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The assembly and use of continuous flow systems for chemical synthesis.
Nature Protocols ( IF 14.8 ) Pub Date : 2017-Nov-01 , DOI: 10.1038/nprot.2017.102
Joshua Britton , Timothy F Jamison

The adoption of and opportunities in continuous flow synthesis ('flow chemistry') have increased significantly over the past several years. Continuous flow systems provide improved reaction safety and accelerated reaction kinetics, and have synthesised several active pharmaceutical ingredients in automated reconfigurable systems. Although continuous flow platforms are commercially available, systems constructed 'in-lab' provide researchers with a flexible, versatile, and cost-effective alternative. Herein, we describe the assembly and use of a modular continuous flow apparatus from readily available and affordable parts in as little as 30 min. Once assembled, the synthesis of a sulfonamide by reacting 4-chlorobenzenesulfonyl chloride with dibenzylamine in a single reactor coil with an in-line quench is presented. This example reaction offers the opportunity to learn several important skills including reactor construction, charging of a back-pressure regulator, assembly of stainless-steel syringes, assembly of a continuous flow system with multiple junctions, and yield determination. From our extensive experience of single-step and multistep continuous flow synthesis, we also describe solutions to commonly encountered technical problems such as precipitation of solids ('clogging') and reactor failure. Following this protocol, a nonspecialist can assemble a continuous flow system from reactor coils, syringes, pumps, in-line liquid-liquid separators, drying columns, back-pressure regulators, static mixers, and packed-bed reactors.

中文翻译:

用于化学合成的连续流系统的组装和使用。

在过去的几年中,连续流动合成(“流动化学”)的采用和机会显着增加。连续流系统提供了改进的反应安全性和加速的反应动力学,并且已经在自动可重构系统中合成了几种活性药物成分。尽管连续流动平台在市场上可以买到,但“实验室内”构造的系统为研究人员提供了灵活,通用且经济高效的替代方案。在这里,我们描述了模块化连续流设备的组装和使用,该设备在短短30分钟内就可以从容易获得且价格适中的零件中获得。组装完成后,提出了通过4-氯苯磺酰氯与二苄基胺在单反应器盘管中进行在线淬灭反应来合成磺酰胺的方法。该示例反应提供了学习一些重要技能的机会,包括反应器构造,背压调节器的装料,不锈钢注射器的组装,具有多个连接的连续流系统的组装以及产率的确定。根据我们在单步和多步连续流合成中的丰富经验,我们还描述了解决常见技术问题的解决方案,例如固体沉淀(“堵塞”)和反应器故障。按照此协议,非专业人员可以用反应器盘管,注射器,泵,在线液-液分离器,干燥塔,背压调节器,静态混合器和填充床反应器组装连续流系统。进行背压调节器的装料,不锈钢注射器的组装,具有多个接头的连续流系统的组装以及产量的确定。根据我们在单步和多步连续流合成中的丰富经验,我们还描述了解决常见技术问题的解决方案,例如固体沉淀(“堵塞”)和反应器故障。按照此协议,非专业人员可以用反应器盘管,注射器,泵,在线液-液分离器,干燥塔,背压调节器,静态混合器和填充床反应器组装连续流系统。进行背压调节器的装料,不锈钢注射器的组装,具有多个接头的连续流系统的组装以及产量的确定。根据我们在单步和多步连续流合成中的丰富经验,我们还描述了解决常见技术问题的解决方案,例如固体沉淀(“堵塞”)和反应器故障。按照此协议,非专业人员可以用反应器盘管,注射器,泵,在线液-液分离器,干燥塔,背压调节器,静态混合器和填充床反应器组装连续流系统。我们还描述了解决常见技术问题的解决方案,例如固体沉淀(“堵塞”)和反应堆故障。按照此协议,非专业人员可以用反应器盘管,注射器,泵,在线液-液分离器,干燥塔,背压调节器,静态混合器和填充床反应器组装连续流系统。我们还描述了解决常见技术问题的解决方案,例如固体沉淀(“堵塞”)和反应堆故障。按照此协议,非专业人员可以用反应器盘管,注射器,泵,在线液-液分离器,干燥塔,背压调节器,静态混合器和填充床反应器组装连续流系统。
更新日期:2017-10-30
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