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CC BY 4.0 · Synthesis 2023; 55(06): 977-988
DOI: 10.1055/s-0042-1751382
paper

The Synthesis of Novel 7-(Substituted benzyl)-4,5-dihydro[1,2,3]triazolo[1,5-a]pyrazin-6(7H)-ones via Tandem Ugi–Huisgen Reactions

Nazariy T. Pokhodylo  ∗
a   Department of Organic Chemistry, Ivan Franko National University of Lviv, Kyryla i Mefodiya, 6, Lviv, 79005, Ukraine
,
Mykola A. Тupychak
a   Department of Organic Chemistry, Ivan Franko National University of Lviv, Kyryla i Mefodiya, 6, Lviv, 79005, Ukraine
,
Evgeny A. Goreshnik
b   Department of Inorganic Chemistry and Technology, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia
,
Mykola D. Obushak
a   Department of Organic Chemistry, Ivan Franko National University of Lviv, Kyryla i Mefodiya, 6, Lviv, 79005, Ukraine
› Institutsangaben
The authors are grateful to the Ministry of Education and Science of Ukraine for financial support of this project (Grant No. 0121U107777).
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Abstract

A convenient method for the synthesis of 2-azido-3-arylpropanoic acids via the Meerwein halogenoarylation reaction of acrylic acid esters with diazonium salts, subsequent nucleophilic substitution of the halogen by an azide, and saponification is developed. The newly formed 2-azido-3-arylpropanoic acids react under the conditions of non-catalytic four-component Ugi reactions, leading to the formation of α-azidoamides in good yields. The use of propargylamine as the amine component allows the formation of Ugi adducts with azide and acetylene motifs ready for intramolecular 1,3-dipolar Huisgen cycloaddition to give the [1,2,3]triazolo[1,5-a]pyrazine annulated system. The Ugi reaction is found to give 2-azido-3-aryl-N-(2-oxo-1,2-disubstituted ethyl)-N-(prop-2-yn-1-yl)propanamides at room temperature without azide–alkyne cycloaddition. These dipeptides are converted into 4,5-dihydro[1,2,3]triazolo[1,5-a]pyrazin-6(7H)-ones in near quantitative yields by heating in toluene. However, when the Ugi reaction is carried out by heating, it results in a one-pot Ugi–Huisgen tandem reaction leading to 4,5-dihydro[1,2,3]triazolo[1,5-a]pyrazin-6(7H)-ones in excellent yields. Moreover, the possibility of the incorporation of a bromovinyl fragment (the synthetic equivalent of an acetylene fragment) via the aldehyde component of the Ugi reaction is demonstrated in an alternative preparation of the [1,2,3]triazolo[1,5-a]pyrazine system.

Key words

azides - 1,2,3-triazoles - [1,2,3]triazolo[1,5-a]pyrazines - Ugi reaction - Huisgen cycloaddition - one-pot - Meerwein reaction

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751382.
  • Supporting Information


Publikationsverlauf

Eingereicht: 02. September 2022

Angenommen nach Revision: 27. September 2022

Artikel online veröffentlicht:
09. November 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by/4.0/)

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