Green synthesis of coumarinyl Schiff bases utilizing choline chloride-based deep eutectic solvents

Coumarins, as highly bioactive heterocycles, possess a wide spectrum of biological, pharmacological, and therapeutic properties, which are strongly structure dependent. Schiff bases bearing coumarin moiety in conjunction with imino group (-C=N-) form a significant class of compounds widely used in medicinal and pharmaceutical chemistry.

Deep eutectic solvents (DESs) are often described as green media for many synthetic pathways, whose properties can be adjusted using different molar ratios of initial components.

The aim of this study was to synthesize coumarinyl Schiff bases using ChCl-based DES as a reaction media and a catalyst, as well. Firstly, we prepared 2-cyanoacetohydrazide (3) from hydrazine hydrate (1) and ethyl cyanoacetate (2). Schiff bases (5a-j) were prepared by refluxing an equimolar amount of 3 and different aldehydes (4a-j), in ethanol, with 2-3 drops of acetic acid. Afterwards, the synthesis of coumarinyl Schiff bases (7a-j) was performed in ChCl:urea (1:2) DES, by mixing the equimolar amounts of compounds 5a-j and 2,5-dihydroxybenzaldehyde (6).

Hereby, we applied an environmentally friendly approach, utilizing a solvent made of biodegradable components, with low toxicity and vapor pressure. DESs are proven the excellent media for all these reactions, while the isolation of the final product was easy, and included only the addition of water and filtration.