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Synthesis of dihydroquinazolines from 2-aminobenzylamine: N(3)-aryl derivatives with electron-withdrawing groups

The sequential N-functionalization of 2-aminobenzylamine (2-ABA) followed by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing electron-withdrawing groups. The sequence involves an initial S(N)Ar displacement, N-acylati...

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Autores principales: Gruber, Nadia, Díaz, Jimena E, Orelli, Liliana R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178284/
https://www.ncbi.nlm.nih.gov/pubmed/30344774
http://dx.doi.org/10.3762/bjoc.14.227
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author Gruber, Nadia
Díaz, Jimena E
Orelli, Liliana R
author_facet Gruber, Nadia
Díaz, Jimena E
Orelli, Liliana R
author_sort Gruber, Nadia
collection PubMed
description The sequential N-functionalization of 2-aminobenzylamine (2-ABA) followed by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing electron-withdrawing groups. The sequence involves an initial S(N)Ar displacement, N-acylation and MW-assisted ring closure. Remarkably, the uncatalyzed N-arylation of 2-ABA led to the monosubstitution product using equimolar amounts of both reagents. The individual steps were optimized achieving good to excellent overall yields of the desired heterocycles, avoiding additional protection and deprotection steps. A mechanistic interpretation for the cyclodehydration reaction promoted by trimethylsilyl polyphosphate (PPSE) is also proposed on the basis of literature data and our experimental observations.
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spelling pubmed-61782842018-10-19 Synthesis of dihydroquinazolines from 2-aminobenzylamine: N(3)-aryl derivatives with electron-withdrawing groups Gruber, Nadia Díaz, Jimena E Orelli, Liliana R Beilstein J Org Chem Full Research Paper The sequential N-functionalization of 2-aminobenzylamine (2-ABA) followed by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing electron-withdrawing groups. The sequence involves an initial S(N)Ar displacement, N-acylation and MW-assisted ring closure. Remarkably, the uncatalyzed N-arylation of 2-ABA led to the monosubstitution product using equimolar amounts of both reagents. The individual steps were optimized achieving good to excellent overall yields of the desired heterocycles, avoiding additional protection and deprotection steps. A mechanistic interpretation for the cyclodehydration reaction promoted by trimethylsilyl polyphosphate (PPSE) is also proposed on the basis of literature data and our experimental observations. Beilstein-Institut 2018-09-26 /pmc/articles/PMC6178284/ /pubmed/30344774 http://dx.doi.org/10.3762/bjoc.14.227 Text en Copyright © 2018, Gruber et al. https://creativecommons.org/licenses/by/4.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0). Please note that the reuse, redistribution and reproduction in particular requires that the authors and source are credited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms)
spellingShingle Full Research Paper
Gruber, Nadia
Díaz, Jimena E
Orelli, Liliana R
Synthesis of dihydroquinazolines from 2-aminobenzylamine: N(3)-aryl derivatives with electron-withdrawing groups
title Synthesis of dihydroquinazolines from 2-aminobenzylamine: N(3)-aryl derivatives with electron-withdrawing groups
title_full Synthesis of dihydroquinazolines from 2-aminobenzylamine: N(3)-aryl derivatives with electron-withdrawing groups
title_fullStr Synthesis of dihydroquinazolines from 2-aminobenzylamine: N(3)-aryl derivatives with electron-withdrawing groups
title_full_unstemmed Synthesis of dihydroquinazolines from 2-aminobenzylamine: N(3)-aryl derivatives with electron-withdrawing groups
title_short Synthesis of dihydroquinazolines from 2-aminobenzylamine: N(3)-aryl derivatives with electron-withdrawing groups
title_sort synthesis of dihydroquinazolines from 2-aminobenzylamine: n(3)-aryl derivatives with electron-withdrawing groups
topic Full Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178284/
https://www.ncbi.nlm.nih.gov/pubmed/30344774
http://dx.doi.org/10.3762/bjoc.14.227
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