Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides and their tautomerism

Two complementary pathways for the preparation of N-substituted 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides (5) were proposed and successfully realized in the synthesis of 20 representative examples. These methods use the same types of starting materials viz. succinic anhydride, aminoguanidine...

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Main Authors: Lim, Felicia Phei Lin, Tan, Lin Yuing, Tiekink, Edward R. T. *, Dolzhenko, Anton V
Format: Article
Language:English
Published: Royal Society of Chemistry 2018
Subjects:
Online Access:http://eprints.sunway.edu.my/846/
http://eprints.sunway.edu.my/846/1/Tiekink%20Synthesis%20of%203-5.pdf
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author Lim, Felicia Phei Lin
Tan, Lin Yuing
Tiekink, Edward R. T. *
Dolzhenko, Anton V
author_facet Lim, Felicia Phei Lin
Tan, Lin Yuing
Tiekink, Edward R. T. *
Dolzhenko, Anton V
author_sort Lim, Felicia Phei Lin
building SU Institutional Repository
collection Online Access
description Two complementary pathways for the preparation of N-substituted 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides (5) were proposed and successfully realized in the synthesis of 20 representative examples. These methods use the same types of starting materials viz. succinic anhydride, aminoguanidine hydrochloride, and a variety of amines. The choice of the pathway and sequence of the introduction of reagents to the reaction depended on the amine nucleophilicity. The first pathway started with the preparation of N-guanidinosuccinimide, which then reacted with amines under microwave irradiation to afford 5. The desired products were successfully obtained in the reaction with aliphatic amines (primary and secondary) via a nucleophilic opening of the succinimide ring and the subsequent recyclization of the 1,2,4- triazole ring. This approach however failed when less nucleophilic aromatic amines were used. Therefore, an alternative pathway, with the initial preparation of N-arylsuccinimides and their subsequent reaction with aminoguanidine hydrochloride under microwave irradiation, was applied. The annular prototropic tautomerism in the prepared 1,2,4-triazoles 5 was studied using NMR spectroscopy and X-ray crystallography.
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spelling sunway-8462020-10-07T09:02:02Z http://eprints.sunway.edu.my/846/ Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides and their tautomerism Lim, Felicia Phei Lin Tan, Lin Yuing Tiekink, Edward R. T. * Dolzhenko, Anton V QD Chemistry Two complementary pathways for the preparation of N-substituted 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides (5) were proposed and successfully realized in the synthesis of 20 representative examples. These methods use the same types of starting materials viz. succinic anhydride, aminoguanidine hydrochloride, and a variety of amines. The choice of the pathway and sequence of the introduction of reagents to the reaction depended on the amine nucleophilicity. The first pathway started with the preparation of N-guanidinosuccinimide, which then reacted with amines under microwave irradiation to afford 5. The desired products were successfully obtained in the reaction with aliphatic amines (primary and secondary) via a nucleophilic opening of the succinimide ring and the subsequent recyclization of the 1,2,4- triazole ring. This approach however failed when less nucleophilic aromatic amines were used. Therefore, an alternative pathway, with the initial preparation of N-arylsuccinimides and their subsequent reaction with aminoguanidine hydrochloride under microwave irradiation, was applied. The annular prototropic tautomerism in the prepared 1,2,4-triazoles 5 was studied using NMR spectroscopy and X-ray crystallography. Royal Society of Chemistry 2018-06-12 Article PeerReviewed text en http://eprints.sunway.edu.my/846/1/Tiekink%20Synthesis%20of%203-5.pdf Lim, Felicia Phei Lin and Tan, Lin Yuing and Tiekink, Edward R. T. * and Dolzhenko, Anton V (2018) Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides and their tautomerism. RSC Advances, 8 (40). pp. 22351-22360. ISSN 2046-2069 http://www.rsc.li/rsc-advances DOI: 10.1039/c8ra04576c
spellingShingle QD Chemistry
Lim, Felicia Phei Lin
Tan, Lin Yuing
Tiekink, Edward R. T. *
Dolzhenko, Anton V
Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides and their tautomerism
title Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides and their tautomerism
title_full Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides and their tautomerism
title_fullStr Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides and their tautomerism
title_full_unstemmed Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides and their tautomerism
title_short Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides and their tautomerism
title_sort synthesis of 3-(5-amino-1h-1,2,4-triazol-3-yl) propanamides and their tautomerism
topic QD Chemistry
url http://eprints.sunway.edu.my/846/
http://eprints.sunway.edu.my/846/
http://eprints.sunway.edu.my/846/
http://eprints.sunway.edu.my/846/1/Tiekink%20Synthesis%20of%203-5.pdf