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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9268355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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