Abstract

The developments around flow processing technology have paved the way for new avenues and perspectives to consider in the field of organic chemistry and engineering. In this study, customized flow equipment was utilized to develop and optimize the Mitsunobu reaction. The flow reactor was a prototype of a simple tubular reactor based on the plug flow reactor concept. The experimentation methodology was designed through the statistical design of experiments approach to minimize the number of experiments. The molar ratios of cyclohexanol (1) and o-cresol (2) and interaction effects of triphenylphosphine, diisopropyl azodicarboxylate were studied in detail. The reaction profile of flow experiments agreed with the batch conditions adding noteworthy improvements to the overall reaction time, selectivity, and yield towards the desired product 1-(cyclohexyloxy)-2-methylbenzene (3). The Mitsunobu reaction in batch condition would take on an average of 3 to 5 h, which was effectively accomplished in 30 to 45 mins in this flow reactor. The generated mathematical model is in good agreement with the reaction conditions. We believe that the process could be executed continuously without a break, readily scaled to kilogram quantities in a short time without further development.

Graphic abstract

Mitsunobhu reaction in continuous process

中文翻译：

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连续过程的发展：光延反应的前景

摘要

流动处理技术的发展为有机化学和工程领域中的新途径和新观点铺平了道路。在这项研究中，使用定制的流动设备来开发和优化Mitsunobu反应。流动反应器是基于活塞流反应器概念的简单管式反应器的原型。通过统计实验设计方法来设计实验方法，以最大程度地减少实验次数。环己醇（1）与邻甲酚（2）的摩尔比）和三苯基膦，偶氮二异丙基二异丙酯的相互作用效应进行了详细研究。流动实验的反应曲线与分批条件一致，从而增加了总反应时间，选择性和收率，从而获得了所需产物1-（环己氧基）-2-甲基苯（3）。分批进行的Mitsunobu反应平均需要3到5个小时，这在此流动反应器中有效地在30到45分钟内完成。所生成的数学模型与反应条件高度吻合。我们相信，该过程可以不间断地连续执行，很容易在短时间内将其缩放到千克量，而无需进一步开发。

图形摘要

连续过程中的Mitsunobhu反应