Issue 17, 2021

Studies on chemoselective synthesis of 1,4- and 1,2-dihydropyridine derivatives by a Hantzsch-like reaction: a combined experimental and DFT study

Abstract

In the experimental process of preparing diethyl 3,5-dicarboxylate-1,4-dihydropyridine (1,4-DHP) by a Hantzsch-like reaction, it was found that a by-product named diethyl 3,5-dicarboxylate-1,2-dihydropyridine (1,2-DHP) was produced in the reaction. To discuss this phenomenon, the effects of the reaction conditions on the yield ratio of 1,4-DHP and 1,2-DHP were studied by using aromatic amines, aromatic aldehydes and ethyl propiolate as raw materials. The mechanisms for the formation of 1,4-DHP and 1,2-DHP were proposed based on the isolated intermediate named diethyl 4-((phenylamino)methylene)pent-2-enedioate generated by the Michael addition of aniline and ethyl propiolate. The transition state structures were optimized and the reaction energy barriers of intermediates in the speculated mechanisms were calculated by DFT calculations at the M062X/def2TZVP//B3LYP-D3/def-SVP level. It was found that the reaction energy barriers and dominant configurations of intermediates IM2 and IM3′ are the determinants for the chemoselectivity. Together, these results demonstrate a high chemoselectivity in the synthesis of 1,4-DHPs and 1,2-DHPs by a Hantzsch-like reaction and that 1,4-DHPs and 1,2-DHPs can be easily obtained under different conditions.

Graphical abstract: Studies on chemoselective synthesis of 1,4- and 1,2-dihydropyridine derivatives by a Hantzsch-like reaction: a combined experimental and DFT study

Supplementary files

Article information

Article type
Paper
Submitted
18 nóv. 2020
Accepted
29 mar. 2021
First published
30 mar. 2021

Org. Biomol. Chem., 2021,19, 3882-3892

Studies on chemoselective synthesis of 1,4- and 1,2-dihydropyridine derivatives by a Hantzsch-like reaction: a combined experimental and DFT study

P. Li, S. Wang, N. Tian, H. Yan, J. Wang and X. Song, Org. Biomol. Chem., 2021, 19, 3882 DOI: 10.1039/D0OB02289F

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