Synthesis method of p-toluene sulfonic acid pleuromutilin ester

Abstract

The invention relates to a synthesis method of p-toluene sulfonic acid pleuromutilin ester. Especially, the method includes: under catalysis of three inorganic alkalis, i.e. sodium hydroxide, potassium hydroxide or sodium carbonate, reacting pleuromutilin with p-toluenesulfonyl chloride for 0.5-1.5h in a methyl isobutyl ketone solvent at 50-65DEG C, conducting washing and distillation of the solvent, thus obtaining the p-toluene sulfonic acid pleuromutilin ester with yield of 95-96.5% and chromatographic purity of 97-98.1%. The method has the advantages of environmental-friendliness, worker health promotion, low production cost, short synthesis reaction time and high yield.

Description

1. Technical field [0001] The invention belongs to the technical field of fine chemicals, and relates to a synthesis method of pleuromutilin p-toluenesulfonate, especially pleuromutilin truncated under the catalysis of sodium hydroxide, potassium hydroxide or sodium carbonate, three inorganic bases A method for obtaining pleuromutilin p-toluenesulfonate by reacting p-toluenesulfonyl chloride with p-toluenesulfonate. 2. Background technology [0002] Pleuromutilin p-toluenesulfonate (1) is prepared by reacting pleuromutilin (2) with p-toluenesulfonyl chloride (p-TsCl): [0003] [0004] The English chemical name of 1 is: 14-desoxy-14-[(tosyloxyacetyl)oxy]mutilin, the English chemical name of pleuromutilin (2) is 14-Deoxy-14-[(hydroxyacetyl)oxy]mutilin, both The difference is that in 1, the p-toluenesulfonyl carboxyl group replaces the hydroxyl group in pleuromutilin. For the convenience of patent writing, according to the nomenclature of p-toluenesulfonic acid derivative...

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Problems solved by technology

Triethylamine is toxic, highly irritating, and volatile. It fumes in the air, pollutes the environment, and affects the health of workers.

In addition, the performance of triethylamine catalyzing the synthesis reaction is low, and the input amount of triethylamine in the synthesis is often greater than the input amount of pleuromutilin, as reported above by Wang Liqiang et al. In the synthesis reaction, the input molar ratio of pleuromutilin and triethylamine is: 1: 1.1

In addition, due to the low catalytic performance of triethylamine, the reaction time also needs to be very long, such as in the synthesis reaction of pleuromutilin p-toluenesulfonate reported by Wang Liqiang et al. In production, the production cycle of pleuromutilin p-toluenesulfonate is long and the production efficiency is low

In the study, we tried to shorten the reaction time by increasing the reaction temperature, but because triethylamine is easily oxidized in the air, the result is that the reaction solution turns brown and the reaction impurities increase.

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