Cargando…

Benzylic deuteration of alkylnitroaromatics via amine‐base catalysed exchange with deuterium oxide

This paper describes the deuterium‐labelling of alkylnitroaromatics by base‐catalysed exchange with deuterium oxide. As the alkyl protons alpha to the aromatic ring are the most acidic sites in the molecule, regioselective hydrogen isotope exchange at this benzylic location leads to a regiospecifica...

Descripción completa

Detalles Bibliográficos
Autores principales: Maddocks, Stephen, Samuri, Nurul F., Ridge, Katerina, Cunningham, Ian D., Lockley, William J. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10107807/
https://www.ncbi.nlm.nih.gov/pubmed/36453978
http://dx.doi.org/10.1002/jlcr.4008
_version_ 1785026687429246976
author Maddocks, Stephen
Samuri, Nurul F.
Ridge, Katerina
Cunningham, Ian D.
Lockley, William J. S.
author_facet Maddocks, Stephen
Samuri, Nurul F.
Ridge, Katerina
Cunningham, Ian D.
Lockley, William J. S.
author_sort Maddocks, Stephen
collection PubMed
description This paper describes the deuterium‐labelling of alkylnitroaromatics by base‐catalysed exchange with deuterium oxide. As the alkyl protons alpha to the aromatic ring are the most acidic sites in the molecule, regioselective hydrogen isotope exchange at this benzylic location leads to a regiospecifically deuterated product. The exchange labelling takes place in good yields and with high atom% abundance in the presence of an appropriate nitrogen base. Alkylated 2,4‐dinitrobenzenes deuterate at room temperature under catalysis by triethylamine, whilst alkylated 2‐nitro‐ or 4‐nitrobenzenes and related mono‐nitroaromatics require higher temperatures and catalysis by 1,5‐diazobicyclo[4.3.0]non‐5‐ene (DBN). The labelling reactions require an inert gas atmosphere, but otherwise are simple and high yielding with no obvious byproducts. Those compounds in which the benzylic protons are in an ortho‐orientation with respect to the nitro group label somewhat more slowly than the analogues where there is a para relationship. In addition, higher alkyl homologues undergo benzylic deuteration at slower rates than methyl.
format Online
Article
Text
id pubmed-10107807
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-101078072023-04-18 Benzylic deuteration of alkylnitroaromatics via amine‐base catalysed exchange with deuterium oxide Maddocks, Stephen Samuri, Nurul F. Ridge, Katerina Cunningham, Ian D. Lockley, William J. S. J Labelled Comp Radiopharm Research Article This paper describes the deuterium‐labelling of alkylnitroaromatics by base‐catalysed exchange with deuterium oxide. As the alkyl protons alpha to the aromatic ring are the most acidic sites in the molecule, regioselective hydrogen isotope exchange at this benzylic location leads to a regiospecifically deuterated product. The exchange labelling takes place in good yields and with high atom% abundance in the presence of an appropriate nitrogen base. Alkylated 2,4‐dinitrobenzenes deuterate at room temperature under catalysis by triethylamine, whilst alkylated 2‐nitro‐ or 4‐nitrobenzenes and related mono‐nitroaromatics require higher temperatures and catalysis by 1,5‐diazobicyclo[4.3.0]non‐5‐ene (DBN). The labelling reactions require an inert gas atmosphere, but otherwise are simple and high yielding with no obvious byproducts. Those compounds in which the benzylic protons are in an ortho‐orientation with respect to the nitro group label somewhat more slowly than the analogues where there is a para relationship. In addition, higher alkyl homologues undergo benzylic deuteration at slower rates than methyl. John Wiley and Sons Inc. 2022-12-16 2023-01 /pmc/articles/PMC10107807/ /pubmed/36453978 http://dx.doi.org/10.1002/jlcr.4008 Text en © 2022 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Maddocks, Stephen
Samuri, Nurul F.
Ridge, Katerina
Cunningham, Ian D.
Lockley, William J. S.
Benzylic deuteration of alkylnitroaromatics via amine‐base catalysed exchange with deuterium oxide
title Benzylic deuteration of alkylnitroaromatics via amine‐base catalysed exchange with deuterium oxide
title_full Benzylic deuteration of alkylnitroaromatics via amine‐base catalysed exchange with deuterium oxide
title_fullStr Benzylic deuteration of alkylnitroaromatics via amine‐base catalysed exchange with deuterium oxide
title_full_unstemmed Benzylic deuteration of alkylnitroaromatics via amine‐base catalysed exchange with deuterium oxide
title_short Benzylic deuteration of alkylnitroaromatics via amine‐base catalysed exchange with deuterium oxide
title_sort benzylic deuteration of alkylnitroaromatics via amine‐base catalysed exchange with deuterium oxide
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10107807/
https://www.ncbi.nlm.nih.gov/pubmed/36453978
http://dx.doi.org/10.1002/jlcr.4008
work_keys_str_mv AT maddocksstephen benzylicdeuterationofalkylnitroaromaticsviaaminebasecatalysedexchangewithdeuteriumoxide
AT samurinurulf benzylicdeuterationofalkylnitroaromaticsviaaminebasecatalysedexchangewithdeuteriumoxide
AT ridgekaterina benzylicdeuterationofalkylnitroaromaticsviaaminebasecatalysedexchangewithdeuteriumoxide
AT cunninghamiand benzylicdeuterationofalkylnitroaromaticsviaaminebasecatalysedexchangewithdeuteriumoxide
AT lockleywilliamjs benzylicdeuterationofalkylnitroaromaticsviaaminebasecatalysedexchangewithdeuteriumoxide