HK1056360B - Process for preparing pesticidal intermediates - Google Patents

Description

Process for preparing pesticidal intermediates

This application is a divisional application of Chinese patent application No. 98802977.4 entitled "method for preparing insecticide intermediate" filed on 25.2.1998.

Technical Field

The present invention relates to a process for the preparation of pesticidal intermediates, and to novel 2-arylhydrazonosuccinonitrile compounds, and to 2-arylhydrazonosuccinonitrile compounds.

Technical Field

Published European patent Nos. 0295117 and 0234119 describe the preparation of pesticidally active phenylpyrazole compounds and 5-amino-1-aryl-3-cyanopyrazole intermediate compounds for use in the synthesis. Various methods for the preparation of these compounds are known. However, there is a need to provide improved methods for the preparation of these compounds and their intermediate compounds.

Aryl hydrazines are known to undergo Michael addition reactions with electron deficient olefins such as acrylonitrile in polar protic solvents such as alcohols, followed by oxidation in basic media to give 5-amino-1-arylpyrazoles, as described, for example, in U.S. Pat. No. 4824960. However, the applicant of the present invention has not found any information reporting the reaction of hydrazine with fumaronitrile. Oxidation of N, N' -diarylhydrazines to azo compounds is known, as are N-alkylhydrazines and N-arylhydrazines, which are substituted on only one nitrogen atom, but they are generally unstable and decompose into nitrogen and hydrocarbons (see j. march, Advanced Organic Chemistry, third edition, page 1062). Palladium catalyzed dehydrogenation of α -hydrazononitriles to hydrazone based cyanides in the presence of cyclopentene is described by y.h.kim and y.choi in a paper published in Tetrahedron letters 1996, volume 37, pages 8771-4. However, the applicant is not aware of any other information about the oxidation of hydrazine to form hydrazones. Furthermore, the descriptions of Kim and Choi are limited to the derivatives of unsubstituted phenylhydrazine and no suggestion is made that oxidation of hydrazine derivatives of fumaronitrile can be achieved.

Disclosure of the invention

It is a first object of the present invention to provide a convenient process for the preparation of 5-amino-1-aryl-3-cyanopyrazole pesticidal intermediates in high yield and purity.

It is another object of the present invention to provide a process for the preparation of 2-arylhydrazonosuccinonitrile compounds which are useful as intermediates in the preparation of 5-amino-1-aryl-3-cyanopyrazole insecticides.

It is still another object of the present invention to provide a method for preparing 2-arylhydrazinosuccinonitrile compounds.

It is a further object of the present invention to provide novel intermediates useful in the preparation of compounds having pesticidal activity.

These and other objects of the invention will be apparent from the following description and may be achieved in whole or in part by the present invention.

One aspect of the present invention provides a process for the preparation of a compound of formula (I) by ring formation of a compound of formula (II), as shown in the following reaction scheme Sc 1:

wherein W is nitrogen or-CR₄；R₂、R₄、R₅、R₆Independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, R₇S(O)_n-, nitro, cyano, and-SF₅；R₃Is as defined for R₂Or from 1 to 5 substituents selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, R₇S(O)_n-, nitro, cyano, and-SF₅Phenyl optionally substituted with the groups of (a), which groups may be the same or different; r₇Is alkyl or haloalkyl; n is 0, 1 or 2.

Unless otherwise specified in the specification, "alkyl" means a straight-chain or branched alkyl group having 1 to 6 carbon atoms (preferably 1 to 3). Unless otherwise indicated, "haloalkyl" and "haloalkoxy" are each a straight-chain or branched alkyl, alkoxy group of 1 to 6 carbon atoms (preferably 1 to 3) substituted by one or more halogen atoms selected from fluorine, chlorine, bromine.

Preferred compounds of formula (I) have one or more of the following characteristics: r₂Is halogen or hydrogen; r₃Represents halogen, halogenAlkyl (preferably trifluoromethyl), haloalkoxy (preferably trifluoromethoxy), R₇S(O)_p-、-SF₅Or from 1 to 3 substituents selected from trifluoromethyl, trifluoromethoxy, difluoromethyl, -S (O)_nCF₃Dichlorofluoromethyl, chlorodifluoromethyl, chlorodifluoromethoxy, dichlorofluoromethoxy and halogen-substituted phenyl groups, which may be the same or different; r₄Is halogen; r₅And R₆Is hydrogen.

Particularly preferred compounds of formula (I) have one or more of the following characteristics: -W represents-CR₄，R₄Is halogen; r₃Represents haloalkyl, haloalkoxy, or-SF₅；R₅And R₆Represents hydrogen.

The most preferred compound of formula (I) is 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) pyrazole.

The above reaction Sc1 for obtaining the compound of formula (I) is generally carried out in the presence of a base, which may be organic or inorganic. Examples of suitable organic bases are amines, such as triethylamine or pyridine. Examples of suitable inorganic bases are alkali, or alkaline earth metal hydroxides, acetates, carbonates, or bicarbonates such as sodium hydroxide or carbonate, or preferably ammonia (aqueous or gaseous). Generally, the molar ratio of the compound of formula (I) to the base ranges from about 1: 10 to about 10: 1. The reaction may also be carried out in the presence of a phase transfer catalyst, for example, quaternary ammonium salts such as benzyltrimethylammonium chloride, trioctylmethylammonium chloride, tetramethylammonium chloride, tetra-n-propylaminium bromide, n-dodecyltrimethylammonium chloride, tetra-n-butylammonium chloride, and n-tetradecyltrimethylammonium bromide. The reaction is typically carried out in a solvent, suitable solvents including alcohols (preferably ethanol), or non-aqueous-miscible solvents, especially halogenated hydrocarbons such as dichloroethane or dichloromethane, non-miscible solvents being suitable when a phase transfer catalyst is used. Water may also be selected as a co-solvent. The reaction temperature is usually about-20 to 50 ℃ and preferably about 0 to 20 ℃.

According to another feature of the present invention, there is also provided a process for the preparation of a compound of formula (II) by oxidation of a compound of formula (III), as shown in the following reaction scheme Sc 2:

w, R therein₂、R₃、R₅And R₆Is as defined above.

Preferred pairs of compounds of formula (II) W, R₂、R₃、R₅And R₆Are as defined above for the compounds of formula (I). The most preferred compound of formula (II) is 2- (2, 6-dichloro-4-trifluoromethyl-phenylhydrazono) succinonitrile.

The compound of formula (II) obtained may be a mixture of cis and trans isomers, all such forms being included within the scope of the present invention.

Suitable oxidising agents for the above reaction scheme for forming compounds of formula (II) Sc2 include quinones such as benzoquinone, peroxides such as hydrogen peroxide, hypohalites such as sodium hypochlorite, or alkali metal hydroxides such as sodium hydroxide in the presence of air, or preferably salts of metals or metal oxides such as copper dichloride or mercury oxide. This reaction is usually carried out in a solvent. Suitable solvents include aromatic halogenated or non-halogenated hydrocarbons such as toluene or chlorobenzene, nitriles such as acetonitrile, or amides such as N, N-dimethylformamide. The reaction temperature is usually about 20 to 150 ℃ and preferably about 50 to 100 ℃.

According to a further feature of the present invention, there is provided a process for preparing a compound of formula (II) by reacting a compound of formula (IV), an enol thereof, or an enolate thereof with a diazonium salt of formula (V), as shown in the following reaction scheme Sc 3:

here W, R₂、R₃、R₅And R₆As defined in the above reaction scheme Sc1, X is typically an anionic group of an inorganic acid, such as hydrogen sulfate or chloride.

The compounds (IV) are generally in the form of enolates, preferably alkali metal salts, such as potassium or sodium enolates.

The reaction scheme Sc3 described above for the reaction of a compound of formula (IV) with a compound of formula (V) to form a compound of formula (II) occurs via coupling and deformylation. When the compound (IV) used is a metal enolate, the reaction is usually carried out in a sufficient excess of a mineral acid such as sulfuric acid and hydrochloric acid (the mineral acid is usually present when the diazotization reaction is carried out in the same vessel), converting the metal enolate into a free enol. Solvents such as acetic acid, water, halogenated hydrocarbons such as dichloromethane or dichloroethane, halogenated aromatic compounds such as chlorobenzene, acetonitrile, N-dimethylformamide or, preferably, alcohols such as ethanol are generally used. The reaction may also be carried out in the presence of a buffering agent such as sodium acetate. After the coupling stage, a weak base such as ammonium hydroxide solution is typically added to produce a weak alkaline solution to complete the reaction, e.g., a pH of about 8. The reaction temperature is usually about-20 to 50 ℃ and preferably about 0 to 20 ℃.

The diazonium salts of formula (V) above are generally prepared by in situ reaction of a compound of formula (Va):

diazotization of W, R₂、R₃、R₅And R₆The meaning of (a) is as defined above, using conditions known in the literature, generally 1 molar equivalent of sodium nitrite and a mineral acid such as hydrochloric acid or sulfuric acid is used.

According to a further feature of the present invention, the compound of formula (II) may also be prepared by reacting a compound of formula (VI) with a diazonium salt of formula (V) wherein W, R is present₂、R₃、R₅、R₆And X is as defined above, W, R in the compound of formula (II)₂、R₃、R₅And R₆The meaning of which is the same as that defined in the above reaction scheme Sc1, in a compound of formula (VI):

ra is an alkyl group, preferably an ethyl group.

The reaction conditions employed are the same as those described in the above reaction scheme Sc 3.

According to a further feature of the present invention, the compound of formula (III) above may be prepared by the reaction of an arylhydrazine of formula (VII) with a compound of formula (VIII), as shown in the following reaction scheme Sc 4:

w, R therein₂、R₃、R₅And R₆Have the same meaning as defined in the above reaction scheme Sc 1.

The compounds of formula (VIII) are known and can be used in the form of the cis isomer maleonitrile or, preferably, the trans isomer fumaronitrile. Mixtures of the two isomers may also be used. Arylhydrazines of the formula (VII) are known or can be prepared by known methods.

W, R of preferred compounds of formula (III)₂、R₃、R₅And R₆Preferably the same as described above for the compound of formula (I). Optimization ofThe compound of formula (III) is selected to be 2- (2, 6-dichloro-4-trifluoromethylphenyl) butanedinitrile.

The above reaction to form the compound of formula (III) may be carried out in a variety of solvents, preferably polar solvents such as alcohols. Polar aprotic solvents such as N-methylpyrrolidone, N-dimethylformamide, or dimethylsulfoxide are particularly preferred. Another preferred aspect is to heat the mixture of compounds of formulae (VII) and (VIII) in the absence of a solvent to effect the reaction.

Catalysts such as tetra-alkyl ammonium salts such as N-benzyltrimethyl ammonium hydroxide, or alanine may also be used in the reaction.

The reaction temperature is usually about 20 to 150 ℃ and preferably about 80 to 100 ℃.

The reaction may be carried out in a molar ratio of compound of formula (VIII) to compound of formula (VII) of about 1: 10 to about 10: 1, preferably about 1: 1 to about 5: 1, particularly preferably about 1.1: 1.

The compounds of formulae (II) and (III) described above are novel and thus form a further feature of the present invention.

The following non-limiting examples illustrate the invention. And recording an NMR spectrum by using deuterated chloroform as a solvent. Hplc refers to high performance liquid chromatography, m.p. refers to melting point.

Example 1

Preparation of 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) pyrazole (reaction scheme Sc1)

Ammonia (20 μ l of 8% aqueous ammonia) was added to a mixture of 2- (2, 6-dichloro-4-trifluoromethylphenylhydrazono) succinonitrile (0.077 g) with ethanol (1 ml) and water (0.2 ml) at 0 ℃ and after 10 minutes the mixture was extracted (dichloromethane) and evaporated to give the title compound (0.076 g, 97% yield) in 98% purity (from Hplc).

Example 2

Preparation of 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) pyrazole (reaction scheme Sc1)

2- (2, 6-dichloro-4-trifluoromethylphenylhydrazono) succinonitrile (1.0 g) was stirred with sodium bicarbonate (40 ml of saturated aqueous solution) and dichloromethane (915 ml) at 20 ℃ and pH 9 for 3 hours. Sodium carbonate solution was added until pH 11 and stirring was continued overnight. A small amount of sodium hydroxide solution was added to bring the pH to 12, and after 3 hours a small amount of Aliquat336 (trade mark, trioctylmethylammonium chloride) was added and the reaction was complete after 2 hours. The dichloromethane extract was washed (water and brine), dried (sodium sulfate) and evaporated to give the title compound.

Example 3

Preparation of 2- (2, 6-dichloro-4-trifluoromethylphenylhydrazono) succinonitrile (scheme Sc2)

A mixture of 2- (2, 6-dichloro-4-trifluoromethylphenylhydrazino) succinonitrile (0.323 g) and copper dichloride (0.175 g) was heated in chlorobenzene at 60 ℃ for 6 hours, after filtration and evaporation, to give the title compound and 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) pyrazole in a ratio of 7: 1, which was eluted with dichloromethane by silica gel column chromatography to give the pure title compound as a mixture of cis and trans isomers, NMR (trans isomer) 3.6(s, 2H), 7.57(s, 2H), 8.82(s, 1H, D.sub.₂O exchange), NMR (cis isomer) 3.56(s, 2H), 7.59(s, 2H), 8.27(s, 1H, D may be used₂O exchange).

Example 4

Preparation of 2- (2, 6-dichloro-4-trifluoromethylphenylhydrazono) succinonitrile (scheme Sc3)

Sodium nitrite (3.9 g) was added to stirred concentrated sulfuric acid (12.8 ml) and heated at 80 ℃ until dissolved. Acetic acid (25 ml) was added at 30 ℃.2, 6-dichloro-4-trifluoromethylphenylaniline (10.0 g) and acetic acid (25 ml) were added to the mixture at 20 ℃ for 10 minutes or longerThe temperature is maintained below 25 ℃. The mixture was heated at 55 ℃ for 50 minutes, sodium nitrite (0.65 g) and acetic acid (10 ml) were added, after 20 minutes heating to 70 ℃ was carried out and sulfuric acid (2.8 ml) was added. After 20 minutes, the cooled mixture was added to a mixture of the potassium salt of 2-hydroxymethylbutanedinitrile (7.6 g) and sodium acetate (35.6 g) in water and acetic acid (70 ml) at 10 ℃. After warming to 20 ℃ over 1 hour, dichloromethane was added and ammonium hydroxide solution (210 ml) was added to bring the pH to 8. The organic phase was separated, washed (water and brine), dried (sodium sulfate) and evaporated to give the subject red-brown solid compound (18.1 g). Recrystallization from hexane/tert-butyl methyl ether gave the title pure compound (6.85 g), m.p. 80-82 deg.C, NMR3.6(s, 2H), 7.66(s, 2H), 9.03(s, 1H, available as D₂O exchange).

Example 5

Preparation of 2- (2, 6-dichloro-4-trifluoromethylphenylhydrazino) succinonitrile (scheme Sc4)

A mixture of 2, 6-dichloro-4-trifluoromethylphenylhydrazine (1.0 g) and fumaronitrile (1.0 g) in dimethylsulfoxide (10 ml) was heated at 100 ℃ for 7 hours. The cooled mixture was diluted with water and extracted (ether), evaporated and crystallized from dichloromethane/hexane to give the title compound (0.828 g, 63%), m.p. 101-.

Example 6

Preparation of 2- (phenylhydrazino) succinonitrile (scheme Sc4)

A mixture of phenylhydrazine (4.29 g) and fumaronitrile (3.1 g) in which phenylhydrazine was used as the solvent was heated at 75-80 ℃ for 20 h, purified by flash silica gel chromatography and crystallized from dichloromethane/hexane to give the title compound (3.29 g, 45%) m.p. 97-98 ℃.

While the invention has been described in terms of various preferred embodiments, those skilled in the art will recognize that various changes, substitutions, omissions, and alterations can be made without departing from the spirit of the invention. Accordingly, the scope of the invention is to be defined only by the following claims, including equivalents thereof.

Claims (1)

1. A process for the preparation of a compound of formula (III),

wherein W is nitrogen or-CR₄；

R₂、R₄、R₅And R₆Independently selected from hydrogen, halogen, C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Alkoxy radical, C_1-6Haloalkoxy, R₇S(O)_n-, nitro, cyano and-SF₅；

R₃Is hydrogen, halogen, C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Alkoxy radical, C_1-6Haloalkoxy, R₇S(O)_n-, nitro, cyano, -SF₅Or 1-5 selected from halogen and C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Alkoxy radical, C_1-6Haloalkoxy, R₇S(O)_n-, nitro, cyano and-SF₅Phenyl substituted with the groups of (a), which groups may be the same or different;

R₇is C_1-6Alkyl or C_1-6A haloalkyl group;

n is 0, 1 or 2;

the process comprises reacting an arylhydrazine having the formula (VII):

with a compound of formula (VIII):

CH (CN) ═ CH (CN) (VIII), W in the formula (VII) and the radical R₂、R₃、R₅And R₆Is as defined in formula (III).