Mechanistic Elucidation of Zirconium-Catalyzed Direct Amidation
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- 作者：Helena Lundberg ; Fredrik TinnisJiji Zhang ; Andrés G. Algarra ; Fahmi HimoHans Adolfsson
- 刊名：Journal of the American Chemical Society
- 出版年：2017
- 出版时间：February 15, 2017
- 年：2017
- 卷：139
- 期：6
- 页码：2286-2295
- 全文大小：706K
- ISSN：1520-5126
文摘
The mechanism of the zirconium-catalyzed condensation of carboxylic acids and amines for direct formation of amides was studied using kinetics, NMR spectroscopy, and DFT calculations. The reaction is found to be first order with respect to the catalyst and has a positive rate dependence on amine concentration. A negative rate dependence on carboxylic acid concentration is observed along with S-shaped kinetic profiles under certain conditions, which is consistent with the formation of reversible off-cycle species. Kinetic experiments using reaction progress kinetic analysis protocols demonstrate that inhibition of the catalyst by the amide product can be avoided using a high amine concentration. These insights led to the design of a reaction protocol with improved yields and a decrease in catalyst loading. NMR spectroscopy provides important details of the nature of the zirconium catalyst and serves as the starting point for a theoretical study of the catalytic cycle using DFT calculations. These studies indicate that a dinuclear zirconium species can catalyze the reaction with feasible energy barriers. The amine is proposed to perform a nucleophilic attack at a terminal η2-carboxylate ligand of the zirconium catalyst, followed by a C–O bond cleavage step, with an intermediate proton transfer from nitrogen to oxygen facilitated by an additional equivalent of amine. In addition, the DFT calculations reproduce experimentally observed effects on reaction rate, induced by electronically different substituents on the carboxylic acid.