MXPA01007842A - New process for preparing pesticidal intermediates - Google Patents

Abstract

The invention relates to a process for the preparation of a compound of formula (I):wherein W, R1, R2 and R3 are as defined in the description.

Description

NEW PROCESS FOR THE PREPARATION OF PESTICIDE INTERMEDIARY COMPOUNDS FIELD OF THE INVENTION This invention relates to novel processes for the preparation of pesticides or pesticide intermediates (particularly 5-amino-1-aryl-3-cyanopyrazole derivatives).

BACKGROUND OF THE INVENTION Publications of European Patent Numbers 0295117 and 0234119 describe the preparation of phenylpyrazole compounds active as pesticides and intermediates of 5-amino-1-aryl-3-cyanopyrazole, used in their synthesis. Various methods for the preparation of those compounds are known. The present invention seeks to provide improved or more economical methods for the preparation of pesticides and intermediary compounds useful in their preparation.

REF .: 131703 DESCRIPTION OF THE INVENTION A first object of the present invention is to provide a convenient process for the preparation of active phenylpyrazole compounds such as pesticides or pesticidal intermediates of 5-amino-1-aryl-3-cyanopyrazole, which are obtained in high yield and high purity. A second object of the present invention is to provide a convenient process for the preparation of active phenylpyrazole compounds such as pesticides or pesticidal intermediates of 5-amino-1-aryl-3-cyanopyrazole, which benefits without the need of the diazotization step, and that therefore avoid problems such as the dangers that are known to occur in such reactions. A third object of the present invention is to provide a process for the preparation of active phenylpyrazole compounds such as pesticides or 5-amino-1-aryl-3-cyanopyrazole pesticide intermediates, which is simple to carry out and which uses starting less expensive than in the known methods. A still further object of the present invention is to provide novel intermediate compounds in the manufacture of active compounds as pesticides. These and other objects of the invention will become apparent from the following description, and are achieved in whole or in part by the present invention. Accordingly, the present invention provides a process (A) for the preparation of a compound of formula (I): OR) wherein W represents nitrogen or -CR; R1 represents halogen, haloalkyl (preferably trifluoromethyl), haloalkoxy (preferably trifluoromethoxy), R5S (0) n-, or -SF5; R < represents hydrogen or halogen (for example chlorine or bromine); R3 represents hydrogen or R6S (0) ra-; R4 represents halogen (for example chlorine or bromine); R5 and R6 represent alkyl or haloalkyl; and and n represent 0, 1 or 2, process comprising the reaction of a compound of formula (II): wherein R1, R, R3 and W are as defined hereinabove, R7 represents a leaving group (preferably chlorine or bromine) and R8 represents chlorine or bromine (preferably R7 and R8 each represent chlorine), with a cyanide salt . The reaction is carried out via dicyano intermediates of formula (III). wherein R1, R2, R3 and W are as defined hereinabove, which generally become cyclic under the conditions of the reaction, thereby providing a simple and convenient process. Optionally the intermediates of the formula (III) can be made cyclic in the presence of a base according to the known methods. The compounds of formula (II) and (III) can exist as a mixture of syn and anti isomers. Unless otherwise specified in the present specification, "alkyl" means straight or racemic alkyl having one to six carbon atoms (preferably one to three). Unless otherwise specified, "haloalkyl" and "haloalkoxy" are straight or branched chain alkyl or alkoxy each having one to six carbon atoms (preferably one to three) substituted by one or more halogen atoms selected of fluorine, chlorine or bromine. The cyanide salts suitable for the above reaction, to form compounds of formula (I) include alkali metal cyanides, such as potassium, sodium or lithium cyanide, alkaline earth metal cyanides or ammonium cyanide. Potassium cyanide or sodium cyanide are preferred. The reaction is generally carried out in a solvent. Suitable solvents for use include nitriles such as acetonitrile, amides such as N-methylpyrrolidinone, sulfoxides such as dimethisulfoxide, ethers such as tetrahydrofuran or alcohols such as ethanol. Water can be used as a cosolvent. The reaction temperature is generally from about -20 ° C to the reflux temperature of the solvent, and preferably from about 0 ° C to about 20 ° C. Generally, 2 to 5 molar equivalents of cyanide are used and preferably from about 2 to about 3 equivalents. In the formulas (I), (II) and (III) and in the formulas represented hereinafter, the preferred values of the symbols are the following: R1 represents haloalkyl (preferably trifluoromethyl), haloalkoxy (preferably trifluoromethoxy) or - SF5, W represents -CR, R2 and R4 represent halogen (preferably chlorine); RJ represents a hydrogen atom, RS (0) m-; wherein R c represents optionally halogenated methyl ethyl (preferably trifluoromethyl); and R7 and R8 represent chloro. Particularly preferred compounds of formula (I) include: 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole; 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole; 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole; and 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-ethylsulfinylpyrazole. The process is particularly useful for the preparation of compounds wherein R3 represents hydrogen, and most preferably for 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole. In the formulas (II) and (III) and in the formulas represented above, the most preferred values of the symbols are the following: R1 represents trifluoromethyl; W represents -CR; R2, R4, R7 and R8 represent chlorine; and R3 represents hydrogen. According to a further feature of the present invention, the above process (A) can be combined with additional process steps (B) and (C) as defined hereinafter. Step (B) of the process comprises the reaction of a compound of formula (IV): (IV) wherein R1, R2, R3, R7 and W are as defined hereinabove, with a chlorinating or brominating agent, to give a compound of formula (II) wherein R1, R2, R3, R7, R8, and W are as defined hereinabove. Suitable chlorinating agents are thionyl chloride, phosphoryl chloride, phosphorus trichloride, phosphorus pentachloride, or a mixture of triphenylphosphine and carbon tetrachloride. Broming agents that can be used include thionyl bromide, phosphoryl bromide or a mixture of triphenylphosphine and carbon tetrabromide. Preferably the process is carried out using a chlorinating agent. A preferred chlorinating agent is phosphoryl chloride. Solvents that can be used include ethers, aromatic hydrocarbons such as toluene, aromatic halogenated hydrocarbons such as chlorobenzene, or halogenated hydrocarbons such as dichloroethane. The reaction temperature is generally from 0 ° C to 120 ° C, preferably from 70 ° C to 90 ° C. Step (C) of the process comprises the reaction of an arylhydrazine compound of formula (V): IV) wherein R1, R2, and W are as defined hereinabove; with a compound of formula (VI): R3R7CHCOR9 (VI) wherein R3 and R7 are as defined above, and R9 represents a leaving group preferably a chlorine or bromine atom (generally both R7 and R9 represent a chlorine atom); to give a compound of formula (IV) as defined above. The reaction for obtaining the compounds of formula (IV) can generally be carried out in a solvent such as halogenated hydrocarbons for example dichloromethane, ethers for example, tetrahydrofuran or dioxane, or N, N-dialkylamides for example N, -dimethylformamide, and a temperature of -20 ° C to 50 ° C, preferably from 0 ° C to 20 ° C. The above combination of step (A) of the process, preceded by step (B) of the process, preceded by step (C) of the process, represents in certain aspects an improvement over the prior art. The above compounds of the formulas (II) and (IV) are novel and therefore constitute a further feature of the present invention. Where R3 is different from hydrogen, the compounds of the formula (III) are novel. The compounds of the formula (VI) are known. Intermediate 5-amino-1-aryl-3-cyanopyrazole compounds of formula (I) obtained by process (A) of the invention, wherein R 3 represents hydrogen, can be used in the preparation of phenylpyrazole derivatives active as pesticides of formula (VII) according to the following reaction scheme: wherein the symbols used above are as previously defined herein. The following non-limiting examples illustrate the invention. NMR spectra are recorded, using deuterochloroform as solvent.

Example 1 Preparation of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-cyanopyrazole A solution of N '- (2,6-dichloro-4-trifluoromethylphenyl) -chloroacetohydrazonoyl chloride (1.1 grams) in ethanol (6 milliliters) is added over 25 minutes to a stirring solution of sodium cyanide (0.475 grams) in ethanol (6 milliliters) and water (6 milliliters). The temperature rises to 32 ° C. After 15 minutes an addition of ethanol (4.5 milliliters) and water (3 milliliters) is made and stirred for 15 minutes at 20 ° C. Another addition of water is made (3 milliliters) and the mixture is filtered. The residue is dissolved in ethanol, concentrated and purified by chromatography on silica gel eluting with dichloromethane to give the title compound (0.55 grams), obtained with a yield of 53%.

Example 2 Preparation of N '- (2,6-dichloro-4-trifluoromethylphenyl) -chloroacetohydrazonoyl chloride Phosphoryl chloride (500 microliters, 1.7 equivalents) is added in one portion to a stirred solution of N '- (2,6-dichloro-4-trifluoromethylphenyl) -chloroacetohydrazide (1.0 grams, 3.11 mmol) in toluene (20 milliliters) and it is heated at 70 ° C under an argon atmosphere for 20 hours. The cold mixture is evaporated and the residue is extracted with cyclohexane. The extracts are combined and evaporated to give the title compound (0.971 grams) as an orange oil, NMR 4.4 (s, 2H), 7.55 (s, 2H), 7.7 (s, 1H). The yield is 90%.

Example 3 Preparation of N '- (2,6-dichloro-4-tri luoromethylphenyl) -chloroacetohydrazide A solution of chloroacetyl chloride (2.3 milliliters, 1.08 equivalents) in anhydrous dichloromethane (30 milliliters) is added over 30 minutes to a stirred solution of 2,6-diclors-4-trifluoromethylphenylhydrazine (6.1 grams, 24.89 mmol) in anhydrous dichloromethane. (60 milliliters) maintaining the temperature between 5 ° C and 12 ° C under an argon atmosphere. The mixture is then stirred for 12 hours at 20 ° C. A solution of sodium hydroxide (11.2 milliliters to 10%) and dichloromethane are added, and the organic phase is washed (water), dried (magnesium sulfate) and evaporated to give the title compound (7.25 grams) as a solid white, NMR 4.05 (s, 2H), 6.77 (s, 1H), 7.47 (s, 2H), 8.6 (s, 1H). The yield is 91%. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (10)

CLAIMS Having described the invention as above, the property contained in the following claims is claimed as property:

1 . A process for the preparation of a compound of formula (I):

(I) wherein W represents nitrogen or -CR; R * represents halogen, haloalkyl, haloalkoxy, RS (0) n-, or -SF5; R 2 represents hydrogen or halogen R 3 represents hydrogen or R 6 S (0) m-; R4 represents halogen; R5 and R6 represent alguyl or haloalguyl; and m and n represent 0, 1 or 2; process comprising the reaction of a compound of formula (II): wherein R1, R2, R3, and W are as defined hereinabove, R7 represents a leaving group and R8 represents chloro or bromo, with a cyanide salt. 2. A process according to claim 1, characterized in that the cyanide salt is an alkali metal cyanide, an alkaline earth metal cyanide or ammonium cyanide.

3. A process according to claim 1 or 2, characterized in that it is carried out in a solvent selected from nitriles, amides, sulfoxides, ethers or alcohols, optionally in the presence of water.

4. A process according to claims 1 to 3, characterized in that 2 to 5 molar equivalents of cyanide are used.

5. A process according to any of claims 1 to 4, characterized in that the compound of formula (II) is prepared by a process comprising the reaction of a compound of formula (IV): (IV) wherein R1, R2, R3, R7 and W are as defined in claim 1, with a chlorinating or brominating agent; and the compound of formula (IV) is prepared by a process comprising the reaction of a compound of formula (V): (V) wherein R1, R2 and W are as defined in claim 1, with a compound of formula (VI): R3R7CHCOR9 (VI) wherein R3 and R7 are as defined in claim 1, and R9 represents a leaving group.

6. A process according to claim 5, characterized in that a chlorinating agent is used for the preparation of the compound of formula (II) from the compound of formula (IV), and is selected from thionyl chloride, phosphoryl chloride , phosphorus trichloride, phosphorus pentachloride and a mixture of triphenylphosphine and carbon tetrachloride.

7. A process according to any of the preceding claims, characterized in that: R1 represents trifluoromethyl, trifluoromethoxy or -SF5; W represents -CR4; R2 and R4 represent chlorine or bromine; R3 represents a hydrogen atom, or R6S (0) m-; wherein R6 optionally represents halogenated methyl or ethyl; and R7 and R8 represent chloro.

8. A process according to any of the preceding claims, characterized in that: R1 represents trifluoromethyl; W represents -CR4; R2, R4, R7 and R8 represent chlorine; and R3 represents hydrogen.

9. A compound of formula (II) or (IV) characterized in that R1, R2, R3, R7, R8 and W are as defined in claim 1 or claim 5.

10. A compound of formula (III): ÍIII) characterized in that R1, R2, R3 and W are as defined in claim 1, with the exclusion of compounds wherein R3 represents hydrogen.