Mild regioselective halogenation of activated pyridines with N-bromosuccinimide

Regioselective mono and dihalogenations of amino, hydroxy and methoxy pyrid ines (2-, 3-, and 4-substituted) as well as 2,6-dimethoxy pyridine with N-b romosuccinimide in different solvents have been studied. Reactivity of the substrates decreases in the order amino > hydroxy > methoxy and regioselect ivity depends on the position of the substituent (2-substituted > 3-substit uted). In most of the cases we obtained monobrominated derivatives regiosel ectively and in high yields. Hydroxy and amino pyridines can also be dibrom inated in almost quantitative yield with 2 equivalents of NBS.