Escribà-Gelonch Marc, Noël Timothy, Hessel Volker
Micro Flow Chemistry and Process Technology, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
Org Process Res Dev. 2018 Feb 16;22(2):147-155. doi: 10.1021/acs.oprd.7b00318. Epub 2017 Dec 20.
Herewith a new process concept for synthesis is presented which combines both UV-photoirradiation and high-p,T intensification (photo-high-p,T) in continuous flow. The application of this procedure to Vitamin D synthesis promotes thermal shifting of the equilibrium from the reaction intermediate to the product. This is enabled by microreactors which allow operation under harsh conditions such as the high temperature used here. This provides, to our best knowledge, a new kind of process combination (novel process window). As a result, in less than 1 min, 42% conversion of 7-dehydrocholesterol can be achieved giving a 17% yield and 40% selectivity of Vitamin D. This approach enhances productivity by up to 2 orders of magnitude compared with the current capillary based vitamin D synthesis, because, under the microflow conditions, photochemistry can be performed at fairly high concentration and up to 20 times faster.
在此提出一种新的合成工艺概念，该概念将紫外线光照射和高温高压强化（光高温高压）结合在连续流中。将此方法应用于维生素D合成可促进平衡从反应中间体向产物的热转移。这是通过微反应器实现的，微反应器允许在诸如此处使用的高温等苛刻条件下运行。据我们所知，这提供了一种新型的工艺组合（新型工艺窗口）。结果，在不到1分钟的时间内，7-脱氢胆固醇的转化率可达42%，维生素D的产率为17%，选择性为40%。与目前基于毛细管的维生素D合成相比，这种方法将生产率提高了多达2个数量级，因为在微流条件下，光化学可以在相当高的浓度下进行，速度快达20倍。
