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 hyd...

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Main Authors: Lim, F., Tan, L., Tiekink, E., Dolzhenko, Anton
Format: Journal Article
Published: Royal Society of Chemistry 2018
Online Access:http://hdl.handle.net/20.500.11937/69766
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author Lim, F.
Tan, L.
Tiekink, E.
Dolzhenko, Anton
author_facet Lim, F.
Tan, L.
Tiekink, E.
Dolzhenko, Anton
author_sort Lim, F.
building Curtin 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. Graphical abstract: Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides and their tautomerism
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spelling curtin-20.500.11937-697662019-01-29T05:34:53Z Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides and their tautomerism Lim, F. Tan, L. Tiekink, E. Dolzhenko, Anton 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. Graphical abstract: Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides and their tautomerism 2018 Journal Article http://hdl.handle.net/20.500.11937/69766 10.1039/c8ra04576c http://creativecommons.org/licenses/by/3.0/ Royal Society of Chemistry fulltext
spellingShingle Lim, F.
Tan, L.
Tiekink, E.
Dolzhenko, Anton
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
url http://hdl.handle.net/20.500.11937/69766