Eötvös Loránd University, Budapest, Hungary.
J Org Chem. 2011 Nov 4;76(21):8749-55. doi: 10.1021/jo201439u. Epub 2011 Oct 11.
One of the most widespread synthetic routes to coumarins is the condensation of esters and phenols via the Pechmann reaction. Despite the industrial and technological importance of the reaction, its mechanism is still poorly understood. We have explored several possible reaction paths by DFT calculations at the M05-2X/6-31+G* level. Amphoteric groups and the solvent have a crucial role in the frequent proton-transfer steps of the mechanisms; therefore, we have employed a mixed solvent model, where we combined the implicit PCM model together with an explicit water molecule placed at the actual proton transfer region. The Gibbs free-energy profiles of the possible routes suggest that three parallel channels (featuring water elimination, trans-esterification, and electrophilic attack) operate simultaneously. Enolic routes have prohibitively high activation barriers rendering these paths untenable. The calculated profiles indicate that in each feasible route the first elementary step has the highest activation energy. Reaction intermediates identified on the free-energy profiles can explain several experimental observations.
香豆素最广泛的合成途径之一是通过 Pechmann 反应缩合酯和酚。尽管该反应具有工业和技术重要性，但它的机理仍未被很好地理解。我们已经通过在 M05-2X/6-31+G* 水平上的 DFT 计算探索了几种可能的反应途径。两性基团和溶剂在机制的频繁质子转移步骤中起着至关重要的作用；因此，我们采用了混合溶剂模型，其中我们将隐式 PCM 模型与放置在实际质子转移区域的显式水分子相结合。可能途径的吉布斯自由能曲线表明，三个平行的通道（具有消除水、酯交换和亲电攻击的功能）同时起作用。烯醇途径的活化能过高，使得这些途径不可行。计算得到的曲线表明，在每个可行的途径中，第一步的活化能最高。在自由能曲线上确定的反应中间体可以解释几个实验观察结果。
