Catalyst-Free Green Synthesis of Pyrazole Derivatives: A Sustainable Approach

Abstract: Pyrazole derivatives attract significant interest because of their biological and pharmacological activities. This review covers catalyst-free methods for synthesizing pyrazole heterocycles. Several environmentally friendly protocols, including one-pot and multicomponent reactions, have been developed using eco-friendly solvents, such as water, ethanol, glycerol, or polyethylene glycol. Notably, these reactions are performed efficiently without the use of harmful transition metal catalysts, yielding excellent results, short reaction times, and a simple workup. These methods, utilizing both bottom-up and top-down approaches, have been optimized with techniques, such as ultrasound-assisted synthesis, ball milling, and thermal activation to improve sustainability and energy efficiency. The lack of toxic reagents and the use of biodegradable media make these processes suitable for industrial and pharmaceutical use. Overall, this review highlights the effectiveness of catalyst-free methods as strong strategies for the environmentally friendly synthesis of various biologically active pyrazole-based structures.