A Combination of natural deep eutectic solvents and microflow technology: a sustainable innovation for the tandem synthesis of 3-aminohexahydrocoumarins

Nowadays, in different research areas the interest in deep eutectic solvents (DESs) is growing as green substitutes to conventional ionic liquids (ILs), such as electrochemistry, extraction, or biocatalysts. These compounds are basically formed from two or three safe, inexpensive and environmentally friendly components [1].On the other hand, microreactors as a functional component of microfluidic devices, have many advantages compared to batch reactors, including a short reaction time, low cost, portability, reduced reagent consumption, and a high surface-to-volume ratio [2].Dihydrocoumarin and aminocoumarin derivatives possess significant bioactivities such as cytotoxic, anti-inflammatory, inhibiting histone deacetylase, and antibiotic.Upon the aforementioned explanation and in continuation of our recent investigation on green chemistry especially developing microflow synthesis, herein we would like to present the first efficient, and environmentally friendly consecutive microflow synthesis of the N-(2,5-dioxo-3,4,5,6,7,8-hexahydro-2Hchromen-3-yl)acetamide framework utilizing hippuric acid, aryl aldehyde, acetic anhydride and 1,3-dicarbonyl compounds in choline chloride (ChCl)/urea as a biorenewable solvent. This reaction is the first flow methodology described using NADES as eco-friendly, nontoxic, and green solvent and catalyst compared to the common volatile organic compounds (VOC).