Novel green protocols for the synthesis of tetrahydropyrazolopyrazolones

Abstract

1,3 – Dipolar cycloadditions represent an important method for obtaining novel bicyclic heterocycles which is of great importance due to their medicinal application and diverse bioactivity such as antitumor, antibacterial and etc. The most suitable way for the synthesis of bicyclic heterocycles such as pyrazolopyrazolones is based on dipolar cycloaddition of azomethine imines and enones. This reaction was explored to develop more sustainable protocols by using less toxic chemicals and different sources of energy. Herein novel green protocols for the synthesis of tetrahydropyrazolopyrazolones are presented. These green protocols avoid hazardous AlCl3 and CH2Cl2 which were used until now, and implement green sources of irradiation. In this research, acetic acid has proved itself as a great catalyst for this type of reaction. Different azomethine imines and enones were submitted to the reaction in the presence of acetic acid for 12 h. A series of ten tetrahydropyrazolopyrazolones is successfully synthesized. The impact of ultrasound and microwave irradiation was also investigated. Three novel protocols for the synthesis of tetrahydropyrazolopyrazolones were established. The best results with significant improvement in yield, reaction time, and cleaner reaction conditions were observed when acetic acid and microwave irradiation were used. These novel protocols for the synthesis of pyrazolopyrazolones based on the usage of acetic acid as a catalyst and ultrasound and microwave irradiation represent a noteworthy advancement in research of sustainable methods for obtaining heterocycles.