Open access peer-reviewed chapter

One-Pot Synthesis of Coumarin Derivatives

Written By

Inul Ansary and Abu Taher

Submitted: 29 June 2019 Reviewed: 04 August 2019 Published: 22 October 2019

DOI: 10.5772/intechopen.89013

From the Edited Volume

Phytochemicals in Human Health

Edited by Venketeshwer Rao, Dennis Mans and Leticia Rao

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Abstract

Coumarin derivatives have a myriad of applications in medical science, biomedical research, and many industrial branches. For this reason, many efforts are being dedicated to the development of novel and more practical methods for synthesizing these compounds. This chapter describes several methods of one-pot synthesis of coumarin derivatives, including von Pechmann condensation, Knoevenagel condensation, Baylis-Hillman reaction, Michael addition, Kostanecki reaction, vinyl phosphonium salt-mediated electrophilic reaction, and Heck-lactonization reaction. The methods are compared with each other, and the advantages and disadvantages of each of them are addressed.

Keywords

  • coumarin derivatives
  • one-pot synthesis
  • methods and procedures
  • advantages and disadvantages

1. Introduction

Coumarin (2H-chromen-2-one) derivatives have spawn great interest over the years because of their significant biological importance [1]. They are associated with various biological activities viz. antiviral [2, 3], antibacterial [4, 5], antimicrobial [6], anticoagulant [7], anti-inflammatory [8, 9], anticancer [1011], anticonvulsant [12], antioxidant [13], antifungal [14, 15], and anti-HIV [16]. They also possess the properties like inhibition of platelet aggregation [17] and inhibition of steroid 5α-reductase [18]. Besides, they are attracting considerable attention of chemists due to their wide range of applications such as optical brighteners [19], photosensitizers [20], fluorescent and laser dyes [21], and additives [22] in food, perfumes, cosmetics, and pharmaceuticals. The novel compounds are also utilized in drug and pesticidal preparations [23]. Considering these multifarious activities of coumarins, synthetic chemists are actively engaged in developing new and superior methods for the isolation of coumarin derivatives. The most widely used method for their synthesis is Pechmann reaction [24, 25, 26, 27], which involves the condensation between phenols and β-keto esters, in the presence of an acid catalyst. This method employs both homogeneous catalysts such as concentrated H2SO4 [24, 25], trifluoroacetic acid (TFA) [28], and Lewis acids (LA) such as AlCl3 [29], ZnCl2 [30], ZrCl4 [31], TiCl4 [32], etc. and heterogeneous catalysts such as cation-exchange resins [33], Nafion resin/silica composites [34], zeolite H-BEA (H-beta, SiO2/Al2O3 = 14) [35], and other solid acids.

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2. Methods to synthesize coumarin derivatives

2.1 Pechmann condensation reaction

The general reaction sequence of Pechmann reaction and its mechanism, shown in Figure 1, involves an esterification/transesterification between the phenol 1 and β-keto ester 2 in the presence of protonic acid or Lewis acid (LA) catalyst to produce species 4 followed by an attack to the activated carbonyl carbon by the aromatic ring at ortho-position to yield the new ring in species 5. Finally, dehydration of species 5 affords coumarin derivative 2.

Figure 1.

Mechanism for the acid-catalyzed Pechmann condensation.

A series of substituted coumarins 8 have been synthesized in 25–77% yields by the reactions of substituted phenols 6 with ethyl acetoacetate 7 in the presence of zinc-iodine mixture in refluxing toluene (Figure 2) [36]. It is observed that phenols containing electron-donating substituent like ▬CH3 group result in higher yields compared to unsubstituted phenols and phenols having electron-withdrawing group such as NO2 group.

Figure 2.

Synthesis of substituted coumarins.

When 3-(N,N-dimethylamino)phenol 9 is subjected to react with ethyl 2-acetamide-3-oxobutyrate 10 in the presence of anhydrous ZnCl2 in absolute ethanol under reflux condition, the acetamido coumarin 11 is obtained only in 12.4% yield (Figure 3) [30].

Figure 3.

Synthesis of acetamido coumarin.

Substituted coumarins 14 have been achieved in moderate to good yields from substituted phenols 12 and methyl acetoacetate 13 under conventional and microwave heating, respectively, catalyzed by concentrated H2SO4 (Figure 4) [37]. It is found that the reactions using the latter method are faster coupled with product in better yields compared to former one.

Figure 4.

Synthesis of substituted coumarins.

Synthesis of substituted coumarins 16 in 62–98% yields has also been described by Maheswara et al. [38] via reactions of substituted phenols 1 with β-keto esters 15 in the presence of a heterogeneous catalyst, HClO4.SiO2 under solvent-free conditions (Figure 5, Condition A). The aforementioned method involves recoverable cheap catalyst and shorter reaction time with high product yields. However, relatively lower yields (35–55%) of substituted coumarins 16 have been isolated from the similar starting precursors catalyzed by Amberlyst-15 acidic catalyst [39] in toluene under refluxing condition (Figure 5, Condition B).

Figure 5.

Synthesis of substituted coumarins.

Pechmann condensation reactions for the synthesis of substituted coumarins using various homogeneous and heterogeneous catalysts have been reported in literature and some important ones are summarized in Table 1.

Table 1.

Synthesis of substituted coumarins via Pechmann condensation reactions.

From Table 1, it is quite evident that the reactions under microwave as well as ultrasound irradiation occur at a faster rate than those of the conventional methods (entries 10, 14, 15, 16, 25, 31, 32, and 39). Unsubstituted phenol produces lower yields of corresponding coumarin derivatives and/or requires longer reaction time (entries 2–4, 7, 10, 12, 13, 24, 28, 30, and 38), higher temperature (entries 2, 3, 7, and 12), and excess amount of catalysts (entries 7 and 12) than di- and trihydric phenols. This may presumably be due to the less reactivity of unsubstituted phenol toward Pechmann condensation reaction compared to di- and trihydric phenols. In addition, the substitution of an electron-donating group such as m/p-Me or p-OMe in the phenols leads to decrease of catalytic activity and, hence, requires longer reaction time and/or gives rise to lower yields of products (entry 13). The reactivity of monohydric phenols having electron-withdrawing groups such as m-NH2 and m-OMe is also lowered compared with simple di- and trihydric phenols (entries 19, 28, and 37). 1-Naphthol and 2-naphthol need longer reaction time (entries 13, 33, and 39) and/or furnish products with lower yields (entries 13, 37, and 40) compared to other phenols, due to the presence of another phenyl ring. However, better yield of benzocoumarin is obtained from the reaction between 1-naphthol and more reactive β-keto ester, ethyl 4-chloro-3-oxobutanoate (entry 37). It is interesting to note that β-keto ester having phenyl group at the β-position such as ethyl 3-oxo-3-phenylpropanoate is found to be less reactive in Pechmann condensation with resorcinol and 1,3-dihydroxy-5-methyl benzene due to the presence of conjugated keto center, which lengthens the reaction time than in the reactions of EAA and/or ethyl 4-chloro-3-oxobutanoate with resorcinol and 1,3-dihydroxy-5-methyl benzene (entries 21, 28, and 37). Besides, the reactivity of different types of phenols and β-keto esters, catalyst efficiency, and solvent effect of Pechmann condensation has also been studied. It is observed that TiCl4 (entry 5) is the most effective catalyst as far as reaction time is considered, whereas montmorillonite K-10 (entry 1) and sulfated zirconia (SZr) (entry 9) are found to be less effective. Ionic liquids (ILs) such as 1-butyl-3-methylimidazolium hexafluorophosphate [bmim]PF6 and 1,3-disulfonic acid imidazolium hydrogen sulfate (DSIMHS) have been used as effective and reusable catalysts and reaction media as well (entries 6 and 18).

Lewis acid−surfactant-combined catalyst (LASC) such as nano-TiO2 on dodecyl-sulfated silica support (NTDSS) is used as a reusable and highly effective catalyst for Pechmann condensation of phenols containing different types of substituents in water led to excellent product yields (entry 20). Other recyclable solid acid catalysts have also been employed in Pechmann condensation reactions leading to coumarin derivatives in good to excellent yields under solvent-free (entries 22–24, 26–27, 29–30, and 42), microwave irradiation (entry 25) and/or ultrasound irradiation (entry 39) conditions.

More importantly, sulfonic acid-supported silica-coated magnetic nanoparticles (Fe3O4@SiO2@PrSO3H), CuFe2O4 nanoparticles, and zirconium(IV) complex grafted silica coated magnetic nanoparticles are found to be the most efficient catalysts toward Pechmann condensation, in which case the catalyst can be effortlessly separated by external magnet after completion of the reaction and reused for 22, 6, and 5 consecutive runs, without any significant loss in catalytic efficiency (entries 33–35).

Pechmann condensation of pyrogallol and resorcinol with ethyl acetoacetate over nanosponge MFI zeolite in comparison with conventional zeolites (MFI, BEA, and USY) and other layered MFI (lamellar, pillared, and self-pillared) have been investigated. It is important to note that the nanosponge catalysts exhibit the best catalytic performance with respect to the products’ selectivity in the liquid-phase condensation reactions among all the investigated zeolites (entry 36).

On the other hand, the catalytic behavior of metal–organic frameworks such as Cu-benzene-1,3,5-tricarboxylate (CuBTC) and Fe-benzene-1,3,5-tricarboxylate (FeBTC) is investigated and compared with large-pore zeolites, beta (BEA), and ultrastable Y (USY) (entry 41). It is clear that zeolites BEA and USY are found to be more active catalysts in transformations of the most active substrates like resorcinol and pyrogallol but a low conversion of naphthol is observed. However, almost total transformation of naphthol (93–98% conversion) to the target product occurs within 23 h of the reaction time over metal–organic frameworks, CuBTC and FeBTC. Catalytic activity of many other catalysts under different reaction conditions is delineated in the recently published review [80].

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 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.

Figure 6.

Synthesis of 3-substituted coumarins.

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].

Figure 7.

Synthesis of coumarin 3-carboxylic acid derivatives.

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.

Figure 8.

Synthesis of 3-aryl coumarin derivatives.

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].

Figure 9.

Synthesis of coumarin-substituted benzimidazoles/benzoxazoles.

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].

Figure 10.

Synthesis of 3-acetyl coumarin.

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

Figure 11.

Synthesis of 3-substituted coumarins.

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 media and catalyst as well.

Figure 12.

Synthesis of 3-substituted coumarins.

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

Figure 13.

Synthesis of 3-substituted coumarins.

Synthesis of substituted coumarins via Knoevenagel condensation using various organic catalysts such as piperidine, ammonia, L-lysine, L-proline, benzoic acid, etc. has been reported in literature and some are summarized in Table 2.

Table 2.

Synthesis of substituted coumarins via Knoevenagel condensation reactions.

It is quite evident that in Table 2 several methodologies for the synthesis of substituted coumarins using different organic catalysts are established. Among these, L-proline-catalyzed reactions offer high yields (entry 3), which explains synthesis of 3-substituted coumarins by the condensation of o-hydroxybenzaldehydes with a variety of active methylene compounds catalyzed by 1,3-dimethyl imidazolium methyl sulfate [MMIm][MSO4] and L-proline. Another L-proline-catalyzed synthesis of coumarins is known, but in that case, the yield is very poor (entry 4). Similar result is also observed under L-lysine-catalyzed synthesis of coumarins (entry 5).

A series of 3-phenyl substituted coumarin analogues have been achieved via a two-step process involving esterification using 1,1-carbonyldiimidazole (CDI) followed by condensation reaction in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) under mild conditions (entry 1).

Microwave-assisted synthesis of coumarins is also known, which not only reduces the reaction time but also increases the yields of the products (entries 2, 6, and 7).

Benzocoumarin derivatives have been synthesized from 1-hydroxy-4-methyl-naphthalene-2-carbaldehyde and compounds containing active methylene group via piperidine-catalyzed Knoevenagel condensation reaction (entry 8). Moreover, benzothiazolyl coumarins with isothiocyanate functionality have been synthesized from commercially available 2-hydroxy-4-nitro benzoic acid in the presence of piperidine in ethanol (entry 9).

Application of sonochemistry for the synthesis of different coumarin derivatives is also useful due to better yield and shorter reaction time compared with the classical procedures (entry 10).

6,8-Diiodocoumarin derivatives have also been synthesized in good yields by Knoevenagel condensation using piperidine as catalyst (entry 11). The reaction of 3-ethoxysalicylaldehyde with ethyl acetoacetate in the presence of piperidine leads to 3-acetyl-8-ethoxycoumarin (entry 12).

2.3 Baylis-Hillman reaction

Baylis-Hillman strategy has been employed to the synthesis of substituted coumarins as shown in Figure 14. When 2-hydroxybenzaldehydes 18 are subjected to react with methyl acrylate 39a (R2 = Me) in the presence of DABCO (1,4-Diazabicyclo[2.2.2]octane), a mixture of chromenes 40 and coumarins 41 are formed [101, 102]. However, similar reactions of 2-hydroxybenzaldehydes 18 with tert-butyl acrylate 39b (R2 = tBu) under classical method [103] and/or microwave irradiation [104] afford corresponding Baylis-Hillman adducts 42, which undergo cyclization under reflux in AcOH yielding a mixture of 3-substituted chromene 43 and coumarin 44. Treatment of the Baylis-Hillman adducts 42 with concentrated HCl in refluxing AcOH produces 3-(chloromethyl) coumarins 45 in excellent yields. Moreover, the reaction of 42 with HI under reflux in a mixture of Ac2O and AcOH furnishes 3-methyl coumarins 46, which upon further reaction with SeO2 affords the corresponding 3-formyl coumarins 47.

Figure 14.

Synthesis of 3-substituted coumarins.

The suggested mechanism for the formation of the coumarin derivatives 44/45/46 is shown in Figure 15.

Figure 15.

Possible mechanism for the formation of 3-substituted coumarins.

Kaye et al. have also demonstrated the synthesis of substituted coumarins employing Baylis-Hillman strategy in different ways as shown in Figure 16 [105, 106].

Figure 16.

Synthesis of 3-substituted coumarins.

2.4 Kostanecki reaction

4-Arylcoumarins 59 have been synthesized in good yields employing Kostanecki reaction between 2-hydroxybenzophenones 57 and acetic anhydride 58 in the presence of DBU under mild condition (Figure 17) [107].

Figure 17.

Synthesis of 4-arylcoumarins.

The mechanism of the Kostanecki reaction is outlined in Figure 18.

Figure 18.

Mechanism for Kostanecki reaction.

Similarly, 3,4-disubstituted coumarins 65 are isolated from readily available 2-acyloxybenzophenones 64 under Kostanecki reaction conditions (Figure 19) [107].

Figure 19.

Synthesis of 3,4-disubstituted coumarins.

2.5 Michael addition reaction

Michael addition could be applied [108] to the synthesis of 3-aroylcoumarins 68 in good yields from easily available 2-hydroxybenzaldehydes 66 and α-aroylketene dithioacetals (AKDTAs) 67 in the presence of a catalytic amount of piperidine in refluxing THF (Figure 20).

Figure 20.

Synthesis of 3-aroylcoumarins.

The reaction proceeds via initial Michael addition followed by intramolecular aldol condensation reaction as depicted in Figure 21.

Figure 21.

Probable mechanism for the formation of 3-aroylcoumarins.

2.6 Wittig reaction

Kumar and coworkers [109] have reported the synthesis of substituted coumarins 3 from phenolic compounds 23 containing ortho-carbonyl group and triphenyl (α-carboxymethylene)phosphorane imidazole ylide 73 via intramolecular Wittig cyclization in good yields (Figure 22). All the reactions proceed via formation of the phosphorane intermediates 74 as established by spectroscopic results.

Figure 22.

Synthesis of substituted coumarins.

2.7 Vinyl phosphonium salt-mediated electrophilic substitution reaction

A series of 4-carboxy(ethyl/methyl) coumarins 76 have been synthesized in good yields from substituted phenols 1 and di(ethyl/methyl)acetylene-dicarboxylate 75 in the presence of phosphinite ionic liquid (IL-OPPh2) under solvent-free microwave irradiation conditions (Figure 23) [110]. It is noticed that the diphenylphosphine group in ionic liquid accelerates the reaction.

Figure 23.

Synthesis of 4-carboxy(ethyl/methyl) coumarins.

The proposed mechanism for the formation of coumarins 76 via vinyl phosphonium salt-mediated electrophilic substitution is shown in Figure 24.

Figure 24.

Proposed mechanism for the synthesis of substituted coumarins via vinyl phosphonium salt-mediated electrophilic substitution.

4-Carboxymethyl coumarins 82 have been synthesized by Yavari et al. [111] in moderate to excellent yields from the reactions of substituted phenols 1 and dimethyl acetylenedicarboxylate (DMAD) 81 in the presence of triphenylphosphine (Figure 25) via vinyl triphenylphosphonium salt-mediated aromatic electrophilic substitution reaction as mentioned in Figure 24. Similar results are found from the given starting materials under microwave irradiation in shorter reaction time [112].

Figure 25.

Synthesis of 4-carboxymethyl coumarins.

However, reactions of di- and trihydric phenols with dimethyl acetylenedicarboxylate (DMAD) in the presence of triphenylphosphine in toluene under reflux afford polyfunctionalized coumarin analogues along with unwanted by-products in appreciable amount (Figure 26) [113].

Figure 26.

Synthesis of polyfunctionalized coumarin analogues.

Similar reactions of 2-hydroxybenzaldehydes 18 with di(ethyl/methyl)acetylenedicarboxylates 75 leads to the corresponding 4-carboxy(ethyl/methyl)-8-formyl coumarins 93 in moderate to good yields (Figure 27) [114].

Figure 27.

Synthesis of 4-carboxy(ethyl/methyl)-8-formyl coumarins.

The methodology has also been employed to the synthesis of angular pyridocoumarins 97/98 and benzo-fused 6-azacoumarin 100 as shown in Figure 28 [115].

Figure 28.

Synthesis of pyridocoumarins and benzo-fused azacoumarin.

2.8 Palladium-catalyzed reactions

Palladium-catalyzed reactions between substituted phenols 101 and ethyl propiolates 102 lead to substituted coumarins 103/104 (Figure 29) [116, 117].

Figure 29.

Synthesis of substituted coumarins.

Unsymmetrical monohydric phenols having m-OMe or m-Me substituent as respectively in 3-methoxyphenol and m-cresol show regioselectivity toward the formation of a new bond in coumarins, which occurs at the para position to the methoxy group, and therefore, the regioisomers 103 are found to be formed predominantly over 104. However, symmetrical dihydric phenol with OMe substituent like that in 5-methoxybenzene-1,3-diol affords the regioisomer 104 predominantly over 103 under the reaction condition applied. This may be due to the steric effects of the R4 group of ethyl propiolate 102, which dominates over the electronic effect of the methoxy group of the phenol.

A proposed mechanism for the formation of coumarins 103/104 is shown in Figure 30.

Figure 30.

Possible mechanism for Pd-catalyzed synthesis of coumarins.

Substituted coumarins 3 have been synthesized in moderate yields (42–69%) via Pd(OAc)2-catalyzed reaction of substituted phenols 1 with substituted propiolic acid 110 (R3 = CO2H) in TFA under mild conditions (Figure 31, Condition A) [118]. However, a mixture of catalysts FeCl3 and AgOTf showed better catalytic efficiency toward yields (60–93%) of coumarin derivatives 3 (Figure 31, Condition B). Propiolic acid ester 110 (R3 = CO2Et) also furnishes the desired products 3 upon reactions with substituted phenols 1 under specified conditions as provided in Figure 31 (Conditions C and D) [119, 120, 121].

Figure 31.

Synthesis of substituted coumarins.

4,6-Disubstituted coumarins 113 have been achieved employing palladium-catalyzed tandem Heck-lactonization of the Z- or E-enoates 112 with o-iodophenols 111 (Figure 32, Conditions A, B, and C) [122, 123].

Figure 32.

Synthesis of 4,6-disubstituted coumarins.

For Heck-lactonization, the enoate Z-112a is found to be more reactive than its E-isomer, leading to the corresponding coumarin 113 in good yields (68–84%) under all reaction conditions studied. The enoate Z-112b leads to coumarin derivative 113 in relatively lower yields (42–56%), which may be due to the presence of the bulky tBu ester group that hampers the lactonization step. Moreover, the reactivity of E-enoates depends on the β-substituent. E-enoates 112c (R2 = CH2CHMe2, R3 = CH3) and 112d (R2 = R3 = CH3) having CH2CHMe2 and CH3 group, respectively, at the β-carbon, and their double bonds are therefore less sterically hindered than that in E-enoate 112a. This reduced hindering is a major factor for the higher reactivity of E-enoates 112c and 112d than E-enoate 112a.

Palladium-catalyzed carbonylative annulation of terminal alkynes 110 (R2 = H; R3 = nPr, Ph, SiMe3, SiEt3, CO2Et, etc.) with o-iodophenols 111 affords 3-substituted coumarins 114 (R2 = H) in poor yields (18–36%) (Figure 33) [124]. On the other hand, both 3- and 4-substituted coumarins 114 (R2 = H) and 115 (R2 = H) have been synthesized from o-iodophenols 111 and terminal alkynes 110 (R2 = H; R3 = nC4H9, nC8H17) bearing long alkyl chain. In addition, a wide variety of 3,4-disubstituted coumarins 114/115 (R2, R3 ≠ H) have also been achieved in moderate to good yields (43–78%) via carbonylative annulation between o-iodophenols 111 and internal alkynes 110 (R2, R3 ≠ H) [125].

Figure 33.

Synthesis of 3, and 4-substituted and 3,4-disubstituted coumarins.

The suggested mechanism of the carbonylative annulation is presented in Figure 34. The carbonylative annulation process is believed to proceed via (a) oxidative addition of o-iodophenol 111 to Pd(0), (b) insertion of alkyne 110 into the aryl-palladium complex 116, (c) CO insertion into the resulting vinylic palladium species 118, and (d) nucleophilic attack of the phenolic oxygen on the carbonyl carbon of the acylpalladium complex 119 with simultaneous regeneration of the Pd(0) catalyst.

Figure 34.

Possible mechanism for the synthesis of coumarins via carbonylative annulation.

3,4-Disubstituted coumarins 121 are also isolated in good to excellent yields from readily available 2-(1-hydroxyprop-2-ynyl)phenols 120 via palladium-catalyzed dicarbonylation process in the presence of KI in MeOH at room temperature (Figure 35) [126].

Figure 35.

Synthesis of 3,4-disubstituted coumarins.

Furthermore, electrophilic palladium-catalyzed cycloisomerization of brominated arylpropiolates 122 followed by Suzuki coupling with arylboronic acids furnishes 4-arylcoumarins 123 in moderate to good yields (Figure 36) [127]. This strongly suggests that a single loading of catalyst Pd(OAc)2 could be used to conduct sequential reactions for the synthesis of substituted coumarins.

Figure 36.

Synthesis of 4-arylcoumarins.

2.9 Other methods

CuOAc-catalyzed hydroarylation of methyl phenylpropiolates 124 having a methoxy methyl (MOM)-protected hydroxyl group at the ortho-position with various arylboronic acids followed by acidic workup leads to 4-arylcoumarins 59 in good to excellent yields (Figure 37) [128].

Figure 37.

Synthesis of 4-arylcoumarins.

Substituted coumarins 126 are obtained in moderate to excellent yields by Yb(OTf)3-catalyzed reactions of substituted phenols 1 with alkylidene Meldrum’s acid 125 in CH3NO2 at 100°C (Figure 38) [129].

Figure 38.

Synthesis of substituted coumarins.

A series of 3-alkylcoumarins 128 are obtained in moderate yields from 2-hydroxybenzaldehydes 18 and α,β-unsaturated aldehydes 127 via generation of N-heterocyclic carbenes (NHC) in ionic liquid under conventional heating (Figure 39, Condition A) and/or microwave irradiation conditions (Figure 39, Condition B) [130].

Figure 39.

Synthesis of 3-alkylcoumarins.

3-Benzoylcoumarins 130/131 and coumarin-3-carbaldehydes 47 have also been isolated in moderate to good yields from the reactions of 2-hydroxybenzaldehydes 18/19 with phenylpropionyl chloride 129a and/or propionyl chloride 129b under esterification conditions (Figure 40) [131].

Figure 40.

Synthesis of 3-benzoyl coumarins and coumarin-3-carbaldehyde.

An electrochemical method has been developed for the synthesis of 6H-benzo[c]chromen-6-ones 133 in good to excellent yields from biphenyl-2-carboxylic acids 132 via radical arene carbon–oxygen bond formation reaction (Figure 41) [132]. The method involves DDQ as a redox mediator, inexpensive glassy carbon electrodes to facilitate an intramolecular lactonization of biphenyl-2-carboxylic acid derivatives, and 2,6-lutidine as an additive, in 0.1 M nBu4NClO4 electrolyte mixture of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP).

Figure 41.

Synthesis of 6H-benzo[c]chromen-6-ones.

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3. Concluding remarks

In this chapter, we have discussed a plethora of methods for the one-pot synthesis of coumarin derivatives and their advantages and/or demerits compared to other methods. Both the Pechmann as well as Knoevenagel condensation reactions under microwave and/or ultrasound irradiation conditions, and catalyzed by ionic liquids and/or solid acids have several advantages including high products yields, diminutive reaction times, ease of isolation of products, recycle of catalysts, and green aspects by avoiding toxic catalysts and solvents. Chemo- and regioselective syntheses of 3-substituted coumarins have been reported via Baylis-Hillman reactions under mild conditions. On the other hand, vinyl phosphonium salt-mediated electrophilic substitution reactions of phenols afford 4-carboxyalkyl coumarin derivatives in good yields under neutral conditions. This method offers significant advantages for the synthesis of coumarins having acid sensitive functional groups. In contrast, the most widely used method von Pechmann condensation requires acidic conditions. Moreover, palladium-catalyzed Heck lactonization protocol has been employed for the regioselective synthesis of coumarin derivatives from o-iodophenols and enoates. It is revealed that this reaction is sensitive to steric hindrance around the double bound in the enoates. Regioselective synthesis of 3,4-disubstituted coumarins achieved from substituted 2-iodophenols and alkynes containing different substituents via palladium-catalyzed carbonylative annulative process is sensitive to the steric bulk of the alkynes, and alkynes bearing tertiary alkyl substituents generally fail to undergo annulation. Unsymmetrical alkynes produce mixtures of regioisomers with generally only modest selectivity. Kostanecki reaction protocol furnishes a notable improvement in reaction conditions for coumarin synthesis and gives rise to the advantage of its synthetic capability, especially for highly functionalized 4-arylcoumarins with structural diversity.

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Acknowledgments

Dr. I. Ansary and Dr. A. Taher highly acknowledge the Department of Chemistry (Burdwan University) and Burdwan Raj College, respectively, for infrastructural facilities.

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Conflict of interest

The authors declare no conflict of interest.

References

  1. 1. Kumar S, Saini A, Sandhu JS. LiBr-mediated, solvent free von Pechmann reaction: Facile and efficient method for the synthesis of 2H-chromen-2-ones. ARKIVOC. 2007;2007:18-23. DOI: 10.3998/ark.5550190.0008.f03
  2. 2. Zembower DE, Liao S, Flavin MT, Xu ZQ , Stup TL, Buckheit RW, et al. Structural analogues of the calanolide anti-HIV agents. Modification of the trans-10,11-dimethyldihydropyran-12-ol ring (ring C). Journal of Medicinal Chemistry. 1997;40:1005-1017. DOI: 10.1021/jm960355m
  3. 3. Završnik D, Muratović S, Makuc D, Plavec J, Cetina M, Nagl A, et al. Benzylidene-bis-(4-hydroxycoumarin) and benzopyrano-coumarin derivatives: Synthesis, 1H/13C-NMR conformational and X-ray crystal structure studies and in vitro antiviral activity evaluations. Molecules. 2011;16:6023-6040. DOI: 10.3390/molecules16076023
  4. 4. Nawrot-Modranka J, Nawrot E, Graczy K. In vivo antitumor, in vitro antibacterial activity and alkylating properties of phosphorohydrazine derivatives of coumarin and chromone. European Journal of Medicinal Chemistry. 2006;41:1301-1309. DOI: 10.1016/j.ejmech.2006.06.004
  5. 5. EI-Saghier AMM, Naili MB, Rammash BK, Saleh NA, Kreddan KM. Synthesis and antibacterial activity of some new fused chromenes. ARKIVOC. 2007;2007:83-91. DOI: 10.3998/ark.5550190.0008.g09
  6. 6. Creaven BS, Egan DA, Kavanagh K, McCann M, Mahon M, Noble A, et al. Synthesis and antimicrobial activity of copper(II) and silver(I) complexes of hydroxynitrocoumarins: X-ray crystal structures of [Cu(hnc)2(H2O)2].2H2O and [Ag(hnc)] (hncH = 4-hydroxy-3-nitro-2H-chromen-2-one). Polyhedron. 2005;24:949-957. DOI: 10.1016/j.poly.2005.03.006
  7. 7. Golfakhrabadi F, Abdollahi M, Ardakani MRS, Saeidnia S, Akbarzadeh T, Ahmadabadi AN, et al. Anticoagulant activity of isolated coumarins (suberosin and suberenol) and toxicity evaluation of Ferulago carduchorum in rats. Pharmaceutical Biology. 2014;52:1335-1340. DOI: 10.3109/13880209.2014.892140
  8. 8. Ronad P, Dharbamalla S, Hunshal R, Maddi V. Synthesis of novel substituted 7-(benzylideneamino)-4-methyl-2H-chromen-2-one derivatives as anti-inflammatory and analgesic agents. Archiv der Pharmazie: Chemistry in Life Sciences. 2008;341:696-700. DOI: 10.1002/ardp.200800057
  9. 9. Lin CM, Huang ST, Lee FW, Sawkuo H, Lin MH. 6-Acyl-4-aryl/alkyl-5,7-dihydroxycoumarins as anti-inflammatory agents. Bioorganic & Medicinal Chemistry. 2006;14:4402-4409. DOI: 10.1016/j.bmc.2006.02.042
  10. 10. Wang CJ, Hsieh YJ, Chu CY, Lin YL, Tseng TH. Inhibition of cell cycle progression in human leukemia HL-60 cells by esculetin. Cancer Letters. 2002;183:163-168. DOI: 10.1016/S0304-3835(02)00031-9
  11. 11. Dexeus FH, Logothetis CJ, Sella A, Fitz K, Amato R, Reuben JM, et al. Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology. 1990;8:325-329. DOI: 10.1200/JCO.1990.8.2.325
  12. 12. Bhat MA, Siddiqui N, Khan SA. Synthesis of novel thioureido derivatives of sulfonamides and thiosemicarbazido derivatives of coumarin as potential anticonvulsant and analgesic agents. Indian Journal of Pharmaceutical Sciences. 2006;68:120-124. DOI: 10.4103/0250-474X.22984
  13. 13. Tyagi YK, Kumar A, Raj HG, Vohra P, Gupta G, Kumari R, et al. Synthesis of novel amino and acetyl amino-4-methylcoumarins and evaluation of their antioxidant activity. European Journal of Medicinal Chemistry. 2005;40:413-420. DOI: 10.1016/j.ejmech.2004.09.002
  14. 14. Sardari S, Mori Y, Horita K, Micetich RG, Nishibe S, Daneshtalab M. Synthesis and antifungal activity of coumarins and angular furanocoumarins. Bioorganic & Medicinal Chemistry. 1999;7:1933-1940. DOI: 10.1016/S0968-0896(99)00138-8
  15. 15. Stein AC, Alvarez S, Avancini C, Zacchino S, von Poser G. Antifungal activity of some coumarins obtained from species of Pterocaulon (Asteraceae). Journal of Ethnopharmacology. 2006;107:95-98. DOI: 10.1016/j.jep.2006.02.009
  16. 16. Chen Y, Zhang Q , Zhang B, Xia P, Xia Y, Yang Z-Y, et al. Anti-AIDS agents. Part 56: Synthesis and anti-HIV activity of 7-thia-di-O-(−)-camphanoyl-(+)-cis-khellactone (7-thia-DCK) analogs. Bioorganic & Medicinal Chemistry. 2004;12:6383-6387. DOI: 10.1016/j.bmc.2004.09.038
  17. 17. Cravotto G, Nano GM, Palmisano G, Tagliapietra S. An asymmetric approach to coumarin anticoagulants via hetero-Diels–Alder cycloaddition. Tetrahedron: Asymmetry. 2001;12:707-709. DOI: 10.1016/S0957-4166(01)00124-0
  18. 18. Fan GJ, Mar W, Park MK, Choi EW, Kim K, Kim S. A novel class of inhibitors for steroid 5α-reductase: Synthesis and evaluation of umbelliferone derivatives. Bioorganic & Medicinal Chemistry Letters. 2001;11:2361-2363. DOI: 10.1016/S0960-894X(01)00429-2
  19. 19. Zahradnik M. The Production and Application of Fluorescent Brightening Agents. Chichester: John Wiley & Sons; 1992
  20. 20. Hepworth JD, Gabbutt CD, Heron BM. In: Katritzky AR, Rees CW, Scriven EFV, editors. Comprehensive Heterocyclic Chemistry II. Vol. 5. Oxford: Pergamon Press; 1996. pp. 301-350
  21. 21. Green GR, Evans JM, Vong AK. In: Katritzky AR, Rees CW, Scriven EFV, editors. Comprehensive Heterocyclic Chemistry II. Vol. 5. Oxford: Pergamon Press; 1996. pp. 469-500
  22. 22. O’Kennedy R, Coumarins TRD. Biology, Applications and Mode of Action. Chichester: John Wiley & Sons; 1997
  23. 23. Meuly WC, Kirk-Othmer. Encyclopedia of Chemical Technology. 3rd ed. Vol. 7. New York: John Wiley & Sons; 1979. p. 196
  24. 24. von Pechmann H, Duisberg C. Ueber die Verbindungen der Phenole mit Acetessigäther. Berichte der Deutschen Chemischen Gesellschaft. 1883;16:2119-2128. DOI: 10.1002/cber.188301602117
  25. 25. von Pechmann H, Duisberg C. Neue Bildungsweise der Cumarine. Synthese des Daphnetins. I. Berichte der Deutschen Chemischen Gesellschaft. 1884;17:929-979. DOI: 10.1002/cber.188401701248
  26. 26. Panetta A, Rapoport H. New syntheses of coumarins. The Journal of Organic Chemistry. 1982;47:946-950. DOI: 10.1021/jo00345a009
  27. 27. Miyano M, Dorn CR. Mirestrol. I. Preparation of the tricyclic intermediate. The Journal of Organic Chemistry. 1972;37:259-268. DOI: 10.1021/jo00967a017
  28. 28. Woods LL, Sapp J. A new one-step synthesis of substituted coumarins. The Journal of Organic Chemistry. 1962;27:3703-3705. DOI: 10.1021/jo01057a519
  29. 29. Sethna SM, Shah NM, Shah RC. Aluminium chloride, a new reagent for the condensation of β-ketonic esters with phenols. Part I. The condensations of methyl β-resorcylate, β-resorcylic acid, and resacetophenone with ethyl acetoacetate. Journal of the Chemical Society. 1938:228-232. DOI: 10.1039/JR9380000228
  30. 30. Corrie JET. A convenient synthesis of N-(7-dimethylamino-4-methylcoumarin-3-yl)-maleimide incorporating a novel variant of the Pechmann reaction. Journal of the Chemical Society. Perkin Transactions. 1990;(7):2151-2152. DOI: 10.1039/P19900002151
  31. 31. Smitha G, Reddy SC. ZrCl4-catalyzed Pechmann reaction: Synthesis of coumarins under solvent-free conditions. Synthetic Communications. 2004;34:3997-4003. DOI: 10.1081/SCC-200034821
  32. 32. Valizadeh H, Shockravi A. An efficient procedure for the synthesis of coumarin derivatives using TiCl4 as catalyst under solvent-free conditions. Tetrahedron Letters. 2005;46:3501-3503. DOI: 10.1016/j.tetlet.2005.03.124
  33. 33. John EVO, Israelstam SS. Notes. Use of cation exchange resins in organic reactions. I. The Von Pechmann reaction. The Journal of Organic Chemistry. 1961;26:240-242. DOI: 10.1021/jo01060a602
  34. 34. Laufer MC, Hausmann H, Hölderich WF. Synthesis of 7-hydroxycoumarins by Pechmann reaction using Nafion resin/silica nanocomposites as catalysts. Journal of Catalysis. 2003;218:315-320. DOI: 10.1016/S0021-9517(03)00073-3
  35. 35. Hoefnagel AJ, Gunnewegh EA, Downing RS, van Bekkum H. Synthesis of 7-hydroxycoumarins catalysed by solid acid catalysts. Journal of the Chemical Society, Chemical Communications. 1995:225-226. DOI: 10.1039/C39950000225
  36. 36. Chavan SP, Shivasankar K, Sivappa R, Kale R. Zinc mediated transesterification of β-ketoesters and coumarin synthesis. Tetrahedron Letters. 2002;43:8583-8586. DOI: 10.1016/S0040-4039(02)02006-3
  37. 37. Singh V, Singh J, Kaur KP, Kad GL. Acceleration of the Pechmann reaction by microwave irradiation: Application to the preparation of coumarins. Journal of Chemical Research, Synopses. 1997:58-59. DOI: 10.1039/A605672E
  38. 38. Maheswara M, Siddaiah V, Damu GLV, Rao YK, Rao CV. A solvent-free synthesis of coumarins via Pechmann condensation using heterogeneous catalyst. Journal of Molecular Catalysis A: Chemical. 2006;255:49-52. DOI: 10.1016/j.molcata.2006.03.051
  39. 39. Holden MS, Crouch RD. The Pechmann reaction. Journal of Chemical Education. 1998;75:1631. DOI: 10.1021/ed075p1631
  40. 40. Li T-S, Zhang Z-H, Yang F, Fu C-G. Montmorillonite clay catalysis. Part 7. An environmentally friendly procedure for the synthesis of coumarins via Pechmann condensation of phenols with ethyl acetoacetate. Journal of Chemical Research, Synopses. 1998:38-39. DOI: 10.1039/a703694i
  41. 41. Potdar MK, Mohile SS, Salunkhe MM. Coumarin syntheses via Pechmann condensation in Lewis acidic chloroaluminate ionic liquid. Tetrahedron Letters. 2001;42:9285-9287. DOI: 10.1016/S0040-4039(01)02041-X
  42. 42. Bose DS, Rudradas AP, Babu MH. The indium(III) chloride-catalyzed von Pechmann reaction: A simple and effective procedure for the synthesis of 4-substituted coumarins. Tetrahedron Letters. 2002;43:9195-9197. DOI: 10.1016/S0040-4039(02)02266-9
  43. 43. Potdar MK, Rasalkar MS, Mohile SS, Salunkhe MM. Convenient and efficient protocols for coumarin synthesis via Pechmann condensation in neutral ionic liquids. Journal of Molecular Catalysis A: Chemical. 2005;235:249-252. DOI: 10.1016/j.molcata.2005.04.007
  44. 44. Alexander VM, Bhat RP, Samant SD. Bismuth(III) nitrate pentahydrate—A mild and inexpensive reagent for synthesis of coumarins under mild conditions. Tetrahedron Letters. 2005;46:6957-6959. DOI: 10.1016/j.tetlet.2005.07.117
  45. 45. Reddy BM, Patil MK, Lakshmanan P. Sulfated CexZr1−xO2 solid acid catalyst for solvent free synthesis of coumarins. Journal of Molecular Catalysis A: Chemical. 2006;256:290-294. DOI: 10.1016/j.molcata.2006.05.001
  46. 46. Rodríguez-Domínguez JC, Kirsch G. Sulfated zirconia, a mild alternative to mineral acids in the synthesis of hydroxycoumarins. Tetrahedron Letters. 2006;47:3279-3281. DOI: 10.1016/j.tetlet.2006.03.030
  47. 47. Reddy YT, Sonar VN, Crooks PA, Dasari PK, Reddy PN, Rajitha B. Ceric ammonium nitrate (CAN): An efficient catalyst for the coumarin synthesis via Pechmann condensation using conventional heating and microwave irradiation. Synthetic Communications. 2008;38:2082-2088. DOI: 10.1080/00397910802029091
  48. 48. Kotharkar SA, Bahekar SS, Shinde DB. Chlorosulfonic acid-catalysed one-pot synthesis of coumarin. Mendeleev Communications. 2006;16:241-242. DOI: 10.1070/MC2006v016n04ABEH002256
  49. 49. Lakouraj MM, Bagheri N, Hasantabar V. Synthesis and application of nanocrystalline-cellulose-supported acid ionic liquid catalyst in Pechmann reaction. International Journal of Carbohydrate Chemistry. 2013;2013:1-8. DOI: 10.1155/2013/452580
  50. 50. Puri S, Kaur B, Parmar A, Kumar H. Ultrasound-promoted greener synthesis of 2H-chromen-2-ones catalyzed by copper perchlorate in solventless media. Ultrasonics Sonochemistry. 2009;16:705-707. DOI: 10.1016/j.ultsonch.2009.04.002
  51. 51. Ranjbar-Karimi R, Hashemi-Uderji S, Mousavi M. Selectfluor promoted environmental-friendly synthesis of 2H-chromen-2-ones derivatives under various reaction conditions. Journal of the Iranian Chemical Society. 2011;8:193-197. DOI: 10.1007/BF03246215
  52. 52. DeGrote J, Tyndall S, Wong KF, VanAlstine-Parris M. Synthesis of 7-alkoxy-4-trifluoromethylcoumarins via the von Pechmann reaction catalyzed by molecular iodine. Tetrahedron Letters. 2014;55:6715-6717. DOI: 10.1016/j.tetlet.2014.10.025
  53. 53. Prajapati D, Gohain M. Iodine a simple, effective and inexpensive catalyst for the synthesis of substituted coumarins. Catalysis Letters. 2007;119:59-63. DOI: 10.1007/s10562-007-9186-6
  54. 54. Wu J, Diao T, Sun W, Li Y. Expeditious approach to coumarins via Pechmann reaction catalyzed by molecular iodine or AgOTf. Synthetic Communications. 2006;36:2949-2956. DOI: 10.1080/00397910600773692
  55. 55. Shirini F, Yahyazadeh A, Mohammadi K. A solvent-free synthesis of coumarins using 1,3-disulfonic acid imidazolium hydrogen sulfate as a reusable and effective ionic liquid catalyst. Research on Chemical Intermediates. 2015;41:6207-6218. DOI: 10.1007/s11164-014-1733-3
  56. 56. Zhang Y, Zhu A, Li Q , Li L, Zhao Y, Wang J. Cholinium ionic liquids as cheap and reusable catalysts for the synthesis of coumarins via Pechmann reaction under solvent-free conditions. RSC Advances. 2014;4:22946-22950. DOI: 10.1039/c4ra02227k
  57. 57. Khalafi-Nezhad A, Haghighi SM, Panahi F. Nano-TiO2 on dodecyl-sulfated silica: As an efficient heterogeneous Lewis acid-surfactant-combined catalyst (HLASC) for reaction in aqueous media. ACS Sustainable Chemistry & Engineering. 2013;1:1015-1023. DOI: 10.1021/sc4000913
  58. 58. Karami B, Kiani M. ZrOCl2.8H2O/SiO2: An efficient and recyclable catalyst for the preparation of coumarin derivatives by Pechmann condensation reaction. Catalysis Communications. 2011;14:62-67. DOI: 10.1016/j.catcom.2011.07.002
  59. 59. Ma Z, He M, Zhang H, Ma J, Yuan H. Hydrophobic perfluoroalkylsulfonyl imide solid acid as catalyst of esterification and Pechmann condensation. Chinese Journal of Organic Chemistry. 2014;34:2255-2261. DOI: 10.6023/cjoc201406027
  60. 60. Palaniappa S, John A. A novel polyaniline–fluoroboric acid–dodecylhydrogensulfate salt: Versatile reusable polymer based solid acid catalyst for organic transformations. Journal of Molecular Catalysis A: Chemical. 2005;233:9-15. DOI: 10.1016/j.molcata.2005.02.002
  61. 61. Dabiri M, Salehi P, Zolfigol MA, Baghbanzadeh M. Silica sulfuric acid as an efficient and reusable catalyst for the Pechmann synthesis of coumarins under solvent-free conditions. Heterocycles. 2007;71:677-682. DOI: 10.3987/COM-06-10956
  62. 62. Ghodke S, Chudasama U. Solvent free synthesis of coumarins using environment friendly solid acid catalysts. Applied Catalysis A: General. 2013;453:219-226. DOI: 10.1016/j.apcata.2012.12.024
  63. 63. Ahmed AI, El-Hakam SA, Elghany MAA, El-Yazeed WSA. Synthesis and characterization of new solid acid catalysts, H3PW12O40 supported on nanoparticle tin oxide: An efficient catalyst for the preparation of 7-hydroxy-4-methylcoumarin. Applied Catalysis A: General. 2011;407:40-48. DOI: 10.1016/j.apcata.2011.08.020
  64. 64. Albadi J, Shirini F, Abasi J, Armand N, Motaharizadeh T. A green, efficient and recyclable poly(4-vinylpyridine)-supported copper iodide catalyst for the synthesis of coumarin derivatives under solvent-free conditions. C. R. Chimie. 2013;16:407-411. DOI: 10.1016/j.crci.2012.10.002
  65. 65. Rahmatpour A, Mohammadian S. An environmentally friendly, chemoselective, and efficient protocol for the preparation of coumarin derivatives by Pechman condensation reaction using new and reusable heterogeneous Lewis acid catalyst polystyrene-supported GaCl3. C. R. Chimie. 2013;16:271-278. DOI: 10.1016/j.crci.2013.01.006
  66. 66. Karami B, Khodabakhshi S, Eskandari K. Alternative two-step route to khellactone analogues using silica tungstic acid and sodium hydrogen phosphate. Chemical Papers. 2013;67:474-1478. DOI: 10.2478/s11696-013-0411-z
  67. 67. Zareyee D, Serehneh M. Recyclable CMK-5 supported sulfonic acid as an environmentally benign catalyst for solvent-free one-pot construction of coumarin through Pechmann condensation. Journal of Molecular Catalysis A: Chemical. 2014;391:88-91. DOI: 10.1016/j.molcata.2014.04.013
  68. 68. Vahabi V, Hatamjafari F. Microwave assisted convenient one-pot synthesis of coumarin derivatives via Pechmann condensation catalyzed by FeF3 under solvent-free conditions and antimicrobial activities of the products. Molecules. 2014;19:13093-13103. DOI: 10.3390/molecules190913093
  69. 69. Prousis KC, Avlonitis N, Heropoulos GA, Calogeropoulou T. FeCl3-catalysed ultrasonic-assisted, solvent-free synthesis of 4-substituted coumarins. A useful complement to the Pechmann reaction. Ultrasonics Sonochemistry. 2014;21:937-942. DOI: 10.1016/j.ultsonch.2013.10.018
  70. 70. Esfahani FK, Zareyee D, Yousefi R. Sulfonated core-shell mgnetic nanoparticle (Fe3O4@SiO2@PrSO3H) as a highly active and durable protonic acid catalyst; synthesis of coumarin derivatives through Pechmann reaction. ChemCatChem. 2014;6:3333-3337. DOI: 10.1002/cctc.201402547
  71. 71. Baghbanian SM, Farhang M. CuFe2O4 nanoparticles: A magnetically recoverable and reusable catalyst for the synthesis of coumarins via Pechmann reaction in water. Synthetic Communications. 2014;44:697-706. DOI: 10.1080/00397911.2013.835423
  72. 72. Sharma RK, Monga Y, Puri A. Zirconium(IV)-modified silica@magnetic nanocomposites: Fabrication, characterization and application as efficient, selective and reusable nanocatalysts for Friedel-Crafts, Knoevenagel and Pechmann condensation reactions. Catalysis Communications. 2013;35:110-114. DOI: 10.1016/j.catcom.2013.02.016
  73. 73. Kim J-C, Ryoo R, Opanasenko M, Shamzhy M, Cejka J. Mesoporous MFI zeolite nanosponge as a high performance catalyst in the Pechmann condensation reaction. ACS Catalysis. 2015;5:2596-2604. DOI: 10.1021/cs502021a
  74. 74. Karami B, Kiani M, Hoseini MA. In(OTf)3 as a powerful and recyclable catalyst for Pechmann condensation without solvent. Chinese Journal of Catalysis. 2014;35:1206-1211. DOI: 10.1016/S1872-2067(14)60090-5
  75. 75. Wang H. Magnesium bis(trifluoromethane)sulfonimide: An efficient catalyst for the synthesis of coumarins under solvent-free conditions. Monatshefte fuer Chemie. 2013;144:411-414. DOI: 10.1007/s00706-012-0823-4
  76. 76. Khaligh NG. Ultrasound-assisted one-pot synthesis of substituted coumarins catalyzed by poly(4-vinylpyridinium) hydrogen sulfate as an efficient and reusable solid acid catalyst. Ultrasonics Sonochemistry. 2013;20:1062-1068. DOI: 10.1016/j.ultsonch.2013.01.001
  77. 77. Mokhtary M, Najafizadeh F. Polyvinylpolypyrrolidone-bound boron trifluoride (PVPP-BF3); a mild and efficient catalyst for synthesis of 4-metyl coumarins via the Pechmann reaction. C. R. Chimie. 2012;15:530-532. DOI: 10.1016/j.crci.2012.03.004
  78. 78. Opanasenko M, Shamzhy M, Čejka J. Solid acid catalysts for coumarin synthesis by the Pechmann reaction: MOFs versus zeolites. ChemCatChem. 2013;5:1024-1031. DOI: 10.1002/cctc.201200232
  79. 79. Jadhav NH, Sakate SS, Rasal NK, Shinde DR, Pawar RA. Heterogeneously catalyzed Pechmann condensation employing the tailored Zn0.925Ti0.075O NPs: Synthesis of coumarin. ACS Omega. 2019;4:8522-8527. DOI: 10.1021/acsomega.9b00257
  80. 80. Zambare AS, Khan FAK, Zambare SP, Shinde SD, Sangshetti JN. Recent advances in the synthesis of coumarin derivatives via Pechmann condensation. Current Organic Chemistry. 2016;20:798-828. DOI: 10.2174/1385272820666151026224227
  81. 81. Kumar BV, Naik HSB, Girija D, Kumar BV. ZnO nanoparticle as catalyst for efficient green one-pot synthesis of coumarins through Knoevenagel condensation. Journal of Chemical Sciences. 2011;123:615-621. DOI: 10.1007/s12039-011-0133-0
  82. 82. Karami B, Farahi M, Khodabakhshi S. Rapid synthesis of novel and known coumarin-3-carboxylic acids using stannous chloride dihydrate under solvent-free conditions. Helvetica Chimica Acta. 2012;95:455-460. DOI: 10.1002/hlca.201100342
  83. 83. Sripathi SK, Logeeswari K. Synthesis of 3-aryl coumarin derivatives using ultrasound. International Journal of Organic Chemistry. 2013;3:42-47. DOI: 10.4236/ijoc.2013.31004
  84. 84. Nourmohammadian F, Norozy S. Application of non-corrosive acids in three-component, one-pot synthesis of commercial coumarin dye. Progress in Color, Colorants and Coatings. 2010;03:102-109. DOI: not available
  85. 85. Gholap SS, Deshmukh UP, Tambe MS. Synthesis and in-vitro antimicrobial screening of 3-cinnamoyl coumarin and 3-[3-(1H-indol-2-yl)-3-aryl-propanoyl]-2H-chromen-2-ones. Iranian Journal of Catalysis. 2013;3:171-176. DOI: not available
  86. 86. Shaabani A, Ghadari R, Rahmati A, Rezayan AH. Coumarin synthesis via Knoevenagel condensation reaction in 1,1,3,3-N,N,N',N'-tetramethylguanidinium trifluoroacetate ionic liquid. Journal of the Iranian Chemical Society. 2009;6:710-714. DOI: 10.1007/BF03246160
  87. 87. Verdía P, Santamarta F, Tojo E. Knoevenagel reaction in [MMIm][MSO4]: Synthesis of coumarins. Molecules. 2011;16:4379-4388. DOI: 10.3390/molecules16064379
  88. 88. Valizadeh H, Gholipour H. Imidazolium-based phosphinite ionic liquid (IL-OPPh2) as reusable catalyst and solvent for the Knoevenagel condensation reaction. Synthetic Communications. 2010;40:1477-1485. DOI: 10.1080/00397910903097310
  89. 89. Heravi MM, Ansari P, Saeedi M, Tavakoli-Hosseini N, Karimi N. Green and practical synthesis of benzopyran and 3-substituted coumarine derivatives by Bronsted acid ionic liquid [(CH2)4SO3HMIM][HSO4]. Bulletin of the Chemical Society of Ethiopia. 2011;25:315-320. DOI: 10.4314/bcse.v25i2.65915
  90. 90. Roussaki M, Kontogiorgis CA, Hadjipavlou-Litina D, Hamilakis S, Detsi A. A novel synthesis of 3-aryl coumarins and evaluation of their antioxidant and lipoxygenase inhibitory activity. Bioorganic & Medicinal Chemistry Letters. 2010;20:3889-3892. DOI: 10.1016/j.bmcl.2010.05.022
  91. 91. Nourmohammadian F, Gholami MD. Microwave-promoted one-pot syntheses of coumarin dyes. Synthetic Communications. 2010;40:901-909. DOI: 10.1080/00397910903026699
  92. 92. Han J, Xin Y, Zhao J, Zhu S. L-Proline catalyzed condensation–cyclization tandem process: Facile and effective synthesis of 3-polyfluoroalkanesulfonyl coumarin. Journal of Fluorine Chemistry. 2011;132:409-413. DOI: 10.1016/j.jfluchem.2011.04.001
  93. 93. You X, Yu H, Wang M, Wu J, Shang Z. A Green method for the synthesis of 3-substituted coumarins catalyzed by L-lysine in water via Knoevenagel condensation. Letters in Organic Chemistry. 2012;9:19-23. DOI: 10.2174/157017812799303953
  94. 94. Lunkad AS, Sawant RL. Conventional and microwave assisted synthesis of some new derivatives of coumarin containing pyrazoline and investigation of their antibacterial and antifungal activities. International Journal of Pharmaceutical Sciences and Research. 2018;9:2852-2858. DOI: 10.13040/IJPSR.0975-8232.9(7).2852-58
  95. 95. Ajani OO, Nwinyi OC. Microwave-assisted synthesis and evaluation of antimicrobial activity of 3-{3-(s-aryl and s-heteroaromatic)acryloyl}-2H-chromen-2-one derivatives. Journal of Heterocyclic Chemistry. 2010;47:179-187. DOI: 10.1002/jhet.298
  96. 96. Sashidhara KV, Kumar A, Kumar M, Sonkar R, Bhatia G, Khanna A. Novel coumarin derivatives as potential antidyslipidemic agents. Bioorganic & Medicinal Chemistry Letters. 2010;20:4248-4251. DOI: 10.1016/j.bmcl.2010.05.023
  97. 97. Bhusal RP, Cho PY, Kim SA, Park H, Kim HS. Synthesis of green emitting coumarin bioconjugate for the selective determination of flu antigen. Bulletin of the Korean Chemical Society. 2011;32:1461-1462. DOI: 10.5012/bkcs.2011.32.5.1461
  98. 98. De Souza M, da Silveira Pinto L. Sonochemistry as a general procedure for the synthesis of coumarins, including multigram synthesis. Synthesis. 2017;49:2677-2682. DOI: 10.1055/s-0036-1590201
  99. 99. El-Wahab AHFA, Mohamed HM, El-Agrody AM, Bedair AH, Eid FA, Khafagy MM, et al. Synthesis and reactions of some new diiodocoumarin derivatives bearing side chains and some of their biological activities. American Journal of Chemistry. 2011;1:1-8. DOI: 10.5923/j.chemistry.20110101.01
  100. 100. Mohamed HM, Abd El-Wahab AHF, Ahmed KA, El-Agrody AM, Bedair AH, Eid FA, et al. Synthesis, reactions and antimicrobial activities of 8-ethoxycoumarin derivatives. Molecules. 2012;17:971-988. DOI: 10.3390/molecules17010971
  101. 101. Kaye PT, Robinson RS. Dabco-catalysed reactions of salicylaldehydes with acrylate derivatives. Synthetic Communications. 1996;26:2085-2097. DOI: 10.1080/00397919608003567
  102. 102. Bacsa J, Kaye PT, Robinson RS. Novel products from Baylis-Hillman reactions of salicylaldehydes. South African Journal of Chemistry. 1998;51:47-54. Available at: https://hdl.handle.net/10520/AJA03794350_1721
  103. 103. Kaye PT, Musa MA, Nocanda XW. Efficient and chemoselective access to 3-(chloromethyl)coumarins via direct cyclisation of unprotected Baylis-Hillman adducts. Synthesis. 2003;2003:531-534. DOI: 10.1055/s-2003-37655
  104. 104. Olomola TO, Klein R, Kaye PT. Convenient synthesis of 3-methylcoumarins and coumarin-3-carbaldehydes. Synthetic Communications. 2012;42:251-257. DOI: 10.1080/00397911.2010.523491
  105. 105. Kaye PT, Musa MA. A convenient and improved Baylis-Hillman synthesis of 3-substituted 2H-1-benzopyran-2-ones. Synthesis. 2002;2002:2701-2706. DOI: 10.1055/s-2002-35984
  106. 106. Kaye PT, Musa MA. Application of Baylis–Hillman methodology in the synthesis of coumarin derivatives. Synthetic Communications. 2003;33:1755-1770. DOI: 10.1081/SCC-120018937
  107. 107. Hwang I-T, Lee S-A, Hwang J-S, Lee K-I. A facile synthesis of highly functionalized 4-arylcoumarins via Kostanecki reactions mediated by DBU. Molecules. 2011;16:6313-6321. DOI: 10.3390/molecules16086313
  108. 108. Rao HSP, Sivakumar S. Condensation of r-aroylketene dithioacetals and 2-hydroxyarylaldehydes results in facile synthesis of a combinatorial library of 3-aroylcoumarins. The Journal of Organic Chemistry. 2006;71:8715-8723. DOI: 10.1021/jo061372e
  109. 109. Upadhyay PK, Kumar P. A novel synthesis of coumarins employing triphenyl(a-carboxymethylene)-phosphorane imidazolide as a C-2 synthon. Tetrahedron Letters. 2009;50:236-238. DOI: 10.1016/j.tetlet.2008.10.133
  110. 110. Valizadeh H, Gholipour H, Mahmoudian M. Phosphinite ionic liquid (IL-OPPh2) as a recyclable reagent for the efficient synthesis of coumarins under microwave irradiation conditions. Journal of the Iranian Chemical Society. 2011;8:862-871. DOI: 10.1007/BF03245917
  111. 111. Yavari I, Hekmatshoar R, Zonouzi A. A new and efficient route to 4-carboxymethylcoumarins mediated by vinyltriphenylphosphonium salt. Tetrahedron Letters. 1998;39:2391-2392. DOI: 10.1016/S0040-4039(98)00206-8
  112. 112. Hekmatshoar R, Souri S, Rahimifard M, Faridbod F. Novel synthesis of oxygenated coumarins from substituted phenols mediated by vinyl triphenylphosphonium salt under microwave irradiation. Phosphorus, Sulfur and Silicon. 2002;177:2827-2833. DOI: 10.1080/10426500214882
  113. 113. Yavari I, Adib M, Hojabri L. Vinyltriphenylphosphonium salt mediated synthesis of functionalized coumarins. Tetrahedron. 2001;57:7537-7540. DOI: 10.1016/S0040-4020(01)00703-7
  114. 114. Majumdar KC, Ansary I, Samanta S, Roy B. Aromatic electrophilic substitution vs. intramolecular Wittig reaction: Vinyltriphenylphosphonium salt mediated synthesis of 4-carboxyalkyl-8-formyl coumarins. Synlett. 2011;2011:0694-0698. DOI: 10.1055/s-0030-1259534
  115. 115. Galariniotou E, Fragos V, Makri A, Litinas KE, Nicolaides DN. Synthesis of novel pyridocoumarins and benzo-fused 6-azacoumarins. Tetrahedron. 2007;63:8298-8304. DOI: 10.1016/j.tet.2007.05.102
  116. 116. Trost BM, Toste FD. A new palladium-catalyzed addition: A mild method for the synthesis of coumarins. Journal of the American Chemical Society. 1996;118:6305-6306. DOI: 10.1021/ja961107i
  117. 117. Trost BM, Toste FD, Greenman K. Atom economy. Palladium-catalyzed formation of coumarins by addition of phenols and alkynoates via a net C-H insertion. Journal of the American Chemical Society. 2003;125:4518-4526. DOI: 10.1021/ja0286573
  118. 118. Kotani M, Yamamoto K, Oyamada J, Fujiwara Y, Kitamura T. A convenient synthesis of coumarins by palladium(II)-catalyzed reaction of phenols with propiolic acids. Synthesis. 2004;2004:1466-1470. DOI: 10.1055/s-2004-822360
  119. 119. Kutubi Md S, Hashimoto T, Kitamura T. Improved synthesis of coumarins by iron(III)-catalyzed cascade reaction of propiolic acids and phenols. Synthesis. 2011;2011:1283-1289. DOI: 10.1055/s-0030-1258473
  120. 120. Park KH, Jung IG, Chung YK. Synthesis of coumarins catalyzed by heterobimetallic Co/Rh nanoparticles. Synlett. 2004;2004:2541-2544. DOI: 10.1055/s-2004-834826
  121. 121. Leão RAC, De Moraes PF, Pedro MCBC, Costa PRR. Synthesis of coumarins and neoflavones through zinc chloride catalyzed hydroarylation of acetylenic esters with phenols. Synthesis. 2011;2011:3692-3696. DOI: 10.1055/s-0031-1289576
  122. 122. Fernandes TA, Carvalho RCC, Goncalves TMD, da Silva AJM, Costa PRR. A tandem palladium-catalyzed heck-lactonization through the reaction of ortho-iodophenols with b-substituted acrylates: Synthesis of 4,6-substituted coumarins. Tetrahedron Letters. 2008;49:3322-3325. DOI: 10.1016/j.tetlet.2008.03.037
  123. 123. Fernandes TA, Vaz BG, Eberlin MN, da Silva AJM, Costa PRR. Palladium-catalyzed tandem Heck-lactonization from o-iodophenols and enoates: Synthesis of coumarins and the study of the mechanism by electrospray ionization mass spectrometry. The Journal of Organic Chemistry. 2010;75:7085-7091. DOI: 10.1021/jo1010922
  124. 124. Kadnikov DV, Larock RC. Palladium-catalyzed carbonylative annulation of terminal alkynes: Synthesis of coumarins and 2-quinolones. Journal of Organometallic Chemistry. 2003;687:425-435. DOI: 10.1016/S0022-328X(03)00786-1
  125. 125. Kadnikov DV, Larock RC. Palladium-catalyzed carbonylative annulation of internal alkynes: Synthesis of 3,4-disubstituted coumarins. The Journal of Organic Chemistry. 2003;68:9423-9432. DOI: 10.1021/jo0350763
  126. 126. Gabriele B, Mancuso R, Salerno G, Plastina P. A novel palladium-catalyzed dicarbonylation process leading to coumarins. The Journal of Organic Chemistry. 2008;73:756-759. DOI: 10.1021/jo702243m
  127. 127. Li K, Zeng Y, Neuenswander B, Tunge JA. Sequential Pd(II)-Pd(0) catalysis for the rapid synthesis of coumarins. The Journal of Organic Chemistry. 2005;70:6515-6518. DOI: 10.1021/jo050671l
  128. 128. Yamamoto Y, Kirai N. Synthesis of 4-arylcoumarins via Cu-catalyzed hydroarylation with arylboronic acids. Organic Letters. 2008;10:5513-5516. DOI: 10.1021/ol802239n
  129. 129. Fillion E, Dumas AM, Kuropatwa BA, Malhotra NR, Sitler TC. Yb(OTf)3-catalyzed reactions of 5-alkylidene meldrum’s acids with phenols: One-pot assembly of 3,4-dihydrocoumarins, 4-chromanones, coumarins, and chromones. The Journal of Organic Chemistry. 2006;71:409-412. DOI: 10.1021/jo052000t
  130. 130. Toräng J, Vanderheiden S, Nieger M, Bräse S. Synthesis of 3-alkylcoumarins from salicylaldehydes and α,β-unsaturated aldehydes utilizing nucleophilic carbenes: A new umpoled domino reaction. European Journal of Organic Chemistry. 2007;2007:943-952. DOI: 10.1002/ejoc.200600718
  131. 131. Majumdar KC, Samanta S, Ansary I, Roy B. An unusual one-pot synthesis of 3-benzoylcoumarins and coumarin-3-carbaldehydes from 2-hydroxybenzaldehydes under esterification conditions. RSC Advances. 2012;2:2137-2143. DOI: 10.1039/C2RA00820C
  132. 132. Li L, Yang Q , Jia Z, Luo S. Organocatalytic electrochemical C–H lactonization of aromatic carboxylic acids. Synthesis. 2018;50:2924-2929. DOI: 10.1055/s-0036-1591558

Written By

Inul Ansary and Abu Taher

Submitted: 29 June 2019 Reviewed: 04 August 2019 Published: 22 October 2019