Department of Chemistry, Bogaziçi University, Bebek, Istanbul, 34342, Turkey.
Faculty of Pharmacy, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34752, Turkey.
Org Biomol Chem. 2020 Mar 25;18(12):2233-2241. doi: 10.1039/c9ob02556a.
Recently, Sarigul and Dogan have synthesized a number of enantiomerically enriched axially chiral atropoisomeric 2-thiohydantoins by the reaction of l-amino acid ester salts and o-aryl isothiocyanates in the presence of triethyl amine (TEA) in dichloromethane. The non-axially chiral derivative 5-methyl-3-phenyl-2-thiohydantoin gave a racemic product whereas the axially chiral 5-methyl-3-o-bromophenyl-2-thiohydantoin was less prone to racemize at C5 of the heterocyclic ring. In this study, we present a computational study (M06-2X/6-311+G(d,p) for C, H, O, N and S; M06-2X/6-311++G(3df,3pd) for Br) in order to propose plausible mechanisms for the racemization and cyclization steps for 2-thiohydantoin derivatives. The study includes rationalization based on steric as well as the electrostatic effects to elucidate the epimerization differences at C5.
最近，Sarigul 和 Dogan 在三乙胺（TEA）存在下，用 l-氨基酸酯盐和邻芳基异硫氰酸酯在二氯甲烷中反应，合成了许多对映体富集的轴手性轴向手性 2-硫代海因。非轴手性衍生物 5-甲基-3-苯基-2-硫代海因得到外消旋产物，而轴手性 5-甲基-3-邻溴苯基-2-硫代海因在杂环环的 C5 上不易外消旋。在这项研究中，我们进行了计算研究（M06-2X/6-311+G(d,p) 用于 C、H、O、N 和 S；M06-2X/6-311++G(3df,3pd) 用于 Br），以提出 2-硫代海因衍生物的外消旋和环化步骤的合理机制。该研究包括基于空间和静电效应的合理化，以阐明 C5 处的差向异构化差异。
