| 97% |
With diazabicyclo[2.2.2]octane incorporated on Fe3O4 magnetic nanoparticles In neat (no solvent) at 90℃; for 0.583333h; Green chemistry; |
|
| 97% |
With sulfonic acid supported on the silica coated Fe3O4 nanoparticles In neat (no solvent) at 130℃; for 0.416667h; Green chemistry; chemoselective reaction; |
|
| 97% |
With organosulfonic acid functionalized silica-coated magnetic nanoparticles at 120℃; for 0.74h; Green chemistry; |
General Synthesis of Coumarins by Pechmann Reaction:
General procedure: Amixture of phenol (2 mmol), β-keto ester (2 mmol), and catalyst(0.3 mol%) was heated and magnetically stirred at 120 °C for theappropriate time under solvent-free conditions (Table 4). Inmany cases, the coumarins separated out as a solid mass on theinner wall of the flask at the end of the reaction. Upon completionof the reaction (monitored by TLC), the reaction mixturewas cooled to room temperature, hot EtOH (5 mL) was added,and the mixture was stirred for 15 min. The catalyst wasremoved from the reaction mixture by magnetic separation.The ethanolic solution was evaporated, the residue was pouredonto crushed ice, and the resulting crude product was filteredoff and recrystallized from ethanol to afford pure coumarin. |
| 96% |
at 20℃; for 0.0833333h; |
|
| 96% |
With CAN; mesoporous silica for 0.0333333h; microwave irradiation; |
|
| 96% |
With bispyridine cobalt(II) chloride for 0.0333333h; Microwave irradiation; neat (no solvent); |
|
| 96% |
With sulfonic acid modified nanostructured CMK-5 In neat (no solvent) at 130℃; for 0.333333h; Green chemistry; |
2 General procedure for the Pechmann condensation
General procedure: In a round bottom flask, CMK-5-SO3H (0.034 g, 3 mol%) wasadded to the mixture of phenolic compound (1 mmol) and ethylacetoacetate (1 mmol) at 130C and the reaction mixture stirredfor the appropriate time (Table 2). The progress of reaction was monitored by TLC (eluent, n-hexane:ethyl acetate, 4:1). After the completion of the reaction, the reaction mixture was diluted with ethanol and filtrated to obtain the crude product. Com-pounds with purity below 95% were further purified using column chromatography on silica gel and then recrystallized from hot ethanol to afford pure coumarin derivatives. All compounds were identified by comparison of 1H NMR, and 13C NMR with those reported (see Supporting information for copy of 1H and 13C spectra of products). Spectroscopic data for selected examples listed below. |
| 96% |
With 1,3-disulfonic acid imidazolium hydrogen sulfate at 75℃; for 0.166667h; Green chemistry; |
General procedure: A mixture of the phenolic compound (1 mmol), ethyl acetoacetate (EAA) or methyl acetoacetate (MAA, 1 mmol) and 1,3-disulfonic acid imidazolium hydrogen sulfate (DSIMHS, 0.07 mmol, 22.75 mg) was heated in an oil bath (75 °C) under stirring. The progress of the reaction was monitored by TLC. After completion, the mixture was allowed to cool. Then, the resulting mixture was diluted with ethylacetate (5 mL) and the catalyst was separated through decantation. The organic phase obtained was washed with water (2 x 5 mL) and the solvent was evaporated under reduced pressure, which yielded the crude product. Recrystallization in ethanol or an ethanol-water system gives the requested coumarin in high yields. |
| 95% |
With mesoporous silica SBA-15-Ph-PrSO3H at 130℃; for 0.416667h; |
|
| 95% |
With mesoporous silica for 0.0416667h; Microwave irradiation; |
|
| 95% |
With pentafluoroanilinium trifluoromethanesulfonate In toluene at 110℃; for 3h; chemoselective reaction; |
4.1. Typical experimental procedure
General procedure: A mixture of resorcinol (1 mmol), ethyl acetoacetate or methyl acetoacetate (1.1 mmol) dissolved in 3 ml toluene, and PFPAT (10 mol%) was refluxed with stirring for 3 h. The reaction mixture, after being cooled to room temperature was poured onto crushed ice and stirred for 5-10 min. The crystalline product was collected by filtration under suction (water aspirator), washed with ice-cold water (40 ml) and then recrystallized from hot ethanol to afford pure 7-hydroxy-4-methylcoumarin as colorless prisms (90%), mp 185-187 °C. The filtrate was concentrated under reduced pressure and then recrystallized from hot hexane to recover the PFPAT for subsequent use. |
| 95% |
With copper(II) ferrite In lithium hydroxide monohydrate at 20℃; |
General Procedure for the Preparation of Coumarins
General procedure: Resorcinol (1 mmol) and ethyl acetoacetate (1.2 mmol) were placed in a 10 ml,round-bottomed flask in H2O (3mL). Sequentially CuFe2O4 (5 mol%, 12 mg) wasadded. After completion of the reaction, the catalyst was separated from the reactionmixture with an external magnet, and the catalyst was washed several times withH2O and dried under vacuum. Water (10mL) was added to the resulting reactionmixture, followed by extraction with EtOAc (35 mL). The collected organic phaseswere dried with Na2SO4, and the solvent was removed under vacuum to give the correspondingcoumarin, which did not require any further purification. The physicaldata (mp, NMR) of these known compounds were found to be identical with thosereported in the literature. Spectroscopic data for selected examples are shown. |
| 95% |
With 1,1'-butylenebispyridinium hydrogen sulfate In neat (no solvent) at 20℃; for 0.416667h; Green chemistry; |
General procedure for the coumarin derivatives 3a-3m
General procedure: In a round-bottom flask (25 mL), (Bbpy)(HSO4)2 (10 mg, 2.4 mol %) was added tothe mixture of 3-hydroxy phenol (5.0 mmol) and ethyl acetoacetate (5.0 mmol) and the reaction mixture stirred at ambient temperature for the appropriate time (Table 2). The progress of reaction was monitored by TLC (eluent, n-hexane:ethylacetate, 4:1). After the completion of the reaction, water (10.0 mL) was added to the reaction mixture, and the catalyst was recovered by filtration. Evaporation of the solvent from the filtrate and recrystallization of the solid residue from hot ethanol afforded the pure products in good to excellent yields. |
| 95% |
With 2-amino pyrimidine nanocellulose-supported palladium nanoparticles In neat (no solvent) at 130℃; for 0.5h; |
|
| 94% |
With dodeca-tungstophosphoric acid In toluene for 0.5h; Reflux; |
|
| 94% |
With zirconium orthophosphate at 160℃; for 0.25h; Microwave irradiation; chemoselective reaction; |
|
| 94% |
With xanthan sulfuric acid at 20℃; for 0.333333h; Neat (no solvent); |
|
| 94% |
With zirconium tetrachloride In toluene at 80℃; Inert atmosphere; |
|
| 94% |
With perchloric acid; mesoporous silica In lithium hydroxide monohydrate at 130℃; for 1.5h; |
4.2. Synthesis of 7,8-dihydroxy-4-methylcoumarin (1a)
Pyrogallol (1 mM), ethyl acetoacetate (1.1 mM) and HClO4·SiO2 (50 mg) were mixed and stirred at 130 ◦C in a pre-heated oil bath for 90 min {HClO4·SiO2 was prepared by adding perchloric acid 70% aqueous solution (12.5 mM) to silica gel (23.6 g, 230-400 mesh) suspension in diethyl ether. This mixture was kept under vacuum for 72 h at 100 °C to yield HClO4-SiO2}. After cooling, the reaction mixture was filtered. The filtrate was concentrated and the resulting residue was washed with ethyl acetate twice. The combined ethyl acetate layer was evaporated to give a solid residue [29,30]. This was chromatographed over silica gel using DCM-methanol to give compound 1a. 7,8-Dihydroxy-4-methyl-2H-chromen-2-one (1a): Yellow amorphous powder, yield: 94%; mp: 241-242 °C; FT-IR νmax (KBr, cm-1): 3416, 3233, 3080, 1648, 1609, 1513, 1457, 1300, 1026; APCI-MS m/z:191.1000 [M-H]-, 192.9500 [M+H]+. |
| 93% |
With ytterbium trifluoromethanesulfonate at 85℃; for 1h; |
|
| 93% |
With MnSb2O6-chitosan nanocomposite In neat (no solvent) at 80℃; for 0.666667h; |
|
| 92% |
at 80℃; for 24h; |
|
| 92% |
at 80℃; for 0.333333h; |
|
| 92% |
With hydrotalcite In neat (no solvent) at 70℃; for 0.666667h; Green chemistry; |
Typical procedure for synthesis of coumarin
General procedure: A mixture of phenols (0.0025 mol) and dicarbonyl (0.0025 mol) were heated at 70C under solvent free conditions using hydrotalcite (Mg-Al-CO3,50 mg) as a catalyst. The time taken by different phenols in reaction was as mentioned in Table 4. After completion of the reaction(TLC analysis using ethyl acetate:petroleum ether, 1:3), the reac-tion mixture was cooled to room temperature and poured in coldwater. The solid mass was filtered. It was dissolved in ethanol andfiltered. The solid hydrotalcite got separated as solid. The filtratehaving product soluble in ethanol was concentrate to crystallize theproduct. Hydrotalcite was washed with ethanol to remove organic impurity. |
| 92% |
With cobalt(II) supported on mesoporous SBA-15 nanocatalyst In neat (no solvent) at 100℃; for 3h; Green chemistry; |
2.2 Pechmann Reactions
General procedure: To a mixture of phenol (1 mmol) and b-ketoester(1 mmol), Co/SBA-15 (0.001 mmol) was added at 100 C.The mixture was stirred for 3 h (Table 2). The progress ofthe reaction was monitored by thin layer chromatography(TLC). After the complete conversion of the starting materials,as indicated by TLC, ethanol (10 mL) was added tothe reaction mixture was filtered and the solid residualcatalyst was washed with ethyl acetate (2 9 10 mL) andthen dried at 50 C. After this, it could be used for the nextrun. The filtrate was recrystallised from ethanol to get thepure product. The products were characterized according totheir 1H and 13CNMR, IR, and melting point data. |
| 92% |
With Cu(II) supported on 5-oxo-2,5-dihydropyrrole-3-carboxylate functionalized magnetic nano Fe3O4 nanocatalyst In neat (no solvent) at 100℃; for 2h; |
3.2.3. General procedure for Pechmann reactions to prepare coumarin derivativesby Cu(II)-OHPC-Fe3O4 as nanoctalyst
General procedure: To a mixture of ethyl acetoacetate (1 mmol) and phenol derivatives was added 0.5 mol% Cu(II)-OHPC-Fe3O4 as nanocatalyst at 100 C under solvent-free conditions. Whenthe reaction was completed (as monitored by TLC (n-hexane/EtOAc, 9:1, Rf valence:0.52)), the reaction mixture was cooled to room temperature. After that, the reactionmixture was dissolved in dichloromethane (10 ml) and Cu(II)-OHPC-Fe3O4 nanoparticlecatalyst was separated by an external magnet for 5 min. The solution containing theproduct was removed by vacuum and the residual solid was recrystallized using ethanol.The product was obtained as a powder. Eventually, the isolated catalyst waswashed several times with dried CH2Cl2, dried under vacuum at 60 C to give the pureCu(II)-OHPC-Fe3O4 nanoparticle catalyst. |
| 91% |
With silicium tetrachloride at 85℃; for 1h; |
|
| 91% |
With sulfonic chloride acid at 10℃; for 0.166667h; |
|
| 91% |
With TiO2-Pr-SO3H In neat (no solvent) at 90℃; for 0.466667h; Green chemistry; |
2.4. General procedure
General procedure: A mixture of substrate (1 mmol), methyl or ethyl acetoacetate (1 mmol) and TiO2-Pr-SO3H (8 mg) was taken in a 25-mL round bottomed flask equipped with a condenser. The mixture was heated in an oil bath at 90 °C under stirring and the reaction was monitored by TLC. After completion, the mixture was allowed to cool, ethyl acetate (5 mL) was added and the catalyst was recovered by filtration, washed with ethyl acetate (5 mL), dried and reused according to the procedure mentioned above. Evaporation of the solvent from the filtrate and recrystallization of the solid residue from hot ethanol afforded the requested coumarins in high yields. The results are given in Table 2 and spectral data and melting points are in good agreement with those reported in the literature [24-29]. |
| 91% |
With meglumine sulfate (Ms) In neat (no solvent) at 60 - 70℃; for 0.1h; Microwave irradiation; Green chemistry; |
General procedure for the synthesis of coumarines
General procedure: Phenol derivative (2.5 mmol), β-diketne (2.5 mmol) and catalytic amount of meglumine sulfate (0.04 g) were mixed and heated at 100C in thermal conditions. In microwave conditions, the reaction mixture subjected to microwave irradiation at power of 600W and 60-70C for 6 minutes. The progress of the reaction was monitored by TLC. After the completion of reaction, the reaction mixture was cooled to room temperature and 10 ml of EtOH was added. Then, obtained mixture poured into crushed ice and stirred for 10 min. The crude product was collected by filtration, washed with ice cold distilled water and recrystallized from hot ethanol to afford pure corresponding pure product. |
| 90% |
With toluene-4-sulfonic acid for 0.00833333h; microwave irradiation; |
|
| 90% |
With 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) at 120℃; for 0.75h; |
|
| 90% |
With vanadium(III) trichloride at 50 - 55℃; for 2h; |
|
| 90% |
With thiourea S,S-dioxide at 80℃; for 4h; |
|
| 90% |
With poly(4-vinylpyridinium) hydrogen sulfate (PVPHS) In neat (no solvent) for 0.133333h; Sonication; |
General procedure for the preparation of coumarins
General procedure: In a 25-mL batch reactor equipped with a distillation condenser the mixture of phenols (1.0 mmol), β-keto esters (2.0 mmol) and PVPHS (10 mg, 0.02 mmol) was stirred and irradiated with ultrasonic of low power (with a frequency of 35 kHz and a nominal power 200 W). The temperature of the reaction mixture started to rise. After 2 min of irradiation, the ultrasound source was switched off. Since the Pechmann reaction proved to be exothermic, the reaction mixture continued to rise in temperature. After completion of the reaction (monitored by TLC), ethanol was added to the reaction mixture and the catalyst was recovered by filtration. The filtrate was concentrated in vacuum, and the crude product was washed with water, dried and slowly recrystallized in ethanol or ethanol-water system. The melting point, IR, 1H NMR and mass spectroscopic techniques were used to analyze the products and compared with the authentic samples. |
| 90% |
With poly(4-vinylpyridine)-supported copper iodide In neat (no solvent) at 80℃; for 0.2h; Green chemistry; |
General procedure
General procedure: A mixture of the phenol (1 mmol), ethyl acetoacetate or methyl acetoacetate (1 mmol) and poly(4-vinylpyridine)-CuI (0.1 g) was heated in an oil bath (80 °C) for the appropriate times according to Table 1. The progress of the reaction was monitored by TLC. After completion, the mixture reaction was allowed to cool, ethyl acetate (5 mL) was added and the catalyst was recovered to use subsequently by filtration. Evaporation of the solvent from the filtrate and recrystallization of the solid residue from hot ethanol (0.83-0.91 mmol) afforded the pure products in high yields. |
| 90% |
With polyacrylonitrile fiber-supported poly(ammoniummethanesulfonate) In toluene at 110℃; for 4h; |
|
| 90% |
With succinimide-N-sulfonic acid In neat (no solvent) at 50℃; for 0.416667h; |
2.3. General procedure for the preparation of coumarins
General procedure: A mixture of the phenol derivative (1 mmol), β-keto ester (1 mmol), and SuSA (25 mg, 0.096 mmol) was stirred at 50 °C under solvent-free conditions. After completion of the reaction (monitored by TLC), EtOAc (2 x 10 mL) was added to the resulting solidified mixture, and the catalyst was separated by decantation. The organic phase was washed with water (2 x 5mL) and dried over MgSO4. Evaporation of the solvent under reduced pressure yielded the crude product, which was purified by recrystallization in ethanol or ethanol-water to give the pure product as colorless prisms, pale yellow, or white powders. The recovered catalyst, after drying, was reused in the next run without further purification. All of the synthesized coumarin derivatives were identified by their physical and spectral data. In addition, the melting points were measured for all of the products and were compared with the corresponding reported melting points. The spectral data of the selected products are as follows. |
| 90% |
With glutamic acid In neat (no solvent) at 110℃; for 0.25h; Green chemistry; |
Typical procedure adopted for the synthesis of 7-hydroxy-4-methyl-2H-chromen-2-one (S1)
General procedure: A mixture of resorsinol (1 mmol), ethylacetoacetate (1 mmol), and glutamic acid (20 mol%)was stirred at 110°C for a 15 min. The progress ofthe reaction was monitored by using TLC. Aftercompletion of the reaction, the solid catalyst(glutamic acid) was washed with water, and finallypurified by recrystallization in ethanol/water.Data of compounds (S1-S5) |
| 90% |
With sulfuric acid at 20℃; for 16h; |
|
| 90% |
With iron(III) trifluoride In neat (no solvent) at 110℃; for 0.116667h; Microwave irradiation; Green chemistry; chemoselective reaction; |
3.2. Typical Procedure Adopted for the Synthesis of 7-Hydroxy-4-Methyl-Chromen-2-One (4)
General procedure: A mixture of resorsinol (1 mmol), ethyl acetoacetate (1 mmol), and FeF3 (0.05 g) was ground in an open Pyrex beaker and the homogenized mixture was heated by microwave irradiation for about 7 min, as indicated in Table 1. The progress of the reaction was monitored by using TLC (ethylacetate/n-hexane: 1/2). After complete conversion as indicated by TLC, the mixture was extracted with petroleum ether (3 × 30 mL) and washed with water (3 × 30 mL). The crude products were purified by recrystallization from ethanol (95%) to afford pure products. Data for new compounds are listed below: |
| 90% |
With lewis acid grafted sulfonated carbon(at)titania composite [C(at)TiO2-SO3-SbCl2] In neat (no solvent) at 120℃; for 0.75h; Green chemistry; |
General procedure for the C(at)TiO2-SO3-SbCl2 catalyzed synthesis of coumarins via Pechmann reaction
General procedure: a 25 cm3 round bottom flask, 0.1 g CTiO2-SO3-SbCl2(1 mol% Sb) was added to the mixture of phenolic compound (1 mmol) and ethyl acetoacetate (1 mmol) and the reaction mixture was stirred for the appropriate time at 120 C under solvent-free conditions. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with 30 cm3 hot ethanol and the catalyst was separated by simple filtration to obtain the crude product. Compounds with purity below 95 % were further purified using column chromatography on silica gel and then recrystallized from hot ethanol to afford the pure coumarin derivatives. |
| 89% |
With [bmim]Cl*2AlCl3 at 30℃; for 0.166667h; |
|
| 89% |
With iodine In toluene at 80℃; |
|
| 89% |
at 150℃; for 0.75h; |
|
| 89% |
With copper (II) bromide at 80℃; for 0.25h; neat (no solvent); |
|
| 89% |
With silica gel supported zirconyl chloride octahydrate at 90℃; for 0.666667h; |
|
| 89% |
With L-ascorbic acid at 180℃; Microwave irradiation; |
2.2. General Procedure for the Synthesis of Coumarins
General procedure: Mixture of phenols 6a-d (0.5g, 4.55 mmol), ethyl acetoacetate(0.60mL, 4.77 mmol) and L-ascorbic acid (3.7g,4.55 mmol) was heated either on a preheated oil bath or undermicrowave irradiation, at 180°C for 10-15 min. Aftercompletion of reaction (TLC check), the reaction mixturewas cooled to room temperature and the flask was sonicatedby adding water (10mL). The crude product was filtered oversuction-pump and washed with excess of water (3 × 10 mL)to remove L-ascorbic acid. The solid obtained was dried andcrystallized by using ethanol to give the corresponding coumarinsin high yield. The purity of products was confirmedby satisfactory spectroscopic data. Similarly, phenol 6e(0.5mL, 4.77 mmol), ethyl 3-oxo-phenylpropanoate (0.82mL,4.77 mmol) and L-ascorbic acid (3.7g, 4.55 mmol) was usedfor the synthesis of 5,7-dihydroxy-4-phenyl-chromen-2-one8e. |
| 89% |
With Stannic tetrachloride grafted on silica gel at 120℃; for 0.333333h; |
Pechmann condensation catalyzed by SnCl4 grafted on silica gel:
General procedure: To a mixture of phenol (10 mmol) and β-ketoester(11 mmol), SnCl4 grafted on silica gel (5 mol%) was added and rapidly stirred at 120 °C for the appropriate time(Table 5). After completion of the reaction, ethanol was added to the reaction mixture and the mixture was stirred for 15 min to enable the precipitate dissolved. The mixture was then filtered to recover the catalyst, washed with ethanol,and the ethanol solution was evaporated on a rotatory evaporator under reduced pressure to obtain the crude product.The solid residue was recrystallized from ethanol/water to afford pure crystals of the proper coumarins in excellent yields. |
| 89% |
With tartaric acid In neat (no solvent) at 180℃; for 0.05h; Microwave irradiation; Green chemistry; |
General procedure for Synthesis of Coumarins 3
General procedure: A mixture of phenol (1, 0.5 g), β-keto ester (2, 1.0 eq.) and tartaric acid (1.0 eq.) was heated either in an oil bath, preheated at 180 °C for 5 min or in microwave reactor for 3 min. After completion of reaction (TLC check), the reaction mixture was allowed to cool at room temperature and water (10 mL) was added. The solid obtained on stirring was filtered and washed with water. Crude product was purified by recrystalization using aqueous ethanol. |
| 89% |
With sulfuric acid for 2h; Reflux; |
Synthesis of 7,8-dihydroxy-4-methyl coumarin (II).
A mixture of pyrogallol (1, 0.01 mol) and ethyl acetoacetate(0.01 mol) in the presence of concentrated sulphuricacid (1 mL) was heated under reflux on a waterbath for 2 h, then cooled and poured into water. Theresulting solid was collected after filtration, washedwith water, dried and crystallized with ethanol to give7,8-dihydroxy-4-methyl coumarin (II) as pale-yellowcrystals, yield 89%, m.p. 225°C, IR (KBr, max cm-1):3420-3350 (br. OH), 1725 (C=O), 1615, 1585 (C=C),1121, 1079 (C-O). 1H NMR (DMSO-d6) : 2.32 (s,3H, CH3), 6.08 (s, 1H, H-3 of coumarin ring), 6.81 (d,1H, H-6 of coumarin ring), 7.05 (d, 1H, H-5 of coumarinring), 6.18 (d, 1H, H-6 of coumarin ring)ppm.13C NMR (DMSO-d6) : 160.76 (C-2), 154.44(C-7), 149.78 (C-8), 143.69 (C-9), 132.58 (C-4),115.90 (C-10), 113.22 (C-5), 112.53 (C-6), 110.59 (C-3),18.44 (C-11) ppm. Anal. calcd. for C10H8O4 (192).Calculated: C, 62-50, H, 4.16. Found: C, 62.32, H, 4.01. |
| 88% |
With scandium trifluoromethanesulphonate at 80℃; for 2h; |
|
| 88% |
With 1-n-butyl-3-methylimidazolium tetrafluoroborate; trichlorophosphate for 0.25h; Microwave irradiation; |
|
| 88% |
With Polyvinylpolypyrrolidone supported BF3 complex In ethanol for 2.5h; Reflux; |
|
| 88% |
With poly(4-vinylpyridinium)perchlorate In neat (no solvent) at 20℃; for 0.3h; Irradiation; |
2.5 General procedure for the preparation of coumarins
General procedure: In a 25 mL batch reactor equipped with a distillation condenser the mixture of phenols (1 mmol), β-keto esters (2 mmol) and P(4-VPH)ClO4 (50 mg) was stirred and irradiated under ultrasonic irradiation (with a frequency of 35 kHz and a nominal power 200 W) at ambient temperature for the time mentioned in the Table 1. Ethyl acetoacetate was taken 2 equiv. for the proper solubility of phenol and ease of proper stirring of the reaction mixture. After completion of the reaction (monitored by TLC), ethanol was added to the reaction mixture and the catalyst was recovered by filtration. The filtrate was concentrated in vacuum, and the crude product was washed with water, dried and slowly re-crystallized in ethanol or ethanol-water system. The melting point, IR, 1H NMR and mass spectroscopic techniques were used to analyze the products and compared with the authentic samples. |
| 87% |
With yttrium(III) nitrate hexahydrate at 90℃; for 1.16667h; Green chemistry; |
|
| 87% |
With Sawdust-SO3H at 110℃; for 0.416667h; Green chemistry; |
General procedure for substituted coumarins.
General procedure: A well stirred mixture of a phenol derivative (1.0 mmol), ethyl acetoacetate (1.2 mmol) and SD-SO3H (0.05 g, 0.24 mmol) was heated at 110°C under solvent-free conditions. Upon completion of the reaction, as indicated by TLC, CHCl3 was added and the catalyst was filtered off. The filtrate was evaporated and the residue purified by recrystallization from ethanol to give the corresponding pure product. Melting points and 1H NMR spectra of the products were compared with and matched well the reference data. |
| 86% |
With N-methylimidazolium sulphomethylsulfonate In neat (no solvent) at 80℃; for 3h; |
General procedures for the synthesis of coumarin
General procedure: In a typical experiment, resorcinol (15 mmol), ethyl acetoacetate (15 mmol), and IL (0.75 mmol) were taken in round-bottom flask equipped with a distillation condenser and stirredat 80 °C for the desired reaction time. At the end of reaction, the reaction mixture was cooled to room temperature and ice-cold water was added to the mixture. The crude products were collected by filtration and finally purified by recrystallizing from ethanol. The products were confirmed by 1H NMR, 13C NMR, HRMS, and the results are in good agreement with those reported in the literature. The filtrate containing IL was washed with diethyl ether and dried in a vacuum evaporator to recover the IL for the next run. |
| 84% |
With poly(4-vinylpyridine)-supported sulfuric acid at 65℃; for 0.166667h; Microwave irradiation; Neat (no solvent); |
|
| 83% |
Stage #1: ethyl 3-oxobutanoate; 2-hydroxyresorcinol With glacial acetic acid Schlenk technique;
Stage #2: With 3-methyl-1-(butyl-4-sulfonyl)imidazolium trifluoromethanesulfonate at 80℃; for 8h; Schlenk technique; |
|
| 82% |
With aminosulfonic acid at 130℃; for 0.416667h; |
|
| 82% |
With niobium pentachloride at 80℃; for 0.333333h; |
|
| 82% |
With 1-methyl-3-(3-sulphopropyl)imidazolium methyl sulphate at 100 - 110℃; for 0.333333h; Ionic liquid; |
|
| 82% |
With polystyrene supported GaCl3 In ethanol for 1.08333h; Reflux; Green chemistry; |
|
| 82% |
With aminosulfonic acid In neat (no solvent) at 130℃; for 4h; Sealed tube; |
Synthetic procedures and characterization data for products 3a-o.
General procedure: A mixture of the phenol (1a-g) (1 mmol) with the β-ketoester (2a-e) (1.5 mmol) was added to a sealed reaction vial in the presence of sulfamic acid (0.097 g, 10 mol %), and then the reaction mixture was heated to 130 °C or 100 °C (depending on the β-ketoester employed) and the appropriated reaction time (see Table 2). After completion, the reaction mixture was cooled to room temperature and dissolved in 5 mL of hot ethanol. Sulfamic acid is partially soluble in ethanol and is filtered off and recovered. Afterward, ice water and crushed ice were added until the product precipitated. The compound was then filtered, washed with water, and dried under lyophilization given the final product. The products 3d, 3f, 3l, 3n were further purified by flash column chromatography to yield the pure products (hexane/ethyl acetate 7:3). |
| 81% |
With bismuth(III) chloride at 28 - 30℃; for 0.25h; sonication; |
|
| 81% |
With sulfuric acid |
|
| 80% |
at 80℃; for 0.5h; |
|
| 80% |
With sulfuric acid for 1h; |
|
| 80% |
With sulfuric acid at -5 - 5℃; for 2h; |
|
| 80% |
With phosphoric acid at 60℃; |
General procedure for the synthesis of 4-methyl-hydroxycoumarins.
General procedure: In a round bottom flask equipped with a magnetic bar andcondenser, 31.7 mmol of phenol and 31.7 mmol of freshly distilled ethylacetoacetate were dissolved in 40 mL of phosphoric acid and the mixturewas stirred at 60 C. The reaction was monitored by TLC up to thecomplete consumption of the corresponding phenol. After completion,the reaction was quenched with cold water. The crude product wasfiltered and crystallized from the methanol-water producing the corresponding4-methyl-coumarins. |
| 79% |
With tris(pentafluorophenyl)borate In neat (no solvent) at 70℃; for 1.25h; Sealed tube; |
General experimental procedure
General procedure: In a sealed tube, a mixture of 100 mg phenol (1.06 mmol)and 138.28 mg ethyl acetoacetate (1.06 mmol) was heated(70 °C) in the presence of 16.32 mg B(C6F5)3 (0.03 mmol).After the completion of reaction, as indicated by TLCanalysis, the reaction mixture after being cooled to room temperature, was poured onto 40 g crushed ice and stirredfor 5-10 min. The solid products were filtered off, washedwith ice-cold water, and recrystallized from hot ethanol toafford pure coumarin derivatives 3. The known compoundswere identified by comparison of their spectral data andphysical properties with the reported literature. |
| 78% |
With perchloric acid at 20℃; for 6h; |
7,8-dihydroxy-4-methyl-2H-chromen-2-one (22).
To a mixture of 1,2,3-phenenyl triacetate (5.0 mmol) and ethyl acetoacetate (7.5 mmol) was added drop-wise perchloric acid (6.0 ml) at room temperature and stirred for 6 h. After completion of the reaction as indicated by TLC, the reaction mixture was poured slowly into a mixture of ice-water (50 ml) with stirring. The resultant suspension was filtered and the collected solid was washed with water and dried, then the crude compound was recrystallized from methanol to produce compound 22 as a light whitesolid with a yield of 78%. 1H NMR (600 MHz, DMSO) δ 10.05 (s, 1H),9.28 (s, 1H), 7.09 (d, J = 8.6 Hz, 1H), 6.82 (d, J = 8.6 Hz, 1H), 6.13 (d, J= 1.1 Hz, 1H), 2.36 (s, 3H); 13C NMR (151 MHz, DMSO) δ 160.67,154.40, 149.87, 143.79, 132.62, 115.95, 113.23, 112.58, 110.65, 18.72;HRMS (ESI) for C10H8O4, Calcd 192.0423, found 192.0355 [M H]-. |
| 76% |
With sulfuric acid at 25℃; for 48h; |
|
| 76% |
With amberlyst-15; toluene at 100℃; for 0.5h; microwave irradiation; |
|
| 76.9% |
With 3-ethyl-1-(butane sulfonic acid)imidazolium hydrogen sulfate at 70℃; for 0.5h; |
|
| 75% |
With nanosilica molybdic acid 2 In neat (no solvent) at 80℃; for 0.333333h; Green chemistry; |
General procedure for the synthesis of coumarinderivatives 5a-o
General procedure: In a general experimental procedure, β-ketoester 3(1 mmol) was added to a mixture of substituted phenol4 (1 mmol) and SMA NPs 2 (5 mol%) in a solvent-freetube. The reaction mixture was stirred in a preheated oilbath (80 °C). After the completion of the reaction, the precipitateobtained was extracted with ethyl acetate, washedwith water (3 × 10 ml) and dried to obtain the product.The remaining insoluble solid catalyst in aqueous phasewas separated by filtration, washed with ethyl acetate |
| 74% |
With iron(III) chloride at 70℃; for 10h; |
|
| 73% |
With trichloroacetic acid In neat (no solvent) at 100℃; for 1.5h; |
|
| 72% |
With Sulfate; zirconium oxide at 150℃; for 3h; |
|
| 72% |
With titanium(IV) tetrachloride In ethanol at 20℃; |
|
| 70% |
With silica-supported methanesulfonic acid catalyst In α-octadecene at 160℃; for 2h; |
|
| 70% |
With nano-BFn/cellulose In neat (no solvent) at 85℃; for 2h; Green chemistry; |
General procedure for the synthesis of 7-hydroxycoumarin derivatives
General procedure: A mixture of phenol (1 mmol), -keto ester (1 mmol) and a catalytic amount ofnano-BFn/cellulose (0.06 g) was stirred at 85 °C. After an appropriate time that thereaction was completed, the mixture was dissolved in hot isopropyl alcohol to separatethe insoluble catalyst by a simple filtration. After cooling the solution, some crushed ice was added to it. The solid product was appeared and collected by filtration.To find out the reusability of catalyst, the recovered catalyst was washed withchloroform, dried and used for three times under the same reaction conditions |
| 69% |
With toluene-4-sulfonic acid at 60℃; for 0.166667h; |
|
| 69% |
With sulfuric acid at 20℃; for 18h; |
|
| 68% |
at 130℃; for 1h; |
|
| 66% |
With montmorillonite K-10 In toluene for 10h; Heating; |
|
| 65% |
In toluene for 6h; Heating; |
|
| 64% |
With zirconium(IV) oxychloride at 80℃; for 24h; |
|
| 58% |
With trifluorormethanesulfonic acid at 20 - 85℃; |
6
Pyrogallol (100mg, 0.793mmol) and trifluoromethanesulfonic acid (39mg, 0.793mmol) were added to a round-bottomed flask, ethyl acetoacetate (83μL, 0.952mmol) was slowly added at room temperature, and the mixture was kept in a solvent-free condition. Stir in an oil bath at 85°C until the raw material reaction is complete.The reaction solution was slowly poured into ice water (20mL), extracted with dichloromethane (20mL×3), the dichloromethane layer was washed with saturated sodium bisulfite (20mL×3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure After purification by silica gel column chromatography with eluent dichloromethane/methanol (30:1), 57.8 mg of pale yellow solid was obtained, with a yield of 58%. |
| 56% |
In neat (no solvent) at 80℃; for 0.833333h; |
11 Example 11
Experimental method: 0.2 mmol of DES catalyst ChCl/PTSA, 2 mmol of 1,2,3-benzenetriol, 2 mmol of ethyl acetoacetate was added to a 25 mL round bottom flask, and the reaction was stopped after stirring at 80 ° C for 50 min. .After completion of the reaction, the mixture was cooled to room temperature, and an ice-water mixture was added to allow the product to be analyzed, filtered, and washed twice with water to obtain a crude product.Recrystallization from an ethanol-water solution gave 7,8-dihydroxy-4-methylcoumarin in a yield of 56%. |
| 55% |
With ferric(III) chloride In neat (no solvent) for 0.2h; Sonication; Green chemistry; |
3.2.1 Ultrasound method
General procedure: A mixture of the appropriate phenol 1a-e (3.73mmol), β-ketoester 2a-c (7.46mmol) and anhydrous FeCl3 (0.373mmol, 81mg) was placed in a 10mL glass tube and was sonicated (20kHz, 130W nominal power) for 1-20min until completion of the reaction checked by TLC. The tube during sonication was immersed in a cooling bath set at 20°C. For compounds 3a, 3b, 3c, 3f, 3j the reaction mixture solidified upon completion of the reaction, due to product precipitation. Subsequently, ethanol (5mL) was added, and the product 3a-j crystallized upon dropwise addition of water (15mL). The solid was filtered washed with water and was recrystallized from ethanol/water. The final product was then dried under high vacuum over P2O5. |
| 25% |
With sulfuric acid for 2.5h; Inert atmosphere; Cooling with ice; |
|
|
With sulfuric acid |
|
|
With sulfuric acid; lithium hydroxide monohydrate |
|
|
With diphosphorus pentoxide |
|
|
With phosphoric acid |
|
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