Azoles. Part 8. Metallation and bromine → lithium exchange reactions of polyhalogenothiazoles

Abstract

2,4-Dichloro- and 2,4-dibromo-thiazole were deprotonated at position-5 with LiNPr₂ⁱ in THF at –78 °C and the resulting lithium compound was quenched with various reagents, to yield various trisubstituted thiazoles. 2,5-Dibromo-4-chlorothiazole reacted with n-butyl lithium in THF at –78 °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-Dibromo-thiazole 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 °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 ¹H NMR spectroscopy. The 5-bromine-atom is the most reactive and greater selectivity is obtained with methyllithium.