Process for the manufacture of insecticidal, nematicidal and acaricidal 2-aryl-3-subst. -5-(trifluoromethyl)pyrrole compounds from N-(subst. benzyl)-2,2,2-trifluoroacetimidoyl chloride compounds

Abstract: There is provided a process for the manufacture of insecticidal, nematicidal and acaricidal 2-aryl-3-substituted-5-(trifluoromethyl)pyrrole compounds via the condensation of an N-(substituted benzyl)-2,2-2-trifluoroacetimidoyl chloride compound with an α-halo-α,β-unsaturated nitrile, ester or nitro compound.

Description: BACKGROUND OF THE INVENTION The present invention relates to a process of manufacturing certain 2-aryl-3-substituted 5-(trifluoromethyl)pyrroles. Although other processes to manufacture such pyrroles are known, previous processes have suffered from certain problems. For example, 2-Aryl-3-substituted-5-(trifluoromethyl) - pyrrole compounds useful as insecticides, nematicides and acaricides and the preparation thereof by the reaction of an azalactone with an α-halo-α,β-unsaturated nitrile, ester or nitro compound are known (US-A-5 030 735 and J. Org. Chem. 43, 4273-4276 (1978)) However, such previously known processes have required for example, lengthy preparations of amino acids or costly starting materials. An 1,3-dipolar addition to an ylide is known from Chem. Abs. 107 (1987), 217 202e. It is an object of the present invention to provide a new and industrially advantageous process for the manufacture of insecticidal, nematicidal and acaricidal 2-aryl-3-substituted-5-(trifluoromethyl)pyrrole compounds. SUMMARY OF THE INVENTION The present invention relates to an efficient process for the manufacture of insecticidal, nematicidal and acaricidal 2-aryl-3-substituted-5-(trifluoromethyl)pyrrole compounds of formula I wherein M and Q are each independently H, F, Cl, Br, CN, NO 2 , CF 3 . Surprisingly, it has been found that 2-aryl-3-substituted-5-(trifluoromethyl)pyrrole compounds of formula I may be prepared by a single step reaction between an N-(substituted)benzyl-2,2,2-trifluoroacetimidoyl chloride compound of formula II wherein M and Q are as described above and an α-halo-α,β-unsaturated nitrile, ester or nitro compound of formula III X is Cl or Br in the presence of a base and a solvent in accordance with claim 1. DETAILED DESCRIPTION OF THE INVENTION The process preferably comprises reacting a formula II N-(substituted) benzyl-2,2,2-trifluoroacetimidoyl chloride compound as described above with at least about one molar equivalent, preferably about one to four molar equivalents of a formula III α-halo-α,β-unsaturated nitrile, as described above and at least one molar equivalent, preferably one to four molar equivalents, of the base defined in claim 1 in the presence of the solvent defined in claim 1 preferably at a temperature range of 5°C to 100°C preferably 5°C to 70°C to form 2-aryl-3-substituted-5-(trifluoromethyl)pyrrole compounds of formula I. Alternatively, the formula I 2-aryl-3-substituted-5-(trifluoromethyl)pyrrole compounds may be prepared by forming the formula III α-halo-α,β-unsaturated nitrile in situ. This process comprises reacting a formula II N-(substituted benzyl)-2,2,2-trifluoroacetimidoyl chloride compound with at least one molar equivalent of an α,β-dihalo nitrile of formula IV wherein X is Cl or Br in the presence of at least about two molar equivalents of the base and the solvent in accordance with claim 1. The process preferably comprises reacting a formula II N-(substituted benzyl)-2,2,2-trifluoro-acetimidoyl chloride compound as described above with at least one molar equivalent, preferably about one to four molar equivalents, of a formula IV α,β-di-halo nitrile as described above and at least two molar equivalents, preferably two to five molar equivalents, of the base in the presence of the solvent preferably at a temperature range of 5°C to 100°C preferably 5°C to 70°C to form 2-aryl-3-substituted-5-(trifluoromethyl)pyrrole compounds of formula I. The formula I compound may be isolated by conventional techniques such as dilution of the reaction mixture with water and filtration or, alternatively, extraction with a suitable solvent. Suitable extraction solvents include water-immiscible solvents such as ether, ethyl acetate, toluene, methylene chloride. Preferred bases are sodium carbonate, potassium carbonate and triethylamine. Reaction solvents used in the present invention are carboxylic acid amides such as N,N-dimethylformamide and N-methylpyrrolidinone ; nitriles such as acetonitrile; ethers such as tetrahydrofuran and dioxane; and sulfoxides such as dimethyl sulfoxide. Preferred reaction solvents are N,N-dimethylformamide and acetonitrile. Certain starting compounds of formula III (α-halo-α,β-unsaturated nitrile compounds) are described in US-A-5,068,390. In order to facilitate a further understanding of the invention, the following examples are presented to illustrate more specific details thereof. EXAMPLE 1 Preparation of 2,2,2-Trifluoro-N-(p-chlorobenzyl)-acetimidoyl chloride A mixture N-(p-chlorobenzyl)-2,2,2-trifluoro-acetamide (100.0 g, 0.421 mol) and phosphorus pentachloride (87.7 g, 0.421 mol) is heated to 100°C, stirred for two hours and vacuum distilled to obtain the title product as a clear colorless liquid (66.3 g, bp 110°-112°C/7.5 mm Hg). Following the above procedure, but using the appropriately substituted N-benzyl-2,2,2-trifluoro-acetamide yields N-(o-chlorobenzyl)-2,2,2-trifluoro-acetimidoyl chloride, bp 78°-85°C/2.55 mm Hg and N-(3,4-dichlorobenzyl)-2,2,2-trifluoroacetimidoyl chloride, bp 121°-126°C/2.7 mm Hg. EXAMPLE 2 Preparation of 2-(p-Chlorophenyl)-5-(trifluoromethyl)-pyrrole-3-carbonitrile in the presence of triethylamine and N,N-dimethylformamide A solution of 2,2,2-trifluoro-N-(p-chloro-benzyl)acetimidoyl chloride (10.0 g, 0.039 mol) and 2-chloroacrylonitrile (4.1 g, 0.047 mol) in N,N-di-methylformamide (50 mL) is cooled to 5°C, treated with triethylamine (8.78 g, 0.086 mol) below 10°C until half of the triethylamine is added, warmed to room temperature, treated with the remaining triethylamine, stirred at 45°C for three hours and diluted with water. The aqueous mixture is filtered to obtain a solid which is dried under vacuum to give the title product as a brown solid (8.1 g). EXAMPLE 3 Preparation of 2-(p-Chloronhenyl)-5-(trifluoromethyl)-pyrrole-3-carbonitrile from 2,3-dichloropropionitrile A solution of 2,2,2-trifluoro-N-(p-chloro-benzyl)acetimidoyl chloride (10.0 g, 0.039 mol) and 2,3-dichloropropionitrile (5.81 g, 0.047 mol) in N,N-dimethylformamide is cooled to 5°C and treated with a solution of triethylamine (17.4 mL, 0.125 mol) in N,N-dimethylformamide. When the addition is half complete, the cooling bath is removed and the reaction mixture is treated with the remaining triethylamine solution, stirred for three hours and poured into water. The aqueous mixture is filtered to obtain a solid which is washed with water and dried under vacuum to give the title product as a pale brown solid (8.0 g). EXAMPLE 4 Preparation of 2-(p-chlorophenyl)-5-(trifluoromethyl)-pyrrole-3-carbonitrile in the presence of sodium carbonate and N,N-dimethylformamide A solution of 2,2,2-trifluoro-N-(p-chloro-benzyl)acetimidoyl chloride (30.0 g, 0.117 mol) and 2-chloroacrylonitrile (12.31 g, 0.141 mol) in N,N-dimethylformamide (150 mL) is treated portionwise with sodium carbonate (27.28 g, 0.257 mol) over one hour (slight exotherm), stirred at 55°C for two hours and diluted with water. The aqueous mixture is filtered to obtain the title product as a brown solid (25.7 g, mp 228°-229°C). EXAMPLE 5 Preparation of 2-(4-Chloro-3-nitrophenyl)-5-(trifluoromethyl)pvrrole-3-carbonitrile A mixture of N-(4-chloro-3-nitrobenzyl)-2,2,2-trifluoroacetamide (6.0 g, 0.0212 mol) and phosphorus pentachloride (8.9 g, 0.0427 mol) is heated to 100°C for three hours, concentrated in vacuo to remove excess phosphorus pentachloride and triturated with methylene chloride to obtain a solution of N-(4-chloro-3-nitrobenzyl)-2,2,2-trifluoroacetimidoyl chloride in methylene chloride. The methylene chloride solution is treated with 2-chloroacrylonitrile (2.5 mL, 0.0319 mol) and triethylamine (5.9 mL, 0.0422 mol), stirred overnight at room temperature, diluted with water and extracted with ethyl acetate. The combined organic extracts are washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo to obtain a residue. Chromatography of the residue using silica gel and a 4:1 hexanes/ethyl acetate solution gives the title product as a yellow solid (0.65 g, mp 258°-260°C). Following the above procedure, but using the appropriately substituted N-benzyl-2,2,2-trifluoro-acetamide yields 2-(p-nitrophenyl)-5-(trifluoromethyl)-pyrrole-3-carbonitrile, mp 258°-261°C and 2-(2-chloro5-nitrophenyl)-5-(trifluoromethyl)pyrrole-3-carboni-trile, mp 196°-201°C. EXAMPLE 6 Preparation of 2-(3,4-Dichlorophenyl)-5-(trifluoromethyl) pyrrole-3-carbonitrile A solution of N-(3,4-dichlorobenzyl)-2,2,2-trifluoroacetimidoyl chloride (20.0 g, 0.069 mol) and 2-chloroacrylonitrile (7.2 g, 0.082 mol) in N,N-di-methylformamide is cooled to 5°C and treated with a solution of triethylamine (22 mL, 0.16 mol) in N,N-di-methylformamide (38 mL). When the addition is half complete, the cooling bath is removed and the reaction mixture is treated with the remaining triethylamine solution, stirred for two hours and diluted with water. The aqueous mixture is filtered to obtain the title product as a tan solid (18.38 g, mp 230°-232°C). EXAMPLE 7 Preparation of 2-(o-Chlorophenyl)-5-(trifluoromethyl)-pyrrole-3-carbonitrile A solution of N-(o-chlorobenzyl)-2,2,2-tri-fluoroacetimidoyl chloride (10.0 g, 0.039 mol) and 2-chloroacrylonitrile (4.1 g, 0.047 mol) in N,N-di-methylformamide is cooled to 5°C and treated with a solution of triethylamine (12.0 mL, 0.086 mol) in N,N-dimethylformamide (10 mL). When the addition is one-quarter complete, the cooling bath is removed and the reaction mixture is treated with the remaining triethylamine solution, stirred for three hours, diluted with water and extracted with methylene chloride. The combined organic extracts are washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo to obtain an oil. Flash chromatography of the oil using silica gel and a 1:6 ethyl acetate/heptane solution gives an oil. Crystallization of the oil from heptane gives the title product as a solid (8.5 g, mp 151°-152.5°C).

Claims: A process for the preparation of a 2-aryl-3-cyano-5-(trifluoromethyl)pyrrole compound having the structural formula wherein M and Q are each independently H, F, Cl, Br, CN, NO 2 or CF 3 , which comprises reacting an N- (substituted benzyl) -2,2,2-trifluoroacetimidoyl chloride compound having the structural formula wherein M and Q are as described above either (a) with at least one molar equivalent of an α-halo-α,β-unsaturated nitrile compound having the structural formula wherein X is Cl or Br and at least one molar equivalent of a base selected from the group consisting of an alkali metal carbonate, a tri-(C 1 -C 4 )-alkylamine, an alkali metal hydroxide, an alkali metal acetate, 4-dimethylaminopyridine and pyridine in the presence of a solvent selected from the group consisting of a carboxylic acid amide, a nitrile, an ether and a sulfoxide in a temperature range of 5 °C to 100 °C to form the 2-aryl-3-cyano-5-(trifluoromethyl)-pyrrole compound, or (b) with at least one molar equivalent of an α,β-dihalo nitrile compound having the structural formula wherein X is Cl or Br and more than two molar equivalents of a base selected from the group consisting of an alkali metal carbonate, a tri-(C 1 -C 4 )-alkylamine, an alkali metal hydroxide, an alkali metal acetate, 4-dimethylaminopyridine and pyridine in the presence of a solvent selected from the group consisting of a carboxylic acid amide, a nitrile, an ether and a sulfoxide in a temperature range of 5 °C to 100 °C to form the 2-aryl-3-cyano-5-(trifluoromethyl)-pyrrole compound. The process according to claim 1 wherein the nitrile compound is present in the amount of 1 to 4 molar equivalents and wherein according to (a) the base is present in the amount of 1 to 4 molar equivalents, or according to (b) the base is present in the amount of 2 to 5 molar equivalents. The process according to claim 1 wherein the base is an alkali metal carbonate or a tri-(C 1 -C 4 )-alkylamine and the solvent is N,N-dimethylformamide, acetonitrile or tetrahydrofuran. The process according to claim 3 wherein the base is triethylamine, sodium carbonate or potassium carbonate and the solvent is N,N-dimethylformamide or acetonitrile. The process according to claim 1 wherein M and Q are each independently H, F, Cl, Br or CF 3 .

Inventors: KARMESWARAN VENKATARAMAN, KUHN DAVID GEORGE, KARMESWARAN, VENKATARAMAN, KUHN, DAVID GEORGE
Applicants: BASF AG, BASF AKTIENGESELLSCHAFT
Application year: 1992
Main classification: C07D207
IPC codes: A01N43, C07D207