抗球虫药物妥曲珠利的合成过程中醚化反应的工艺改进

Process improvement on etherification of coccidiostatic drug toltrazuril synthesis

对抗球虫药物妥曲珠利的合成工艺中醚化反应过程进行工艺改进.醚化反应由对三氟甲硫基苯酚(TFMP)和2-氯-5-硝基甲苯(CNT)生成3-甲基-4-(4-三氟甲硫基苯氧基)硝基苯(TFME).反应过程中用碳酸钾代替氢氧化钠,另外采用"二步法"进行醚化反应,先进行酚脱水再醚化,减少反应体系内水的含量,经过两次改进,醚化反应时间由原来的65 h缩短到48 h,3-甲基-4-(4-三氟甲硫基苯氧基)硝基苯(TFME)的产品质量由94%提高到96%以上,以TFMP计的收率由91.53%,提高到93.34%,此工艺为妥曲株利的合成创造有利条件.

The process improvement on etherification of coccidiostatic drug toltrazuril synthesis is studied in this paper.Used 4-（trifluoro methylthio） phenol（TFMP） and 2-chloro-5-nitrotoluene（CNT） to etherify 3-methyl-4-（4-trifluoromethylthiobenzoxy）-nitrobenzene（TFME）.In this reaction,potassium carbonate is used to replace sodium hydroxide.Based on ＂two step method＂,etherification is carried out after dehydration.After two times process improvement,reaction time of etherification is shorten from 65 hr to 48 hr,and the product quality of 3-methyl-4-（4-trifluoromethylthiobenzoxy）-nitrobenzene（TFME）is raised from 94% to 96%,TFMP total yield is raised from 91.53% to 93.34%.This process improvement provides an advantage to toltrazuril synthesis.