Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines

The Friedländer synthesis offers efficient access to substituted quinolines from 2-aminobenzaldehydes and activated ketones in the presence of a base. The disadvantage of this procedure lies in the fact that relatively few 2-aminobenzaldehyde derivatives are readily available. To overcome this probl...

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Autores principales: Fobi, Kwabena, Bunce, Richard A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268355/
https://www.ncbi.nlm.nih.gov/pubmed/35807369
http://dx.doi.org/10.3390/molecules27134123
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author Fobi, Kwabena
Bunce, Richard A.
author_facet Fobi, Kwabena
Bunce, Richard A.
author_sort Fobi, Kwabena
collection PubMed
description The Friedländer synthesis offers efficient access to substituted quinolines from 2-aminobenzaldehydes and activated ketones in the presence of a base. The disadvantage of this procedure lies in the fact that relatively few 2-aminobenzaldehyde derivatives are readily available. To overcome this problem, we report a modification of this process involving the in situ reduction of 2-nitrobenzaldehydes with Fe/AcOH in the presence of active methylene compounds (AMCs) to produce substituted quinolines in high yields. The conditions are mild enough to tolerate a wide range of functionality in both reacting partners and promote reactions not only with phenyl and benzyl ketones, but also with β-keto-esters, β-keto-nitriles, β-keto-sulfones and β-diketones. The reaction of 2-nitroaromatic ketones with unsymmetrical AMCs is less reliable, giving a competitive formation of substituted quinolin-2(1H)-ones from the cyclization of the Z Knoevenagel intermediate which appears to be favored when certain large groups are adjacent to the AMC ketone carbonyl.
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spelling pubmed-92683552022-07-09 Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines Fobi, Kwabena Bunce, Richard A. Molecules Article The Friedländer synthesis offers efficient access to substituted quinolines from 2-aminobenzaldehydes and activated ketones in the presence of a base. The disadvantage of this procedure lies in the fact that relatively few 2-aminobenzaldehyde derivatives are readily available. To overcome this problem, we report a modification of this process involving the in situ reduction of 2-nitrobenzaldehydes with Fe/AcOH in the presence of active methylene compounds (AMCs) to produce substituted quinolines in high yields. The conditions are mild enough to tolerate a wide range of functionality in both reacting partners and promote reactions not only with phenyl and benzyl ketones, but also with β-keto-esters, β-keto-nitriles, β-keto-sulfones and β-diketones. The reaction of 2-nitroaromatic ketones with unsymmetrical AMCs is less reliable, giving a competitive formation of substituted quinolin-2(1H)-ones from the cyclization of the Z Knoevenagel intermediate which appears to be favored when certain large groups are adjacent to the AMC ketone carbonyl. MDPI 2022-06-27 /pmc/articles/PMC9268355/ /pubmed/35807369 http://dx.doi.org/10.3390/molecules27134123 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fobi, Kwabena
Bunce, Richard A.
Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines
title Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines
title_full Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines
title_fullStr Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines
title_full_unstemmed Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines
title_short Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines
title_sort domino nitro reduction-friedländer heterocyclization for the preparation of quinolines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268355/
https://www.ncbi.nlm.nih.gov/pubmed/35807369
http://dx.doi.org/10.3390/molecules27134123
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