An Unexpected and Green Synthetic Protocol for Ethyl 1-Aroyl/Aroylmethyl-5-methyl-3-methylthiopyrazole-4-carboxylates: High Regioselectivity in Alkylation and Acylation Reactions between N-1 and N-2 of a Pyrazole Ring

Two series, totaling twelve, of new compounds, ethyl 1-aroyl/(aroylmethyl)-5-methyl-3-methylthiopyrazole-4-carboxylates (5/6), have been synthesized via highly regioselectively acylation and alkylation reactions of ethyl 3-methyl-5-methylthio-1 H-pyrazole-4-carboxylate (2a) with aroyl chloride (3) and eco-friendly reagents alpha-tosyloxysubstituted acetophenones (4), respectively, and a green protocol has been developed. The acylation reactions were carried out under ultrasound irradiation, and the alkylation reactions were under microwave irradiation and ultrasound irradiation, respectively. Conventional reaction conditions, as well as the use of alpha-bromosubstituted acetophenone (4′) have also been applied in the synthesis of some randomly selected compounds in both series and have generated identical compounds correspondingly. Unexpected structures of compounds were unambiguously determined by X-ray crystallographic analysis.