A Facile Synthetic Approach to 3-Halo-4-substituted-1,5-dihydro-4H-1,2,4-triazoline-5-thiones Based on Retro-Michael Addition

doi:10.1007/s40242-017-7044-5

Chemical Research in Chinese Universities ›› 2017, Vol. 33 ›› Issue (4): 587-593.doi: 10.1007/s40242-017-7044-5

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A Facile Synthetic Approach to 3-Halo-4-substituted-1,5-dihydro-4H-1,2,4-triazoline-5-thiones Based on Retro-Michael Addition

TIAN He^1,2, LIU Yuqiang², LI Xingwei², XIE Yafei², LIU Changying², WANG Jianwu¹, ZHAO Guilong²

1. School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. China;
2. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, P. R. China

Received:2016-12-14 Revised:2017-02-14 Online:2017-08-01 Published:2017-04-05
Contact: WANG Jianwu, ZHAO Guilong E-mail:zhao_guilong@126.com;jwwang@sdu.edu.cn
Supported by:
Supported by the Key Projects of Tianjin Science and Technology Support Plan，China（No.16YFZCSY00910），the Tianjin Natural Science Foundation，China（Nos.12JCYBJC18800，13JCQNJC13700） and the Shandong Natural Science Foundation，China（No.ZR2015BM028）.

Abstract

Abstract:

A facile 3-step synthetic approach to 3-halo-4-substituted-1,5-dihydro-4H-1,2,4-triazoline-5-thiones (1a-1k) from corresponding unhalogenated 8a-8i was developed based on the strategy of retro-Michael addition, with the key steps being regioselective S-alkylation of compounds 8a-8i with ethyl 3-iodopropionate(12c) and alkaline cleavage of the propionate protecting group via retro-Michael addition. The synthetic approach was characterized by simplicity of operation and wide substrate scope.

Key words: Synthetic approach, Protecting group, Triazole, Halogenation, Regioselectivity, Retro-Michael addition

TIAN He, LIU Yuqiang, LI Xingwei, XIE Yafei, LIU Changying, WANG Jianwu, ZHAO Guilong. A Facile Synthetic Approach to 3-Halo-4-substituted-1,5-dihydro-4H-1,2,4-triazoline-5-thiones Based on Retro-Michael Addition[J]. Chemical Research in Chinese Universities, 2017, 33(4): 587-593.

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A Facile Synthetic Approach to 3-Halo-4-substituted-1,5-dihydro-4H-1,2,4-triazoline-5-thiones Based on Retro-Michael Addition

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