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Synthesis 2011(8): 1243-1248  
DOI: 10.1055/s-0030-1258470
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Multigram Synthesis of 1-(Difluoromethyl)imidazoles and -benzimidazoles

Vadym Levterova, Oleksandr O. Grygorenko*a,b, Pavel K. Mykhailiuk*a,b, Andrey A. Tolmacheva,b
a Enamine Ltd., Alexandra Matrosova Street 23, 01103 Kiev, Ukraine
b Department of Chemistry, Kiev National Taras Shevchenko University, Volodymyrska Street 64, 01033 Kiev, Ukraine
Fax: +380(44)2351273; e-Mail: gregor@univ.kiev.ua; e-Mail: pavel.mykhailiuk@gmail.com;
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Publication History

Received 30 November 2010
Publication Date:
10 March 2011 (online)

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Abstract

An expedient approach to the difluoromethylation of imidazoles­ and benzimidazoles has been developed. The key feature of the procedure is the gradual generation of the difluoromethylation reagent in the reaction mixture, which is achieved by the simultaneous addition of chlorodifluoromethane and alkali. The method is applicable to functionalized substrates and allows the corresponding 1-(difluoromethyl)imidazoles and -benzimidazoles to be prepared in 60-95% yield on a hundred-gram scale.

Key words

fluorine compounds - heterocycles - imidazoles - benzimidazoles - difluoromethylation

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23

We did not consider the NaH-THF system used in one of the reports (see ref.¹5) due to the high flammability of the reagent, especially on a multigram scale.