Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Ave., ON, N9B 3P4, Windsor, Canada.
Department of Chemistry, University of Michigan, 930 N University Ave., Ann Arbor, MI, 48109, USA.
Chemistry. 2021 Feb 15;27(10):3440-3448. doi: 10.1002/chem.202004208. Epub 2021 Jan 18.
Alkylating reagents based on thioimidazolium ionic liquids were synthesized and the influence of the anion on the alkylation reaction mechanism explored in detail using both experimental and computational methods. Thioimidazolium cations transfer alkyl substituents to nucleophiles, however the reaction rate was highly dependent on anion identity, demonstrating that the anion is not innocent in the mechanism. Detailed analysis of the computationally-derived potential energy surfaces associated with possible mechanisms indicated that this dependence arises from a combination of anion induced electronic, steric and coordinating effects, with highly nucleophilic anions catalyzing a 2-step process while highly non-nucleophilic, delocalized anions favor a 1-step reaction. This work also confirms the presence of ion-pairs and aggregates in solution thus supporting anion-induced control over the reaction rate and mechanism. These findings provide new insight into an old reaction allowing for better design of cationic alkylators in synthesis, gene expression, polymer science, and protein chemistry applications.
基于硫代咪唑鎓离子液体的烷基化试剂被合成，并通过实验和计算方法详细探讨了阴离子对烷基化反应机制的影响。硫代咪唑鎓阳离子将烷基取代基转移到亲核试剂上，然而反应速率高度依赖于阴离子的特性，表明阴离子在反应机制中并非无足轻重。对与可能的机制相关的计算所得势能面的详细分析表明，这种依赖性源于阴离子诱导的电子、空间和配位效应的组合，高亲核性阴离子催化两步反应，而高非亲核性、离域阴离子则有利于一步反应。这项工作还证实了离子对和聚集体在溶液中的存在，从而支持阴离子诱导对反应速率和机制的控制。这些发现为这一古老的反应提供了新的见解，使我们能够更好地设计用于合成、基因表达、聚合物科学和蛋白质化学应用的阳离子烷基化剂。
