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Updated: Jun 29, 2025

Preparation of Binary and Ternary Deep Eutectic Systems
Published on: October 31, 2019
A Sustainable Synthetic Approach to Tacrine and Cholinesterase Inhibitors in Deep Eutectic Solvents under Aerobic
Luciana Cicco1, Filippo Maria Perna1, Vito Capriati1
1Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Consorzio Interuniversitario Nazionale "Metodologie e Processi Innovativi di Sintesi" (C.I.N.M.P.I.S.), Via E. Orabona 4, I-70125 Bari, Italy.
Abstract:
An enhanced, sustainable, and efficient method for synthesizing tacrine, achieving a 98% yield, has been developed by replacing volatile organic compounds with more eco-friendly solvents such as deep eutectic solvent (DESs). The optimized protocol scales easily to 3 g of substrate without yield loss and extends successfully to tacrine derivatives with reduced hepatotoxicity. Particularly notable is the synthesis of novel triazole-based derivatives, yielding 90-95%, by integrating an in situ preparation of aryl azides in DESs with N-propargyl-substituted tacrine derivatives. Quantitative metrics validate the green aspects of the reported drug development processes.
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