Synthesis of 3-Cyano-2-fluoropyridines

Abstract

The synthesis of 3-cyano-2-fluoropyridines from readily available precursors was achieved via nucleophilic substitution of a leaving group in the 2-postion with KF or Bu4NF in polar aprotic solvents such as DMF and DMSO. Ionic tetrahydrothiophenium fragment is the most effective leaving group, the methanesulfonyl moiety is a somewhat less effective, and Brand Cl- are the least effective. Relatively mild conditions of the reaction between (2- pyridyl)-tetrahydrothiophenium salts and KF, as well as the convenience of one-step synthesis of these salts from 2(1H)-pyridinethiones, make these salts the compounds of choice for the preparation of ring-fluorinated pyridines.