Synthesis of new thiazole-2, -4, and -5-yl-(amino)methylphosphonates and phosphinates: unprecedented cleavage of thiazole-2 derivatives under acidic conditions

An efficient and reliable synthesis of new thiazole-(amino)methylphosphonic, phosphinic acids, and phosphine oxides is reported. The synthetic protocol is based on nucleophilic addition of phosphorous species to thiazole derived imines. Unexpectedly, it was discovered that heating of thiazole-2-yl-(amino)methylphosphonates and phosphinates with aqueous HCl leads to their decomposition resulting in a rupture of the C–P bond, rejecting of the phosphorus containing fragment and formation of the corresponding secondary N-(thiazole-2-yl-methyl)-alkylamines. Two alternative mechanisms for this cleavage are postulated.