Department of Chemistry, Science Laboratories, Durham University, South Road, Durham, UK DH1 3LE.
Chem Commun (Camb). 2010 Mar 21;46(11):1813-23. doi: 10.1039/b923093a. Epub 2010 Feb 9.
Despite the amide formation reaction being one of the key cornerstone reactions in organic chemistry, the direct amide formation is both little used and little explored. Acceptance of the feasibility and general applicability of the reaction depends upon the ability of researchers to bring it into the mainstream by development of: (1) an understanding of the mechanism of the reaction; and (2) the design of catalysts which promote the reaction on a wide range of substrates and under ambient conditions. From the earliest report of the direct amide formation in the 19th century, there have been relatively few reports of mechanistic studies, though it is clear that there is not a simple relationship between ease of direct amide formation and the pK(a) of the carboxylic acid and amine, or whether salt ammonium carboxylate formation is important. Consequently, direct amide formation has historically been run under higher temperature conditions. However, more recently, stoichiometric and catalytic boron compounds have been developed that considerably reduce the reaction temperatures under which direct amide formation will proceed. Limited attempts at mechanistic studies point to the formation of acyloxyborate or boronate species acting essentially as mixed anhydrides, though the exact order of these systems remains to be categorically determined.
尽管酰胺形成反应是有机化学中的关键基石反应之一，但直接酰胺形成反应的应用既少又不被广泛探索。该反应的可行性和普遍适用性的接受程度取决于研究人员通过以下方面的发展将其引入主流：（1）对反应机制的理解；（2）设计在广泛的底物和环境条件下促进反应的催化剂。自 19 世纪直接酰胺形成的最早报道以来，虽然很明显，直接酰胺形成的容易程度与羧酸和胺的 pK(a)之间，或者盐铵羧酸盐形成是否重要，并没有简单的关系，但相对较少有关于其机制的研究报告。因此，直接酰胺形成在历史上是在较高的温度条件下进行的。然而，最近，开发了等物质的量和催化硼化合物，大大降低了直接酰胺形成进行的反应温度。对机制研究的有限尝试表明，酰氧基硼酸盐或硼酸酯物种的形成基本上作为混合酸酐起作用，尽管这些体系的确切顺序仍有待明确确定。
