Synthesis method of p-toluene sulfonic acid pleuromutilin ester

A technology of pleuromutilin ester and p-toluenesulfonic acid, which is applied in the preparation of sulfonic acid ester, organic chemistry and other directions, can solve the problems of low production efficiency, long reaction time, low catalytic performance of triethylamine, etc., and achieves improved synthesis efficiency. and productivity, environmentally friendly worker health, and the effect of shortening the synthesis reaction time

Inactive Publication Date: 2013-12-18
大英九合药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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

Method used

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  • Synthesis method of p-toluene sulfonic acid pleuromutilin ester

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Experimental program
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Effect test

Embodiment 1

[0015] 378.5 grams (1mol) of pleuromutilin were added to 1500 milliliters of methyl isobutyl ketone, and then 209.4 grams (1.1mol) of p-toluenesulfonyl chloride and a content of 40 grams (1mol), 30% sodium hydroxide solution in water. After the dropwise addition, the temperature was raised to 60° C. for 0.5 hour reaction. After the reaction solution was cooled to room temperature, the organic layer was separated, washed with water (800 ml × 3), dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 506.6 grams of white pleuromutilin p-toluenesulfonate Solid, yield 95.1%, its chromatographic purity analyzed by high pressure liquid chromatography is 97%.

Embodiment 2

[0017] 378.5 grams (1mol) of pleuromutilin were added to 1500 milliliters of methyl isobutyl ketone, and then 209.4 grams (1.1mol) of p-toluenesulfonyl chloride and 56 grams (1mol) of concentration were added under stirring. It is 25% potassium hydroxide aqueous solution. After the dropwise addition, the temperature was raised to 50° C. and the reaction was carried out for 0.5 hours. After the reaction solution was cooled to room temperature, the organic layer was separated, washed with water (800 ml×3), dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 514.0 grams of white pleuromutilin p-toluenesulfonic acid solid , the yield was 96.5%, and its chromatographic purity was 97.2% as analyzed by high pressure liquid chromatography.

Embodiment 3

[0019] Add 189.3 grams (0.5 mol) of pleuromutilin to 800 ml of methyl isobutyl ketone, then add 104.7 grams (0.55 mol) of p-toluenesulfonyl chloride and a content of 53 grams (0.5 mol) of saturated aqueous sodium carbonate solution. After the dropwise addition, the temperature was raised to 65° C. and the reaction was carried out for 1.5 hours. After the reaction solution was cooled to room temperature, the organic layer was separated, washed with water (600 ml × 3), dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 253.0 grams of white pleuromutilin p-toluenesulfonic acid solid , the yield was 95.0%, and its chromatographic purity was 98.1% as analyzed by high-pressure liquid chromatography.

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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...

Claims

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Application Information

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IPC IPC(8): C07C309/73C07C303/28
Inventor 穆万勇刘忠东
Owner 大英九合药业有限公司
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