Nitrothiazoles, reactions with nucleophiles

The reaction of 2-bromo-5-nitrothiazole with weakly basic secondary aliphatic amines gave the expected 2-amino products. The isomeric 5-bromo-2-nitrothiazole with such amines gave mixtures of the expected 5-amino products along with 2-aminated 5-nitrothiazole rearrangement products. A mechanism was proposed which involves the slow thermal isomerisation of the 5-bromo-2-nitrothiazole to the much more reactive 2-bromo isomer which competes, in the case of relatively weak amine nucleophiles, with direct but slow displacement of the 5-bromo group to form the normal displacement product <96JHC1191>. 

A serious limitation of VNS is connected with its mechanism, namely, conversion of intermediate ct adducts into the VNS products via bimolecular base-induced p-elimination. To cause the reaction, it is therefore necessary that these adducts be produced in a reasonable concentration. Indeed, low nucleophilic carbanions, such as dimethyl chloromalonate, do not react with moderately electrophilic nitrobenzene because of unfavorable equilibrium of the addition step, but react nicely with more electrophilic nitrothiazoles (Scheme 8) [34]. 

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