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CAS No. : | 91-64-5 | MDL No. : | MFCD00006850 |
Formula : | C9H6O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZYGHJZDHTFUPRJ-UHFFFAOYSA-N |
M.W : | 146.14 | Pubchem ID : | 323 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 10 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 42.48 |
TPSA : | 30.21 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.2 cm/s |
Log Po/w (iLOGP) : | 1.75 |
Log Po/w (XLOGP3) : | 1.39 |
Log Po/w (WLOGP) : | 1.79 |
Log Po/w (MLOGP) : | 1.65 |
Log Po/w (SILICOS-IT) : | 2.5 |
Consensus Log Po/w : | 1.82 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.29 |
Solubility : | 0.742 mg/ml ; 0.00508 mol/l |
Class : | Soluble |
Log S (Ali) : | -1.63 |
Solubility : | 3.44 mg/ml ; 0.0235 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -3.59 |
Solubility : | 0.0377 mg/ml ; 0.000258 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.74 |
Signal Word: | Danger | Class: | 6.1 |
Precautionary Statements: | P501-P270-P264-P301+P310+P330-P405 | UN#: | 2811 |
Hazard Statements: | H301 | Packing Group: | Ⅲ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | at -10 - -5℃; for 1 h; | The procedure was adopted from ref.1 (Roy et al. 2011) Three-neck flask (250 mL) fitted with a condenser, thermometer and dropping funnel was charged with coumarin (1) (10 g, 68.5 mmol) and 50 mL of concentrated sulfuric acid (0.935 mol). After cooling the solution at -10 °C, the mixture of concentrated sulfuric acid (15 mL, 0.28 mol) and fuming nitric acid (5 mL, 0.12 mol)) was added dropwise during 1 h (temperature kept bellow -5 °C). Consequently, the mixture was poured on ice, the precipitate was filtered off a recrystallized from acetic acid. Yield: 11.26 g (86 percent) of white solid. Mp 191–192.5 °C (ref.2 reports 188 – 190 °C). Proton and carbon NMR data are in accordance with ref.3 1H NMR (400.13 MHz, CDCl3): δ = 6.60 (d, J = 9.5 Hz, 1H); 7.48 (d, J = 9.0 Hz, 1H); 7.83 (d, J = 9.5 Hz, 1H); 8.42 (dd, J = 9.0 Hz; 2.5 Hz, 1H); 8.46 (d, J = 2.5 Hz, 1H) ppm.13C NMR (100.62 MHz, CDCl3): δ = 118.1; 118.8; 118.8; 123.7; 126.6; 142.2; 144.0; 157.5; 158.8 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With aluminum oxide; copper dichloride In chlorobenzene for 25h; Heating; | |
74% | With oxone||potassium monopersulfate triple salt; potassium chloride; N-(n-butyl)-2-methylbenzamide In dichloromethane; water at 20℃; for 5h; diastereoselective reaction; | |
62.1% | With N-chloro-succinimide; copper(II) chloride monohydrate In acetonitrile at 82℃; for 26h; regioselective reaction; | 2. The general synthetic procedure General procedure: To a 50 mL flask, the coumarin (1 mmol), appropriate amount of NXS, the Lewisacid catalyst and 20 mL anhydrous solvent were added in. The mixture was heated toreflux with a condenser under the protection of a drying tube. The reaction progresswas monitored by TLC. When the reaction was completed, the mixture was cooled toroom temperature. The solvent was removed by vacuum rotary evaporation, and theresidue was dispensed in 25 mL 5% sodium hydrogen sulfite (NaHSO3) aqueoussolution and then extracted with 25 mL ethyl acetate (EtOAc) for three times. Theorganic layer was combined, washed with 10 mL water and dried over anhydroussodium sulphate (Na2SO4). After the solvent was removed, the crude product waspurified by silica gel (300-400 mesh) column chromatograph. |
56% | With hydrogenchloride; 3-chloro-benzenecarboperoxoic acid In N,N-dimethyl-formamide for 0.5h; Ambient temperature; | |
42% | With hydrogenchloride; N,N,N,N-tetraethylammonium tetrafluoroborate In acetonitrile at 23℃; for 9h; Electrolysis; | 3-chloro-2H-chromen-2-one General procedure: All reactions were carried out in a 10 mL three-necked flask, Graphite felt (1.0 cm × 1.0 cm × 0.5 cm) as anode and platinum plate (1.0 cm × 1.0 cm × 0.2 mm) as cathode. These two electrodes were connected to a DC regulated power supply. To the flask was added Et4NBF4 (0.1 M), substrate (0.3mmol,1equiv), and HCl (1.8 mmol, 6 equiv.) in MeCN (10 mL) with a magnetic stir bar. The mixture was electrolyzed using constant current conditions at room temperature under magnetic stirring for proper time in monitored by TLC (3 to 10 hours). The mixture was concentrated under reduced pressure, extracted with DCM for three times (3 × 20 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by chromatography on silica gel to afford the desired product. |
With chloroform durch Einleiten von Chlor und Behandeln mit alkoh. Kali; | ||
With phosphorus pentachloride at 200℃; Behandeln des Reaktionsproduktes mit Wasser; | ||
With tetrachloromethane; chlorine at 70℃; Erwaermen des Reaktionsprodukts mit wss. Loesungen von Natriumcarbonat, Natriumhydrogencarbonat oder Ammoniak.; | ||
With pentachloroethane; chlorine at 200℃; | ||
With tetrachloromethane; chlorine at 200℃; Irradiation; | ||
With chlorine | ||
With chloroform durch Einleiten von Chlor und anschliessendes Erhitzen; | ||
With chlorine In chloroform Ambient temperature; | ||
With chlorine In tetrachloromethane | ||
146.1 mg | With N-chloro-succinimide; copper(II) choride dihydrate; zinc(II) chloride In acetonitrile at 82℃; for 16h; | 1 Synthesis of 3-chlorocoumarin In 25mL three-necked flask equipped with a stirrer, thermometer and reflux condenser was added 20ml of acetonitrile and, then followed by adding coumarin (1mmol, 146mg), metal salt catalyst cupric chloride CuCl2 · 2H2O (4mmol, 684mg) and zinc chloride ZnCl2 (1mmol, 136mg) and NCS (2mmol, 667.7mg), coumarin, copper chloride, zinc chloride, the NCS was dissolved in acetonitrile and the mixture was stirred at reflux for 82 16h, cooled. The resultant mixture was distilled under reduced pressure (100 to vacuum distillation under the conditions of vacuum degree of 200mmHg, temperature 45 ~ 55 ) remove the acetonitrile, the reaction was quenched with water, the resulting material remaining 50ml of deionized water was added and extracted with 50ml of ethyl acetate, taking the organic phase, the remaining aqueous phase extracted with ethyl acetate, extraction was repeated a total of three times, the combined organic phase 3 times with 20ml saturated brine the organic phase was washed once, dried over anhydrous sodium sulfate to give 3-chloro-fragrant coumarin crude product. 3-chloro-coumarin was concentrated to dryness under reduced pressure The crude product was purified by column chromatography (silica gel 300-400 mesh, constituent of petroleum ether: ethyl acetate = 1: 0 to 97: 3 by volume solvent gradient elution) to give compound 3-chloro-coumarin, was 146.1mg, yield 90.6%, to recover unreacted coumarin 15.2mg |
With hydrogenchloride; 3-chloro-benzenecarboperoxoic acid In N,N-dimethyl-formamide at 20℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; mercury(II) oxide Behandeln mit Kaliumperoxodisulfat und Erwaermen des nach dem Erhitzen mit wss. Salzsaeure und Natriumhydrogensulfit erhaltenen Reaktionsprodukts mit wss. Quecksilber(II)-chlorid-Loesung; | ||
With potassium peroxomonosulphate; iron(II) sulfate Behandeln des Reaktionsprodukts mit verd. Schwefelsaeure; | ||
Multi-step reaction with 2 steps 1.1: potassium hydroxide / water / Reflux 1.2: 8 h / Reflux 2.1: alkali / water; ethanol / Reflux 2.2: 2 h / -10 - 20 °C / pH 10-11 |
Multi-step reaction with 2 steps 1.1: potassium hydroxide / water / Reflux 1.2: 8 h / Reflux 2.1: alkali / water; ethanol / Reflux 2.2: 2 h / -10 - 20 °C / pH 10-11 | ||
With glucose-6-phosphate dehydrogenase; DL-dithiothreitol; human cytochrome P450 2A6; NADP; 1,2-dilauroyl-sn-glicero-3-phosphatidylcholine; NADPH-P450 reductase In aq. phosphate buffer at 37℃; for 0.0333333h; Enzymatic reaction; | Enzymatic assays General procedure: Assays were done as described previously (4) with minorchanges. Typical incubations included 0.2 M P450 4A11, 0.4M NADPH-P450 reductase, 0.4 M b5, 150 M L--dilauroylsn-glycero-3-phosphocholine (DLPC; Sigma-Aldrich), 100 mMpotassium phosphate buffer (pH 7.4), and the indicated concentrationof lauric acid ([1-14C]lauric acid, usually added as anaqueous 10 mM solution of sodium laurate) in a final volume of0.25 ml. b5 was included because it stimulates the catalyticactivity (4). Following temperature equilibration to 37 °C for 5min, reactions were initiated by the addition of an NADPHregeneratingsystem consisting of 0.5 mM NADP, 10 mM glucose6-phosphate, and 1 IU ml1 yeast glucose 6-phosphate dehydrogenase (66). Reactions generally proceeded at 37 °C for2 min and were terminated with 1.0 ml of ethyl acetate containing0.1% CH3CO2H (v/v), and, following mixing with a vortexdevice, the mixtures were centrifuged (103 g for 10 min). A0.8-ml aliquot of the ethyl acetate layer (upper phase) was transferredto a clean tube, and the solvent was removed under anN2stream.The dried extracts were dissolved in 200l of a 1:1 mixture ofH2O/CH3CN containing 0.1% CH3CO2H (v/v) and 10 Mbutylated hydroxytoluene, and aliquots were analyzed on areversed-phase (octadecylsilane, C18) HPLC column (5 m,2.1 100 mm (Waters, Milford, MA)) coupled with a radioactivitydetector (-RAM, IN/US Systems, Tampa, FL). Reactionproducts and substrate were eluted at a flow rate of 0.6 mlmin1 using an increasing linear gradient ofCH3CN(including0.1% (v/v) HCO2H) from 35 to 95% (v/v) over 30 min.Assays with P450s other than P450 4A11 were performed asdescribed previously, with the modification of either preincubationwith DTT (1 mM) for 10 min or not (the DTT remainedin the reactions): P450 2C8-paclitaxel as substrate (67), P4502C9-tolbutamide as substrate (68), P450 2D6-bufuralol assubstrate (69), P450 3A4-nifedipine as substrate (70), P45019A1-testosterone as substrate (71), P450 21A2-progesteroneas substrate (72), P450 2A6-coumarin as substrate (73), andP450s 1B1-, 1A1-, and 1A2-7-ethoxyresorufin as substrate(74). | |
Multi-step reaction with 3 steps 1.1: sulfuric acid; nitric acid / 1 h / 0 - 20 °C 2.1: zinc; ammonium chloride / methanol; tetrahydrofuran / 18 h / 20 °C 3.1: sulfuric acid; sodium nitrite / water / 0.5 h / 20 °C 3.2: 1 h / 140 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sulfuric acid; nitric acid | |
98% | Stage #1: coumarin With sulfuric acid at 4℃; for 0.166667h; Stage #2: With guanidine nitrate | Synthesis of 6-nitro-coumarin a 6-nitro-coumarin a was synthesied accroding to the lit (Wang et al. 2015). The concentrated sulphuric acid (29 mL) was added to coumarin (0.1 mol, 14.6 g) at 4 °C, and the mixture was stirred for 10 min. Then guanidine nitrate (0.1 mol, 12.2 g) was added slowly. The reaction was monitored by TLC. After completion of the reaction, the resulting mixture was slowly poured into crushed ice and the resulting solid was separated by filtration and washed successively with water. The product was dried to get white compound a in yield of 98%; HPLC>98.0% |
92% | With ammonium cerium(IV) nitrate; acetic acid at 20℃; for 2h; |
90% | With sulfuric acid; nitric acid at -20℃; for 1h; | |
88% | With sulfuric acid; nitric acid at -5 - 20℃; | |
88% | With sulfuric acid; nitric acid at 20℃; for 1h; | |
88% | With sulfuric acid; nitric acid at -50 - 20℃; for 1h; | |
88% | With sulfuric acid; nitric acid at 0℃; for 1h; | 3.2. 6-Nitrocoumarin Coumarin was nitrated with mixed acid in an ice bath. Coumarin (1.00 g, 7.1 mmol) was dissolvedin conc. H2SO4 (5 mL) and temperature was maintained at 0 C and then 5 mL mixed acid (HNO3and H2SO4 (conc.) in 1:3 volume ratio) was added. The mixture was stirred keeping at 0 C for 1 h.Water at 0 C (50 mL) was added to precipitate obtaining A white precipitate of 6-nitrocoumarin.It was then filtered and washed thorough with cold water (10 mL). The compounds were dried a 60 Covernight. The identity of the compound was determined by 1H NMR and used as was obtained.Yield, 1.20 g (88%). 1H NMR (400.133 MHz, CDCl3) /ppm H50 8.43 (d, 4J50-70 = 2.4 Hz, 1H), H70 8.40(dd, 3J7’-80 = 9.0, 4J70-50 = 2.5 Hz, 1H), H40 7.80 (d, 3J40-30 = 9.7 Hz, 1H), H80 7.47 (d, 3J80-70 = 9.0 Hz, 1H),H30 6.59 (d, 3J30-40 = 9.7 Hz, 1H). (Figure S3). |
86% | With sulfuric acid; nitric acid at 0 - 20℃; for 1h; | |
86% | With sulfuric acid; nitric acid at -10 - -5℃; for 1h; | 6-Nitrocoumarin (2) The procedure was adopted from ref.1 (Roy et al. 2011) Three-neck flask (250 mL) fitted with a condenser, thermometer and dropping funnel was charged with coumarin (1) (10 g, 68.5 mmol) and 50 mL of concentrated sulfuric acid (0.935 mol). After cooling the solution at -10 °C, the mixture of concentrated sulfuric acid (15 mL, 0.28 mol) and fuming nitric acid (5 mL, 0.12 mol)) was added dropwise during 1 h (temperature kept bellow -5 °C). Consequently, the mixture was poured on ice, the precipitate was filtered off a recrystallized from acetic acid. Yield: 11.26 g (86 %) of white solid. Mp 191-192.5 °C (ref.2 reports 188 - 190 °C). Proton and carbon NMR data are in accordance with ref.3 1H NMR (400.13 MHz, CDCl3): δ = 6.60 (d, J = 9.5 Hz, 1H); 7.48 (d, J = 9.0 Hz, 1H); 7.83 (d, J = 9.5 Hz, 1H); 8.42 (dd, J = 9.0 Hz; 2.5 Hz, 1H); 8.46 (d, J = 2.5 Hz, 1H) ppm.13C NMR (100.62 MHz, CDCl3): δ = 118.1; 118.8; 118.8; 123.7; 126.6; 142.2; 144.0; 157.5; 158.8 ppm. |
85% | In nitric acid | 1.G G. In greater detail, coumarin (10g, 68 mmol) was nitrated as described in the literature with an excess of fuming nitric acid overnight at room temperature to give 6-nitrocoumarin as the only major product. The 6-nitrocoumarin exhibited the following characteristics: Yield 85%. 1 H NMR (DMSO-d6) 8.74 (d, J=3 Hz, 1H), 8.42 (dd, J=3, 9 Hz, 1H), 8.24 (d, J=10 Hz, 1H), 7.63 (d, J=9 Hz, 1H), 6.70 (d, J=10 Hz, 1H). |
85% | With sulfuric acid; nitric acid; acetic acid | |
64.8% | With sulfuric acid; nitric acid at 0℃; for 2h; | 1.1 (1) Synthesis of 6-nitro-2H-benzopyran-2-one (II): Add HNO3 (1.3g, 20.1mmol) and H2SO4 10mL to a 250mL three-necked flask.Stir under ice salt bath and maintain the temperature at 0 °C.2 mL of H2SO4 dissolved in coumarin (2.9 g, 20 mmol) was added dropwise through a constant pressure dropping funnel, and then the temperature was maintained at 0 ° C for about 2 h.TLC detects the reaction completely,Pour the reaction into a 300 mL ice-water mixture.Stirring while stirring, the solid precipitated after the ice melted, suction filtration, and the filter cake was vacuum dried.Made a yellow solid,The yield was 64.8%. |
With sulfuric acid; nitric acid; acetic acid | ||
With sulfuric acid; nitric acid | ||
durch Nitrierung; | ||
With nitric acid | ||
With sulfuric acid; nitric acid; acetic acid | ||
With sulfuric acid; nitric acid | ||
With sulfuric acid; nitric acid | ||
With sulfuric acid; nitric acid | ||
With nitric acid | ||
With sulfuric acid; nitric acid at 0 - 5℃; for 2h; | ||
With sulfuric acid; nitric acid In water at 0 - 20℃; for 1h; | ||
1.14 g | With sulfuric acid; nitric acid at 0 - 20℃; for 1h; | |
With sulfuric acid; potassium nitrate at -10℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30%Chromat. | With Glomerella cingulata NBRC 5952; In water; dimethyl sulfoxide; at 27℃; for 168h;Culture medium; Microbiological reaction; Enzymatic reaction; | Precultured G. cingulata (5 mL) was transferred into a 500 mL Erlenmeyer flask containing 300 mL of medium. Cultivation was carried out at 27 C with stirring (ca. 120 rpm) for 3 days. After the growth of G. cingulata, 50 mg of 1 in 1.0 mL of dimethyl sulfoxide (DMSO) was added into the medium and cultivated for an additional 7 days, together with two controls, which contained either mycelia with medium or substrate dissolved in DMSO with medium. No metabolic product was observed in two controls. After the fermentation, the culture medium and mycelia were separated by filtration. The medium was saturated with NaCl and extracted with EtOAc. The mycelia were also extracted with EtOAc. Each EtOAc extract was combined, the solvent was evaporated, and a crude extract (423 mg) was obtained. The extract was distributed between 5% NaHCO3 aq and EtOAc, and EtOAc phase was evaporated to give a neutral fraction (159 mg). No metabolite was detected by TLC and HPLC. The alkali phase was acidified to pH 3 with 1 N HCl and distributed between water and EtOAc. The EtOAc phase was evaporated, and the acidic fraction (264 mg) was obtained. Metabolites were detected from both fractions by TLC and HPLC, respectively. The acidic fraction was dissolved in acetone (5 mL), and CH2N2 (1 mL) was added to the fraction. The solution was evaporated, and the methylation fraction was obtained. The methylation fraction was subjected to silica-gel column chromatography (CC) (silica gel 60, 230-400 mesh, Merck) with a n-hexane-Et2O gradient (9:1 to 1:4) to yield compound 2a (25 mg). Compound 2a (13 mg) was dissolved in MeOH (1 mL), 1% NaOH (2 mL) added to the solution, and the solution was refluxed for 30 min. The solution was acidified to pH 3 with 1 N HCl and distributed between EtOAc and water. The EtOAc phase was evaporated to give 2 (9 mg, Rt=6.6 min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With formic acid In methanol; water Ambient temperature; | |
100% | With hydrogen In ethyl acetate for 0.833333h; Ambient temperature; Irradiation; | |
99% | With hydrogen In acetic acid for 12h; |
99% | With 2C2H3O2(1-)*Pd(2+)*3Na(1+)*C18H12O9PS3(3-); hydrogen; glycerol at 100℃; for 2h; Schlenk technique; | |
96% | With hydrogen In ethyl acetate Ambient temperature; | |
94% | With sodium tetrahydroborate; hydrogen; nickel dichloride In isopropyl alcohol at 40℃; for 6h; | Reduction of oct-1-ene (1). General procedure: Anhydrous nickel(II) chloride, 1.75 g (14 mmol), was added to a suspension of 1.1 g (30 mmol) of NaBH4 in 20 mL of propan-2-ol to obtain a black colloidal solution. Hydrogen was passed through the solution at a flow rate of 15-20 mL/min, 34 g (0.3 mol) of oct-1-ene (1) was added, and the mixture was stirred for 6 h at 50-60 °C. The mixture was cooled, 1 mL of water was added to accelerate coagulation of the catalyst, the precipitate was filtered off, the solvent was removed from the filtrate by distillation through a column, and the residue was distilled. Yield 28 g (0.246 mol, 82%), bp 124-127°C[20]. Mass spectrum, m/z (Irel, %): 114 (5) [M]+, 85(25), 71 (20), 57 (33), 43 (100). |
93% | With methanol; palladium diacetate; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In dichloromethane at 25℃; for 12h; Schlenk technique; Inert atmosphere; | 42 Replace the gas environment in the Shrek tube with a nitrogen environment, add coumarin 0.25 mmol, palladium acetate 0.0025 mmol, methylene chloride 0.5 mL, methanol 0.275 mmol, add pinacol borane 0.275 mmol under stirring, and react at room temperature After 12 hours, the reaction solution obtained after the completion of the reaction was subjected to column chromatography, and the target product obtained in 93% yield was a colorless liquid. |
93% | With methanol; palladium diacetate; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In dichloromethane at 25℃; for 12h; Sealed tube; Inert atmosphere; chemoselective reaction; | |
90% | With nickel In tetrahydrofuran at 20℃; for 0.25h; | |
90% | With hydrogen; acetic acid for 48h; | |
85% | With Raney nickel (50percent Ni-Al) In sodium hydroxide at 90℃; for 1.5h; | |
85% | With sodium hydrogen telluride In ethanol for 5h; Heating; | |
84% | With hydrogen In acetic acid for 3h; | |
83% | With hydrogen In ethanol at 50℃; for 3h; | |
81% | With H2SiEt2; C32H43BCeF15Si6 at 25℃; for 0.166667h; Inert atmosphere; | |
71% | With methanol; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate at 20℃; for 16h; Inert atmosphere; Irradiation; Sealed tube; | |
60% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; tetrahydroxydiboron; water; triethylamine In tetrahydrofuran at 30℃; for 12h; Schlenk technique; Inert atmosphere; | |
50% | With baker's yeast; D-glucose In ethanol at 35 - 38℃; for 48h; | |
18% | With [Ir(COD)((4S)-iPr-Phox)]tetrakis[(3,5-trifluoromethyl)phenyl]borate; hydrogen; N-ethyl-N,N-diisopropylamine In toluene at 20℃; for 8h; Autoclave; | |
With nickel at 160 - 200℃; Hydrogenation.unter Druck; | ||
With Pd-BaSO4; ethanol Hydrogenation; | ||
With nickel; benzene at 130℃; Hydrogenation; | ||
With nickel; benzene at 85℃; Hydrogenation; | ||
With diethyl ether; nickel at 100℃; Hydrogenation; | ||
With methanol; nickel Hydrogenation; | ||
With ethanol; platinum Hydrogenation; | ||
With palladium; acetic acid Hydrogenation; | ||
With tetralin; palladium; toluene | ||
99 % Chromat. | With sodium hydrogen telluride In ethanol for 4h; Ambient temperature; | |
With hydrogen In acetic acid | ||
With triethylsilane; silica gel 1.) benzene, room temperature, 16 h, 2.) petroleum ether, ethyl acetate; Yield given. Multistep reaction; | ||
With hydrogen In ethanol for 2h; Ambient temperature; | ||
With sodium hydrogen telluride In ethanol Ambient temperature; Yield given; | ||
With potassium chloride; hydrogen In methanol; water for 0.166667h; catodically pretreated Raney-Ni-powder; other times; hydrogenation in presence of pyridine and coumarine; change of potential during the hydrogenation; | ||
Multi-step reaction with 2 steps 1: water; sodium amalgam 2: Bei der trocknen Destillation | ||
99 %Spectr. | With triethylsilane; indium tribromide; allyl-trimethyl-silane In toluene at 70℃; for 24h; | |
With hydrogen In glycerol at 100℃; for 3h; | 2.2. Pd-catalysed hydrogenation General procedure: 1 mmol of alkene (146 mg for (E)-4-phenyl-but-3-en-2-one;146 mg for coumarin; 165 mg for 4-nitroacetophenone; 180 mg fortrans-stilbene) was added to a 1 mL of solution of preformed nanoparticlesin glycerol (0.01 mmol Pd, 1.0 mol%). The resulting mixture was stirred at room temperature under argon in a Fisher-Porter bottle. The system was then pressurized with dihydrogen (3 bar) and stirred at100 °C for 3 h. The mixture was then cooled to room temperature. The catalytic mixture was extracted with dichloromethane (3 × 10 mL) and the combined organic phases were dried over anhydrous Na2SO4,filtered and the solvent evaporated under reduced pressure. | |
With Old Yellow Enzyme 1; NADH In tert-butyl methyl ether; dimethyl sulfoxide at 30℃; for 24h; Enzymatic reaction; | ||
With 5% Pd-BaSO4; hydrogen In tetrahydrofuran at 74.84℃; for 2h; Autoclave; | ||
79 %Chromat. | With hydrogen In glycerol at 80℃; for 2h; | |
99 %Spectr. | With borane-ammonia complex; 2-H-1,3-di-tert-butyl-2,3-dihydro-1H-1,3,2-diazaphosphole In [D3]acetonitrile at 50℃; for 1h; regioselective reaction; | |
With hydrogen In methanol at 20℃; for 80h; chemoselective reaction; | ||
With hydrogen In toluene at 100℃; for 15h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | To a stirred solution of the known coumarin 11 (0.0342mmol) in acetic acid (20mL) at room temperature, a solution of bromine (0.0685mmol) was added dropwisely over a time period of 1h. After the addition completed, the reaction was poured onto ice/water (300mL) and neutralized with NaOH solution (10%). The formed precipitate was filtered and dissolved in DCM (150mL) and was used in the next step without further purification. Triethyl amine was added dropwise to the ice cold solution of the dibromocoumarin in DCM. After 1h the reaction was quenched with HCl (10%, 100mL), the bromocoumarin was extracted with DCM (20mL, 3x), dried (anh, CaCl2), concentracted in vacuo and the crude product was recrystallized from ethanol (75%) to give 3-bromocoumarin 12 as colorless solid. (7.2g, 94%); the spectral data are consistent with that reported in literature.35 | |
90% | Coumarin (2.92 g, 20 mmol), oxone (14.8 g, 24 mmol), CH2Cl2 (80 mL) and HBr (22 mL, 44 mmol) were added to a two-necked round-bottomed flask under nitrogen, with magnetic stirring. The solution was left at room temperature for 2 h. After that, Et3N (8.7 mL, 60 mmol) was added dropwise, after which the solution was followed by GC. After consumption of the entire amount of coumarin, the mixture was extracted with two 50 mL portions of ethyl acetate. The organic phase was dried with MgSO4 and concentrated under a vacuum, giving an orange solid. 3-Bromo-2H-chromen-2-one (1): Yield 90%. 1H NMR (CDCl3, 300 MHz) delta (ppm) 7.27-7.36 (m, 2H), 7.45 (d, J = 7.62 Hz), 7.57 (t, J = 7.06 Hz, 1H), 8.10 (s, 1H). 13C NMR (CDCl3, 75 MHz) delta (ppm) 111.8, 116.8, 119.3, 125.0, 127.1, 132.0, 144.4, 153.2, 157.0. EM m/z (%) 224 (69), 196 (20), 145 (28), 89 (100), 63 (37). M. p = 110-111 C (Lit) (Kim e Park, 2004). | |
61.2% | With N-chloro-succinimide; copper(II) chloride monohydrate; In acetonitrile; at 82℃; for 28h; | General procedure: To a 50 mL flask, the coumarin (1 mmol), appropriate amount of NXS, the Lewisacid catalyst and 20 mL anhydrous solvent were added in. The mixture was heated toreflux with a condenser under the protection of a drying tube. The reaction progresswas monitored by TLC. When the reaction was completed, the mixture was cooled toroom temperature. The solvent was removed by vacuum rotary evaporation, and theresidue was dispensed in 25 mL 5% sodium hydrogen sulfite (NaHSO3) aqueoussolution and then extracted with 25 mL ethyl acetate (EtOAc) for three times. Theorganic layer was combined, washed with 10 mL water and dried over anhydroussodium sulphate (Na2SO4). After the solvent was removed, the crude product waspurified by silica gel (300-400 mesh) column chromatograph. |
52.1% | Coumarin (0.73 g, 5 mmol) and Oxone (3.7 g, 6 mmol) were added to a Schlenk flask and protected by argon.Add DCM to dissolve (20 mL),An additional 2N HBr (5.5 mL, 11 mm01) aqueous solution was added,The reaction liquid turned red-brown turbid liquid.After 6h reaction at room temperature,Triethylamine (2.1 mL, 15 mmol) was then slowly added dropwise,First joined the red disappeared,Then there will be a lot of bubbles,Solution color turns green,Finally, it became slightly red,The TLC tracking reaction (PE / EA = 10: 1, v / v) disappeared to the starting point,The reaction mixture was extracted with dichloromethane (30 mL × 3)The combined organic layers were dried over anhydrous sodium sulfate and dried.The crude product was purified by silica gel column chromatography (eluent:PE-PE / EA = 10: 1, v / v),Eluate collection,After spinning, 0.59 g of a white solid product (compound of Formula 3a) was obtained,Yield 52.1% | |
33% | With bromine; In chloroform-d1; at 0 - 20℃; | Step 1 : 3-bromo-2H-chromen-2-one (87a) Bromine (0.35 ml_, 6.84 mmoles, 1 eq.) was added dropwise to a stirred solution of coumarin (1 g, 6.84 mmoles, 1 eq.) in chloroform (1 0 ml_) at 0 C. The reaction mixture was allowed to gradually warm to room temperature overnight. Triethylamine (2 ml_) was added and the reaction mixture was washed with water (2 x 1 0 ml_). The organic phase was dried over Na2S04 and evaporated under reduced pressure. The residue was chromatographed on silica gel (SNAP 50) eluting with 5% EtOAc in petroleum ether to give 504 mg of 3-bromo-2H-chromen-2-one 87a as a white solid (Y=33%). LC-MS (M- H+) = 225.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 6% 2: 76% | With ammonia; calcium In tetrahydrofuran at -33℃; for 2h; other reagents: lithium, sodium, liq. ammonia; | |
1: 25% 2: 65% | With ammonia; lithium In tetrahydrofuran at -33℃; for 2h; other reagents: calcium, sodium, liq. ammonia; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With ytterbium(III) trifluoromethanesulfonate hydrate at 80℃; for 0.0333333h; Microwave irradiation; | General procedure for coumarin synthesis by MW irradiation An open reaction vessel containing a mixture of the phenol (1.0 mmol), propiolic acid (1.1 mmol), and Yb(OTf)3 hydrate (0.1 mmol) was put in the MW apparatus and irradiated at 200 W (80 °C) for 2 min. The reaction was monitored by TLC (eluent CH2Cl2 / MeOH 99:1). The crude solid obtained was diluted with Et2O and the resulting suspension filtered under vacuum to separate the catalyst, the precipitate washed several times with Et2O. The filtrate was washed twice with a 5% NaHCO3 solution (10 mL) dried over MgSO4 and evaporated to dryness under vacuum yielding the desired product. Coumarin (entry 1). White solid. Analytical data were in full agreement with those recorded for an authentic sample from the commerce. Anal. Calcd. for C9H6O2: C, 73.97; H, 4.14; O, 21.90. Found: C, 73.95; H, 4.12; O, 21.92. |
76% | With trifluoroacetic acid In chlorobenzene at 100℃; for 1h; Inert atmosphere; | General Procedure forthe Synthesis of Coumarin Derivatives. General procedure: A mixture of Phenol derivatives (1) (1.0 mmol), trifluoromethanesulfonic acid (1.0 mmol) and propiolic acid (2a) (0.5 mmol) in PhCl (3.0 mL) was stirred at 100 °C for 1 h. After completion of reaction as indicated by TLC, the reaction mixture was poured into H2O, neutralized with NaHCO3 solution and extracted CH2Cl2. The organic layer was washed with 2M NaOH, dried over anhydrous MgSO4. The solvent was removed in vaccum, and the products were purified by silica gel columnchromatography (EtOAc-Hex) to give the desired product 3. |
76% | With trifluorormethanesulfonic acid In chlorobenzene at 100℃; for 2h; | 1 Preparation of coumarin (1a) A mixture of phenol (1.0 mmol), trifluoromethanesulfonic acid (1.0 mmol) and propiolic acid (0.5 mmol) in chlorobenzene (PhCl, 3.0 mL) And stirred for 2 hours.After confirming the completion of the reaction by TLC,The reaction mixture was poured into water,After neutralization with NaHCO3 solution,Extraction with dichloromethane (CH2CI2).The obtained organic layer was washed with 2M NaOH and then dried over anhydrous MgSO4. The solvent was removed by vacuum treatment,The product was purified by silica gel column chromatography (EtOAc-Hex) to give the title compound.White solid (55.4 mg, 76%). |
41% | at 120℃; for 0.25h; microwave irradiation (180 W); | |
33% | With trifluoromethane sulfonic acid silver salt; trifluoroacetic acid at 40℃; for 48h; | |
33% | With ferric(III) chloride; trifluoromethane sulfonic acid silver salt; trifluoroacetic acid In 1,2-dichloro-ethane at 60℃; for 15h; | |
With trifluorormethanesulfonic acid In chlorobenzene at 100℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With tetrabutylammomium bromide; copper(I) bromide In pyridine; N,N-dimethyl-formamide at -10 - -5℃; for 8h; Electrolysis; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 50 percent / baker's yeast; aq. D-glucose / ethanol / 48 h / 35 - 38 °C 2: LiAlH4 / diethyl ether / 5 h / Heating 3: pyridine / 0 °C 4: aq. NaOH / propan-2-ol / 5 h / 70 - 80 °C | ||
Multi-step reaction with 2 steps 1: Lawesson's reagent / toluene / Heating 2: Raney nickel / diethyl ether / 1.) -15 deg C, 2.) -10 deg C, 2 min | ||
Multi-step reaction with 2 steps 1: sodium; alcohol 2: alcoholic hydrochloric acid / 150 °C |
Multi-step reaction with 2 steps 1: ethanol; copper oxide-chromium oxide / 250 °C / 73550.8 - 147102 Torr / Hydrogenation 2: phosphorus (III)-bromide; benzene / erwaermen des Reaktionsgemisches mit wss.Natronlauge | ||
Multi-step reaction with 3 steps 1: LiBH4; diethyl ether / 20 °C 2: Erhitzen unter vermindertem Druck 3: palladium/charcoal; acetic acid / Hydrogenation | ||
Multi-step reaction with 2 steps 1: triethylsilane; indium tribromide; allyl-trimethyl-silane / toluene / 24 h / 70 °C 2: triethylsilane; indium tribromide / toluene | ||
Multi-step reaction with 2 steps 1: triethylsilane; indium tribromide; allyl-trimethyl-silane / toluene / 24 h / 70 °C 2: indium tribromide / chloroform |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride In toluene at 20 - 85℃; for 4h; | 3 To a suspension of NaH (14.9 g of a 60% dispersion in mineral oil, 0.31 mol ; 1.1 equiv. , oil washed away with hexane under argon atmosphere) in toluene (93 ml) is added at room temperature the solution of 9-decen-1-ol (53.2 g, 0.341 mol, 1.1 equiv. ) in toluene (93 ml). The solution of coumarin (45.3 g, 0.31 mol, 1.0 equiv. ) in toluene (93 ml) is then added within 30 min via dropping funnel. The temperature of the oilbath is raised slowly to 85°C within 30 min, upon which steady evolution of hydrogen is observed. During the following 3 h stirring at 85°C a gelatine-like orange mixture is formed which is then cooled to room temperature. The solution of phosgene in toluene (20%, 100 mi, 0.18 mol 0.6 equiv. ) is added over 45 min. During the addition, the gel becomes liquid again and the reaction is cooled with an icebath. The mixture is left stirring for 16 h at room temperature, then the excess phosgene is removed by purging with Argon. The mixture is poured on 200 ml 2N aq. HCI and 200 g ice. The phases are separated and the organic layer is washed three times each with water and water/brine 1: 1. After drying the over MgS04, the volatiles are removed i. RV and the residue dried at 0.05 mbar/50°C for 30 min. From this, 107.1 g of product were obtained as a pale yellow oil which contains the 83% of the title compound (= 90% yield) besides some mixed carbonates. A sample is further purified via column flash chromatography on Si02 eluting with hexane/MTBE 4: 1 to isolate analytically pure product as a colourless oil. IR (film) : 1784m, 1713s, 1638m, 1202vs, 758s. 'H-NMR (400 MHz, CDC13) : 7.89 (d, J=16, 2H), 7.67 (dd, J=7.6, 1.2, 2H), 7.46-7. 30 (m, 6H), 6.53 (d, J=16, 2H), 5.08 (sym. m, 2H), 4.26 (sym. m, 4H), 1.99 (sym. m, 4H), 1.80- 1.15 (4 series of m, 10H), 1.67 (s, 6H), 1.59 (s, 6H), 0.95 (d, J=6.4, 6H). '3C-NMR (100 MHz, CDCI3) : 166.5 (s), 151.3 (s), 149.2 (s), 137.3 (d), 131.3 (s), 131.2 (d), 128.1 (d), 127.0 (s), 126.9 (d), 124.5 (d), 122.3 (d), 121.3 (d), 63.3 (t), 37.0 (t), 35.5 (t), 29.6 (d), 25.7 (q), 25.4 (t), 19.4 (q), 17.6 (q). MS (Ei 70 eV): 631 (5, M+), 493 (10), 475 (100), 431 (26), 337 (65). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In succinic acid diethyl ester | 3 EXAMPLE 3 EXAMPLE 3 1.5 g of hexahydrocoumarin and 0.5 g of 5% Pd/C in 20 cc of diethyl succinate were loaded in a flask. The mix was heated to 220° C. for three hours. A mix containing coumarin and dihydrocoumarin formed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With H2 In acetic acid; ethyl acetate | 1.B B. B. Preparation of Ethyl 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylate In a pressure bottle, the chromone (12.07 g, 0.044 mol) was dissolved in 210 mL of acetic acid. 10% Pd/C (7.2 g) catalyst was added to this solution and the bottle was pressurized with 52 psi of H2 gas. The reaction was agitated for 23 hours. The catalyst was removed by filtration through a celite pad in a sintered glass funnel. The catalyst was washed with EtOAc. The solvent was removed from the filtrate and the resulting oil was azeotroped with toluene providing 12 g of brown oil. The material was purified on a Waters Prep 500 HPLC, equipped with silica gel cartridges, running a 5% to 40% EtOAc/Hexane gradient over 50 min at a flow rate of 250 mL/min and collecting 500 mL fractions. The purified chroman was obtained as a pink oil (10 g, 86%). TLC: Rf=0.50 (40% EtOAc/Hexane). 1H NMR (CDCl3) δ6.73 (d, 1, J=8.20 Hz), 6.37 (d, 1, J=8.20 Hz), 4.78 (s(br), 1), 4.75 (m, 1), 4.25 (m, 2), 2.68 (m, 4), 2.16 (m, 2), 1.60 (m, 2), 1.29 (t, 3, J=7.07 Hz), 0.99 (t, 3, J=7.34 Hz). |
86% | With H2 In acetic acid; ethyl acetate | 10.G F. G. Preparation of Ethyl 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylate. In a parr bottle, chromone (12.07 g, 0.044 mol) was dissolved in 210 mL of acetic Acid. 10% Pd/C (7.2 g) catalyst was added to this solution and the bottle was pressurized with 52 psi of H2 gas. The reaction was agitated for 23 h. The catalyst was removed by filtration through a celite pad in a sintered glass funnel. The catalyst was washed with EtOAc. The solvent was removed from the filtrate and the resulting oil was azeotroped with toluene providing 12 g of brown oil. The material was purified on a Waters Prep 500 HPLC, equiped with silica gel cartridges, running a 5% to 40% EtOAc/Hexane gradient over 50 min at a flow rate of 250 mL/min and collecting 500 mL fractions. The purified chroman was obtained as a pink oil (10 g, 86%). TLC: Rf=0.50 (40% EtOAc/Hexane). 1 H NMR (CDCl3)δ6.73 (d,1,J=8.20 Hz), 6.37 (d,1,J=8.20 Hz), 4.78 (s(br), 1), 4.75 (m,1), 4.25 (m,2), 2.68 (m, 4), 2.16 (m,2), 1.60 (m,2), 1.29 (t,3,J=7.07 Hz), 0.99 (t,3,J=7.34 Hz). |
86% | With H2 In acetic acid; ethyl acetate | 9.C B. C. Preparation of Ethyl 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylate. In a parr bottle, chromone (12.07 g, 0.044 mol) was dissolved in 210 mL of acetic acid. 10% Pd/C (7.2 g) catalyst was added to this solution and the bottle was pressurized with 52 psi of H2 gas. The reaction was agitated for 23 h. The catalyst was removed by filtration through a celite pad in a sintered glass funnel. The catalyst was washed with EtOAc. The solvent was removed from the filtrate and the resulting oil was azeotroped with toluene providing 12 g of brown oil. The material was purified on a Waters Prep 500 HPLC, equiped with silica gel cartridges, running a 5% to 40% EtOAc/Hexane gradient over 50 min at a flow rate of 250 mL/min and collecting 500 mL fractions. The purified chroman was obtained as a pink oil (10 g, 86%). TLC: Rf=0.50 (40% EtOAc/Hexane). 1H NMR (CDCl3)δ6.73 (d,1 J=8.20 Hz) 6.37 (d,1,J=8.20 Hz), 4.78 (s(br), 1), 4.75 (m,1), 4.25 (m,2), 2.68 (m, 4), 2.16 (m,2), 1.60 (m,2), 1.29 (t,3,J=7.07 Hz), 0.99 (t,3,J=7.34 Hz). |
86% | With hydrogen In acetic acid; ethyl acetate | 12.G F. G. Preparation of Ethyl 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylate. In a Parr bottle, chromone (12.07 g, 0.044 mole) was dissolved in 210 ml of acetic acid. A catalyst (10% palladium/activated carbon) (7.2 g) was added to this solution and the bottle was pressurized with 52 psi of hydrogen gas. The reaction was agitated for 23 hours. The catalyst was removed by filtration through a Celite pad in a sintered glass funnel. The catalyst was washed with ethyl acetate. The solvent was removed from the filtrate and the resulting oil was azeotroped with toluene providing 12 g of brown oil. The material was purified on a Waters Prep 500 HPLC, equipped with silica gel cartridges, running a 5% to 40% ethyl acetate/hexane gradient over 50 minutes at a flow rate of 250 ml/min and collecting 500 ml fractions. The purified chroman was obtained as a pink oil (10 g, 86%). TLC: Rf=0.50 (40% EtOAc/Hexane). 1 H NMR (CDCl3) δ6.73 (d, 1, J=8.20 Hz), 6.37 (d, 1, J=8.20 Hz), 4.78 (s(br), 1), 4.75 (m, 1), 4.25 (m, 2), 2.68 (m, 4), 2.16 (m, 2), 1.60 (m, 2), 1.29 (t, 3, J=7.07 Hz), 0.99 (t, 3, J=7.34 Hz). |
86% | With H2 In acetic acid; ethyl acetate | 13.B Preparation of 7-[3-(4-acetyl-2-ethyl-5-hydroxyphenoxy)propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid. STR18 B. Preparation of Ethyl 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylate. In a pressure bottle, the chromone (12.07 g, 0.044 mole) was dissolved in 210 ml of acetic acid. 10% palladium on activated carbon (7.2 g) catalyst was added to this solution and the bottle was pressurized with 52 psi of H2 gas. The reaction was agitated for 23 hours. The catalyst was removed by filtration through a Celite pad in a sintered glass funnel. The catalyst was washed with ethyl acetate. The solvent was removed from the filtrate and the resulting oil was azeotroped with toluene providing 12 g of brown oil. The material was purified on a Waters Prep 500 HPLC, equiped with silica gel cartridges, running a 5% to 40% ethyl acetate/hexane gradient over 50 minutes at a flow rate of 250 ml/minutes and collecting 500 ml fractions. The purified chroman was obtained as a pink oil (10 g, 86%). TLC: Rf=0.50 (40% ethyl acetate/hexane). 1 H NMR (CDCl3) δ6.73 (d, 1, J=8.20 Hz), 6.37 (d, 1, J=8.20 Hz), 4.78 (s(br), 1), 4.75 (m, 1), 4.25 (m, 2), 2.68 (m, 4), 2.16 (m, 2), 1.60 (m, 2), 1.29 (t, 3, J=7.07 Hz), 0.99 (t, 3, J=7.34 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In methyl 3-(2-oxcyclohexyl)propionate | 1 EXAMPLE 1 EXAMPLE 1 In a four-necked flask were charged 300 g of methyl 3-(2-oxcyclohexyl)propionate and 2.1 g of 5% palladium-on-activated carbon egg shell catalyst in which 5% of palladium based on the carrier amount was supported on the carrier ('Water-containing 5% Pd-on-carbon Powder E-Type' produced by N.E. Chemcat Co.). The mixture was heated in a nitrogen atmosphere at 250°C for 10 hours with stirring at 240 rpm. The temperature was elevated up to 270°C over a period of 1 hour, and the reaction was continued at that temperature for 15 hours with stirring at 500 rpm. After completion of the reaction, the catalyst was removed by filtration. Gas chromatography analysis of the filtrate revealed that the conversion of methyl 3-(2-oxocyclohexyl)propionate was 100% and the yields of coumarin and 3,4-dihydrocoumarin were 38.4% by mol and 35.2% by mol, respectively, based on the amount of the starting methyl 3(2-oxocyclohexyl)propionate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With dmap; 4-mesityl-3-(4-methoxyphenyl)-1-phenyl-4H-1,2,4-triazol-1-ium perchlorate In ethyl acetate at 80℃; for 15h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Stage #1: Citronellol With sodium hydride In toluene at 20 - 85℃; for 2.58333h; Stage #2: coumarin In toluene at 80℃; for 2.75h; | 1 To a suspension of NaH (114 g of a 60%-dispersion in mineral oil, 2.85 mol) in toluene (500 ml) is added at room temperature a solution of citronellol (468 g, 3.0 mol) in toluene (800 ml) over 50 min via dropping funnel. The temperature is raised to 85°C (bath) over 60 min and stirring continued for further 45 min. Then a solution of coumarin (219 g, 1.5 mol) in toluene (800 ml) is added over 75 min. After further 90 min stirring at 80°C (inside temperature), the deep orange suspension is cooled to 55°C and poured on a mixture of 2.5 kg crushed ice and 280 mi 37% aq. HCI-solution. The reaction flask is rinsed twice with 500 ml toluene. Upon stirring for 10 min the colour of the organic layer fades to a pale yellow. The organic layer is washed twice with water, then with brine/water 1: 1 and dried over MgS04. After concentrating in the rotary evaporator the excess citronellol is distilled off using a short path apparatus (110-125°C/0. 03 mbar, head 82°C) to obtain 240 g of citronellol and 463 g of a brownish residue. The latter is dissolved in 600 ml hexane containing 18 ml acetone and crystallized at-25°C. After filtration and drying 320 g (71 %) of product are obtained as white crystals, m. p. 37- 39°C. IR (film) : 3500-3100br, 1673vs, 1633w, 1619w, 1598s, 1450s. 'H-NMR (400 MHz, CDCI3) : 8.10 (d, J=16,2H), 7.79 (s, 1H), 7.44 (dd, J=7.6, 1.2, 1H), 7.22-7. 18 (m, 1H), 6.69 (d, J=16, 2H), 5.09 (sym. m, 1H), 4.28 (sym. m, 24H), 2.00 (sym. m, 2H), 1.80-1. 15 (series of m, 5H), 1.68 (d, J=0.4, 3H), 1.60 (s, 3H), 0.95 (d, J=6.8, 3H). '3C-NMR (100 MHz, CDCI3) : 169.1 (s), 155.9 (s), 141.3 (d), 131.4 (d), 131.2 (s), 129.1 (d), 124.5 (d), 121.5 (s), 120.3 (d), 117.8 (d), 116.4 (d), 63.4 (t), 36.9 (t), 35.3 (t), 29.4 (d), 25.6 (q), 25.3 (t), 19.3 (q), 17.6 (q). MS (El 70 eV): 302 (<1, M+), 165 (15), 147 (83), 138 (45), 81 (100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: 9-Decen-1-ol With sodium hydride In toluene at 20℃; for 1.41667h; Stage #2: coumarin In toluene at 20 - 85℃; for 3.5h; | 2 To a suspension of NaH (271 g of a 60%-dispersion in mineral oil, 6.81 mol) in toluene (1200 ml) is added at room temperature a solution of 9-decen-1-ol (1060 g, 6.81 mol) in toluene (1500 ml) over 75 min via dropping funnel. After 10 min stirring a solution of coumarin (495 g, 3.39 mol) in toluene (1800 ml) is added over 75 min. The temperature is raised to 85°C (bath) over 45 min. After further 90 min stirring at 80°C (inside temperature), the deep orange suspension is cooled to 50°C and poured on a mixture of 4 I 10% aq. H2S04-solution and 2 1 of MTBE. The organic layer is washed with saturated aq. NaHCO3-solution, followed by water and brine. After concentrating i. RV the excess of 9-decen-1-ol is removed by thin film evaporation (130°C, 0.05 mbar) to leave 1064 g of residue which is crystallized from hexane at 5°C. From this, 775 g (75%) of product are obtained as pale yellow crystals, m. p. 58°C. IR (film) : 3197br, 1670vs, 1598vs, 1451s. 'H-NMR (400 MHz, CD13) : 8.09 (d, J=16, 2H), 7.64 (s, 1H), 7.45 (d, J=8, 1H), 7.23- 7.19 (m, 1H), 6.90-6. 86 (m, 2H), 6.68 (d, J=16, 1H), 5.84-5. 77 (sym. m, 1H), 5.01-4. 91 (m, 2H), 4.23 (t, J=8,2H), 2.03 ("q", J=8,2H), 1.71 (quint, J=8,8), 1.39-1. 29 (m, 1 H). '3C-NMR (100 MHz, CDCI3) : 169.0 (s), 155.8 (s), 141.1 (d), 139.1 (d), 131.4 (d), 129.1 (d), 121.5 (s), 120.3 (d), 117.8 (d), 116.4 (d), 114.0 (t), 65.0 (t), 33.7 (t), 29.3 (t), 29.3 (t), 29.1 (t), 29.0 (t), 28.8 (t), 28.6 (t), 25.8 (t). MS (El 70 eV): 302 (10, M+), 164 (8), 178 (100), 118 (37). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7.2% | Stage #1: 6-amino-2-methylbenzothiazole With hydrogenchloride; sodium nitrite In water at -5℃; Stage #2: coumarin With copper(II) choride dihydrate; sodium acetate In water; acetone at 0℃; for 1.5h; | 3-(2-Methylbenzo[d]thiazol-6-yl)-2H-chromen-2-one 1. A solution of sodium nitrite (7.6 g) in water (12 ml) was added dropwise at -5 °C to a stirred mixture of hydrochloric acid (25 ml), water (20 ml) and 6-amino-2-methylbenzothiazole 4 (16.4 g) to give diazonium salt 5. Then the solutionof 5 was filtered and added dropwise to a vigorously stirred mixture of coumarin 6 (14.6 g), acetone (120 ml), AcONa·3H2O (27.5 g), CuCl2·2H2O(5 g) and H2O (10 ml) cooled to 0 °C. Nitrogen evolution continued for 1.5 h. Meanwhile, the reaction mixture reached room temperature. The reaction mixture was steam distilled to collect ~1 dm3 of the distillate. After cooling, CHCl3 (500 ml) was added to the residue in the distillation flask. The flask contents were stirred with a mechanical stirrer and a dark resinous precipitate was filtered off on a Büchner funnel. The precipitate was washed with CHCl3. The filtrate was transferred into a separating funnel to separate the lower chloroform layer, which was concentrated to 1/3 in vacuo. The residue was subjected to column chromatography on Al2O3 using CHCl3 as the eluent. According to UV spectroscopic data, the first portions of the eluate contained coumarin ( λmax = 215, 280 and 312 nm), while the next portions were yellow and contained compound 1. These portions of the eluate were concentrated in vacuo and the residue was recrystallized from EtOH to give 2.1 g (7.2%) of 1 as cream-coloured crystals with mp 193-195 °C. UV spectrum [EtOH, λmax/nm(ε)]: 215 (41320), 235 (sh, 19533),270 (13147), 310 (sh, 21411), 335 (25167). 1H NMR (CDCl3) δ: 2.85(s, 3 H, Me), 7.7 (d, 1H, H-5, J 8 Hz), 7.9 (s, 1H, H-7), 8.0 (d, 1H, H-4,J 8 Hz), 8.25 (s, 1H, H-8), 7.2-7.6 (m, 4 H, Ar). MS (ESI), m/z: 294.0610[M + H]+ (calc. for C17H11NO2S: 294.059) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine; In dichloromethane; at 20℃; for 48h; | First react with coumarin and liquid bromine in dichloromethane solution for 48 hours at room temperature.Wash with plenty of saturated sodium carbonate solution, extract with dichloromethane,After removing excess solvent by a rotary evaporator, it was filtered by methanol and dried to obtain a yellow solid powder.The crude product was separated and purified on a 200-300 mesh silica gel column using dichloromethane-n-hexane (volume ratio: 2:5) as an eluent to obtain a brominated coumarin derivative at the 6 position. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63%; 8% | With dipotassium peroxodisulfate; silver nitrate; In water; dimethyl sulfoxide; at 20℃; for 24h;Inert atmosphere; Schlenk technique; Sealed tube; | General procedure: A 10mL oven-dried Schlenk-tube was charged with AgNO3 (3.4mg, 10mol%), coumarin (1, 0.2mmol, 1.0equiv), and K2S2O8 (108mg, 0.4mmol, 2.0equiv). The tube was evacuated and backfilled with nitrogen (three times). alpha-Oxocarboxylic acids (2, 0.48mmol, 2.4equiv) in DMSO/H2O (1:1) 2mL were added by syringe. The tube was then sealed and the mixture was stirred for 24h at room temperature. Upon completion of the reaction, the mixture was diluted with EtOAc, filtered through a pad of Celite, and the filtrate was then removed under vacuo. The residue was purified with chromatography column on silica gel (gradient eluent of EtOAc/petroleum ether: 1:30 to 1:15) to give the corresponding products 3 or 4 in yields listed in Tables 2 and 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With dipotassium peroxodisulfate; silver nitrate; In water; dimethyl sulfoxide; at 20℃; for 24h;Inert atmosphere; Schlenk technique; Sealed tube; | General procedure: A 10mL oven-dried Schlenk-tube was charged with AgNO3 (3.4mg, 10mol%), coumarin (1, 0.2mmol, 1.0equiv), and K2S2O8 (108mg, 0.4mmol, 2.0equiv). The tube was evacuated and backfilled with nitrogen (three times). alpha-Oxocarboxylic acids (2, 0.48mmol, 2.4equiv) in DMSO/H2O (1:1) 2mL were added by syringe. The tube was then sealed and the mixture was stirred for 24h at room temperature. Upon completion of the reaction, the mixture was diluted with EtOAc, filtered through a pad of Celite, and the filtrate was then removed under vacuo. The residue was purified with chromatography column on silica gel (gradient eluent of EtOAc/petroleum ether: 1:30 to 1:15) to give the corresponding products 3 or 4 in yields listed in Tables 2 and 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tert.-butylhydroperoxide; cobalt(II) chloride hexahydrate; 1,8-diazabicyclo[5.4.0]undec-7-ene at 75℃; for 1h; Sealed tube; regioselective reaction; | |
80% | With di-tert-butyl peroxide; copper diacetate; potassium iodide In tetrahydrofuran at 100℃; for 24h; Inert atmosphere; | 4.2 General procedure General procedure: 0.6 mmol DTBP in 1.5 mL THF was added into the 10 mL flask charged with 0.2 mmol coumarin, 10 mol % Cu(OAc)2, 20 mol % KI. The reaction mixture was stirred at 100 °C for specified hours, then cooled down to room temperature. Filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (elute: EtOAc/Petroleum ether 1/3-1/10, v/v) to give the desired product. |
73% | With 1,4-diaza-bicyclo[2.2.2]octane; di-tert-butyl peroxide at 120℃; for 6h; |
73% | With di-tert-butyl peroxide; potassium iodide at 120℃; for 20h; Sealed tube; | |
68% | With tert.-butylhydroperoxide In water at 120℃; for 24h; Sealed tube; regioselective reaction; | |
65% | With 1,4-diaza-bicyclo[2.2.2]octane; tert.-butylhydroperoxide; iron(III) chloride In water; benzene at 120℃; for 36h; regioselective reaction; | |
26% | With tert-Butyl peroxybenzoate; copper diacetate at 100℃; for 24h; Schlenk technique; Inert atmosphere; Sealed tube; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 3-methylcinnamic acid; coumarin With cyclomaltooctaose In water for 10h; Sonication; Stage #2: for 24h; Irradiation; | 3.1 Experimental procedure General procedure: The host (γ-CD) was purchased from CDT, Inc. and used as received. The guests, solvents, and drying agents were purchased from commercial sources (Sigma-Aldrich, Fischer Scientific, and MP Biomedicals LLC) and used as received. Host-guest complexes are prepared by typically subjecting 50mg of γ-CD, and one equivalent of each guest in 2mL of water to sonication for 5h, followed by 5h of stirring. Resulting insoluble white precipitate (inclusion complex) was isolated by filtration and washed with water, cold methanol and ether to remove uncomplexed components. The precipitate was dried under vacuum and used for future experiments. The powder prepared as mentioned above was placed between two Pyrex glass plates and irradiated for at least 24h. Irradiations were performed with a medium pressure mercury vapor lamp immersed in a water-cooled Pyrex jacket. Following irradiation, the inclusion complexes are dissociated through biphasic extraction with water and ethyl acetate. The organic layer was separated; residual water was removed using anhydrous Na2SO4, the solvent rotary evaporated, and the final sample dried under high-vacuum. The dried samples were then subject to 1H NMR (300MHz) analysis in CDCl3. The heterodimer in cases of cinnamic acid-6-methyl coumarin, and cinnamic acid-coumarin were isolated through flash chromatography over silica gel column using ethyl acetate dichloromethane (5:95) solvent mixture. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water for 10h; Sonication; | 3.1 Experimental procedure General procedure: The host (γ-CD) was purchased from CDT, Inc. and used as received. The guests, solvents, and drying agents were purchased from commercial sources (Sigma-Aldrich, Fischer Scientific, and MP Biomedicals LLC) and used as received. Host-guest complexes are prepared by typically subjecting 50mg of γ-CD, and one equivalent of each guest in 2mL of water to sonication for 5h, followed by 5h of stirring. Resulting insoluble white precipitate (inclusion complex) was isolated by filtration and washed with water, cold methanol and ether to remove uncomplexed components. The precipitate was dried under vacuum and used for future experiments. The powder prepared as mentioned above was placed between two Pyrex glass plates and irradiated for at least 24h. Irradiations were performed with a medium pressure mercury vapor lamp immersed in a water-cooled Pyrex jacket. Following irradiation, the inclusion complexes are dissociated through biphasic extraction with water and ethyl acetate. The organic layer was separated; residual water was removed using anhydrous Na2SO4, the solvent rotary evaporated, and the final sample dried under high-vacuum. The dried samples were then subject to 1H NMR (300MHz) analysis in CDCl3. The heterodimer in cases of cinnamic acid-6-methyl coumarin, and cinnamic acid-coumarin were isolated through flash chromatography over silica gel column using ethyl acetate dichloromethane (5:95) solvent mixture. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; for 10h;Sonication; | General procedure: The host (gamma-CD) was purchased from CDT, Inc. and used as received. The guests, solvents, and drying agents were purchased from commercial sources (Sigma-Aldrich, Fischer Scientific, and MP Biomedicals LLC) and used as received. Host-guest complexes are prepared by typically subjecting 50mg of gamma-CD, and one equivalent of each guest in 2mL of water to sonication for 5h, followed by 5h of stirring. Resulting insoluble white precipitate (inclusion complex) was isolated by filtration and washed with water, cold methanol and ether to remove uncomplexed components. The precipitate was dried under vacuum and used for future experiments. The powder prepared as mentioned above was placed between two Pyrex glass plates and irradiated for at least 24h. Irradiations were performed with a medium pressure mercury vapor lamp immersed in a water-cooled Pyrex jacket. Following irradiation, the inclusion complexes are dissociated through biphasic extraction with water and ethyl acetate. The organic layer was separated; residual water was removed using anhydrous Na2SO4, the solvent rotary evaporated, and the final sample dried under high-vacuum. The dried samples were then subject to 1H NMR (300MHz) analysis in CDCl3. The heterodimer in cases of cinnamic acid-6-methyl coumarin, and cinnamic acid-coumarin were isolated through flash chromatography over silica gel column using ethyl acetate dichloromethane (5:95) solvent mixture. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: The host (gamma-CD) was purchased from CDT, Inc. and used as received. The guests, solvents, and drying agents were purchased from commercial sources (Sigma-Aldrich, Fischer Scientific, and MP Biomedicals LLC) and used as received. Host-guest complexes are prepared by typically subjecting 50mg of gamma-CD, and one equivalent of each guest in 2mL of water to sonication for 5h, followed by 5h of stirring. Resulting insoluble white precipitate (inclusion complex) was isolated by filtration and washed with water, cold methanol and ether to remove uncomplexed components. The precipitate was dried under vacuum and used for future experiments. The powder prepared as mentioned above was placed between two Pyrex glass plates and irradiated for at least 24h. Irradiations were performed with a medium pressure mercury vapor lamp immersed in a water-cooled Pyrex jacket. Following irradiation, the inclusion complexes are dissociated through biphasic extraction with water and ethyl acetate. The organic layer was separated; residual water was removed using anhydrous Na2SO4, the solvent rotary evaporated, and the final sample dried under high-vacuum. The dried samples were then subject to 1H NMR (300MHz) analysis in CDCl3. The heterodimer in cases of cinnamic acid-6-methyl coumarin, and cinnamic acid-coumarin were isolated through flash chromatography over silica gel column using ethyl acetate dichloromethane (5:95) solvent mixture. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; for 10h;Sonication; | General procedure: The host (gamma-CD) was purchased from CDT, Inc. and used as received. The guests, solvents, and drying agents were purchased from commercial sources (Sigma-Aldrich, Fischer Scientific, and MP Biomedicals LLC) and used as received. Host-guest complexes are prepared by typically subjecting 50mg of gamma-CD, and one equivalent of each guest in 2mL of water to sonication for 5h, followed by 5h of stirring. Resulting insoluble white precipitate (inclusion complex) was isolated by filtration and washed with water, cold methanol and ether to remove uncomplexed components. The precipitate was dried under vacuum and used for future experiments. The powder prepared as mentioned above was placed between two Pyrex glass plates and irradiated for at least 24h. Irradiations were performed with a medium pressure mercury vapor lamp immersed in a water-cooled Pyrex jacket. Following irradiation, the inclusion complexes are dissociated through biphasic extraction with water and ethyl acetate. The organic layer was separated; residual water was removed using anhydrous Na2SO4, the solvent rotary evaporated, and the final sample dried under high-vacuum. The dried samples were then subject to 1H NMR (300MHz) analysis in CDCl3. The heterodimer in cases of cinnamic acid-6-methyl coumarin, and cinnamic acid-coumarin were isolated through flash chromatography over silica gel column using ethyl acetate dichloromethane (5:95) solvent mixture. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: The host (gamma-CD) was purchased from CDT, Inc. and used as received. The guests, solvents, and drying agents were purchased from commercial sources (Sigma-Aldrich, Fischer Scientific, and MP Biomedicals LLC) and used as received. Host-guest complexes are prepared by typically subjecting 50mg of gamma-CD, and one equivalent of each guest in 2mL of water to sonication for 5h, followed by 5h of stirring. Resulting insoluble white precipitate (inclusion complex) was isolated by filtration and washed with water, cold methanol and ether to remove uncomplexed components. The precipitate was dried under vacuum and used for future experiments. The powder prepared as mentioned above was placed between two Pyrex glass plates and irradiated for at least 24h. Irradiations were performed with a medium pressure mercury vapor lamp immersed in a water-cooled Pyrex jacket. Following irradiation, the inclusion complexes are dissociated through biphasic extraction with water and ethyl acetate. The organic layer was separated; residual water was removed using anhydrous Na2SO4, the solvent rotary evaporated, and the final sample dried under high-vacuum. The dried samples were then subject to 1H NMR (300MHz) analysis in CDCl3. The heterodimer in cases of cinnamic acid-6-methyl coumarin, and cinnamic acid-coumarin were isolated through flash chromatography over silica gel column using ethyl acetate dichloromethane (5:95) solvent mixture. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With di-tert-butyl peroxide; copper diacetate; potassium iodide In tetrahydrofuran at 100℃; for 24h; Inert atmosphere; | 4.2 General procedure General procedure: 0.6 mmol DTBP in 1.5 mL THF was added into the 10 mL flask charged with 0.2 mmol coumarin, 10 mol % Cu(OAc)2, 20 mol % KI. The reaction mixture was stirred at 100 °C for specified hours, then cooled down to room temperature. Filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (elute: EtOAc/Petroleum ether 1/3-1/10, v/v) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 5% active carbon-supported ruthenium; hydrogen; In methanol; at 130℃; under 75007.5 Torr; for 3h;Autoclave; | The hydrogenation of coumarin was carried out in a 25-mL stainless steel autoclave under constant hydrogen pressure. A commercial catalyst TYPE 97 PASTE (surface area 1000 m2/g, moisture content 52.3%, uniform metal location, mean particle size 25 mum) from Johnson Matthey with the composition of 5wt% Ru on active carbon (Ru/C) was used for the hydrogenation. Into the autoclave were inserted 2.8 g of coumarin, 0.14 g of the catalyst in the powder form and 14 mL of solvent. The reaction was carried out at 130 C and from 2-10 MPa of hydrogen pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 5% active carbon-supported ruthenium; hydrogen; In methanol; at 130℃; under 75007.5 Torr; for 3h;Autoclave; | The hydrogenation of coumarin was carried out in a 25-mL stainless steel autoclave under constant hydrogen pressure. A commercial catalyst TYPE 97 PASTE (surface area 1000 m2/g, moisture content 52.3%, uniform metal location, mean particle size 25 mum) from Johnson Matthey with the composition of 5wt% Ru on active carbon (Ru/C) was used for the hydrogenation. Into the autoclave were inserted 2.8 g of coumarin, 0.14 g of the catalyst in the powder form and 14 mL of solvent. The reaction was carried out at 130 C and from 2-10 MPa of hydrogen pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With dipotassium peroxodisulfate; methyl tri-n-octyl ammonium hydrogen sulfate In chlorobenzene at 100℃; for 8h; Sealed tube; regioselective reaction; | General procedure for the preparation of 3-(4-methylbenzoyl)-2H-chromen-2-one (3b). In a 5 mL sealed tube, a mixture of coumarin 1a (0.073 g, 0.5 mmol), 4-methylbenzaldehyde 2b (0.120 g, 1 mmol), K2S2O8 (0.162 g, 0.6 mmol), Aliquat 336 (0.061 g, 30 mol %) in chlorobenzene (1.5 mL) was stirred at 100 °C for 8 h. After reaction completion, as indicated by TLC, the reaction mixture was cooled to ambient temperature and treated with saturated aqueous NaHCO3 (5 mL). The product was extracted with ethyl acetate (2 × 3 mL) and the combined organic phase dried over MgSO4, filtered and the solvent evaporated under reduced pressure. The residue was purified by column chromatography using n-hexane-EtOAc (10:1) as eluent to afford 3b as colorless crystals, 0.111 g (84%). 1H NMR (300.1 MHz, CDCl3): δ = 2.43 (s, 3H), 7.28 (d, J = 7.6 Hz, 2H), 7.29-7.47 (m, 2H), 7.54-7.72 (m, 2H), 7.80 (d, J = 7.9, 2H), 8.06 (s, 1H). 13C NMR (75.5 MHz, CDCl3): δ = 21.8, 116.9, 118.2, 124.9, 127.2, 129.1, 129.3, 129.8, 133.5, 133.6, 144.9, 145.0, 154.6, 158.5, 191.2. |
73% | With tert.-butylhydroperoxide In water; chlorobenzene at 100℃; for 20h; Sealed tube; regioselective reaction; | |
61% | With tert.-butylhydroperoxide; copper(II) oxide In water at 90℃; for 24h; Sealed tube; regioselective reaction; |
60% | With tert.-butylhydroperoxide; iron(III) chloride hexahydrate In chlorobenzene at 80℃; for 10h; | 1 Example 1. Preparation of 3- (4-methylbenzoyl) coumarin derivative when R = -CH3, R1 = R2 = -H In a 25 mL reaction flask, coumarin (0.5 mmol, 73 mg) and p-methylbenzaldehyde (1.5 mmol, 180 mg) were addedSolution was dissolved in 5.0 mL of chlorobenzene followed by FeCl3 6H2O (0.05 mmol, 13.5 mg) and t-BuOOH (1.5 mmol, 195 mg).The reaction was carried out under heating with stirring in an oil bath at a reaction temperature of 80 ° C. The reaction was carried out by TLC. The reaction time was 10 h. After the reaction, the solvent was distilled off under reduced pressure. Ten mL of ethyl acetate was added to the residue, washed twice with 20 mL of saturated NaHCO3 and once with 10 mL of saturated brine. The phases were dried over anhydrous Na2SO4 and the solution was concentrated and purified by silica gel column chromatography (washedDeg.]: Ethyl acetate / petroleum ether = 1/10) to give 0.079 g of colorless crystals in 60% yield. |
55% | With tert.-butylhydroperoxide; iron(II) chloride In chlorobenzene at 120℃; for 12h; Schlenk technique; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With boron tribromide In dichloromethane at 50℃; for 5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane-d2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With caesium carbonate; toluene-4-sulfonic acid hydrazide; In dimethyl sulfoxide; at 100℃; for 36h; | General procedure: 4.3. General procedure for synthesis of 5, 9 (5aa as an example) A mixture of phenylglyoxal monohydrate 1a (152.2 mg,1.0 mmol), tosylhydrazine 2 (186.2 mg, 1.0 mmol), ethyl acrylate 4a(150.1 mg, 1.5 mmol), and Cs2CO3 (977.4 mg, 3.0 mmol) was addedto dried DMSO (20 mL), and stirred at 100 C. After the completionof the reaction, 100 mL of water was then added to the mixture,which was then extracted with EtOAc three times (3100 mL). Theproduct was dried over anhydrous Na2SO4 and concentrated underreduced pressure. The residue was then puried by column chro-matography on silica gel (petroleum ether/EtOAc) to afford thedesired product 5aa. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With caesium carbonate; toluene-4-sulfonic acid hydrazide; In dimethyl sulfoxide; at 100℃; for 36h; | General procedure: 4.3. General procedure for synthesis of 5, 9 (5aa as an example) A mixture of phenylglyoxal monohydrate 1a (152.2 mg,1.0 mmol), tosylhydrazine 2 (186.2 mg, 1.0 mmol), ethyl acrylate 4a(150.1 mg, 1.5 mmol), and Cs2CO3 (977.4 mg, 3.0 mmol) was addedto dried DMSO (20 mL), and stirred at 100 C. After the completionof the reaction, 100 mL of water was then added to the mixture,which was then extracted with EtOAc three times (3100 mL). Theproduct was dried over anhydrous Na2SO4 and concentrated underreduced pressure. The residue was then puried by column chro-matography on silica gel (petroleum ether/EtOAc) to afford thedesired product 5aa. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With potassium permanganate; In acetonitrile; at 80℃; for 3h;Schlenk technique; | General procedure: In a 50 mL Schlenk tube, a solution of coumarins 1 (orquinolinone derivatives 4) (0.5 mmol), arylhydrazines 2(1.0 mmol), and KMnO4 (1.5 mmol, 237 mg) in CH3CN (10mL) was stirred at 80C for 3.0 h. After the reaction wasfinished, the mixture was diluted with saturated NaClsolution (50 mL). Then the aqueous layer was extractedwith EtOAc (3 × 15 mL). The organic phase was dried overanhydrous Na2SO4 and concentrated under vacuum. Thecrude product was purified by silica gel column chromatographyusing ethyl acetate/petroleum ether (1:5 to 2:1) aseluant to obtain the desired product 3 (or 5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With potassium permanganate; In acetonitrile; at 80℃; for 3h;Schlenk technique; | General procedure: In a 50 mL Schlenk tube, a solution of coumarins 1 (orquinolinone derivatives 4) (0.5 mmol), arylhydrazines 2(1.0 mmol), and KMnO4 (1.5 mmol, 237 mg) in CH3CN (10mL) was stirred at 80C for 3.0 h. After the reaction wasfinished, the mixture was diluted with saturated NaClsolution (50 mL). Then the aqueous layer was extractedwith EtOAc (3 × 15 mL). The organic phase was dried overanhydrous Na2SO4 and concentrated under vacuum. Thecrude product was purified by silica gel column chromatographyusing ethyl acetate/petroleum ether (1:5 to 2:1) aseluant to obtain the desired product 3 (or 5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With sodium carbonate In water at 80℃; for 16h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In toluene at 25℃; for 0.583333h; Inert atmosphere; UV-irradiation; Flow reactor; diastereoselective reaction; | 1. GENERAL PROCEDURE FOR THE CONTINUOUS-FLOW REACTIONS Coumarin (2a, 219.2 mg, 5 equiv, 1.5 mmol) was introduced into a 12 mL vial under nitrogen atmosphere and dissolved in 5 mL of degassed toluene. Then, 2-methylbenzophenone (1a, 55 μL, 1 equiv, 0.3 mmol) was added in one portion and the solution was further bubbled with nitrogen for 5 min. The resultant solution was pumped into the MFP and irradiated by a 9 W 365 nm bulb with a residence time of 35 min. The product solution was collected into a 7 mL vial. Subsequently, the solvent was removed by rotary evaporation and the crude subjected to flash column chromatography on silica gel(9:1 hexane/EtOAc) yielding pure 4a (white solid), as a single diastereoisomer in >98%yield (100.1 mg, 0.293 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With iron(III) chloride; sulfur In ethanol at 60℃; for 2h; Sealed tube; | 1 Example 1 Add 1 mmol of coumarin to the reaction vessel.Sodium trifluoroacetate 1 mmol,Elemental sulfur 1mmol,0.01 mmol of ferric chloride and 2 ml of ethanol,Sealing reaction at 60 ° C for 2 hours,After the reaction is completed, column chromatography is performed.The following target compounds were obtained:Performing a nuclear magnetic spectrum analysis on the above white solid powder, After identification,The spectral data corresponds to the structural formula,It was proved that the synthesis was 3-trifluoromethylthio-coumarin,The yield was 97%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tris[2-phenylpyridinato-C2,N]iridium(III); trifluoroacetic acid; In dimethyl sulfoxide; at 25℃; for 24.0h;Inert atmosphere; Irradiation; Green chemistry; | Coumarin (0.5 mmol, 73 mg),<strong>[17720-64-8]N-acetoxyphthalimide</strong> (1.0 mmol, 205 mg),Ir(ppy)3 (0.025mmol, 16.4mg)And trifluoroacetic acid (0.5 mmol, 57 mg)Add 5mL single-mouth reaction bottle,Add DMSO (1.0 mL) as solvent,Under the protection of the N2 atmosphere,The reaction was carried out under 3w white light irradiation at a temperature of 20 C for 24 hours.After the reaction,The reaction system is washed with water,After extracting with dichloromethane,The liquid separation is an organic layer and a water layer.After the organic layer is dried over anhydrous sodium sulfate,The solvent was evaporated under reduced pressure to give a yellow oil.The yellow oil is separated by column chromatography.a mixture of petroleum ether and ethyl acetate in a volume ratio of 25:1 as an eluent,Collect the eluate containing the target compound,Evaporate the solvent and dry it 57mg white crystal 3-methylcoumarin,The yield is 71%.Its chemical structure is: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With fac-tris(2-phenylpyridinato-C<SUP>2</SUP>,N)iridium(III); trifluoroacetic acid In dimethyl sulfoxide at 20℃; for 24h; Schlenk technique; Inert atmosphere; Irradiation; regioselective reaction; | |
87% | With tris(2-phenylpyridinato-N,C2′)iridium(III); trifluorormethanesulfonic acid In dimethyl sulfoxide at 25℃; for 24h; Inert atmosphere; Irradiation; Green chemistry; | 12 Example 12 Coumarin (0.5 mmol, 73 mg),N-(2-methyl)propanoyloxyphthalimide (0.75 mmol, 238 mg), Ir(ppy) 3 (0.01 mmol, 6.5 mg)And trifluoromethanesulfonic acid (0.25 mmol, 37.5 mg)Add 5mL single-mouth reaction bottle,Add DMSO (1.0 mL) as solvent,Under the protection of the N2 atmosphere,The reaction was carried out under 3w white light irradiation at a temperature of 25 ° C for 24 h.After the reaction,The reaction system is washed with water,After extracting with dichloromethane,The liquid separation is an organic layer and a water layer.After the organic layer is dried over anhydrous sodium sulfate,The solvent was evaporated under reduced pressure to give a yellow oil.The yellow oil is separated by column chromatography.a mixture of petroleum ether and ethyl acetate in a volume ratio of 30:1 as an eluent,Collect the eluate containing the target compound,The solvent was evaporated and dried to give 82 mg of white crystals of 3-isopropyl coumarin.The yield is 87% and its chemical structural formula is: |
84% | With N,N,N,N,-tetramethylethylenediamine; triphenylphosphine; sodium iodide In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere; Irradiation; Sealed tube; regioselective reaction; | Typical procedure General procedure: coumarin (1a, 0.2 mmol), cyclohexyl N-hydroxyphthalimide ester (2a, 0.24 mmol), NaI (1.5 equiv.), PPh3 (20 mmol %), TMEDA (2.0 equiv.), DMF (1.0 mL) were placed in 10 mL Schlenk tube under N2 atmosphere, then stirred under 20 W blue light for 3 h and monitored by GC or GC-MS or TLC. After completion of the reaction, the reaction mixture was diluted with EtOAc and washed with H2O. The organic layer was dried with anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel and eluted with petroleum ether/ethyl acetate to afford the pure products. |
74% | With 1,4-diaza-bicyclo[2.2.2]octane; tris(2,2′-bipyridine)ruthenium(II) dichloride hexahydrate In N,N-dimethyl acetamide at 20℃; for 2h; Schlenk technique; Sealed tube; Irradiation; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With silver(I) acetate; palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 100℃; for 24h; Schlenk technique; Sealed tube; regioselective reaction; | Synthesis of 3-Substituted 4-Aroylcoumarins (3); General Procedure General procedure: In an oven-dried Schlenk tube equipped with a stir bar, 3-substituted coumarin 2 (0.3 mmol), iodoaren 1 (0.33 mmol), Pd(OAc)2 (10 mol%, 0.0067 g), BINAP (10 mol%, 0.0186 g), and AgOAc (0.6 mmol, 0.1 g), a balloon filled with CO (1 atm) was connected to the Schlenk tube by the side tube and the system was purged three times. Toluene (2 mL) was then added to the tube by using a syringe. The Schlenk tube was heated at 100 °C for 10 h. When the reaction was complete (detected by TLC), the mixture was cooled to r.t., and the reaction was quenched with H2O (10 mL) and extracted with CH2Cl2 (3 × 10 mL). The combined organic layer was dried over anhydrous Na2SO4 and evaporatedin vacuum. The residue was purified by column chromatography on silica gel to afford the corresponding product 3. |
70% | With manganese; cobalt 2,2'-bipyridine dibromide; trifluoroacetic acid In acetonitrile at 80℃; Schlenk technique; Sealed tube; regioselective reaction; | 3-Aroylcoumarins 3; General Procedure General procedure: In an oven-dried Schlenk tube equipped with a stir bar, CoBr2/Bpy (7 mol%, 13.1 mg), and Mn powder (1.5 mmol, 82 mg) were placed in MeCN (1.5 mL). The reaction mixture was activated by a trace of trifluoroacetic acid (0.1 mmol, 7.6 µL). Then, the mixture was stirred for 10 min at r.t. In a vial, aryl halide 1 or aryl triflate 1 (0.6 mmol, 1.2 equiv) and coumarin 2 (0.5 mmol, 1.0 equiv) were dissolved in MeCN (1.5 mL) and added to the Schlenk tube. Next, a balloon filled with CO (1 atm) was connected to the Schlenk tube by the side tube and the system was purged three times. The Schlenk tube was heated at 80 °C for 16 h. When the reaction was completed (detected by TLC), the mixture was cooled to r.t. The reaction was quenched with aq 2 N HCl or NH4Cl (20 mL) and extracted with CH2Cl2 (3 * 10 mL). The combined organic layers were dried (anhyd Na2SO4) and evaporated in vacuum. The residue was purified by column chromatography (n-hexane/EtOAc 6:1) on silica gel to afford the corresponding 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With silver(I) acetate; palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 100℃; for 24h; Schlenk technique; Sealed tube; regioselective reaction; | Synthesis of 3-Substituted 4-Aroylcoumarins (3); General Procedure General procedure: In an oven-dried Schlenk tube equipped with a stir bar, 3-substituted coumarin 2 (0.3 mmol), iodoaren 1 (0.33 mmol), Pd(OAc)2 (10 mol%, 0.0067 g), BINAP (10 mol%, 0.0186 g), and AgOAc (0.6 mmol, 0.1 g), a balloon filled with CO (1 atm) was connected to the Schlenk tube by the side tube and the system was purged three times. Toluene (2 mL) was then added to the tube by using a syringe. The Schlenk tube was heated at 100 °C for 10 h. When the reaction was complete (detected by TLC), the mixture was cooled to r.t., and the reaction was quenched with H2O (10 mL) and extracted with CH2Cl2 (3 × 10 mL). The combined organic layer was dried over anhydrous Na2SO4 and evaporatedin vacuum. The residue was purified by column chromatography on silica gel to afford the corresponding product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With N-ethyl-N,N-diisopropylamine; iron(II) chloride In toluene at 130℃; for 45h; Inert atmosphere; Schlenk technique; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With manganese; cobalt 2,2'-bipyridine dibromide; trifluoroacetic acid In acetonitrile at 80℃; Schlenk technique; Sealed tube; regioselective reaction; | 3-Aroylcoumarins 3; General Procedure General procedure: In an oven-dried Schlenk tube equipped with a stir bar, CoBr2/Bpy (7 mol%, 13.1 mg), and Mn powder (1.5 mmol, 82 mg) were placed in MeCN (1.5 mL). The reaction mixture was activated by a trace of trifluoroacetic acid (0.1 mmol, 7.6 µL). Then, the mixture was stirred for 10 min at r.t. In a vial, aryl halide 1 or aryl triflate 1 (0.6 mmol, 1.2 equiv) and coumarin 2 (0.5 mmol, 1.0 equiv) were dissolved in MeCN (1.5 mL) and added to the Schlenk tube. Next, a balloon filled with CO (1 atm) was connected to the Schlenk tube by the side tube and the system was purged three times. The Schlenk tube was heated at 80 °C for 16 h. When the reaction was completed (detected by TLC), the mixture was cooled to r.t. The reaction was quenched with aq 2 N HCl or NH4Cl (20 mL) and extracted with CH2Cl2 (3 * 10 mL). The combined organic layers were dried (anhyd Na2SO4) and evaporated in vacuum. The residue was purified by column chromatography (n-hexane/EtOAc 6:1) on silica gel to afford the corresponding 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With manganese; cobalt 2,2'-bipyridine dibromide; trifluoroacetic acid; In acetonitrile; at 80℃; under 760.051 Torr;Schlenk technique; Sealed tube; | General procedure: In an oven-dried Schlenk tube equipped with a stir bar, CoBr2/Bpy (7 mol%, 13.1 mg), and Mn powder (1.5 mmol, 82 mg) were placed in MeCN (1.5 mL). The reaction mixture was activated by a trace of trifluoroacetic acid (0.1 mmol, 7.6 µL). Then, the mixture was stirred for 10 min at r.t. In a vial, aryl halide 1 or aryl triflate 1 (0.6 mmol, 1.2 equiv) and coumarin 2 (0.5 mmol, 1.0 equiv) were dissolved in MeCN (1.5 mL) and added to the Schlenk tube. Next, a balloon filled with CO (1 atm) was connected to the Schlenk tube by the side tube and the system was purged three times. The Schlenk tube was heated at 80 C for 16 h. When the reaction was completed (detected by TLC), the mixture was cooled to r.t. The reaction was quenched with aq 2 N HCl or NH4Cl (20 mL) and extracted with CH2Cl2 (3 * 10 mL). The combined organic layers were dried (anhyd Na2SO4) and evaporated in vacuum. The residue was purified by column chromatography (n-hexane/EtOAc 6:1) on silica gel to afford the corresponding 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With manganese; cobalt 2,2'-bipyridine dibromide; trifluoroacetic acid; In acetonitrile; at 80℃; under 760.051 Torr;Schlenk technique; Sealed tube; | General procedure: In an oven-dried Schlenk tube equipped with a stir bar, CoBr2/Bpy (7 mol%, 13.1 mg), and Mn powder (1.5 mmol, 82 mg) were placed in MeCN (1.5 mL). The reaction mixture was activated by a trace of trifluoroacetic acid (0.1 mmol, 7.6 µL). Then, the mixture was stirred for 10 min at r.t. In a vial, aryl halide 1 or aryl triflate 1 (0.6 mmol, 1.2 equiv) and coumarin 2 (0.5 mmol, 1.0 equiv) were dissolved in MeCN (1.5 mL) and added to the Schlenk tube. Next, a balloon filled with CO (1 atm) was connected to the Schlenk tube by the side tube and the system was purged three times. The Schlenk tube was heated at 80 C for 16 h. When the reaction was completed (detected by TLC), the mixture was cooled to r.t. The reaction was quenched with aq 2 N HCl or NH4Cl (20 mL) and extracted with CH2Cl2 (3 * 10 mL). The combined organic layers were dried (anhyd Na2SO4) and evaporated in vacuum. The residue was purified by column chromatography (n-hexane/EtOAc 6:1) on silica gel to afford the corresponding 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With manganese; cobalt 2,2'-bipyridine dibromide; trifluoroacetic acid In acetonitrile at 80℃; Schlenk technique; Sealed tube; regioselective reaction; | 3-Aroylcoumarins 3; General Procedure General procedure: In an oven-dried Schlenk tube equipped with a stir bar, CoBr2/Bpy (7 mol%, 13.1 mg), and Mn powder (1.5 mmol, 82 mg) were placed in MeCN (1.5 mL). The reaction mixture was activated by a trace of trifluoroacetic acid (0.1 mmol, 7.6 µL). Then, the mixture was stirred for 10 min at r.t. In a vial, aryl halide 1 or aryl triflate 1 (0.6 mmol, 1.2 equiv) and coumarin 2 (0.5 mmol, 1.0 equiv) were dissolved in MeCN (1.5 mL) and added to the Schlenk tube. Next, a balloon filled with CO (1 atm) was connected to the Schlenk tube by the side tube and the system was purged three times. The Schlenk tube was heated at 80 °C for 16 h. When the reaction was completed (detected by TLC), the mixture was cooled to r.t. The reaction was quenched with aq 2 N HCl or NH4Cl (20 mL) and extracted with CH2Cl2 (3 * 10 mL). The combined organic layers were dried (anhyd Na2SO4) and evaporated in vacuum. The residue was purified by column chromatography (n-hexane/EtOAc 6:1) on silica gel to afford the corresponding 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With manganese; cobalt 2,2'-bipyridine dibromide; trifluoroacetic acid In acetonitrile at 80℃; Schlenk technique; Sealed tube; regioselective reaction; | 3-Aroylcoumarins 3; General Procedure General procedure: In an oven-dried Schlenk tube equipped with a stir bar, CoBr2/Bpy (7 mol%, 13.1 mg), and Mn powder (1.5 mmol, 82 mg) were placed in MeCN (1.5 mL). The reaction mixture was activated by a trace of trifluoroacetic acid (0.1 mmol, 7.6 µL). Then, the mixture was stirred for 10 min at r.t. In a vial, aryl halide 1 or aryl triflate 1 (0.6 mmol, 1.2 equiv) and coumarin 2 (0.5 mmol, 1.0 equiv) were dissolved in MeCN (1.5 mL) and added to the Schlenk tube. Next, a balloon filled with CO (1 atm) was connected to the Schlenk tube by the side tube and the system was purged three times. The Schlenk tube was heated at 80 °C for 16 h. When the reaction was completed (detected by TLC), the mixture was cooled to r.t. The reaction was quenched with aq 2 N HCl or NH4Cl (20 mL) and extracted with CH2Cl2 (3 * 10 mL). The combined organic layers were dried (anhyd Na2SO4) and evaporated in vacuum. The residue was purified by column chromatography (n-hexane/EtOAc 6:1) on silica gel to afford the corresponding 3. 3-Benzoyl-2H-chromen-2-one (3a)12a Yield: 0.096 g (77%); white solid; mp 132-134 °C (Lit.12a mp 134-136 °C). IR (KBr): 3054, 1715, 1601, 1491, 1240, 1045, 798 cm-1. 1H NMR (300.1 MHz, CDCl3): δ = 8.10 (s, 1 H), 7.90 (d, J = 7.4 Hz, 2 H), 7.55-7.76 (m, 3 H), 7.49 (t, J = 7.4 Hz, 2 H), 7.28-7.46 (m, 2 H). 13C NMR (75.4 MHz, CDCl3): δ = 191.7, 158.5, 154.8, 145.6, 136.2, 133.9, 133.7, 129.6, 129.3, 128.6, 126.9, 125.0, 118.2, 116.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With manganese; cobalt 2,2'-bipyridine dibromide; trifluoroacetic acid In acetonitrile at 80℃; Schlenk technique; Sealed tube; regioselective reaction; | 3-Aroylcoumarins 3; General Procedure General procedure: In an oven-dried Schlenk tube equipped with a stir bar, CoBr2/Bpy (7 mol%, 13.1 mg), and Mn powder (1.5 mmol, 82 mg) were placed in MeCN (1.5 mL). The reaction mixture was activated by a trace of trifluoroacetic acid (0.1 mmol, 7.6 µL). Then, the mixture was stirred for 10 min at r.t. In a vial, aryl halide 1 or aryl triflate 1 (0.6 mmol, 1.2 equiv) and coumarin 2 (0.5 mmol, 1.0 equiv) were dissolved in MeCN (1.5 mL) and added to the Schlenk tube. Next, a balloon filled with CO (1 atm) was connected to the Schlenk tube by the side tube and the system was purged three times. The Schlenk tube was heated at 80 °C for 16 h. When the reaction was completed (detected by TLC), the mixture was cooled to r.t. The reaction was quenched with aq 2 N HCl or NH4Cl (20 mL) and extracted with CH2Cl2 (3 * 10 mL). The combined organic layers were dried (anhyd Na2SO4) and evaporated in vacuum. The residue was purified by column chromatography (n-hexane/EtOAc 6:1) on silica gel to afford the corresponding 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With manganese; cobalt 2,2'-bipyridine dibromide; trifluoroacetic acid In acetonitrile at 80℃; Schlenk technique; Sealed tube; regioselective reaction; | 3-Aroylcoumarins 3; General Procedure General procedure: In an oven-dried Schlenk tube equipped with a stir bar, CoBr2/Bpy (7 mol%, 13.1 mg), and Mn powder (1.5 mmol, 82 mg) were placed in MeCN (1.5 mL). The reaction mixture was activated by a trace of trifluoroacetic acid (0.1 mmol, 7.6 µL). Then, the mixture was stirred for 10 min at r.t. In a vial, aryl halide 1 or aryl triflate 1 (0.6 mmol, 1.2 equiv) and coumarin 2 (0.5 mmol, 1.0 equiv) were dissolved in MeCN (1.5 mL) and added to the Schlenk tube. Next, a balloon filled with CO (1 atm) was connected to the Schlenk tube by the side tube and the system was purged three times. The Schlenk tube was heated at 80 °C for 16 h. When the reaction was completed (detected by TLC), the mixture was cooled to r.t. The reaction was quenched with aq 2 N HCl or NH4Cl (20 mL) and extracted with CH2Cl2 (3 * 10 mL). The combined organic layers were dried (anhyd Na2SO4) and evaporated in vacuum. The residue was purified by column chromatography (n-hexane/EtOAc 6:1) on silica gel to afford the corresponding 3. |
Tags: 91-64-5 synthesis path| 91-64-5 SDS| 91-64-5 COA| 91-64-5 purity| 91-64-5 application| 91-64-5 NMR| 91-64-5 COA| 91-64-5 structure
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