通过混合微包装床/微管反应器在望远镜多级流合成中提高反应兼容性:适用于cyproflanilide和broflanilide
Xingyu Zhang1,2, Gangqin Huang1, Yihui Ou3
1Key Laboratory of Molecule Synthesis and Function Discovery (Fujian Province University), College of Chemistry, Fuzhou University, Fuzhou 350108, China.
JACS Au
|August 29, 2025
概括
使用微包装床反应器和微管式反应器的新型混合流系统克服了望远镜合成中的挑战. 这种方法可以有效地连续制造关键的制药和农业化学品.
科学领域:
- 化学工程
- 有机合成
- 连续制造
背景情况:
- 望远镜多级流合成对于连续制造药物至关重要,但由于跨级不兼容性而面临挑战.
- 在连续反应中,变化的反应条件阻碍了没有中间分离的过程的整合.
研究的目的:
- 开发一个混合流系统,集成微包装床反应器 (μPBR) 和微管状反应器 (μTR),以解决跨阶段不兼容性.
- 证明这种混合系统在有效的连续合成N-酸和复杂杀虫剂中的应用.
主要方法:
- 设计了一种混合流系统,将μPBR用于异质催化和μTR用于同质反应.
- 该系统应用于N--N-氨酸的四步合成,包括氧还原,还原性氨化,胺合和水解.
- 使用二-18-皇冠-6和定制的流量配置开发了一个可扩展的双相硫酸脱协议.
主要成果:
- 在没有中间分离的情况下,N--N-氨基5a (87%在15.5分钟内) 和5b (84%在13.8分钟内) 的高产量得到了实现.
- 完成了昆虫杀虫剂赛普罗夫拉尼利德和布罗夫拉尼利德的八步连续合成.
- 通过可扩展的双相硫脱协议实现了每天千克的杀虫剂中间产量.
结论:
- 混合流系统有效地解决了望远镜流合成中的反应不兼容问题.
- 这一战略显著提升了连续制造过程的实际实施和可扩展性.
- 开发的系统为制药和农业化学品中的复杂分子提供了多功能性.
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