2.4- Dichlorobenzyl chloride

The following were introduced into a 1 liter flask provided with a reflux condenser 206 g (1 mol) of p-(1,1,3,3-tetramethylbutyl)-phenol,147 g (0.75 mol) of 2,4-dichlorobenzyl chloride, 27 g (0.2 mol) of pure melted zinc chloride, and 750 ml of anhydrous chloroform. 

A suspension of 10.3 parts of the a-(2,4-dichlorophenyl)imidazole-1-ethanol thus obtained and 2.1 parts of sodium hydride in 50 parts of dry tetrahydrofuran is stirred and refluxed for 2 hours. After this reaction time, the evolution of hydrogen is ceased. Then there are added successively 60 parts dimethylformamide and 8 parts of 2,4-dichlorobenzyl chloride and stirring and refluxing are continued for another 2 hours. The tetrahydrofuran is removed at atmospheric pressure. The dimethylformamide solution Is poured onto water. 

Ye et al. reported that the reduction of 2,4-dichlorophenyl-2-chloroethanone 1 with potassium borohydride in dimethylformamide to give 90% a-chloromethyl-2,4-dichlorobenzyl alcohol 2. Alkylation of imidazole with compound 2 in dimethyl formamide in the presence of sodium hydroxide and triethylbenzyl ammonium chloride, gave l-(2,4-dichlorophenyl-2-imidazolyl)ethanol 3 and etherification of 3 with 2,4-dichlorobenzyl chloride under the same condition, 62% yield of miconazole [9]. 

Materials Imidazole ui-Bromo-2,4-dichloroacetophenone 2,4-Dichlorobenzyl chloride Sodium borohydride Sodium hydride Nitric acid ... 

Diehlorophenyl)-2-(1 H-imidazoM-yl)ethanone oxime Sodium hydride 2,4-Dichlorobenzyl chloride Nitric acid... 

The second central intermediate is 2,4-dichloro-phenylacetyl chloride 10, which is synthesized from 2,4-dichlorobenzyl chloride by cyanide exchange, saponification and acid chloride preparation. 

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