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CAS No. : | 553-86-6 | MDL No. : | MFCD00005856 |
Formula : | C8H6O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ACZGCWSMSTYWDQ-UHFFFAOYSA-N |
M.W : | 134.13 | Pubchem ID : | 68382 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.12 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 35.99 |
TPSA : | 26.3 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.16 cm/s |
Log Po/w (iLOGP) : | 1.62 |
Log Po/w (XLOGP3) : | 1.35 |
Log Po/w (WLOGP) : | 1.15 |
Log Po/w (MLOGP) : | 1.54 |
Log Po/w (SILICOS-IT) : | 2.23 |
Consensus Log Po/w : | 1.58 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.97 |
Solubility : | 1.45 mg/ml ; 0.0108 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.5 |
Solubility : | 4.2 mg/ml ; 0.0313 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -2.54 |
Solubility : | 0.383 mg/ml ; 0.00286 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.65 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H317-H319 | Packing Group: | N/A |
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 |
---|---|---|
99% | at 50℃; for 0.5 h; | Reference Example 263 A mixture of 2-coumaranone (25.00 g), a10percent solution (30 ml) of hydrogen chloride in methanol and methanol (30 ml) was stirred at50 C for 30 minutes. The reaction solution was concentrated. Ethyl acetate and aqueous sodium hydrogen carbonate were added to the residue and the mixture was extracted. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried(MgS04) and concentrated. The residue was subjected to silica gel column chromatography, and methyl (2-hydroxyphenyl) acetate (30.60 g, yield99percent) was obtained as a colorless oil from a fraction eluted with diethyl ether. H-NMR(CDC13) g : 3.68 (2H, s), 3.74 (3H, s), 6.86-6. 93 (2H,m), 7.10(1H, dd, J=7.2, 1.6 Hz), 7.16-7. 20(1H, m), 7.35 (1H, <Desc/Clms Page number 248>brs). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.1% | With iron(III) sulfate; In toluene; for 6h;Reflux; | 2) To the 500 mL reaction flask,50.7 g (90%, 0.3 mol) of o-hydroxyphenylacetic acid obtained in step (1),35 mL of toluene and 0.5 g of anhydrous ferric sulfate were added, and the reaction was heated under reflux. The reaction was collected in a water separator And the reaction was carried out for 6 hours. HPLC analysis showed that the content of o-hydroxyphenylacetic acid was 0.86%, cooled and filtered to remove sodium chloride and ferric sulfate. The filtrate was distilled under reduced pressure to recover toluene and benzofuran-2-(3H)-one, the product was 99.1% pure, and the yield was 96.1% (calculated as o-hydroxyphenylacetic acid). |
95.7% | With potassium hydrogensulfate; In toluene; | In a 2000 ml three-neck round bottom flask with a water separator, 220 g of o-hydroxyphenylacetic acid, 1000 ml of toluene and 5 g of sulfur were added.Potassium hydrogen hydride, refluxed to the absence of water, and cooled to room temperature, the solid sulfonic acid catalyst was filtered off, and toluene was recovered under reduced pressure to obtain 193 g.Crude benzofuran-2-(3H)-one, added 150 ml of toluene, stirred with heating for 2 hours, cooled and crystallized, filtered to give a white solid185.6 g, yield 95.7%, mother liquor applied. |
85% | With toluene-4-sulfonic acid; In toluene; at 110℃; for 6h;Catalytic behavior; | (2) Add (1.36 g, 8.9 mmol) of Compound 1, p-toluenesulfonic acid (53 mg, 5 mol%), 100 mL of toluene in a 100 mL eggplant-shaped bottle, and react at 110 C for 6 hours. The reaction solution was poured into ice water, extracted with ethyl acetate, and the organic phase was removed by spin-dry column chromatography to obtain benzofuranone with a mass of 1.02g and a yield of 85%. |
With acetic anhydride; at 110℃; for 2.5h;Inert atmosphere; Large scale; | 82 kg of o-hydroxyphenylacetic acid,350L acetic anhydride was added to the reactor, heated to 110 C under the protection of nitrogen,After the reaction for 2.5h, 115kg of trimethyl orthoformate was added and reacted at 110 C for 21h. During the reaction, oil-water separation of the low boiling point substance was achieved. After the reaction was completed, the reaction mixture was distilled under reduced pressure at 90 C to obtain a black oil To the black oil, 24 L of methanol was added, heated to reflux, and then cooled to crystallize, Filtering to obtain 3 - (- methoxy) - methylene benzofuran-2 (3-hydro) -one; | |
With toluene-4-sulfonic acid; at 120 - 130℃; for 4h; | Namely, o-hydroxyphenylacetic acid 3 g (19.7 mmol), p-toluenesulfonic acid 1.75 mmol, refluxing at 120-130 C. for 4 h, crude benzofuranone was obtained, and silica gel column chromatography of petroleum ether/ethyl acetate system was selected. The technology separates and purifies the product. Then, 1.5 mmol of benzofuranone, 3 mmol of substituted benzaldehyde, 10 ml of triethylamine, and 15 ml of acetic anhydride were added to the round-bottomed flask and refluxed at 80C for 12 hours.After TLC tracking was monitored and the reaction was complete, the product was spin-dried under vacuum and extracted three times with ethyl acetate. The ethyl acetate phase was collected and dried over anhydrous sodium sulfate overnight. The product was vacuum-dried.. According to the polarity of the reaction crude product, use one of the unfolding systems in petroleum ether/dichloromethane, petroleum ether/ethyl acetate, petroleum ether/acetone, petroleum ether/dichloromethane/ethyl acetate, and adjust to an appropriate ratio. Comprehensive use of recrystallization, silica gel column chromatography, preparative thin layer chromatography and other techniques for separation, purification, respectively, to obtain a series of benzobutyrolactone derivatives, according to the addition of different substituted benzaldehyde eventually get carried different R groups Benzolactone derivatives.The purification process is exemplified by the substituent R being a phenyl group: the obtained crude phenylbenzobutyrolactone is respectively used in petroleum ether/dichloromethane, petroleum ether/ethyl acetate and petroleum ether at a volume ratio of 10:1. The three acetone solvent systems were developed on TLC plates. The petroleum ether/dichloromethane and petroleum ether/acetone systems were unable to separate the product and the magazine spots, while the petroleum ether/ethyl acetate solvent system allowed the product to Completely separated from impurities, so choose petroleum ether/ethyl acetate solvent as silica gel column chromatography eluent. Column chromatography using wet packing, loading, gradient elution, eluent: petroleum ether: ethyl acetate (V/V) = 20:1?10:1, followed by thin layer chromatography to monitor the product, rotating The collected eluent was concentrated under reduced pressure with an evaporator to give the final product (yield 90%, purity 90%). In order to obtain a compound with higher purity, the obtained product is recrystallized in a petroleum ether: ethyl acetate solvent system, and about 1 g of the product is picked into a 100 mL beaker, 10 mL of ethyl acetate solution is added to completely dissolve it, and then 80 mL is added. About petroleum ether and stir evenly, place the beaker in a ventilated place and keep it for about 2 days.To the yellow crystals precipitated on the beaker wall, the end product phenyl-benzo-butyrolactone with a purity of more than 99% can be obtained by scraping with a medicine spoon, and the final yield is about 80%.Other compounds can be purified as described above. | |
With phosphorus pentoxide; acetic acid; In toluene; for 6h;Reflux; | Compound 1 (304 g, 2 mmol), toluene (2 L), glacial acetic acid (0.5 L), and phosphorus pentoxide (500 g) were charged to the reactor and heated to reflux for 6 h.After the reaction was completed, it was cooled to room temperature, and ice water was slowly added thereto, and the mixture was extracted three times with ethyl acetate.The organic phase was dried over anhydrous sodium sulfate and evaporated to dryness.A small portion of the column chromatography was taken out to obtain a white needle crystal of Compound 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | hydrogenchloride; at 50℃; for 0.5h; | Reference Example 263 A mixture of 2-coumaranone (25.00 g), a10% solution (30 ml) of hydrogen chloride in methanol and methanol (30 ml) was stirred at50 C for 30 minutes. The reaction solution was concentrated. Ethyl acetate and aqueous sodium hydrogen carbonate were added to the residue and the mixture was extracted. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried(MgS04) and concentrated. The residue was subjected to silica gel column chromatography, and methyl (2-hydroxyphenyl) acetate (30.60 g, yield99%) was obtained as a colorless oil from a fraction eluted with diethyl ether. H-NMR(CDC13) g : 3.68 (2H, s), 3.74 (3H, s), 6.86-6. 93 (2H,m), 7.10(1H, dd, J=7.2, 1.6 Hz), 7.16-7. 20(1H, m), 7.35 (1H, <Desc/Clms Page number 248>brs). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9.1 g | With sodium tetrahydroborate; In tetrahydrofuran; at 0 - 30℃; for 5h; | (1) The reaction bottle containing the organic solvent tetrahydrofuran is cooled to 0 C, then, 1.26 g of a reducing agent sodium borohydride and 8.9 g of a benzofuranone were successively added to the reaction flask. At a heating temperature of 30 C, the reaction was carried out for 5 h, and after the reaction was completed, the reaction solution was cooled to 0 C. And adding HCl to the cooled reaction solution for quenching,Concentrated, extracted with methyl tert-butyl ether, the organic phase is then dried over anhydrous sodium sulfate, filtered, concentrated filtrate to obtain 9.1 g of 2-hydroxyphenylethanol; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 56% 2: 9% 3: 7% | With hydrogen iodide In 1,4-dioxane at 120℃; for 42h; | |
1: 36% 2: 7 % Spectr. 3: 9 % Spectr. | With tetrakis(triphenylphosphine) palladium(0); hydrogen iodide In 1,4-dioxane at 120℃; for 42h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With N-chloro-succinimide In acetonitrile for 168h; | |
70% | With N-chloro-succinimide In acetonitrile for 72h; Inert atmosphere; | |
With N-chloro-succinimide In acetonitrile at 20℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With aluminium(III) triflate; tris(2,4-pentanedionato)ruthenium(III); hydrogen; [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine] In tetrahydrofuran at 160℃; for 12h; Autoclave; | |
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 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In einer 100 ml Batchapparatur wurden in 250ml Wasser 2,7g (0,02mol) 2-Allylphenol aufgenommen und auf 15C abgekuehlt und mit Entschaeumer versetzt. Danach wurden 0,96g (0,02mol) Ozon durch die Loesung durchgeleitet. Nach beendeter Ozonolyse wurde der Ozonstrom abgeschaltet und 15 Minuten lang mit Stickstoff inertisiert. Anschliessend wurde der Reaktionsansatz in einen 2-Halskolben mit Rueckflusskuehler ueberfuehrt und auf 60C erhitzt. Die Reaktion wurde mittels Duennschichtchromatographie kontrolliert. Nach beendeter Reaktion wurde bei 50C mit 3 mal mit je 50ml Toluol extrahiert und die bereinigten Extrakte auf Rueckflusstemperatur erhitzt und gleichzeitig das gebildete Wasser mittels Wasserabscheider abgetrennt. Anschliessend wurde das Toluol durch Eindampfen entfernt. Es wurden 2,2g 2-Coumaron (85% d.Th.) erhalten |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With trichlorophosphate; In chloroform; for 18h;Schlenk technique; Inert atmosphere; Reflux; | General procedure: According to the literature procedure,21 2-chloro-3-benzofurancarboxaldehyde was prepared by the reaction of 2-coumaranone (1.34 g, 10.0 mmol) with anhydrous DMF (2.49 g, 34.1 mmol) and POCl3 (3.88g, 25.3 mmol) in CHCl3 (21.2 mL), and isolated in 57% yield (1.03 g) as a pale yellow solid by column chromatography on silica gel (hexane/EtOAc = 10/1). Its spectral and analytical data are shown below because they were not provided in reference 21. |
47% | With trichlorophosphate; In chloroform; at 0℃;Reflux; | Benzofuran-2 (3H) -one (Compound 1) (1.063 g, 7.9 mmol) and dimethylformamide (DMF; 1.8 mL, 23.7 mmol) were dissolved in chloroform (10 mL)POCl 3 (1.7 mL, 18.2 mmol) was added at 0 C. and the mixture was stirred for 5 minutes. Thereafter, the reaction mixture was heated under reflux overnight and cooled to room temperature. A 2N sodium hydroxide aqueous solution was added to adjust the pH to 7, and then extracted with methylene chloride. The obtained organic layer was washed with water, then washed with saturated brine, and dried with anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 80: 1) To obtain 0.675 g (3.74 mmol) of Compound 2 (yield: 47%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.6% | With 2-hydroxypyridin; In dichloromethane; at 20℃; | To a solution of lactone (2 mmol) and 2- hydroxypyridine (0.2 mmol) in anhydrous dichloromethane (5 mL) was added an amine (2.2 mmol) . The mixture was stirred at room temperature for 6 to 24 h. After the reaction, water (20 mL) was added. The reaction mixture was transferred to a separating funnel and extracted with dichloromethane, .CH2Cl2 (3 * 10 mL) . The solvent extracts were concentrated under reduced pressure to give a crude product, which was purified by silica gel column chromatography (using hexane/ethyl acetate, 1:1 v/v as eluent) or preparative HPLC (using the protocol set out in "Analytical Protocols" above) to give the final product . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With potassium <i>tert</i>-butylate In PEG 300 at 25℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | Stage #1: 4-oxo-but-2-enoic acid ethyl ester With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; benzoic acid In toluene at 20℃; for 0.0833333h; Stage #2: benzofuran-2(3H)-one In toluene at 20℃; for 16h; optical yield given as %ee; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63%; 24% | With Calcium tetrakis(pentafluorophenyl)borate; dihydrogen peroxide; oxalic acid; In water; 1,2-dichloro-ethane; at 50℃; for 6h; | As shown in Tables 5 and 6, the Baeyer-Villiger oxidation reaction was investigated using various reactive substrates. As the catalyst, a borate salt of Li or Ca was used. In general, although the catalytic activity of a Ca borate salt was higher, since a Li borate salt was a commercially available product, and the amount thereof to be used was small due to its low molecular weight, the Li borate salt was first used (Examples 57, 58, 66 to 71, and 73). However, when the Li borate salt was not sufficient depending on the reactive substrate, and the chemical yield of the product was low, the Ca borate salt was used as the catalyst (Examples 59 to 65, 72, and 74 to 76). In Examples 66 to 72, when a cyclobutanone derivative was used as the reactive substrate, a corresponding lactone was obtained at a high yield in each case. Among the above Examples, in Examples 69 and 70, although an unstable reactive substrate, which had a halogen group at one carbon and a hydroxy group or a siloxy group at the carbon adjacent thereto and which was liable to form an epoxy ring, was used, no epoxidation occurred. Major product of Example 72: White solid. TLC, Rf=0.17 (hexane-EtOAc=4:1); 1H NMR (CDCl3, 400 MHz) delta 5.34 (s, 2H), 7.50 (d, J=7.8 Hz, 1H), 7.55(t, J=7.3 Hz, 1H), 7.70 (t, J=7.3 Hz, 1H), 7.94 (d, J=7.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) delta 69.8, 122.2, 125.8, 129.1, 134.1, 146.6, 171.2. [0099] Minor product of Example 72: Colorless oil. TLC, Rf=0.36 (hexane-EtOAc=4:1); 1H NMR (CDCl3, 400 MHz) delta 3.75 (s, 2H), 7.10-7.16 (m, 2H), 7.28-7.33(m, 2H); 13C NMR (CDCl3, 100 MHz) delta 33.1, 110.9, 123.2, 124.2, 124.8, 129.0, 154.8, 174.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With 1,4-diaza-bicyclo[2.2.2]octane; In dichloromethane; at 20℃; for 48h; | General procedure: 4.2.19 (<strong>[553-86-6]2-Coumaranone</strong>)-3-spiro-1'-[2'-hydroxy-2'-methyl-5'-nitro-6'-phenylcyclohexane] (3e) According to the general procedure, reaction was performed between 2-coumaranone (0.5 mmol, 67 mg) and (E)-5-nitro-6-phenyl-hex-5-en-2-one (1a, 0.5 mmol, 109.5 mg) in dichloromethane (4 mL) in the presence of DABCO (0.5 mmol, 56 mg) at ambient temperature for 2 days; Yield: 79% (139 mg); IR (KBr): nu 3530, 1786, 1549, 1375 cm-1; 1H NMR (400 MHz, CDCl3): delta 7.59 (dd, J=7.6 Hz and 2 Hz, 1H), 7.21-7.10 (m, 2H), 7.07-6.88 (br, 5H), 6.77 (dd, J=7.6 Hz and 1.2 Hz, 1H), 5.82 (td, J=11.6 Hz and 4.4 Hz, 1H), 4.19 (d, J=12.0 Hz, 1H), 2.72-2.58 (m, 2H), 2.45-2.35 (m, 1H), 1.93-1.80 (m, 2H), 0.99 (s, 3H); 13C NMR (100 MHz, CDCl3): delta 176.35, 153.00, 134.05, 129.50, 128.30, 127.95, 126.86, 125.75, 124.18, 110.33, 84.67, 72.24, 61.79, 48.21, 32.78, 27.06, 26.19. HRMS (ESI) m/z: [M+Na]+ calcd for C20H19NO5Na 376.1161; found 376.1171. The enantiomeric excess (ee 79%) was determined by HPLC with a Chiralpak AD-H (i-PrOH/hexanes: 10/90; flow rate: 1.0 mL/min; lambda=220 nm); tR (major)=9.86 min; tR (minor)=12.93 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With sodium sulfate; triethylamine In toluene for 6h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: sodium sulfate; triethylamine / toluene / 6 h / Reflux 2: (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; benzoic acid / chloroform / 72 h / -20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: 2-benzofuranylboronic acid mida ester With potassium hydrogen bifluoride In methanol; water at 70℃; for 2h; Stage #2: With Oxone In methanol; water at 18℃; for 0.166667h; | |
Multi-step reaction with 2 steps 1: methanol; water / 4 h / 70 °C 2: oxone / water; acetone / 2 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium acetate; In acetic acid; at 85℃; for 8h; | 0.24 g N-methyl-indole-2,3-dione (1.5 mmol) was dissolved in 15 ml acetic acid, added with 0.37 g anhydrous sodium acetate (4.5 mmol) solid, stirred until dissolved and then added with 0.2 g benzofuran-2-one (1.5 mmol). The reaction was maintained at 85 C. for 8 hours and then terminated. The cooled reaction mixture was poured into 200 ml ice water and thoroughly mixed. A purple solid was crystallized, filtered, desiccated and purified through column chromatography (dichloromethane: ethyl acetate=6: 1, v/v). The product was re-crystallized with dichloromethane and petroleum ether. 0.21 g of the purified dark purple solid product, N-methyl-1?-oxo-isoindigo (93), was obtained, with a yield of 62%, m.p.232-233 C. ; IR (KBr, v, cm-1): 3442,3238, 3131, 3022, 1702, 1618, 1591, 1485, 1463, 1398, 1324, 1282, 1214, 1106, 1047, 868 594; (0122) 1H-NMR(CDCl3, 300 MHz)delta: 9.31(d, J=8.00 Hz, 1H, Ar-H), 9.05(d, J=8.00 Hz, 1H, Ar-H), 7.49-7.43(m, 2H, Ar-H), 7.28-7.24(m, 1H, Ar-Hs), 7.16-7.12(m, 2H, Ar-H), 6.82(d, J=7.50 Hz, 1H, Ar-H), 3.32(s, 3H, N-CH3); (0123) ESI-MS m/z: 278.1 [M+H]+, 300.1 [M+Na]+, C17H11NO3(277.3) (0124) Anal. for C17H11NO3 Calcd(%): C 73.64, H 4.00, N 5.05; (0125) Found (%): C 73.51, H 4.09, N 5.14. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium acetate; In acetic acid; at 85℃; for 8h; | N-ethyl-5-azaindole-2,3-dione (0.26 g, or 1.5 mmol) was dissolved in 15 ml acetic acid, added with 0.37 g anhydrous sodium acetate (4.5 mmol) solid, stirred until dissolved and then added with 0.2 g benzofuran-2-one (1.5 mmol). The reaction was maintained at 85 C. for 8 hours and then terminated. The cooled reaction mixture was poured into 200 ml ice water and thoroughly mixed. A purple solid was crystallized, filtered, desiccated and purified through column chromatography (dichloromethane: ethyl acetate=6: 1, v/v). The product was re-crystallized with dichloromethane and petroleum ether. 0.28 g of the purified dark purple solid product, N-ethyl-1?-oxo-5-azaisoindigo (127), was obtained, with a yield of 65%, m.p. 212214 C. ; IR (KBr, v, cm-1): 3434, 3121, 2985, 1718, 1695, 1606, 1479, 1456, 1398, 1384, 1159, 1105, 983, 762, 638; (0129) 1H-NMR(CDCl3, 300 MHz)delta: 9.29(d, J=8.40 Hz, 1H, Ar-H), 9.01(d, J=8.40 Hz, 1H, Ar-H), 7.52-7.47(m, 2H, Ar-H), 7.23-7.20(m, 1H, Ar-Hs), 7.05-7.02(m, 1H, Ar-H), 6.72(s, 1H, Ar-H), 3.86(q, 2H, N-CH2), 1.32(t, 3H, CH3); (0130) ESI-MS m/z: 293.1[M+H]+, 315.1[M+Na]+, C17H12N2O3(292.3) (0131) Anal. for C17H12N2O3 Calcd(%): C 69.86, H 4.14, N 9.58; (0132) Found(%): C 69.99, H 4.05, N 9.46 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With sodium acetate; In acetic acid; at 85℃; for 8h; | N-methyl-7-azaindole-2,3-dione (0.24 g, or 1.5 mmol) was Dissolved in 15 ml acetic Acid, added with 0.37 g anhydrous sodium acetate (4.5 mmol) solid, stirred until dissolved and then added with 0.2 g benzofuran-2-one (1.5 mmol). The reaction was maintained at 85 C. for 8 hours and then terminated. The cooled reaction mixture was poured into 200 ml ice water and thoroughly mixed. A purple solid was crystallized, filtered, desiccated and purified through column chromatography (dichloromethane: ethyl acetate =6: 1, v/v). The product was re-crystallized with dichloromethane and petroleum ether. 0.25 g of the purified dark purple solid product, N-methyl-1?-oxo-7-azaisoindigo (139), was obtained, with a yield of 61%, m.p.261263 C. ; IR (KBr, v, cm-1): 3438, 3175, 3126, 1697, 1618, 1598, 1457, 1403, 1384, 1347, 1101, 984; (0136) 1H-NMR(DMSO-d6, 300 MHz)delta: 9.32(d, J=8.20 Hz, 1H, Ar-H), 9.04(d, J=8.20 Hz, 1H, Ar-H), 7.50-7.44(m, 2H, Ar-H), 7.29-7.25(m, 1H, Ar-Hs), 7.17-7.14(m, 1H, Ar-H), 6.83(d, J=7.80 Hz, 1H, Ar-H), 3.35(s, 3H, N-CH3); (0137) ESI-MS m/z: 279.1[M+H]+, 301.1[M+Na]+, C16H1oN2O3(278.3) (0138) Anal. for C16H1oN2O3Calcd(%): C 69.06, H 3.62, N 10.07; (0139) Found (%): C69.11, H 3.51, N 10.16. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With C33H28F5N3O2; potassium carbonate; In toluene; at 0℃; for 48h; | General procedure: To a 25 mL flask was added catalysts 5g (0.04 mmol, 23.7 mg), K2CO3 (0.24 mmol, 33.2 mg), 3 or 6 or 8 (0.24 mmol) and toluene (1.5 mL). After the mixture was stirred at 0 C for 5 min, a solution of 2 (0.20 mmol) in toluene (1.5 mL) was slowly added. The reaction was stirred at 0 C for 48 h. After that, the solvent was removed and the residue was directly subjected to silica gel column chromatography (petroleum ether/ethyl acetate as eluent) to give (3+3) annulation product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium methylate; In methanol; at 20℃; | To a stirred solution of sodium methoxide(184 mg (8 mmol) Na in 20 mL MeOH) were added 300 mg(2 mmol) benzofuranone 2a and 300 mg (2 mmol) 4-formylbenzoicacid (2 mmol). The mixture was stirred 2-5 h at r.t., neutralizedwith conc. HCl to pH 1-2 and was diluted with 20 mL ofwater. The residue was filtered, washed with water, and crystallizedfrom DMF-MeOH mixture (1:1) with yield of 513 mg (91%)compound 3d as a yellow solid. Mp 315-317 C; 1H NMR(400 MHz, DMSO-d6) d 6.71 (1H, dd, 3J = 8.5 Hz, 4J = 2.0 Hz, H-5),6.76-6.83 (2H, m, H-7, 2a), 7.62 (1H, d, 3J = 8.5, H-4), 7.95-8.07(4H, m, H-20, 30, 50, 60), 11.27 (1H, s, 6-OH), 13.09 ppm (1H, s, 40-COOH); 13C NMR (100 MHz, DMSO-d6) d 98.76, 108.86, 112.56,113.27, 126.16, 129.73, 130.93, 131.00, 136.32, 148.34, 166.85,168.14, 181.42 ppm; IR (KBr): mmax 3070, 3594, 1687, 1578, 1313,1287, 1131, 1111 cm1; MS (APCI) m/z (%): 283.2 (100) [M+H]+;Anal. calcd for C16H10O5: C, 68.09; H, 3.57. Found: C, 68.32; H, 3.39. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.4% | With nitric acid; acetic anhydride; acetic acid at 0 - 20℃; for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium hydride; In tetrahydrofuran; toluene; mineral oil; at 20℃; for 6h;Cooling with ice; | (1.47 mol) was placed in a mixture of 140 mL / 140 mL of THF / toluene, stirred in an ice-water bath, and 94 g (0.7 mol) was added dropwise at 10 to 20 C,Benzofuranone, 122.5 g (0.7 mol)3-chlorobenzoyl chloride in 70 mL / 50 mL of THF / toluene solution, add 10-20 C for 6 hours, add 1200 mL Reduction of THF by distillation under reduced pressure. 450 mL of 3M hydrochloric acid and 200 mL of water were added dropwise and the organic phase was washed with water Twice, saturated sodium chloride once, the organic phase concentrated, adding methanol to recrystallize, 156g3- (hydroxy (3-chlorophenyl) methylene) benzofuran-2 (3H) -one. Yield 82%, HPLC purity 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium hydride; In tetrahydrofuran; toluene; mineral oil; at 20℃; for 6h;Cooling with ice; | (1.4 mol) of sodium hydride (1.47 mol) was placed in a mixture of 140 mL / 140 mL of THF / toluene, stirred with ice-water bath, and 94 g (0.7 mol) of benzofuranone was added dropwise at 10 to 20 C,153 g (0.7 mol)3-bromobenzoyl chloride in 70 mL / 50 mL of THF / toluene solution was added, and the mixture was stirred at 10 to 20 C for 6 hours. 1200 mL of toluene The THF was recovered by distillation under reduced pressure. Dropping 450 mL of 3M hydrochloric acid, 200 mL of water, and separating the organic phase with water Times, saturated sodium chloride once, organic phase concentration, adding methanol to recrystallize, get 182g3- (hydroxy (3-bromophenyl) methylene) benzofuran-2 (3H) -one. Yield 82%, HPLC purity 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With sodium hydride; In tetrahydrofuran; toluene; mineral oil; at 20℃; for 6h;Cooling with ice; | 59 g of 60% sodium hydrogen (1.47 mol) was placed in a 140 mL / 140 mL THF / toluene mixture,(0.7 mol) of benzofuranone, 108 g (0.7 mol) of benzofuranone was added dropwise at 10 to 20 C,3-methylbenzoyl chloride70 mL / 50 mL THF / toluene solution, add 10-20 C for 6 hours, add 1200mL A Reduction of THF by distillation under reduced pressure. 450 mL of 3M hydrochloric acid and 200 mL of water were added dropwise and the organic phase was washed with water Twice, saturated sodium chloride once, the organic phase concentrated, adding methanol to recrystallize, get 139g3- (hydroxy (3-methylphenyl) methylene) benzofuran-2 (3H) -one. Yield 79%, HPLC purity 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium hydride; In tetrahydrofuran; toluene; mineral oil; at 20℃; for 6h;Cooling with ice; | 0.8 g of 60% sodium hydrogen (0.02 mol), 4 mL of THF, 1.34 g (0.01 mol) of benzofuranone was added dropwise at 10-20 C,1.7 g (0.01 mol) of m-methoxybenzoyl chloride and 2 mL of THF.10-20 C for 6 hours. TLC showed the reaction was completed by adding 20mL of aqueous 3M HCl solution, 30mL ethyl acetate stirring, the organic phase washed twice,Saturated salt water once. The organic phase was dried and 9 mL of methanol was added to recrystallize to give 2.2 g of product, yield 82%, HPLC purity 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium hydride; In tetrahydrofuran; toluene; mineral oil; at 20℃; for 6h;Cooling with ice; | 59 g of 60% sodium hydrogen (1.47 mol) was placed in a 140 mL / 140 mL THF / toluene mixture,Ice water bath cooling and stirring,A solution of 94 g (0.7 mol) of benzofuranone and 98 g (0.7 mol) of benzoyl chloride in 70 mL / 50 mL of THF / toluene was added dropwise at 10-20 C,Add 10-20 C stirring for 6 hours, add 1200mL toluene distillation under reduced pressure to recover THF.Dropping 450 mL of 3M hydrochloric acid, 200 mL of water, the organic phase washed twice, Saturated sodium chloride once, the organic phase concentrated, adding methanol to recrystallize, get 150g3- (hydroxy (phenyl) methylene) benzofuran-2 (3H) -one. 90% yield, HPLC purity 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With triethylamine; for 1h;Reflux; | General procedure: Substituted salicylaldehyde derivative 3 (455 mg, 3.7 mmol) and 2-coumaranone 4 (500 mg, 3.7 mmol) were mixed together in a round bottom flask. To it triethylamine (15 mL) was added and refluxed for 1 h. After 1 h triethylamine was removed under vacuum and the crude solid was recrystallized from ethanol to afford pure product 3-(2-hydroxyphenyl)-2H-chromen-2-one 2a-2o. |
97% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol salicylaldehyde 2a,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6a,The yield is 97%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With triethylamine; for 1h;Reflux; | General procedure: Substituted salicylaldehyde derivative 3 (455 mg, 3.7 mmol) and 2-coumaranone 4 (500 mg, 3.7 mmol) were mixed together in a round bottom flask. To it triethylamine (15 mL) was added and refluxed for 1 h. After 1 h triethylamine was removed under vacuum and the crude solid was recrystallized from ethanol to afford pure product 3-(2-hydroxyphenyl)-2H-chromen-2-one 2a-2o. |
95% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2h,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6h,The yield is 95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2n,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6n,The yield is 97%. |
96% | With triethylamine; for 1h;Reflux; | General procedure: Substituted salicylaldehyde derivative 3 (455 mg, 3.7 mmol) and 2-coumaranone 4 (500 mg, 3.7 mmol) were mixed together in a round bottom flask. To it triethylamine (15 mL) was added and refluxed for 1 h. After 1 h triethylamine was removed under vacuum and the crude solid was recrystallized from ethanol to afford pure product 3-(2-hydroxyphenyl)-2H-chromen-2-one 2a-2o. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2m,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6m,The yield is 97%. |
90% | With triethylamine; for 1h;Reflux; | General procedure: Substituted salicylaldehyde derivative 3 (455 mg, 3.7 mmol) and 2-coumaranone 4 (500 mg, 3.7 mmol) were mixed together in a round bottom flask. To it triethylamine (15 mL) was added and refluxed for 1 h. After 1 h triethylamine was removed under vacuum and the crude solid was recrystallized from ethanol to afford pure product 3-(2-hydroxyphenyl)-2H-chromen-2-one 2a-2o. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With triethylamine for 1h; Reflux; | 4.2.1. General procedure for the synthesis of substrates 2a-2o19 General procedure: Substituted salicylaldehyde derivative 3 (455 mg, 3.7 mmol) and 2-coumaranone 4 (500 mg, 3.7 mmol) were mixed together in a round bottom flask. To it triethylamine (15 mL) was added and refluxed for 1 h. After 1 h triethylamine was removed under vacuum and the crude solid was recrystallized from ethanol to afford pure product 3-(2-hydroxyphenyl)-2H-chromen-2-one 2a-2o. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With triethylamine; for 1h;Reflux; | General procedure: Substituted salicylaldehyde derivative 3 (455 mg, 3.7 mmol) and 2-coumaranone 4 (500 mg, 3.7 mmol) were mixed together in a round bottom flask. To it triethylamine (15 mL) was added and refluxed for 1 h. After 1 h triethylamine was removed under vacuum and the crude solid was recrystallized from ethanol to afford pure product 3-(2-hydroxyphenyl)-2H-chromen-2-one 2a-2o. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With triethylamine for 1h; Reflux; | 4.2.1. General procedure for the synthesis of substrates 2a-2o19 General procedure: Substituted salicylaldehyde derivative 3 (455 mg, 3.7 mmol) and 2-coumaranone 4 (500 mg, 3.7 mmol) were mixed together in a round bottom flask. To it triethylamine (15 mL) was added and refluxed for 1 h. After 1 h triethylamine was removed under vacuum and the crude solid was recrystallized from ethanol to afford pure product 3-(2-hydroxyphenyl)-2H-chromen-2-one 2a-2o. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine; for 1h;Reflux; | General procedure: Substituted salicylaldehyde derivative 3 (455 mg, 3.7 mmol) and 2-coumaranone 4 (500 mg, 3.7 mmol) were mixed together in a round bottom flask. To it triethylamine (15 mL) was added and refluxed for 1 h. After 1 h triethylamine was removed under vacuum and the crude solid was recrystallized from ethanol to afford pure product 3-(2-hydroxyphenyl)-2H-chromen-2-one 2a-2o. |
89% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2q,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6q,The yield is 89%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2p,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6p,The yield is 90%. |
86% | With triethylamine; for 1h;Reflux; | General procedure: Substituted salicylaldehyde derivative 3 (455 mg, 3.7 mmol) and 2-coumaranone 4 (500 mg, 3.7 mmol) were mixed together in a round bottom flask. To it triethylamine (15 mL) was added and refluxed for 1 h. After 1 h triethylamine was removed under vacuum and the crude solid was recrystallized from ethanol to afford pure product 3-(2-hydroxyphenyl)-2H-chromen-2-one 2a-2o. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2b,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6b,The yield is 82%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2c,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6c,The yield is 94%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2g,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6g,The yield is 84%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2i,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6i,The yield is 95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2j,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removal of the solvent, the residue was purified by column chromatography on silica gel to give the product 6j,The yield is 86%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2k,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6k,The yield is 93%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2l,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6l,The yield is 81percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2o,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6o,The yield is 83%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2r,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6r,The yield is 87%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2s,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6s,The yield is 97%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2t,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6t,The yield is 92percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2u,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6u,The yield is 88%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2d,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6d,The yield is 73percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2e,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to afford the product 6e,The yield is 74%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube; | 0.20 mmol of compound 5,0.24 mmol of compound 2f,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to give the product 6f,The yield is 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.5% | With acetic anhydride; at 95 - 100℃; | Add in a four-necked flaskBenzofuranone400 g (2.98 mol) of trimethyl orthoformate 600 g (5.66 mol) and 670 ml of acetic anhydride,And in the bottle with a 20cm long distillation column,Filler for the glass spring,Distillation reaction,The temperature in the reaction flask was slowly raised to 95-100 C,Warming about 2-3h,Insulation about 10h.During the reaction,Distillation column distillation reaction generated low boiling methyl acetate,While reducing the entrainment of trimethyl orthoformate and acetic anhydride and other raw materials,Cool slightly to 100 C under reduced pressure,No solution and then extracted 1h,Join toluene stirring to dissolve,The untreated direct use of the next step (quantitative yield 96.5%). |
96.8% | With acetic anhydride; at 40 - 90℃; | The metered o-chlorophenylacetic acid, 32% liquid alkali, and the catalyst 1 are put into the autoclave, the stirring is started, the nitrogen gas is pressurized to 0.45 MPa, and the temperature is raised to 145 C. After the reaction, the material is transferred to the acid hydrolysis kettle;The material is cooled to below 25 C, and the mixture is slowly added to the acid hydrolysis tank with concentrated hydrochloric acid to adjust the pH value to 6.5. During the process of adjusting the pH value, the control temperature is lower than 22 C;The metered toluene is placed in a dehydration kettle, heated to 110 C, and dehydrated by azeotropic distillation. After the dehydration is completed, the material is transferred to a loop kettle; the metered concentrated sulfuric acid is placed in a loop kettle and stirred with the dehydrated material. , using jacketed circulating water to control the temperature inside the kettle at 70 C;After the end of the cyclization, put the material into the alkali washing kettle, start stirring, add the metered sodium bicarbonate, sodium hydroxide or sodium bicarbonate solution, the alkali washing temperature is controlled at 50 C, and the layer is allowed to stand. After the alkali washing is completed, Transfer organic materials to the washing kettle;The metered water is placed in a water washing kettle, stirred with the material, the temperature is controlled at 50 C, and after standing and layering, the upper layer is transferred to the concentrating kettle;Open the vacuum system of the concentrator, the vacuum system will control the vacuum to -0.1MPa or more, slowly increase the temperature under vacuum, start to remove the toluene, when the temperature of the kettle rises to 80 C, when the toluene is not produced, switch to the benzofuranone finished product tank , began to collect benzofuranone, until the end, the distillation residue is collected and treated as hazardous waste;The metered trimethyl orthoformate and acetic anhydride and the synthetic benzofuranone are successively put into the synthesis kettle, and the temperature is slowly raised to 90 C to start receiving methyl acetate, and the temperature of the synthesis kettle is controlled to not exceed 100 by the reflux ratio of the column. C, when the temperature of the tower rises, the methyl acetate is not produced, the reaction is finished, the material is cooled to 80 C, and then transferred to the deacidification kettle;The deacidification kettle is first evacuated, vacuum is pumped to -0.1 MPa or more, and the temperature of the controlled material is controlled at 80 C to start deacetation. After the deacidification is completed, the material is cooled to 40 C and transferred to a dissolution kettle;The metered toluene is placed in the dissolution kettle, and after the material is thoroughly stirred, the organic layer material is transferred to the water washing kettle, and the water layer material is subjected to waste treatment;The metered water is placed in a water washing kettle, and the material is stirred and heated to 50 C, and the layer is allowed to stand, the residual acid and impurities are washed away, and the organic layer is transferred to the desolvent kettle;Open the vacuum system of the desolvent kettle, control the vacuum to above -0.097MPa, control the temperature of the desolvent kettle material to 80 C, start the azeotrope of detoluene and water, and then remove the toluene after the end to control the methoxybenzofuranone. The concentration of 55%, the end of the desolvation, cooling and transfer the material to the metering tank of methoxybenzofuranone;The purity of 3-(a-methoxy)-methylenyl<strong>[553-86-6]benzofuran-2(3H)-one</strong> was determined by HPLC to be 99.2%, and the yield was 96.8%. |
at 110℃; for 21h;Large scale; | 82 kg of o-hydroxyphenylacetic acid,350L acetic anhydride was added to the reactor, heated to 110 C under the protection of nitrogen,After the reaction for 2.5h, 115kg of trimethyl orthoformate was added and reacted at 110 C for 21h. During the reaction, oil-water separation of the low boiling point substance was achieved. After the reaction was completed, the reaction mixture was distilled under reduced pressure at 90 C to obtain a black oil To the black oil, 24 L of methanol was added, heated to reflux, and then cooled to crystallize, Filtering to obtain 3 - (- methoxy) - methylene benzofuran-2 (3-hydro) -one; |
With zinc(II) chloride; at 110℃; for 4h; | Previous take material,Trimethyl orthoformate (265 g, 2.5 mmol), zinc chloride (13.6 g, 0.1 mol) was added, and the temperature was raised to 110 C to continue the reaction for 4 h. After the reaction was completed, the temperature was lowered.Ethyl acetate and water were added to the reaction mixture, and the organic phase was separated and concentrated under reduced pressure to give Compound 3.The product was used in the next step without purification. A small portion of the column was taken out to give Compound 3 as a yellow-green solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With iodine; In tetrahydrofuran; at 80℃; for 24h; | 1 · 34 g (10 mmol) of 2-coumaranone,1.83 g (10 mmol) of dibenzo [b, d] furan-4-amine,3.32 g (10 mmol) of 10- (naphthalen-1-yl) anthracene-9-carboxaldehyde and0.013 g (0.5 mmol) of iodine (I2) was dissolved in 150 mL of THF and then stirred at a temperature of 80 C for 24 hours. The reaction solution was cooled to room temperature.Then, the organic layer was extracted three times by using 60 mL of water and 60 mL of diethyl ether. The organic layer was dried by using magnesium sulfate and the solvent was evaporated. The obtained residue was separated and purified by silica gel column chromatography to prepare 3.67 g (60%) of compound 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | General procedure: To a 25 mL round bottomed flask was added different substituted oxindoles 8 (0.2 mmol, 1.0 equiv.) and bromoethylsulfonium salt 9 (132.99 mg, 0.3 mmol, 1.5 equiv.), DMF (2 mL). The mixture was stirred at room temperature for 5min and Et3N (61.88 mg, 0.6 mmol, 3.0 equiv.) was added into reaction system. The mixture was stirred for 6h at room temperature until the reaction completed, quenched with saturated ammonium chloride solution (5 mL), and was extracted with EtOAc (3×30 mL). The combined organic layer washed with H2O (2×10 mL), dried with anhydrous sodium sulfate. After concentration, product was purified using column chromatography on silica gel with suitable eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0 - 20 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen / ethanol / 20 °C / Inert atmosphere 3: N,N,N',N'-tetramethyl-1,8-diaminonaphthalene / 80 °C / Inert atmosphere | ||
Multi-step reaction with 3 steps 1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0 - 20 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen / ethanol / 20 °C / Inert atmosphere 3: N,N,N',N'-tetramethyl-1,8-diaminonaphthalene / 80 °C / Inert atmosphere | ||
Multi-step reaction with 3 steps 1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0 - 20 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen / ethanol / 20 °C / Inert atmosphere 3: N,N,N',N'-tetramethyl-1,8-diaminonaphthalene / 80 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With aluminum (III) chloride; In tetrachloromethane; at 20℃; for 6h; | Add 1.00g of alpha-chloroacetic acid phenol ester produced in the first step to 10ml of carbon tetrachloride, and the Friedel-Crafts reaction takes place under the condition of 0.04g of anhydrous AlCl3, the reaction temperature is 20 ,The reaction time is 3h.The yield was 83%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With piperidine In N,N-dimethyl acetamide at 150℃; for 6h; Inert atmosphere; diastereoselective reaction; |
Tags: 553-86-6 synthesis path| 553-86-6 SDS| 553-86-6 COA| 553-86-6 purity| 553-86-6 application| 553-86-6 NMR| 553-86-6 COA| 553-86-6 structure
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Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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