In this article, we investigate reaction solvent design using COSMO-RS thermodynamics in conjunction with computer-aided molecular design (CAMD) techniques. CAMD using COSMO-RS has the distinct advantage of being a method based in quantum chemistry, which allows for the incorporation of quantum-level information about transition states, reactive intermediates, and other important species directly into CAMD problems. This work encompasses three main additions to our previous framework for solvent design (Austin et al., Chem Eng Sci. 2017;159:93–105): (1) altering the group contribution method to estimate hydrogen-bonding and non-hydrogen-bonding σ-profiles; (2) ab initio modeling of strong solute/solvent interactions such as H-bonding or coordinate bonding; and (3) solving mixture design problems limited to common laboratory and industrial solvents. We apply this methodology to three diverse case studies: accelerating the reaction rate of a Menschutkin reaction, controlling the chemoselectivity of a lithiation reaction, and controlling the chemoselectivity of a nucleophilic aromatic substitution reaction. We report improved solvents/mixtures in all cases. © 2017 American Institute of Chemical Engineers AIChE J, 2017

中文翻译：

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基于COSMO的计算机辅助分子/混合物设计：专注于反应溶剂

在本文中，我们将结合使用COSMO-RS热力学和计算机辅助分子设计（CAMD）技术来研究反应溶剂的设计。使用COSMO-RS的CAMD具有作为基于量子化学的方法的显着优势，它允许将有关过渡态，反应性中间体和其他重要物种的量子级信息直接纳入CAMD问题。这项工作包括对我们以前的溶剂设计框架的三个主要补充（Austin等人，Chem Eng Sci。2017; 159：93–105）：（1）更改基团贡献方法以估计氢键和非氢键。粘合σ型材; （2）从头开始建模强大的溶质/溶剂相互作用，例如H键或配位键；（3）解决混合物设计中仅限于普通实验室和工业溶剂的问题。我们将此方法应用于三个不同的案例研究：加速Menschutkin反应的反应速率，控制锂化反应的化学选择性和控制亲核芳香族取代反应的化学选择性。我们报告在所有情况下改进的溶剂/混合物。©2017美国化学工程师学会AIChE的Ĵ，2017年