4 -Bromoimidazole, halogen-metal exchange

However, the real advantage of halogen-metal exchange is that metala-tion can now occur at the 5-position without the need to protect the 2-position. Thus the lithiation of l-methyl-5-bromoimidazole at -80°C gave the 5-lithio derivative, which was successfully reacted with acetaldehyde at that temperature (Scheme 47) (73JOC3762). The choice of halogen... 

Careful choice of reaction conditions allows 2-lithiation even in the presence of groups susceptible to attack by the reagent. At — 100°C in THE 4,5-dicyano-l-methylimidazole forms the 2-lithio compound at — 80°C butyllithium attacks one of the nitrile functions <92JHCI09I>. Even 4- and 5-chloroimidazoles can be 2-lithiated, as can 4-bromoimidazole, but when the 2-position is blocked halogen-metal exchange and direct lithiation can occur elsewhere <94JMC332>. 

Metal-halogen exchange of 4(5)-bromoimidazole nsing n-bntyllithium, or of 4(5)-iodoimidazole, using methylmagnesinm chloride with lithinm chloride, " is possible without iV-protection. 

Complementarily, the lithiation of a SEM protected 2-phenylsulfonylimidazole takes place at C-4. Metal-halogen exchange of 4(5)-bromoimidazole is possible without protection. ... 

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