WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, UK.
Chemistry. 2013 Jul 15;19(29):9655-62. doi: 10.1002/chem.201301011. Epub 2013 Jun 13.
The direct microwave-mediated condensation between 3-oxetanone and primary amides and thioamides has delivered moderate to good yields of (hydroxymethyl)oxazoles and (hydroxymethyl)thiazoles. The reactions use a sustainable solvent and only require short reaction times. These are highly competitive methods for the construction of two classes of valuable heteroarenes, which bear a useful locus for further elaboration. Electronic structure calculations have shown that the order of events involves chalcogen atom attack at sp(3) carbon and alkyl-oxygen cleavage. The critical role of acid catalysis was shown clearly, and the importance of acid strength was demonstrated. The calculated barriers were also fully consistent with the observed order of thioamide and amide reactivity. Spontaneous ring opening involves a modest degree of C-O cleavage, moderating the extent of strain relief. On the acid-catalysed pathway, C-O cleavage is less extensive still, but proton transfer to the nucleofuge is well advanced with the carboxylic acid catalysts, and essentially complete with methanesulfonic acid.
3-氧杂环戊酮与伯酰胺和硫代酰胺的直接微波介导缩合反应，以中等至良好的收率得到了（羟甲基）恶唑和（羟甲基）噻唑。该反应使用了一种可持续的溶剂，并且只需要很短的反应时间。这些方法在构建两类有价值的杂芳环方面具有很强的竞争力，它们具有进一步修饰的有用位置。电子结构计算表明，反应过程涉及杂原子对 sp(3) 碳原子的攻击和烷氧键的断裂。酸催化的关键作用得到了清晰的展示，酸强度的重要性也得到了证明。计算得到的势垒与观察到的硫代酰胺和酰胺反应活性顺序完全一致。自发开环涉及适度的 C-O 断裂，从而减轻了应变释放的程度。在酸催化途径中，C-O 断裂的程度仍然较小，但羧酸催化剂的质子转移到离去基团已经很先进，而甲磺酸则基本上完全转移。
