Abstract: Traditional organic solvents often pose environmental and toxicity concerns in the synthesis of active pharmaceutical ingredients (APIs), the cornerstone of pharmaceutical drugs. Deep eutectic solvents (DESs), characterized by their versatility and efficiency as both solvents and catalysts, offer a promising alternative for sustainable drug synthesis. The dual capacity of DESs as green solvents and catalysts holds significant potential for enhancing the sustainability and efficiency of drug-synthesis processes. This study comprehensively explores the synthesis of various drug scaffolds, including those relevant to central nervous system (CNS) disorders, inflammation, cancer, and other therapeutic areas. By examining reaction mechanisms and parameters, the research provides valuable insights into the high yields achievable using DESs. The review also highlights the effectiveness of different types of DESs in drug synthesis, including natural DESs (NADESs), reactive DESs (RDESs), water-based DESs (WDESs), and ionic liquid-based DESs (ILDESs). Among these, NADESs are the most commonly used, with choline chloride (ChCl)–based DESs standing out as the most popular, utilized in over 30 different combinations mentioned in the review. The most frequently used ChCl-based DES was ChCl/urea, followed by ChCl/taurine. The collected data provide important information, including optimal DES combinations, ratios, concentrations, and reaction conditions for producing drug scaffolds with the highest yields. The numerous synthetic results presented in this article demonstrate that widespread adoption of DESs in both research and industrial settings could have a significant positive environmental impact, owing to their low toxicity, renewability, affordability, and energy-efficient catalytic properties. This review offers a thorough exploration of the use of DESs in drug synthesis. By analyzing key chemical equations, reaction procedures, reaction mechanisms, yields, and critical parameters from reported studies, this report aims to present a valuable resource to guide researchers in optimizing synthetic strategies and advancing the application of DESs in pharmaceutical chemistry.
Mukhtar et al. (Tue,) studied this question.