Solvent Dependent Benzylic Radical Bromination of Aromatic Sulfonyl Chlorides

We have studied the solvent dependent radical bromination of toluene sulfonyl chlorides. The use ofacetonitrile allows to avoid chlorinated solvents and to improve the yield and the reproducibility of theprocess. Keywords : Radical bromination, N -bromosuccinimide, benzyl bromide, aromatic sulfonyl chloride.Recently, we developed a series of bradykinin B2receptor antagonists potentially useful for airwaysinflammatory pathologies.[1,2] The central part of thestructure of compounds belonging to this series ischaracterized by the building block 2,4-dichloro-3-methylbenzenesulfonyl, as shown for compound MEN16132 (Scheme 1 ). In the course of our research project, weneeded to assess the synthesis of the said building block andof few analogues differently substituted in the aromatic ring.Therefore we studied a method of radical bromination of 2,4-dichloro-3-methylbenzenesulfonyl chloride ( 1 ) [3] to yield 3-The accepted mechanism is a free-radical process, where N -bromosuccinimide (NBS) is used as a source of low-concentration bromine [5], which produces bromine radicals,initiates the reaction, and consumes the liberated HBr by aionic process. [6] A lot of variants to such process have alsobeen reported, i. e. the use of 2,2'-azobis(2-methylpro-pionitrile) (AIBN) or benzoyl peroxide (Bz