410545-51-6Relevant articles and documents
Practical synthesis of 4-fluoro-2-(methylthio)benzylamine and the corresponding sulfone and sulfonamide
Perlow, Debra S.,Kuo, Michelle S.,Moritz, H. Marie,Wai, John S.,Egbertson, Melissa S.
, p. 1887 - 1897 (2008/02/03)
Practical syntheses of 4-fluoro-2-(methylthio)benzylamine 1 and the corresponding 2-methylsulfonyl analog 2 are reported. The methylthio moiety was introduced regioselectively by two methods. In the first method, metallation of 4-fluoro-2-bromobenzoic acid, followed by treatment with dimethyl disulfide resulted in an easily isolated intermediate, which was suitable for further elaboration to the benzylamine 1. In the second method, selective nucleophilic aromatic substitution of 2,4-difluorobenzonitrile with methanethiolate was explored, and a mechanistic rationale was offered for solvent effects on regioselectivity. Optimized conditions furnished the key 4-fluoro-2-(methylthio) benzonitrile for further functionalization to the 2-methylsulfonyl-4- fluorobenzylamine 2. In addition, the analogous sulfonamide 3 was prepared in a straightforward manner from 5-fluoro-2-methylbenzenesulfonyl chloride. Copyright Taylor & Francis Group, LLC.
