Synthesis of Novel 5-Chlorinated 2-Aminothiophenes Using 2,5-Dimethylpyrrole as an Amine Protecting Group

A new synthetic methodology towards substituted 2-amino-5-chlorothiophenes is described. Compounds of this type are important as building blocks for oligomers used in polymer research. Easily available 2-aminothiophenes underwent Paal-Knorr reaction to protect the free amino group before electrophilic substitution. Although the chlorination was predicted to proceed at the thiophene ring, only free positions of 2,5-dimethylpyrrole were substituted. To direct chlorination to the thiophene ring acetamido derivative was prepared first and then chlorinated. Transamination with hexane-2,5-dione created a 2,5-dimethyl pyrrole ring from the acetamido group. In the final step, after treatment with hydroxylamine dihydrochloride, the pyrrole ring is removed and a free amino group is regenerated.