s, 3H), of 4.16 (m, 1H), 5,95 (width d, 1H), 7,1-7,3 (m, 2H), 7,39 (s, 1H), and 7.4 (m, 1H), to 7.84 (d, 1H), and 8.50 (d, 1H), 10,24 (wide s, 1H).

EXAMPLE 7

Obtaining N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To a solution of the product of benzoxazinone EXAMPLE 6 Stage D (4,50 g, 10,18 mmol) in tetrahydrofuran (THF; 70 ml) was added dropwise methylamine (2.0 M solution in THF, 15 ml, 30.0 mmol) and the reaction mixture was stirred at room temperature for 5 minutes. Tertrahydrofuran ring the solvent evaporated under reduced pressure and the remaining solids were purified by chromatography on silica gel to obtain 4.09 g of the above compounds, the compound of the present invention, in the form of a white solid, melting at 185-186°C.

1H NMR (DMSO-d6) δ 2,17 (s, 3H), 2,65 (d, 3H), 7,35 (d, 1H), 7,46 (DD, 1H), 7,65 (DD, 1H), 7,74 (s, 1H), 8,21 (d, 1H), 8,35 (Shir kV, 1H), total of 8.74 (d, 1H), accounted for 10.39 (s, 1H).

EXAMPLE 8

Obtain 3-chloro-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

Stage A: On the teaching of 3-chloro-N,N-dimethyl-1H-pyrazole-1-sulfonamida

To a solution of N-diethylaminophenol (188,0 g, 1.07 mol) in dry tetrahydrofuran (1500 ml) at -78°C was added dropwise a solution of 2.5 M n-utility (472 ml, 1.18 mol) in hexane, keeping the temperature below -65°C. Upon completion of addition the reaction mixture was maintained at -78°C for an additional 45 minutes, after which time was added dropwise a solution of hexachloroethane (279 g, 1.18 mol) in tetrahydrofuran (120 ml). The reaction mixture is kept for one hour at -78°C, was heated to -20°C and then quickly cooled with water (1 l). The reaction mixture was extracted with methylene chloride (4x500 ml); the organic extracts were dried over magnesium sulfate and concentrated. The crude product was further purified by chromatography on silica gel, using methylene chloride as eluent, to obtain the titled compound as a yellow oil (160 g).

1H NMR (CDCl3) δ of 3.07 (d, 6H), 6,33 (s, 1H), to 7.61 (s, 1H).

Stage B: 3-chloropyrazole

To triperoxonane acid (290 ml) was added dropwise to the product of chloropyrazole (160 g) from step A, and the reaction mixture was stirred at room temperature for 1.5 hours and then concentrated under reduced pressure. The residue was placed in hexane, the insoluble solids were filtered off and the hexane was concentrated to obtain the crude product as oil. Untreated the i.i.d. product is further purified by chromatography on silica gel using as eluent ether/hexane (40:60) to give the titled product as a yellow oil (64,44 g). 1H NMR (CDCl3) δ to 6.39 (s, 1H), 7,66 (s, 1H), 9,6 (wide s, 1H).

Stage C: 3-chloro-2-(3-chloro-1H-pyrazole-1-yl)pyridine

To a mixture of 2,3-dichloropyridine (92,60 g, 0,629 mol) and 3-chloropyrazole (i.e. the product from step B) (64,44 g, 0,629 mol) in N,N-dimethylformamide (400 ml) was added potassium carbonate (147,78 g, 1.06 mol), and then the reaction mixture was heated to 100°C for 36 hours. The reaction mixture was cooled to room temperature and slowly poured into ice-cold water. The precipitated solids were filtered and washed with water. A solid residue on the filter was placed in ethyl acetate, dried over magnesium sulfate and concentrated. The crude solid was chromatographically on silica gel using as eluent 20% ethyl acetate/hexane to obtain the above product as a white solid (39.75).

1H NMR (CDCl3) δ to 6.43 (s, 1H), 7,26 (m, 1H), of 7.90 (d, 1H), of 8.09 (s, 1H), to 8.41 (d, 1H).

Stage D: 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid

To a solution of the pyrazole nucleus of the product from step C (39.75 g, 186 mmol) in dry tetrahydrofuran (400 ml) at -78°C was added dropwise a solution of 2.0 M of diisopropylamide lithium (93 ml, 186 mmol) in tetrahydrofuran. Carbon dioxide was barbotirovany through the amber-yellow solution within 14 minutes, after this time the solution became pale brownish-yellow. otdavali alkaline reaction 1 N. aqueous solution of sodium hydroxide and was extracted with simple ether (2x500 ml). Aqueous extracts were acidified using 6 N. hydrochloric acid and was extracted with ethyl acetate (3×500 ml). An ethyl acetate extracts were dried over magnesium sulfate and concentrated to obtain the above product in the form of not-quite-white solid (42,96 g). (Product from another faction on a similar methodology melted at 198-199°C)

1H NMR (DMSO-d6) δ 6,99 (s, 1H), 7,45 (m, 1H), to 7.93 (d, 1H), 8,51 (d, 1H).

Stage E: Obtain 6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it

To a solution of methanesulfonamide (of 6.96 g, 61,06 mmol) in acetonitrile (150 ml) was added dropwise a mixture of the product carboxylic acid from step D (15.0 g, 58,16 mmol) and triethylamine (5,88 g, 58,16 mmol) in acetonitrile (150 ml) at -5°C. the Reaction mixture then was stirred for 30 minutes at 0°C. Then was added 2-amino-3-methyl-5-chlorobenzoyl acid from EXAMPLE 6, Stage A (10,79 g, 58,16 mmol) and stirring continued for an additional 10 minutes. Then was added dropwise a solution of triethylamine (11,77 g, 116,5 mmol) in acetonitrile, keeping the temperature below 10°C. the Reaction mixture was stirred for 60 minutes at 0°C, and then added methanesulfonamide (of 6.96 g, 61,06 mmol). The reaction mixture then was heated to room temperature and dopolnitelnyefunktsii 2 hours. The reaction mixture was then concentrated and the crude product was chromatographically on silica gel, using as eluent methylene chloride to obtain the named product as yellow solid (9.1 g).

1H NMR (CDCl3) δ is 1.81 (s, 3H), 7,16 (s, 1H), 7,51 (m, 2H), 7,98 (d, 2H), 8,56 (d, 1H).

Stage F: Obtain 3-chloro-N-[4-chloro-2-methyl]-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of the product of benzoxazinone Stage E (6,21 g, 15,21 mmol) in tetrahydrofuran (100 ml) was added Isopropylamine (to 4.23 g, 72,74 mmol) and the reaction mixture was then heated to 60°C, was stirred for 1 hour and then cooled to room temperature. Tertrahydrofuran ring the solvent evaporated under reduced pressure, and the remaining solids were purified by chromatography on silica gel with obtaining these compounds, the compounds of the present invention in the form of a white solid substance (of 5.05 g), melting at 173-175°C.

1H NMR (CDCl3) δ of 1.23 (d, 6H), to 2.18 (s, 3H), is 4.21 (m, 1H), 5,97 (d, 1H), 7,01 (m, 1H), 7,20 (s, 1H), 7,24 (s, 1H), 7,41 (d, 1H), 7,83 (d, 1H), 8,43 (d, 1H), 10,15 (wide s, 1H).

EXAMPLE 9

Obtain 3-chloro-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of the product of benzoxazinone EXAMPLE 8, Stage E (6,32 g, 15,47 mmol) in tetrahydrofuran (50 ml) was added to the methylamine (2.0 M solution in THF, 38 ml, 77,38 mmol)and the reaction mixture was heated to 60°C, was stirred for 1 hour and then cooled to room temperature. Tertrahydrofuran ring the solvent evaporated under reduced pressure and the remaining solids were purified by chromatography on silica gel with obtaining these compounds, the compounds of the present invention, in the form of a white solid substance (of 4.57 g), melting at 225-226°C.

1H NMR (CDCl3) δ of 2.15 (s, 3H), of 2.93 (s, 3H), 6,21 (d, 1H), 7,06 (s, 1H), 7,18 (s, 1H), 7,20 (s, 1H), 7,42 (m, 1H), 7,83 (d, 1H), 8,42 (d, 1H), 10,08 (wide s, 1H).

EXAMPLE 10

Obtain 3-Bromo-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

Stage a: 3-bromo-N,N-dimethyl-1H-pyrazole-1-sulfonamida

To a solution of N-dimethylsulphamoyl (44,0 g, 0,251 mol) in dry tetrahydrofuran (500 ml) at -78°C was added dropwise a solution of n-utility (2.5 M in hexane, 105,5 ml, 0,264 mol) keeping the temperature below -60°C. During the additions were formed dense substance. Upon completion of addition the reaction mixture was held for an additional 15 minutes after which time was added dropwise a solution of 1,2-dibromotetrachloroethane (90 g, 0.276 mol) in tetrahydrofuran (150 ml), keeping the temperature below -70°C. the Reaction mixture became bright orange; mixing what was prodoljali for an additional 15 minutes. Bath -78°C was removed and the reaction was rapidly cooled with water (600 ml). The reaction mixture was extracted with methylene chloride (4x), and the organic extracts were dried over magnesium sulfate and was kontsetrirovannoe. The crude product is further purified by chromatography on silica gel, using as eluent methylene chloride/hexane (50:50), to obtain the titled product as a clear colorless oil (57,04 g).

1H NMR (CDCl3) δ of 3.07 (d, 6H), 6,44 (m, 1H), 7.62mm (m, 1H).

Stage B: 3-bromopyrazole

To triperoxonane acid (70 ml) was slowly added bromopyrazole product (57,04 g) from step A. the Reaction mixture was stirred at room temperature for 30 minutes and then concentrated under reduced pressure. The residue was placed in hexane, the insoluble solids were filtered off and the hexane evaporated to obtain the crude product as oil. The crude product is further purified by chromatography on silica gel, using as eluent ethyl acetate/dichloromethane (10:90), with oil. This oil was placed in dichloromethane, neutralized with an aqueous solution of sodium bicarbonate, extracted with methylene chloride (3x), dried over magnesium sulfate and concentrated to obtain the named product as a white solid (25,9 g), TPL 61-64°C.

1H NMR (CDCl3) δ 6,37 (who, 1H), to 7.59 (d, 1H), 12,4 (wide s, 1H).

Stage C: Obtain 2-(3-bromo-1H-pyrazole-1-yl)-3-chloropyridine

To a mixture of 2,3-dichloropyridine (27.4 g, 185 mmol) and 3-bromopyrazole (i.e. the product from step B) (25.4 g, 176 mmol) in dry N,N-dimethylformamide (88 ml) was added potassium carbonate (48.6 g, 352 mmol)and the reaction mixture was heated to 125°C for 18 hours. The reaction mixture was cooled to room temperature and poured into ice water (800 ml). Formed precipitate. The settled solids was stirred for 1.5 hours, filtered and washed with water (2×100 ml). A dense precipitate on the filter was placed in methylene chloride and washed successively with water, 1 N. hydrochloric acid, saturated aqueous sodium bicarbonate and saline. The organic extracts were then dried over magnesium sulfate and concentrated to obtain and 39.9 g of pink solid. The crude solid is suspended in hexane and was intensively stirred for 1 hour. The solids were filtered, washed with hexane and dried to obtain the above product in the form of not quite white powder (30,4 g) with a purity of >94%determined by NMR. This substance was used without further purification in Stage D.

1H NMR (CDCl3) δ of 6.52 (s, 1H), 7,30 (DD, 1H), 7,92 (d, 1H), with 8.05 (s, 1H), 8,43 (d, 1H).

Stage D: 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carbon is Oh acid

To a solution of the pyrazole nucleus of the product from step C (30,4 g, 118 mmol) in dry tetrahydrofuran (250 ml) at -76°C was added dropwise a solution of diisopropylamide lithium (118 mmol) in tetrahydrofuran such a rate to keep the temperature below -71°C. the Reaction mixture was stirred for 15 minutes at -76°C, and then barbotirovany carbon dioxide for 10 minutes, heats up to -57°C. the Reaction mixture was heated to -20°C and sharply cooled water. The reaction mixture was concentrated and then put into water (1 l) and ether (500 ml)and then added an aqueous solution of sodium hydroxide (1 N., 20 ml). Water extracts were washed simple with ether, and acidified with hydrochloric acid. The precipitated solids were filtered, washed with water and dried to obtain the above product in the form of a yellowish-brown solid (27.7 g). (Product from another faction on a similar methodology melted at 200-201°C)

1H NMR (DMSO-d6) δ to 7.25 (s, 1H), 7,68 (DD, 1H), 8,24 (d, 1H), 8,56 (d, 1H).

Stage E: Getting 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-it

For the conversion of product pyrazolylborate acid from EXAMPLE 10, Stage D (1.5 g, 4,96 mmol) and 2-amino-3-methyl-5-chlorbenzoyl acid (0,92 g, 4,96 mmol) of the above product in the form of a solid substance was the methodology used, analogically of EXAMPLE 6, Stage D.

1H NMR (CDCl3) δ a 2.01 (s, 3H), 7,29 (s, 1H), 7,42 (d, 1H), 7,95 (d, 1H), 8,04 (m, 1H), of 8.25 (s, 1H), compared to 8.26 (d, 1H).

Stage F: Obtain 3-bromo-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of benzoxazinone with Stage E (0.20 g, 0.44 mmol) in tetrahydrofuran was added Isopropylamine (0,122 ml of 1.42 mmol)and the reaction mixture was heated to 60°C for 90 minutes and then cooled to room temperature. Tertrahydrofuran ring the solvent evaporated under reduced pressure, and the remaining solids were ground into powder with simple ether, filtered and dried to obtain these compounds, the compounds of the present invention, in the form of a solid (150 mg), TPL 159-161°C.

1H NMR (CDCl3) δ to 1.22 (d, 6H), are 2.19 (s, 3H), is 4.21 (m, 1H), of 5.99 (m, 1H), 7,05 (m, 1H), 7,22 (m, 2H), 7,39 (m, 1H), 7,82 (d, 1H), to 8.41 (d, 1H).

EXAMPLE 11

Obtain 3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of benzoxazinone EXAMPLE 10, Stage E (0.20 g, 0.44 mmol) in tetrahydrofuran was added methylamine (2.0 M solution in THF, 0,514 ml of 1.02 mmol)and the reaction mixture was heated to 60°C for 90 minutes and then cooled to room temperature. Tertrahydrofuran ring the solvent evaporated under reduced pressure and the remaining solid particles Rast is Raleigh in powder with ether, was filtered and dried to obtain these compounds, the compounds of the present invention, in the form of a solid (40 mg), TPL 162-164°C.

1H NMR (CDCl3) δ to 2.18 (s, 3H), 2.95 and (s, 3H), 6,21 (m, 1H), 7,10 (s, 1H), 7,24 (m, 2H), 7,39 (m, 1H), 7,80 (d, 1H), 8,45 (d, 1H).

The following EXAMPLE 12 illustrates an alternative obtain 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid, which can be used to obtain, for example, 3-chloro-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide and 3-chloro-N-[4-chlor-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide, by means of additional stages, presented in Examples 8 and 9.

EXAMPLE 12

Obtain 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid

Stage A: Obtain ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolecarboxylate (differently called ethyl 1-(3-chloro-2-pyridinyl)-3-pyrazolidine-5-carboxylate)

A 2-liter chetyrehosnuju flask equipped with a mechanical stirrer, thermometer, dropping funnel, partial condenser hot reflux (reflux) and the valve input of nitrogen, download absolute ethanol (250 ml) and ethanolic solution of ethoxide sodium (21%, 190 ml, 0,504 mol). The mixture was heated to boiling point under reflux at about 83�B0; C. it was Then treated with 3-chloro-2(1H)-pyridinone the hydrazone (68,0 g, 0,474 mol). The mixture was re-heated to the boiling temperature under reflux for 5 minutes. The yellow suspension was then treated dropwise with diethylmaleate (88,0 ml, 0,544 mol) over 5 minutes. While adding significantly increased the intensity of the boil under reflux. By the end of adding all of the original substance dissolved. The resulting orange-red solution was kept under reflux for 10 minutes. After cooling to 65°C, the reaction mixture was treated with glacial acetic acid (50,0 ml, 0,873 mol). Formed precipitate. The mixture was diluted with water (650 ml), causing the dissolution of the precipitate. The orange solution was cooled in an ice bath. The product began to precipitate at 28°C. the Suspension was kept at about 2°C for 2 hours. This product was isolated by filtration, washed with aqueous ethanol (40%, 3×50 ml)and then air dried on the filter for about 1 hour. The named compound was obtained in the form of vysokobarotermicheskogo light orange powder (70,3 g, 55% yield). Significant impurities according to the1H NMR was not observed.

1H NMR (DMSO-d6) δ to 1.22 (t, 3H), 2,35 (d, 1H), 2.91 in (DD, 1H), 4,20 (kV, 2H), 4,84 (d, 1H), 7,20 (DD, 1H), 7,92 (d, 1H), 8,27 (d, 1H), 10,18 (s, 1H).

Stage: Obtain ethyl 3-PI is p-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (differently called ethyl 1-(3-chloro-2-pyridinyl)-3-chloro-2-pyrazolin-5-carboxylate)

A 2-liter chetyrehosnuju flask equipped with a mechanical stirrer, a thermometer, a partial condenser hot reflux (reflux) and the valve input of nitrogen, downloaded acetonitrile (1000 ml), ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolecarboxylate (i.e. the product of Stage A) (91,0 g of 0.337 mol) and phosphorus oxychloride (35,0 ml, the 0.375 mol). Adding phosphorus oxychloride and the mixture was warmed up from 22 to 25°C and the formed precipitate. The light yellow suspension was heated to boiling point under reflux at 83°C for 35 minutes, after which the precipitate was dissolved. The resulting orange solution was kept under reflux for 45 minutes, after which it became dark green. The partial condenser hot irrigation supplied distillation attachment and deleted 650 ml of solvent by distillation. In another 2-liter chetyrehosnuju flask equipped with a mechanical stirrer, was placed sodium bicarbonate (130 g, 1.55 mol) and water (400 ml). Concentrated the reaction mixture was added to a suspension of sodium bicarbonate for 15 minutes. The resulting biphasic mixture was intensively stirred for 20 minutes, at this time, the continued evolution of gas. The mixture was diluted with dichloromethane (250 ml)and then was stirred for 50 minutes. The mixture Celite® 545 diatomaceous accelerator filter (11 g)and then filtered to remove a black resinous substance, which interfere with the separation of the phases. Since the filtrate was slowly divided into separate phases, it was diluted with dichloromethane (200 ml) and water (200 ml) and treated a large number of Celite® 545 (15 g). The mixture was filtered and the filtrate was transferred into a separating funnel. Separated heavier dark green organic layer. A loose layer (50 ml) was re-filtered, and then added to the organic layer. The organic solution (800 ml) was treated with magnesium sulfate (30 g) and silica gel (12 g), and the suspension was stirred by a magnet within 30 minutes. The suspension was filtered to remove the magnesium sulfate and silica gel, which became dark green-blue color. The filter cake was washed with dichloromethane (100 ml). The filtrate was concentrated on a rotary evaporator. This product consisted of a dark yellow oil (92.0 g, 93% yield). Observed through1H NMR only significant impurities amounted to 1% of the initial substances and 0.7% acetonitrile.

1H NMR (DMSO-d6) δ to 1.15 (t, 3H), 3,26 (DD, 1H), to 3.58 (DD, 1H), 4,11 (kV, 2H), 5.25-inch (DD, 1H), 7,00 (DD, 1H), to 7.84 (d, 1H), 8,12 (d, 1H).

Stage C: Obtain ethyl 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (differently called ethyl 1-(3-chloro-2-pyridinyl)-3-chloropyrazole-5-carboxylate)

A 2-liter h is direcgory flask, equipped with a mechanical stirrer, a thermometer, a partial condenser hot reflux (reflux) and the valve input of nitrogen, downloaded ethyl 3-chloro-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (i.e. the product of Stage B) (95% clear, with 99.5 g, 0,328 mol), acetonitrile (1000 ml), sulfuric acid (98%, of 35.0 ml, 0,661 mol). Adding sulfuric acid and the mixture was samaragreaves from 22 to 35°C. After stirring in techenie few minutes the mixture was treated with potassium persulfate (140 g, 0,518 mol). The suspension was heated to the boiling temperature under reflux at 84°C for 4.5 hours. The resulting orange suspension while still warm (50-65°C), was filtered to remove the fine white precipitate. The filter cake was washed with acetonitrile (50 ml). The filtrate was concentrated to approximately 500 ml on a rotary evaporator. In another 2-liter chetyrehosnuju flask equipped with a mechanical stirrer, was loaded water (1250 ml). The concentrated reaction mass is added to the water for about 5 minutes. The product was isolated by filtration, washed with water acetonitrile (25%, 3×125 ml), once washed with water (100 ml)and then dried overnightin the vacuumat room temperature. This product consisted of orange crystalline powder (79,3 g, 82% yield). Observed1H NMR only the significant impurities amounted to about 1.9% water and 0.6% of acetonitrile.

1H NMR (DMSO-d6) δ of 1.09 (t, 3H), of 4.16 (q, 2H), 7,31 (s, 1H), 7,71 (DD, 1H), scored 8.38 (d, 1H), 8,59 (d, 1H).

Stage D: 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (differently named 1-(3-chloro-2-pyridinyl)-3-chloropyrazole-5-carboxylic acid)

In a 1-liter chetyrehosnuju flask equipped with a mechanical stirrer, thermometer and nitrogen valve, downloaded ethyl 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (i.e. the product of Stage C) is 97.5% clean, 79,3 g, 0,270 mol), methanol (260 ml), water (140 ml), pellets of sodium hydroxide (13,0 g, 0,325 mol). Adding sodium hydroxide and the mixture was samaragreaves from 22 to 35°C, and the original substance began to dissolve. After stirring for 45 minutes at ambient conditions has dissolved all of the original substance. The resulting dark orange-brown solution was concentrated to approximately 250 ml on a rotary evaporator. Then the concentrated reaction mixture was diluted with water (400 ml). The aqueous solution was extracted with ether (200 ml). Then the aqueous layer was transferred into a 1-liter Erlenmeyer flask equipped with a magnetic stirrer. This solution was treated dropwise with concentrated hydrochloric acid (36,0 g, 0,355 mol) over about 10 minutes. The product was isolated by filtration, re-suspended in water (2×200 ml), once washed with water (100 ml), and the ATEM was air-dried on the filter for 1.5 hours. This product consisted of crystalline light brown powder (58,1 g, 83% yield). The only significant impurity observed using1H NMR, was 0.7 percent of the ether.

1H NMR (DMSO-d6) δ then 7.20 (s, 1H), 7,68 (DD, 1H), of 8.25 (d, 1H), 8,56 (d, 1H), 13,95 (wide s, 1H).

The following EXAMPLE 13 illustrates an alternative obtain 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid, which can be used to obtain, for example, 3-bromo-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide and 3-bromo-N-[4-chlor-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide, additional stages are illustrated in Examples 10 and 11.

EXAMPLE 13

Obtain 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid

Stage A1: Obtain ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (differently called ethyl 1-(3-chloro-2-pyridinyl)-3-bromo-2-pyrazolin-5-carboxylate) using oxybromide phosphorus

In a 1-liter Canareggio flask equipped with a mechanical stirrer, a thermometer, a partial condenser hot reflux (reflux) and the valve input of nitrogen, downloaded acetonitrile (400 ml), ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolecarboxylate (i.e. the product of EXAMPLE 12, Stage A) (50.0 g, 0.185 mol and oxybromide phosphorus (34,0 g, 0,119 mol). The orange suspension was heated to the boiling temperature under reflux at 83°C for 20 minutes. The resulting turbid orange solution was heated under reflux for 75 minutes, during this time formed a dense yellowish-brown crystalline residue. The partial condenser hot irrigation had with distillation attachment and collected turbid colorless distillate (300 ml). In another 1-liter chetyrehosnuju flask equipped with a mechanical stirrer, was loaded sodium bicarbonate (45 g, 0.54 mol) and water (200 ml). Concentrated the reaction mixture was added to a suspension of sodium bicarbonate for 5 minutes. The resulting biphasic mixture was intensively stirred for 5 minutes, at this time, the continued evolution of gas. The mixture was diluted with dichloromethane (200 ml)and then was stirred for 75 minutes. The mixture was treated with 5 g of Celite® 545 diatomaceous amplifier filter, and then filtered to remove a brown resinous substance. The filtrate was transferred into a separating funnel. Separated the brown organic layer (400 ml)and then treated with magnesium sulfate (15 g) and activated carbon Darco® G60 (2.0 g). The resulting suspension was stirred by a magnet within 15 minutes, and then filtered to remove the magnesium sulfate and the Glu. The green filtrate was treated with silica gel (3 g) and stirred for several minutes. Dark green-blue silica gel was removed by filtration and the filtrate was concentrated on a rotary evaporator. This product consisted of a light amber oil (58,6 g, 95% yield)which crystallized upon standing. The only significant impurity observed using1H NMR, was 0.3% acetonitrile.

1H NMR (DMSO-d6) δ to 1.15 (t, 3H), 3,29 (DD, 1H), 3,60 (DD, 1H), 4,11 (kV, 2H), 5,20 (DD, 1H), 6,99 (DD, 1H), to 7.84 (d, 1H), 8,12 (d, 1H).

Stage A2: Obtain ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate using pentabromide phosphorus

In a 1-liter Canareggio flask equipped with a mechanical stirrer, a thermometer, a partial condenser hot reflux (reflux) and the valve input of nitrogen, downloaded acetonitrile (330 ml), ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolecarboxylate (i.e. the product of EXAMPLE 12, Stage A) (52,0 g, rate of 0.193 mol), and pentabromide phosphorus (41,0 g, 0,0952 mol). The orange suspension was heated to the boiling temperature under reflux at 84°C for 20 minutes. The resulting dark red mixture was heated under reflux for 90 minutes, during this time formed a dense yellowish-brown crystalline residue. Partial con is Nestor hot irrigation had with distillation attachment and collected turbid colorless distillate (220 ml). In another 1-liter chetyrehosnuju flask equipped with a mechanical stirrer, was loaded sodium bicarbonate (40 g, 0.48 mol) and water (200 ml). Concentrated the reaction mixture was added to a suspension of sodium bicarbonate for 5 minutes. The resulting biphasic mixture was intensively stirred for 10 minutes, in that time stopped the gas. The mixture was diluted with dichloromethane (200 ml) and then was stirred for 10 minutes. The mixture was treated with Celite® 545 diatomaceous accelerator filtering (5 g)and then filtered to remove purple resinous substance. The filter cake was washed with dichloromethane (50 ml). The filtrate was transferred into a separating funnel. Separated purple-red organic layer (400 ml)and then treated with magnesium sulfate (15 g) and activated carbon Darco® G60 (2.2 g). The suspension was stirred by a magnet within 40 minutes. The suspension was filtered to remove the magnesium sulfate and charcoal. The filtrate was concentrated on a rotary evaporator. This product consisted of a dark amber oil (61,2 g, 95% yield), crystallized upon standing. The only significant impurity observed using1H NMR, was 0.7% acetonitrile.

1H NMR (DMSO-d6) δ to 1.15 (t, 3H), 3,29 (DD, 1H), 3,60 (DD, 1H), 4,11 (kV, 2H), 5,20 (DD, 1H), 6,99 (DD, 1H), to 7.84 (d, 1H), 8,12 (d, 1H).

Stage B: Obtain ethyl 3-br the m-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (differently called ethyl 1-(3-chloro-2-pyridinyl)-3-bromopyrazole-5-carboxylate)

In a 1-liter Canareggio flask equipped with a mechanical stirrer, a thermometer, a partial condenser hot reflux (reflux) and the valve input of nitrogen, downloaded ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (i.e. the product of Stages A1 and A2) (40,2 g, 0,121 mol), acetonitrile (300 ml) and sulfuric acid (98%, at 13.0 ml, 0,245 mol). Adding sulfuric acid and the mixture was samaragreaves from 22 to 36°C. After stirring for several minutes, the mixture was treated with potassium persulfate (48,0 g, 0,178 mol). The suspension was heated to the boiling temperature under reflux at 84°C for 2 hours. The resulting orange suspension is still warm (50-65° (C) was filtered to remove a white precipitate. The filter cake was washed with acetonitrile (2×50 ml). The filtrate was concentrated to about 200 ml on a rotary evaporator. In another 1-liter chetyrehosnuju flask equipped with a mechanical stirrer, was loaded water (400 ml). The concentrated reaction mass is added to the water for about 5 minutes. The product was isolated by filtration, washed successively water acetonitrile (20%, 100 ml) and water (75 ml)and then air-dried on the filter for 1 hour. This product consisted of orange crystalline powder (36,6 g, 90% yield). The only significant primes the mi, observed1H NMR, were 1% of the unknown substance and 0.5% acetonitrile.

1H NMR (DMSO-d6) δ of 1.09 (t, 3H), of 4.16 (q, 2H), 7,35 (s, 1H), 7,72 (DD, 1H), 8,39 (d, 1H), 8,59 (d, 1H).

Stage C: 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (differently named 1-(3-chloro-2-pyridinyl)-3-bromopyrazole-5-carboxylic acid)

300 ml Canareggio flask equipped with a mechanical stirrer, thermometer and nitrogen valve, downloaded ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (i.e. the product of Stage (B) (98,5% clean, 25,0 g, 0,0756 mol), methanol (75 ml), water (50 ml), and pellets of sodium hydroxide (3,30 g, 0,0825 mol). Adding sodium hydroxide and the mixture was samaragreaves from 29 to 34°C and initial substance began to dissolve. After stirring for 90 minutes at ambient conditions, dissolved all of the original substance. The resulting dark orange solution was concentrated to approximately 90 ml on a rotary evaporator. Concentrated the reaction mixture then was diluted with water (160 ml). The aqueous solution was extracted with ether (100 ml). Then the aqueous layer was transferred into a 500 ml Erlenmeyer flask, equipped with a magnetic stirrer. This solution was treated dropwise with concentrated hydrochloric acid (8,50 g, 0,0839 mol) over about 10 minutes. This product was isolated by filtration, VN is V suspended in water (2× 40 ml), the top layer was once washed with water (25 ml)and then air-dried on the filter for 2 hours. This product consisted of crystalline, yellowish-brown powder (20,9 g, 91% yield). The only significant impurities observed using1H NMR were about 0.8% of an unknown substance and 0.7% of the ether.

1H NMR (DMSO-d6) δ to 7.25 (s, 1H), 13,95 (wide s, 1H), 8,56 (d, 1H), of 8.25 (d, 1H), 7,68 (DD, 1H).

The following EXAMPLE 14 illustrates an alternative obtain ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate, which can be used for cooking, for example, ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (i.e. the product of EXAMPLE 13, Stage B).

EXAMPLE 14

Obtain Ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate from ethyl 3-chloro-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate using hydrogen bromide.

The hydrogen bromide was passed through a solution of ethyl 3-chloro-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (i.e. the product of EXAMPLE 12, Stage B) (8,45 g of 29.3 mmol) in dibromomethane (85 ml). After 90 minutes stopped the flow of gas and the reaction mixture was washed with an aqueous solution of sodium bicarbonate (100 ml). The organic phase was dried and evaporated under reduced pressure to obtain the titled product as oil (9.7 g, 99% yield), Chris is alisauskas when standing.

1H NMR (CDCl3) δ to 1.19 (t, 3H), 3,24 (1/2 of AB in the sample avj, J=9,3, 17.3 Hz, 1H), 3,44 (1/2 of AB in the sample avj, J=11,7, 17.3 Hz, 1H), 4,18 (kV, 2H), 5.25 IN X from AVH, 1H, J=9,3, to 11.9 Hz), 6,85 (DD, J=4,7, 7.7 Hz, 1H), 7,65 (DD, J=1,6, 7,8 Hz), 8,07 (DD, J=1,6, 4.8 Hz, 1H).

The following EXAMPLE 15 illustrates obtain ethyl 1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[[(4-were)sulfonyl]oxy]-1H-pyrazole-5-carboxylate, which can be used for the preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate according to the method similar to the method described in EXAMPLE 14.

EXAMPLE 15

Obtain ethyl 1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[[(4-were)sulfonyl]oxy]-1H-pyrazole-5-carboxylate

To a mixture of ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolecarboxylate (i.e. the product of EXAMPLE 12, Stage A) (10.0 g, 37,1 mmol) and p-toluensulfonate (7,07 g, 37,1 mmol) in dichloromethane (100 ml) was added drop wise addition of triethylamine (3.75 g, 37,1 mmol) at 0°C. further added portions of the p-toluensulfonate (0.35 g, to 1.83 mmol) and triethylamine (0,19 g, 1.88 mmol). The reaction mixture was then left to warm to room temperature and was stirred overnight. Then the mixture was diluted with dichloromethane (200 ml) and washed with water (3×70 ml). The organic phase was dried and evaporated to obtain the above product in the form of oil (13,7 g, 87% yield), which was slowly formed crystals. The product, as stylizowane from ethyl acetate/hexanol, melted at 99,5-100°C.

IR (nuol) ν 1740, 1638, 1576, 1446, 1343, 1296, 1228, 1191, 1084, 1027, 948, 969, 868, 845 cm-1.

1H NMR (CDCl3) δ to 1.19 (t, 3H), of 2.45 (s, 3H), 3,12 (1/2 of AB in the sample avj, J=17,39 Hz, 1H), 3.33 and (1/2 of AB in the sample avj, J=17,5, and 11.8 Hz, 1H), 4.16 the (q, 2H), 5,72 (X from AVH, 1H, J=9, 11.8 Hz, 1H), 6,79 (DD, J=4,6, and 7.7 Hz, 1H), was 7.36 (DD, J=8,4, 2H), 7,56 (DD, J=1,6, 7,8 Hz, 1H), 7,95 (d, J=8,4 Hz, 2H), 8,01 (DD, J=1,4, 4.6 Hz, 1H).

EXAMPLE 16

Obtaining N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxamide

Stage A: Obtain ethyl 1-(3-chloro-2-pyridinyl)-2,3-dihydro-3-oxo-1H-pyrazole-5-carboxylate

To a suspension of ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolecarboxylate (i.e. the product of EXAMPLE 12, Stage (A) (27 g, 100 mmol), stirred in dry acetonitrile (200 ml)was added sulfuric acid (20 g, 200 mmol) in one portion. The reaction mixture was razziali before formation of a pale green, almost transparent solution before re-thicken before the formation of a pale yellow suspension. For one portion was added potassium persulfate (33 g, 120 mmol), and then the reaction mixture was heated at a low boil under reflux for 3.5 hours. After cooling using an ice bath the precipitate white solids were removed by filtration and discarded. The filtrate was diluted with water (400 ml)and then was extracted three times with ethyl EF the rum (700 ml). Concentration of the combined ether extracts to reduced volume (75 ml) caused precipitation is not quite white solid (3.75 g), which was collected by filtration. The mother solution of ether were further concentrated to obtain a second output not quite white precipitate (4,2 g), which was also collected by filtration. From the aqueous phase also precipitated not quite white solid; it is solid (4.5 g) was collected by filtration to obtain the total amount 12,45 g of the named compound.

1H NMR (DMSO-d6) δ of 1.06 (t, 3H), 4,11 (kV, 2H), 6,34 (s, 1H), and 7.6 (t, 1H), 8,19 (d, 1H), and 8.5 (d, 1H), 10,6 (s, 1H).

Stage: Obtain ethyl 1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxylate

To a suspension of ethyl 1-(3-chloro-2-pyridinyl)-2,3-dihydro-3-oxo-1H-pyrazole-5-carboxylate (i.e. the product of Stage A) (0.8 g, 3 mmol), stirred in dry acetonitrile (15 ml) at -5°C, was added potassium carbonate (0.85 grams, 6,15 mmol). This suspension was stirred for 15 minutes at 20°C. the Mixed slurry is then cooled to 5°C, was added dropwise 2,2,2-triptorelin triftorbyenzola (0.8 g, of 3.45 mmol). The reaction mixture was heated to room temperature and then heated to the boiling temperature under reflux, during which time thin layer chromatography showed complete reaction. To the reaction is Oh mixture was added water (25 ml), which then was extracted with ethyl ether. The ether extract was dried over magnesium sulfate and concentrated to obtain these compounds (of 1.05 g) as a pale yellow oil.

1H NMR (CDCl3) δ to 1.21 (t, 3H), 4,20 (kV, 2H), 4,63 (kV, 2H), 6,53 (s, 1H), and 7.4 (t, 1H), 7,9 (d, 1H), and 8.5 (d, 1H).

Stage C: Obtain 1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxylic acid

To a stirred solution of ethyl 1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxylate (i.e. the product of Stage (B) (0,92 g, 2.8 mmol) in methanol (15 ml) was added water (5 ml), which caused the turbidity of the reaction mixture. An aqueous solution of sodium hydroxide (50%, 1.5 g, 19.2 mmol) was added dropwise, and the reaction mixture was stirred at room temperature for 30 minutes, during which the reaction mixture was again transparent. Was added water (20 ml) and the reaction mixture was extracted with ethyl ether, which was discarded. The aqueous phase was acidified to pH 2 using concentrated hydrochloric acid, and then extracted with ethyl acetate (50 ml). An ethyl acetate extract was washed with water (20 ml) and brine (20 ml), dried over magnesium sulfate and concentrated to obtain these compounds, isolated as a white solid (0.8 g).

1H NMR (DMSO-d6) δ and 4.9 (q, 2H), 6.75 in (s, 1H), and 7.6 (t, 1H), and 8.2 (d, 1H), 8,55 (d, H), 13,7 (wide s, 1H).

Stage D: Obtain 6-chloro-8-methyl-2H-3,1-benzoxazin-2,4(1H)-dione

To a suspension of 2-amino-3-methyl-5-chlorbenzoyl acid (i.e. the product of EXAMPLE 6, Stage A) (97 g, 520 mmol), stirred in dry dioxane (750 ml) at room temperature was added dropwise trichloromethylcarbonate (63 g, 320 mmol). The reaction mixture is slowly exothermically heated to 42°C, and the solid is almost completely dissolved before again formed a thick slurry. After this suspension was stirred at ambient temperature for 2.5 hours, the named compound was isolated by filtration, washed with ethyl ether, and dried to obtain the product of these compounds are obtained in the form of a white solid (98 g).

1H NMR (DMSO-d6) δ 2,3 (s, 3H), of 7.70 (s, 1H), of 7.75 (s, 1H), and 11.2 (s, 1H).

Stage E: Obtain 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it

To a suspension of 1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxylic acid (i.e. the product of Stage C) (7.9 g, 24 mmol), stirred in dichloromethane (100 ml)was added N,N-dimethylformamide (4 drops). Oxalicacid (4,45 g, 35 mmol) was added dropwise over 45 minutes. The resulting solution was stirred at room temperature for 4 hours, and then concentri is ovali under vacuum. The selected acid chloride acid was dissolved in dry acetonitrile (10 ml) was added to a suspension of 6-chloro-8-methyl-2H-3,1-benzoxazin-2,4(1H)-dione (i.e. the product of Stage D) (4.9 g, 23 mmol), stirred in dry acetonitrile (14 ml). Added pyridine (10 ml) and this solution was heated at the boiling point under reflux for 6 hours. After cooling using ice baths collected precipitate white solids (9,15 g). Range1H NMR of the collected sediment showed peaks corresponding to the mentioned connection and the residual of the original substance 6-chloro-8-methyl-2H-3,1-benzoxazin-2,4(1H)-dione. A small portion of the collected precipitate was recrystallized from acetonitrile to obtain pure titled product, melting at 178-180°C.

1H NMR (DMSO-d6) δ 1,72 (s, 3H), 4,96 (kV, 2H),? 7.04 baby mortality (s, 1H), and 7.7 (t, 1H), of 7.75 (s, 1H), and 7.9 (s, 1H), 8.3 (l, 1H), and 8.6 (d, 1H).

Stage F: Obtaining N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxamide

To a suspension of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it (i.e. the product of sediment Stage E) (3,53 g, 7.5 mmol) in tetrahydrofuran (15 ml) was added dropwise methylamine (2.0 M solution in THF, 11 ml, 22 mmol)and the resulting solution was stirred at room temperature for 45 minutes. Then thin the chromatography showed that the reaction is complete. Was added ethyl ether (100 ml)and the reaction mixture was stirred for 2 hours until the formed precipitate. The precipitate was collected by filtration, and then recrystallized from acetonitrile to obtain white solids (0,82 g). The second part of the white solid (0.35 g) was precipitated from the mother liquor of acetonitrile and was collected by filtration. The original mother liquor ether/tetrahydrofuran was concentrated to dryness and the remaining solid particles recrystallized from acetonitrile to obtain a third portion of the white solid (0.95 g). Combined three collection components 2,12 g (after drying), these compounds, the compounds of the present invention, isolated in the form of a white solid, melting at 195-197°C.

1H NMR (CDCl3) δ to 2.18 (s, 3H), of 2.92 (d, 3H), of 4.66 (q, 2H), 6,15 (kV, 1H), and 6.6 (s, 1H), 7,2 (s, 1H), 7,25 (s, 1H), 7,35 (m, 1H), and 7.8 (d, 1H), 8,45 (d, 1H), 10.0 g (s, 1H).

The following EXAMPLE 17 illustrates an alternative obtain 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid, which can be used for cooking, for example, 1-(3-chloro-2-pyridinyl)-N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide further stages shown in Example 4.

EXAMPLE 17

Obtain 1-(3-chloro-2-pyridinyl)-3-(three is tormentil)-1H-pyrazole-5-carboxylic acid

Stage a: 3-chloro-2(1H)-pyridinone(2,2,2-Cryptor-1-methylethylidene)hydrazone

1,1,1-Triptorelin (7,80 g, to 69.6 mmol) was added to 3-chloro-2(1H)-pyridinethione (differently-called (3-chloropyridin-2-yl)hydrazine) (10 g, was 69.7 mmol) at 20-25°C. After complete addition, the mixture was stirred for approximately 10 minutes. The solvent was removed under reduced pressure and the mixture was distributed between ethyl acetate (100 ml) and saturated aqueous sodium carbonate (100 ml). The organic layer was dried and evaporated. Chromatography on silica gel (washed with ethyl acetate) gave the product as not quite white solid (11 g, 66% yield), TPL 64-64,5°C (after crystallization from ethyl acetate/hexanol).

IR (nuol) ν 1629, 1590, 1518, 1403, 1365, 1309, 1240, 1196, 1158, 1100, 1032, 992, 800 cm-1.

1H NMR (CDCl3) δ 2,12 (c, 3H), 6,91-6,86 (m, 1H), of 7.64-to 7.61 (m, 1H), 8,33 - 8,32 (m, 2H).

MS m/z 237 (M+).

Stage: Getting ethylhydrocupreine (3-chloro-2-pyridinyl)(2,2,2-Cryptor-1-methylethylidene)hydrazide (differently called ethylhydrocupreine (3-chloro-2-pyridinyl)(2,2,2-Cryptor-1-methylethylidene)hydrazine)

The triethylamine (20,81 g, 0,206 mol) was added to 3-chloro-2(1H)-pyridinone(2,2,2-Cryptor-1-methylethylidene)hydrazone (i.e. the product of Stage A) (32,63 g, 0,137 mol) in dichloromethane (68 ml) at 0°C. Utilisateur (18.75 g, 0,137 mol) in dichloromethane (69 ml) was added dropwise what this mixture at 0° C. the Mixture was left to warm to 25°C approximately 2 hours. The mixture was cooled to 0°C and added dropwise additional portions of ethylchloroformiate (3.75 g, 27,47 mmol) in dichloromethane (14 ml). After about an additional 1 hour the mixture was diluted with dichloromethane (450 ml)and the mixture was washed with water (2×150 ml).

The organic layer was dried and evaporated. Chromatography on silica gel (washed with 1:1 ethyl acetate-hexane) gave the product as a solid (42,06 g, 90% yield), TPL 73,0-73,5°C (after crystallization from ethyl acetate/hexanol).

IR ν (nuol) 1751, 1720, 1664, 1572, 1417, 1361, 1330, 1202, 1214, 1184, 1137, 1110, 1004, 1043, 1013, 942, 807, 836 cm-1.

1H NMR (DMSO-d6, 115° (C) to 1.19 (t, 3H), 1,72 (br s, 3H), 4,25 (kV, 2H), 7,65 (DD, J=8,3, a 4.7 Hz, 1H), to 8.20 (DD, J=7,6, 1.5 Hz, 1H), 8,55 (d, J=3.6 Hz, 1H).

MS m/z 337 (M+).

Stage C: Obtain ethyl 1-(3-chloro-2-pyridinyl)-4,5-dihydro-5-hydroxy-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate

Ethylhydrocupreine (3-chloro-2-pyridinyl)(2,2,2-Cryptor-1-methylethylidene)hydrazide (i.e. the product of Stage (B) (5 g, of 14.8 mmol) in dimethyl sulfoxide (25 ml) was added to hydrate tetrabutylammonium the fluoride (10 g) in dimethyl sulfoxide (25 ml) for 8 hours. Upon completion of the addition the mixture was poured into acetic acid (3.25 g) in water (25 ml). After stirring at 25°C overnight, the mixture was then extracted with toluene (4×25 ml), the combined toluene extracts were washed with water (50 ml), was dried and evaporated to obtain a solid substance. Chromatography on silica gel (washed with 1:2 ethyl acetate : hexane) gave the product as a solid (2.91 in g, 50% yield, containing approximately 5% 3-chloro-2(1H)-pyridinone(2,2,2-Cryptor-1-methylethylidene)hydrazone), TPL 78-78,5°C (after recrystallization from ethyl acetate/hexanol).

IR (nuol) ν 3403, 1726, 1618, 1582, 1407, 1320, 1293, 1260, 1217, 1187, 1150, 1122, 1100, 1067, 1013, 873, 829 cm-1.

1H NMR (CDCl3) δ to 1.19 (s, 3H), 3,20 (1/2 sample ABZ, J=18 Hz, 1H), 3,42 (1/2 sample ABZ, J=18 Hz, 1H), 4,24 (kV, 2H), 6,94 (DD, J=7,9, and 4.9 Hz, 1H), 7,74 (DD, J=7,7, 1.5 Hz, 1H), 8,03 (DD, J=4,7, 1.5 Hz, 1H).

MS m/z 319 (M+).

Stage D: Obtain ethyl 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate

Sulfuric acid (concentrated, 2 drops) was added to ethyl 1-(3-chloro-2-pyridinyl)-4,5-dihydro-5-hydroxy-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate (i.e. the product of Stage (C) (1 g, 2,96 mmol) in acetic acid (10 ml) and the mixture was heated to 65°C for approximately 1 hour. The mixture was left to cool to 25°C and most of the acetic acid was removed under reduced pressure. The mixture was distributed between saturated aqueous sodium carbonate (100 ml) and ethyl acetate (100 ml). Further the aqueous layer was extracted with ethyl acetate (100 ml). The combined organic extracts were dried and evaporated to obtain the product as oil (0.66 g, 77 output).

IR (neat) ν 3147, 2986, 1734, 1577, 1547, 1466, 1420, 1367, 1277, 1236, 1135, 1031, 973, 842, 802 cm-1.

1H NMR (CDCl3) δ of 1.23 (t, 3H), 4,25 (kV, 2H), 7,21 (s, 1H), of 7.48 (DD, J=8,1, the 4.7 Hz, 1H), 7,94 (DD, J=6,62 Hz, 1H), 8,53 (DD, J=4,7, 1.5 Hz, 1H).

MS m/z 319 (M+).

Stage E: Obtain 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

Potassium hydroxide (0.5 g, 85%, 2.28 mmol) in water (1 ml) was added to ethyl 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate (i.e. the product of Stage (D) (0.66 g, 2,07 mmol) in ethanol (3 ml). After about 30 minutes the solvent was removed under reduced pressure and the mixture was dissolved in water (40 ml). This solution was washed with ethyl acetate (20 ml). The aqueous layer was acidified with concentrated hydrochloric acid and was extracted with ethyl acetate (3×20 ml). The combined extracts were dried and evaporated to obtain the product as a solid (0,53 g, 93% yield), TPL 178-179°C (after crystallization from hexane-ethyl acetate).

IR (nuol) ν 1711, 1586, 1565, 1550, 1440, 1425, 1292, 1247, 1219, 1170, 1135, 1087, 1059, 1031, 972, 843, 816 cm-1.

1H NMR (DMSO-d6) δ to 7.61 (s, 1H), to 7.77 (m, 1H), 8.30 to (d, 1H), at 8.60 (s, 1H).

Examples 18 and 19 illustrate an alternative reaction conditions described in EXAMPLE 10, step E and EXAMPLE 8, step E, respectively.

EXAMPLE 18

Getting 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-it

Meth is sulphonylchloride (1.0 ml, 1.5 g, 13 mmol) was dissolved in acetonitrile (10 ml), and the mixture was cooled to -5°C. a Solution of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the product pyrazolylborate acid of EXAMPLE 10, Stage D) (3,02 g, 10 mmol) and pyridine (1.4 ml, 1.4 g, 17 mmol) in acetonitrile (10 ml), was added dropwise within 5 minutes at -5 to 0°C. while adding the formed suspension. The mixture was stirred 5 minutes at this temperature, and then added a mixture of 2-amino-3-methyl-5-chlorbenzoyl acid (i.e. the product of EXAMPLE 6 Stage (A) (1.86 g, 10 mmol) and pyridine (2.8 ml, 2.7 g, 35 mmol) in acetonitrile (10 ml), again rinsing with acetonitrile (5 ml). The mixture was stirred for 15 minutes at -5 to 0°C, and then was added dropwise methanesulfonamide (1.0 ml, 1.5 ml, 13 mmol) in acetonitrile (5 ml) for 5 minutes at a temperature of from -5 to 0°C. the Reaction mixture was stirred another 15 minutes at this temperature, then left to slow warming to room temperature, and stirred 4 h Water (20 ml) was added dropwise, and the mixture was stirred for 15 minutes. Then the mixture was filtered and the solids washed with 2:1 acetonitrile-water (3×3 ml), then acetonitrile (2×3 ml), and dried in nitrogen atmosphere to obtain this product as a pale yellow powder, 4,07 g (90,2% crude yield), melting at 203-205°C. HPLC of this product used with the em Bond® RX-C8 chromatographic column (4.6 mm × 25 cm, eluent 25-95% acetonitrile/pH 3, water)showed a main peak corresponding to the mentioned connection and having to 95.7% of the total area of the peaks chromatography.

1H NMR (DMSO-d6) δ 1,72 (s, 3H) 7,52 (s, 1H), 7,72 for 7.78 (m, 2H), 7,88 (m, 1H), of 8.37 (DD, 1H), to 8.62 (DD, 1H).

EXAMPLE 19

Obtaining 6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it

Methanesulfonamide (1.0 ml, 1.5 g, 13 mmol) was dissolved in acetonitrile (10 ml)and the mixture was cooled to -5°C. a Solution of 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the product of the carboxylic acid of EXAMPLE 8, Stage D) (2.58 g, 10 mmol) and pyridine (1.4 ml, 1.4 g, 17 mmol) in acetonitrile (10 ml), was added dropwise within 5 minutes at -5 0°C. while adding the formed suspension. The mixture was stirred 5 minutes at this temperature, and then added at once 2-amino-3-methyl-5-chlorobenzoyl acid (i.e. the product from EXAMPLE 6, Stage A) (1.86 g, 10 mmol). Then a solution of pyridine (2.8 ml, 2.7 g, 35 mmol) in acetonitrile (10 ml) was added dropwise over 5 min at -5 to 0°C. the Mixture was stirred for 15 minutes at -5 to 0°C, and then was added dropwise methanesulfonamide (1.0 ml, 1.5 ml, 13 mmol) in acetonitrile (5 ml) over 5 min at -5 to 0°C. the Reaction mixture was stirred for 15 minutes at this temperature, then left for a slow nagrevaniya room temperature and stirred 4 o'clock Water (15 ml) was added dropwise, and the mixture was stirred for 15 minutes. Then the mixture was filtered and solids were washed with 2:1 acetonitrile-water (3×3 ml), then acetonitrile (2×3 ml), and dried in nitrogen atmosphere to obtain this product as a pale yellow powder, a 3.83 g (94,0% crude yield), melting at 199-201°C. HPLC product using Bond® RX-C8 chromatographic column (4.6 mm × 25 cm, eluent 25-95% acetonitrile/pH 3 water)showed a main peak corresponding to the mentioned connection, and having 97.8% of the total chromatographic peak area.

1H NMR (DMSO-d6) δ 1,72 (s, 3H), of 7.48 (s, 1H), 7,74-7,80 (m, 2H), 7,87 (m, 1H), of 8.37 (DD, 1H), to 8.62 (DD, 1H).

Using the techniques described herein together with methods known in this field, can be obtained the following compounds of Tables 1-6. In the Tables use the following abbreviations:tmeans tertiary,smeans secondary,nmeans normal, imeans ISO, Me means methyl, Et means ethyl, Pr means propyl, i-Pr means isopropyl and Bu means butyl.

Table 1

Table 2

Table 3

Table 4

Table 5

Table 6

Formulations/Applications

It was found that the compounds of Formula I not only have an excellent effect of controlling phytophagous invertebrate pests, but also have a suitable residual picture content and movement of substances through the plant provides protection for plants developing from vegetative planting material (seedlings), such as a seed, bulb, rhizome, tuber, clubnelukovic, or stem, or stalk of a leaf. (In the context of this description control invertebrate pests" means the suppression of the development bespozvonochnykh pest (num is mortality), causing a significant reduction in eating and other damages and losses caused by pests; and related expressions are defined similarly.) Thus, this invention provides a method of protecting plant seedlings from phytophagous invertebrate pests by contacting seedling or locus seedling with a biologically effective amount of the compounds of Formula I. the Method according to this invention, using a sufficient amount of the compounds of Formula I, has also been described to protect not only the seedling, as well as a new sprout growing from a seedling.

As described herein, "treatment" seedling or locus seedling means the application of the compounds of Formula I, or a composition containing this compound, seedling or the locus of the seedling, so that the compound of Formula I is brought into contact with the seedling; related concepts, such as "impregnation"is defined similarly. Thus, when the seedling brought into contact with a biologically effective amount of the compounds of Formula I, the compound protects it from damage phytophagous invertebrate pests. The compound of Formula I protects not only the outer surface of the seedling, but it will be absorbed by the seedling, forming the seedling containing the compound of Formula I. If the seedling was brought into contact with a sufficient number of connection is of Formula I, adsorbed sufficient for the formation of biologically effective concentrations of the compounds of Formula I within the seedling, and, consequently, seedling comprises a biologically effective amount of compounds of Formula I. If a sufficient amount of the compounds of Formula I are used to increase the concentration of the compounds of Formula I in the seedling to a concentration higher than the minimum for biological efficiency, in this case, the movement of substances in plants can move the biologically effective concentration of the compounds of Formula I to the developing shoots and roots, and also to protect them.

As indicated in this description, the term "invertebrate pests" include arthropods, gastropods and worms, as pests of economic significance. The term "phytophagous invertebrate pests" refers to invertebrate pests, causing damage plants by eating, such as eating the foliage, stem, leaf, fruit or seed tissue, or by exhaustion vascular juices of plants. The term "arthropods" includes insects, mites, centipedes, of, woodlice and simpleno. The term "gastropods include snails, slugs and other Stabilisatoren. The term "round worms" includes herbivorous nematodes (T is p or Class Nematode). Economically important phytophagous invertebrate pests include: larvae detachment of Lepidoptera, such as "marching worms, Cutworm, cabbage moths, and heliothine collection Scoops (for example, deciduous "marching worm"(Spodoptera fugiperdaJ. E. Smith), beet "marching worm"(Spodoptera exiguaHübner), black winter worm(Agrotis ipsilonHufnagel), scoop neither(Trichoplusia niHübner), leafroller caterpillar-Packed tobacco(Heliothis virescensFabricius)); svalilsya, cheglecova moths, caterpillars, building spider nest, mermaidy and pests, skeletonema leaves from the family of the Liquidation (for example, corn borer(Ostrinia nubilalisHübner), caterpillar devouring orange(Amyelois transitellaWalker), scoop fire(Crambus caliginosellusClemens), meadow moths(Herpetogramma licarsisalisWalker)); leafrollers, listorti-Packed, moth and caterpillar pests of fruits in the family Leafroller (e.g., Codling moth(Cydia pomonellaL. (L. means Linnaeus)), moth vine(Endopiza viteanaClemens), tortrix Oriental peach(Grapholita molestaBusck)); and many other economically important Lepidoptera (e.g., the cabbage moth(Plutella xylostellaL.), pink boxed cotton worm(Pectinophora gossypiellaSaunders), Gypsy moth(Lymantria disparL.)); eating the foliage, larvae and adults of the order Coleoptera, including the debt of the spouts from the families of fungus weevils, Weevil, and Curculionidae (e.g., the weevil cotton(Anthonomus grandisBoheman), rice weevil water(Lissorhoptrus oryzophilusKuschel), the rice weevil(Sitophilus oryzaeL.)), small leaf, cucumber beetle blaska, root worms, beetles, Colorado potato beetles and flea-miners the Chrysomelidae (e.g., Colorado potato beetle(Leptinotarsa decemlineataSay), blocka Dlinnaya Western(Diabrotica virgifera virgiferaLeConte)); Khrushchev and other beetles from the family of scarab beetles (for example, garden chafer Japanese(Popillia japonicaNewman) and European standards(Rhizotrogus majalisRazoumowsky)); wireworms from the family of click beetles and bark beetles from the family of Beetles; adult and larvae of earwig squad, including earwig family Earwig (for example, haverty ordinary(Forficula auriculariaL.), black haverty(Chelisoches morioFabricius)); adults and nymphs of troops Bugs and Ramnarine, such as bugs-kanaky of family Kanaki, cicadas from the family of Singing cicadas, cycatki (for example,Empoascaspp.) from the family of Cycatki, delphacidae of families Vulgarity and Delfini, the humpback from the family of the Humpback, listblock family Psyllid, whiteflies from the family of Whiteflies, aphids from the family of Avidity, Phylloxera from the family of Phylloxera, mealybugs from the family of Walochnik, the scale of the families of Podushechnye, the Scale and Giant drawing is s, bugs-lace collection Lace, bugs-defenders of the family of the Defenders, bugs whiteflies (for example,Blissusspp.) and other naselniki of family Naselniki, pennisi family Cercopidae, bugs pumpkin from the family of Crevice, and krasnolipe and krasnolipe cotton from family Krasnolipe; adult and larvae squad Acari (mites)such as clasic spider mites and red mites in the family of Spider mites (e.g., spider mite(Panonychus ulmiKoch), clasic spider bimaculated(Tetranychus urticaeKoch), McDaniel mite(Tetranychus mcdanieliMcGregor)), mites in the family Plastinki (for example, citrus clasic(Brevipalpus lewisiMcGregor)), gall mites and Bud mites in the family Haloorange and other mites that eat the leaves; adult and sub-adult squad Orthoptera, including kuznechikova, real locusts and crickets (e.g., locusts (for example,Melanoplus sanguinipesFabricius,M. differentialisThomas), American locust (for example,Schistocerca americanaDrury), desert locust(Schistocerca gregariaForskal), migratory locust(Locusta migratoriaL.), mole crickets(Gryllotalpaspp.)); adult and sub-adult detachment of Diptera, including leaf-mining flies, midges, Drosophila (Tephritidae), cereal fly (for example,Oscinella fritL.), soil maggots, and other Dlinnoyu; adult and sub-adult troop Bajracharya, t is the number of thrips (Thrips tabaciLindeman) and other trips, eating leaves; and millipedes in the unit of Scutigera; and representatives of the Type or class of the Nematodes, including such important agricultural pests like nematodes root growths of the genusMeloidogyne,nematode pests of the genusPratylenchus,stubby root nematodes of the genusTrichodorus,etc.

Specialists in this field will be clear that not all compounds are equally effective against all pests. The compounds of this invention are particularly active against pests in the unit of Lepidoptera (e.g.,Alabama argillaceaHübner (worm cotton sheet),Archips argyrospilaWalker (tortrix),A. rosanaL. (Listorti Rosanna (Golden) and other species ofArchips (the Russian equivalent none), Ognevka Asian stem (borers of rice stem),Cnaphalocrosis medinalisGuenee (rice leaf roller),Crambus caliginosellusClemens (Ognevka caterpillar corn horses),Crambus teterrellusZincken (Ognevka caterpillar-grass),Cydia pomonellaL. (Codling moth),Earias insulanaBoisduval (Sunny bollworm),Earias vittellaFabricius (scoop (spotted bollworm)),Helicoverpa armigeraHübner (American boxed worm),Helicoverpa zeaBoddie (cotton bollworm),Heliothis virescensFabricius (scoop),Herpetogramma licarsisalisWalker (the beet webworm),Lobesia botranaDenis & Schiffermüller (moth vine),Pectinophora gossypiellaSaunders (pink boxed cotton worm),Phyllocistis citrella Stainton (citrus leafminer (the Russian equivalent none)),Pieris brassicaeL. (large white butterfly),Pieris rapaeL. (small white butterfly),Plutella xylostellaL. (cabbage moth),Spodoptera exiguaHübner (beet "marching worm"),Spodoptera lituraFabricius (tobacco winter worm, cluster caterpillar),Spodoptera frugiperdaJ. E. Smith (deciduous "marching worm"),Trichoplusia niHübner (scoop) andTuta absolutaMeyrick (tomato leafminer (the Russian equivalent is missing). The compounds of this invention are also commercially meaningful action against members of the squad Ramnarine, including:Acyrthisiphon pisumHarris (pea aphid),Aphis craccivoraKoch (black aphids alfalfa).Aphis fabaeScopoli (black aphids bean),Aphis gossypiiGlover (cotton aphid),Aphis pomiDe Geer (aphid Codling),Aphis spiraecolaPatch (aphid Tamagawa),Aulacorthum solaniKaltenbach (aphid vonkova),Chaetosiphon fragaefoliiCockerell (strawberry aphid),Diuraphis noxiaKurdjumov/Mordvilko (aphid, Russian wheat),Dysaphis plantagineaPaaserini (aphid pink),Eriosoma lanigerumHausmann (aphid carovana Apple),Hyalopterus pruniGeoffroy (aphids, mealy plum),Lipaphis erysimiKaltenbach (aphid lookupentry),Metopolophium dirrhodumWalker (cereal aphid),Macrosipum euphorbiaeThomas (potato aphid leaf),Myzus persicaeSulzer (peach aphid),Nasonovia ribisnigriMosley (lettuce aphid),Pemphigusspp. (root aphids and gallarraga aphid),Rhopalosiphum maidisFitch (aphid corn leaf),Rhopalosiphum padiL. t the I ordinary bird-cherry), Schizaphis graminumRondani (cereal aphid common),Sitobion avenaeFabricius (cereal aphid English),Therioaphis maculataBuckton (spotted alfalfa aphid (the Russian equivalent none)),Toxoptera aurantiiBoyer de Fonscolombe (tea aphid), andToxoptera citricidaKirkaldy (citrus aphid);Adelgesspp. (Charles);Phylloxera devastatrixPergande (phylloxera Hickory);Bemisia tabaciGennadius (tobacco whitefly, bemicia tabaci batata),Bemisia argentifoliiBellows &Perring (whiteflies large-leaved Magnolia),Dialeurodes citriAshmead (citrus whitefly) andTrialeurodes vaporariorumWestwood (greenhouse whitefly);Empoasca fabaeHarris (Cicada potato),Laodelphax striatellusFallen (Cicada brown fine),Macrolestes quadrilineatusForbes (Cicada Asteraceae),Nephotettix cinticepsUhler (green leafhopper (the Russian equivalent none)),Nephotettix nigropictusStal (Cicada rice),Nilaparvata lugensStal (brown planthopper (the Russian equivalent none)),Peregrinus maidisAshmead (Cicada corn),Sogatella furciferaHorvath (white-backed planthopper (the Russian equivalent none)),Sogatodes orizicolaMuir (rice delphacid (the Russian equivalent is absent),Typhlocyba pomariaMcAtee (white moth Codling),Erythroneouraspp. (moth vine);Magicidada septendecimL. (periodical cicada (the Russian equivalent is missing));Icerya purchasiMaskell (mealybug Australian grooved),Quadraspidiotus perniciosusComstock (San Jose scale California);Planococcus citriRisso (mealybug citrus);Pseudococcusspp. (mealy worm is s other systems); Cacopsylla pyricolaFoerster (Copperhead pear),Trioza diospyriAshmead (listblock Jurmala). These compounds also have activity against members from the order Hemiptera including:Acrosternum hilareSay (green stink bug (the Russian equivalent none)),Anasa tristisDe Geer (bug pumpkin),Blissus leucopterus leucopterusSay (bug dall),Corythuca gossypiiFabricius (cotton bug),Cyrtopeltis modestaDistant (bug tomatoey),Dysdercus suturellusHerrich-Schäffer (Krasnogo cotton),Euchistus servusSay (brown stink bug (the Russian equivalent none)),Euchistus variolariusPalisot de Beauvois (one-spotted stink bug (the Russian equivalent none)),Graptosthetusspp. (the complex of najemnikov),Leptoglossus corculusSay (leaf-footed pine seed bug),Lygus lineolarisPalisot de Beauvois (klopik meadow),Nezara viridulaL. (bug cotton gardening),Oebalus pugnaxFabricius (rice stink bug (the Russian equivalent none)),Oncopeltus fasciatusDallas (large milkweed bug (the Russian equivalent none)),Pseudatomoscelis seriatusReuter (cotton fleahopper). Other orders of insects controlled by the compounds according to this invention, include Bajracharya (for example,Frankliniella occidentalisPergande (trips Western wheat),Scirthothrips citriMoulton (citrus thrips),Sericothrips variabilisBeach trips soy), andThrips tabaciLindeman (thrips), and Coleoptera (e.g.,Leptinotarsa decemlineataSay (Colorado potato beetle),Epilachna varivestisMulsant (beetle bean Mexico the RCM) and wireworms of the genera Agriotes(Chuck sowing), AthousorLimonius).

The method according to the present invention is applicable for almost all kinds of plants. Seeds that can be treated include, for example, wheat seeds(Triticum aestivumL.), durum wheat(Triticum durumDesf.), barley(Hordeum vulgareL.) oat(Avena sativaL.), rye seed(Secale cerealeL.), maize(Zea maysL.), sorghum(Sorghum vulgarePers.), rice(Oryza sativaL.), wild rice(Zizania aquaticaL.), cotton(Gossypium barbadenseL.G. hirsutumL.), flax(Linum usitatissimumL.), sunflower(Helianthus annuusL.), soybean(Glycine maxMerr.), kidney beans(Phaseolus vulgarisL.), beans (Lima(Phaseolus limensisMacf.), Fava beans(Vicia fabaL.), garden peas(Pisum sativumL.), peanut(Arachis hypogaeaL.), alfalfa(Medicago sativaL.), beet(Beta vulgarisL.), garden salad(Lactuca sativaL.), canola(Brassica rapaL. and In. napusL.)crops of cabbage, such as cabbage, cauliflower and broccoli (Brassica oleraceaL.), turnip(Brassica rapaL.), mustard Sarepta(Brassica junceaCoss.), mustard black(Brassica nigraKoch), tomatoes(Lycopersicon esculentumMill.), potatoes(Solanum tuberosumL.), pepper(Capsicum frutescensL.), eggplant(Solanum melongenaL.), tobacco(Nicotiana tabacum),cucumbers(Cucumis sativusL.), melon musk(Cucumis meloL.), watermelon(Citrullus vulgarisSchrad.), pumpkin(Curcurbita pepoL., C.moschataDuchesne. and C.maximaDuchesne.), carrots(Daucus carotaL.), cinii(Zinnia elegansJacq.), to the Mei (for example, Cosmos bipinnatusCav.), chrysanthemum(Chrysanthemumspp.), melkosopochnik(Scabiosa atropurpureaL.), lion throat(Antirrhinum majusL.), gerbera(Gerbera jamesoniiBolus), Kajima paniculate(Gypsophila paniculataL., G.repensL. and G.elegansBieb.), gvozditsika (for example,Limonium sinuatumMill.,L. sinenseKuntze.), liatris (for example,Liatris spicataWilld.,L. pycnostachyaMichx.,L. scariosaWilld.), Lisianthus (for example,Eustoma grandiflorum(Raf.) Shinn), yarrow (for example,Achillea filipendulinaLam.,A. millefoliumL.), marigold (for example,Tagetes patulaL.T. erectaL.), violet tricolor (for example,Viola cornutaL.V. tricolorL.), balsam (for example,Impatiens balsaminaL.) petunias(Petuniaspp.), geranium(Geraniumspp.) and Coleus (for example,Solenostemon scutellarioides(L.) Codd). Not only seeds, but also roots, tubers, bulbs or globalwave, including their viable slices can be obrabotki in accordance with the invention, for example, from potatoes(Solanum tuberosumL.), Yam(Ipomoea batatasL.), Yam(Dioscorea cayenensisLam. andD. rotundataPoir.), garden onion (for example,Allium cepaL.), Tulip(Tulipaspp.), gladiolus(Gladiolusspp.), Lily(Liliumspp.), Narcissus(Narcissusspp.), Dahlia (for example,Dahlia pinnataCav.), iris(Iris germanicaL. and other species), Crocus(Crocusspp.), anemones(Anemonespp.), hyacinth(Hyacinthspp.), Paducheva Luke citystage(Muscarispp.), freesia (for example,Freesia refractaKlatt,F. armstrongiiW. Wats), decorative panels, the main onion (Alliumspp.), wood sorrel common(Oxalisspp.), Bluebell bifolia(Scilla peruvianaL. and other species), cyclamen(Cyclamen persicumMill. and other species), chionodoxa(Chionodoxa luciliaeBoiss. and other species), sea onion(Puschkinia scilloidesAdams), zantedeschi(Zantedeschia aethiopicaSpreng., Z.elliottianaEngler and other species), gloxinia(Sinnigia speciosaBenth. & Hook.) and tuberous begonias(Begonia tuberhybridaVoss.). In accordance with this invention can be processed portion of the stem, including such plants as sugar cane(Saccharum officinarumL.), clove(Dianthus caryophyllusL.), florists chrysanthemum(Chrysanthemum mortifoliumRamat.), begonia(Begoniaspp.), geranium(Geraniumspp.), of Coleus (for example,Solenostemon scutellarioides(L.) Codd) and poinsettia(Euphorbia pulcherrimaWilld.). In accordance with this invention can be processed slices of leaves, including leaf begonias(Begoniaspp.), African violets (for example,Saintpaulia ionanthaWendl.) and stonecrop(Sedumspp.). The above cereals, vegetables, ornamental (including flowers) and fruit crops are illustrative, and should not be construed as limiting in any cases. A preferred variant implementation of the invention in relation to spectrum control of invertebrate pests and economic values are the seed treatment of cotton, maize, soybeans and rice, and processing of tubers and bulbs potatoes is, Yam, garden onions, tulips, daffodils, Crocus and hyacinth.

The loci of seedlings can be treated with a compound of Formula I with the help of many different ways. All that is needed is to put on a seedling, or close enough to the seedling, biologically effective amount of the compounds of Formula I, so that this connection could be absorbed by this seedling. The compound of the Formula I can be applied by methods such as irrigation growth medium containing a seedling, a solution or dispersion of the compounds of Formula I, by mixing the compounds of Formula I with the growth medium and the cultivation of seedling growth in the treated environment (for example, processing seedling pots), or various kinds of processing seedlings, whereby the compound of Formula I is applied at the seedling before it is grown in the growth environment.

In these methods, the compound of Formula I is mainly used in the form of composition or arrangement with a carrier acceptable for agriculture, including at least one liquid diluents, dry solvents or surfactants. For this invention fits a large number of compounds, the most suitable types of compounds depend on the method of application. As is well known to specialists in this field, the purpose is security and adonispussy transportation, measurement and distribution of chemical, protecting crops, as well as the optimization of its biological effectiveness.

Depending on the application method used formulations include liquids, such as solutions (including mulgirigala concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally may be condensed in the gels. Used compositions additionally include solids, such as dusty, powders, granules, pellets, tablets, films and the like, which may be water-dispersible ("wet") or water-soluble. The active component can be (micro)encapsulated and further formed into a slurry or solid composition; an alternative may be encapsulated the entire composition of the active component (or "covered"). Encapsulation can control or delay the release of the active ingredient. Sprayable formulations can be extended in a suitable medium and used in amounts of spray from about one to several hundred liters per hectare. Vysokokontsentrirovannye composition primarily used as intermediate compounds for the prepared compounds.

The compositions typically contain an effective amount of the active ingredient, a diluent and a surface which is an active ingredient within the following approximate intervals, complements to 100 percent by weight.

Mass%
The active ingredientThinnerSurfactant
Water-dispersible and water-soluble granules, tablets and powders5-900,941-15
Suspensions, emulsions, solutions (including mulgirigala concentrates)5-5040-950-15
Dusty1-2570-990-5
Granules and pellets0,01-995-99,990-15
Strong songs90-990-100-2

Typical solid diluents are described in Watkins et al.,Handbook of Insecticide Dust Diluents and Carriers,2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden,Solvents Guide,2nd Ed., Interscience, New York, 1950.McCutcheon's Emulsifiers and Detergents and McCutcheon''s Functional Materials (North America and International Editions, 2001)The Manufactuing Confection Publ.Co., Glen Rock, New Jersey, as well as Sisely and Wood,Encyclopedia of Surface Active Agents,Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended their use. All formulations can contain minor amounts of add is to to reduce foaming, clumping, oxidation, growth of microorganisms and the like, or thickeners for increasing the viscosity.

Surfactants include, for example, ethoxylated alcohols, ethoxylated ALKYLPHENOLS, ethoxylated esters of sorbitol and fatty acids, ethoxylated amines, ethoxylated fatty acids, esters and oils, diallylmalonate, alkyl sulphates, alkylarylsulfonate, silicon substances, N,N-dialkylamide, glycol esters, phosphate esters, ligninsulfonate, naphthalenesulfonate, condensates of formaldehyde, polycarboxylate and copolymers, including polyoxyethylene/polyoxypropylene block copolymers. Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc, infusorial land, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Liquid diluents include, for example, water, N,N-dimethylformamide, dimethylsulfoxide, N-alkylpyridine, ethylene glycol, polypropyleneglycol, propylene carbonate, dibasic esters, paraffins, alkyl benzenes, alkylnaphthalene, olive, castor oil, flax seed, Tung oil, sesame oil, corn, peanut, cottonseed oil, soybean, rapeseed oil behold the Yeni, and coconut oil, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, and alcohols, such as methanol, cyclohexanol, decanol, benzyl and tetrahydrofurfuryl alcohol.

Solutions, including mulgirigala concentrates can be prepared by simple mixing of the components. Dusty and powders can be prepared by mixing, and grinding in a hammer mill and hydraulic mill. Suspensions are usually prepared by wet grinding; see, for example, U.S. 3060084. Granules and pellets can be prepared by spraying the active substance onto the prepared granular carriers or by agglomeration techniques. Cm. Browning, "Agglomeration",Chemical Engineering,December 4, 1967, pp 147-48,Perry's Chemical Engineer''s Handbook,4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and the publication of the international application WO 91/13546. Pellets can be prepared as described in US 4172714. Water-dispersible and water-soluble granules can be prepared as described in US 4144050, US 3920442 and DE 3246493. Tablets can be prepared as shown in US 5180587, US 5232701 and US 5208030. Films can be prepared as described in GB 2095558 and US 3299566.

For additional information concerning the composition, see T. S. Woods, "The Formulator''s Toolbox - Product Forms for Modern Agriculture" inPesticide Chemistry and Bioscience, The Food-Environmnt Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. Cm. also US 3235361, Col. 6, line 16 to Col. 7, line 19 and Examples 10-41; US 3309192, Col. 5, line 43 by Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; US 2891855, Col. 3, line 66 by Col. 5, line 17 and Examples 1-4; Klingman,Weed Control as a Science,John Wiley and Sons, Inc., New York, 1961, pp 81-96; and Hance et al,Weed Control Handbook,8th Ed., Blackwell Scientific Publications, Oxford, 1989.

Seedling (planting material) or a plant grown from it, can be protected from invertebrate pests in accordance with the present invention, the process comprising contacting seedling or locus seedling with a composition comprising a biologically effective amount of the compounds of Formula I, its N-oxide or its salts acceptable for agriculture. This invention includes the seedling exposed to a composition comprising a biologically effective amount of the compounds of Formula I, its N-oxide or its salts acceptable for agriculture, and an effective amount of at least one other biologically active compound or agent. Compositions used for treatment of seedlings or plants grown from it) according to this invention may also contain (in addition to the Formulas (I) an effective amount of one or more other biologically act the main compounds or agents. Suitable additional compounds or agents include insecticides, fungicides, nematicides, bactericides, acaricides, growth regulators, such as growth promoters roots, chemosterilants, polychemical, repellents, attractants, pheromones, feeding stimulants, other biologically active compounds or entomopathogenic bacteria, virus or fungi for the formation of a multi-component pesticide giving an even broader spectrum of agricultural use. Examples of such biologically effective compounds or agents that can be manufactured formulations of the compounds of this invention are: insecticides such as abamectin, Arafat, acetamiprid, amidolytic (S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, buprofezin, carbofuran, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyfluthrin, beta-cyfluthrin, cigalotrin, lambda cigalotrin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, diflubenzuron, dimetilan, giovanola, emamectin, endosulfan, esfenvalerate, ethiprole, fanatical, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flucythrinate, teaflavin, lufenuron (UR-50701), flufenoxuron, fonofos, halogenated, hexaflumuron, Imidacloprid, indoxacarb, isofenphos is, lufenuron, Malathion, metaldehyde, metamidophos, methidathion, methomyl, methoprene, Methoxychlor, monocrotophos, methoxyfenozide, nithiazine, novaluron, noviflumuron (XDE-007), oxamyl, parathion, parathionmethyl, permethrin, Fort, fosalan, phosmet, phosphamidon, pirimicarb, profenofos, pymetrozine, pyridalyl, pyriproxifen, rotenon, spinosad, spiromesifen (BSN 2060), sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosulfat-sodium, tralomethrin, trichlorfon and triflumuron; fungicides, such as acibenzolar AZOXYSTROBIN, benomyl, blasticidin-S, Bordeaux mixture (sulfate trehosnovnoy copper), bromuconazole, cropropamide, captafol, Captan, carbendazim, chloroneb, CHLOROTHALONIL, copper oxychloride, copper salt, cyflufenamid, having cymoxanil, tsyprokonazolu, cyprodinil, (S) - for 3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide (RH-7281), diclocil (S-2900), declomycin, dicloran, difenoconazol, (S) - for 3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3-(phenylamino)-4H-imidazol-4-one (RP 407213), dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, Dodin, edifenphos, epoxiconazol, famoxadone, fenamidone, fenarimol, fenbuconazole, paneramic (SZX0722), fenpiclonil, fenpropidin, fenpropimorph, fentiazac, fistinginaction, fluazinam, fludyoksonil flamethower (RPA 403397), plumart/fluorin (SYP-L190), fluoxastrobin (HEC 5725), FL is henansal, flusilazol, flutolanil, flutriafol, folpet, foretelling, parallaxis, parameter (S-82658), hexaconazole, ipconazole, iprobenfos, iprodion, isoprothiolane, kasugamycin, kresoxim-methyl, MANCOZEB, MANEB, mefenoxam, mepronil, metalaxyl, metconazole, metamyosyn/phenominalrose (SSF-126), metrafenone (AC 375839), myclobutanil, neo-Asotin (metanational ferric), nicobifen (BAS 510), orysastrobin, oxadixyl, penconazole, pencycuron, provenzal, prochloraz, propamocarb, propiconazol, probenecid (DPX-KQ926), prothioconazole (JAU 6476), pirivenas, pyraclostrobin, Pyrimethanil, PROCHILE, jenoxifen, spiroxamine, sulfur, tebuconazole, tetraconazole, thiabendazol, leflunomid, thiophanate-methyl, thiram, tadini, triadimefon, triadimenol, tricyclazole, Trifloxystrobin, triticonazole, validamycin and vinclozolin; nematicides, such as aldicarb, oxamyl and fenamiphos; bactericides such as streptomycin; acaricides, such as amitraz, chinomethionat, Chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin, fenpropathrin, fenpyroximate, hexythiazox, propargite, and pyridaben tebufenpyrad; and biological agents such asBacillus thuringiensisincluding ssp.aizawaiandkurstaki,the Delta endotoxinBacillus thuringiensis, baculovirus, and entomopathogenic bacteria, viruses and fungi.

A General reference for these agricultural techniques is the only plant protection products is The Pesticide Manual, 12th Edition,C. D. S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2000.

Preferred insecticides and acaricides for mixing with compounds of Formula I include pyrethroids such as cypermethrin, cigalotrin, cyfluthrin and beta-cyfluthrin, esfenvalerate, fenvalerate and tralomethrin; carbamates, such as fanatical, methomyl, oxamyl and thiodicarb; neonicotinoids such as clothianidin, Imidacloprid and thiacloprid; blockers of neuronal sodium channels, such as indoxacarb, insecticidal macrocyclic lactones such as spinosad, abamectin, abamectin, avermectin and emamectin; antagonists γ-aminobutyric acid (GABA), such as endosulfan, ethiprole and fipronil; insecticidal urea, such as flufenoxuron and triflumuron; simulators youth hormones such as giovanola and pyriproxyfen; pymetrozine; and amitraz. Preferred biological agents for mixing with compounds of this invention includeBacillus thuringiensisandBacillus thuringiensisthe Delta endotoxin, as well as natural and genetically modified viral insecticides, including representatives of the family Baculoviridae, and entomopathogenic fungi.

The preferred growth regulators plant for mixing with compounds of the Formula I in compositions for obrabotki sliced stalks are 1H-indole-3-acetic who Isleta, 1H-indole-3-butane acid and 1-naphthalenyloxy acid and their salts acceptable for agriculture, esters and amide derivatives, such as 1-naphthaleneacetic. Preferred fungicides for mixing with compounds of Formula I include fungicides used for seed treatment, such as thiram, MANEB, MANCOZEB and Captan.

In the following examples, all percentages are given by weight and all of the compositions prepared in the usual way. The numbers of compounds are compounds of table pointer A.

An EXAMPLE of A

Wettable powder, %:
Connection 20865,0
Ether dodecylpyridinium2,0
Ligninsulfonate sodium4,0
Silicoaluminate sodium6,0
Montmorillonite (calcinated)23,0

EXAMPLE B

Granules, %:
Connection 48610,0
Granules attapulgite (low-volatile substance, of 0.71/0.30 mm; U.S.S. No. 25-50 lattice sieve)90,0

EXAMPLE C

Extruded extruded pellets, %:
Connection 50925,0
Anhydrous sodium sulfate10,0
Untreated ligninsulfonate calcium5,0
Alkylnaphthalene sodium1,0
Calcium/magnesium bentonite59,0

EXAMPLE D

Mulgirigala concentrates, %:
Connection 51620,0
The mixture of sulfonates, soluble in oil, and esters of polyoxyethylene10,0
Isophorone70,0

For irrigation growth environment data structures must deliver the compounds of Formula I, mainly after dilution with water, in solution or in the form of particles small enough to ensure that they remained dispergirovannykh in the liquid. Water dispersible or soluble powders, granules, tablets, mulgirigala concentrates, concentrates, aqueous suspensions and such compositions are suitable for water irrigation growth environment. Irrigation is best suited to handle the growth environment of relatively high porosity, such as light, soil, or artificial growth medium containing porous mA the materials, such as peat moss, perlite, vermiculite and the like. Liquid for irrigation, containing the compound of the Formula I, can also be added to the liquid growth medium (i.e. hydroponics), which makes the compound of Formula I, part a liquid growth medium. The person skilled in the art will understand that the amount of the compounds of Formula I that are required in the liquid for irrigation for effective control of invertebrate pests (i.e. biologically effective amount) will vary depending on the type of seedling of compounds of Formula I, the duration and extent of the required protection bespozvonochnykh pest, which are controlled and environmental factors. The concentration of the compounds of Formula I in the liquid for irrigation is mainly from 0.01 h/million (ppm) to 10,000 ppm, more typically from about 1 ppm to 100 h/million person skilled in the art will easily be able to determine the biologically effective concentration required for the desired level of control of invertebrate pests.

To handle the growth environment of the compound of the Formula I can be used by mixing it in the form of dry powder or granular composition of the growth medium. Because this method of application does not require pre-dispersion or dissolution in water, dry powder or granular formulations is not what it should be soluble or dispersible in a high degree. At that time, as in the pot for seedlings can be processed all growth environment on agricultural fields for economic and environmental reasons are usually treated only the soil near the seedling. To minimize the difficulties and costs associated with its use, the composition of the compounds of Formula I can be most effectively applied simultaneously with the growing seedling (e.g., seeding). For use inside the furrows, the composition of the Formula I (the most convenient granular composition) is applied after the "Shoe of the sower". For T-band application, the compounds of the Formula I is applied in a band over the row behind the Shoe of the sower and usually behind or before covering catacom. The person skilled in the art will understand that the amount of the compounds of Formula I required locus growth environment for effective control of invertebrate pests (i.e. biologically effective amount will vary depending on the type of seedling, the compounds of Formula I, the desired duration and degree of protection, bespozvonochnykh of pests for which control and environmental factors. The concentration of the compounds of Formula I in the locus of the growth medium is usually from 0.0001 ppm to 100 ppm, more typically about 0.01 ppm to 10 h/million person skilled in the art will easily determine the biologically effective amount is in, needed for the desired level of control of phytophagous invertebrate pests.

The seedling can be processed directly by soaking it in a solution or dispersion of the compounds of Formula I. Although this method of application is used for all types of seedlings, for providing protective control invertebrate pests, for growing plants handling large seeds (e.g., having an average diameter of at least 3 mm) is more efficient than processing of small seeds. Treatment of seedlings, such as tubers, bulbs, globalwave, rhizomes and stems leaves and cuttings, in addition to the seedling may also provide for efficient processing of the developing plants. The compositions used for irrigation growth environment, mainly also used for impregnating treatments. Impregnating the environment contains negoitations liquid, mainly water-based, although it can contain nepatologickou number of other solvents, such as methanol, ethanol, isopropanol, ethylene glycol, propylene glycol, propylene carbonate, benzyl alcohol, dibasic esters, acetone, methyl acetate, ethyl acetate, cyclohexanone, dimethyl sulfoxide and N-organic, which can be used to enhance the solubility of the compounds of Formula I and Pronin is incurred in the seedling. Surfactants can facilitate wetting of the seedling and the penetration of the compounds of Formula I. the person skilled in the art will understand that the amount of the compounds of Formula I required for impregnating environment for effective control of invertebrate pests (i.e. biologically effective amount will vary depending on the type of seedling, the compounds of Formula I, the desired duration and degree of protection, bespozvonochnykh pest, which exercise control, and environmental factors. The concentration of the compounds of Formula I in the impregnating medium is usually from 0.01 ppm to 10000 ppm, more typically from about 1 ppm to 100 h/million person skilled in the art will easily determine the biologically effective concentration needed for the desired level of control of phytophagous invertebrate pests. Steeping time can vary from 1 minute to 1 day or longer. In fact, the seedling may remain in the processing fluid during germination or sprouting (for example, the germination of rice seeds before sowing). Because the shoots and roots out of the Testa (cover seeds, sprout and the root directly in contact with the solution containing the compound of Formula I. For treatment of germinating seeds, crops with large seeds, such to the to rice, processing time is approximately 8 to 48 hours, for example, the typical is about 24 hours. Shorter processing time most heavily used for handling small seeds.

Seedlings can also be coated with a composition comprising a biologically effective amount of compounds of Formula I. the coatings according to this invention is capable of slow release of compounds of Formula I by diffusion in the seedling and the environment. Coating materials include dry dusty or powders, adhesiolysis on seedling under the action of sticky substances such as methylcellulose or the Arabian gum. Coatings can also be prepared from suspension concentrates, water-dispersible powders or emulsions, suspended in water, sprayed on the seedling in a rotating drum and then dried. The compounds of Formula I dissolved in the solvent may be sprayed on the treated seedling, with subsequent evaporation of the solvent. Such compositions preferably include components that promote adhesion of coating materials on the seedling. These compositions can also contain surface-active substances that promote wetting of the seedling. Used solvents should not be phyto-toxic to seedling; mainly, and the use of water, but can be used other volatile solvents of low phytotoxicity, such as methanol, ethanol, methyl acetate, ethyl acetate, acetone, etc. individually or in combination. Volatile solvents are, whose boiling point under normal conditions, approximately less than 100°C. the Drying should be conducted in a way which does not damage the sprout or not cause premature germination or growth.

The thickeners of the coatings can vary from adhesive dusty to thin films and the pellet layer thickness from about 0.5 to 5 mm. Materials to cover the seedlings in this invention can contain more than one adhesive layer, only one of which must contain the compound of Formula I. For small seeds are most suitable, mainly pellets, because of their ability to deliver biologically effective amount of the compounds of Formula I is not limited to the surface of the seed, and drazhirovanie small seeds also facilitates the transfer of seeds and boarding procedures. Due to the large size and surface area large seeds and bulbs, tubers, globalwave and rhizomes and their viable slices are usually not pellitero, but instead covered with powders or thin films.

Seedlings in contact with the compounds of the Formula I, in accordance with this invention includes the t in itself the seeds. Suitable seeds include seeds of wheat, durum wheat, barley, oats, rye seed, maize, sorghum, rice, wild rice, cotton, flax, sunflower, soybeans, kidney beans, Lima beans, Fava beans, garden peas, peanuts, alfalfa, beet, garden salad, canola crops of cabbage, turnip, Sarepta mustard, black mustard, tomato, potato, pepper, eggplant, tobacco,,cucumber, musk melon, watermelon, pumpkin, carrots, cinii, cosmai, chrysanthemums, melkosopochnik, lion's throat, gerberas, Kajima paniculate, gvozditsika, liatris, Lisianthus, yarrow, marigold, violet tricolor, Impatiens, petunias, geraniums and Coleus. Famous are the seeds of cotton, maize, soybeans and rice. Seedlings in contact with the compounds of the Formula I, in accordance with this invention also include rhizomes, tubers, bulbs or globalwave, or their viable slices. Suitable rhizomes, tubers, bulbs or globalwave, or their viable sections include those from potato, sweet potato, Yam, garden onion, Tulip, gladiolus, lilies, daffodils, Dahlia, iris, Crocus, anemones, hyacinth, Paducheva Luke citystage, freesia, decorative bow, common wood sorrel, Bluebell orchids, cyclamen, chionodoxa, sea onion, zantedeschi, gloxinia and tuberous begonias. Features Mimi are rhizomes, tubers, bulbs and globalwave or viable part of the potato, Yam, garden onions, tulips, daffodils, Crocus and hyacinth. Seedlings exposed to compounds of the Formula I, in accordance with this invention also include the stems and stalks of leaves.

In one embodiment, the seedling exposed to the compound of Formula I, is a seedling, covered with a composition comprising a compound of Formula I, itNthe oxide or salt is acceptable for agriculture and the film former or adhesive agent. The compositions of this invention containing a biologically effective amount of the compounds of Formula I, itNthe oxide or salt is acceptable for agriculture and the film former or adhesive agent may additionally contain an effective amount of at least one additional biologically active compound or agent. Known are compositions containing (in addition to the component of the Formula I and the foaming agent and adhesive agent) anthropogenie substance of the group consisting of pyrethroids, carbamates, neonicotinoids, neuronal blockers of sodium channels, insecticidal macrocyclic lactones, antagonists γ-aminobutyric acid (GABA), insecticidal urea and imitators youth of the mountains is over. Also characteristic are the compositions containing (in addition to the component of the Formula I and the film former or adhesive agent) at least one additional biologically active compound or agent selected from the group consisting of abamectin, Arafat, acetamiprid, amidolytic (S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, buprofezin, carbofuran, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyfluthrin, beta-cyfluthrin, cigalotrin, lambda cigalotrin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, diflubenzuron, dimetilan, giovanola, emamectin, endosulfan, esfenvalerate, ethiprole, fanatical, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flucythrinate, teaflavin, lufenuron (UR-50701), flufenoxuron, fonofos, halogenated, hexaflumuron, Imidacloprid, indoxacarb, isofenphos, lufenuron, Malathion, metaldehyde, metamidophos, methidathion, methomyl, methoprene, Methoxychlor, monocrotophos, methoxyfenozide, nithiazine, novaluron, noviflumuron (XDE-007), oxamyl, parathion, parathion-methyl, permethrin, Fort, fosalan, phosmet, phosphamidon, pirimicarb, profenofos, pymetrozine, pyridalyl, pyriproxifen, rotenon, spinosad, spiromesifen (BSN 2060), sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos, tet is flowinfo, thiacloprid, thiamethoxam, thiodicarb, thiosulfat-sodium, tralomethrin, trichlorfon and triflumuron, aldicarb, oxamyl fenamiphos, amitraz, chinomethionat, Chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents such asBacillus thuringiensisincluding ssp.aizawaiandkurstaki,the Delta endotoxinBacillus thuringiensis, baculovirus, and entomopathogenic bacteria, viruses and fungi. Also characteristic are the compositions containing (in addition to the component of the formula I and the film former or adhesive agent) at least one additional biologically active compound or agent selected from fungicides containing groups acibenzolar, AZOXYSTROBIN, benomyl, blasticidin-S, Bordeaux mixture (sulfate trehosnovnoy copper), bromuconazole, cropropamide, captafol, Captan, carbendazim, chloroneb, CHLOROTHALONIL, copper oxychloride, copper salt, cyflufenamid, having cymoxanil, tsyprokonazolu, cyprodinil, (S) - for 3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide (RH-7281), diclocil (S-2900), declomycin, dicloran, difenoconazol, (5)for 3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3-(phenylamino)-4H-imidazol-4-one (RP 407213), dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, Dodin, edifenphos, epoxiconazol, famoxadone, f is amidon, fenarimol, fenbuconazole, paneramic (SZX0722), fenpiclonil, fenpropidin, fenpropimorph, fentiazac, fistinginaction, fluazinam, fludyoksonil flamethower (RPA 403397), plumart/fluorin (SYP-L190), fluoxastrobin (HEC 5725), Fluconazol, flusilazol, flutolanil, flutriafol, folpet, fosetyl-aluminum, parallaxis, parameter (S-82658), hexaconazole, ipconazole, iprobenfos, iprodion, isoprothiolane, kasugamycin, kresoxim-methyl, MANCOZEB, MANEB, mefenoxam, mepronil, metalaxyl, metconazole, metamyosyn/phenominalrose (SSF-126), metrafenone (AC 375839), myclobutanil, neo-Asotin (metanational ferric), nicobifen (BAS 510), orysastrobin, oxadixyl, penconazole, pencycuron, provenzal, prochloraz, propamocarb, propiconazol, probenecid (DPX-KQ926), prothioconazole (JAU 6476), pirivenas, pyraclostrobin, Pyrimethanil, PROCHILE, jenoxifen, spiroxamine, sulfur, tebuconazole, tetraconazole, thiabendazol, leflunomid, thiophanate-methyl, thiram, tadini, triadimefon, triadimenol, tricyclazole, Trifloxystrobin, triticonazole, validamycin and vinclozolin (especially the composition, where at least one biologically active compound or agent selected from the fungicides of the group consisting of Tirana, MANEB, makaseb and Captan).

Mainly material of the present invention, covering the seedling, contains a compound of Formula I, a foaming agent or ADH is Intrusive substance. The material for the coating may additionally contain auxiliaries, such as dispersing agents, surfactants, carriers and optional anti-foam agents and dyes. The person skilled in the art will understand that the amount of the compounds of Formula I required for material to cover for the effective control of invertebrate pests (i.e. biologically effective amount will vary depending on the type of seedling, the compounds of Formula I, the desired duration and degree of protection, bespozvonochnykh pest, which exercise control, and environmental factors. The material for the coating should not delay germination or germination seedling and must be highly effective to reduce damage to plants during the damaging plant life cycle phase bespozvonochnykh pest against which conduct processing. The material for the coating containing a sufficient amount of the compounds of Formula I, can provide regulatory protection from bespozvonochnykh pest approximately 120 days or even longer. Generally the amounts of the compounds of Formula I is in the range of from about 0.001 to 50% by weight of seedling, seed more often in the range of from about 0.01 to 50% by weight of seed, and most typically for large seeds in the interval prima is but from 0.1 to 10% by weight of the seed. However, there may be used a large amount, up to 100% or more, in particular for drazhirovanija small seed to extend protective control bespozvonochnykh pest. For seedlings, such as bulbs, tubers, globalwave and rhizomes and their viable slices, and stem and leaf cuttings, mainly, the amount of the compounds of Formula I is in the range of from about 0.001 to 5% by weight of seedling, using a higher percentage for smaller seedlings. The person skilled in the art can easily determine the biologically effective amount needed for the desired level of control of phytophagous invertebrate pests.

Film former or adhesive agent, which is part of the material to cover the seedling, preferably consists of an adhesive polymer, which may be natural or synthetic and does not have fitotoksicheskie action to cover the seedling. Film former or adhesive agent may be selected from polyvinyl acetate, copolymers of polyvinyl acetate, hydrolyzed polyvinyl acetate, copolymers of polyvinylpyrrolidones, polyvinylene alcohols, copolymers polyvinylene alcohols, polivinilovogo ether copolymer polivinilbutilovy ether-maleic anhydride, waxes, latex polymers, cellulose, including e is icellulse and methylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, polyvinylpyrrolidones, alginates, dextrins, maltodextrins, polysaccharides, fats, oils, proteins, Karay gum, guar gum, tragakant, polysaccharide gums, adhesives, Arabian gum, shellac, polymers and copolymers of vinylidenechloride, polymers and copolymers based on proteins of soybeans, lignosulfonate, acrylic copolymers, starches, polyvinylacetate, sainov, gelatin, carboxymethyl cellulose, chitosan, polyethylene oxide, polymers and copolymers of acrylamide, polyhydroxyethylmethacrylate, monomers of methylacrylamide, alginate, ethyl cellulose, polychloroprene and syrups or mixtures thereof. The preferred film-forming agents and adhesive agents include polymers and copolymers of vinyl acetate, the copolymer of polyvinylpyrrolidones and water-soluble waxes. Especially preferred are the copolymers polyvinylpyrrolidones and water-soluble waxes. Defined above polymers include polymers known in this area and for example some of them are defined as Agrimer® VA 6 and Press® KST. The amount of film former or adhesive agent in the composition is carried out mainly in the range of from about 0.001 to 100% by weight of seedling. For large seeds to icesto agent or adhesive agent is usually in the range of from about 0.05 to 5% by weight of the seed; for small seeds, the number is usually in the range of about 1 to 100%, but can exceed 100% of the mass of seed when drazhirovanii. For other seedlings quantity of film former or adhesive agent is usually in the range from 0.001 to 2% by weight of seedling.

Materials, known as excipients, can also be used in the coatings according to this invention for treatment of seedlings for control of invertebrate pests and well-known specialists in this field. Excipients contribute to the production or processing method of the seedlings and include, but are not limited to, dispersing agents, surfactants, carriers, antifoaming agents and dyes. Used dispersing agents may include anionic surfactants, water-soluble to a high degree, such Borresperse™ CA, Morwet® D425 and the like. Used surfactants may include nonionic surfactants with a high degree of water solubility, as Pluronic® F108, Brij® 78 and the like. Used media may include liquids, like water and oil, which is soluble in water, such as alcohols. Used carriers can also include fillers, as wood flour, clay, AK is ivireanul coal, infusoria earth, finely powdered inorganic particles, calcium carbonate and the like. Clay and inorganic particles, which can be used include calcium bentonite, kaolin, China clay, talc, perlite, mica, vermiculite, silica, quartz powder, montmorillonite and mixtures thereof. Antifoaming agents may include water-dispersible liquid containing paliggenesia siloxanes, as Rhodorsil® 416. The dyes may include water-dispersible liquid coloring composition, as Pro-lzed® Red Colorant. The person skilled in the art will understand that this is not a comprehensive listing of excipients for the compositions, and that can be used other well-known materials, depending on cover seedling, the compounds of Formula I used in coating materials. Suitable examples of excipients for the formulations include those listed here and listed in McCutcheon's 2001, Volume 2: Functional Materials, published by MC Publishing Company. The number of auxiliary substances used for composition, may be different, but basically the mass of the components will be in the range from about 0.001 to 10000% by weight of seedling, the percentages above 100% is mainly use for drazhirovanija small seeds. For depalletising seeds number of excipients in the composition in the basis of the nom is from about 0.01 to 45% by weight of the seed and is usually from about 0.1 to 15% by weight of the seed. For seedlings, other than seeds, the amount of excipients in the composition mainly is approximately from 0.001 to 10% by weight of seedling.

To perform the coating of the seeds according to the present invention can be used conventional methods and coating materials. Dusty or powders can be applied by tumble-proof seedling composition containing the compound of Formula I and an adhesive agent for adhesion of dusty or powder to the seedling and not crumble during packing or transportation. Dusty or powders can also be caused by adding dust or powder directly to the drum for drazhirovanija seedlings and subsequent spraying of liquid media for seed and drying. Dusty and powders containing compound of the Formula I, can also be caused by processing (e.g., immersion) at least part of the seedling solvent, such as water, optionally containing an adhesive agent, and immersing the processed part in the dust or powder. This method can be particularly used to cover sections of the stems. Seedlings can also be immersed in the compositions containing the compounds of Formula I of the wetted powders, solutions, suspoemulsions, mulgirigala concentrates and emulsions in water, and then dried or directly planted in a growth medium. The seedlings, such as bulbs, tubers, Klubnaya the hospitals and rhizomes, you only need one cover layer to provide a biologically effective amount of the compounds of Formula I.

Seedlings can also be coated by spraying the suspension concentrate directly in the apparatus for drazhirovanija seedlings, and then drying seedling. Alternatively, the seedlings can be sprayed other types of compositions, as moistened powders, solutions, suspoemulsions, mulgirigala concentrates and emulsions in water. This method is particularly used for applying film coatings on the seeds. Specialists in this field available in various mechanisms and methods for coating. Suitable methods include the methods listed in P. Kosters et al.,Seed Treatment: Progress and Prospects,1994 BCPC Monograph No. 57 and in the references listed there. Three well-known methods include the use of cover in the dryer, a fluidized bed technique and flowing layers. Seedlings, such as seeds, before coating can be pre-sorted by size. After covering the seedlings dried, and then optional sarantuyaa by migrating into the sorting machine. These machines are known in the prior art, for example, a typical machine used in the calibration of seed corn (maize) in agricultural production.

For seed coating, seed and material to cover mixed in any conventional AP is Arata to cover the seeds. The speed and application depends on the seed. For large oblong seeds such as cotton seeds, suitable apparatus for coating seeds contains a rotating vessel with rising blades, rotating at sufficient rpm to maintain the rotation of the seed, to facilitate uniform coating. For compositions of seed coating applied in liquid form, the coating of the seeds should be for enough time to allow the seeds to dry, minimizing the adhesion of the seed. The use of forced air or heated charge air can increase the speed of application. The person skilled in the art it will be clear that this method can be single or continuous process. As the name implies, continuous process allows the seeds to continuously move through the flow of matter. New seeds are in the vessel in a stationary flow and slip-covered seeds out of the vessel.

The process of seed coating according to the present invention is not limited to thin-film coating and may also include drazhirovanie seeds. The process drazhirovanija usually increases the weight of the seed in 2-100 times and can also be used to improve the shape of the seed for use in mechanical drills. Compositions for drazhirovanija mainly contain solid R is zbavitel, which is usually insoluble granular material, such as clay, limestone, powdered silica, etc. to ensure the volume in addition to the binder substance, such as a synthetic polymer (e.g. polyvinyl alcohol, hydrolyzed polyvinyl acetate, a copolymer polivinilbutilovy ether-maleic anhydride, and polyvinylpyrrolidine) or natural polymer (e.g., alginates, Karay gum, guar gum, tragakant, polysaccharide gum, adhesive substance). After applying a sufficient number of layers, the coating is dried and sorted pellets. The way to obtain pellets (tablets) described in Agrow,The seed Treatment Market,Chapter 3, PJB Publications Ltd., 1994.

For further description of the components of the compositions and methods suitable for coating seedlings a compound of Formula I, see U.S. patents 4443637, 5494709, 5527760, 5834006, 5849320, 5876739, 6156699, 6199318, 6202346 and 6230438 and the publication of the European patent EP-1078563 A1.

The following examples E-H illustrate a method of coating seeds. The numbers of compounds are compounds of Table pointer A.

EXAMPLE E

Preparation of series of cotton seeds coated with the composition containing the Compound 208

Stage 1: Preparing a fluid suspension containing Compound 208

Preparing a fluid suspension containing the components listed in Table 7.

TABLE 7
The number of components in a fluid suspension
ComponentWt.%, including waterWt.%, excluding water
Connection 20815,6052,28
Agrimer® VA 65,0016,76
Press® KST5,0016,76
Borresperse™ CA1,003,35
Pluronic®F-1081,003,35
Brij® 782,006,70
Rhodorsil®4160,200,67
Pro-lzed® Colorant Red0,040,13
Water70,16-

Agrimer® VA 6 is a water-soluble to a high degree, film-forming adhesive substance having a softening point of 106°C, contains the copolymer of polyvinylpyrrolidones and sold by International Specialty Products (ISP). Press® KST is a water-soluble highly film-forming adhesive substance having a drop point 59°C containing ether glycol acid mineral wax sold by Clariant. Borresperse™ CA is a water-soluble high CTE is Yeni anionic dispersant, having a softening point of 132°C containing sugar-free lignosulfonate calcium, sold Borregaard LignoTech. Pluronic® F-108 is a water-soluble to a high degree, non-ionic dispersant, having a melting point of 57°C containing polyoxypropylene-polyoxyethylene block copolymers sold by BASF. Brij® 78 is a water-soluble to a high degree, non-ionic dispersant, having a pour point of 38°C containing stearyl alcohol (POE 20)sold by Uniqema. Rhodorsil® 416 is a water-dispersible liquid antifoaming agent containing polyorganosiloxanes and emulgirujushchie agent sold by Rhodia. Pro-lzed® Red Colorant is a water dispersible ink composition that contains a red pigment, clay, kaolin, and non-ionic surfactant and sold Gustafson.

Suspension media (253,20 g) was prepared by initially dissolving Brij® 78 (6,00 g) in warm water (210,48 g), followed by intensive mixing in Agrimer® VA 6 (15,00 g), Press® KST (15,00 g), Borresperse™ CA (3.00 g), Pluronic® F-108 (3.00 g), Brij® 78 (6,00 g), Rhodorsil® 416 (0.6 g and Pro-lzed® Red Colorant (0.12 g). In a beaker were added the Compound 208 (15.6 g)was then added portion of the thoroughly mixed suspension media (84,4 g), and Compound 208 was put in suspension media with a spatula.

This with the offer then further homogenized using a high-speed rotor-stator disperser Polytron (sold Brinkman Instruments Inc., Cantiague Rd., Westbury, NY 11590 U.S.A.) with 10 mm generator Converter that drobil units Connection 208.

The resulting slurry is then transferred to a pan grinder mill, loaded to 80% capacity 0,5 mm dimensions of the ceramic medium of high density, and cooled in the flowing chilled water 33% ethylene glycol solution through a cooling jacket of the milling chamber. The suspension was recycled through the mill chamber for 13 minutes with rotation of the agitator blades 4300 rpm the End of the circulatory pipe is then moved from the feed hopper of a mill in the flask to collect to get the final rose highly porous fluid suspension (89,5 g).

The diameters of micronized (crushed) of the particles in the suspension were analyzed using laser diffraction. Using the average value of two measurements, the arithmetic mean value of the diameter of the particles was 2,03 μm, 90% were less than a total of 5.21 μm in diameter, 10% of the particles were less than 0.30 microns in diameter, and the average particle diameter was 1.0 μm.

Stage 2: Coating of seed cotton composition containing a Compound 208

Seeds of cotton (Stoneville 4793 RR, 122,5 g) was added to the stainless steel container (12 cm diameter, 11 cm deep)containing two oppositely-directed rising blades for lifting the seed while rotating tank. Was bahritdinova at an angle of 40-45° to the horizon and mechanically rotated at 640 rpm, causing a good mixing and turning of the inside of the tank.

Prepared in Stage 1 fluid suspension was sprayed directly on the seeds in a pelleting drum, providing air pressure 10-11 f/DM2(psi) (69-76 kPa) to produce small droplets. By measuring the mass of the tank, you can determine the amount of fluid suspension sprayed on the seeds. When you turn the seeds manual spray directed into the tank for direct spraying on the centre tumbling the seed layer. Spraying was continued until, until the seed surface does not become sticky, causing the bonding seeds together. The spray is then turned off and the coated seeds were quickly dried by blowing air at low pressure at room temperature from a nozzle mounted to direct air flow into the tank. The growing sound of tumbling seeds provides audio that is covered with seeds dried enough. The drying air flow is then closed and continued spraying using a manual spray. Cycles of spraying and drying continued until the coating on the seeds of the desired quantity of fluid suspension. Then finished drying the seed coating, exposing their weak flow of ambient air for 60 hours.

Mass caused Connection 208 for every ten seeds from each batch was determined by soaking each seed in a ball mill, and then adding the extracting solvent acetonitrile. The extracts were centrifuged and aliquots of the supernatant (supernatant liquid) diluted 10000:1, and then analyzed by LC/MS. The results of the analysis are listed in Table 8.

Table 8
Measurement of coating seed cotton composition Connection 208
DimensionRated 1% loadingRated 2% loadingRated 3% loading
The mass of the fluid suspension sprayed on 122,5 g batch of seeds9,20 g18,94 g30,21 g
The weight of the treated seed lots after drying124,76 g127,10 g129,87 g
The weight of the dried coating on the party treated seedsof 2.26 g4,60 g7,37 g
The average weight of one treated seed*94 mg101 mg115 mg
The average weight of a Connection 208 seed*1.2 mg2.6 mg4.4 mg/td>
The average weight in % Connection 208-covered seed*1,3%2,6%3,8%

* based on 10 repetitions

EXAMPLE F

The receiving party corn seed coated with a composition comprising compounds 208, 484, 486, 502, 509 and 515

Stage 1: get 6 Fluid suspensions containing Compounds 208, 484, 486, 502, 509 and 515

Prepared six fluid suspensions containing one of six active components of the above compounds according to the recipe as shown in Table 9.

Table 9
The number of components in fluid suspensions
ComponentWeight in %, including waterWeight in %, excluding water
Connection 208, 484, 486, 502, 509 and 51515,0051,3
Agrimer® VA 65,0017,1
Press® KST5,0017,1
Borresperse™ CA1,003,42
Pluronic®F-1081,003,42
Brij® 782,006,84
Rhodorsil®4160,200,68
Pro-lzed® Colorant Red0,040,14
Water70,76-

All components other than the active ingredients of the compounds described in example E.

Fluid suspension of each compound was prepared by the method described in example E, step 1. The diameters (i.e. Dia. in Table 10) of the particles in suspension were analyzed by the method also described in EXAMPLE E, step 1. Diameter distribution of the particles obtained after wet grinding, as shown in Table 10.

Table 10
The particle sizes 6 fluid suspensions
Conn. 208Conn. 484Conn. 486Conn. 509Conn. 502Conn. 515
Is Dia. particles =*1.54 μ1,17 mcm0,92 mcm2,24 mcmof 1.03 micronsof 0.68 μm
90% of Dia. Particles <*is 3.08 µm2,37 mcm2,04 mcm4,87 mcm2,30 mcm1,36 mcm
Average Dia. particles1,27 µm0,92 mcm0,59 mcm1,47 mcm0.67 microns0,50 ám
10% of Dia. Particles <*0,35 µm0,30 µm0,27 is km 0.34 micronof 0.27 μmof 0.26 μm

* average of two measurements

"<" means less than

Stage 2: Floor maize seeds separate compositions containing compounds 208, 484, 486, 502, 509 and 515

Seeds of corn (maize) (Pioneer 3146 Lot # C92FA (Parent), 65g) was added to the stainless steel container (8 cm in diameter, 8.3 cm depth)containing two oppositely-directed lifting blades for lifting the seed while rotating tank. The tank is oriented at an angle of 40-45° to the horizon and mechanically rotated at 110 rpm, which gave a good mixing and turning of the inside of the tank.

Per 6 fluid suspensions, prepared in Stage 1, was sprayed directly on the drageeing layer of corn seed, following the General method described in EXAMPLE E, step 2. Then the drying of seeds was completed, leaving the seeds to dry overnight in a chemical fume hood. Achieved a nominal 3% by weight of the coating of each micronized compounds in the corn seed, as shown in Table 11.

Table 11
Measuring corn seed coated with the compositions of individual compounds
DimensionConn. 208Conn. 484Conn. 48 Conn. 509Conn. 502Conn. 515
The mass party of corn seed65 g65 g65,15 g65 g65,04 g64,02 g
The mass of the fluid suspension sprayed on the seed15,28 gof 14.46 g15,49 g15,25 g15,25 g15,31 g
% fluid suspension delivered to the seed91,82%88,62%95,74%92,96%92,82%91,78%
The mass party of the treated seeds after drying68,03 g67,88 g68,48 g68,31 g68,66 g67,93 g
The average weight of the compounds on the seed*2.1 mg1,92 mg2,21 mg2,13 mg2,12 mg2,11 mg
The average weight % of compounds on coated seed*3,14%2.87%of3,28%3,17%3,16%3,19%

* based on 10 repetitions

EXAMPLE G

Getting lots of seeds, coated with compositions containing compounds 208, 276 or 483

Stage 1: Getting 3 fluid suspensions containing compounds 208, 276 or 483

Prepared the ri fluid suspension, each containing one of the above three compounds, according to the recipe shown in Table 9 of EXAMPLE F. the Fluid suspension of each compound was prepared by the method described in EXAMPLE E, step 1. The diameters (i.e. Dia. in Table 10) of the particles in suspension were analyzed by the method also described in EXAMPLE E, step 1. A typical distribution of particle diameters after wet grinding are shown in Table 12.

Table 12
The size of the particles 3 fluid suspensions
Connection 483Connection 502Connection 276
Is Dia. particles =*1.5 mm1,01 mcm1,17 mcm
90% of Dia. Particles <*3,23 mcm2,23 mcm2,37 mcm
Average Dia. particles1,11 mcm0,69 µm0,92 mcm
10% of Dia. Particles <*of 0.33 μmof 0.28 μm0,3 ám

* average of two measurements

"<" means less than

Stage 2: Floor cotton seeds separate compositions containing Compounds 208, 276 or 483

Seeds of cotton (Stoneville 4793 RR, 33g) was added to the stainless steel container (6.5 cm diameter, 7.5 cm g ubina), containing two oppositely-directed lifting blades for lifting the seed while rotating tank. The tank is oriented at an angle of 40-45° to the horizon and mechanically rotated at 100 rpm, which provides good mixing and turning of the inside of the tank.

Three fluid suspensions, prepared in Stage 1, was sprayed on the tumbling party cotton seeds, following the General method described in EXAMPLE E, step 2. Then the drying of seeds was completed, leaving the seeds to dry overnight in a chemical fume hood. Achieved a nominal 3% by weight of the coating of each micronized compounds on cotton seed, as shown in Table 13.

Table 13
Measurement of cotton seeds coated with the compositions of individual compounds
DimensionConnection 483Connection 502Connection 276
Lots lots of cotton seed33 g33 g33 g
The mass of the fluid suspension sprayed on the seed7,35 g7,31 gof 7.25 g
% fluid suspension delivered to the seed91,9%95,77%92,72%
Weight is Artie treated seeds after drying 34,93 g35,05 g34,91 g
The average weight of the compounds on the seed*1,01 mg1,05 mg1,01 mg
The average weight % of compounds on coated seed*2,9%3%2,89%
* based on 10 repetitions

EXAMPLE H

Make a batch of corn seeds coated with a composition comprising a compound 502

Stage 1: Obtaining a fluid suspension containing 15 wt.%/wt. Connection 502

Prepared 15%fluid suspension connection 502 containing the same components except for the compounds listed in Table 9, EXAMPLE F. Fluid suspension connection 502 was prepared according to the method described in EXAMPLE E, step 1. The diameters (i.e. Dia. in Table 10) of the particles in suspension were analyzed by the method also described in EXAMPLE E, step 1. The resulting diameter distribution of particles after wet grinding are shown in Table 14.

Table 14

The size of the particles of a fluid suspension
Connection 502
Is Dia. particles =*0.89 microns
90% of Dia. Particles <*a 1.96 microns
Average Dia. Particles10% of Dia. Particles <*of 0.27 μm
* average of two measurements

"<" means less than

Stage 2: Floor corn seed composition containing a Compound 502

Seeds of corn (maize) (Pioneer 34M94 Hybrid Field Corn, 575 g) was added to the stainless steel container (17 cm diameter, 16 cm depth)containing two oppositely-directed lifting blades for lifting the seed while rotating tank. The tank is oriented at an angle of 40-45° to the horizon and mechanically rotated at 200 rpm, obtaining good mixing and turning of the inside of the tank.

15 wt.%/wt. fluid suspension, prepared in Stage 1, was sprayed directly on a separate party tumbling seeds, following the General method described in EXAMPLE E, step 2. Then the drying of seeds was completed, leaving the seeds to dry overnight in a chemical fume hood. Achieved nominal 0,15, 0,29, 0,58, 1,09, 1,75% by weight of the coating of each micronized compound 502 on corn seed, as shown in Table 15. The average wt.% Connection 502 on coated seed was measured using LC/MS, following the method from step 2 of EXAMPLE E.

Table 15
Measurements for cotton seeds coated component is izia connection 502
DimensionRated 1,75% partyRated 1,09% partyRated 0,58% partyRated 0,29% partyRated 0,15% party
The mass party of corn seed575 g575 g575,22 g575,28 g575 g
The mass of the fluid suspension sprayed on the seed71,17 g44,56 g22,79 g11,94 g5,95 g
% fluid suspension delivered to the target96,11%95,18%97,38%93,42%97,21%
The mass party of the treated seeds after drying592,31 g577,92 g572,15 g578,12 g576,74 g
The calculated weight of the composition delivered to the seed10,26 g6,36 g3.33 g1,67 g0.87 g
Nominal wt.% coating seedsa 1.75%1,09%0,58%0,29%0,15%
The average wt.% Connection 502 on coated seed*1,35%-0,42%-0,13%

* based on 10 repetitions

Obtaining cotton seed, corn seed, pelletizing seeds beet and soybean seeds coated with a composition comprising a compound 855.

Stage 1: Preparing a fluid suspension containing 15% (wt./wt.) connection 855

Preparing a fluid suspension containing the ingredients shown in table 16.

TABLE 16

The number of ingredients in liquid suspension
IngredientWt.%, including waterWt.%, excluding water
Connection 85515,0048,39
Agrimer® VA5,0016,13
Press®KST5,0016,13
Borresperse™ CA1,54,84
Pluronic® F-1081,54,84
Emery 912 Glycerine2,45of 7.90
Rhodorsil® 4160,200,65
Color Coat Green0,351,13
Water69,0-

Agrimer® VA is a film-forming adhesive substance with a high degree of water solubility and melting point 106°comprising the copolymer of polyvinylpyrrolidone and vinyl acetate and sold by International Specialty Products (ISP). Press®KST is a film-forming adhesive substance with high solubility in water and the temperature drop 59°including acid lignite wax and complex polietilenglikolya ether and sold by Clariant. Borresperse™ CA represents the anionic dispersant with a high degree of water solubility and melting point 132°including sugar-free lignosulfonate calcium and sold Borregaard Ligno Tech. Pluronic® F-108 is a nonionic dispersant with a high degree of water solubility and melting point 57°including block copolymers of polyoxypropylene and polyoxyethylene and marketed by BASF. Rhodorsil® 416 is a water-dispersible liquid antifoaming agent comprising polyorganosiloxanes and emulsifier and sold by Rhodia. Color Green Coat is a water-dispersible liquid dye sold Becker Underwood.

The suspension medium (42 g) was obtained by mixing with a magnetic stirrer of all inert ingredients: Agrimer® VA (2.5 g), Press®KST (2.5 g), Borresperse™ CA (0.75 g), Pluronic® F-108 (0,75 m), Emery 912 Glycerine (1,23 g), Rhodorsil® 416 (0.10 g) and Color Coat Green (0.18 g) - water (34,5 g) to dissolve. Connection 855 (3.5 g) was loaded in a container with a volume of 60 ml with a wide inlet. The top was added 28 g of grinding environment of the sodium-calcium is in-silicate glass with particle diameters of 0.5-0.75 mm. Put 25 mm abrasive impeller. And finally, to the suspension was added, thoroughly mixed suspension media (19,833 g) to obtain the pulp. The resulting slurry was stirred with a high speed stirrer with a top drive, cooling in an ice bath. The green suspension with a high degree of fluidity was separated from the environment of grinding. The whole method was twice repeated with getting 43,34 g of a suspension of fine grinding.

The diameters of the crushed particles of the suspension was measured using laser diffraction. Average diameter of particles was of 1.94 μm, 90% of the particles had a diameter less 2,28 μm, 10% of the particles had a diameter less of 0.28 μm, and the median particle diameter was equal to 0.73 ám.

Stage 2: Floor corn seed composition comprising the compound 855

About 67 g of seeds were placed in a stainless steel container with pendelum (inner diameter 8.5 cm, depth 8 cm). The tank is oriented at an angle of 40-45°to the horizontal and rotated mechanically with the speed of 640 rpm, which provides good mixing and turning of the seeds inside the tank. Fluid suspension obtained in stage 1, was sprayed directly on tumbling the seed layer using a two-fluid atomizer. Adjustable air pressure 69-86 KPa produces fine droplets of the suspension. When is perevorachivaniya seeds by hand spray was placed inside the tank to direct the spray into the center of the inverted layer of seeds. Spraying is continued until such time as the surface of the seeds did not become sticky, causing the sticking of seeds. Then spray off and the seeds coated with the coating quickly dried by blowing low pressure air with ambient temperature. The air drying off and continued spraying using a handheld sprayer. The cycle of spraying and drying was repeated until then, until the desired amount of fluid slurry was not applied on the seeds. Weighing a full tank before and after spraying, you can determine the amount of fluid suspension deposited on the seeds. Drying of seeds coated with the coating was completed, additional blowing air in the direction perpendicular to the direction of rotation of the seed. The coating was applied in two seed lots of maize, receiving nominal active dose of 1 mg A.I. per seed and 3 mg A.I. per seed.

TABLE 17

Characteristics of maize seeds with coating compositions connection 855
FeaturesFloor par value of 1 mg AI/seedFloor-nominal 3 mg AI/seed
Weight of seed lots of maize (˜220 seed)66,92 g66,99 g
The mass of the fluid suspension sprayed on seeds 1.66 g4.7 grams
The share suspension, under seeds (%)95,787,7
The weight of the treated seeds after drying67,3768,13 g
The mass of the dried coating on the treated seeds0.45 g1,14 g
The average weight of one treated seed306 mg309,7 mg
The average coating weight per seedof 2.45 mg5, 9 mg
Average weight compounds 855 is based on one seed1.2 mg2, 85 mg

Step 3: cover the seeds with a composition comprising a compound 855

About a 32.6 g of seeds were placed in a small stainless steel container with pendelum (internal diameter 6.5 cm, depth 7.5 cm). The tank is oriented at an angle of 40-45°to the horizontal and mechanically rotated with a speed of 70 rpm, which provides good mixing and overturning the action inside the tank. Fluid suspension obtained in stage 1, was sprayed directly on tumbling the seed layer using a two-fluid atomizer. The coating was applied on two batches of seed cotton in accordance with the method described in stage 2 of example 1, obtaining the nominal active dose mg A.I. the seed and 5 mg A.I. per seed.

TABLE 18

Characteristics of cotton seeds with a coating composition comprising the compound 855
FeaturesFloor par value of 1 mg AI/seedFloor-nominal 3 mg AI/seed
The mass party of cotton seeds (˜341 grain)32,65 g32,68 g
The mass of the fluid suspension sprayed on seeds2,44 g11,99
The share suspension, under seeds (%)94,7493,03
The weight of the treated seeds after drying33,3736,16 g
The mass of the dried coating on the treated seeds0,72 g3,48 g
The average weight of one treated seed97,85 mg106 mg
The average coating weight per seed2.1 mg10,2 mg
Average weight compounds 855 is based on one seed1.0 mg4,94 mg

Stage 4: Floor pelletizing sugar beet seed with a composition comprising a compound 855

About 25,0 g green pelletizing seeds of sugar beets is placed in a small stainless steel container with pendelum (internal diameter 6.5 cm, depth 7.5 cm). The tank is oriented at an angle of 40-45°to the horizontal and mechanically rotated with a speed of 70 rpm, which provides good mixing and overturning the action inside the tank. Fluid suspension obtained in stage 1, was sprayed directly on tumbling the seed layer using a two-fluid atomizer. The coating was applied on one party pelletizing sugar beet seed in accordance with the method described in example I (stage 2), obtaining the nominal active dose of 1.25 mg A.I. per seed.

TABLE 19

Characteristics pelletizing sugar beet seed with a coating containing a compound 855
FeaturesFloor-nominal 1.25 mg AI/seed
The weight of the seed lot (˜1073 seed)25,01 g
The mass of the fluid suspension sprayed on seedsfor 9.47 g
The share suspension, under seeds (%)96,22
The weight of the treated seeds after drying28,08 g
The mass of the dried coating on the treated seedsof 3.07 g
The average weight of one treated seedto 26.2 mg
The average coating weight from the calculation of the one seed 2,89 mg
Average weight compounds 855 is based on one seed1,40 mg

Stage 5: the Coating of soybean seed composition comprising the compound 855

About 75,65 g of soybean seeds were loaded into a small stainless steel container with pendelum (inner diameter of 8.5 cm, depth : 8.0 cm). The tank is oriented at an angle of 40-45°to the horizontal and mechanically rotated with a speed of 70 rpm, which caused a good mixing and turning of the seeds inside the tank. Fluid suspension obtained in stage 1, was sprayed directly on tumbling the seed layer using a two-fluid atomizer. The coating is applied on the two parties of soybean seeds in accordance with the method described in example I (stage 2), obtaining the nominal active dose of 0.625 mg A.I. per seed 1.25 mg / seed.

TABLE 20

Characteristics of soybean seeds with a coating containing a compound 855
FeaturesFloor-nominal 0.625 mg AI/seedFloor-nominal 1.25 mg AI/seed
The mass party of soybean seeds (˜510 seed)75,65 g75,65 g
The mass of the fluid suspension sprayed on seeds2,38 g4.68 g
The share suspension, Dostyk what I seeds (%) 94,795,0
The weight of the treated seeds after drying76,59 g76,99 g
The mass of the dried coating on the treated seeds0,94 gof 1.34 g
The average weight of one treated seed150 mg151 mg
The average coating weight per seedof 1.66 mg2, 66 mg
Average weight compounds 855 is based on one seed0,80 mgof 1.29 mg

EXAMPLE J

Obtaining seed lots of maize and cotton seeds with a coating composition comprising the compound 854

Stage 1: Obtaining a fluid suspension containing compound 854

To prepare a fluid suspension containing the ingredients shown in table 21.

TABLE 21
IngredientThe Mac.%, including waterThe Mac.%, excluding water
Connection 854br15.1548.38 per
Agrimer® VA 65,0016,13
Press®KST5,0016,13
Borresperse™ CA1,54,84
Pluronic® F-108 1,54,84
Emery 912 Glycerine2,45of 7.90
Rhodorsil® 4160,200,65
Color Coat Green0,351,13
Water68,85-

All the ingredients other than the active ingredient described in example 1.

Fluid suspension including a connection 854, obtained by the method described in Example I (stage 1).

The diameters of the crushed particles of the suspension was determined using laser diffraction. Average particle diameter was 0.85 μm, 90% of the particles had a diameter less of 1.81 μm, 10% of the particles had a diameter less than 0.25 μm, and the median particle diameter was equal to 0.73 ám.

Step 2: cover the seeds with a composition comprising a compound 854

About 32,65 g of seeds were placed in a stainless steel container with pendelum (internal diameter 6.5 cm, depth 7.5 cm). The tank is oriented at an angle of 40-45°to the horizontal and mechanically rotated with a speed of 70 rpm, which caused a good mixing and turning of the seeds inside the tank. Fluid suspension obtained in stage 1, was sprayed directly on tumbling the seed layer using a two-fluid atomizer. The coating was applied on three batches of seeds according to the accordance with the General method described in example 1 (stage 2), obtaining the nominal active dose of 0.5 mg, 1.0 mg and 2.0 mg A.I. per seed.

TABLE 22

Characteristics of corn seed with a coating comprising a connection 854
FeaturesFloor par value of 1 mg AI/seedFloor-nominal 3 mg AI/seedFloor par value of 2 mg AI/seed
The mass party of cotton seeds (˜341 seed)34,64 g32,62 g32,69 g
The mass of the fluid suspension sprayed on seedsof 1.34 g2.66 g5,2 g
% suspension aged seedsfor 95.291,587,65
The weight of the treated seeds after drying33,02 g33,37 g34,11 g
The mass of the dried coating on the treated seeds0,38 g0.75 g1.42 g
The average weight of one treated seed96, 8 mg97,86 mg100,03 mg
The average coating weight per seed1,05 mg2,11 mg4,28 mg
Average weight compounds 855 is based on the but the seed 0,51 mg1,02 mg2.07 mg

EXAMPLE TO Obtain whole potatoes with the coating composition containing the compound 855

Stage 1: Preparing a fluid suspension including a connection 855

Prepared fluid suspension nominal concentration of 250 g/l, containing the ingredients shown in table 23.

TABLE 23

The number of ingredients in liquid suspension containing compound 855
IngredientThe Mac.%, including waterWt.%, excluding water
Connection 85523,3058,37
Agrimer® VA 64,5011,27
Press®KST4,5011,27
Borresperse™ CA1,203,01
Pluronic® F-1081,203,01
Emery 912 Glycerine2,255,64
Propylene glycol2,255,64
Legend MK0,070,18
Rhodorsil® 4160,300,75
Color Coat Green0,350,88
Water60,08-0,0

All the ingredients, except for connections, which represents the active ingredient described in example I. the Suspension medium (1095,53 g) for connection 855 was obtained by stirring with a magnetic stirrer all inert solid ingredients with water in a beaker with a volume of 1 l; Agrimer® VA 6 (64,27 g), Press®KST (64,27 g), Borresperse™ CA (17,14 g), Pluronic® F-108 (17,14 g) was mixed with water (858,14 g) to dissolve or the dispersion. The next day was added to the liquid ingredients: propylene glycol (32,14 g), Emery 912 Glycerine (32,14 g), Legend MK (1.0 g), Rhodorsil® 416 (4,28 g) and Color Coat Green (5.0 g) and mixed with a magnetic stirrer for 1 hour to complete the receipt of the suspension medium.

Connection 855 (322,80 g) were loaded into a beaker with a volume of 2 liters was Added, thoroughly mixed suspension media (1095,53 g) obtaining a suspension of the final composition. The suspension was stirred by a stirrer with a top drive at a moderate speed. Then the suspension was subjected to wet grinding in a horizontal bead mill, Eiger 50 Mini VSE. In the chamber of the mill 80% of its volume was loaded chopping environment of soda-lime glass with particle diameters of 0.5-0.75 mm, the Suspension was subjected to wet-milling recirculation way with the mixer rotation speed 4000 rpm for 140 minutes. This method of wet grinding results in the sludge to obtain 1403 g suspension green with a high degree of fluidity.

The diameters of the crushed particles of the suspension was determined using laser diffraction. Average diameter of particles was 0, 96 μm, 90% of the particles had a diameter less of 2.16 μm, 10% of the particles had a diameter less of 0.27 μm, and the median particle diameter was equal to 0.60 μm.

Stage 2: the coating on the tubers

Prepared with a composition including the compound 855, inflicted on whole tubers (red Pontiac, size). The drug was applied from a dropping funnel, located in the middle of the stream of air forced under pressure of 55 kPa, which led to the splitting of drops and obtaining fine mist. The mist was sprayed on one tuber, located at 4-6 cm below the tip of the pipette. In the process of applying the tuber carefully rotated so that chemical treatment covers a third of the surface of the potatoes. The coating with the norms of consumption of 2 and 8 ál of each tuber was led to obtain coverage nominal doses of 0.5 and 2 mg A.I./potatoes.

EXAMPLE L

Getting the whole potatoes with a coating of a composition comprising a compound 502

Stage 1: Obtaining a fluid suspension including a connection 502

Prepared fluid suspension nominal concentration of 250 g/l, containing the ingredients shown in table 24./p>

TABLE 24

The number of ingredients in liquid suspension containing compound 502
IngredientThe Mac.%, including waterWt.%, excluding water
Connection 50223,3058,37
Agrimer® VA 64,4010,79
Press®KST4,4010,79
Borresperse™ CA0,90of 2.21
Pluronic® F-1080,90of 2.21
Emery 912 Glycerine2,255,52
Brij 781,704,17
Propylene glycol2,255,52
Legend MK0,070,17
Rhodorsil® 4160,300,74
Colorfast Purple0,300,73
Water59,23-0,0

All the ingredients, except for connections, which represents the active ingredient described in example I.

Suspension media (1741,03 g) for connection 502 was obtained by mixing with a magnetic stirrer of all inert ingredients in both solid and liquid form in a beaker with a volume of 3 l for the eyes. Agrimer® VA 6 (99,88 g), Press®KST (99,88 g), Borresperse™ CA (20,43 g), Pluronic® F-108 (20,43 g), Brij 78 (38,59 g), propylene glycol (51,08 g), Emery 912 Glycerine (51,08 g). Legend MK (1,59 g), Rhodorsil® 416 (6.81 in) and Colorfast Purple (6.75 g) was stirred with a magnetic stirrer during the night until complete dissolution /dispersion with water (1344,52 g).

Connection 502 (322,80 g) was loaded with a spoon directly on the suspension media and gave the opportunity to the mass spontaneously wetted the inside of the glass with a volume of 3 liters In the process of wetting the suspension is continuously stirred at a moderate speed mixer with a top drive. Then the suspension was subjected to wet grinding in a horizontal bead mill, Eiger 50 Mini VSE. In the chamber of the mill 80% of its volume was loaded chopping environment of the sodium-calcium-silicate glass with a particle size of 0.5-0.75 mm, the Suspension was subjected to wet grinding with a recirculation method, the rotation speed of the stirrer 4000 rpm for 189 minutes. The warmth of frictional heating was removed using circulating in the jacket of the mill building was a mixture of 50:50 etilenglikolevye antifreeze:water. This method of wet grinding resulted in the receipt of 2222,7 g suspension green with a high degree of fluidity.

The diameters of the crushed particles of the suspension was determined using laser diffraction. The average of the dia is the ETP of the particles was 0.86 micron, 90% of the particles had a diameter less of 1.92 μm, 10% of the particles had a diameter less of 0.26 μm, and the median particle diameter was equal to 0.55 m.

Stage 2: Coating of potato tubers fluid suspension, comprising a connection 502

Prepared composition comprising the compound 502, inflicted on whole tubers (red Pontiac, size). The drug was applied from a dropping funnel, located in the middle of the stream of air forced under pressure of 55 kPa, which led to the splitting of drops and obtaining fine mist. The mist was sprayed on one tuber, located at 4-6 cm below the tip of the pipette. In the process of applying the tuber carefully rotated so that chemical treatment covers a third of the surface area of the potato. The coating with the norms of consumption of 2 and 8 ál of each tuber was led to obtain coverage nominal doses of 0.5 and 2 mg A.I./potatoes.

EXAMPLE M Preparation of a fluid suspension including a connection 502 and Imidacloprid

To prepare a fluid suspension containing the ingredients shown in table 25.

TABLE 25

Number of ingredients included in a fluid suspension
IngredientThe Mac.%, including waterWt.%, excluding water
Connection 5027,8026,14
Imidacloprid7,8026,14
Agrimer® VA 65,0016,76
Press®KST5,0016,76
Borresperse™ CA1,003,35
Pluronic® F-1081,003,35
Brij 782,006,70
Rhodorsil® 4160,200,67
Pro-Ized®Colorant Red0,040,13
Water70,16-

All the ingredients, except for connections, which represents the active ingredient described in stage 1 of example E.

Fluid suspension including a connection 502 and Imidacloprid, were prepared in accordance with the method described in example E (stage 1).

EXAMPLE N

Preparing a fluid suspension including a connection 855 and Captan

To prepare a fluid suspension containing the ingredients shown in table 26.

TABLE 26

Number of ingredients included in a fluid suspension
IngredientThe Mac.%, including waterThe Mac.%, excluding water
Soy is inania 855 10,3420,20
Captan31,0360,61
Agrimer® VA 63,45of 6.73
Press®KST3,45of 6.73
Borresperse™ CA0,691,35
Pluronic® F-1080,691,35
Brij 781,382,69
Rhodorsil® 4160,140,27
Pro-Ized®Colorant0,030,05
Red
Water48,80-

All the ingredients, except for connections, which represents the active ingredient described in example E (stage 1).

Fluid suspension including a connection 855 and Captan, was obtained by the method described in example E (stage 1).

The following tests in Biological examples of the invention demonstrate the effectiveness of the methods and compositions of the present invention for protecting plants from individual arthropod pests. Controlling pest protection afforded by these compounds is not limited, however, to these species. To describe compounds see Table-index A. In the index table uses the following abbreviations: t means t is etigny, n means normal, i means ISO, s means secondary, with a mean cycle, Me means methyl, Et means ethyl, Pr means propyl and Bu means butyl; accordingly, i-Pr means isopropyl, s-Bu means of secondary butyl, etc. Abbreviation "Ex." stands for "Example"followed by the indication, in any EXAMPLE get the connection.

The index table And

R1, R5, and R8 are H, except where indicated; means On, except where indicated. "CN" is connected through a carbon than nitrogen; for example, "CN-Ph" means cyanophenyl, not isocyanates.

BIOLOGICAL EXAMPLES of THIS INVENTION

TEST AND

Cotton seeds coated with the composition of Connection 208 of the series of nominal concentrations of 1%nominal 2% nominal 3%, prepared as described in EXAMPLE E, and raw seeds for comparison, planted in pots with sterile soil Sassafras, and were grown in the growth chamber with a 16 hour daylight hours at 28°and 8 hour phase of the dark at 24°C and 50% relative humidity. After 31 days two plants, each with true leaves, were selected from each lot of seeds and removing the cotyledons. Adult Bemisia argentifolii (silverleaf whitefly) was added to the deposition of eggs on the plants and plastic cylinders, covered with a thin piece of paper was placed in the pots. Three days later, the adults were removed and examined the sheets to establish the fact that the deposition of eggs. Fifteen days (approximately six days after put the eggs I), infected leaves were removed from plants and 49-day results were obtained by counting the dead and live nymphs on the underside of leaves. Adult Bemisia argentifolii was re-introduced to re-deposition of eggs on the upper leaves of plants, and plastic cylinders with a thin piece of paper was placed inside pots, as before. Three days later, the adults were removed and the leaves were examined for the presence of eggs. Fifteen days later (about six days after hatching of the eggs), the leaves were removed from plants and 66-day results were obtained by counting the dead and live nymphs on the underside of leaves. The results of the two values of time are summarized in Table A.

Table And

The control of Silverleaf whitefly by covering the seed cotton compositions connection 208
Processing49-day % mortality66-day% mortality
Rated 1% concentration3817
Rated 2% concentration7241
Rated 3% concentration9581
Raw1510

This test demonstrates that the seed coating according to this invention can for imate of cotton plants from ranarridh pest Bemisia argentifolii for more than 9 weeks after sowing.

TEST

Cotton seeds coated with the composition of Connection 208 of the series of nominal concentrations of 1%nominal 2% nominal 3%, prepared as described in EXAMPLE E, and raw seeds for comparison, planted in 10 cm pots using sterile soil Sassafras, and were grown in the growth chamber with 16 hours of light during the day and 8-hour phase of the dark at 25°C and 50% relative humidity. With some plants collected leaves 14 days after planting, cut into 3-4 pieces and put one piece on the hole is covered with a 16-hole semi-transparent plastic trays in a growth chamber. Larvae of Heliothis virescens (tobacco moth-Packed) second stages were added to the parts list (1 larvae/well, 6-10 larvae per treatment/type of sheet), and insect mortality was determined after 48 hours and 96 hours after invasion. Collected leaves from another plant through 64 days after planting, cut into 3-4 pieces, and put one part on the hole is covered with a 16-hole semi-transparent plastic trays in a growth chamber. Larvae of Heliothis virescens (tobacco moth-Packed) in the second age stage was added to parts of the leaves (1 larvae/well, 6-16 larvae per treatment/location sheet), and insect mortality was determined after 72 hours and 96 hours after invasion. The results are summarized in Tables B1 and B2.

Top
TABLE B1

The tobacco control leafroller 14 days after planting using a covering of cotton seeds compositions connection 208
ProcessingThe sheet type48 hours % mortality96 hours % mortality
Rated 1% concentrationTrue033
Seed1070
Rated 2% concentrationTrue1733
Seed30100
Rated 3% concentrationTrue1783
Seed50100
Untreated controlTrue00
Seed0100
TABLE B2

The tobacco control leafroller through 64 days after planting using a covering of cotton seeds compositions connection 208
ProcessingThe position of the sheet*72 hour % mortality96 hours % mortality
Rated 1% concentration2593
Bottom31100
Rated 2% concentrationTop681
Bottom31100
Rated 3% concentrationTop75100
Bottom50100
Untreated controlTop1212
Bottom1919
* Position on the cotton plant from which you removed the sheet.

This test demonstrates that the seed coating in accordance with the present invention can protect plants from cotton lepidopteran pests Heliothis virescens for more than 9 weeks after planting.

TEST

Cotton seeds treated with connection 208, prepared as in EXAMPLE E (nominal 3% of the series) and connections 276, 486 and 502, prepared in EXAMPLE G, and raw seeds for comparison, planted in pots using either sterile Sassafras soil or soil Drummer. The plants were grown in the greenhouse and were selected for testing, when they began to give buds (squares). Leaves from the second node and the ending leaves more than 15 cm were selected for testing (the plant was approximately 5 leaves). Cut the leaf from each plant was cut into 4 parts and each part was placed in the hole with one larva of Heliothis virescens (:Packed tobacco) in the second age. Mortality of larvae was recorded after 96 hours after sampling.

TABLE

Mortality of larvae from eating the leaves of treated seeds grown on two soils types
ConnectionThe soil type96 hours % mortality of larvae
Final listThe base of the plant
208Sassafras35,047,5
Drummer58,379,2
276Sassafras81,381,3
Drummer85,796,4
486Sassafras43,834,4
Drummer57,167,9
502Sassafras25,046,9
Drummer87,575,0
RawSassafras9, 6,3
Drummer16,74,2

TEST D

Corn seeds treated with compounds 208, 484, 486, 502, 509 and 515, prepared in EXAMPLE F, planted in pots with soil Sassafras. The plants were grown to the height of the ring leaves (9th list) in the greenhouse and used to infect 25 species of deciduous "marching worms (larvae of the first age) at the bottom of the ring leaves. Six days after infestation were recorded damage to plants associated with eating. Damage to plants was assessed 0-100% (0 means no eating).

TABLE D

The percentage of damaged plants from eating larvae on maize plants with different treatments seeds
ConnectionDamage to plants
2088
48429
48623
50910
50210
5157
Raw56

TEST E

Corn seeds treated with connection 502, as prepared in EXAMPLE H, in five doses (%) (nominal 1,75%, 1,09%, 0,58%, 0,29% and 0.15%) were sown on agricultural fields near Newark, DE and Donna, TX. When RA is the shadow gave the 5th sheet is at least 10 cm, his cut. For each percent took one cut sheet at least 16 plants, and was placed in the hole with one larva deciduous "marching worm" second age stage. Mortality of larvae was recorded after 72 hours after the invasion.

Maize plot Donna was measured to determine the growth of plants. Larvae were wrapped in the cylinder and record the height from the earth to the farthest tip of the sheet in the cylinder.

TABLE E1

Mortality of larvae from eating the 5th leaf of corn processing seed connection 502
InterestThe percentage of mortality at 72 h
NewarkDonna
a 1.75%100,0to 58.1
1,09%100,071,0
0,58%95,8of 54.8
0,29%87,535,5%
0,15%87,529,0
Raw0,00,0

Table E2

Plant height of maize at the treatment of seeds with the connection 502 in Donna, TX
Seed treatment (par% the NT) Raw0,15%0,29%0,58%1,09%a 1.75%
Height (inches)41, 6440,7642,3644,2845, 3248,32

As can be seen from Table E2, processing connection 502 in this test contributes to the growth of plants.

F TEST

The party of corn seed with a coating of the composition of compounds 855 par value of 1 mg A.I. and 3 mg A.I. obtained in accordance with the method of step 2 of example I, and for comparison, untreated seeds were planted in small terrariums with sterile Matapeake soil and were grown for 14 days. After 14 days, one batch of plants was tested against Pereprinus maidis (cicadas corn), and the other against Spodoptera frugiperda (deciduous "marching worms").

For testing against .maidis around plants have established the cylinder, and the plant was placed 15-20 nymphs of the third age stage. The top of the cylinder is closed by a screen to prevent larvae, but with access of air. The plants were grown in a growth chamber with a 16-hour light period and an 8-hour phase of the dark at 20°C and 50%relative humidity. Six days were counting the dead and live larvae to determine the percentage of mortality.

The second group of plants corn cut off the Torah sheet, cut it into four equal parts and each received portion of the sheet was placed in a separate hole is covered with a 16-hole semi-transparent plastic trays in a growth chamber. On each part of the sheet was placed larva S.frugiperda second stages (1 larva per well), and 48 hours after infection was determined mortality of insects.

TABLE F

Control cicadas corn and deciduous "marching worms 14 days after planting corn with a coating of compositions comprising a compound 855
ProcessingMortality cicadas corn (%)Mortality marching worms (%)
Untreated plants3,20,0
Floor par value of 1 mg AI/seedto 97.143,8
Floor-nominal 3 mg AI/seedof 98.281,3

TEST G

Cotton seeds coated from the composition of compounds 855 par value of 1 mg A.I. and 5 A.I., obtained according to the method of example I (stage 3), and for comparison, untreated seeds were planted in pots with a diameter of 10 cm sterile Matapeake soil and were grown with a 16-hour light period and 8 - hour dark period phase at 25°and relative wet the minute 50%. Plants were tested against Aphis fossypii (cotton aphid), Bemisia argentifolii (whiteflies silver), Heliothis virescens (tobacco moth) and Frankliniella occidentalis (thrip Western wheat), when the first true leaf was reached at a length of about 2 cm

All plants had two remote cotyledons. List of plants tested against A.gossypii, infected about 30 nymphs, which were transferred to the plant with pre-infected cut sheet. Each plant was surrounded by a plastic cylinder and covered with a thin paper. Six days were counting the number of live and dead larvae to determine the percentage of mortality. Another group of plants infected adults .argentifolii for laying eggs on the plants, the pots were shielded plastic cylinders, closed thin paper to bear the adult for 24 hours at 28°With a 16 hour light period and an 8 hour period of the dark phase and a relative humidity of 50%. Adult insects were removed and the leaves were examined to check for eggs. After thirteen days after infection, the sheet was removed and counted the number of dead and live larvae on the underside of the sheet to determine the percentage of mortality. A third group of plants used for testing against H.virescens. The first true leaf was removed, cut in half and placed in the hole (one RL of the next sheet per well) 16-hole poluparadnogo plastic tray with larva .virescens second stages (1 larva per well). The trays were kept in the growth chamber with a 16 hour light period and 8-hour dark period phase at 25°C and 50%relative humidity. Mortality was determined after 96 hours after infection.

TABLE G

Control of cotton aphid, whitefly silver and leaf tobacco when using cotton seeds with a coating of a composition comprising a compound 855
ProcessingMortality cotton aphid (%)Mortality of whiteflies silver (%)Mortality of leaf tobacco (%)
Untreated plants1,530
Floor par value of 1 mg AI/seed72,810083,3
Coating with a nominal value of 5 mg AI/seed82,6100100

TEST N

Cotton seeds with coating compositions connection 855 par value of 1 mg A.I. and 5 mg A.I., obtained according to the method of example I (stage 3), and untreated seeds for comparison were planted in pots with a diameter of 10 cm sterile Matapeake soil and were grown with a 16-hour light period and 8-hour dark period phase at 25°C and 50%relative humidity. Plants were experienced when the first infusion is the second sheet has reached a length of about 2 cm

The plants of cotton tested against F.occidentalis, removing the cotyledons and in pots around the plants have established plastic cylinders. Each plant was infected 50 thrips and the cylinder was closed with a thin piece of paper to keep insects inside the cylinder. Seven days after the making of thrips were identified damage to plants to determine the extent of protection of plants in percent. Plants were cut and soaked with 70% ethanol for calculating remote thrips and determine the effectiveness of the connection.

TABLE N

Control of thrips Western wheat using cotton seeds with a coating composition comprising the compound 855
ProcessingAphid cotton, % protect plantsEfficiency
Untreated plants00
Floor par value of 1 mg AI/seedof 37.822,6
Coating with a nominal value of 5 mg AI/seed78,4to 85.2

The TEST I

Sugar beet seeds with coating compositions connection 855 nominal 1.25 mg A.I obtained according to the method of example I (stage 4), and for comparison, untreated seeds were planted in pots with a diameter of 10 with the sterile Matapeake soil and cultivated in a greenhouse. After the formation of the 5th true leaf plants were tested against Aphis fabae (aphid beet) or Spodoptera exiqua (beet "marching worms").

For testing against .fabae leaves infected about 30 nymphs, which were transferred to plants previously infected cut sheet. Each plant was surrounded by a plastic cylinder and covered with a thin paper. Six days were counting the number of live and dead nymphs to determine the percentage of mortality.

The second group of plants infected six larvae S.exigua third age stage. Each plant was surrounded by a plastic cylinder. Six days was determined by the degree of the damage to plants on a scale of 0-100 (0 = no damage; 100 = all of the material sheet eaten). All plants after infection was kept in the growth chamber with a 16-hour light period and 8-hour dark period phase at 25°C and a relative humidity of 50%.

TABLE I

Control aphids beet or beet "marching worm" in the application of sugar beet seed with a coating composition comprising the compound 855
ProcessingThe mortality of the aphid beet (%)Damage to plants beet "marching worms" (%)
Nobr botania plants 1295
Floor-nominal 1.25 mg AI/seed778

TEST J

The soybean seeds coated from the composition of compounds 855 nominal 0.625 mg A.I. and 1.25 mg A.I obtained according to the method of example I (stage 4), and raw seeds for comparison were planted in pots with a diameter of 10 cm, the Plants were infected Aphis alycines (soybean aphid) on the stage of development of the third trefoil and were grown in the greenhouse. About 30 larvae of the soybean aphid was transferred to the plant with pre-infected cut sheet. Each plant was surrounded by a plastic cylinder and covered with a thin paper. Infected plants tolerated in the environment growth chamber with 16 hours of light during the day and 8-hour dark phase at 25°C and 50%relative humidity. Six days were counting the number of live and dead aphids to determine the efficacy, expressed in percent.

5,8
TABLE J

Control of soybean aphid soybean seeds with a coating composition comprising the compound 855
ProcessingThe number of live aphidsEfficiency (%)
Untreated plants133,6
Floor-nominal 0.625 mg AI/seed95,66
Floor-nominal 1.25 mg AI/seed13,290,16

TEST

Cotton seeds with coating compositions connection 854 nominal 0.5 mg A.I., 1 mg A.I. and 2 mg A.I., obtained as described in example J (stage 2), and for comparison, untreated seeds were vivarelli in 10 cm pots using sterile Matapeake soil and were grown in conditions with a 16-hour light day and 8-hour phase of the dark at 25°C and 50%relative humidity. Plants were tested at the stage of development of the second or third true leaf. They were tested against Aphis gossypii (cotton aphid), Bemisia argentifolii (silverleaf whitefly) and Frankliniella occodentalis (trips wheat in the West).

Plants tested against A.gossypii, had the second true leaf length is approximately 2 see the Two cotyledons and the first true leaf in plants have been removed. The remaining leaf was infected about 30 nymphs A.gossypii, which was transferred to a pre-infected cut sheet. Each plant was surrounded by a plastic cylinder and covered with a thin paper. Six days were counting the number of live and dead nymphs to determine the percentage of mortality.

When tested against .argentifolii or F.occidentalis plants used at the stage of development of this third sheet to a length of about 2 to see All the lower leaves were removed(cotyledons and other true leaves) and the plants were divided into two groups. First a random sample of plants was placed in the fish tank with older individuals .Argentifolii 24 hours of laying in a 16-hour light day and 8-hour phase of the dark at 28°C and 50%relative humidity. Adult insects were removed and plants were examined for the presence of at least 50 eggs on each sheet. Thirteen days after infestation, plants were counting the number of dead and live nymphs on the lower sides of leaves to calculate the percentage of mortality. The second group of plants tested against F.occodentali, around plants have established plastic cylinders. Each plant was infected 25 larvae of thrips and the cylinder was closed with a thin piece of paper to hold insects. Seven days after the making of thrips plants were cut and soaked with 70% ethanol for remote counting thrips and calculating the efficiency of the connection.

TABLE TO

Control of cotton aphid, silverleaf whitefly and thrips Western wheat the use of cotton seeds with coating compositions connection 854
Untreated plantsMortality cotton aphid (%)Mortality of whitefly silverleaf (%)Mortality of leaf tobacco (%)
Niobrara what these plants 100
Floor-nominal 0.5 mg AI/seed91001
Floor par value of 1 mg AI/seed6210015
Floor par value of 2 mg AI/seed9010032

TEST L

The treated tubers were planted by hand in field conditions on the day of processing of tubers. Assessment of Leptinotarsa decemloneata (Colorado potato beetle) was performed at 33 days after planting (DPP). Was positively the total number of larvae per plant and determined the percentage of control. Forty-four after planting recorded the average number of plants damaged Ostrinia nubilalis (corn borer), and determined the percentage of the control.

TABLE L

Control of the Colorado potato beetle and corn borer by application of a coating of potato tubers compositions and compounds 855 or connection 502
ProcessingDose (mg AI/seed)% protection against Colorado potato beetle larvae (33 days after planting)% protection from corn borer (44 days after planting)
Untreated plants000
502-FS0,54858
502-FS21789
855-FS0,52429
855-FS26259

1. The way to protect seedlings or plants grown from them, from insects comprising contacting the seed with a biologically effective amount of the compounds of formula I or its salt, acceptable for agriculture

where a and b represent About;

R1represents N;

R2represents N;

R3represents a C1-C6alkyl;

R4represents a C1-C6alkyl or CN;

R5represents H, C1-C6alkyl or halogen;

R6represents a C1-C6halogenated or halogen;

R7represents pyridinyl, substituted R9;

R8represents N;

each R9represents independently a halogen.

2. The method according to claim 1, where R3represents a C1-C4alkyl; R4attached in position 2; R4represents CH3or CN; R6 represents CF 3or halogen; and R7represents 2-pyridinyl, substituted R9.

3. The method according to claim 2, where R3represents a C1-C4alkyl; R6is a CF3.

4. The method according to claim 3, where R3represents a C1-C4alkyl, and R6represents Cl or Br.

5. The method according to claim 1, for protecting seedlings from insects.

6. The method according to claim 5, comprising the contacting of the seedling to be protected with a biologically effective amount of the compounds of formula I according to claim 1 or its salt, acceptable for agriculture.

7. The method according to claim 5, in which the seedling is a seed.

8. The method according to claim 6, in which the seedling is a seed of maize, cotton, soy, or beet.

9. The method according to claim 8, in which the seedling is a seed of cotton, maize or soybeans.

10. The method according to claim 5, in which the seedling is a potato or a viable part.

11. The method according to claim 5, in which the seedling is covered with a composition comprising as active agent a biologically effective amount of the compounds of formula I or its salts acceptable for agriculture, and the film former or adhesive agent.

12. Composition for controlling insects, covering the seedling, comprising as active agent a biologically effective amount of the compounds of formula I according to claim 1 and the and its salts, acceptable for agriculture and the film former or adhesive agent.

13. The composition according to item 12, additionally containing an effective amount of at least one additional biologically active compound or agent.

14. The composition according to item 13, where the at least one additional biologically active compound or agent selected from arthropodicides neonicotinoids.

15. The composition according to 14, where one additional biologically active compound is an Imidacloprid.

16. The composition according to item 13, where one biologically active compound or agent is a Captan, a fungicide.



 

Same patents:

FIELD: fungicides.

SUBSTANCE: invention relates to fungicide composition containing 2,6-dichloro-N-{[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl}-benzamide (compound I) and mankozeb (compound II), and method for treatment or prophylaxis controlling of phytopathogenic fungi of agriculture cultures using the said composition. Product containing compound I and compound II in weight ratio of from 1/100 to 5/1 also is disclosed.

EFFECT: fungicide composition of high efficiency.

9 cl, 1 tbl, 1 ex

FIELD: agriculture, pest control.

SUBSTANCE: the suggested covering for pest control is made of polymeric material and includes, at least, two layers: the upper layer and the lower one, moreover, the lower layer contains a herbicide and one or more pesticides chosen out of the group pf fungicides and insecticides, as for the upper layer, it contains insecticide and/or fungicides not obligatory. The method deals with applying the above-mentioned covering upon the ground and making incisions in the sites for further planting the seedlings. Polymeric composition contains a herbicide to obtain polymeric covering. The innovation enables to provide high-efficient protection and safety of plants.

EFFECT: higher efficiency of plant protection.

28 cl, 3 dwg, 5 ex, 4 tbl

FIELD: agriculture, pest control.

SUBSTANCE: the suggested covering for pest control is made of polymeric material and includes, at least, two layers: the upper layer and the lower one, moreover, the lower layer contains a herbicide and one or more pesticides chosen out of the group pf fungicides and insecticides, as for the upper layer, it contains insecticide and/or fungicides not obligatory. The method deals with applying the above-mentioned covering upon the ground and making incisions in the sites for further planting the seedlings. Polymeric composition contains a herbicide to obtain polymeric covering. The innovation enables to provide high-efficient protection and safety of plants.

EFFECT: higher efficiency of plant protection.

28 cl, 3 dwg, 5 ex, 4 tbl

FIELD: agriculture, pest control.

SUBSTANCE: the suggested covering for pest control is made of polymeric material and includes, at least, two layers: the upper layer and the lower one, moreover, the lower layer contains a herbicide and one or more pesticides chosen out of the group pf fungicides and insecticides, as for the upper layer, it contains insecticide and/or fungicides not obligatory. The method deals with applying the above-mentioned covering upon the ground and making incisions in the sites for further planting the seedlings. Polymeric composition contains a herbicide to obtain polymeric covering. The innovation enables to provide high-efficient protection and safety of plants.

EFFECT: higher efficiency of plant protection.

28 cl, 3 dwg, 5 ex, 4 tbl

FIELD: agriculture, herbicides.

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EFFECT: compositions of increased effectiveness.

21 cl, 191 tbl, 99 ex

FIELD: organic chemistry, pesticides.

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EFFECT: storage stable products.

9 cl, 7 tbl, 2 ex

FIELD: organic chemistry, pesticides.

SUBSTANCE: invention relates to concentrated pesticide solution, containing 0.5-50 mass/vol.% one or more water insoluble pesticides and lignin in mass ratio lignin/pesticide of 1:10-1:1, dissolved in polar solvent mixable with water in amount to adjust total volume to 100 %. Dispersed in water concentrated pesticide solution is applied onto pests or locus thereof.

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9 cl, 7 tbl, 2 ex

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EFFECT: storage stable products.

9 cl, 7 tbl, 2 ex

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9 cl, 7 tbl, 2 ex

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9 cl, 7 tbl, 2 ex

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EFFECT: enhanced activity of agent.

2 cl, 23 tbl, 6 ex

FIELD: organic chemistry, agriculture.

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EFFECT: valuable biological properties of substances.

1 tbl, 4 ex

FIELD: organic chemistry, agriculture.

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EFFECT: compounds with insecticide activity, useful in insect controlling.

20 cl, 16 tbl, 33 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to ortho-substituted arylamides of formula I , wherein J represents phenyl ring or pyrazole ring each substituted with one or two substitutes independently selected from R5; K represents -NR1C(=A)- or -NR1SO2-; L represents -C(=B)NR2-, -SO2NR2- or -C(=B)-; A and B represent O; R1 and R2 represent H; R3 represents C1-C6-alkyl optionally substituted with one or more substitutes, independently selected from group containing CN, NO2, C1-C4-alkylsulfonyl and C2-C6-alkoxycarbonyl; each R4 independently represents C1-C6-alkyl, halogen or CN; each R5 independently represents C1-C6-alkyl, halogen or C1-C4-haloalkoxy or pyridinyl optionally substituted with one substitute independently selected from R9; wherein R9 represents halogen; n = 1-2; with the proviso, that when K represents -NR1C(=A)- L is not -C(=B)NR2-, and salts thereof, method for insect controlling by using abovementioned compounds. Intermediate for synthesis of target compounds having formula 2 also is disclosed.

EFFECT: compounds with insecticide activity, useful in insect controlling.

15 cl, 21 tbl, 9 ex

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes new substituted derivatives of pyrazole of the general formula (I): wherein n = 0 or 1; group A represents independently hydrogen atom, alkyl group with 1-4 carbon atoms, halogenalkyl group with 1-4 carbon atoms, cycloalkyl group with 3-6 carbon atoms or phenyl group having substituting groups optionally; group D represents hydrogen atom, alkyl group with 1-4 carbon atoms, halogenalkyl group with 1-4 carbon atoms, alkenyl group with 2-4 carbon atoms, alkoxy-group with 1-4 carbon atoms, cycloalkyl group with 3-6 carbon atoms, halogen atom, alkoxycarbonyl group with 1-4 carbon atoms, alkylsulfonyl group with 1-4 carbon atoms or phenyl group; group E represents hydrogen atom, halogen atom or phenyl group; groups R1 and R2 both represent halogen atom; group R3 represents hydrogen atom, alkyl group with 1-4 carbon atoms, halogenalkyl group with 1-4 carbon atoms, alkenyl group with 2-4 carbon atoms, alkynyl group with 2-4 carbon atoms or benzyl group; groups R4 and R5 are similar or different and each represents hydrogen atom, alkyl group with 1-4 carbon atoms, halogenalkyl group with 1-4 carbon atoms, cycloalkyl group with 3-8 carbon atoms that can be substituted with alkyl group with 1-4 carbon atoms, alkenyl group with 2-4 carbon atoms, alkynyl group with 2-4 carbon atoms, cyanomethyl group or phenyl group; or each R4 and R5 group means benzyl group; or each R4 and R5 group represents α- or β-phenethyl group having substituting groups at benzyl ring optionally. Indicated substituting groups represent alkoxy-groups with 1-4 carbon atoms wherein indicated substituting groups substitute hydrogen atom at the arbitrary positions 0-2 of the benzyl ring; or groups R4 and R5 form in common 5-membered or 6-membered aliphatic ring wherein the indicated ring can be substituted with alkyl groups with 1-4 carbon atoms and indicated ring can comprise one or two heteroatoms chosen from nitrogen oxygen and sulfur atom, and a method for their preparing. Also, invention describes herbicide compositions based on compound of the formula (I). Invention provides preparing herbicide compositions showing the strong herbicide effect and broad herbicide spectrum of their effect.

EFFECT: improved preparing method, valuable properties of derivatives and compositions.

7 cl, 6 tbl, 3 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention describes benzoylpyrazoles of the general formula (I): wherein R1 means methyl; R2 means trifluoromethyl; R3 means hydrogen atom, methyl; R4 means methyl, ethyl; R5 means hydrogen atom, phenylsulfonyl substituted with methyl, benzoylmethyl substituted once with nitro-group, and herbicide agent based on thereof. Benzoylpyrazoles are used for selective control of weeds and weed grasses in useful plants.

EFFECT: valuable properties of substances and herbicides.

6 cl, 5 tbl, 7 ex

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention describes a synergetic composition with the effective content of components (A) and (B) wherein (A) means herbicide chosen from the group of compounds of the formula (I): wherein R1, R2, R, X, Y and Z have values given in the invention claim or their salts; (B) means one or some herbicides among the following groups: (B1) selective herbicides with activity in some dicotyledonous cultures against monocotyledonous and dicotyledonous weeds; (B2) selective herbicides with activity in some dicotyledonous cultures against dicotyledonous weeds; (B3) selective herbicides with activity in some dicotyledonous cultures with preferable effect against monocotyledonous weeds. Also, invention describes a method for control against weeds using the proposed composition. Using the combination of proposed herbicides results to the synergetic effect.

EFFECT: valuable herbicide properties of composition.

3 cl, 7 tbl, 2 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention describes a herbicide agent comprising (A) compound of the formula (I): wherein V means a residue from the group (V2) and (V3) wherein R2 means hydrogen atom, alkyl with 1-4 carbon atoms or alkoxyl with 1-4 carbon atoms; R3 means hydrogen atom or alkylsulfonyl with 1-4 carbon atoms; R4 means methyl, ethyl or n-propyl; R means hydroxyl; m = 0; Z means a residue of the formula (Z1): wherein R9 are similar or different and mean halogen atom, halogenalkyl with 1-4 carbon atoms, halogenalkoxyalkyl with 1-4 carbon atoms in halogenalkoxyl moiety and 1-4 carbon atoms in alkyl moiety, alkylsulfonyl with 1-4 carbon atoms or 4,5-dihydroisoxazol-3-yl substituted with cyanomethyl; q means 2 or 3; and (B) surface-active substance of the formula (II): Ry-(EO)x(PO)y(EO)z-Rδ (II) and components (A) and (B) are chosen in the synergetically effective ratio. Also, invention describes a method for control of weeds. Proposed herbicide agents possess herbicide activity against a broad spectrum of economically important monocotyledonous and dicotyledonous weeds.

EFFECT: improved control method, valuable herbicide properties of agents.

3 cl, 4 tbl, 6 ex

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention describes phenyl-substituted heterocyclic 1,3-ketoenols of the formula (I): wherein R1 and R3 mean independently of one another ethyl or (C1-C2)-alkoxy-group; Q means the group of the formula (Q1): or (Q2): wherein R4 and R5 in common with atoms to which they are joined form 5-7-membered cycle that can comprise additionally anellated alkylene chain consisting of 2-6 carbon atoms that, in turn, can comprise two heteroatoms taken among oxygen atom, and indicated cycle can be substituted with halogen atom, hydroxy-group, (C1-C6)-alkoxy-group, (C1-C6)-alkoxy-(C1-C6)-alkoxy-group, (C1-C4)-alkylcarbonyloxy-group, hydroxy-(C1-C4)-alkoxy-group, hydroxycarbonyl-(C1-C2)-alkoxy-group, methoxycarbonyl-(C1-C2)-alkoxy-group, methoxyimino-, methoxyethoxyethoxy-group; R6 and R7 means (C1-C10)-alkyl; R8 means hydrogen atom; X means oxygen atom; R20 means (C1-C10)-alkyl, and also agronomically acceptable salts and isomers of these compounds. Also, invention describes a method for preparing compounds of the formula (I), herbicide agent and a method for control of weed growth based on compounds of the formula (I). Invention provides preparing compounds possessing the herbicide activity.

EFFECT: improved preparing method, valuable properties of compounds and agents.

5 cl, 28 tbl, 5 ex

FIELD: organic chemistry, fungicides, agriculture.

SUBSTANCE: invention describes 1-pyridinyl-2-azolyl-1-(4-fluorophenyl)ethanols of the general formula (I)

wherein X means nitrogen atom (N) or -CH, and their using as fungicides. Proposed compounds possess high fungicide activity and can be used as agricultural, industrial, medicinal and veterinary fungicides.

EFFECT: valuable properties of compounds.

3 cl, 1 tbl, 4 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: claimed mixture from herbicides and antidotes contains (A) herbicidically active substance based on phenylsulfonylureas of formula I and salts thereof (in formula R1 is hydrogen or C1-C6-alkyl; R2 is C1-C3-alkyl; R3 is C1-C3-alkoxy; R4 is hydrogen or C1-C4-alkyl; Hal is fluorine, chlorine, bromine, or iodine); and (B) antidote of formulae II or III , wherein X is hydrogen, halogen, C1-C4-alkyl; C1-C4-alkoxy, nitro or C1-C4-haloalkyl; Z is hydroxyl, C1-C8-alkoxy, C3-C6-cycloalkoxy, C2-C8-alkenyloxy, C2-C8-alkynyloxy; R5 is C1-C2-alkandiyl chain optionally substituted with one or two C1-C4 alkyl residues or (C1-C3-alcoxy)carbonyl; W is bivalent heterocyclic residue; n = 1-5; in weight ratio herbicide/antidote of 100:1-1:100. Also disclosed is method for protection of cultural plants against phytotoxic side effect of herbicidically active substance of formula I. Claimed method includes antidote application of formulae II or III on plant, plant parts, plant seeds or seeding areas before or together with herbicidically active substance in amount of 0.005-0.5 kg/hectare in weight ratio of 100:1-1:100.

EFFECT: mixture for effective selective weed controlling in cultural plant, particularly in maize and grain cultures.

8 cl, 2 ex, 7 tbl

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