Lenev Denis A, Lyssenko Konstantin A, Golovanov Denis G, Buss Volker, Kostyanovsky Remir G
Semenov Institute of Chemical Physics, Russian Academy of Sciences, 4 ul. Kosygina, 119991 Moscow, Russia.
Chemistry. 2006 Aug 16;12(24):6412-8. doi: 10.1002/chem.200501532.
We have shown through racemization kinetics studies that the enantiomerization barriers of the bis-ortho-methyl substituted Tröger bases 2 and 3 in acidic media are raised by 30 kJ mol(-1) relative to the parent compound 1, that is 130.4(4) and 131.6(4) kJ mol(-1), respectively (105 degrees C, pH 1, ethylene glycol). The enantiomerization barrier of para-methoxy-para-nitro substituted Tröger base 4 was determined by dynamic capillary electrophoresis to 96.3(2) kJ mol(-1) (25 degrees C, pH 2.2, H(2)O), which is lower by 5 kJ mol(-1) relative to 1. The influence of deutero-substitution on the racemization rates was also studied. The influence of steric and electronic factors on the enantiomerization barrier was investigated by quantum-mechanical (DFT) calculations. It is shown that enantiomerization takes place in two steps: ring-opening and further interconversion of the monocyclic intermediate. For the interconversion to occur a transition state has to be passed which is sensitive to steric effects. Ortho-substitution by methyl groups significantly increases the energy of this state. Thus, compounds 2 and 3 are the simplest Tröger bases which are configurationally stable in acidic media.
我们通过外消旋动力学研究表明，在酸性介质中，双邻甲基取代的特罗格碱2和3的对映异构化势垒相对于母体化合物1提高了30 kJ·mol⁻¹，分别为130.4(4)和131.6(4) kJ·mol⁻¹（105℃，pH 1，乙二醇）。对甲氧基-对硝基取代的特罗格碱4的对映异构化势垒通过动态毛细管电泳测定为96.3(2) kJ·mol⁻¹（25℃，pH 2.2，水），相对于1低5 kJ·mol⁻¹。还研究了氘取代对外消旋速率的影响。通过量子力学（DFT）计算研究了空间和电子因素对对映异构化势垒的影响。结果表明，对映异构化分两步进行：开环和单环中间体的进一步相互转化。为了使相互转化发生，必须经过一个对空间效应敏感的过渡态。甲基的邻位取代显著增加了该状态的能量。因此，化合物2和3是在酸性介质中构型稳定的最简单的特罗格碱。
