Synthesis of N-(Alkyloxy)pyridine-2(1H)-thiones: Alkylations of the Ambident Nucleophile Pyridine-2(1H)-thione N-Oxide and Attempted Isomerizations of 2-(Alkylthio)pyridine N-Oxide

Article abstract of DOI:10.1021/jo00279a020

Two possible routes for the preparation of N-(alkyloxy)pyridine-2(1H)-thiones (1), namely, nucleophilic substitution of pyridine-2(1H)-thione N-oxide anion (5) and the thermal rearrangemet of isomeric 2-(alkylthio)pyridine N-oxides (6), have been investigated.The ambident nucleophilic anion 5 undergoes both O- and S-alkylation upon treatment with alkyl bromides, chlorides, mesylates, or triflates; the regioselectivity is influenced by the temperature and the nature of the solvent, counterion, alkyl group, and leaving group.Details of the synthesis and characterization of a number of N-(alkyloxy)pyridine-2(1H)-thiones (1) (alkyl = n-propyl, n-butyl, benzyl, neopentyl, methoxymethyl, isopropyl, cyclopentyl, cyclohexyl, and tert-butyl) and 2-(alkylthio)pyridine N-oxides (6) (alkyl = n-propyl, n-butyl, and benzyl) are reported.Attempts to prepare 1 from the thermal rearrangement of 6 were unsuccessful, as 6 proved to be the thermodynamically stable isomer; the benzyl sulfide 1c was converted into its isomer 6c upon heating.Preliminary studies show that this rearrangement occurs in competition with N-O bond homolysis and appears to be catalyzed by molecular oxygen.