A kind of synthetic method of clotrimazole

Abstract

The invention discloses a synthesis method of clotrimazole, and belongs to the technical field of chemical synthesis. According to the method, 2-chlorotrityl chloride and imidazole are taken as raw materials, hexafluoroisopropanol is taken as a solvent, and reaction is performed in an alkali environment. The method has the advantages that the raw materials 2-chlorotrityl chloride and imidazole areeasy to get; the reaction can be performed at room temperature, and the reaction condition is mild; other than previous multistep reaction, the method adopts one-step synthesis and is simple to operate; the method is high in reaction activity, the yield reaches 92 percent, and the raw materials are completely converted; products are convenient to separate, and the reaction has green economical efficiency, and is environmentally friendly.

Description

technical field

[0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for synthesizing clotrimazole. Background technique

[0002] Clotrimazole (Clotrimazole) is a synthetic antifungal drug; especially for deep infection of fungi has a high efficacy. The traditional chemical synthesis methods of clotrimazole include: the condensation synthesis method of ester+Grignard reagent and the synthesis method using o-chlorotoluene as raw materials. The total yield of the latter synthetic route is about 32%, and the total yield of the former synthetic route is slightly It is higher than the latter, but there are many unsafe factors in the former synthetic route; the two are cumbersome to operate, low in yield, with many wastes and long production cycle.

[0003] On the basis of the above two methods, the methods to improve them are:

[0004] Using o-chlorotoluene as raw material, o-chlorotoluene is chlorinated to generate o-...

Examples

Embodiment

[0021] A kind of synthetic method of clotrimazole, the steps are as follows:

[0022] Take 4mmol of 2-chlorotrityl chloride, 8mmol of imidazole and 8mmol of sodium carbonate, add 20mL of hexafluoroisopropanol (HFIP), and stir at room temperature (25°C) for 48h. The reaction formula is as follows:

[0023]

[0024] After the reaction was completed, the reaction was determined by TLC, concentrated and separated by column chromatography.

[0025] The reaction yield was detected to be 92%.

[0026] The clotrimazole prepared by the embodiment of the present invention 1 was added in deuterated chloroform (CDCl 3 ), carry out nuclear magnetic resonance analysis, the result is as follows:

[0027] 1HNMR (500MHz, CDCl 3 )δ7.46(s,1H),7.41(d,J=7.7Hz,1H),7.34(d,J=1.2Hz,7H),7.24(d,J=8.0Hz,1H),7.20(d , J=1.3Hz, 4H), 7.06(s, 1H), 6.93(d, J=7.8Hz, 1H), 6.75(s, 1H).

[0028] 13CNMR (125MHz, CDCl 3 )δ 140.90, 140.38, 139.13, 135.59, 132.23, 130.42, 130.19, 129.87, 128.43, 128.17, 128....

technical field

[0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for synthesizing clotrimazole. Background technique

[0002] Clotrimazole (Clotrimazole) is a synthetic antifungal drug; especially for deep infection of fungi has a high efficacy. The traditional chemical synthesis methods of clotrimazole include: the condensation synthesis method of ester+Grignard reagent and the synthesis method using o-chlorotoluene as raw materials. The total yield of the latter synthetic route is about 32%, and the total yield of the former synthetic route is slightly It is higher than the latter, but there are many unsafe factors in the former synthetic route; the two are cumbersome to operate, low in yield, with many wastes and long production cycle.

[0003] On the basis of the above two methods, the methods to improve them are:

[0004] Using o-chlorotoluene as raw material, o-chlorotoluene is chlorinated to generate o-...

Examples

Embodiment

[0021] A kind of synthetic method of clotrimazole, the steps are as follows:

[0022] Take 4mmol of 2-chlorotrityl chloride, 8mmol of imidazole and 8mmol of sodium carbonate, add 20mL of hexafluoroisopropanol (HFIP), and stir at room temperature (25°C) for 48h. The reaction formula is as follows:

[0023]

[0024] After the reaction was completed, the reaction was determined by TLC, concentrated and separated by column chromatography.

[0025] The reaction yield was detected to be 92%.

[0026] The clotrimazole prepared by the embodiment of the present invention 1 was added in deuterated chloroform (CDCl 3 ), carry out nuclear magnetic resonance analysis, the result is as follows:

[0027] 1HNMR (500MHz, CDCl 3 )δ7.46(s,1H),7.41(d,J=7.7Hz,1H),7.34(d,J=1.2Hz,7H),7.24(d,J=8.0Hz,1H),7.20(d , J=1.3Hz, 4H), 7.06(s, 1H), 6.93(d, J=7.8Hz, 1H), 6.75(s, 1H).

[0028] 13CNMR (125MHz, CDCl 3 )δ 140.90, 140.38, 139.13, 135.59, 132.23, 130.42, 130.19, 129.87, 128.43, 128.17, 128....

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