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Efficient amide formation from arylamines and esters promoted by AlCl3/Et3N: an experimental and computational investigation

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Abstract

Efficient and selective preparation of amides from arylamines and esters has been achieved with an AlCl3/Et3N pair under mild conditions. A large number of arylamines were successfully acylated to the corresponding amides in high yields and short reaction times. For instance, a 94% yield of p-bromoacetanilide was obtained from p-bromoaniline and ethyl acetate in 10 min at room temperature. In addition, a computational study on the N-acylation of amines was performed using density functional theory. It was found that the energy barrier for N-acylation of aniline is 10 kcal/mol higher than that of methylamine. In the presence of AlCl3, the activation energy for the N-acylation of aniline was reduced by 27.7 kcal/mol with the endothermic process becoming exothermic.

Graphical Abstract

In this work, the efficient and selective preparation of amides from arylamines and esters has been performed successfully with an AlCl3/Et3N pair under mild conditions. A large number of arylamines were acylated to the corresponding amides with high yields and short reaction times. In addition, a computational study on the N-acylation of amines has been carried out using the density functional theory (DFT) method.

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Acknowledgement

This work was financially supported by the National Natural Science Foundation of China (Project No 20834002 and No 21003093).

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Authors and Affiliations

  1. Department of Chemistry, Tianjin University, Tianjin, 300072, People’s Republic of China

    Xinli Tong, Zhangshun Ren, Xiaolong Qü, Qiwu Yang & Wenqin Zhang

  2. School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin, 300384, People’s Republic of China

    Xinli Tong

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  1. Xinli Tong
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  2. Zhangshun Ren
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  3. Xiaolong Qü
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  5. Wenqin Zhang
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Correspondence to Wenqin Zhang.

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11164_2012_517_MOESM1_ESM.doc

The computational details, the energy profile for N-acetylation of methylamine, and the energy profile for the N-acetylation of aniline with AlCl3 are contained in the supporting information. (DOC 148 kb)

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Tong, X., Ren, Z., Qü, X. et al. Efficient amide formation from arylamines and esters promoted by AlCl3/Et3N: an experimental and computational investigation. Res Chem Intermed 38, 1961–1968 (2012). https://doi.org/10.1007/s11164-012-0517-x

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  • DOI: https://doi.org/10.1007/s11164-012-0517-x

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