AZOLES .8. METALATION AND BROMINE-] LITHIUM EXCHANGE-REACTIONS OF POLYHALOGENOTHIAZOLES

2,4-Dichloro- and 2,4-dibromo-thiazole were deprotonated at position-5 with LiNPr2i in THF at -78-degrees-C and the resulting lithium compound was quenched with various reagents, to yield various trisubstituted thiazoles. 2,5-Dibromo-4-chlorothiazole reacted with n-butyllithium in THF at -78-degrees-C at position-5 and the resulting lithium derivative gave 2-bromo-4-chloro-5-substituted thiazoles when quenched with the appropriate reagent. Both the 2- and 5-bromine-atoms were reactive in diethyl ether. 2,5-Dibromothiazole failed to deprotonate at position-4 under various reaction conditions, whereas treatment of 2,4,5-tribromothiazole with 1 mole equivalent of n-butyllithium in THF at -90-degrees-C, followed by addition of dimethyl disulfide after 30 min, gave a high yield of the 2,5-bis(methylthio)-compound. The tribromo-compound was also treated with 1 mole equivalent of n-butyllithium or methyllithium under various reaction conditions and the products formed after hydrolysis were analysed by H-1 NMR spectroscopy. The 5-bromine-atom is the most reactive and greater selectivity is obtained with methyllithium.