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A simple method for the synthesis of N-difluoromethylated pyridines and 4-pyridones/quinolones by using BrCF₂COOEt as the difluoromethylation reagent.

ABSTRACT: We describe a novel transition metal-free method for the synthesis of N-difluoromethylated pyridines and 4-pyridones/quinolones by using readily available ethyl bromodifluoroacetate as a fluorine source. The formation of N-difluoromethylated pyridines involves a two-step process in which N-alkylation by ethyl bromodifluoroacetate is followed by in situ hydrolysis of the ester and decarboxylation. Besides optimizing the N-difluoromethylation conditions and assessing the influence of steric and electronic effects on the outcome of the reaction, we have synthesized the N-difluoromethylated analogues of two fluorophores and demonstrated that their spectroscopic properties can be improved through replacement of N-CH₃ group by N-CF₂H.

SUBMITTER: Gandioso A

PROVIDER: S-EPMC9056270 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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A simple method for the synthesis of N-difluoromethylated pyridines and 4-pyridones/quinolones by using BrCF2COOEt as the difluoromethylation reagent.

Gandioso Albert A El Fakiri Mohamed M Rovira Anna A Marchán Vicente V

RSC advances 20200813 50

We describe a novel transition metal-free method for the synthesis of N-difluoromethylated pyridines and 4-pyridones/quinolones by using readily available ethyl bromodifluoroacetate as a fluorine source. The formation of N-difluoromethylated pyridines involves a two-step process in which N-alkylation by ethyl bromodifluoroacetate is followed by in situ hydrolysis of the ester and decarboxylation. Besides optimizing the N-difluoromethylation conditions and asses ...[more]

PMID: 35518226

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