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Minimizing Material Consumption in Flow Process Research and Development: A Novel Approach Toward Robust and Controlled Mixing of Reactants
Organic Process Research & Development ( IF 3.4 ) Pub Date : 2022-08-03 , DOI: 10.1021/acs.oprd.2c00123
Julien Haber 1 , Hannes Ausserwoeger 1 , Claudio Lehmann 1 , Lauriane Pillet 1 , Berthold Schenkel 1 , Bertrand Guélat 1
Affiliation  

Scarce availability of chemical starting materials is a crucial challenge in the development of flow chemical processes. This is particularly important for organometallic reactions, which typically require high flow rates and hence high material consumption, to generate sufficiently short mixing and residence times. To address this issue, micromixers that mix efficiently even at small Re numbers and that have a low tendency of clogging are necessary. Here, we propose the usage of microannular gear pumps as active mixers, which allow the reduction of material consumption by >10-fold while achieving fast mixing times for common organometallic reactions. This novel approach is benchmarked against several commercially available mixers with respect to the mixing time at low flow rates, showing that the gear pumps can achieve fast mixing (< 50 ms) even at <1 mL/min. To assess the crucially important factor of time to blockage in a consistent manner, a novel protocol is developed based on the controlled precipitation of lithium salts during the mixing process. This shows that the gear pump is significantly more robust than common mixers as operation can be maintained for over 2 h. Lastly, we highlight that the microannular gear pump approach allows the manipulation of mixing time at equal residence time, by tuning the rotation speed, thus allowing for characterization of the mixing sensitivity of reactions. Taken together, our multiparametric analysis of common mixing approaches highlights that the usage of microannular gear pumps for active mixing of fast organometallic reactions presents a powerful alternative able to address current limitations of organic process development.

中文翻译:

最小化流动过程研究和开发中的材料消耗:一种实现反应物稳健和可控混合的新方法

化学起始材料的稀缺性是流动化学工艺发展中的一个关键挑战。这对于有机金属反应尤其重要,有机金属反应通常需要高流速并因此需要高材料消耗,以产生足够短的混合和停留时间。为了解决这个问题,需要即使在很小的 Re 值下也能有效混合并且堵塞倾向低的微混合器。在这里,我们建议使用微型环形齿轮泵作为主动混合器,这可以将材料消耗减少 10 倍以上,同时实现常见有机金属反应的快速混合时间。这种新颖的方法在低流速下的混合时间方面与几种市售混合器进行了基准测试,表明齿轮泵可以实现快速混合(< 50 毫秒),即使在 <1 毫升/分钟。为了以一致的方式评估堵塞时间的关键重要因素,开发了一种基于锂盐在混合过程中受控沉淀的新方案。这表明齿轮泵比普通混合器坚固得多,因为可以保持运行超过 2 小时。最后,我们强调微环形齿轮泵方法允许通过调整旋转速度在相等的停留时间下操纵混合时间,从而允许表征反应的混合灵敏度。总之,我们对常见混合方法的多参数分析强调,使用微环形齿轮泵进行快速有机金属反应的主动混合是一种强大的替代方案,能够解决当前有机工艺开发的局限性。
更新日期:2022-08-03
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