Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Szt. Gellért tér 4., Budapest, H-1111, Hungary.
J Org Chem. 2012 Jul 20;77(14):6014-22. doi: 10.1021/jo300745e. Epub 2012 Jul 5.
The reaction energy profiles of the benzoin condensation from three aldehydes catalyzed by imidazol-2-ylidene, triazol-3-ylidene, and thiazol-2-ylidene have been investigated computationally. The barriers for all steps of all investigated reactions have been found to be low enough to indicate the viability of the mechanism proposed by Breslow in the 1950s. The most remarkable difference in the catalytic cycles has been the increased stability of the Breslow intermediate in case of thiazol-2-ylidene (by ca. 10 kcal/mol) compared to the other two carbenes, which results in lower energy for the coupling of the second aldehyde molecule, thus, increasing the reversibility of the reaction. Since the analogous transketolase reaction, being involved in the carbohydrate metabolism of many organisms, requires an initial decoupling-a reverse benzoin condensation-this difference provides a reasonable explanation for the presence of a thiazolium ring in thiamine instead of the otherwise generally more available imidazole derivatives. The "resting intermediate" found by Berkessel and co-workers for a triazole-based catalyst was found more stable than the Breslow intermediate for all of the systems investigated. The (gas phase) proton affinities of several carbenes were compared, the relative trends being in agreement with the available (in aqueous solution) data. The hydrolytic ring-opening reaction of the thiazole-based carbene was shown to be different from that of imidazole-2-ylidenes.
三种醛的苯偶姻缩合反应的咪唑-2-亚基、三唑-3-亚基和噻唑-2-亚基催化的反应能量曲线已通过计算得到了研究。所有研究反应的所有步骤的障碍都被发现足够低，足以表明 Breslow 在 20 世纪 50 年代提出的机制的可行性。在催化循环中最显著的差异是噻唑-2-亚基（约 10 kcal/mol）中 Breslow 中间体的稳定性增加，与其他两种卡宾相比，这导致第二个醛分子的偶联的能量降低，从而增加了反应的可逆性。由于类似的转酮醇酶反应参与了许多生物体的碳水化合物代谢，需要初始解偶联——反向苯偶姻缩合——这种差异为硫胺素中存在噻唑环而不是通常更可用的咪唑衍生物提供了合理的解释。Berkessel 及其同事为基于三唑的催化剂发现的“休息中间体”比所有研究系统中的 Breslow 中间体更稳定。比较了几种卡宾的（气相）质子亲和力，相对趋势与可用的（在水溶液中）数据一致。基于噻唑的卡宾的水解开环反应被证明与咪唑-2-亚基的不同。
