The preparation of novel thiophene-based macrocyclic Mannich bases

A range of macrocyclic thiophene-based Mannich bases containing 10–22-membered rings has been prepared. The starting materials for the synthesis were substances of the type ArO–Z–OAr (where Ar = 2-methoxycarbonyl-3-thienyl and Z = alkyl or heteroalkyl), which were made by the reaction of α,ω-dihalides or -bis(toluene-p-sulfonate)s with two moles of methyl 3-hydroxythiophene-2-carboxylate. Saponification and subsequent decarboxylation of these compounds afforded the corresponding α,ω-bis(3-thienyloxy)alkanes. Macrocyclic Mannich bases were prepared from these ethers by aminomethylation. High dilution conditions were not required in many cases and, in the case of the heteroalkyl-bridged ethers, this is believed to be due to an internal template effect enhancing the yield.