1-(chloromethyl)-2-methyl-3-phenylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 0.62 g (0.011 mole) of potassium hydroxide in 3.65 ml distilled water was added, with stirring, 1.8 g (0.0074 mole) of cis-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylic acid and 14.6 ml of heptane. The reaction mixture was heated at reflux temperature, and the water was collected in a Dean-Stark trap. The anhydrous reaction mixture was then cooled, and 1.5 g (0.0069 mole) of 3-chloromethyl-2-methyl-[1,1'-biphenyl] and 14.6 ml of acetonitrile were added. The reaction mixture was stirred and heated at reflux temperature for 16 hours, then cooled and diluted with water. Diethyl ether was added and the two phases were separated. The aqueous phase was washed with heptane, then with diethyl ether. The organic phase and washings were combined, dried with anhydrous sodium sulfate and filtered. The solvents were removed from the filtrate under reduced pressure to give a yellow oil which was dissolved in methylene chloride and subjected to preparative liquid chromatography. A mixture of hexane and methylene chloride (2:1) was used as eluant. Appropriate fractions, as determined by thin layer and gas liquid phase chromatography, were combined to give 1.6 g of [2-methyl(1,1'-biphenyl)-3-yl]methyl cis-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate as a clear, colorless oil. was added The reaction mixture was heated at reflux temperature the water was collected in a Dean-Stark trap The anhydrous reaction mixture was then cooled The reaction mixture was stirred heated at reflux temperature for 16 hours cooled the two phases were separated The aqueous phase was washed with heptane dried with anhydrous sodium sulfate filtered The solvents were removed from the filtrate under reduced pressure to give a yellow oil which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 0.62 g (0.011 mole) of potassium hydroxide in 3.65 ml distilled water was added, with stirring, 1.8 g (0.0074 mole) of cis-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylic acid and 14.6 ml of heptane. The reaction mixture was heated at reflux temperature, and the water was collected in a Dean-Stark trap. The anhydrous reaction mixture was then cooled, and 1.5 g (0.0069 mole) of 3-chloromethyl-2-methyl-[1,1'-biphenyl] and 14.6 ml of acetonitrile were added. The reaction mixture was stirred and heated at reflux temperature for 16 hours, then cooled and diluted with water. Diethyl ether was added and the two phases were separated. The aqueous phase was washed with heptane, then with diethyl ether. The organic phase and washings were combined, dried with anhydrous sodium sulfate and filtered. The solvents were removed from the filtrate under reduced pressure to give a yellow oil which was dissolved in methylene chloride and subjected to preparative liquid chromatography. A mixture of hexane and methylene chloride (2:1) was used as eluant. Appropriate fractions, as determined by thin layer and gas liquid phase chromatography, were combined to give 1.6 g of [2-methyl(1,1'-biphenyl)-3-yl]methyl cis-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate as a clear, colorless oil. was added The reaction mixture was heated at reflux temperature the water was collected in a Dean-Stark trap The anhydrous reaction mixture was then cooled The reaction mixture was stirred heated at reflux temperature for 16 hours cooled the two phases were separated The aqueous phase was washed with heptane dried with anhydrous sodium sulfate filtered The solvents were removed from the filtrate under reduced pressure to give a yellow oil which

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a dry nitrogen atmosphere, 0.5 g (0.0022 mole) of N,N,2-trimethyl-[1,1'-biphenyl]-3-methanamine was dissolved in 5.5 ml of dry toluene with stirring and the solution was heated to 80° C. A solution of 0.36 g (0.0033 mole) of ethyl chloroformate in 1.1 ml of dry toluene was added dropwise during 5 minutes. The reaction mixture was stirred for 3.3 hours at 80° C., then cooled to room temperature and filtered. The solvent was removed from the filtrate under reduced pressure to give 0.5 g (100% yield) of 3-chloromethyl-2-methyl-[1,1'-biphenyl] as a light orange oil. The reaction mixture was stirred for 3.3 hours at 80° C. cooled to room temperature filtered The solvent was removed from the filtrate under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a dry nitrogen atmosphere, 0.5 g (0.0022 mole) of N,N,2-trimethyl-[1,1'-biphenyl]-3-methanamine was dissolved in 5.5 ml of dry toluene with stirring and the solution was heated to 80° C. A solution of 0.36 g (0.0033 mole) of ethyl chloroformate in 1.1 ml of dry toluene was added dropwise during 5 minutes. The reaction mixture was stirred for 3.3 hours at 80° C., then cooled to room temperature and filtered. The solvent was removed from the filtrate under reduced pressure to give 0.5 g (100% yield) of 3-chloromethyl-2-methyl-[1,1'-biphenyl] as a light orange oil. The reaction mixture was stirred for 3.3 hours at 80° C. cooled to room temperature filtered The solvent was removed from the filtrate under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a dry argon atmosphere a solution of 1.0 g (0.0044 mole) of (E)-(4-difluoromethoxyphenyl)(cyclopropyl)methanone oxime in 50 ml of dry tetrahydrofuran was added to a stirred solution of 0.95 g (0.0044 mole) of 3-chloromethyl-2-methyl [1,1'-biphenyl], 0.29 g (0.0044 mole) of powdered potassium hydroxide, and 0.14 g (0.00044 mole) of tetrabutylammonium bromide in 45 ml of dry tetrahydrofuran. The reaction mixture was stirred at room temperature for approximately 18 hours then evaporated under reduced pressure to give a liquid. The liquid was diluted with methylene chloride, and the mixture washed with water. The aqueous wash was extracted with methylene chloride. The organic phases were combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was evaporated under reduced pressure to give an oil. The oil was subjected to column chromatography on silica gel, eluting with toluene to give 1.73 g of (E)-(4-difluoromethoxyphenyl)(cyclopropyl)methanone O-[(2-methyl[1,1'-biphenyl]-3-yl)methyl]oxime as an oil. then evaporated under reduced pressure to give a liquid the mixture washed with water The aqueous wash was extracted with methylene chloride dried over anhydrous magnesium sulfate filtered The filtrate was evaporated under reduced pressure to give an oil eluting with toluene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner similar to Example 2, the reaction of 0.75 g (0.0034 mole) of (E)-(4-t-butylphenyl)(cyclopropyl)methanone oxime with 0.2 g (0.008 mole) of sodium hydride and 0.74 g (0.0034 mole) of 3-chloromethyl-2-methyl[1,1'-biphenyl] in 25 ml of a 20% solution of N,N-dimethylformamide in toluene produced (E)-(4-t-butylphenyl)(cyclopropyl)methanone O-[(2-methyl[1,1'-biphenyl]-3-yl)methyl]oxime as an oil.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner similar to General Procedure F of European Patent Publication No. 4,754, published Oct. 17, 1979, 1.96 g (0.01 mole) of (E)-(4-chlorophenyl)(cyclopropyl)methanone oxime was treated with 0.23 g (0.01 mole) of sodium ethoxide in 10 ml of ethanol, and the mixture was evaporated to dryness. The residue was dissolved in a minimum amount of solvent consisting of N,N-dimethylformamide and t-butanol (9:1 ratio) and treated with 2.16 g (0.01 mole) of 3-chloromethyl-2-methyl[1,1'-biphenyl] to yield, after purification by column chromatography, 0.83 g of (E)-(4-chlorophenyl)(cyclopropyl)methanone O-[(2-methyl[1,1'-biphenyl]-3-yl)methyl]oxime as an oil. the mixture was evaporated to dryness The residue was dissolved in a minimum amount of solvent to yield after purification by column chromatography, 0.83 g of (E)-(4-chlorophenyl)(cyclopropyl)methanone O-[(2-methyl[1,1'-biphenyl]-3-yl)methyl]oxime as an oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An additional method for preparing the intermediate 3-chloromethyl-2-methyl[1,1'-biphenyl] involves a Sommelet-Hauser rearrangement of N,N,N-trimethyl[1,1'-biphenyl]-2-methanaminium iodide to give 3-dimethylaminomethyl-2-methyl-[1,1'-biphenyl], which is then converted into the 3-chloromethyl derivative by treatment with ethyl chloroformate. The N,N,N-trimethyl-[1,1'-biphenyl]-2-methanaminium iodide starting material may be prepared in four steps from 2-biphenylcarboxylic acid via the acid chloride, dimethyl carboxamide, and dimethylaminomethyl derivatives.