Florenceville connection or agricultural acceptable salt, a composition for combating infection of plants by nematodes, the method of dealing with infection of plants by nematodes and how systemic suppression of plant infection by nematodes

 

(57) Abstract:

The invention relates to florenceville compounds of General formula (X)(Y)C=C(Z)-(CH2)n-Q(I), where X and Y are fluorine; Z is hydrogen, fluorine; n= 1, 3, 5, 7, 9, 11; Q-CH2OTHER6CH2NO2, CHN=CHR2CY2N=C=O, CH2N+R3R4R5W - (C=O)-R11provided that if X and/or Y is fluorine and Q is-(C=O)-R11each X, Y, Z is fluorine, and n = 1, W is the anion of a mineral or organic acid; R2possibly substituted phenyl, R3, R4, R5is hydrogen and the other, R6is hydrogen, (C1-C6)-alkyl, and others, R11-halogen, NHOH, and others, and to their agricultural acceptable salts. The invention relates also to compositions for combating infection of plants by nematodes containing compound of the formula I, to a method of combating infection of plants by nematodes, which includes the processing locus of the plant a compound of formula I, as well as to the way the system suppression of plant infection by nematodes by treating the plants with compound of formula I. 4 C. and 23 C.p. f-crystals, 5 PL.

This invention relates in new florenceville compounds, their agricultural acceptable salts, compositions on their basis to combat the infestation of plants by nematodes is known as VNO means of combating insects and nematodes when introducing them to the ground. U.S. patents NN 3510503, 3654333 and 3780050 disclose such compounds. Later in U.S. patent N 4952580 were described polygaloides, suitable as nematicides, some of which have come down system activity as it can to some extent eliminate the infection with nematodes of the root system during the processing of foliage plants. Most of the compounds described in these patents are non-polar compounds, which is a desirable characteristic for pesticides applied to soil, providing a longer period, but much less effective in the processing of the leaves, to achieve systemic effects. U.S. patent N 4950666 reveals some of the compounds produced by diferuloylmethane, suitable as insecticides and nematicides systemic action. However, there remains a need for means to control nematodes, insects and acaridae that have improved overall mobility and, preferably, low level effective use.

According to the present invention offers florenceville compounds of General formula I:

< / BR>
where

X and Y are fluorine;

Z is hydrogen or fluorine;

n= 1, 3, 5, 7, 9 or 11;

Q represents CH-or (C=O)-RIIprovided that when Q is - (C=O)-RIIeach of X, Y and Z is fluorine, and n = 1;

W-anion of a mineral or organic acid;

R2is phenyl, optionally substituted with at least one group selected from hydrooxide, nitro, halogen, di(C1-C4)alkylamino; or pyrazolyl

R3, R4, R5is hydrogen or taken together with the nitrogen atom of the group Q form pyrrolidinyl or tetraazatricyclo-[3,3,1,1-(Superscript-3-Superscript-7)] Dean;

R6represents hydrogen;(C1-C6) alkyl, optionally substituted amino or tert-butoxycarbonylamino; (C1-C5)alkyl-COOH, optionally substituted by carboxyl group; a (C1-C5)alkyl-CONH2; (C1C5)alkyl-COO - (C1C4)alkyl, (C1-C5)alkyl-COO - (C1C4)alkylphenyl; (C1-C6)alkenyl, substituted with halogen; dihydro-3-oxadiazolidine, thienyl and phenyl, optionally substituted by carboxyla or (C1-C4)alkoxycarbonyl; (C=O)R7where R7represents (C=O)R14; (C1-C6)alkyl, optionally substituted with at least one group selected from the range halogen, amino or (C31-C5), alkyl-COOH or its esters, optionally substituted amino group; (C1-C5)CONH2, optionally substituted amino group; (C1-C6)alkenyl, substituted with halogen; or a N-containing group, which together with carboxamido, represents the balance of urea, optionally substituted (C1-C4)alkyl, possibly substituted by hydroxyl; or

R6taken together with the nitrogen group, Q represents a hydrazine, guanidine, triftormetilfullerenov;

R11represents halogen, NHOH; OR12; SR12; NR12"where R12is hydrogen; (C1-C8)alkyl, optionally substituted by amino or phenyl; phenyl, optionally substituted by a nitro-group;

R12is hydrogen, (C1-C8)alkyl, optionally substituted by amino or phenyl; phenyl, optionally substituted by carboxyla;

R12"is hydrogen, (C1-C6)alkyl;

R13is hydrogen; (C2-C4)alchemission; (C1-C6)alkyl, optionally substituted with at least one group selected from (C1-C4)alkoxycarbonyl, amine, phenyl; (C2-C6)alkinson, optionally substituted carboxyla Nile, optionally substituted by carboxyla; or R12"and R13together with the nitrogen atom of the group NR12"R13form the rest of the natural amino acids of a protein, selected from the range: glycyl, poured, alanyl, asparagus, i.e. phenylalanyl, prolyl, lysyl, morpholinopropan, pyrrolidinyl or pyrazolyl, possibly substituted by carboxyla;

R14represents OH, (C1-C6)alkoxy, NH2or NHNH2or agricultural acceptable salts, provided that when n=1, and X, Y and Z denote fluorine, Q is CH2NH2or mineral salt.

Preferred florenceville compounds, where R2represents a

< / BR>
or florenceville compounds, where n= 1, X and Y each represents a fluorine;

including florenceville connection, where Z represents hydrogen and Q represents CH2NH2or CH2NH3+W-or Z represents fluorine,

for example, percentile connection, where Z is fluorine, Q is a CH2OTHER6and R6is an amide amino acids Q,

or R6is a primary amide amino acids Q, where the basic amino acid is preferably methionine is salad, sulfate, acetate, citrate or 3,4,4-Cryptor-3-butenoate.

Among the preferred compounds can be called florenceville connections, representing a 4.4-debtor-3-butene-1-amine or its agricultural acceptable salt; 3,4,4-Cryptor-3-butenova acid or its agricultural acceptable salt; 3,4,4-Cryptor-3-butene-1-amine 3,4,4-Cryptor-3-butenoate; 2-(3,4,4-Cryptor-1-oxo-3-butenyl)hydrazide of 3,4-Cryptor-3-butenova acid.

The present invention also relates to compositions for combating infection of plants by nematodes, including an active ingredient and additives target. As the active ingredient composition comprises a compound of formula I in an effective amount. Preferably as the active ingredient it contains N-(3,4,4-Cryptor-1-oxo-3-butene-yl)glycine or 3,4,4-triptoreline acid or their salts.

The object of the present invention is also a method of combating infection of plants by nematodes by treating the locus of the plants active compound, which is used as the compound of formula I in an effective amount.

The invention relates also to methods of systemic suppression of plant infection by nematodes by treating the Rast
n= 1, 3, 5, 7, 9 or 11; Q1represents CH2OTHER6(C=O)-R11or CH2NH3W-; each of X, Y and Z represents hydrogen or fluorine, or at least one of X and Y represents fluorine, provided that when Q1is a (C-O)-R11Z predstavljaet a fluorine and n = 1;

R6have the above meanings;

R11represents halogen, NHOH; OR12'; SR12; NR12"R13where R12is hydrogen; (C1-C8)alkyl, optionally substituted by amino or phenyl; phenyl, optionally substituted by a nitro-group and has a polarity, providing the penetration of compounds in the phloem of the leaf without reducing their nematocidal activity; R12'- (C1-C8)alkyl, optionally substituted by amino or phenyl, phenyl, optionally substituted by carboxyla R12"is hydrogen, (C1-C6)alkyl; R13is hydrogen; (C2-C4)alchemission; (C1-C6)alkyl, optionally substituted with at least one group selected from (C1-C4)alkoxycarbonyl, amine, phenyl; (C2-C6)alkinson, optionally substituted carboxyla or phenyl; (C1-C6)alkylamino, replaced the or R13together with the nitrogen atom of the group NR12"R13form the rest of the natural amino acids of a protein, selected from the range: glycyl, poured, alanyl, asparagus, i.e. phenylalanyl, prolyl, lysyl, morpholinopropan, pyrrolidinyl or pyrazolyl, possibly substituted by carboxyla;

W-anion of a mineral or organic acid, or their agricultural acceptable salt in an effective amount.

Preferably as a connection to use the connection, in which n is 1, X and Y each represents a fluorine, in particular, the compound in which Z represents a fluorine, and in which Q1represents CH2N+H3W-and W-an agricultural acceptable anion.

It is preferable to use the compound, which W-represents a chloride, iodide, bromide, oxalate, sulfate, phosphate, acetate, citrate or 3,4,4-Cryptor-3-butenoate or compounds where Z is fluorine and Q1represents COOH or its salt; or Q1represents CH2OTHER6and R6represents the balance 3,4,4-Cryptor-3-butene-1-amine or its salt or a group that can be transformed into it after applying on the plant ILT connection, in which R6represents the balance of methionine.

Another method according to the present invention is a method of systematic suppression of plant infection by nematodes by treating the plants with the active compound, which is used as N-(3,4,4-Cryptor-1-oxo-3-butene-yl)glycine or 3,4,4-triptoreline acid or their agricultural acceptable salt in an effective amount.

In the present description also includes methods of obtaining 3,4,4-Cryptor-3-butene-1-amine and new intermediates - 3,4,4-Cryptor-3-butene-1-tosilata and 3,4,4-Cryptor-3-butene-1-nelfinavir.

Detailed description of the invention

The new compounds of the present invention are suitable for combating infection of plants by nematodes, insects and acaridae. Many of these compounds, being polar, are highly effective system for combat, that is, when they are used for the processing of the leaves or stems of plants, or able to move through the phloem and xylem of the plant and to ensure against nematodes, insects and acaridae on other parts of the plant. I believe that the mechanism of this effect is a rather repellent or disgusting from eating action than on the Yes are introduced into the soil directly. Some compounds can provide both types of impact.

The proposed methods the overall impact on nematodes, insects and acarid use is able to move through the phloem of the compounds of the present invention, or such compounds that have a di - or triptorelin group, substituted CH2Other, or triptorelin group bearing a substituent (C=O)-R, with sufficient polarity to provide Flournoy mobility without eliminating the struggle with it activity tarakanovas particles. There are several different theories regarding Flournoy mobility, according to which compounds with the polarity must be sufficiently mobile in the phloem to spread down the plant. Suppose that the polarity of the molecule as a whole must be sufficient for the molecule to keep her in the phloem, but not so strong that the molecule would not come out.

For effective and systematic fight against nematodes or other pests in the processing of the aerial parts, the connection must be able to penetrate the skin of the foliage or stem of a plant, to penetrate into the phloem and stay there long enough butacite or otherwise to come into contact with the pest to such an extent, to destroy or repel pests and the damage that pests will cause the plant is reduced or eliminated. During the stages of transportation from the exhaust leaves or stems through the plant, the connection may be subjected to chemical reactions such as hydrolysis, or biological reactions, such as enzymatic effect. In addition, you may be prompted compounds that are in contact with the plant, to penetrate into the plant, can undergo reactions that result in a compound which is capable of easily absorbed, move and be effective to prevent the harmful actions the pest. Examples of such compounds are compounds containing protective groups, resistant to UV radiation, which when exposed to natural light, undergo reaction, and the result is the formation of active and moveable joints. Another example is siciliane derivatives of amines.

Therefore, what gets on the foliage or stem of a plant, may not be a connection, which in fact is transported or which actually affects pests. Thus, the methods of the present izobreteny, to purchase a polarity appropriate for the overall impact.

The methods of the present invention include processing plants, preferably foliage 3,4,4-Cryptor-3-butene-1-amine or its salts. In addition, processing can be conducted by a composition comprising an aqueous solution of 3,4,4-Cryptor-3-butene-1-amine or its salts in an agronomically acceptable carrier.

In the above-described methods for combating nematodes preferably, n was equal to 1, and X, Y and Z all represent a fluorine, and preferably, when Q1represents CH2NH3+W-i.e. salt 3,4,4-Cryptor-3-butene-1-amine. When Q1represents CH2Other, it is preferable that R was-amino acid attached through a peptide (amide) bond, preferably - amino acid protein. When Q1represents (C=O)-R, preferably R represents a hydroxyl, and a connection, therefore, will be a 3,4,4-Cryptor-3-butenova acid or its salt, including salt formed with 3,4,4-Cryptor-3-butene-1-amine, that is, 3,4,4-Cryptor-3-butene-1-Amin,4,4 trifter-3-butenoate.

W-could be any agronomically acceptable anion. The number t is t or perakendecilik, for example, F2C=CFCH2COO-.

In addition to the compounds specifically described above, all agronomically acceptable salts of the compounds included in the scope of the invention. For example, the compound of the present invention, having a free amino group can also exist in the protonated form having different associated with her anions, for example, but the example is not restrictive chloride, bromide, iodide, phosphate, oxalate, sulfate, citrate, and acetate. In addition, the counterion can be florancecorporate ion such as F2C=CFCH2COO-. The compound of the present invention containing a carboxyl or hydroxyl group, can exist in the form of salts having different associated with cations, for example, but the example is not restrictive - alkaline earth metals such as sodium, calcium and potassium, magnesium, or Quaternary ammonium ions such as ammonium, mono-, di - or trialkylamine, for example, Isopropylamine, or pyridine. In addition, the cation may be an ion of foralltelphone, such as F2C=CFCH2C-H2NH3+. All such compounds, and other compounds having similar characteristics, being agronomically acceptable, oboznachayut fluorine, chlorine, bromine or iodine, or their derivatives.

The term "alkyl" means a group with a straight or branched chain, containing from 1 to 6 carbon atoms. The term "lower alkyl" means a group that contains from 1 to 4 carbon atoms. The term "aliphatic" means a saturated or unsaturated, straight or branched chain groups containing from 1 to 10 carbon atoms.

The term "alkoxy" means a lower alkyl group attached through an oxygen atom. The term "alkylthio-" means that the lower alkyl group linked through a sulfur atom. The term "alkoxycarbonyl" means a complex of lower alkilany ether carboxylic group.

The term "aliphatic amine" means an aliphatic group in which at least a hydrogen atom is substituted by-NH2. The term "aliphatic carboxylic acid, its esters, complex thioesters and amides" means aliphatic group in which at least one carbon atom is part of carbocycles group-COOH, or complex (lower alkyl) ether complex (lower alkyl) - triavir or amide.

The term "aromatic group" or "aryl" means phenyl, optionally substituted with at least one group, select the and. The term "aromatic group" may also be used for heterocyclic residue such as, for example, thiadiazole, pyridine, thiazole, isothiazol, oxazole, pyrazole, triazole, benzothiazole, thiophene, furan, and the like, and they can also be optionally substituted.

The phrase "amide amino acids Q (or Q1means that R6(or R, respectively) is an amino acid linked through a peptide (amide) linkage with N or CH2OTHER6. The amino acid may be natural, i.e. amino acid protein, or amino acid artificial origin. The amino group of amino acids can be Deputy at any carbon atom in the group, for example, in position , or relative to the carbonyl.

The term "alkyl - or arylhydrazines" means a hydrazine group, a substituted lower alkyl or phenyl group, which, in turn, can be optionally substituted.

The synthesis of compounds

Compounds of the above formula in which X, Y and Z are fluorine, and Q is a derivative-CH2N is, in General, receive, receiving first need triptorelin that, when n=1, is a 3,4,4-Cryptor-3-butene-1-amine. The finding offers improved and new method of making such connection, 4-Bromo-1,1,2-Cryptor-1-butene, which is available commercially, can be directly converted direct interaction with tosylate salt, for example, totalitem silver, mesilate salt or another, giving alphagroup. Formed in the intermediate compounds, for example, 3,4,4-Cryptor-3-butene-1-tosylate or 3,4,4-Cryptor-3-butene-1-mesilate, are new compounds. For this stage should conversion to a derivative phthalimide using salt phthalimide, such as the potassium salt. The reaction can be successfully carried out without the isolation of intermediate tosilata or nelfinavir. Phthalimid then converted into the desired amine interaction with hydrazine. This new way of obtaining 3,4,4-Cryptor-3-butene-1-amine has the advantage that it gives an improved yield compared with the method of synthesis reported before, partly due to the lack of allocation of HBR in the process of conversion of bromine compounds. Thus, N-(3,4,4-Cryptor-3-butenyl)-phthalimide receive more than 80% output, and turn in the desired amine with the release of over 85%. The advantage is that, when the reagent with useplease group choose toilet silver, silver ions can then be the scientists in several ways. For example, to obtain the compound of the present invention, in which n=3, the ethylene oxide can be introduced into the reaction with 4-bromo-1,1,2-Cryptor-1-butene by known methods to obtain 6-hydroxy-1,1,2-Cryptor-1-hexane. This compound can then be converted into an amine salt using taillored and phthalimide as described above for butene. Another way 1,1,2-trichloro-1,2,2-trifluoroethane (G) may be introduced into reaction with alkene or Alcina, containing at the end of bromine, redox conditions, as described in Tetrahedron Letters 31, pp. 1307 - 1308, 1990. The reaction product is then dechlorinate with Zn to obtain triptoreline, which can be converted to the desired amine as described above for butene.

Diferentseerumine can be obtained in two different ways, depending on the position of the fluorine atoms.

To get diversecity at the end, such as 4,4-debtor-3-butene-1-amine hydrochloride may be used in the following way:

< / BR>
Other diversecity, i.e. compounds in which one of X and Y is H, and Z represents F, get:

< / BR>
where

m= 2, 4, 6, 8, 10 or 11; LAH means alumoweld lithium. Isomeric forms (E and Z can be selected washago invention receives two different ways, depending on whether the fluorine at the end or in the middle of the molecule, as shown in the following diagrams:

< / BR>
To get monitorowanie, in which the fluorine is in the middle of the molecule, you can use the following scheme of reactions:

< / BR>
Many other compounds of the present invention, in which Q represents CH2OTHER6then easily get in the interaction of the selected reagent with the corresponding florenceville or its salt by methods known in the art. For example, to get aminopropane, in which R6represents -(C=O)-derivative, the corresponding acid is injected into the interaction with the corresponding fluorinated alkenylamine conventional techniques. The acid may be in the form of galodamadruga or anhydride for the most effective reaction with the amine. For example, when R6represents (C=O)-CF3use the anhydride triperoxonane acid. When you need to derive succinimido acid, can be used succinic anhydride, m when you need to get the derivative of oxalic acid, can be used the acid chloride acid.

When R6is a-amino acid, related the ones with the nitrogen atom, is an amide-amino acids to form a peptide (amide) bond can be used in a typical peptide or amide linking reagents, such as carbonyldiimidazole or DCC. In the case of substituted acid groups, any functional group that can affect or be affected by groups, forming a peptide (amide) bond, must be protected. For example, the functional amino group will be protected tert.-SIDE-group. Acid or alcohol groups can be substituted by the formation of complex or simple benzyl or tert.-butyl esters. Tighrope (sulfhydryl group) can be protected trailvoy group. Then carry out the cleavage of the protective groups, using known methods, to obtain the desired connection.

When R6represents an aliphatic carboxylic acid, there are two ways of synthesis. Need peralkylated can be entered into cooperation with the appropriate electrophilic reagent, for example, guidancearticle. The resulting ester may be used or hydrolyzed to the free acid, which is then known ways mojen in communication with corresponding amino acid.

When R6is a lower aliphatic group, selected peralkylated enter into interaction with the appropriate electrophilic agent, for example, haloalkyl, such as modesty methyl. Preferably, the amine is present in excess relative to haloalkyl in order to minimize further the amine substitution.

When R6is a (C1-C12)alkylamine, as the starting material usually instead amine bromide use or toilet, and enter into interaction with an excess of the desired amine, one amino group which is protected. Further cleavage of the protective groups by known methods will result in the desired product.

When R6taken together with the nitrogen Q or Q1group CH2OTHER6(or RH2Other) is a guanidine, an appropriate peralkylated in the form of a salt, as described above, is injected into the interaction with cyanamide.

When R6taken together with the nitrogen Q or Q1group CH2OTHER6(or CH2Other), represents an alkyl - or arylsulfonate, optionally substituted, corresponding peralkylated enter into interaction with relevant who SUB>1group CH2OTHER6(or CH2Other), is a urea, carbamate, THIOCARBAMATE or hydrazine, selected peralkylated first converted into isocyanate (Q represents CH2N=C= O). This isocyanate is produced by interaction of the amine with diphenylcarbohydrazide and after that at high temperature produces isocyanate, in accordance with the following scheme

< / BR>
From isocyanate can be obtained from other compounds in the interaction with ammonia or amines to obtain urea, with alcohols to obtain carbamates, tiospirone for receiving THIOCARBAMATE, or hydrazines for receiving semicarbazides. In the latter case, the hydrazine must be substituted, for example, tert. -SIDE-by group, and then the protective group must be removed to obtain the formation.

Compounds in which Q represents CH2N=CH-R2also receive from the corresponding peralkylated, for example, 3,4,4-Cryptor-buten-amine. It is introduced in the reaction, using known methods, with the appropriate aromatic aldehyde, preferably with benzaldehyde, for example, p-(N,N-dimethylamino)-benzaldehyde or 2-hydroxy-5-nitrobenzaldehyde.

United from peralkylated, for example, 3,4,4-Cryptor-3-butene-1-amine. The amino group quaternized by known methods, for example, excess haloalkyl, for example, iodotope bromide. Thus can be obtained connection 3,4,4-Cryptor-3-butyltrichlorosilane.

For other compounds in which Q represents CH2N+R3R4R5W-can be used peralkylated. For example, when R3, R4and R5taken together with the nitrogen atom, form a cyclic Quaternary ammonium group, the corresponding cyclic amine, for example, hexamethylenetetramine, enter into interaction with peralkylated to get the desired Quaternary ammonium compound. When one of R3, R4and R5represents a hydroxyl group, the compound is produced by interaction of peralkylated with excess O-trimethylsilylmethylamine to get forankringsprocessen, protected O-trimethylsilyl, which is then hydrolized with methanol, and then treated with acid to obtain the salt of the desired hydroxylamine.

The compound in which Q represents CH2NO2can be obtained by known methods from ftoran acids and their derivatives, that is, when Q is a (C=O)-RII(X, Y, and Z are F) is similar to some of the compounds disclosed in U.S. patent 4950666, but cannot be obtained by the method of Wittig reaction. Get them in a completely different way, by conversion of 4-bromo-1,1,2-Cryptor-1-butene in alcohol through the intermediate ester. For example, to obtain the phenylacetate of triptorelin use of phenylacetic acid, then the ester hydrolyzing and get tripcomputer, and then oxidized to the acid, as shown in the diagram

< / BR>
Acids with longer chain in which n = 3, 5, etc. can be obtained in the same way from halides with a longer chain, obtained as described above. Derivatives of these acids, for example, salts, esters, amides, etc. can be easily obtained by methods known to experts.

The details of such reactions are given in the following examples of specific syntheses, which are given for illustration, and do not imply any restrictions.

Example of synthesis 1

Getting 3,4,4-Cryptor-3-butene-1-amine and its salts

a) 25 g (0,0896 mol) tosilata silver in 100 ml of acetonitrile at room temperature and slow stirring of 13.2 g (0.07 mol) of 4-bromo-1,1,2-Cryptor-1-butene. Neobratim refrigerator. After cooling, the precipitate is filtered, and the solvent removed from the filtrate under reduced pressure. To the residue add 10 ml of ethyl acetate and then washed 3 times with water and dried over magnesium sulfate. To this an ethyl acetate solution of 3,4,4-Cryptor-3 - buttonset add 25 ml of DMF and 16.7 g (0.09 mol) of phthalimide potassium. This reaction mixture is stirred at the boiling temperature under reflux for 24 hours. After cooling, the precipitate is filtered and washed with ethyl acetate, which combined with the filtrate, washed once with water, once with 5% NaOH solution and then 3 times with water and finally dried on magnesium sulfate. The solvent is removed under reduced pressure and get accounted for 14.45 g of N-(3,4,4-Cryptor-3-butenyl)phthalimide in the form of a solid reddish-brown color.

b) To 13,91 g (0,054 mol) of the product of stage a), dissolved in 100 ml of ethanol, add 1,76 g (0,054 mol) of anhydrous hydrazine. The reaction mixture was then stirred at the boiling point under reflux for 3 hours. Then slowly, through the reflux condenser, add 40 ml conc. HCl and the mixture is stirred at the boiling point under reflux for a further 2 hours. After cooling the reaction mixture the atom. The combined filtrates washed with ether, and the ether layer discarded. The aqueous layer was cooled in an ice bath, and then add 50% NaOH until then, until the solution becomes alkaline. The aqueous layer was then extracted twice with chloroform and the combined chloroform extracts containing the desired amine, dried over magnesium sulfate.

c) In a chloroform solution of stage (b) to highlight the hydrochloric salt of the desired amine, bubbled excess of gaseous HCl. After stirring for 15 minutes, the chloroform is removed under reduced pressure and the gain of 7.4 g of the hydrochloride 3,4,4-Cryptor-3-butene-1-amine as a white solid, so pl. 191 - 193oC. This compound I used in the biological tests described below.

d) Other amine salts can be obtained in a similar fashion, or they can be obtained from the hydrochloric salt by a method widely known in the art. For example, chlorotoluron salt can be neutralized again to the free amine. The excess of free amine is then added to various acids, dissolved in methanol, and get the right kind of salt.

Example of synthesis 2

Obtain hydrochloride of N-(3,4,4-Cryptor-3-bouteille

(compound 9)

(a) To the 34.4 g (0.34 mol) of triethylamine. Then at room temperature is added dropwise at 16.1 g (0,105 mol) of methylpropanoate and the reaction mixture was stirred at room temperature for 4 hours. The precipitate is filtered off and the solvent removed from the filtrate under reduced pressure. To the residue is added ether, and the resulting mixture is stirred for 20 minutes. Additionally, the formed precipitate is filtered off and the ether filtrate bubbled excess anhydrous gaseous HCl. The formed precipitate is filtered off, washed with ether and dried under reduced pressure, get to 23.4 g of methyl ester of N-(3,4,4-Cryptor-3-butenyl)-glycine-hydrochloride, compound 8, in the form of a white solid, yield 96%.

b) Compound 8 - 19 g (of 0.081 mol) is refluxed in 90 ml of 6N HCl. After removal of the solvent under reduced pressure the residue is stirred for 2 hours in air. The precipitate is filtered off, washed with ether and dried under reduced pressure, get 16,25 g named the title compound as a white solid, yield 92%, so pl. 186 - 188oC.

Example of synthesis 3

Obtain hydrochloride of N-(3,4,4-Cryptor-3-butenyl)valine

(compound 10)

a) To a solution of 8,88 g (0,053 mol) of the hydrochloride METI is spengiu added dropwise 4 g (0,021 mol) 4-bromo-1,1,2-Cryptor-1-butene, and the reaction mixture is stirred for 7 days. The solvent is removed under reduced pressure. To the residue is added ether, and the precipitate is filtered off. Aired them filtrate removed under reduced pressure. The remainder chromatographic by high performance liquid chromatography (7% ethyl acetate in hexane), and allocate 0.33 g of the desired amine, dissolved in ether and treated with excess gaseous HCl. The formed precipitate is filtered off and dried, get to 0.29 g of the hydrochloride of the methyl ester of N-(3,4,4-Cryptor-3-butenyl)-valine, connection 49.

b) during the night at the boiling point under reflux heated to 0.47 g (0,0017 mol) of the compound 49 in 10 ml ^N HCl. The reaction mixture is cooled and the solvent is removed under reduced pressure. The residue is suspended in ether and the product is filtered off, get 0,43 g named in the title compound in the form of a solid white color, yield 98%.

Example of synthesis 4

Synthesis of N,N'-bis-(3,4,4-Cryptor-3-butenyl)Academica

(compound 21)

To 4 g (0,0248 mol) of compound I and and 3.72 g (0,037 mol) of triethylamine in 30 ml of THF is added slowly 0,79 g (0,0062 mol) of oxalicacid. All this stirred over night at room temperature. The precipitate is filtered off, the tank is filtered, washed with water and dried. The crude product is recrystallized from ethyl acetate and get 0,46 g named in the title compound in the form of a solid reddish-brown color, yield 24%, so pl. 139 - 141oC.

Example of synthesis of 5

Synthesis of 4-oxo-4-[(3,4,4-Cryptor-3-butenyl)amino]butenova acid

(connection)

Mix 0.8 g (0,005 mol) of compound I with (0,005 mol) of succinic anhydride in 30 ml of THF. To this mixture is added 0.015 mol of triethylamine with stirring. The mixture is stirred at room temperature for 48 hours. The solvent is removed by evaporation, and the residue is dissolved in water and acidified with conc. HCl. The desired product is filtered and recrystallized from a mixture of ethyl acetate and cyclohexane, to obtain 0.7 g named in the title compound in the form of needle-like crystals, so pl. 64 - 66oC.

Example of synthesis 6

Synthesis of 4-nitro-2-[[(3,4,4-Cryptor-3-butenyl)imino]methyl]phenol

(compound 23)

To 0,005 to 5 moles-nitrosalicylaldehyde in 20 ml ethanol add 0.005 moles of NaOH in the form of a 10% aqueous solution. To this solution was added 0.005 moles of compound I in 20 ml of ethanol. The resulting mixture is stirred for 3 hours at room temperature and then for 5 hours at 50oC. Until reacts is lowke connection in the form of needle-like crystals yellow so pl. 96 - 98oC.

Example of synthesis of 7

Synthesis of bromide N-(3,4,4-Cryptor-3-butenyl)of hexamethylenetetramine

(compound 26)

Heat 10 g (0,053 mol) 4-bromo-1,1,2-Cryptor-1-butene, 3.7 g (0,026 mol) of hexamethylenetetramine and 27 ml of chloroform at the boiling point under reflux for 6.5 hours. The precipitate is filtered from the hot reaction mixture and washed with 50 ml of hot chloroform. The product is dried in vacuum and obtain 1.1 g named in the title compound in the form of a solid white color, yield 13%.

Example of synthesis 8

Synthesis of hydrochloride 3,4,4-Cryptor-N-hydroxy-3-butene-1-amine

(compound 27)

To 15 g of O-TMS-hydroxylamine dried in the flame of the high pressure tube, purged with nitrogen, add 7.5 g (0,027 mol) 3,4,4-Cryptor-3-potentsiala. The tube is sealed and the reaction mixture was stirred overnight at 75oC. After desantirovaniya liquid sludge liquid is distilled and collected product, which boils at 29oC at 1 mm RT.art., and obtain 0.8 g named in the title compound, protected O-TMS. It stirred in methanol in 5 ml over night. Then the reaction mixture was bubbled excess of gaseous HCl. The solvent is removed with the La.

Example 9 synthesis

Synthesis of 2-(3,4,4-Cryptor-3-butenyl)hydrazide benzoic acid

(compound 28)

To 20 g (0.147 mol) of benzoylhydrazone and 3.7 g (0,037 mol) of triethylamine in 60 ml of DMF, add 7 g (0,037 mol) 4-bromo-1,1,2-Cryptor-1-butene, and the mixture is stirred for 2 days at room temperature. The solid substance is filtered off and the solvent removed from the filtrate under reduced pressure. To the residue is added ether and suspended in 1 hour. The precipitates are then filtered. The ether removed from the filtrate under reduced pressure. The remainder chromatographic by high performance liquid chromatography (40% ethyl acetate in hexane), to obtain 1.35 g named the title compound as a pale yellow solid, yield 15%, so pl. 74 - 76oC.

Example 10 synthesis

Synthesis of hydrochloride of N-(3,4,4-Cryptor-3-butenyl)of hydrazine

(compound 29)

Refluxed overnight 1 g (0,0041 mol) of the compound 28, obtained as described in example 9 in 10 ml of 6N HCl. After cooling, a precipitate by-product. The aqueous layer was washed 4 times with ether. Water is removed under reduced pressure and obtain 0.6 g named the title compound as a sticky brown homestudent 30)

Boil 3 g (0,0186 mol) of compound I and 0.78 g (0,0186 mol) of cyanamide under reflux in 25 ml of absolute ethanol for 4 days. The solvent is removed under reduced pressure and the residue is dried under reduced pressure, get 3,66 g named the title compound as an amber viscous oil, yield 97%.

Example 12 synthesis

Synthesis of 3,4,4-Cryptor-3-butylnitrite

(compound 31)

To 4 g (0,026 mol) of silver nitrate in 30 ml of CH3CN is added dropwise 2.6 g (0.14 mol) of 4-bromo-1,1,2-Cryptor-1-butene. All this stirred overnight in the dark at room temperature. The precipitate is filtered off and the solvent is removed under reduced pressure. Water added to the residue and the product extracted with ether. The ether is washed 3 times with water, dried over magnesium sulfate and removed under reduced pressure to obtain 250 mg of a crude substance, which is distilled and get named in the title compound, so Kip. 25 - 28oC when 0,85 Torr.

Example of synthesis 13

Synthesis of N-(3,4,4-Cryptor-3-butenyl)urea

(compound 32)

To 2 g (0,0124 mol) of compound I and 2.5 g (0,024 mol) of triethylamine in 14 ml THF added 1.5 g (0,0124 mol) TMS-isocyanate. The mixture is stirred over night at room temperature the making. The resulting solid is suspended in ether. The ether is decanted from nerastvorimogo substances and removed under reduced pressure. To the residue is added methanol, stirred over night at room temperature and then removed under reduced pressure. The residue is suspended in a mixture of ether and petroleum ether (1:1), the solid is filtered off and dried under reduced pressure to obtain 0.6 g named in the title compound, yield 30%, so pl. 86 - 88oC.

Example 14 synthesis

Synthesis of N-(p-trifloromethyl)-3,4,4-Cryptor-3-butene-1-amine

(compound 33)

Compound I (0.01 mol) is mixed with 100 ml of methylene chloride and added dropwise to p-triftormetilfullerenov (0.01 mol) in 20 ml of methylene chloride. The mixture is cooled and stirred, then add 0,023 of moles of triethylamine. After stirring for 4 hours at room temperature add 100 ml of water and the two layers separated. Methylenchloride layer is washed with a solution of NaHCO3in water, and dried over magnesium sulfate. The solvent is evaporated and the white residue is recrystallized from ethyl acetate and cyclohexane, 2,6 get named in the title compound as white crystals, so pl. 68 - 70oC.

b) is Dissolved in ether, 1.5 g (0,0051 mol) of the compound 34 and the resulting solution barbiturat excess of gaseous HCl. The reaction mixture is stirred for 5 hours at room temperature. The resulting white precipitate is filtered off and dried under reduced pressure to obtain 1.1 g named in the title compound in the form of a solid white color, yield 98%, so pl. 164 - 166oC.

Example 16 synthesis

Synthesis of 3,4,4-Cryptor-3-butenova acid (compound 44) and its salts

a) 50 g (of 0.37 mol) of phenylacetic acid and 55.9 g (of 0.37 mol) 1st the mixture is stirred at the boiling point under reflux for 2 days. After cooling, the solvent is removed under reduced pressure. To the residue water is added and the product extracted with ether. The ether extract is washed 2 times with 5% NaOH, 2 times with water, dried over magnesium sulfate and the ether removed under reduced pressure; get 40,87 g triptoreline ester of phenylacetic acid. This ether is added to 7.2 g (0.18 mol) of NaOH dissolved in 70 ml of water. All this vigorously stirred over night at room temperature. The reaction mixture was added ether to proektirovanii the reaction product. The separated ether layer is dried over magnesium sulfate and distilled. Collect the product, receiving 15,78 g of 4-hydroxy-1,1,2-Cryptor-1-butene in the form of a light fluid, so Kip. 120oC at 760 mm RT.article.

b) To 84,27 g (0.843 mol) of chromium trioxide in 500 ml of acetic acid and 75 ml of water is added dropwise 26,43 g (0.21 mol) of the alcohol obtained in (a), keeping the temperature below 10oC. After complete addition, the reaction mixture is stirred at 5oC for 2 hours and then at room temperature. The mixture was then diluted with 1 l of water and extracted twice with ether. The combined ether layers are washed 3 times with water, dried over magnesium sulfate and then the solvent is removed under reduced pressure. About varaut in ether and then twice extracted with saturated NaHCO3. Merged layers NaHCO3washed 3 times with ether and then acidified with conc. HCl. The product is then extracted with ether. The ether extract is washed 3 times with water, dried over magnesium sulfate and the ether removed under reduced pressure; it is produced by 8.22 g named in the title compound in the form of a light liquid.

c) Can be obtained connection 44, and then neutralized by known methods to any agronomically acceptable salt. This includes salt triptorelin, such as 3,4,4-Cryptor-3-butene-1-amine, obtained in example 1.

Example 17 synthesis

Synthesis of 3,4,4-Cryptor-3-butene-1-amide

(compound 45)

To 1 g (0,0071 mol) of the compound 44, obtained as in example 16 dissolved in 20 ml of anhydrous THF, added to 1.15 g (0,0071 mol) of carbonyldiimidazole. After stirring for 20 minutes the reaction mixture was bubbled excess anhydrous gaseous NH3and the mixture is stirred over night at room temperature. Then the solvent is removed under reduced pressure. To the residue is added ethyl acetate and the resulting mixture is extracted with 2 times 1-% HCl, dried over magnesium sulfate and the solvent is removed under reduced pressure. The crude product is then sublimate (50 - 55oC pH">

Example 18 synthesis

Synthesis of 2,2,2-Cryptor-N-(3,4,4-Cryptor-3-butenyl)ndimethylacetamide

(compound 50)

To 1.07 g (0,0066 mol) of compound I and 0.67 g (0,0066 mol) of triethylamine in 10 ml of THF added 1.7 g (0,008 mol) triperoxonane anhydride and the mixture is stirred over night at room temperature. The solid substance is filtered off and the solvent is removed under reduced pressure. To the residue water is added and the product extracted with ether. Added to the ether extract, 0.5 ml of triethylamine, washed 4 times with water, dried over magnesium sulfate and removing the ether under reduced pressure. The product is distilled from the residue receive 0.5 g named in the title compound in the form of a light liquid; yield 35;.

Example 19 synthesis

Synthesis of 1,1,2-Cryptor-4-isocyanate-1-butene

(compound 72)

a) Mixing anhydrous pyridine and 0,033 mole of compound 1, and cooled to 0oC. Type of 0.022 mole of diphenylcarbohydrazide and the reaction mixture was stirred over night at room temperature in a nitrogen atmosphere. The resulting suspension is poured into ice water, the precipitate is filtered off and washed with water. The precipitate is dissolved in a solution of ether in ethyl acetate, dried over magnesium sulfate and concentrated. Obtained through the trifter-3-butenyl)urea; yield 65%; so pl. 116 - 177oC.

b) is Heated in a nitrogen atmosphere to 0.016 moles of urea stage a) until no fumes formed during pyrolysis. Collect named in the title compound, as it Argonauts get 1,67 g connection in the form of light oil.

Example 20 synthesis

Synthesis of 4-methyl-N-[[(3,4,4-trifilo-3-butenyl)amino]carbonyl]benzene-sulfonamida (compound 75)

At room temperature, stirred 0.01 mol of compound I in 40 ml of THF, adding at this time, 0.01 mol of p-toluensulfonate. Carry out the cooling and add 0.01 mol of triethylamine. The mixture is stirred at room temperature for 48 hours and the solvent is removed under reduced pressure. The residue is dissolved in methylene chloride and washed with 3 times 50 ml of water. The solution is dried over magnesium sulfate and the solvent evaporated. The residue is recrystallized from ethanol and obtain 1.1 g named the title compound as white crystals, so pl. 134 - 136oC.

Example 21 synthesis

Synthesis of the hydrochloride of 4-amino-1,1-debtor-1-butene (compound 46)

a)is Heated to 48oC 100 g (of 0.68 mol) phthalimide in 250 ml of ethanol and 0.08 g of sodium methoxide, and added dropwise 50,8 g (of 0.91 mol) is the product is recrystallized from methylene chloride and dried in vacuum. Receive 150 g of white crystals.

b) Melt 51,63 g of triphenylphosphine and dissolved in 100 ml of dry dimethylacetamide. The solution is cooled to -5oC and added dropwise 41,34 g (0,197 mol) dibromodifluoromethane. Add 20,0 g (0,0984 mol) of the product of stage a), dissolved in 70 ml of methylene chloride, and after that add 12,88 g Zn-catalyst. The mixture is stirred for 2 hours and filtered. The filtrate is separated using 200 ml of methylene chloride in 200 ml of water. The organic layer is washed twice with water and extracted with 100 ml of 5% sodium hydroxide solution, 100 ml of 10% HCl and 200 ml of water. The solvent is removed in vacuum, and get N-(4,4-debtor-3-butenyl)phthalimide.

c) Mix of 51.0 g (0,215 mol) of the product of stage b) with 250 ml of ethanol and 24,11 g of hydrazine. After stirring and heating at the boiling point under reflux for 45 minutes to the mixture 71,38 g HCl and 70 ml of water, and continue boiling under reflux for 30 minutes. The solvent is removed under reduced pressure and the remaining mixture was partitioned between 300 ml of water and 200 ml of methylene chloride. Raise the pH of the aqueous layer 12 of aqueous 50% sodium hydroxide solution, and the mixture is extracted twice with methylene chloride (200 ml). United is in added to 30 g of sodium hydroxide (plates) and distilled off the free amine. Amin added to 50 ml of 6N HCl and water are removed under reduced pressure, get 13,31 named in the title compound, compound 46, in the form of white crystals.

From the connection 46 can be obtained dipterology derivatives of triptorelin obtained in the previous examples, for example, the hydrochloride of the methyl ester of N-(4,4-debtor-3-butenyl)glycine (compound 76).

Example 22 synthesis

Synthesis of 5,6,6-Cryptor-5-hexenoic acid (compound 104)

a) In a 1-liter flask under nitrogen atmosphere was placed 5.5 g (0,226 mol) magnesium turnings and 250 ml of anhydrous ether. Added dropwise to 40 g (0,212 mol) 4-bromo-1,1,2-triptorelin up until will be followed by a vigorous return return phlegmy. The remainder is then added dropwise with such a rate as to maintain gentle process of returning phlegmy. After complete addition, the reaction mixture is still stirred for 30 minutes. The reaction mixture is then cooled to a temperature of between -30oC and -50oC using a mixture of dry ice with acetone. Following this type of 4.04 g CuI and then to 8.5 ml of 0.017 mol) of condensed ethylene oxide. This mixture is left to stand at a temperature of from -30oC to -10oC for 20 minutes and then heated up at room temperature for 3 days. Then slowly add 200 ml of 10% HCl, followed by 35 ml conc. HCl. After stirring for 2 hours the precipitate is filtered off. The separated ether layer was washed 1 time with water, 1 time with saturated NaHCO3again 1 time with water, dried over MgSO4and remove the solvent in vacuo. The remainder of double-distilled. Collect 4.8 g of a fraction boiling at 58 - 59oC at 2 mm RT.article.

b) To 3 g (0.019 mol) of the compound obtained in stage a), 48 ml of acetone is added 15 ml of reagent John (Fieser and Fieser, vol. I., p. 142) dropwise, and during the additives keep the temperature at approximately 20oC using an ice bath. After complete addition, the reaction mixture is stirred for another half hour at room temperature. Separate chromate salt, passing the reaction mixture through silica gel. After washing with acetone, the acetone removed in vacuo. The residue is diluted with water and the product extracted with ether. The ether is washed 3 times with water, dried over MgSO4and the ether removed in vacuo. The crude product is dissolved in ether and extracted with saturated NaHCO3. Layer NaHCO3washed with ether, then acidified with conc. HCl. the desired product goes into the ether. The ether extract is washed once with water, dried over MgSO4and the ether removed-N-hydroxy-3-butanamide (compound 105)

To 1.0 g (0,0071 mol) of the compound 44 in 10 ml of anhydrous THF type of 1.16 g (0,0071 mol) of carbonyldiimidazole. After 20 minutes, add 0.75 g (0,0071 mol) of O-TMS-hydroxylamine (Aldrich) to the reaction mixture. All this was stirred at room temperature for 2 days. Then the solvent is removed in vacuum. The residue is dissolved in ethyl acetate and washed 2 times the minimum quantity of 10% HCl. An ethyl acetate solution is dried over MgSO4and the solvent is removed in vacuum. The residue is then mixed with methanol for 2 hours. The methanol is removed in vacuo. The remainder of the sublimate (80oC at 102 mm RT.cent.). Sublimated solid 3 times mixed with a mixture of ether and petroleum ether (solvent decanted each time), then recrystallized from a mixture of 30% ethyl acetate with hexane, receive 100 mg of product as a white solid, so pl. 99 - 100oC.

Example 24 synthesis

Synthesis of (2,2-dimethyl-1,3-dioxolane-4-yl)methyl ether, 3,4,4-Cryptor-3-butenova acid (compound 106)

To 1.0 g (0,0071 mol) of the compound 44 in 10 ml of anhydrous THF type of 1.16 g (0,0071 mol) of carbonyldiimidazole. After 20 minutes add 0,94 g (0,0071 mol) 2,2-dimethyl-1,3-dioxolane-4-ylmethanol and the reaction mixture was stirred at room iny the ether is washed 4 times with water, dried over MgSO4and remove the solvent in vacuo; gain of 0.44 g of product as a light liquid.

Example 25 synthesis

Synthesis of methyl ester 4-[(3,4,4-Cryptor-3-butenyl)amino)] benzoic acid (compound 107)

Gently heated 4.1 g (or 0.027 mol) of methyl-4-aminobenzoate and 2 g (0,00714 mol) 3,4,4-Cryptor-3-potentsiala when 130oC for 4 hours. The resulting product is dissolved (after cooling) in ethyl acetate. The precipitate is filtered off, the ethyl acetate is washed once with water, dried over MgSO4and removed in vacuum. The crude product chromatografic by high performance liquid chromatography (15% ethyl acetate in hexane); obtain 1.48 g of product as a light liquid, which is transformed into a solid substance, so pl. 47 - 49oC.

Example 26 synthesis

Synthesis of 4-[3,4,4-Cryptor-3-butenyl)amino]benzoic acid

(compound 109)

At room temperature during the night mix 1 g (0,00386 mol) of the compound 107 and 0.15 g (0,00386 mol) of NaOH in 10 ml of water and 10 ml ethanol. The solvent is removed in vacuum. To the residue water is added and washed once with ether. The aqueous layer was then acidified with conc. HCl. The formed precipitate is filtered off, washed with water and dried; obtain 0.33 g of the C of monohydrochloride (2-[3,4,4-Cryptor-3-lutenyl)amino] ndimethylacetamide (compound 108)

To 15 g (0,093 mol) of compound I of 9.6 g (0,093 mol) of triethylamine and 180 ml of THF is added slowly to 3.9 g (0,028 mol) of bromoacetamide, and stirred overnight at room temperature. The precipitate is filtered off and the solvent is removed in vacuo from the filtrate. The residue twice mixed with a mixture of ether with methylene chloride and every time the precipitate is filtered off. Then bubbled into the solution an excess of gaseous HCl, the resulting precipitate filtered off, washed with ether and dried in vacuum. The product is dissolved in water and the aqueous solution washed twice with ether. Water is removed in vacuum and the resulting crude product is recrystallized from ethanol, receive 2,39 g of the product as white solid, so pl. 198 - 200oC.

Example 28 synthesis

Synthesis 7,8,8-Cryptor-7-octinomos acid

(compound 84)

A solution of 4-pamakani acid (8,35 g, 0.05 mol) in anhydrous THF (100 ml) is treated by adding dropwise, minimetallurgical (0,051 mol, 17 ml of a 3M solution in THF) at -25oC and stirring for 15 minutes. The solution further stirred for 15 minutes at 0oC and treated delimitercharacters (0.002 mol, 20 ml of 0.1 M solution in THF) followed by - 3,4,4-Cryptor-3-butenylamine at 0oC for 2 hours and at room temperature over night. The solution is then poured into 400 ml of ether and 150 ml of 10; aqueous sulfuric acid. The ether layer is extracted with 10% NaOH (2 x 50 ml). The aqueous layer was washed with ether, acidified with conc. HCl and extracted with ether (3 x 100 ml). The ethereal extract is dried, concentrated and the residue is distilled under vacuum; obtain 4.1 g of the desired product as a colorless liquid, yield 42; so bales. 125 - 127oC (10 Torr).

Example 29 synthesis

Synthesis phenylmethylene ether, 3,4,4-Cryptor-3-butenova acid

(compound 113)

A solution of 3,4,4-Cryptor-3-butylchloride (2.8 g 0,0176 mol) and benzyl alcohol (0.9 g 0,0083 mol) in 20 ml of dichloromethane is heated at the boiling point under reflux for 40 hours. The solution is cooled to room temperature, diluted with dichloromethane (15 ml), washed sequentially with 5; sodium bicarbonate solution, water and malevil solution, and dried. Evaporation of solvent gives a 1.75 g of analytically pure product as a pale yellow oil, yield 92%.

Example 30 synthesis

Synthesis of 4-nitrophenylamino ether, 3,4,4-Cryptor-3-butenova acid

(compound 117)

A solution of 4-NITROPHENOL) 1.10 g, 0,0079 mol) and 3,4,4-Cryptor-3-butenolide (1.85 g is remesiana. The mixture was stirred at -78oC for 10 minutes and left to reach room temperature. The reaction mixture was diluted with ether (20 ml), mixed with 15 ml of 2N HCl. The organic layer is successively washed with water, 5; bicarbonate sodium salt solution and dried. Dark brown residue obtained after evaporation of the solvent, is purified by passing through a short column with silica gel, and get to 1.9 g of the product as a brown solid; yield 91%, so pl. 58 - 62oC.

Example 31 synthesis

Synthesis of 2-(3,4,4-Cryptor-1-oxo-3-butenyl)hydrazide 3,4,4-Cryptor-3-butenova acid (compound 120)

A solution of 3,4,4-Cryptor-3-butenolide (2.4 g, 0,0151 mol) in dry ether (20 ml) is treated by adding dropwise, anhydrous hydrazine (0,48 g, 0.15 mol) under stirring at -78oC. the Mixture is left to warm to room temperature, the white precipitate is filtered and dissolved in ethyl acetate. An ethyl acetate solution is washed with 5% sodium bicarbonate and dried. Evaporation of solvent gives 1.1 g of the desired product as a white solid; yield 47;, so pl. 191 - 193oC.

Example 32 synthesis

Synthesis of S-oktilovom ether, 3,4,4-Cryptor-3-potentialby acid

(compound 121)

Cm is 12 hours. The crude product is purified by passing through a column of silica gel, and obtain 1.2 g of the desired product as a pale yellow oil; yield 91%.

Example 33 synthesis

Synthesis of the hydrochloride of S-2-aminoethylamide ether, 3,4,4-Cryptor-3-potentialby acid (compound 127)

A mixture of 3,4,4-Cryptor-3-butylchloride (2.5 g, 0,00158 mol) and 2-aminoethanethiol-hydrochloride (1,14 g 0,010 mol) is slowly heated to the boiling temperature under reflux for 15 minutes. The mixture is cooled to room temperature, treated with dry ether and filtered. The product is recrystallized from absolute ethanol and obtain 0.8 g named in the title compound in the form of not quite white solid, yield 34%, so pl. 95 - 115oC.

Example 34 synthesis

Synthesis of monohydrochloride 2-aminoethylamide ether, 3,4,4-Cryptor-3-butenova acid (compound 130)

A solution of 3,4,4-Cryptor-3-butenolide (1.97 g, 0,0124 mol) and N-Cretu-SIDE-aminoethanol (1,61 g 0,010 mol) in dry ether (20 ml) is treated with triethylamine (1.25 g, 0,0124 mol) at -78oC and under stirring. The mixture is stirred for 30 minutes and left to reach room temperature, and then poured into 20 ml of water. The ether layer is successively washed with 5; bicarbonate Nay temperature for 30 minutes. The precipitate is filtered off and dried; obtain 1.6 g named the title compound as a white solid, yield 77%, so pl. 94 - 100oC.

Example 35 synthesis

Synthesis of methyl ester [(3,4,4-Cryptor-3-butenyl)amino]-octoxynol acid (compound 142)

A solution of 3,4,4-Cryptor-3-butene-1-amine (12.5 g, 0.1 mol) and triethylamine (10.1 g, 0.1 mol) in dry ether (200 ml) is treated by adding dropwise, oxalylamino (12.3 g, 0.1 mol, 30 ml of ether at 0oC and under stirring. The mixture is stirred at room temperature for 30 minutes and treated with 30 ml of water. The organic layer is successively washed with 2N HCl, water, 5% sodium bicarbonate and brine, and dried. The residue obtained after evaporation of the solvent, purified by distillation and get 16,42 g of the desired product as a white solid; yield 78; so pl. 33 - 34oC.

Example 36 synthesis

Synthesis of N-(3,4,4-Cryptor-3-butenyl)Academica

(compound 143)

A solution of compound 142 (5.0 g, 0,0237 mol) in methanol (50 ml) is saturated with dry gaseous ammonia at room temperature. The precipitate is filtered off, washed with methanol and dried; receive and 3.16 g named the title compound as a white solid, yield Islami (compound 144)

A solution of compound 142 (4,22 g, 0.02 mol) in absolute ethanol (50 ml) is treated with hydrazine monohydrate (1.6 g, to 0.032 mol) with stirring. The precipitate is filtered off, washed with ethanol and dried; gain of 2.54 g named the title compound as a white solid, yield 60; so pl. 145 - 200oC.

Example 38 synthesis

Synthesis of [(3,4,4-Cryptor-3-butenyl)amino]octoxynol acid (compound 145)

A solution of compound 142 (3,16 g, 0.015 mol) in methanol (25 ml) is treated with a solution of NaOH (0.8 g, 0.02 mol) in water (5 ml). The solution was stirred at room temperature for 30 minutes and concentrated. The residue is dissolved in water (20 ml) and extracted with dichloromethane (2 x 30 ml). The aqueous layer was acidified with conc. HCl and extracted with ethyl acetate. The organic layer is dried and evaporated; obtain 0.75 g named the title compound as a white solid, yield 25;, so pl. 95 - 100oC.

Example 39 synthesis

Synthesis of N-butyl-3,4,4-Cryptor-3-butanamide

(compound 103)

To a mixture of water (15 ml), dichloromethane (15 ml) and n-butylamine (2,34 g to 0.032 mol) is added 2.5 g (0,0158 mol) 3,4,4-Cryptor-3-butenolide at 0oC and under stirring. After stirring for 30 minutes the organic layer posledovatelnostyakh in the title compounds as white solids; the output 92;, so pl. 34 - 36oC.

Example 40 synthesis

Synthesis of 2-[(3,4,4-Cryptor-1-oxo-3-butenyl)amino]benzoic acid

(compound 128)

To a mixture of 3-aminobenzoic acid (1,37 g, 0.01 mol), sodium bicarbonate (0.84 g, 0.01 mol), water (20 ml) and dichloromethane (20 ml) is added 2.2 g (0,0139 mol) 3,4,4-Cryptor-3-butenolide at 0oC and under stirring. After stirring for 15 minutes at room temperature the mixture is diluted with ethyl acetate (100 ml) and water (50 ml). The organic layer was washed with 2N HCl and brine, and dried. The residue obtained after evaporation of the solvent, proscout with dry ether and filtered; receive 1,8 named the title compound as a pale pink solid, yield 69;, so pl. 252 - 255oC.

Example 41 synthesis

Synthesis of 2,4-dihydro-4-[[(3,4,4-Cryptor-3-butenyl)amino] methylene] -3H-pyrazole-3-one (compound 131)

A solution of 3,4,4-Cryptor-3-butene-1-amine (2.25 g, 0.018 mol) and 4,5-dihydro-5-oxo-1H-pyrazole-4-carboxaldehyde (1.12 g, 0.01 mol) in absolute ethanol (30 ml) is heated at boiling temperature under reflux for 15 minutes. The solution is concentrated and the residue is recrystallized from a mixture of ether and dichloromethane; get 1,49 g named in the title SNES 3,4,4-Cryptor-3-butanolide (compound 101)

To 46,7 g (0,334 mole) freshly 3,4,4-Cryptor-3-butenova acid (compound 44) in 100 ml of dichloromethane containing 2 drops of dimethylformamide, at 0oC added 31 ml (355 mol) of oxalicacid within 5 minutes. The mixture was stirred at 0oC and left overnight to warm to ambient temperature. The mixture is quickly distilled into fractions under normal pressure through a 20-cm column in the Game, equipped with a short distillation head. Pure acid chloride obtained as a colorless liquid, of 31.8 g (yield 60%), so Kip. 90 - 97oC (oil bath temperature 130oC). When stored at room temperature is slow decomposition.

Other halides, such as 3,4,4-Cryptor-3-butylbromide can be obtained from compound 101, or similar method of connection 44.

As is obvious to experts in the field of machinery, other active acidic compounds, such as symmetric or asymmetric anhydrides or imidazolidinyl, can be obtained from acids or halides of the present invention, and may be suitable for methods of pest control that are described here.

Example 43 synthesis

Synthesis of 1,1-dimethylethylene arrnage in 40 ml of water, at 0oC add 20 ml of dichloromethane and subsequently added 5.6 g (33.4 mmol) of the hydrochloride of tet.-butilhioscina. To the mixture in several stages within 5 minutes add the 5.25 g (a 33.2 mmol) of 3,4,4-Cryptor-3-butanolide (compound 101). The mixture is stirred for 30 minutes at 0oC and the phases are separated. The aqueous phase is extracted with dichloromethane and the combined organic phases, diluted with ether and washed with saturated aqueous sodium chloride. The solution is dried over magnesium sulfate and concentrated. The residue is distilled using a tube with a ball extending at 90 - 95oC (0.1 mm, RT.article ), and get 6.85 g (82;) colorless crystalline solid, so pl. 52 - 54oC.

Example 44 synthesis

Synthesis of N-(3,4,4-Cryptor-1-oxo-3-butenyl)glycine

(compound 91)

To 7.7 g (30.4 mmol) of 1,1-dimethylethylene ester of N-(3,4,4-Cryptor-1-oxo-3-butenyl)glycine (compound 90) add 8 ml triperoxonane acid. The solution was stirred at ambient temperature for 24 hours and concentrated. The residue is recrystallized from a mixture of ethyl acetate and ether, to obtain 1.7 g of colorless crystals, so pl. 115 - 116oC. Uterine fluid concentrate from a mixture of ethyl acetate with an ester of bicrystalline
Synthesis of hydrochloride of N-(2-amino-ethyl)-3,4,4-Cryptor-3-butanamide

(compound 96)

a) To 3.5 g (21.9 mmol) of 1,1-dimethylethylene ether (2-amino-ethyl)carbamino acid (obtained as described in Krapcho, A. P. Kuell, C. S. Synthetic Communications, 1990, 20, 2559 - 2564) in 40 ml dichloromethane at 0oC add 15 ml of water and 2.02 g (24 mmol) of sodium bicarbonate. The mixture is stirred for 5 minutes and within 2 minutes add of 3.46 g (21.9 mmol) of 3,4,4-Cryptor-3-butanolide (compound 101). During the addition a white precipitate is formed. Mixture was allowed to warm to ambient temperature and to dissolve the product, add 150 ml of dichloromethane. The phases are separated and the organic phase is mixed with anhydrous sodium sulfate, filtered and concentrated. The residue is recrystallized from ethyl acetate and get 4,25 g (69%) of a white solid substance, so pl. 123 - 124oC.

(b) of 2.45 g (8.69 mmol) of the carbamate obtained in stage a), in 15 ml of methanol at ambient temperature is added a solution of HCl in methanol, prepared by the addition of 0.68 ml (6.5 mmol) of acetylchloride to 5 ml of methanol with vigorous stirring. The mixture was stirred at ambient temperature for 3 hours and concentrated. Recrystallization of the residue from a mixture of 2-prop the hydrochloric salt in the form of colorless plates, so pl. 145 - 147oC. the output of the two portions is 470 mg (33%).

Example 46 synthesis

Synthesis of monohydrochloride 7,8,8-Cryptor-7-octene-1-amine

(compound 59)

a) In 1-liter, 4-neck flask is charged with magnesium turnings (15,4 g, 0,635 mol) and anhydrous THF (100 ml) in an atmosphere of N2. Add a few crystals of iodine and the mixture is heated until then, until there is no longer the colour of iodine. Add dropwise a solution of 1-bromo-3,4,4-Cryptor-3-butene (100 g, 0,529 mol) in anhydrous THF (500 ml) with such speed, that THF was quietly seething and dripped into the mixture. After completion of the addition (about 1 hour) the solution is heated at the boiling point under reflux for 30 minutes. The solution is cooled to 30oC and transferred to an addition funnel under pressure N2using a tube, and leaving in the flask unreacted magnesium chip.

b) In a 3-liter, 4-neck flask is charged with 1,4-dibromobutane (to 114.4 g, 0,530 mol, 63,3 ml), delimitercharacters (80 ml 0.1 M solution in THF, 8.0 mmol) and anhydrous THF (250 ml). The mixture is cooled to 5oC and process, adding dropwise, the Grignard reagent obtained in stage a), with stirring at 5 to 10oC. Adding complete in 30 minutes. The mixture was then stirred at (1200 ml), cooled in a bath of ice water, and slowly treated with 5% sulfuric acid (500 ml). The ether layer is successively washed with 5% sulfuric acid (300 ml), water (200 ml), saturated NaHCO3(200 ml), brine (200 ml) and dried MgSO4. The solvent is evaporated and the residue is distilled under reduced pressure; get 100,2 g crude product as a colourless oil, so pl. 85 - 100oC for 35 mm RT.article This fraction is dissolved in dimethyl sulfoxide (DMSO) (400 ml, anhydrous) and treated BaN3(88.4 g of 1.36 mmol) under stirring at room temperature. After a few minutes formed a thick layer of white crystalline substance, add a further 20 ml of DMSO and vigorously stirred for 1 hour. The mixture is then treated with 600 ml of water and extracted with ether (2 600 ml). The ether extract washed with water (3 x 300 ml), brine (300 ml) and dried with MgSO4. Evaporation of solvent gives 77.0 g of light yellow oil. This oil is dissolved in 400 ml of DMSO and treated in one portion of triphenylphosphine (225 g, 0,858 mol) with stirring. The reaction mixture was cooled in an ice-water bath until until no longer stand the heat, and stirred at room temperature for 5 hours. Then doba is OK filtered. The filtrate is washed with water and the ether layer is extracted with 10; HCl. The aqueous layer was then extracted with dichloromethane and concentrated under reduced pressure. The residue is treated with 60% toluene in absolute ethanol and evaporated to remove traces of water. The residue (10.1 g) is a pale-yellow solid, yield of 8.7%

Example 47 synthesis

Synthesis of monohydrochloride 5,6,6-Cryptor-5-HEXEN-1-amine (compound 74)

(a) To the magnesium turnings (26.7 g, 1,7 ml) in dry ether (500 ml) add a few crystals of iodine. The mixture is heated until then, until it boils ether, and add 4-bromo-1,1,2-Cryptor-1-butene (189 g, 1.0 mol) in dry ether (400 ml) dropwise and under stirring, and with such speed that the ether is boiled slowly. Add takes 1.5 hours. When you are finished adding, add 200 ml of dry ether and the mixture is heated at boiling temperature under reflux for 30 minutes. The mixture is cooled to - 30oC and added CuI (19,0 g, 0.1 mol). The ethylene oxide condensed in the drip funnel, using a mixture of dry ice and acetone (55 g, 1.25 mol), is added dropwise and stirring at -30oC for approximately 30 minutes. The mixture is then left to reach room temperature overnight. Then socioi extracted with ether. The combined ether extracts are washed with saturated NaHCO3followed by a saline solution, and dried over MgSO4. After careful evaporation of the solvent to obtain 195 g of oil red. Distillation under reduced pressure to give 155 g of colorless oil, so Kip. 90 - 100oC 80 75 mm RT.article The product is then treated with 1.5 l of hexane and washed 4 times with water. The hexane layer is dried over anhydrous Na2SO4and concentrate, get 100 g of the light oil, which is distilled under reduced pressure, and get 95 g 5,6,6-Cryptor-5-hexanol in the form of a light oil, the yield of 61.7%.

b) a Solution of methylchloride (46,5 ml, 600 mmol) in dichloromethane (250 ml) is added dropwise to a solution of the alcohol obtained in stage a) (77.0 g, 500 mmol) and triethylamine (104,5 ml, 750 mmol) in dichloromethane (750 ml) at -25oC under stirring. Stirring is continued for 30 minutes at -20oC. the mixture is Then treated with 10% HCl (300 ml) and the organic layer washed with 10% HCl (200 ml) and then saturated NaHCO3(200 ml), brine (200 ml) and dried over MgSO4. Evaporation of solvent gives 116 g of a yellow oil. It is dissolved in DMSO (400 ml) and injected into the interaction with NaN3(65 g, 1000 mmol) at room temperature for neither room temperature for 5 hours and add conc. the ammonium hydroxide. The mixture is stirred at room temperature overnight. The reaction mixture was then diluted with ether (1500 ml) and extracted with water. The precipitate is filtered off and the ether layer washed with water and extracted with 10% HCl. The aqueous layer was again extracted 3 times with dichloromethane, and concentrated in a rotary evaporator under reduced pressure; get the desired product as a pale yellow solid, 74,6 g, yield to 78.7%.

Using the methods and source materials described above and illustrated in the previous examples, receive and other compounds. Below is a table of compounds which can be obtained as indicated above.

SONGS

For normal use of the compounds of formula I, generally used in free form, without mixing or dilution, and are typically used in suitably composed of a composition compatible with the method of application, and containing an effective amount of the compounds. Compounds of the present invention, like most agricultural products, can be mixed with acceptable agricultural surface-active agents and carriers normally employed for facilitating the dispersion is aktivnosti substances. The proposed connection can be used, for example, in the form of liquids to plants, Farrukh Dustov or granules, in areas where it is required to conduct pest control, and the type of application varies depending on the pest and the environment. Thus, the compounds of the present invention can be included in the granules large, Farrukh Dustov, wettable powders, emulsifiable concentrates, slurries and the like.

The granules may contain porous and non-porous particles, such as particles attapulgite clay or sand, for example, which serve as carriers for the proposed connection. Granular particles are relatively large in diameter, usually 400 to 2500 microns. The particles are either impregnated with the compound of the invention from a solution, or covered by the connection, and sometimes use the adhesive. Granules usually contain 0.05 - 10%, preferably 0.5 to 5%, of the active ingredient.

Dusty are mixtures of compounds with finely ground solids such as talc, attapulgite clay, kieselguhr, pyrophyllite, honey, diatomaceous earth, calcium phosphates, carbonates of calcium and magnesium, sulfur, various flours, and other organic and reorganize is and have an average particle size less than 50 microns. Typical gustova composition contains 1 part of the compound and 99 parts of talc.

Compounds of the present invention can be manufactured in the form of liquid concentrates by dissolution or emulsification in suitable liquids and into solid concentrates by mixing with talc, clays, and other known solid carriers used in chemical products for agriculture. The concentrates are compositions containing 5 to 50% of the active compound and 95 to 50% inert material, which includes surface-active dispersing agents, emulsifiers and wetting, but the experiment can be used and a higher concentration of active ingredient. In the practical application of the liquid for atomization of the concentrates are diluted with water or other liquids, and when used in the form of Farrukh Dustov their diluted with an additional amount of solid carrier.

Typical composition of 50% wettable powder will contain 50% (weight/weight) of active ingredient, 22% attapulgite diluent, 22% kaolin diluent and 6% sodium salts of sulfonated Kraft lignin as an emulsifier.

Typical carriers for the solid to the strong adsorbent easily wettable inorganic diluents. A suitable composition of the solid concentrate may contain 1.5 parts of sodium lignosulfonate and sodium lauryl, as wetting, 25 parts of active connections and 72 parts attapulgite clay.

Production concentrates suitable for the transportation of low-melting products of the present invention. Such concentrates receive, melting low-melting solids, together with 1% or more of the solvent to obtain a concentrate which does not harden when cooled to the freezing point of the pure product or to a lower temperature.

Suitable liquid concentrates include the emulsifiable concentrates, which are homogeneous liquid or paste compositions, easily dispersible in water or other liquid carriers. They can also consist of active compound and a liquid or solid emulsifying agent, or they may also contain a liquid carrier such as xylene, heavy aromatic naphtha fraction, isophorone and other relatively non-volatile organic solvents. When applied, these concentrates are dispersed in water or other liquid carriers, and when="ptx2">

Typical composition of emulsifiable concentrate (50 g per liter) will consist of 5.9 percent (weight/weight) of the compounds of the invention, emulsifiers and 1.80% of the mixture of the calcium salt dodecylbenzensulfonate and nonionic condensation products of 6-molar ethylene oxide with Nonylphenol, 2.7% of a mixture of calcium salts dodecylbenzensulfonate and nonionic condensation products of 30-molar ethylene oxide with Nonylphenol, 1,50% nonionic paste simple ether polyalkyleneglycol, and 88,10% cleared in xylene as a solvent.

Typical surface-active wetting, dispersing agents and emulsifying agents used in compositions for agriculture include, for example, alkyl - and aryl-sulfonates and sulfates and their sodium salts, alkylarylsulfonate, including fatty methyltaurine, alcylaryl polyether alcohols, sulfated higher alcohols, polyvinyl alcohols, polyethylene oxides, sulfonated vegetable and animal oils, sulfonated petroleum oil distillates, esters of fatty acids and polyhydric alcohols and addition products of ethylene oxide such esters and adducts of long-chain mercaptans and ethylene oxide. Surface-active substance typically contains 1 to 15 wt.% the active ingredient.

awn is dissolved at the desired concentration, such as water, acetone or other organic solvents. The preferred composition for the treatment of the foliage is an aqueous solution, usually containing glycerin and such surfactant like Tween 20, and as a rule, 1% glycerol, and 0.1% Tween 20.

The compositions can be formulated and applied with the right ingredients, with pesticide activities, including insecticides, acaricides, fungicides, growth regulators, herbicides, fertilizers, etc.

APPLICATIONS

The present invention provides ways of dealing with different pests that harm crops, namely, nematodes, insects and mites. With the infection of plants by any of these pests can be controlled by applying to the processing of parts of a plant an effective amount of any of compounds of the present invention. Processing may be performed in various ways, including processing compound or composition containing the soil before or after sowing or emergence of seedlings, and seeds or parts of seeds before or during sowing, and foliage, stems or trunks of plants. The treatment can be carried out in a period of growth not just once, with a break between obreros, which is the struggle, the ambient temperature and humidity levels. In addition, the processing mode can be influenced by the age or size of the plant.

The methods of the present invention can be applied to different cultures. These crops include, but are not limited to, fruit and vegetable crops, such as potatoes, sweet potatoes, carrots, tomatoes, grapes, peaches, citrus fruits, bananas, corn and cultural soybeans, tobacco, and cotton.

The compounds of formula I of the present invention can be used to combat any filepathandname nematodes. Insects that can be controlled by the methods of the present invention include, but are not limited to, foliar pests such as aphids, peach, and pests, emerging in the soil, such as South Dlinnaya blaska. Acarida, which can be treated by methods of the present invention include, but are not limited to, mites spider bimaculated. Tests conducted with several compounds of the present invention, showing an insufficient level of combat worm or the Colorado potato beetle.

EXAMPLES TEST

A. Tests with tomato and soybean cyst nematode

Join the Yves nematodes root knot (Meloidogyne incognita). Connection experience, treating foliage and wetting the soil. The results of four different methods of testing are presented in table A. testing Methods described below.

METHOD 1. Processing leaves of tomato plants

Plant tomato with "Rutgers" grow one plant in a pot size 2,5x18,8 see 19 days after planting both sides of the leaves are sprayed with the test compound at the concentrations indicated in table A. compound is prepared by dissolving each first in-water or acetone, in accordance with the purpose, and is mixed with water containing 0.05% Tween 20 and 1.0% of glycerol. For each group of tests are sprayed with four plants 29 ml. Plants are left to dry before they are placed in the camera for cultivation, in which the temperature is maintained at 25 - 28oC. Here they irrigate, but not enough to prevent dripping of drops from the leaves on the ground. After 2 to 3 days after chemical treatment on the roots and the soil applied with a pipette suspension larvae 2,4500 on the potty. 3 weeks after inoculation the number of injuries on the washed leaves compared to the amount of damage on the control leaves treated with water. The results are expressed as percentage correct by sabinian, (1) tomato plants are planted in pots size 7,5x6,3 cm and (2) the inoculation is carried out, causing the pipette approximately 8,000 eggs in 5 ml of soil in each pot at 20 days after planting. The next day, each plant sprayed with 4 ml solution for processing. The degree of damage determined 3 weeks after inoculation. Use the rating scale from 0 to 3, where 0 is the extensive damage and 3 means no damage.

METHOD 3. Treatment of soil under soybean seeds

Two cultural seed of soybean CV"Williams" is placed in each pot size 2.5 cm2and inoculant approximately 8,000 eggs. Add compound 1 mg per pot in 2 ml of the solution prepared as described in method 1. For each level of processing used one pot. The seeds are covered with vermiculite and slightly moisten. Plants limited irrigate once a day for 4 weeks. Then assess the condition of the washed roots, as in method 2.

METHOD 4. Tillage under tomato plants

Follow the stages of method 2, except that the next day after inoculation soil treatment, causing the pipette 4 ml of solution treatment on the soil in each pot. Corrupted, and the response of tomato

Perform phase of method 2 and 4, except that tomato plants grown in pots of size 5,h,0 cm2and the inoculation is carried out, causing the pipette approximately 7,000 eggs in 4 ml of soil in each pot 20 days after planting. The next day after inoculation process the soil, causing the pipette 2 ml of working solution into each pot on the soil surface, and spray the leaves 1.5 ml of working solution. Damage assessed 3 weeks after inoculation, as in method 2.

B. Tests with soybean cyst nematodes

The connection I feel to the efficiency in the fight against soybean cyst nematode (Heterodera glycines) in the processing of the leaves. Sandy soil infect approximately 100 soybean cyst nematodes on 1 cm3soil. Approximately 350 cm3contaminated soil was placed in each pot with base 25,8 cm2. Three seeds of soybean, Glycine max = variations Williams-82, is placed on the surface of the contaminated soil and covered with a layer of uncharged sandy soil.

Processing leaves begin when the plant reaches the stage of development of a single sheet. Treatment is carried out as a single, spraying this one sheet, or spend several consecutive sprays - one is in water of 1% glycerol and 0.1% Tween 20. In each treatment the surface of the soil cover to prevent contact of the substance with the soil. The treatment is carried out to the point of growth, using doses indicated below.

Final evaluation of the disease are approximately 5 weeks after planting by counting the number of cysts on each root system. The elimination of the disease is defined as the percentage reduction of the average number of cysts on the roots of treated plants compared to the inoculated treated with a control composition consisting of water, glycerol and Tween 20 .

C. Tests with insects and acaridae

The compounds I of the present invention are tested for effectiveness in combating lexicom spider bimaculated, Tetranychus urticae or TSSM, peach aphids, Myzus persicae or GPA, and South dinosau blascoe, Diabrotica undecimpunctata or CPW, when processing of the leaves.

At the beginning of testing to determine action against aphids three-week plants of Chinese cabbage (Brassica chinensis) infect older peach aphid insects with pieces of leaves from cultivated plants. Re-infected plants left in the chambers for growing up until the insect will not grow more than forty insect on the sheet. For ispitnih materials are dissolved directly in the aqueous composition, containing 1% glycerol and 0.1% Tween 20. Plants are sprayed to the point of growth, putting a solution on both upper and lower surface of leaves. Each test solution is sprayed on 5 plants. Sprayed plants move under the hood, where they were kept up until they are dry. Plants are again transferred into the chamber to grow for 5 days, before determining the final result of the action.

For tests with bimaculated spider lexicom use soybean (Glycine max) at the stage of a single sheet, or cotton (Gossypium hirsutum), which fully opened cotyledons. With cultivated plants infected adult mites and their eggs, remove the leaf discs made using the drill for feeding tubes # 6, put them on the top surface of the first sheet of soybean, or on the upper surface of the cotyledon leaves of cotton plants. After the mites will spread and infect the whole plant (6 - 10 days), leaf disks removed. The most uniformly infected plants are selected for testing and sprayed with test solutions as described above, using 5 plants per treatment. 5 days after treatment to check all the sheets and consider adult mites on the changes compared to treated water composition.

Tests with South dinosau blascoe carried out using seeds of maize (Zea mays), which are sown in 4 in each of the 7.5-cm pots and grown in a greenhouse until the height of the plant is approximately 15 cm In surface soil near the roots of each plant scratched the small holes, and the holes are placed 10 larvae dinosau of a flea the first stage of development. The next day after infection the leaves of maize plants are sprayed to the point of growth of the tested solutions of the same composition as described above. 7 days after spraying larvae extracted from the soil, soaking pots 10M solution of MgSO4. Average number of larvae for each treatment and calculate the percentage correct.

D. Treatment of seed potatoes

The compounds I of the present invention are tested for effectiveness in the fight against nematode brown outgrowth (Meliodogine incgnita) in the processing of potato seed pieces. Connections are also experiencing, processing leaves, for comparison.

Potato tubers are cut so that each piece remained at least 2 buds. For each level of processing pieces of tubers weighed and placed in a mixture of compounds and sufficient izmelchennostju until until you have covered the surface, and planted one piece 3.8 l (1-gallon) pot. Each pot inoculant 50,000 eggs.

When processing the leaves of each plant are sprayed with a solution of compound I in water with 1% glycerol and 0.05% Tween 20 . Spraying do so, in order to spread the compound over the surface of all the leaves. Each plant sprayed 4 times with an interval in 2 weeks, and inoculant either at planting or within 3 days before processing. The results are presented in table D.

1. Florenceville compounds of General formula I

< / BR>
where X and Y are fluorine;

Z is hydrogen or fluorine;

n= 1, 3, 5, 7, 9 or 11;

Q - CH2OTHER6CH2NO2CH2N = CHR2CH2N = C = O, CH2N+R3R4R5W-or (C = O) - R11provided that when Q is - (C = O) - R11Z is fluorine, and n = 1, W-anion of a mineral or organic acid;

R2is phenyl, optionally substituted with at least one group selected from hydroxyl, nitro, halogen, di(C1- C4)alkylamino, or pyrazolyl;

R3- R5is hydrogen or taken with the nitrogen atom of the group Q form pyrrolidinyl or tetraazatricyclo-[3,3,1,1-(Superscript-RET-butoxycarbonylamino, (C1- C5)alkyl-COOH, optionally substituted carboxyl group, (C1- C5)alkyl-CONH2, (C1- C5)alkyl-COO - (C1- C4)-alkyl, (C1- C5)alkyl-COO - (C1- C4)alkylphenyl, (C1- C6)alkenyl, substituted with halogen, dihydro-3-oxadiazolidine, thienyl and phenyl, optionally substituted by carboxyla or (C1- C4)alkoxycarbonyl, (C = O)R7where R7- (C = O)R14, (C1- C6)alkyl, optionally substituted with at least one group selected from the series halogen, amino or (C1- C6)cycloalkyl, tert-butoxycarbonylamino, hydroxyl, phenyl, (C1- C4)allylthiourea, (C1- C5)alkyl-COOH or its esters, optionally substituted amino group, (C1- C5)alkyl-CONH2, optionally substituted amino group, (C1- C6)alkenyl, substituted with halogen, or N-containing group which, taken together with carboxamido, represents the balance of urea, optionally substituted (C1- C4)-alkyl, possibly substituted by hydroxyl, or R6taken together with the nitrogen group, Q represents a hydrazine, guanidine, triftormetilfullerenov;
UB> - C8)alkyl, optionally substituted by amino or phenyl, phenyl, optionally substituted by a nitro-group;

R12- (C1- C8)alkyl, optionally substituted by amino or phenyl, phenyl, optionally substituted by carboxyla;

R12- - hydrogen, (C2- C6)alkyl;

R13is hydrogen, (C2- C4)alchemission, (C1- C6)alkyl, optionally substituted with at least one group selected from (C1- C4)alkoxycarbonyl, amine, phenyl, (C2- C6) alkinson optionally substituted by carboxyla or phenyl, (C1- C6)alkylamino, replaced by carboxyla or (C1- C4)alkoxycarbonyl, phenyl, optionally substituted by carboxyla;

or R12"and R13together with the nitrogen atom of the group NR12R13form the rest of the natural amino acids of a protein selected from a range glycyl, poured, alanyl, asparagus, phenyl alanyl, prolyl, lysyl, and morpholinopropan, pyrrolidinyl or pyrazolyl, possibly substituted by carboxyla;

R14- OH, (C1- C6)alkoxy, NH2or NHNH2,

or agricultural acceptable salts, provided that when n = 1, and X, Y and the fact that what R2represents a

< / BR>
3. Connection on p. 1, characterized in that n = 1, X and Y are fluorine.

4. Connection on p. 3, wherein Z is hydrogen, and Q is CH2NH2or CH2NH+3W-.

5. Connection on p. 3, wherein Z is fluorine.

6. Connection on p. 5, wherein Q is CH2OTHER6and R6- amide amino acids q

7. Connection on p. 6, wherein R6- amid the main amino acids q

8. Connection on p. 7, wherein the basic amino acid is methionine.

9. Connection on p. 1, characterized in that W-- chloride, iodide, bromide, oxalate, sulfate, phosphate, acetate, citrate or 3,4,4-Cryptor-3-butenoate.

10. Connection on p. 1, characterized in that it is a 4,4-debtor-3-butene-1-amine or its agricultural acceptable salt.

11. Connection on p. 1, characterized in that it is a 3,4,4-Cryptor-3-butenova acid or its agricultural acceptable salt.

12. Connection on p. 1, characterized in that it is a 3,4,4-Cryptor-3-butene-1-amino-3,4,4-Cryptor-3-butenoate.

13. Connection on p. 1, characterized in that the submission is RBI with infection of plants by nematodes, including an active ingredient and additives target, characterized in that as the active ingredient it contains a compound of formula I under item 1 in an effective amount.

15. The composition according to p. 14, characterized in that as the active ingredient it contains N-(3,4,4-Cryptor-1-oxo-3-butene-yl)glycine, or 3,4,4-triptoreline acid, or their salts.

16. The way to combat infection of plants by nematodes by treating the locus of the plants active compound, characterized in that active compound is used as a compound of formula I under item 1 in an effective amount.

17. The way the system suppression of plant infection by nematodes by processing plants active compound, characterized in that active compound is used as a compound of General formula

< / BR>
where n= 1, 3, 5, 7, 9 or 11;

Q1- CH2OTHER6(C = O) - R11or CH2N+H3W-;

X, Y and Z each is hydrogen or fluorine, or at least one of X and Y is fluorine, provided that when Q1- (C = O) - R11Z is fluorine and n = 1;

R6is hydrogen, (C1- C8)alkyl, optionally substituted amino or tert-butoxycarbonylamino, (C1- C55)alkyl-COO - (C1- C4)alkyl, (C1- C5)-alkyl-COO - (C1- C4)alkylphenyl, (C1- C6)alkenyl, substituted with halogen, dihydro-3-oxadiazolidine, thienyl and phenyl, optionally substituted by carboxyla or (C1- C4)alkoxycarbonyl, (C = O)R7where R7- (C = O)R14, (C1- C6)alkyl, optionally substituted with at least one group selected from the series halogen, amino or (C1- C6-cycloalkyl, tert-butoxycarbonylamino, hydroxyl, phenyl, (C1- C4)allylthiourea, (C1- C5)alkyl-COOH or its esters, optionally substituted amino group, (C1- C5)alkyl CONH2, optionally substituted amino group, (C1- C6)alkenyl, substituted with halogen, or N-containing group which, taken together with carboxamido, represents the balance of urea, optionally substituted (C1- C4)alkyl, possibly substituted by hydroxyl, or R6taken together with the nitrogen group Q1is a hydrazine, guanidine, triftormetilfullerenov;

R11- halogen, NHOH1, OR12, SR12,NR12R13where R12is hydrogen, (C1oppai, and has a polarity, providing the penetration of compounds in the phloem of the leaf without reducing their nematocidal activity;

R12-(C1- C8)alkyl, optionally substituted by amino or phenyl, phenyl, optionally substituted by carboxyla;

R12is hydrogen, (C1- C6)alkyl;

R13is hydrogen, (C1- C4)alchemission, (C1- C6)alkyl, optionally substituted with at least one group selected from (C1- C4)alkoxycarbonyl, amine, phenyl, (C2- C6)alkinson, optionally substituted carboxyla or phenyl, (C1- C6)alkylamino, replaced by carboxyla or (C1- C4)alkoxycarbonyl, phenyl, optionally substituted by carboxyla, or

R12and R13together with the nitrogen atom of the group NR12R13form the rest of the natural amino acids of a protein selected from a range glycyl, poured, alanyl, asparagus, i.e. phenylalanyl, prolyl, lysyl or morpholinopropan, pyrrolidinyl or pyrazolyl, possibly substituted by carboxyla;

W-anion of a mineral or organic acid,

or agricultural acceptable salt in an effective amount.

1 CLASS="ptx2">

19. The method according to p. 18, characterized in that the link quality is used as a compound in which Z is fluorine.

20. The method according to p. 19, characterized in that the link quality is used as a compound in which Q1- CH2N+H3W-,W-an agricultural acceptable anion.

21. The method according to p. 20, characterized in that the link quality is used as a compound in which W-represents a chloride, iodide, bromide, oxalate, sulfate, phosphate, acetate, citrate or 3,4,4-Cryptor-3-butenoate.

22. The method according to p. 19, characterized in that the link quality is used as a compound in which Q1- COOH or its salt.

23. The method according to p. 19, characterized in that the link quality is used as a compound in which Q1- CH2OTHER6.

24. The method according to p. 23, characterized in that the link quality is used as a compound in which R6represents the balance 3,4,4-Cryptor-3-butene-1-amine or its salt or a group which is transformed in him after application to the plant or inside plants.

25. The method according to p. 23, characterized in that the quality of the connection use the connection, in which R6- analsyt connection, in which R6the residue is methionine.

27. The way the system suppression of plant infection by nematodes by treating the plants with the active compound, characterized in that active compound using N-(3,4,4-Cryptor-1-oxo-3-butene-yl)glycine, or 3,4,4-triptoreline acid, or their agricultural acceptable salt in an effective amount.

Priority points:

01.03.91 on PP.1, 2 - 12, 14, 16, 18 - 25;

03.02.92 on PP.1, 13, 15, 17, 26, 27.

 

Same patents:

-aminocarboxylate, the method of production thereof, pharmacologically active composition based on them and the way to prevent the development of disease" target="_blank">

The invention relates to derivatives of N-phenyl-alkyl-substituted alpha-aminocarboxylic formula (1):

< / BR>
where R represents a furyl, thienyl, pyridyl or unsubstituted or substituted phenyl; A represents -(CH2)m- or -(CH2)p-X-group, in which X is-O-, -S - or-NR4-; R1, R2, R3, R4, n, m, p are defined in the description of the invention; and R5and R6independently are hydrogen or C1-C6-alkyl, and their pharmaceutically acceptable salts

The invention relates to the field of organic chemistry, and in particular to a method for producing amides of unsaturated acids of the General formula 1

Q Q1CR2= CR3CR4= CR5C(X) OTHER1(1) or their salts, where Q denotes phenyl, pyridyl, naphthyl, degloving, each of which may be substituted by 1-3 substituents selected from the group:1-C6alkyl, C1-C6alkoxy, CF3, halogen, Q1-1,2-cyclopropyl ring, possibly substituted C1-C4the alkyl, R2, R3, R4and R5denote identical or different groups, including hydrogen, C1-6alkyl group, or C1-6 haloalkyl group; one of the radicals necessarily mean hydrogen, X denotes an oxygen atom, R1denotes hydrogen or C1-6the alkyl may contain as substituents DIOXOLANYL group, cyclo(C3-C6)alkyl, possessing insecticidal activity
The invention relates to chemistry, in particular to the field of production, composition and application of tools for processing plants

The invention relates to a repellent for repelling insects which comprises at least one alkyl ester of a fatty acid having from 1 to 4 carbon atoms in the alkyl group, at least one natural, identical to natural or synthetic fatty alcohol as the active substance, at least one natural or identical to natural vegetable or animal oil as a carrier

The invention relates to agriculture, but rather to crop production, and refers to substances that have a regulating effect on biochemical processes in plant cells, leading to improved quality of the end product of the process of growing plants, defined biological value accumulated therein of compounds necessary for human nutrition

The invention relates to agriculture, namely, to the means of protection of plants against diseases, in particular, compositions for immunizing plants against various phytopathogens

The invention relates to agriculture, in particular, to means of regulating plant growth

The invention relates to a new simple cyclohexanehexol esters and herbicide compositions on their basis

Herbicide tool // 2049394

The invention relates to new oksimnymi derived cyclohex-2-EN-1-it, which can find application in agriculture, and chemical methods of plant protection, and in particular to methods of inhibiting the growth of unwanted plants, using the new Aksinya derivatives cyclohex-2-EN-1-it
Up!