Ultrasound-promoted iodination of pyrazoles in aqueous medium

Abstract

Several pharmacological activities have been devoted to pyrazole containing molecules. In particular, 4-iodopyrazoles have been employed as key starting materials in cross-coupling chemistry and metal-iodine exchange reactions that focus on the synthesis of such biologically important compounds. Unfortunately, existing methods for the synthesis of 4-iodopyrazoles are not in agreement with the environmental requirements due to a series of drawbacks including the use of large excess of reagents, the generation of toxic waste and long reaction times. Recently, we developed a fast and mild reaction condition for the iodination of aromatic compounds using an I 2 /H 2 O 2 system water as a nonflammable and innocuous solvent and ultrasonic irradiation as energy source. In this work, we present the application of this methodology for the iodination of pyrazoles (Scheme). Initially, a series of pyrazoles were efficiently prepared starting from 1,3-dicarbonyl compounds and hydrazines under ultrasonic irradiation. Three examples from the pyrazoles were subjected to the iodination condition shown above. Iodopyrazoles were obtained in 63-65% yields.