Recent Advances in the Synthesis of Coumarin Derivatives from Different Starting Materials

Abstract

The study of coumarin dates back to 1820 when coumarin was first extracted from tonka bean by Vogel. Compounds containing coumarin backbone are a very important group of compounds due to their usage in pharmacy and medicine. Properties and biological activities of coumarin derivatives have a significant role in the development of new drugs. Therefore, many different methods and techniques are developed in order to synthesize coumarin derivatives. Coumarin derivatives could be obtained from different starting materials with various methods but with big differences in yield. This review summarized various methods, techniques and reaction conditions for synthesis of coumarins from different compounds such as aldehydes, phenols, ketones and carboxylic acids.

Keywords: Knoevenagel condensation; Pechmann reaction; coumarins; synthesis.

Figure 1

Six basic groups of natural coumarins.

Scheme 1

Green synthesis of coumarin derivatives in deep eutectic solvent.

Scheme 2

Coumarin derivatives obtained in aqueous media with ChCl as catalyst.

Scheme 3

Cyclization reaction of phenyl 3-phenylpropiolate with various aldehydes.

Scheme 4

Cyclization reactions of 4-methoxybenzaldehyde and various alkynoates.

Scheme 5

Synthesis of coumarin derivatives in the presence of piperidine and acetic acid as catalysts.

Scheme 6

One-pot synthesis of coumarin-3-carboxylic acids in water.

Scheme 7

Synthesis of different coumarins from active methylene compounds and salicylaldehydes.

Scheme 8

Phenyliododiacetate mediated reaction of salicylaldehydes and α-substituted ethylacetates.

Scheme 9

Green method for synthesis of coumarin-3-carboxylic acids under ultrasound irradiation.

Scheme 10

Synthesis of 3-substituted coumarins between salicylaldehydes and 1,3-dicarbonyl compounds in presence of nano MgFe₂O₄.

Scheme 11

Synthesis of 2H-chromene-3-carboxylates in presence of piperidine in toluene.

Scheme 12

Synthesis of 3-arylcoumarins via Perkin condensation in the presence of anhydride and trimethylamine.

Scheme 13

One-pot synthesis of cyanocoumarins in presence of T3P, trimethylamine and butyl acetate.

Scheme 14

Synthesis of coumarin derivatives trough reaction of carboxylic acids and 2-hydroxy-3-methoxybenzaldehyde.

Scheme 15

Synthesis of coumarin-3-carboxylic esters in multicomponent reaction in the presence of FeCl₃.

Scheme 16

Three-component one-pot synthesis of 3-benzoxazole coumarins.

Scheme 17

Synthesis of pyrazolylcoumarins in a multicomponent reaction.

Scheme 18

Synthesis of coumarin-chalcone compounds in multicomponent reaction.

Scheme 19

Microwave assisted four-component synthesis of 3-N-sulfonylamidine coumarins.

Scheme 20

Two-step synthesis of bromoacetylcoumarin under microwave irradiation.

Scheme 21

Three and four-step synthesis of N-(2-(1H-indol-3-yl)ethyl)-2-oxo-2H-chromene-3-carboxamides.

Scheme 22

Two-step synthesis of substituted 3-cyanocoumarins under microwave irradiation.

Scheme 23

One-pot synthesis of fluorescent colorant in deep eutectic solvents.

Scheme 24

Synthesis of substituted 3-aminocoumarins in two-step reaction.

Scheme 25

Synthesis of substituted 3-amino-4-bromocoumarins in the presence of bromodimethylsulfonium bromide.

Scheme 26

Four-step reaction in synthesis of coumarin derivatives.

Scheme 27

Efficient two-step synthesis of hydroxylated 3-phenylcoumarins.

Scheme 28

One-pot two-step synthesis of 3-aryl coumarins in the presence of Ph₃P/I₂-Et₃N.

Scheme 29

Ultrasound assisted synthesis of 3-phenylcoumarin derivatives in presence of tetrahydrofuran and K₂CO₃.

Scheme 30

Efficient synthesis of 3-aryl coumarin derivatives in presence of N-methylmorpholine.

Scheme 31

Solvent-free synthesis of 3-aryl coumarins in the presence of DABCO as the catalyst.

Scheme 32

Synthesis of substituted coumarin derivatives from salicylaldehydes and ketene.

Scheme 33

Solvent-free synthesis of coumarin-3-carboxylic acids under microwave irradiation.

Scheme 34

Synthesis of 3-substituted coumarins catalyzed by iron (III) chloride.

Scheme 35

Synthesis of 3-substituted coumarins in the presence of potassium phtalamide.

Scheme 36

Synthesis of substituted coumarins catalyzed by Fe₃O(BPDC)₃.

Scheme 37

Synthesis of 3-cyanocoumarins performed under heating and microwave conditions.

Scheme 38

Synthesis of coumarin derivatives in presence of starch sulfuric acid.

Scheme 39

Coumarins synthesis via Pechmann condensation with sulfuric acid as a catalyst.

Scheme 40

Solvent-free synthesis of 4-methylcoumarins under microwave irradiation.

Scheme 41

Solvent-free Pechmann condensation of coumarin derivatives in the presence of cellulose nanocrystal supported palladium nanoparticles.

Scheme 42

Synthesis of coumarin derivatives in the presence of magnetic-core-shell-like Fe₃O₄@Boehmite-NH₂-Co^II NPs.

Scheme 43

Condensation reaction of phenols and β-ketoesters catalyzed by FeCl₃·6H₂O.

Scheme 44

Synthesis of 4-methyl coumarin derivatives via Pechmann condensation.

Scheme 45

Solvent-free synthesis of coumarin derivatives with meglumine sulfate as a catalyst.

Scheme 46

Alumina sulfuric acid catalyzed reaction between phenolic compounds and β-ketoesters.

Scheme 47

Pechmann synthesis of coumarins in the presence of triethylammonium hydrogen sulfate as a catalyst.

Scheme 48

Synthesis of coumarin derivatives in the presence 1,3,5-trichloroisocyanuric acid.

Scheme 49

Ultrasound assisted solvent-free synthesis of 4-substituted coumarins.

Scheme 50

Synthesis of 7-hydroxy-4-methyl coumarin in presence of H₂SO₄ under ultrasonic irradiation.

Scheme 51

Synthesis of 4-methyl coumarins in PEG-SO₃H catalyzed reaction.

Scheme 52

Four-step syntheses of polyphenolic hybrid-coumarins.

Scheme 53

Three-step synthesis of furanocoumarin.

Scheme 54

Solvent-free synthesis of substituted coumarins catalyzed by Wells-Dawson heteropolyacid (H₆P₂W₁₈O₆₂).

Scheme 55

Palladium catalyzed synthesis of coumarin derivatives.

Scheme 56

Synthesis of coumarin-3-carboxylic acids under microwave irradiation.

Scheme 57

Synthesis of coumarin derivatives via Knoevenagel condensation in green solvents.

Scheme 58

Synthesis of 3,4-disubstituted coumarins in presence of FeCl_3.

Scheme 59

Two-step synthesis of 4-hydroxy-3-(hetero aryl Azo) coumarins.

Scheme 60

One-pot two-step synthesis of 3-aryl-4-methylcoumarins.

Scheme 61

Synthesis of 3-cyano-4-methylcoumarions in presence of iodine as a catalyst. Coumarin derivatives synthesized from carboxylic acids.

Scheme 62

Synthesis of coumarin derivatives performed by Li et al.

Scheme 63

Radical cyclization of α-keto acids and alkynoates in coumarin derivatives synthesis.

Scheme 64

Silver-promoted decarboxylative annulation of 3-acylcoumarins.