Amide derivative and fungicidal composition based on it

 

(57) Abstract:

Usage: in agriculture. The inventive amide derivative f-ly I, where X1, R1, R2, R3the corresponding values, and fungicidal composition based on it. Connection structure f-ly I . 1 C.p. f-crystals, 7 PL. 13 Il.

The invention relates to novel condensed heterocyclic compounds or their salts, and their intermediate compounds, method of their production and the fungicide on their basis for the processing of agricultural and horticultural crops.

Some types of amide compounds having fungicidal activity against pathogenic fungi causing various diseases of plants. For example, compounds disclosed in published application N 135364/1988 patent Japan, will not pass the examination of novelty, published application N A on Europatent and published application N A patent of great Britain, have activity against fungi pathogens downy mildew of grape vines and cucumbers and pathogenic fungi of tomato and potato. However, such compounds do not have sufficient regulatory action and do not provide security.

You created the I and drugs based on them to suppress plant diseases.

Downy mildew and other diseases of plants and fruit trees have a tendency to the emergence and spread during heavy rains. Accordingly, the desired compounds, which are not washed off by rain (dodeactivate), have good action to combat diseases of plants to treat them without damaging cultivated plants, and have low toxicity relative to warm-blooded animals and fish.

The inventors have conducted intensive studies to solve the above problems and has been condensed heterocyclic compounds of General formula I and their salts, which are determined to have an excellent effect against various types of plant diseases, especially downy mildew along with excellent dodeactivate, while not damaging the plants, and which are less toxic relative to warm-blooded animals and fish. These compounds can be obtained industrially.

Thus, the present invention relates to a condensed heterocyclic compound of General formula

Q-CONH-CH I where Q is a condensed heterocyclic group containing nitrogen atom, substituted or negatively electrons, or its salts.

The present invention also relates to a method for obtaining a condensed heterocyclic compound I or its salt in the interaction of compounds of General formula

Q-CO-Z II where Q is above in the formula I value, and Z denotes a leaving group or its salt with a compound of General formula

H2N-CH III where X and Y are specified in formula I, value, or its salt.

In addition, the present invention relates to a fungicide to protect agricultural and horticultural crops on the basis of condensed heterocyclic compounds of General formula I or its salts.

In accordance with another variant of the present invention offers a condensed heterocyclic compound based on carboxylic acids of General formula

Q1-CO-Z IV where Q1means condensed heterocyclic group containing a nitrogen atom in the head of the bridge, as in the following formulas

R1, R1N

N, RR1, R1,

R2, R1or R1< / BR>
where R1WITH1-6-alkyl, halogen, C1-4-alkoxy, C1-4-alkylthio,6-10-aryloxy,6-10-aaltio, alkoxycarbonyl, Fe is l, halogen, nitro, aminosulfonates, mono - or disubstituted, alkylsulfonyl, alkoxycarbonyl, formyl, cyano, phenyl, substituted phenyl or aromatic heterocyclic group, provided that when Q1means

and R1means COOH2CH3then either one of R2and R1is another group other than hydrogen, and Z denotes a leaving group, or its salt.

In accordance with another variant of the present invention provides a method of obtaining compounds of General formula

Q2-CO-Z VIII where Q2means a group of the General formula

R1RR1, R1,

R1or R1< / BR>
where R1, R2and R3have the values indicated above, or its salt, which comprises the interaction of the compounds of General formula

V where the core means the group of pyridine, pyridazine, pyrimidine or pyrazine, which is not substituted or substituted C1-6-alkyl, halogen, nitro-, amino-, sulfo-, mono - or dialkylamino, alkoxycarbonyl, formyl, cyano, phenyl, substituted phenyl or aromatic heterocyclic group, and Z denotes a leaving group, or its salt with a compound of General formula

W--CO-R1VI is e, I or its salts of the present invention is a new structure, characterized by the combination of specific groups, namely condensed heterocyclic group containing the nitrogen atom in the head part of the bridge with the carbonyl group, which is different from the known amide compounds. The advantage of this connection is that it has a good effect of inhibition of downy mildew and fungal diseases of plants, excellent water resistance, do not damage plants and less toxic relative to warm-blooded animals and fish.

The preferred embodiment of the invention.

In formulas I and II Q denotes condensed heterocyclic group containing a nitrogen atom in the head of the bridge, which is substituted or unsubstituted. Condensed heterocyclic group containing a nitrogen atom in the head of the bridge, means a condensed heterocyclic group, where the atom(s) "head" or "tail" bridge connection, both or any one of them is ionized by a nitrogen atom. Condensed heterocyclic group containing an atom in the head part of the bridge, denoted by Q, is a group formed when removing one hydrogen atom connected with SOEDINENIYa, presents, for example, the General formula D or E (see Fig. 1), where a and b represent a heterocyclic nucleus containing a heteroatom of nitrogen, which is not substituted or substituted.

These condensed heterocyclic groups may be represented, for example, the General formula E or W (see Fig. 1).

Preferred of them is the group represented in the left part of this equation.

N-containing heterocyclic nucleus represented by the rings a and b, means 4-8-membered, preferably 5 to 6 membered heterocycle containing one to four nitrogen atoms, which, in addition, may include from one to three oxygen atoms and/or from one to three sulfur atoms, possibly mono - or diocesana. Such heterocyclic nucleus may be optionally fused with a 5-6-membered aliphatic cycle (for example, cyclopentane, cyclohexane), an aromatic cycle (e.g., benzene or naphthalene), or by a heterocycle (preferably 5 to 6 membered heterocycle).

Among these condensed heterocyclic nuclei, the preferred group formed by condensation of 5 - and 6-membered nucleus.

In the above formula the core and preferably is CL, containing one to two nitrogen atoms and one sulfur atom, possibly mono - or docilely.

Cores a and b can be substituted by 1-3 substituents (1IN2IN3) having the same or different values, as indicated below.

In particular, the group represented by the General formula And (see Fig. 1) includes, for example, represented by the General formulas (see Fig. 2), where a' group forming a condensed ring at positions [1, 2] imidazole ring; And" group forming a condensed ring at positions [1, 5] imidazole ring; And"' group forming a condensed ring at positions [1, 5] pyrazol ring; And"" group forming a condensed ring at the positions (1, 2) pyrrole ring; A group forming a condensed ring in positions (3, 4) triazole ring;1IN2and IN3have the following values.

Group And And" And" or A" contains from one to four, preferably from three to four carbon atoms as atom forming a ring, and may optionally contain one to three nitrogen atoms, oxygen and/or sulfur (which may be represented mono - or douceline form).

The most preferable group represented by the General formula M (see Fig. 2).

Examples of the condensed rings represented by the skeleton of General formula (see Fig. 3) include the following: (see Fig. 4).

Examples of the condensed rings represented in the skeleton group of General formula (see Fig. 5) include the following: (Fig. 6).

Examples of the condensed rings represented by a skeleton group of General formula (see Fig. 7) includes (see Fig. 8).

Examples of the condensed rings represented by a skeleton group of General formula (see Fig. 9) includes (see Fig. 10).

Examples of the condensed rings represented by a skeleton group of General formula (see Fig. 11) includes (see Fig. 12).

In particular to these condensed heterocyclic groups include the following:

imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, imidazo[1,2-C]pyrimidine, imidazo[1,2-a] pyrazin, imidazo[1,2-b] pyridazin, imidazo[1,2-b]-(1,2,4-triazine, imidazo[2,1-a] imidazole, imidazo[1,2-b]pyrazole, imidazo[2,1-b]thiazole, imidazo[2,1-b] -(1,3,4-thiazole, 2,3-dihydroimidazo [2,1-b]thiazole, pyrazolo[1,5-a] pyrimidine, pyrazolo[5,1-a] thiazole, pyrazolo[1,5-a] pyridine, pyrrolo[1,3-b] preformulai N (see Fig. 13) includes a group represented by, for example, the General formula P (see Fig. 13), where a1and IN2each has the following value.

In particular, as an example 6N-(1,2,4)-triazolo[1,2-b] -(1,2,3,4)-tetrasil, 1H-(1,2,4)triazolo[1,2-a] -(1,2,4)triazol, (1,2,3)-triazolo[2,1-a]-(1,2,3)- Treaty of a 4-(1,2,4)-triazolo[1,2-a]pyridazine-4 and 6N-pyrazolo[1,2-a]-(1,2,4,5)-tetrasil.

The substituents IN1IN2and IN3the condensed heterocyclic group for Q can be the same or different values. Examples of these substituents include hydrogen, nitro-, amino-, hydroxyl -, cyano-, C1-3-acyl(formyl and so on), carbarnoyl, carboxyl, alkoxycarbonyl (for example, C1-4-alkoxycarbonyl such as methoxycarbonyl, etoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl and so on), alphagraph, halogen (chlorine, bromine, iodine, fluorine, etc.)1-4-alkoxy (methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy and so on), WITH6-10-aryloxy (phenoxy and so on ), WITH6-10-arylcarbamoyl (benzoyl, etc.)6-10aryl (phenyl, etc)7-10-aralkyl (benzyl, phenethyl and so on), WITH3-7-cycloalkyl (cyclohexyl and so on ), WITH1-4-alkylthio (methylthio, ethylthio, etc etc), WITH7-10-Uralkali (benzylthio and so on ), mono - or dialkylamino (for example, mono - or di-C1-4-alkylsulfonyl, for example mono - or dimethylsulphamoyl, mono - or diethylcarbamoyl, mono - or di-n-propyl - sulfamoyl)1-6-alkyl (methyl, ethyl, propyl, isopropyl, pentyl, hexyl and so on), substituted phenyl (mono-, di-, tri - or chetyrehkolenny substituted phenyl, such as 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-forfinal, 4-bromophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl, 2,4-differenl, 2,6-differenl and so on), mono-, di-, tri - or Tetra-C1-4-alkyl substituted phenyl, such as 2-methyl - phenyl, 3-were, 4-ethylphenyl, 4-isopropylphenyl, 2,4-dimetilfenil, 2,5-dimetilfenil, 3,4-dimetilfenil, 2,5-diethyl - phenyl, 2,4,6-trimetilfenil etc., mono-, di-, tri - or Tetra-C1-4-alkoxy-substituted phenyl, such as 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-acid etc., mono-, di-, tri - or Tetra-C1-4- alkylthiomethyl phenyl, for example 2-methylthiophenyl, 3,4-dimethylthiophenol etc. 2-chloro-4-nitrophenyl, 4-nitrophenyl, 2-methyl-4-AMINOPHENYL, 2-bromo-4-nitrophenyl, 2-nitro-4-were, and so on), aromatic heterocyclic group (five - or six-membered heterocyclic group such as pyridyl, furyl, thienyl, UB>1-6-alkyl, phenyl or substituted phenyl.

Q1in the formula IV means condensed heterocyclic group containing a nitrogen atom in the head part of the bridge is represented by the following formula:

R1, R1N

N, RR1, R1,

R2, R1or R1< / BR>
As the substituents R1, R2and R3use the same or different substituents, which are the above values, but any one of R2and R3means a group except hydrogen atom, if Q1means

R2and R1means of SOON2CH3.

Examples of the substituent R1include1-6-alkyl, halogen, C1-4-alkoxy, C1-4-alkylthio,6-10-aryloxy,6-10-aaltio, alkoxycarbonyl, phenyl, substituted phenyl or aromatic heterocyclic group, as described in the above1IN2and IN3. Examples of the substituents R2and R3are hydrogen, nitro-, amino-, alphagraph, formyl, cyano or phenyl, and C1-6-alkyl, halogen, mono - or di-alkylsulfonyl, alkoxycarbonyl, substituted phenyl or aromatic heterocyclic group, as described in the above

Preferred groups Q1are Q' or Q", which are described below.

The symbol X in the General formula I is a hydrogen atom or a group attached through an atom, O, S or N. a Group attached through a carbon atom may be alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl or aralkyl or aromatic heterocyclic group containing a chemical bond at a carbon atom, a group attached through an 0 atom can be alkoxy, aryloxy or aralkylamines; group attached via the S atom can be alkylthio, aaltio or arkitip; and group attached via the N atom can be alkylamino-, arylamino or aralkylamines, or an aromatic heterocyclic group having a chemical bond of atom n

The above alkyl group or the alkyl residue haloalkyl, alkoxy, alkylthio and alkylamino includes a group of straight or branched chain, containing from one to ten carbon atoms, for example methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, n-octyl, n-decyl, etc.

As indicated etail, 3 Metall, 3-butenyl or etc.

As cycloalkyl group may be represented by a three-to six-membered group, such as cyclopropyl, cyclopentyl, cyclohexyl, or etc.

As cycloalkenyl group can be used three or four-membered group, for example cyclopropyl, cyclopentyl, cyclohexenyl or etc.

As the aryl group and the aryl residue aryloxy, aaltio and arylamino can be represented group containing six to ten carbon atoms, such as phenyl, tolyl, xylyl, naphthyl or etc.

As aranceles group or Arakelova residue aralkylated, Uralkali-, and aralkylamines may be a group containing 7-10 carbon atoms, for example benzyl, phenethyl or etc.

As the aromatic heterocyclic group having a chemical bond of an atom can be represented by a five - or six-membered aromatic heterocyclic group, for example

, , and N

As the aromatic heterocyclic group having a chemical bond at the N atom can be represented by a five - or six-membered N-containing group, for example

, N, and N

Each of the above groups, prisoedinyaemsya-, hydroxyl, cyano, carboxyl, alphagroup, halogen (fluorine, chlorine, bromine and so on), alkoxygroup containing from one to four carbon atoms (methoxy, ethoxy, and so on), allylthiourea containing from one to four carbon atoms (methylthio, ethylthio and so on), phenylthiourea, menzilcioglu etc.

Suitable examples of X include a hydrogen atom, a C1-10-alkyl, C2-4alkenyl,1-10-alkoxy,1-10-alkylthio, phenyl, halogen-substituted phenyl, an aromatic heterocyclic group containing a chemical bond of an atom or N or similar To the specific examples of these groups include the following, which are listed as examples for the above IN1IN2and IN3.

The symbol Y in the General formula I is a group that draws electrons, for example, cyano-, carnemolla, thiocarbamoyl or trichlorethylene group or etc.

The compounds of the present invention that are of particular interest include groups of the following formula I':

Q-CONH-CH I'where Q' denotes a group of the formula

B (one of the values IN1' and2' represents a C1-6-alkyl, phenyl or substituted phenyl, and the other value represents a hydrogen atom), X is ü the atom C.

Another group of compounds I of interest is the group of the following formula I"

Q-CONH-CH I"where Q" means

B (B1" means phenyl or substituted phenyl, IN2" the atom of hydrogen or C1-6-alkyl), phenyl, fluoro-substituted phenyl, thienyl or furyl.

WITH1-6is an alkyl group and substituted phenyl group, are given as examples for1IN2and IN3suitable for IN1'IN1"IN2' and2"formulas I and I". Galijasevic phenyl for X may represent a phenyl group substituted by 1 to 4 halogen atoms selected from fluorine, chlorine, bromine, etc. as fluoro-substituted phenyl group for X" can be used ortho-, meta - or paraterphenyl, ortho-, meta-, para-differenl or 2,4,6-tryptophanyl. Aromatic heterocyclic group having a chemical bond of the atom, of the above for X, can be used as a group for X'.

It is preferable example of symbols Q' and Q" refers

where n is 0, 1, 2, 3 or 4, l1-4-alkyl, C1-4-alkoxy, C1-4-allylthiourea or halogen, with the same or different values. Substituted phenyl groups mentioned above for the IN1

The compounds I of the present invention contain asymmetric carbon atom, and the present invention includes within its scope each of the isomers due to the asymmetric carbon atom and their mixture.

As salts of the compounds of formula I of the invention can be used salt formed during the interaction of an alkali metal or alkaline earth metal such as sodium, magnesium, potassium, calcium, etc., with an acid group (for example, carboxypropyl and so on) contained as a substituent, or a salt formed during the interaction of inorganic acids, for example hydrochloric, phosphoric, sulfuric acid, etc. or organic acids, for example oxalic, acetic, benzoic acid with an alkaline group contained in the substituent (s) or condensed heterocycle.

Carboxylic acids of formula II and IV c condensed heterocycle, which is used as the source materials of the present invention, or their salts can be obtained by the method similar to a known (see jour. J. Org. Chem. so 37, S. 3107, 1972; J. Org. Chem. so 36, c. 2678, 1971; J. Org. Chem. so 42, 4197 S., 1977; J. Med. Chem. so 17, 645 S., 1974; J. Med. Chem. so 20, S. 386, 1977; J. Med. Chem. so 15, S. 982, 1972; J. Med. Chem. so 28, S. 876, 1985; Tetrahedron Lett, T. 21, S. 2195, 1980, J. Chem. Soc. Perkin is the returns, for example, when interacting aromatic heterocyclic aminocarbonyl acid, its reactive derivative or salt with the compound of the formula VI or VII.

In particular, compound VII or its salt, which is often used among the new compounds IV or their salts can be obtained by reacting the compounds of formula V or its salt with the compound VI and compound VII.

In formulas II, IV, V and VIII, Z denotes a leaving group, and accordingly, the group Z may denote-COOH or its reactive derivative. Thus, compound II or its salt can be represented by a carboxylic acid of the formula

Q COOH II' where Q' is listed above values, or its reactive derivative, or its salt;

compound V or its salt can be represented by a carboxylic acid of the formula

V' where the ring has the values indicated above, or its reactive derivative or its salt;

compound VIII or its salt can be represented by a carboxylic acid of the formula

Q2COOH VIII' where Q2has the values indicated above, or its reactive derivative, or its salt, respectively.

Examples of reactive derivatives of u and VIII' are the anhydrides of the acids, active amides, active esters or etc.

The following are specific examples of such reactive derivatives.

Anhydrides of acids may be represented by mixed anhydrides with alojamiento acids (e.g. hydrochloric acid or Hydrobromic acid), esters of carbonic acid, aliphatic carboxylic acids (e.g. acetic, trimethyloxonium, valerianic, isovalerianic or trichloroacetic acids) or aromatic carboxylic acids (e.g. benzoic acid), symmetrical anhydrides of the acids.

As an active amides can be amides with pyrazole, imidazole, 4-substituted imidazole, dimethylpyrazole or benztriazoles.

As active esters can be represented by a complex of methyl, ethyl, methoxymethyl, propargilovyh, 4-nitrophenyloctyl, 2,4-dinitrophenoxy, trichloranisole, pentachlorophenoxy or methylsulfinylbutyl esters or other esters with 1-hydroxy-1H-2-pyrrolidone, N-hydroxysuccinimide or N-hydroxyphthalimide.

Such reactive derivatives at the carboxyl group selected accordingly and used in C is acyclically aminocarbonyl acid and carboxylic acid II', IV', V' and VIII' can be used in its free form (for example, in the form of carboxylic acid) preferably in the presence of a condensing reagent such as N,N'-dicyclohexylcarbodiimide, N-cyclohexyl-N'-morpholinobutyrophenone, N-cyclohexyl-N'-(4-diethylaminoethoxy)carbodiimide or N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide. In addition, the above carboxylic acids can be used in the form of salts with alkali or alkaline earth metal.

The symbol W in formulas VI and VII means a halogen atom, for example chlorine, bromine or fluorine. Ring in the formula V can be pyridine, pyridazinyl, pyrimidine or pyrazinium ring which may be substituted by a group mentioned in the R3, Q2in the preferred embodiment, has a value Q' or Q".

The above reaction can be conducted without using a solvent or in any solvent, and optionally in the presence of a condensing reagent such as a Foundation. As suitable solvents can be used alcohols such as ethanol, isopropanol etc., aromatic hydrocarbons such as benzene, toluene, xylene, golozhabernyi hydrocarbons, for example methylene chloride, chloroform, tetrachlormethane acetone, methyl ethyl ketone etc., NITRILES such as acetonitrile, propionitrile etc., amides such as dimethylformamide, dimethylacetamide etc., esters such as methyl acetate, ethyl acetate, butyl acetate, etc. or mixtures thereof. If necessary, you can use a mixed solvent consisting of water and an aromatic or Alojamientos hydrocarbon. The solvent is usually used in an amount of from 1 to 50 parts (by weight) is preferably from 5 to 10 parts relative to the carboxylic acids or their reactive derivatives or salts.

The reaction can be accelerated by adding bases to the solvent. As a suitable base can be used tertiary amines such as triethylamine, pyridine, 4-dimethylaminopyridine, DBU (1,8-diazabicyclo(5,4,0)-undecene-7), and so on, hydroxide, carbonate or bicarbonate of alkali or alkaline earth metal or an alcoholate of an alkali metal, for example sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, sodium alcoholate, or ORGANOMETALLIC salt such as n-utillity. The specified base is used usually in an amount of from 1 to 5 equivalents, preferably 1 to 3 equivalents relative to the carboxylic acid, Este from 1.1 to 2.0 mol per 1 mol of carboxylic acid or its reactive derivative, or salt in this reaction. This reaction can be conducted at room temperature (for example, in the range of 10 to 30aboutC) or at elevated temperature (for example, from 30 to 100about(C) to speed up interaction. The reaction time depends on the reaction temperature, and the reaction usually lasts from 15 minutes to 24 hours, preferably from 30 minutes to 10 o'clock

Thus, the obtained compound II or IV can be distinguished and clear in the form of a free base known method, for example by chromatography on silica gel (kieselgel R 60 manufactured by Merck and Co, Inc. using as eluent solvent is chloroform, ethyl acetate and so on), or to isolate and purify the salt accession acid when using inorganic acids such as hydrochloric, sulfuric, phosphoric, or organic acids such as acetic, benzosulfimide, a pair of toluensulfonate, methanesulfonate, citric, tartaric, oxalic, propionic, maleic, malic, malonic, fumaric, almond, ascorbic acid, in the traditional way using known techniques, such as concentration, concentration under reduced pressure, extraction, phase transfer, crystallization, paracrystalline is the", the join can be converted into a salt by interaction with alkali or alkaline earth metal, as was cited as an example earlier in accordance with the traditional method, which you can then select and clear by known means.

Condensed heterocyclic derivatives of carboxylic acids II or IV or its salt obtained in accordance with the above reaction can also be turned into nitrosamine connection normal reaction nitration or alojamiento connection using halogenides reagent, for example N-bromosuccinimide (NBs), N-chlorosuccinimide (NCS) or etc.

Amines III and their salts (salts with acids mentioned above in the compounds II and IV, can be obtained in a known manner.

Compound I or its salt can usually be obtained by interaction of the compound (II) or its salt without the use of a solvent or in an appropriate solvent in the presence of an appropriate base or a condensing reagent. The solvent can be used aromatic hydrocarbons such as benzene, toluene, xylene, golozhabernyi hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride, etc the amides, for example dimethylformamide, dimethylacetamide, esters such as methyl acetate, ethyl acetate, butyl acetate or mixtures thereof. If necessary, you can use a mixture consisting of water and an aromatic or Alojamientos hydrocarbon.

The solvent is usually used in a ratio of from 1 to 50 parts (by weight), preferably from 5 to 10 parts relative to the compound (II) or its salt. The above reaction can be accelerated by adding bases to the solvent. As a suitable base can be used tertiary amines such as triethylamine, pyridine, DBU (1,8-diazabicyclo[5,4,0]undec-7-ene), hydroxides, carbonates or bicarbonates of alkali or alkaline earth metal or alkali metal alcoholate, for example sodium carbonate, potassium bicarbonate, sodium hydroxide, potassium alcoholate, sodium, or metal organic salt, such as n-utility and so on This basis is usually used in an amount of from 1 to 20 equivalents, preferably 2 to 5 equivalents relative to the compound (II) or its salt. Suitable condensing reagents can be used thionyl chloride, the acid chloride phosphoric acid, carbonyldiimidazole, N-methyl-2-bromopyridine iodide, DICYCLOHEXYL occhialino from 2 to 5 equivalents relative to the compound (II) or its salt.

During the interaction, compound II or its salt is used in an amount of from 1.1 to 1.5 mol per 1 mol of compound III or salts thereof. The reaction can be conducted under cooling with bringing to room temperature (in the range of from 20 to 30aboutC), or at elevated temperature, for example in the range of from about 30 to 100aboutWith to speed up interaction. Although the reaction time depends on the reaction temperature, but the reaction usually lasts from 15 minutes to 15 hours, and in the preferred embodiment, from about 20 minutes to 8 o'clock

Thus obtained compound I can be identified and clear in the form of the free base in a known manner, for example by chromatography on silica gel (kieselgel 60 manufactured by Merck and Co. Inc. using as eluent solvent is chloroform, ethyl acetate, or to isolate and purify the salt accession acid when using inorganic acids such as hydrochloric, sulfuric, phosphoric acid, etc. or organic acids, for example acetic benzosulfimide, para-toluenesulfonic acid, methanesulfonate, citric, tartaric, oxalic, propionic, maleic, malic, malonic, fumaric, almond, ascorbic acid, in the traditional way. In the event that Sogdiana can be converted into a salt using an alkaline or alkaline-earth metal, which you can then isolate and purify the well-known methods.

The compounds of formula I of the present invention have an excellent effect of preventing and regulating various types of plant diseases caused by pathogenic fungi, especially downy mildew of vegetables, such as cucumbers, Chinese cabbage, onions, beans and fruit trees, for example, vines, citrus, Apple trees, rot of tomato, potato, eggplant, green pepper, pumpkin. In addition, the proposed compounds of formula I and their salts have sustained fungicidal effect over a much longer period of time after applying them to plants (extended benefits), their fungicidal activity decreases to a lesser extent due to a small wash their rain after application by spraying method (dodeactivate). Thus, the proposed compounds I or their salts exhibit sufficient effects even in the rainy season, when often downy mildew, a disease, followed by the decay of plants. Moreover, we offer you the compounds I and their salts possess security and better ability as is in the attitude of the fish.

The proposed compounds of formula I or their salts can be used as a fungicide in the traditional form of agricultural pesticides. In particular, depending on the intended purpose in the preferred embodiment, it is possible to use one, two or more types of the proposed compounds I in the form of an emulsifiable concentrate, an oily preparation, spray solution, wettable powder, powder, granules, ointments, which can be formulated with an appropriate carrier or carriers in the traditional way, for example, by dissolving or dispersing them in a liquid medium, mixing with a suitable solid carrier or adsorption is carried on a solid carrier. If necessary, to the above drugs, which can be obtained by any conventional method, it is possible to add the emulsifier, suspendisse agent, spray, wetting agent, moisturizing agent, binder, stabilizer, etc.

The preferred flow rate of compound I of the present invention or its salts for the whole fungicidal composition is from about 1 to 80 wt. for emulsifiable concentrate or wettable powder, from about 0.1 to 10 wt. for preparation in the form of oil or powder is from the intended target. Emulsifiable concentrates, wettable powders, etc. before use to the desired degree bred and fill (for example to 100-5000-fold volume of water or so on, and then sprayed them.

As a suitable liquid carrier (solvent) can be used, for example, water, alcohols (methanol, ethanol, n-propanol, isopropyl alcohol, ethylene glycol), ethers (dioxane, tetrahydrofuran, onomatology ether of ethylene glycol, onomatology ether of diethylene glycol, onomatology ether of propylene glycol), ketones (acetone, methyl ethyl ketone), aliphatic hydrocarbons (kerosene, light oil, fuel oil, machine oil), aromatic hydrocarbons (benzene, toluene, xylene, solvent-naphtha, methylnaphthalene), golozhabernyi hydrocarbons (methylene chloride, chloroform, carbon tetrachloride), amides acid (dimethylformamide, dimethylacetamide), esters (ethyl acetate, butyl acetate, ether of glycerol and fatty acids), NITRILES (acetonitrile, propionitrile) or so on These liquid carriers may be used separately, and in the form of arbitrary mixtures thereof.

As a suitable base for ointments can be used, for example, polyethylene glycol, pectin, esters of polyhydric with the oz, sodium alginate, bentonite, higher alcohols, polyhydric alcohols, such as glycerin, petrolatum, white petrolatum, liquid paraffin, lard, various vegetable oils, lanolin, anhydrous lanolin, hard grease, tar, etc., These grounds can be used both separately and in the form of arbitrary mixtures thereof, or in combination with surface-active substance, the following as an example.

As surface-active substances used if necessary, as an emulsifier, sprayer, wetting agents, dispersant, etc. can be applied nonionic or anionic surfactants, such as Soaps, polyoxyalkylene esters (for example Nonalmanufactured by Jakemoto Gushi K. K. Japan), alkyl sulphates (e.g. Emal Emal 10 40manufactured by Kao-Atlas K. K. Japan), alkyl sulphonates (for example NeogenThe Neogene Tmanufactured by Dai-ichi Kojyo Seiyaku K. K. Japan), Neoplexmanufactured by Kao-Atlas K. K. Japan, ethers of polyethylene glycol (for example, Nonpol 85, Nonpol 100, Nonpol 160manufactured by Sanyo Kasli K. K., Japan) esters of polyhydric alcohols/P> The fungicide of the present invention can be applied at any time, since the processing of seeds, seedlings (seedlings) until harvest. The proposed fungicide can be used to prevent outbreaks of plants during the preliminary preparation, as well as for the treatment of diseases of plants by adding it after the appearance of the disease commonly known method.

The amount of compound I of the present invention or its salts, used as an agricultural pesticide, may vary depending on conditions such as the stage of plant development and the area of cultivation of plants, in which shall be entered the pesticide, the type of disease plants, fire outbreak, time and method of application of the fungicide, etc. Compound I or its salt is used usually in an amount of about 3 to 300 g, preferably about 10 to 100 g / 10 ar. The concentration of the applied active ingredient is preferably from 10 to 1000 h/million Fungicide usually contribute directly by scattering, dusting or sprinkling it directly on the plant or pollinated seeds. The number, concentration and method of application if you wish to change to ensure safe and effective use of fungicide types of fungicides (for example, the fungicide on the basis of organochlorine compounds, fungicide based on organophosphorus compounds, fungicide based on organic sulfur compounds, benzimidazole fungicide type, copper-containing fungicide, phenol fungicide, a triazole fungicide type, pyrimidine fungicide type, fungicide type acrylic acid, fungicide type sulfenamide, fungicide types of amino acids, the fungicide in the form of antibiotic, and so on), insecticides (for example, a natural insecticide, insecticide type carbamates, insecticides based on organophosphorus compounds, insecticide type phytotoxin, a synthetic PYRETHROID, and so on), acaricides, nematicides, herbicides, hormones for plants the plant growth regulators, stabilizers, synergists, attractants, repellents, otdushivayuschikh substances, pigments, fertilizers, nutrients for plants, various amino acids, low - or high-molecular phosphoric acid or so on, To obtain a synergistic effect can also add metal salts (for example, copper chloride, copper sulfate, and so on).

The proposed compounds I and their salts have excellent protective or preventive effect in compounds or their salts are not washed off, have excellent resistance to rain and hence demonstrate excellent protective and preventive action especially during the rainy period. The compounds I or their salts decrease the spread of diseases of vegetable crops and fruit trees and can be used as the preferred fungicide, not causing any significant harm to the crop.

And with n s t a n d s 1. Protection from disease of tomatoes.

The compound of the invention dissolved in dimethylformamide (concentration of 1 wt. ), then the resulting solution was added xylene (concentration 0.2 wt.) and tween-20 (concentration of 0.02 wt.). The resulting mixture was diluted with water to a predetermined concentration of the active ingredient. To the specified solution is added wetting agent, D approzimately company Takeda Chemical Industries, LTD., containing 20% (wt./wt) nonylphenoxy ether of polyoxyethylene and 12% Liminality calcium in the amount of 0.05% (wt./wt), the final concentration of obtaining the spray solution. This solution is sprayed on the seedlings of tomato plants about four weeks of age) until runoff solution drops. After drying the plants in the air carry out the inoculation suspension, containing the Le inoculation of plants incubated in a humid room when 17aboutC for 5 days. After that, assess the extent of injury by disease of plants. The measure of protection provided in accordance with the following factors:

The measure of protection 3; size of the defeat 0-5%

The measure of protection 2; the area of damage 6-15%

The measure of protection 1; lesions 16-30%

The measure of protection 0; lesions of 31% or more.

The results obtained are presented in table. 1.

And with n s t a n d s 2. Protection against downy mildew of cucumbers.

According to the method described in test 1, get solution for spray containing compound of the present invention at a given concentration, which POPs on young seedlings (approximately three weeks of age) cucumbers to drip drops of the specified solution. After drying plants, air suspension containing zoosporangia causative agent of downy mildew of cucumbers (concentration of about 105/ml) inoculant by means of spraying. After inoculation the plants stand in a damp room for 6 days. After that, assess the area of the lesion plant disease, while the measure of protection provided in accordance with the following factors:

Display; the horse defeat 16-30%

The measure of protection 0; lesions of 31% or more.

The results are shown in table. 2.

And with n s t a n d s 3. Protection of grapevine against downy mildew.

According to the method described in test 1, get solution for spraying containing compound of the present invention at a given concentration, which is then sprayed on young seedlings of grapes (about six weeks of age) before draining the specified solution drops. After drying in air suspension containing zoosporangia causative agent of downy mildew of grapes (concentration of approximately 105/ml) inoculant by spraying. After inoculation the plants stand in a damp room at the 18aboutC for 10 days. After that evaluate the degree of the damage to plants, while the measure of protection determined on the basis of the following factors:

The measure of protection 3; size of the defeat 0-5%

The measure of protection 2; the area of damage 6-15%

The measure of protection 1; lesions 16-30%

The measure of protection 0; lesions of 31% or more.

The results obtained are presented in table. 3.

In table. 1-3 rooms in the column of the test seimaden above test results it is seen, the compounds I of the invention and their salts have an excellent effect for protection against downy mildew and prevent diseases of vegetable crops and fruit trees.

The invention is explained in more detail in the following examples, but it should not be limited to these examples. Elution during column chromatography was performed under conditions of thin-layer chromatography (TLC). TLC was performed using kieselgel 60F 254 (Art. 5715), manufactured by Merck and Co. as a TLC plate, the same solvent used as an elution solvent column chromatography, which is used as manifesting solvent and UV detector as a means for detection. As silica gel that fills the column used kieselgel 60 (70-230 mesh. Art. 7734), manufactured by Merck and Co. Under an NMR spectrum mean PAMR (1H NMR), and as an internal and external standard of tetramethylsilane was used. NMR spectrum measured by the spectrometer type Varian em 390 (90 Hz) if not otherwise stated. Each value given in h/million Numerical value in parentheses indicates the rate of mixing by volume of each solvent used is the reamers and tables, has the following values:

S singlet, d doublet, m multiplet, t triplet, br broad, I the coupling constant, HZ HZ CD Cl3heavy chloroform, DMSOd6 heavy dimethyl sulfoxide; (except exit): wt./wt.

Under room temperature with a temperature in the range from 15 to 25aboutC.

P R I m e R 1. Synthesis of methyl ester of imidazo[1,2-a]pyridine-8-carboxylic acid (compound 1-1).

47% Pomodoro (2.5 ml, 14.4 mmol) was added to diethoxymethane (2.0 ml, 13,2 mmol) and the resulting mixture was stirred at 50aboutC for 2 h Then the reaction mixture is cooled to room temperature and add ethanol (7.0 ml) and sodium bicarbonate (1.0 g, to 11.9 mmol). The mixture is stirred and the precipitated precipitate is filtered off. To the obtained filtrate was added methyl ether 2-aminonicotinic acid (1.0 g, 6.6 mmol), sodium bicarbonate (2.0 g, of 13.8 mmol) and ethanol (7.0 ml) and the resulting mixture is heated under reflux for 4 hours, the Reaction mixture was cooled to room temperature and add it saturated aqueous solution of sodium bicarbonate. The resulting mixture was extracted with dichloromethane (100 ml x 3), the extract obtained was washed with water, dried over anhydrous magnesium sulfate MgSO4UNT: chloroform, and then a mixture of chloroform and methanol 9:1), the result is the target compound (0.6 g, yield 55%) as yellow crystals, so pl. 67-69aboutC.

P R I m m e R 2. Synthesis of methyl ester of 2-Mei[1,2-a]pyridine-8-carbon - howl acid (compound 1-3)

Bromoacetone (6.5 g, and 42.7 mmol) and methyl ester of 2-aminonicotinic acid (4.8 g, to 31.5 mmol) was added to ethanol (50 ml) and the resulting mixture is refluxed for 17 hours, the Reaction mixture was cooled to room temperature, the solvent is distilled off under reduced pressure. To the residue was added saturated aqueous sodium bicarbonate solution (50 ml) and the resulting mixture extracted with chloroform (100 ml x 3). The extract is washed with water, dried on MgSO4and evaporated under reduced pressure. The concentrate is purified column chromatography on silica gel (eluent:chloroform and then a mixture of chloroform and methanol 9:1). Get the target compound (4.0 g, yield 85%) as an oily substance.

P R I m e R 3. Synthesis of bromhidrosis ethyl ester of 2-phenyl-imidazo[1,2-a] pyridine-8-carboxylic acid (compound 1-25).

Bromide pencil (11,0 g, 55.3 mmol) and ethyl ester of 2-aminonicotinic acid (8,68 g of 52.2 mmol) was added to methyl ethyl ketone (100 is atoi temperature during the night and after collecting the precipitated crystals by filtration obtain the target compound (16.3 g, output 89,96%) in the form of crystals, so pl. 174-176aboutC.

P R I m e R 4. Synthesis of methyl ester of 3-chloro-2-methylimidazo[1,2-a]pyridine - 8-carboxylic acid (compound 1-15)

Methyl ester 2-methylimidazo[1,2-a]pyridine-8-carboxylic acid (5.3g of 27.9 mmol) was dissolved in chloroform (30 ml) and the resulting solution was added N-chlorosuccinimide (3.7 g of 27.9 mmol), conducting interaction at room temperature for 40 minutes Then the reaction mixture was added 10% aqueous sodium bicarbonate solution (80 ml) and the resulting mixture is stirred for 30 minutes the Organic layer is separated from the reaction mixture, and the aqueous layer was extracted with chloroform (10ml X3). The extracts are combined, washed with water, dried over gSO4and concentrate under reduced pressure. The concentrate is purified column chromatography on silica gel (eluent: chloroform), resulting in a gain of the target compound (3.6 g, yield 57%) as an oily substance.

P R I m e R 5. Synthesis of methyl ester of 3-dimethylaminomethyl-2-methylimidazo[1,2-a] pyridine-8-carboxylic acid (compound 1-17).

To acetonitrile (10 ml) was added 37% formaldehyde (0.3 ml) and acetic acid, and 50% aqueous solution of dimethylamine (0.3 ml), slowly pribavlyayut[1,2-a]pyridine-8-carboxylic acid and the interaction continues at a temperature of 50aboutC for 2 h and then at room temperature for 2.5 hours, the Reaction mixture was evaporated under reduced pressure, and then neutralized with a saturated aqueous solution NaH3. The resulting solution was extracted with dichloromethane, the extract washed with water, dried over anhydrous sodium sulfate and after evaporation under reduced pressure to obtain the target compound (0,48 g, yield 52%), so pl. 123-124aboutC.

P R I m e R 6. Synthesis of 2-methylimidazo[1,2-a]pyridine-8-carboxylic acid (compound 1-4).

Methyl ester 2-methylimidazo[1,2-a]pyridine-8-carboxylic acid (4.0 g, 21 mmol) dissolved in a mixture consisting of ethanol (45 ml) and water (20 ml), and then add sodium hydroxide (2.5 g, 63 mmol). The resulting mixture is refluxed for 30 minutes, the Reaction mixture was cooled to room temperature, and then evaporated under reduced pressure. To the concentrate was added water, then the mixture is brought to pH 4 by the introduction of concentrated hydrochloric acid. The precipitated crystals are collected by filtration, resulting in a gain of the target compound (2.3 g, yield 64%).

P R I m e R 7. Synthesis of 2-phenylimidazo[1,2-a]-pyridine-8-carboxylic acid (compound 1-26).

Bromohydrin atalog NaOH (200 ml) and ethanol (100 ml), then the resulting mixture was refluxed for 1 h, the Reaction mixture was cooled to room temperature, and the alcohol is distilled off under reduced pressure. The residue was adjusted to pH 4 by the introduction of concentrated hydrochloric acid. The precipitated crystals are collected by filtration, resulting in a gain of the target compound (56.7 g, yield 98.4 per cent) in the form of crystals, so pl. 226aboutWITH

P R I m e R 8. Synthesis of 2-chloromethylketone[1,2-a]pyridine-8-carboxylic acid (compound 1-90).

Ethyl ester of 2-chloromethylketone[1,2-a]pyridine-8-carboxylic acid (8,4 g, and 24.2 mmol) was added to concentrated hydrochloric acid (100 ml) and the resulting mixture is refluxed for 5 hours, the Reaction mixture was cooled to room temperature and set the pH to 4 with the introduction of a saturated aqueous solution of sodium bicarbonate. Deposited crystals are collected by filtration to yield the target compound (56.7 g, yield 98.4 per cent) in the form of crystals, so pl. 250aboutWith (Razlog.).

P R I m e R 9. Synthesis of 3-nitro-2-(4-nitrophenyl)-imidazo[1,2-a]pyridine-3-carboxylic acid (compound 1-96).

Ethyl ester of 2-phenylimidazo[1,2-a]pyridine-8-carboxylic acid (2.9 g, 10 mmol) is dissolved in concentrated RA) at 10aboutC. After introducing the resulting mixture was stirred at room temperature for 30 min, then poured into ice water and the pH is adjusted to 7 by adding 20% NaOH. The precipitated crystals are collected by filtration, representing a complex ethyl ester of the titled compound (3.6 g, yield of 99.2%). The solution of these crystals in concentrated hydrochloric acid (35 ml) is refluxed for 1.5 h, after which it is cooled to room temperature. After filtration of the precipitated crystal and drying obtain the target compound (2.9 g, 87.3%), so pl.>300aboutC.

P R I m e R 10. Synthesis of 3-nitroimidazo[1,2-a]pyridine-8-carboxylic acid (compound 1-125 N).

Ethyl ester of 2-ethoxycarbonylmethyl[1,2-a]pyridine-8-carboxylic acid (3.8 g, 14.5 mmol) was dissolved in concentrated sulfuric acid (10 ml) and the resulting solution was gradually added 70% nitric acid (1.5 ml) at 10aboutC. the resulting mixture was stirred at room temperature for 30 min, then poured into ice water and set to pH 7 by the introduction of a 20% sodium hydroxide. After filtration of the precipitated crystals receive the ethyl ester of 2-etoxycarbonyl-3-nitroimidazo[metal in concentrated hydrochloric acid (35 ml) is refluxed for 1.5 h and then cooled to room temperature. The precipitated crystals are collected by filtration and after drying obtain the target compound (1.2 g, yield of 74.3%), with so pl. 300about.

P R I m e R 11. Synthesis of ethyl ester of 3-formyl-2-phenylimidazo[1,2-a] pyridine-8-carboxylic acid (compound 1-119).

To the solution containing bromohydrin ethyl ester 2-phenylimidazo[1,2-a] pyridine-8-carboxylic acid (14,7 g, 4 mmol) in dimethylformamide (8 ml) was added dropwise to the acid chloride phosphoric acid (2 ml), keeping the reaction temperature below 15aboutC. Then the reaction is carried out at room temperature for 30 min and 2 hours at 70aboutC. After completion of the reaction, the reaction mixture is cooled, poured into ice water and adjusted pH to 7 with the introduction of a 20% aqueous sodium hydroxide. The precipitated crystals are collected by filtration and recrystallization from ethanol obtain the target compound (1.0 g, 85.5% of output) in the form of colorless crystals, so pl. 139aboutC.

P R I m e R 12. Synthesis of ethyl ester of 3-cyano-2-phenylimidazo[1,2-a]pyridine-8-carboxylic acid (compound 1-121).

Bromohydrin ethyl ester 2-phenylimidazo[1,2-a] pyridine-8-carboxylic acid (1,96 g to 5.35 mmol) and triethylamine (0.55 g, 5,44 mmol) was added to acetonitrile (20 ml). Then found acetonitrile (5 ml) at an internal reaction temperature from 0 to 20aboutC. Then the mixture was kept at room temperature for 1 h after the reaction mixture is concentrated under reduced pressure. The resulting concentrate, which was added water, then extracted with dichloromethane, the extract washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue is purified by chromatography on a column of silica gel (eluent: chloroform) to obtain the target compound (1.06 g, yield 67,9%) in the form of crystals, so pl. 87-89aboutC.

P R I m e p 13. Synthesis of ethyl ester of 2-ethoxycarbonylmethyl[1,2-a] pyridine-8-carboxylic acid (compound 1-123).

A mixture consisting of ethyl ether bronirovochnoy acid (2.3 g, 10.2 mmol) and ethyl ester of 2-aminonicotinic acid (1.7 g, 10 mmol) in methyl ethyl ketone (17 ml) is boiled for 5 hours After completion of the reaction the mixture is cooled to room temperature and removal of the solvent is distilled off under reduced pressure. The residue to which was added saturated aqueous sodium bicarbonate solution (50 ml, extracted with chloroform. The extract is washed with water, dried over MgSO4and evaporated under reduced pressure. The residue is purified by chromatography on a column of silica gel (eluent:utilize is 14. Synthesis of ethyl ester of 2-methyl-3-sulfonamides[1,2-a] imidazo[1,2-a]pyridine-8-carboxylic acid (compound 1-127).

To a solution containing ethyl ester 2-methylimidazo[1,2-a]pyridine-8-carboxylic acid (1.2 g, 5.9 mmol) in chloroform (15 ml) was added chlorosulfonyl (0.6 ml). The mixture is refluxed for 3 h, and then evaporated under reduced pressure. The precipitation of the crystals are collected by filtration, washed with plenty of water and after drying obtain the target compound (1.2 g, 71.4%) in the form of crystals, so pl. 247-250aboutWith (Razlog.).

P R I m e R 15. Synthesis of ethyl ester of 2-methyl-3-N-methylsulfonylamino[1,2-a]-PI - ridin-8-carboxylic acid (compound 1-129).

Ethyl ester of 2-methyl-3-sulfonamides[1,2-a]pyridine-8-carboxylic acid (1.7 g) and tri-n-Propylamine (2.6 g) was added to acetonitrile (17 ml). Then to the mixture was added the acid chloride phosphoric acid (1.1 ml), maintaining the internal reaction temperature in the range of 50-60aboutC. thereafter, the mixture is maintained at the same temperature for 1 h After completion of the reaction, the mixture is evaporated under reduced pressure and to the residue is added water. The precipitated crystals are collected by filtration,about acid (1.2 g, 66,3%) in the form of crystals, so pl. 182-183aboutC.

The obtained crystals (1.2 g) dissolved in acetonitrile (12 ml) and the resulting solution was added dropwise 40% aqueous solution of methylamine (0.75 g) in acetonitrile (3 ml) at an internal reaction temperature of 0 to 10aboutC. Then the mixture was incubated at room temperature for 1 h After completion of the reaction, the mixture is evaporated under reduced pressure. Concentrate, to which are added water, brought to pH 7 by introducing dilute hydrochloric acid. The precipitated crystals are collected by filtration, washed with water and after drying obtain the target compound (1.1 g, yield 93,2%) in the form of crystals, so pl. 184-185aboutC.

P R I m e R 16. Synthesis of 2-chloroimidazo[1,2-a]pyridine-8-carboxylic acid (compound 1-135).

A mixture of diethyl ether posledney malonic acid (26 ml) and ethyl ester of 2-aminonicotinic acid (13.3 g) is subjected to interaction with 80-90aboutC for 6 h in nitrogen atmosphere. After completion of the reaction the mixture is cooled to room temperature and add acetone (100 ml). The precipitated crystals are collected by filtration output bromhidrosis 3,8-dietoksikarbonil-2-hydroxyamides[1,2-a]peridiocally at 160aboutC for 2 h in an autoclave. After the reaction the excess acid chloride phosphoric acid is distilled off under reduced pressure. To the residue was added ethanol and the resulting mixture was evaporated under reduced pressure. The concentrate is purified column chromatography on silica gel (eluent: chloroform) to give 2-chloro-3,8-diethoxycarbonyl[1,2-a] pyridine (compound 1-133) (2.2 g, yield of 40.3%) in the form of crystals, so pl. 105-106aboutC.

The obtained crystals (0.9 g) dissolved in ethanol (10 ml) and the resulting solution was added 10% sodium hydroxide (5 ml). The mixture was kept at room temperature for 1 h, and then bring it to pH 4 by addition of concentrated hydrochloric acid. The crystals precipitated in the precipitate, collected by filtration, washed with water and after drying receive 2 chloroimidazo[1,2-a] pyridine-3,8-dicarbo new acid (0.73 g, yield 100%) as crystals, so pl. 210-212aboutWith (Razlog.). Then the mixture of the obtained crystals (0.73 g) in concentrated hydrochloric acid (5 ml) is refluxed for 2 hours the Reaction solution is brought to pH 4 by the addition of saturated aqueous sodium bicarbonate solution with the formation of crystals of the target compound (0.5 g, yield of 83.9%), so pl. 237about

-(2-Furyl) - aminoacetonitrile (0.7 g, 5.5 mmol) dissolved in acetonitrile (20 ml) and to the resulting solution under stirring was added the acid chloride of imidazo[1,2-a] pyridine-8-carboxylic acid (1.0 g, 5.5 mmol). The resulting mixture is subjected to interaction at room temperature for 2 hours After completion of the reaction the solvent is distilled off from the reaction mixture under reduced pressure. To the residue was added water (20 ml), saturated aqueous sodium bicarbonate solution (50 ml) and chloroform (50 ml) and the resulting mixture is stirred. The organic layer is separated, dried over anhydrous magnesium sulfate and concentrated. The concentrate is purified column chromatography on silica gel (eluent: ethyl acetate/n-hexane, 2:1). Get the target compound (0.16 g, yield 11%) in the form of crystals, so pl. 149-151aboutC.

P R I m e R 18. Synthesis(imidazo[1,2-a]pyridine-5-ylcarbonyl-(2-furyl) acetonitrile (compound 2-134).

-(2-Furyl) - aminoacetonitrile (0.7 g, 5.5 mmol) dissolved in acetonitrile (20 ml) and the resulting solution was added the acid chloride of imidazo[1,2-a] pyridine-5-carboxylic acid (1.0 g, 5.5 mmol). The resulting mixture is subjected to interaction at room temperature for 2 hours After completion of the reaction the solvent prowess is chloroform (50 ml) and the resulting mixture is stirred. The organic layer is separated, dried over anhydrous magnesium sulfate and evaporated. The residue is purified column chromatography on silica gel (eluent:methanol/chloroform, 1:9) to obtain the target compound (0.9 g, yield 64%) as amorphous solid.

P R I m e R 19. Synthesis of(2-phenylimidazo[1,2-a]pyridine-8-ylcarbonyl)-(2 - furyl)acetonitrile (compound 2-24).

2-Phenyl-imidazo[1,2-a] pyridine-8-CT - oil acid (1.5 g, 5.5 mmol) was added to dry tetrahydrofuran (100 ml), and then to the resulting mixture is slowly added carbonyldiimidazole (1.5 g, 5.5 mmol) under stirring at room temperature in a nitrogen atmosphere. The mixture is stirred at room temperature for 8 h, and then added -(2-furyl)- -aminoacetonitrile (0.7 g, 5.5 mmol) and the reaction is carried out at room temperature for 5 hours the Solvent is distilled from the reaction mixture under reduced pressure, the obtained residue was added water (20 ml) and ethyl acetate (50 ml), then stirred. The organic layer is separated, dried over anhydrous magnesium sulfate, and then evaporated. The concentrate is purified column chromatography on silica gel (eluent: ethyl acetate/n-hexane, 1:1) obtain the target compound (0.9 g, yield 64%) in the form of a crystal is clonicel (compound 2-10).

3 Chloroimidazo[1,2-a] pyridine-3-Carbo - new acid (1.8 g, 9.2 mmol) was added to thionyl chloride (20 ml) and the resulting mixture is refluxed for 30 minutes under stirring and then evaporated under reduced pressure. The crude acid chloride -(2-furyl)- -aminoacetonitrile (1.1 g, 8.5 mmol) was added to acetonitrile (50 ml) and the interaction is carried out at room temperature for 1 h under stirring. The solvent is removed from the reaction mixture under reduced pressure. Then to the residue was added water (20 ml), saturated aqueous sodium bicarbonate solution (50 ml) and chloroform, and then stirred. The organic layer is separated, dried over anhydrous magnesium sulfate, and then evaporated. The residue is purified column chromatography on silica gel (eluent:ethyl acetate/n-hexane, 1: 2), the result is the target compound (0.6 g, yield 22%) as crystals, so pl. 142-143aboutC.

P R I m e R 21. Synthesis of(2-phenylimidazo[1,2-a]pyridine-8-ylcarbonyl)-(3-chlorophenyl)acetonitrile (compound 2-35).

2 Phenylimidazo[1,2-a] pyridine-8-CT - oil acid (1.0 g, 4.2 mmol), -(3-chlorophenyl)aminoacetonitrile (0,77 g, 4.5 mmol) and NaHCO3(1.1 g, of 13.1 mmol) was added to acetonitrile (10 ml). CHL is th mixture under stirring, cooling with ice. The mixture was incubated produced at room temperature for 10 h, the solvent is removed from the reaction mixture under reduced pressure, and then to the residue was added water (50 ml) and bring the mixture to pH 7 with saturated aqueous sodium bicarbonate solution. The mixture is then extracted with a mixture of solvents dichloromethane/ethyl acetate (10:1), (100 MLH). The obtained extract is dried over anhydrous magnesium sulfate and evaporated. To the residue was added acetonitrile (5 ml) and precipitated crystals are collected by filtration. The result is the target connection (0,44 g, yield of 27.2%) in the form of crystals, so pl. 210-211aboutC.

P R I m e R 22. Synthesis -(3-dimethylaminoethyl-2-phenylimidazo[1,2-a]pyridine-8 - incorperating-(3-forfinal) acetonitrile (compound 2-79).

To acetonitrile (10 ml) was added 37% formaldehyde (0.3 ml) and acetic acid (0.4 ml), after which the resulting mixture is slowly added 50% aqueous solution of dimethylamine (0.3 ml) at 0aboutWith stirring. To the resulting mixture are added -(2-phenylimidazo[1,2-a]pyridine-8-ylcarbonyl)-(3-forfinal)acetonitrile (1.0 g, 2.7 mmol) and stirred the mixture at 50aboutC for 2 h, and then for 2.5 hours at room temperature. After that reacts is. actor extracted with dichloromethane, and the extract washed with water, dried over anhydrous sodium sulfate, followed by evaporation under reduced pressure. The resulting concentrate is purified column chromatography on silica gel (eluent:chloroform to obtain the target compound (0,47 g, yield 40.8 per cent) in the form of crystals, so pl. 123-124aboutC.

P R I m e R 23. Synthesis of(3-methylsulfonylmethane[1,2-a]pyridine-8-Ilker-Beniamino)-(2-furyl) acetonitrile (compound 2-122).

-(2 Methylthiopyrimidine[1,2-a] PI - ridin-8 ylcarbonyl)-(2-furyl)Aceto - nitrile (0.33 g, 1 mmol) was added to the chloroform (10 ml), and then to this mixture was added m-chlormadinone acid (0.25 g, 1.1 mmol) at a temperature of 5aboutC. the mixture is Then stirred at room temperature for 2.5 hours, and then treated reaction mixture, saturated aqueous sodium bicarbonate. The chloroform layer is separated, washed with water, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The concentrate is purified column chromatography, or on silica gel (eluent:ethyl acetate) to obtain the target compound (0.1 g, yield 30.3 per cent) in the form of crystals, so pl. 214-216aboutC.

P R I m e R 24. Synthesis of(2-t is stoaway -(2-triptoreline[1,2-a]pyridine-8-ylcarbonyl)- (3-forfinal)acetonitrile (1.26 g) and chlorosulphonate (0.5 ml) in chloroform (13 ml) is refluxed for 1.5 hours The reaction solution is concentrated under reduced pressure and to the residue is added water. The precipitated crystals are collected by filtration and recrystallization from ethanol obtain the target compound (0.45 g, yield 34,1%) in the form of crystals, so pl. 118-120aboutC.

The compounds of formula II, obtained using the same methods described in examples 1-16 are shown in table. 4, the melting point and data analysis of NMR in table. 5.

The compounds of formula I, obtained by similar methods described in examples 17-24 are given in table. 6, the melting point and data analysis of NMR in table. 7.

Composition 1. Emulsifiable concentrates are prepared by mixing the following components, wt. Connection 2-2 20 Xylene 75 Polyoxyethylenated - arrowy ether (Monipol 85) 5

Part 2

Wettable powders are prepared by mixing and grinding the following components, wt. Connection 2-24 50 Diatomaceous earth 44 Polyoxyethylenated - arrowy ether 6 Monipol 85)

Part 3.

Powders are prepared by mixing the following mixture, wt. Connection 2-27 3 Clay 40 Talc 57

1. Fungicidal composition comprising an active ingredientmono derived and the target additives, characterized in that order gain
where X furyl, methylphenyl, thienyl, phenyl which may be substituted once by halogen, stands, methoxy, trifluoromethyl, twice-halogen, matiltan, methylpyrrole, pyridyl, benzyl, methyl;

R1hydrogen, thienyl, phenoxy, naphthyl, C1C6-alkyl, trifluoromethyl, methyl, substituted by chlorine, methoxy, methylthio, methylsulfonyl, phenoxy, phenylthio; phenyl, perhaps once substituted C1C3-alkyl, C1- C3-alkoxy, halogen, nitro, dimethylamino, phenyl, sulfo, hydroxy, phenyl, durationally the same or different groups selected from C1C4-alkyl, methoxy, halogen, nitro, methylthio, methylsulfinyl, methylsulphonyl, tetramethylene, phenylthio, cyclohexyl; thiazolyl;

R2hydrogen, halogen, amino, phenyl, formyl, nitro, cyano, sulfo, methyl which may be substituted by dimethylamino, morpholino, sulfo, SO2NHCH3N= CHC6H5;

R3hydrogen, methyl,

or its salts, such as hydrochloride or oxalate in the following ingredients, wt.

The active ingredient 3-50

The target additive and the Rest

2. Amide derivative of General formula

< / BR>
where X furyl, thienyl, methylphenyl, phenyl,1hydrogen, thienyl phenoxy, naphthyl C1C4-alkyl, trifluoromethyl, substituted by chlorine, methoxy, methylthio, methylsulfinyl, phenoxy, phenylthio, phenyl, perhaps once substituted C1C3-alkyl, C1- C3-alkoxy, halogen, nitro, dimethylamino, phenyl, sulfhydrate, phenyl, doubly substituted the same or different groups selected from C1- C4-alkyl, methoxy, halogen, nitro, methylthio, methylsulfinyl, methylsulphonyl, tetramethylene, phenylthio, cyclohexyl, thiazolyl;

R2hydrogen, halogen, amino, phenyl, formyl, nitro, cyano, sulfo, methyl which may be substituted by dimethylamino, morpholino, sulfo, SO2NHCH, N CHC6H5;

R3hydrogen, methyl,

or its salts, such as hydrochloride or oxalate.

 

Same patents:

The invention relates to new derivatives of 1-phenylimidazole formula 1

CFN< / BR>
where R represents a hydrogen atom or methyl;

x represents a fluorine atom, a chlorine atom or a nitro-group;

y represents a fluorine atom or a chlorine atom;

z represents a hydrogen atom, a fluorine atom, a chlorine atom or a bromine atom, a process for the preparation of these compounds and insecticides containing as active components of these compounds

The invention relates to new pyridine containing heterocyclic compounds, in particular new 1,3-dioxane-5-silt derived alkenovich acids containing pyridyloxy residue attached to position 4 of the 1,3-dioxane ring

The invention relates to new derivatives of glycerol General formula

where k=1 or 0;

Lower alkyl or arylalkyl;

R1acetyl, 2-alkoxybenzyl or aryl;

n=0 or an integer from 1 to 3;

The group G formula< / BR>
orX-

A is selected from groups of formula:

(1) -NH-(CH2)where R2, R3and R4lowest alkoxygroup;

(2) -NH-(CH2)SO2-NH-R5where R5hydrogen, alkyl, or CHp=1 or 2;

(3) -NX-R6where the X group is-CH - or a nitrogen atom; R6group-СОR7where R7alkyl or alkoxy, or a group-0-C0-NH-R8where R8alkyl;

(4) -NH< / BR>
(5) -NH-(CH2)3-OR10where R10alkyl;

(6) -NH-(CH2)10-NH-CO-NR11R12where R11and R12lower alkyl;

(7) -NH-CHNO

(9) -NH-(CH2)5-0-(CH2)5-0-(CH2)5-H

(10) -NH-(CH2)3-0-CO-NH-R14where R14alkyl;

(11) -NH-CH< / BR>
(12)CHwhere m=0 or from 1 to 6; R9, R15and R16the same or different and represent hydrogen or alkoxygroup, provided that when k=0, group a sure formula

The invention relates to chemical means of protection of plants, particularly to the new connection formulas

CH3OOCOOHH2Nhave a weed-killing activity

The invention relates to a new compound, which can find application in agriculture as a herbicide, namely, N-furfurylaminopurine formula

< / BR>
The specified connection, properties, method of preparation and application are not described in literature

The invention relates to a method of combating fungi on plants by practicing their new derivatives of 2-aniline-pyrimidine of the General formula I

NNwhere R1hydrogen, halogen; C1-C3-alkyl, C1-C2-halogenated,1-C3-alkoxy;

R2hydrogen, halogen;

R3WITH1-C4-alkyl, C1-C3-halogenated, cyclopropyl;

R4unsubstituted or substituted with halogen, methyl cyclopropyl

The invention relates to herbicide compositions containing herbicide BIPYRIDILIUM dichloride salt as the active ingredient

The invention relates to new derivatives of benzo(b)naphthiridine General formula

R(I) where R1hydrogen, alkyl or hydroxyl radical;

R2hydrogen, linear or branched C1-C4-alkyl, foralkyl, cycloalkyl, alkyloxyalkyl or alkylamino radical;

R3WITH1-C4-alkyl, and R4and R5different and mean hydrogen or C1-C4-alkyl;

or R3hydrogen or alkyl, or cycloalkyl and R4and R5individually, each means hydrogen;

R6hydrogen or fluorine;

n is 1 or 2, or their salts, possess antibacterial property

The invention relates to methods of producing furan 1,3-dioxanes, which are used as the physiologically active substances

The invention relates to the field of pest control, in particular fungicidal means on the basis pyrrol-carbonitrile and methods of combating fungi

The invention relates to the field of pest control, in particular fungicidal means on the basis pyrrol-carbonitrile and methods of combating fungi

FIELD: agriculture.

SUBSTANCE: invention describes a method for feeding potato and tomato with 6-benzylaminopurine an aqueous solution taken in the concentration 10-4 M and growing pants up to preparing harvest according to technology accepted for the culture crop. Invention proposes 3-fold treatment of plants for vegetation: at the lateral branching phase, at onset of forming economically value organs and immediately after the growth termination. Method provides the effective enhancing the productivity of the most important vegetable crops - tomato and potato.

EFFECT: improved enhancing method.

6 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: method involves using product containing spermatozoa treated by drying with freezing to humidity level of 1% and having injured membrane or spermatozoon head so that spermatozoon nucleus retains its genetic validity enough for fertilization. The spermatozoon heads fertilize an isolated oocyte after rehydration and microinjection being done. The retained genetic integrity is enough for fertilizing an oocyte and producing living descendants. Method involves collecting living mature spermatozoa, making spermatozoa suspension in special purpose physiological medium, freezing the spermatozoa suspension for producing frozen spermatozoa, drying the frozen spermatozoa or spermatozoa heads in vacuum to humidity level of 1%, making rehydration of spermatozoa or spermatozoa heads with injured membrane and selecting those retaining nucleus of genetic integrity. The selected spermatozoa or spermatozoa heads are used for fertilizing isolated oocytes with living descendants being produced.

EFFECT: enhanced effectiveness in producing living descendants.

39 cl, 5 dwg, 1 tbl

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes a method for preparing compounds of the formula (I):

wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):

wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,

(IVa)

or (IVb) ,

wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.

EFFECT: improved preparing method.

9 cl, 12 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention relates to new substituted benzoylketones of the general formula (I): , all possible tautomeric forms and possible salts that can represent active substance as a component of herbicide agent. In the formula (I) A means (C1-C4)-alkyl; R1 means cyclo-(C3-C6)-alkyl; R2 means hydrogen atom (H), cyano-group (CN); R3 means hydrogen atom (H), halogen atom, CF3, (C1-C4)-alkylsulfonyl; R4 means halogen atom; X means groups: or wherein R5 means (C1-C4)-alkyl, (C1-C4)-alkoxy-group, (C1-C4)-alkylthio-group, di-(C1-C6-alkyl)-amino-group; R6 means (C1-C4)-alkyl, (C1-C4)-alkoxy-group, cyclo-(C3-C6)-alkyl; n = 0 or 1 including all possible tautomeric forms and possible salts. Compounds of the formula (I) elicit herbicide activity and can be used in herbicide composition.

EFFECT: valuable properties of compounds.

3 cl, 1 sch, 3 tbl, 13 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention relates to new substituted benzoylketones of the general formula (I): , all possible tautomeric forms and possible salts that can represent active substance as a component of herbicide agent. In the formula (I) A means (C1-C4)-alkyl; R1 means cyclo-(C3-C6)-alkyl; R2 means hydrogen atom (H), cyano-group (CN); R3 means hydrogen atom (H), halogen atom, CF3, (C1-C4)-alkylsulfonyl; R4 means halogen atom; X means groups: or wherein R5 means (C1-C4)-alkyl, (C1-C4)-alkoxy-group, (C1-C4)-alkylthio-group, di-(C1-C6-alkyl)-amino-group; R6 means (C1-C4)-alkyl, (C1-C4)-alkoxy-group, cyclo-(C3-C6)-alkyl; n = 0 or 1 including all possible tautomeric forms and possible salts. Compounds of the formula (I) elicit herbicide activity and can be used in herbicide composition.

EFFECT: valuable properties of compounds.

3 cl, 1 sch, 3 tbl, 13 ex

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention describes new 5-chlorodifluoromethyl-1,3,4-thiadiazole-2-yl-oxyacetanilides of the general formula (I): , wherein n means 1 or 2; R means n-propyl or isopropyl, n-butyl, isobutyl, sec.-butyl or tert.-butyl; X means halogen atom, alkyl or alkoxyl comprising 1-4 carbon atoms, and a herbicide agent containing thereof. Compounds elicit the better herbicide activity as compared with the known analogous acetanilides.

EFFECT: improved and valuable properties of compounds.

6 cl, 3 tbl, 3 ex

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