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[1]黎浩,刘一粟,祝 宏*,等.恩康唑的制备工艺研究[J].武汉工程大学学报,2025,47(06):600-606.[doi:10.19843/j.cnki.CN42-1779/TQ.202309011]
　LI Hao,LIU Yishu,ZHU Hong*,et al.Study of the synthetic process of enilconazole[J].Journal of Wuhan Institute of Technology,2025,47(06):600-606.[doi:10.19843/j.cnki.CN42-1779/TQ.202309011]
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《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
47
期数:
2025年06期
页码:
600-606
栏目:
现代大化工
出版日期:
2025-12-31

文章信息/Info

Title:
Study of the synthetic process of enilconazole
文章编号:
1674 - 2869（2025）06 - 0600 - 07
作者:
黎浩; 刘一粟; 祝 宏*; 张银博; 袁航
武汉工程大学化工与制药学院，湖北 武汉 430205

Author(s):
LI Hao; LIU Yishu;  ZHU Hong*;  ZHANG Yinbo;  YUAN Hang
School of Chemical Engineering and Pharmacy，Wuhan Institute of Technology, Wuhan 430205, China
关键词:
恩康唑; 原料药; 合成工艺; 优化
Keywords:
enilconazole;  active pharmaceutical ingredient (API);  synthetic process;  optimization
分类号:
R914.5
DOI:
10.19843/j.cnki.CN42-1779/TQ.202309011
文献标志码:
A
摘要:
广谱杀真菌剂恩康唑系比利时杨森公司开发，属二类新兽药，但目前国内无拥有兽药批文的原料药和制剂生产厂家。在系统剖析国内外恩康唑合成路线后，针对传统路线中硝化、高压加氢等高危步骤及总收率≤30%的缺陷，设计绿色新工艺：以廉价咪唑为起始原料，先与3-氯-1-丙烯在离子液体中完成区域选择性N-烷基化，随后与2,2′,4′-三氯苯乙酮经硼氢化钠-三氟化硼乙醚协同还原，避免高压氢化；最后以碳酸钾/PEG-400催化O-烷基化，得到不低于欧洲药典标准的恩康唑原料药。
Abstract:
Enilconazole, a broad-spectrum fungicide originally developed by Janssen Pharmaceutica (Belgium), is classified as a Category II new veterinary drug in China, where there are no manufacturers with either its active pharmaceutical ingredient (API) or formulated products approvals. Based on a systematic analysis of existing synthetic routes, a novel green pathway was designed to overcome the critical limitations of conventional approaches—specifically, the hazardous nitration and high-pressure hydrogenation steps and the low overall yield (≤30%). The synthesis started with commercially available imidazole, which underwent regioselective N-alkylation with 3-chloro-1-propene in an ionic liquid medium. The resulting intermediate was then chemoselectively reduced using a sodium borohydride-boron trifluoride etherate system, thereby eliminating the need for high-pressure hydrogenation. Finally, O-alkylation catalyzed by potassium carbonate/PEG-400 afforded enilconazole API that consistently complied with European Pharmacopoeia specifications.

参考文献/References:

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备注/Memo

备注/Memo:
收稿日期：2023-09-16
基金项目：武汉工程大学第十六届研究生教育创新基金（CX2024252）
作者简介：黎 浩，硕士研究生。Email：1254208163@qq.com
*通信作者：祝 宏，教授。Email:2806358119@qq.com
更新日期/Last Update: 2026-01-05