One-pot Microwave-assisted Synthesis of Pyrazolopyrimidines from 5-Amino-4-thiocyanato-pyrazoles with Vilsmeier Reagent

A facile one-pot microwave-assisted synthesis of pyrazolopyrimidines and pyrazolothiazoles was developed by reacting 5-amino-4-thiocyanato-pyrazoles with Vilsmeier Reagent (PBr3/foramide). The reaction gave the corresponding pyrazolopyrimidines as major products in good yields (61-85 %) and pyrazolothiazoles as minor products (11-23 % yields). The plausible reaction mechanism was proposed to account for the transformation of pyrazolopyrimidines and pyrazolothiazoles through two paths A and B. In path A, the reaction leading to the formation of pyrazolopyrimidines proceeded through four sequential steps, including acidic catalyzed cascade dethiocyanation/cyclization, Vilsmeier reaction, ring expansion, and deamination. The formation of the pyrazolothiazole in path B was caused by the nucleophilic heterocyclization reaction involving the sulfur nucleophilic reaction of thiocyanate (R-SC equivalent to N) and the departure of a cyanamide. Based on the experimental results, we observed that the path A for the formation of pyrazolopyrimidines was more favorable.