**2.2 Knoevenagel condensation reaction**

An efficient green one-pot synthetic method for the synthesis of 3-substituted coumarin derivatives **21/22** has been observed by Knoevenagel condensation of various *o*-hydroxybenzaldehydes **18/19** with 1,3-dicarbonyl compounds **20** using

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nano-ZnO catalyst under microwave or thermal conditions, which affords moderate to good yield of the products (**Figure 6**) [81]. Reactions under microwave-irradiation conditions are found to be more convenient than thermal conditions.

Various coumarin-3-carboxylic acid derivatives **25/26** have been synthesized in good yields using catalytic amounts of SnCl2.2H2O under solvent-free condition (**Figure 7**) [82].

Ultrasound irradiation technique is also useful to synthesize 3-aryl coumarin derivatives. Treatment of *o*-hydroxybenzaldehydes **18** with aryl substituted acetyl chloride **27** in the presence of K2CO3 as a catalyst in tetrahydrofuran (THF) using ultrasound irradiation leads to the formation of 3-aryl coumarin derivatives **28** in moderate to high yields (**Figure 8**) [83]. This green method appears to be a convenient and simple pathway than that of conventional heating.

Coumarin-substituted benzimidazole or benzoxazole derivatives **32** that are known as coumarin dyes have been synthesized in good yields from 4-diethylamino-2-hydroxybenzaldehyde **29**, ethyl cyanoacetate **30**, and ortho-phenylenediamine/phenylenehydroxyamine derivatives **31** in the presence of reusable green solid acid like HZSM-5 zeolite, heteropoly acids, e.g., tungstophosphoric acid (H3PW12O40), and/or tungstosilicic acid (H4O40SiW12) in *n*-pentanol or water and even solvent-free conditions (**Figure 9**) [84].

Cellulose sulfonic acid (CSA) is an efficient catalyst for the synthesis of 3 substituted coumarin via Knoevenagel condensation reaction. Thus, 3-acetyl coumarin **34** is obtained in 88% yield in the reaction between salicylaldehyde **33** and ethyl acetoacetate **7** in the presence of CSA under solvent-free conditions (**Figure 10**) [85].

**113**

**Figure 10.**

*Synthesis of 3-acetyl coumarin.*

**Figure 8.**

**Figure 9.**

*Synthesis of 3-aryl coumarin derivatives.*

*Synthesis of coumarin-substituted benzimidazoles/benzoxazoles.*

*One-Pot Synthesis of Coumarin Derivatives DOI: http://dx.doi.org/10.5772/intechopen.89013*

media and catalyst as well.

under heating condition (**Figure 11**, Condition C) [87].

Shaabani et al. [86] have described the synthesis of 3-substituted coumarins **21** in good yields via Knoevenagel condensation of 2-hydroxybenzaldehydes **18** with β-dicarbonyl compounds **35** in the presence of a recyclable ionic liquid 1,1,3,3-*N*,*N*,*N*′,*N*′-tetramethylguanidinium trifluoroacetate (TMGT) under thermal heating (**Figure 11**, Condition A) and/or microwave irradiation conditions (**Figure 11**, Condition B). 3-Substituted coumarins **21** are also synthesized from similar starting precursors using the 1,3-dimethylimidazolium methyl sulfate [MMIm][MSO4] ionic liquid in the presence of L-proline as an additional promoter

Imidazolium based phosphinite ionic liquid (IL-OPPh2) catalyzed synthesis of 3-substituted coumarin derivatives has been reported in literature; when *o*-hydroxy benzaldehydes **18** are treated with active methylene containing compounds **35** in the presence of IL-OPPh2 catalyst at 60°C, 3-substituted coumarin derivatives are obtained in moderate to good yields (**Figure 12**) [88]. TSIL plays both the reaction

Reactions of *o*-hydroxybenzaldehydes **18** with activated methylene compounds **35** catalyzed by Bronsted acid ionic liquid (BAIL) and 1-(4-sulfonic acid)butyl-3-methylimidazolium hydrogen sulfate [(CH2)4SO3HMIM][HSO4] in water lead to

Synthesis of substituted coumarins via Knoevenagel condensation using various organic catalysts such as piperidine, ammonia, L-lysine, L-proline, benzoic acid,

3-substituted coumarin derivatives in good yields (**Figure 13**) [89].

etc. has been reported in literature and some are summarized in **Table 2**.
