engleski

A Synthesis of Coumarin Derivatives via Knoevenagel Condensation in Green Solvents

Nowadays, the biologically active compounds attract considerable attention due to their various biological and pharmaceutical properties. Many of these compounds can be extracted from plants, but due to their increased use for medical purposes, they are increasingly synthesized in laboratories. Coumarins are an important class of biologically active compounds and play an important role in nature, acting as the plant growth hormones and growth regulators, participating in a respiration control, photosynthesis, and defense against infections. Coumarins are also attributed to a range of medical applications, such as the anticancerogenic, antioxidant, and anti‐HIV one, acting as an enzyme inhibitor, vasorelaxant, anticoagulant, an antibacterial agent, and much more. Among many reactions for coumarin synthesis (the Pechmann condensation reaction, Witting, Claisen, Reformatsky, and Kontanecki‐Robinson reaction), the most used reaction is the Knoevenagel condensation. An important factor in chemical synthesis is a usage of the environment‐friendly solvents. One of the green approaches in synthesis is a usage of the deep eutectic solvents (DESs) as the reaction media. The DESs possess many desired properties, such as a low toxicity, high availability, low inflammability, high recyclability, low volatility and low price. The aim of this work was to synthesize the coumarin derivatives via Knoevenagel condensation using the green solvents (DESs) under conditions established to be the best ones by a previously performed screening. A model reaction of salicylaldehyde and dimethyl malonate was performed in 20 different DESs at 80 °C. Choline chloride was used as a hydrogen bond acceptor, and 20 other components like urea, carboxylic acids, sugars or amides were the hydrogen bond donors. ChCl:Urea (ChCl:U, 1:2) is proven to be the best solvent, which afforded a yield of 50.5%, followed by the ChCl:N-methylurea (1:3) with a yield of 45.1%. Based on the obtained results, a series of coumarin derivatives was synthesized from the substituted salicylaldehydes and dimethyl malonate, diethyl malonate, or ethyl benzoylacetate.

deep eutectic solvents ; synthesis ; coumarins

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