A Sustainable Synthetic Approach to Tacrine and Cholinesterase Inhibitors in Deep Eutectic Solvents under Aerobic Conditions

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.

Iron‐Based Deep Eutectic Solvents: Key Players for Amide and Sulfonamide Synthesis and Alcohol Oxidation

“…The few reported applications encompass: (a) the synthesis of 2,3dihydrofurans; [7] (b) the synthesis of pillar[n]arenes; [8] (c) the depolymerization of polyethylene terephthalate; [9] (d) the catalytic conversion of lignin into methyl p-hydroxycinnamate; [10] (e) the cellulose conversion into gluconic acid; [11] (f) the hydration of alkynes to carbonyl compounds; [12] (g) the Meyer-Schuster rearrangement of propargylic alcohols at room temperature and under aerobic conditions; [13] (h) benzylation reactions mediated by FeCl 3 -based DESs; [14] and (i) the synthesis of tacrine and cholinesterase inhibitors. [15] The selective N-alkylation of primary amides and sulfonamides as well as the oxidation of alcohols to carbonyl compounds are sought-after transformations in organic chemistry. These processes yield crucial products serving as important precursors and intermediates in drug synthesis and discovery, as well as in the production of fine chemicals, plasticizers, synthetic materials, vitamins, and fragrances.…”

Sustainable Synthesis of the Active Pharmaceutical Ingredient Atenolol in Deep Eutectic Solvents

“…Although the efficient methods that lead to the formation of enantiomerically pure ( S )-atenolol can be of interest to the pharmaceutical industry and academia, the proposed routes use multistep procedures with a low overall yield, thus not aligning with the current environmental challenges [ 17 , 18 , 19 ]. A recent approach suggests the use of glycerol as an eco-friendly reaction medium for the last step in atenolol synthesis [ 22 , 23 ]. Consequently, the development of a more efficient and practical green route to the atenolol API remains an important synthetic goal to minimize the environmental impact of such pharmaceutical processes.…”