Green Chemistry Approaches to the Synthesis of Coumarin Derivatives

Abstract

This review is a compilation of the green synthetic methods used in the synthesis of coumarin derivatives. Coumarins are a class of compounds with a pronounced wide range of biological activities, which have found their application in medicine, pharmacology, cosmetics and food industry. Their biological activity and potential application are highly dependent on their structure. Therefore, many researchers have been performing the synthesis of coumarin derivatives on a daily basis. High demands for their synthesis often result in an increased generation of different waste chemicals. In order to minimize the utilization and generation of toxic organic substances, green synthetic methods are applied in this manner. These methods are getting more attention in the last few decades. Green chemistry methods cover a wide range of methods, including the application of ultrasound and microwaves, ionic liquids and deep eutectic solvents, solvent-free synthesis, mechanosynthesis and multicomponent reactions. All typical condensation reactions for coumarin synthesis like Knoevenagel, Perkin, Kostanecki-Robinson, Pechmann and Reformansky reactions, have been successfully performed using these green synthetic methods. According to the authors mentioned in this review, not only these methods reduce the utilization and generation of toxic chemicals, but they can also enhance the reaction performance in terms of product yields, purity, energy consumption and post-synthetic procedures when compared to the conventional methods. Due to the significance of coumarins as biologically active systems and the recent demands of reducing toxic solvents, catalysts and energy consumption, this review provides a first full literature overview on the application of green synthetic methods in the coumarin synthesis. It covers a literature search over the period from 1995-2019. The importance of this work is its comprehensive literature survey on a specific class of heterocyclic compounds, and those researchers working on the coumarin synthesis can find very useful information on the green synthetic approaches to their synthesis. There are some reviews on the coumarin synthesis, but most of them cover only specific reactions on coumarin synthesis and none of them the whole range of green chemistry methods.

Trending Topics on Coumarin and Its Derivatives in 2020

“…Due to the length of this general overview, synthetic strategies for obtaining new coumarins have not been discussed in detail. To find information on the most recent synthetic pathways, we recommend the manuscripts by Molnar and co-authors [ 81 ] and Kovač and co-authors [ 82 ], both from 2020. To find an overview of the wide range of biological activities of coumarins, a 2020 review by Pinto and co-authors [ 1 ] is strongly recommended.…”

Synthetic Routes to Coumarin(Benzopyrone)-Fused Five-Membered Aromatic Heterocycles Built on the α-Pyrone Moiety. Part 1: Five-Membered Aromatic Rings with One Heteroatom

“…Alizadeh et al reported a sequential three-component reaction of salicylaldehydes 60 , β-keto esters 61, and p -toluenesulfonylmethyl isocyanide (TosMIC) ( 62 ) via [ 1 , 3 ] acyl shift to give 2-acyl[1] benzopyrano[3,4- e ]pyrrol-4-ones 63 ( Scheme 18 ) [ 67 ]. A simple workup procedure, mild reaction conditions, lack of side products, and good yields of 62%–95% are the main aspects of this method.…”

“…Coumarins are a family of benzopyrones (1,2-benzopyrones or 2 H -[1]benzopyran-2-ones), which represent an important family of oxygen-containing heterocycles, widely distributed in nature [ 1 , 2 , 3 , 4 ]. Coumarins display a broad range of biological and pharmacological activities, [ 5 , 6 ] such as antiviral [ 7 , 8 , 9 , 10 ], anticancer [ 11 , 12 , 13 ], antimicrobial [ 14 , 15 ], and antioxidant [ 16 , 17 , 18 ] activities.…”

Synthetic Routes to Coumarin(Benzopyrone)-Fused Five-Membered Aromatic Heterocycles Built on the α-Pyrone Moiety. Part II: Five-Membered Aromatic Rings with Multi Heteroatoms

“…Coumarin is one of the benzopyrones (1,2-benzopyrones or 2H-[1] benzopyran-2-ones) and represents an important family of oxygen-containing heterocycles widely distributed in nature [ 1 ]. The incorporation of another heterocyclic moiety into coumarin enriches the properties of the parent structure and the resulting compounds may exhibit promising properties [ 2 , 3 , 4 , 5 ]. Certain derivatives of 3,4-heterocycle-fused coumarins play an important role in medicinal chemistry and have been extensively used as versatile building blocks in organic synthesis [ 2 , 3 , 5 , 6 , 7 ].…”

“…The incorporation of another heterocyclic moiety into coumarin enriches the properties of the parent structure and the resulting compounds may exhibit promising properties [ 2 , 3 , 4 , 5 ]. Certain derivatives of 3,4-heterocycle-fused coumarins play an important role in medicinal chemistry and have been extensively used as versatile building blocks in organic synthesis [ 2 , 3 , 5 , 6 , 7 ]. Many examples of biologically active coumarins containing 3,4-heterocycles-fused were cited in the literature [ 2 , 3 , 8 ] including antimicrobial [ 9 , 10 , 11 , 12 ], antiviral [ 13 , 14 ], anticancer [ 15 , 16 , 17 ], antioxidant [ 18 , 19 ], and anti-inflammatory [ 20 , 21 ] activities.…”