A Computational Approach to Solvent Selection for Tandem Reactions: A Tool for Process Intensification

精细化学工业生产率的重大损失是因为经常需要在不同的溶剂和不同的条件下在单一过程中执行不同的步骤。这就需要回收中间体，增加生产成本和时间。一个有希望显著提高这类过程效率的方法是发展串联反应，在这个反应中，几个键在同一反应体系中形成。为了使这种反应成为现实，必须为反应机理中的所有步骤确定合适的溶剂和反应条件。这通常是一项非常困难的任务，需要洞察和艰苦的试错过程。在这里，我们建议开发一种系统的方法来识别合适的溶剂，结合物理有机化学家的实验工具和化学工程师的计算工具。我们将使用动态动力学拆分方法来证明这种方法用于合成对映体纯的化合物，特别是在醇的酰化的情况下。拟议的方法将有可能彻底改变此类反应系统的设计方式。除了这些科学成就外，这种合作还将包括几项旨在刺激化学和化学工程领域长期创新的活动。这两名调查人员将花时间学习对方的技术，教授对方的学生，并与他们两所机构--华威和伦敦帝国理工学院的其他学者接触。

Major losses in productivity in the fine chemicals industry arise from the frequent need to carry out different steps within a single process in different solvents and under different conditions. This requires the recovery of intermediates, increasing the cost and time of production. A promising approach to improve significantly the efficiency of such processes is to develop tandem reactions, in which several bonds are formed in the same reaction system. In order to make such reactions a reality, one must identify suitable solvents and reaction conditions for all steps in the mechanism. This is usually a very difficult task, which requires insight and a painstaking trial-and-error process. Here, we propose to develop a systematic approach to the identification of suitable solvents, by combining the experimental tools of physical organic chemists and the computational tools of chemical engineers. We will demonstrate this approach using the dynamic kinetic resolution method for the synthesis of enantiomerically pure compounds, particularly for the case of the acylation of alcohols. The proposed approach will have the potential to revolutionise the way such reaction systems are designed.In addition to these scientific achievements, this collaboration will entail several activities aimed to stimulate long-term innovation at the interface of chemistry and chemical engineering. The two investigators will spend time learning each other's techniques, teaching each other's students, and engaging with other academics at their two institutions, Warwick and Imperial College London.