Process for preparing o-nitrobenzonitriles

Abstract: The invention relates to a process for the preparation of compounds of formula (I): wherein: R 1 represents C 1-4 haloalkyl, fluorine, chlorine or bromine; and R 2 represents hydrogen or C 1-4 alkoxy; which process comprises the reaction of the corresponding orthonitrofluorobenzene of formula (II): wherein R 1 and R 2 are as hereinbefore defined, with an alkali metal cyanide, in a non aqueous solvent optionally in the presence of a catalyst.

Description: This invention relates to novel processes for preparing intermediates (particularly 4-cyano-3-nitrobenzotrifluoride) useful in the preparation of pesticides. Pesticidal 4-benzoylisoxazoles, particularly 5-cyclopropylisoxazole herbicides and intermediate compounds in their synthesis, are described in the literature, for example in European Patent Publication Nos. 0418175, 0527036, 0560482, 0609798 and 0682659. Various methods for preparing these compounds are known, for example in European Patent Publication Nos. 0608713 and 0613719 and Japanese Patent Publication Nos. 3090057 and 56079662, which describe processes for preparing aromatic cyanides by reaction of an aromatic halide with an alkali cyanide. The present invention seeks to provide improved methods for the preparation of pesticides and the intermediate compounds useful in preparing them. It is therefore an object of the present invention to provide a novel process for the preparation of ortho-nitrobenzonitrile compounds. It is a further object of the present invention to provide a process for the preparation of ortho-nitrobenzonitrile compounds which proceeds with high selectivity. The present invention allows these objects to be met in whole or in part. Summary of the Invention The present invention accordingly provides a process for the preparation of an ortho-nitrobenzonitrile compound of formula (I): wherein: R 1 represents C 1-4 haloalkyl (preferably trifluoromethyl), fluorine, chlorine or bromine; and R 2 represents hydrogen or C 1-4 alkoxy; which process comprises the reaction of the corresponding ortho-nitrofluorobenzene of formula (II): wherein R 1 and R 2 are as hereinbefore defined, with an alkali metal cyanide, in a non aqueous solvent optionally in the presence of a catalyst. Certain compounds of formula (I) are known and a number of processes for their preparation and conversion into herbicidal 4-benzoylisoxazole derivatives have been described in the European Patent Applications cited above. Compounds of formula (II) are known or may be prepared by known methods. In formulae (I) and (II) and in the formulae depicted hereinafter, preferred values of the symbols are as follows:- Preferably R 1 represents trifluoromethyl, fluorine or bromine; and R 2 represents hydrogen or methoxy. In a particularly preferred embodiment of the invention R 1 represents trifluoromethyl and R 2 represents hydrogen. Detailed Description of the Invention The above preparation of compounds of formula (I) from compounds of formula (II) is performed with an alkali metal cyanide (for example sodium cyanide or potassium cyanide). Sodium cyanide is preferred. The amount of cyanide used is generally from 1-2 molar equivalents, preferably from 1-1.1 molar equivalents. A number of non-aqueous solvents are suitable, for example nitriles such as acetonitrile or benzonitrile; ethers such as tetrahydrofuran or diglyme (diethylene glycol dimethyl ether); amides such as N,N-dimethylformamide or N-methylpyrrolidone; ketones such as methyl isobutyl ketone; esters such as methyl benzoate or n-butyl acetate; dimethylsulphoxide or sulpholane. Preferably the solvent is chosen from benzonitrile, acetonitrile, tetrahydrofuran or N,N-dimethylformamide. The reaction is generally conducted in a solvent with less than about 1% by volume water content, preferably less than about 0.5%, even more preferably less than about 0.1%, typically from about 0.005 to about 0.05%. It will however be understood that in certain cases slightly more or less water may be tolerated, depending on the nature of the solvents used and the temperature of the reaction, the compound of formula (I) to be prepared and other reaction conditions. Preferably a catalyst is used, which may be selected from ammonium salts (such as tetraalkylammonium or trialkylbenzylammonium chlorides, bromides or hydrogen sulphate salts, in which the alkyl groups are straight- or branched-chain containing from one to six carbon atoms, such as tetramethylammonium bromide); or preferably guanidinium salts (such as hexabutylguanidinium chloride or hexamethylguanidinium chloride). The amount of catalyst when employed is generally from 0.01 to 0.3 molar equivalent, preferably from 0.05-0.25 molar equivalent. Generally the reaction temperature is from 20°C to the boiling point of the solvent, preferably from 30°C to 180°C, and more preferably from 60°C to 100°C. The compounds of formula (I) obtained by the process of the present invention may be used in the preparation of herbicidally active 4-benzoylisoxazole derivatives, for example according to the following reaction scheme:- The 4-benzoylisoxazoles of formula (III) are described in for example European Patent Publication Nos. 0418175, 0527036 and 0560482. The following non-limiting examples illustrate the invention. Example 1 Preparation of 4-cyano-3-nitrobenzotrifluoride from 4-fluoro-3-nitrobenzotrifluoride using an alkali metal cyanide A mixture of 4-fluoro-3-nitrobenzotrifluoride (1mmol) and sodium cyanide or potassium cyanide (1mmol), and acetonitrile or benzonitrile (1ml/mmol) were mixed at 20°C and heated for 6 hours at 80°C to give the title product. The results are shown in Table 1, from which it can be seen that the use of sodium cyanide gives good selectivity. Cyanide Solvent Conversion (%) Yield (%) Selectivity (%) NaCN CH3CN 79 45 57 KCN CH3CN 76 38 49 NaCN PhCN 45 36 80 KCN PhCN 35 26 74 Example 2 Preparation of 4-cyano-3-nitrobenzotrifluoride from 4-fluoro-3-nitrobenzotrifluoride using sodium cyanide: effect of solvent, temperature and catalyst: A mixture of 4-fluoro-3-nitrobenzotrifluoride (1mmol) and sodium cyanide (1mmol) and N,N-dimethylformamide, acetonitrile, tetrahydrofuran or benzonitrile (1ml/mmol) were mixed at 20°C and heated for 6 hours to give the title product. The results are shown in Table 2, from which it may be observed that benzonitrile (PhCN) gave the highest selectivity. Solvent Temp (°C) Conversion (%) Yield (%) Selectivity (%) DMF 80 95 35 37 DMF 40 83 38 46 DMF 25-30 80 31 39 CH3CN 80 79 45 57 THF 80 69 39 56 PhCN 80 45 36 80 The above experimental procedure was repeated at 80°C but in the presence of a catalyst (0.2 equivalent) and acetonitrile, tetrahydrofuran or benzonitrile (1ml/mmol). The catalysts used were hexabutylguanidinium chloride or tetrabutylammonium bromide. The results (shown in Table 3) indicate that the use of hexabutylguanidinium chloride as catalyst gave very good selectivity especially in tetrahydrofuran or benzonitrile. Catalyst Solvent Time Conversion (%) Yield (%) Selectivity (%) CH3CN 13h 47 33 70 THF 6h 45 40 90 PhCN 6h 42 40 95 CH3CN 13h 88 47 54

Claims: A process for the preparation of a compound of formula (I): wherein: R 1 represents C 1-4 haloalkyl, fluorine, chlorine or bromine; and R 2 represents hydrogen or C 1-4 alkoxy; which process comprises the reaction of the corresponding ortho-nitrofluorobenzene of formula (II): wherein R 1 and R 2 are as hereinbefore defined, with an alkali metal cyanide, in a non aqueous solvent which may have a water content of less than 1% by volume in the presence of a catalyst wherein the catalyst is selected from ammonium salts and guanidinium salts. A process according to claim 1 in which the alkali metal cyanide is sodium cyanide. A process according to claim 1 or 2 in which 1-2 molar equivalents of cyanide is used. A process according to any one of the preceding claims in which the solvent is benzonitrile, acetonitrile, tetrahydrofuran or N,N-dimethylformamide. A process according to any one of the preceding claims in which R 1 represents trifluoromethyl, fluorine or bromine; and R 2 represents hydrogen or methoxy. A process according to any one of the preceding claims in which R 1 represents trifluoromethyl; and R 2 represents hydrogen.

Inventors: VIAUVY AGNES, VIAUVY, AGNES, Viauvy, Agnès
Applicants: BAYER CROPSCIENCE SA, BAYER CROPSCIENCE S.A.
Application year: 1998
Main classification: C07C253
IPC codes: C07C205, C07C253, C07C255