JPS60199877A - Production of 1-((o-chlorophenyl)diphenylmethyl) imidazole - Google Patents

Abstract

PURPOSE:The reaction between (o-chlorophenyl)diphenylmethyl bromide and N-acylimidazole enable industrially easy production of the titled compound which has been widely used for clinical purposes, because of its high antibacterial activity, in high yield. CONSTITUTION:(o-Chlorophenyl)dimethyl brmide of formula II is allowed to react with an N-acylimidazole of formula III (R is acyl) in a solvent such as acetonitrile at 20-25 deg.C for tens minutes to 2hr, then the reaction mixture is diluted with water and made alkaline by adding an alkaline substance such as sodium carbonate, then extracted with a solvent such as chloroform to give 1-[(o-chlorophenyl)diphenylmethyl]imidazole (called chlotrimazole) in high yield.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 1-[(0-chlorophenyl)zophenylmethel]imidazole (hereinafter referred to as "clotrimazole") represented by the following formula (1>).

[Che
m, Ber, 93 r 570Q, page 576;
Japanese Patent Publication No. 47-18752], and is currently widely used in clinical practice.

Conventionally, as a method for producing clotrimazole, (o
- Chlorophenyl] Basic method of reacting zophenyl methyl halide with imidazole silver salt, etc. (Japanese Patent Publication No. 47-
Various improved manufacturing methods have been reported, including Japanese Patent No. 18752). However, these methods each had their own drawbacks and were not necessarily satisfactory as industrial methods.

Therefore, the present inventor conducted various studies in order to provide an industrial method, and as a result, completed a novel method different from conventionally known methods.

The method of the present invention is carried out by the following reaction formula.

(1) (1) (wherein R represents an acyl group) That is, the present invention provides (0-chlorophenyl)zophenylmethylbromide (n) and N-acylimidazole (
ll) to produce clotrimazole (1).

To carry out the present invention, compounds (n) and (I) may be reacted in a suitable solvent at a temperature of 20 to 25°C for several tens of minutes to two hours. As the solvent, for example, acetonitrile, dimethylformamide, bilicin, etc. are used.

After the reaction, the reaction solution is diluted with water, made alkaline by adding an alkaline substance, and extracted with a solvent such as chloroform to obtain clotrimazole (1) in high yield.

Next, an example will be given and explained.

Example 1 (,-chlorophenyl)zophenylmethylbromide 4
0? (0,112 mol) dried acetonyl)・Ryl 60-
to which 1 N-acetylimidazole was suspended and stirred.
3.5 f (0.12 mol) are added at a temperature of 20-25°C. If this is allowed to react at the same temperature for 30 minutes to 1 hour, a uniform pale yellow bath liquid will be obtained. After diluting the reaction solution with water and making it alkaline with sodium carbonate, the oily substance that separates is extracted with chloroform. After washing the extract with water and drying with Glauber's salt,
The solvent is evaporated to give a yellow oil 532. This was repeatedly recrystallized from cyclohexane-benzene, and the melting point was 14.
Clotrimazole as white crystals exhibiting a temperature of 2 to 143°C 30.
8f (80% yield) is obtained.

The IR and NMR spectra of this product completely matched those of the standard product. − Applicant Ichikawa Chemical Research Institute Co., Ltd.

Claims (1)

[Scope of Claims] (0-chlorophenyl)zophenyl represented by r, methyl bromide is added to 1-c represented by N-acylimitaso.
A method for producing (o-chlorophenyl)zophenylmethyl]imidazole.