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CAS No. : | 90-47-1 | MDL No. : | MFCD00005060 |
Formula : | C13H8O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | JNELGWHKGNBSMD-UHFFFAOYSA-N |
M.W : | 196.20 | Pubchem ID : | 7020 |
Synonyms : |
|
Num. heavy atoms : | 15 |
Num. arom. heavy atoms : | 14 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 59.99 |
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) : | -5.09 cm/s |
Log Po/w (iLOGP) : | 2.28 |
Log Po/w (XLOGP3) : | 3.39 |
Log Po/w (WLOGP) : | 2.95 |
Log Po/w (MLOGP) : | 2.06 |
Log Po/w (SILICOS-IT) : | 3.5 |
Consensus Log Po/w : | 2.84 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.88 |
Solubility : | 0.0257 mg/ml ; 0.000131 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.7 |
Solubility : | 0.0388 mg/ml ; 0.000198 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -5.29 |
Solubility : | 0.00101 mg/ml ; 0.00000513 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.76 |
Signal Word: | Danger | Class: | 6.1 |
Precautionary Statements: | P301+P310-P305+P351+P338 | UN#: | 2811 |
Hazard Statements: | H301-H315-H319 | 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 |
---|---|---|
41% | at 100℃; for 5 h; Inert atmosphere | Example 1Synthesis of Example Compound A-7[0143][Chem. 19]C6H5Me/EtOH/Na2C03a<7. A - 7[0144] To a 100 mL round-bottomed flask, the following reagents and solvents were placed.Xanthone : 5.0 g (26 mmol)Bromine: 16 g (102 mmol)Iodine: 50 mg (0.20 mmol)Acetic acid: 20 mL[0145] The resulting reaction solution was refluxed for 5 hours at 100 °C under heating and stirring in nitrogen. Upon completion of the reaction, chloroform and a saturated aqueous sodium sulfite solution were added to the reaction solution and stirring was continued until the color of bromine was lost. The organic layer was separated, washed with a saturated aqueous sodium carbonate solution, dried with magnesium sulfate, and filtered. The solvent in the filtrate was distilled away at a reduced pressure. The precipitated solid was purified with a silica gel column (toluene: 100percent). As a result, 2.9 g (yield: 41percent) of 2- bromoxanthone and 2.2 g (yield: 25percent) of 2 , 7-dibromoxanthone were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With tert.-butylhydroperoxide; 1-n-butyl-3-methylimidazolim bromide; In water; at 55℃; for 12.0h; | General procedure: Charged 0.5 mmol of 1,3-diphenylprop-2-yn-1-ol 15a (104 mg, 0.5 mmol), 0.5 mL of [bmim]Br and TBHP (0.5 mL, 3.6 mmol) were taken in a round bottom flask and heated to 55 C until completion of the reaction. The reaction course was monitored by TLC. After completion of the reaction, the crude mixture was extracted with ethyl acetate (3 * 4 mL). The organic layer was concentrated under reduced pressure and purified by column chromatography on silica gel to afford the desired product, 1,3-diphenylprop-2-yn-1-one 15b as yellow oil; |
91% | With tert.-butylhydroperoxide; In water; at 100℃; for 24.0h; | General procedure: Caution. tert-Butyl hydroperoxide is an exceptionally dangerous chemical that is highly reactive, flammable, and toxic. It is corrosive to skin and mucous membranes and causes respiratory distress when inhaled. A solution of secondary alcohol (1 mmol) and 70% TBHP (6 or 10 equiv.) was stirred at 100 C for 24 h. The reaction mixture was quenched with the saturated solution of sodium thiosulfate (5 mL) and extracted with dichloromethane (3 x 10 mL). The combined dichloromethane extracts were dried over anhydrous Na2SO4 and filtered, and then the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel with PE or PE/EtOAc as the eluent to obtain the desired products. |
90% | With Iodine monochloride; caesium carbonate; In dichloromethane; at 0 - 20℃; for 5.0h;Green chemistry; | General procedure: Starting alcohols (1.00 g, 1.0 eq) specified in Table 3 were dissolved in 10 mL of dried CH2Cl2 (for substrates in entries 8-20 in Table 3, 30 mL of dried CH2Cl2 was used), and the resulting mixture was stirred in an ice-water bath, followed by addition of Cs2CO3 (3.0 eq). The suspension was stirred at this temperature, and ICl (1.5 eq) dissolved in 2 mL of CH2Cl2 was added dropwise. After addition, the reaction mixture was stirred at room temperature until the reaction completed as indicated by TLC analysis, which was conducted at 0.5-h intervals.The reaction mixture was subjected to aqueous workup described previously to yield the pure carbonyl compounds specified in Table 3. |
90% | With N-Bromosuccinimide; potassium acetate; In dichloromethane; water; at 20℃; for 10.0h;Green chemistry; | General procedure: A solution of diphenylmethanol (1 mmol), NBS (1.3equiv.), KOAc (1.5 equiv.) H2O (1.5 mL), and CH2Cl2 (0.5mL) was magnetically stirred in 25 mL flask at room temperaturefor 10 h. The reaction mixture was added into water(10 mL), and extracted with EtOAc (3 × 10 mL). The combinedEtOAc extracts were dried over anhydrous MgSO4,filtrated, and then the solvent was removed under reducedpressure. The residue was purified by the flash columnchromatography on silica gel with PE or PE/EtOAc as theeluent to obtain the desired products. The oxidation productswere identified by GC-MS and 1H NMR. |
With anthracene; diiron(IV) mu-oxo-bis(5,10,15-tripentafluorophenylcorrole); In acetonitrile; for 24.0h;Irradiation; Photolysis;Catalytic behavior; | General procedure: A Rayonet photoreactor (RPR-100) with a wavelength rangeof 400-500 nm (max= 420 nm) from 300 W mercury lamps(RPR-4190×12) was used for the photocatalytic reactions. Thephotochemical reactions typically consisted of 1.0-1.5 mg of[Fe(TPFC)]2O (approximate 0.5-1 mol) in 5 mL of acetonitrile con-taining over 4 mmol of organic substrates. Dry oxygen gas wasbubbled through the solution as it was irradiated. Aliquots ofthe reaction solution at constant time interval were analyzedby GC/MS spectrometer (Agilent GC6890/MS5973) to determinethe formed products and yields with an internal standard (1,2,4-trichlorobenzene). The trend in the product yields roughly parallelsirradiation time. Monitoring reaction by UV-vis spectroscopy indi-cated that no significant degradation of catalyst 3 was found after24 h photolysis |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With oxygen; In toluene; at 100℃; for 188h; | General procedure: Ir1 was activated by heating at 135C during 2h. Then, a mixture of benzyl alcohol (310muL, 323mg, 3mmol) and preactivated Ir1 (46mg, 1.3mol%) in toluene (1mL) was charged into a reactor tube. We purged three times (pressurizing/depressurizing cycles) with oxygen and left for 23 h at 100C under an oxygen atmosphere (balloon). Upon cooling to room temperature, the reaction mixture was filtered through celite using CH2Cl2 and dried to give the benzaldehyde (305mg, 97% yield). |
99% | With tert.-butylnitrite; oxygen; acetic acid; 2,3-dicyano-5,6-dichloro-p-benzoquinone; In 1,2-dichloro-ethane; at 20℃; for 12h;Irradiation; Schlenk technique; Sealed tube; | General procedure: A 15-mL Schlenk tube equipped with a magnetic stirrer bar was charged with <strong>[92-83-1]xanthene</strong> (1a; 182 mg, 1.0 mmol) and DDQ (2.3mg, 1 mol%). The air in the tube was replaced with O2 and the tube was sealed with a rubber plug. TBN (5.9 muL, 5 mol%), AcOH(12.0 mg, 20 mol%), and DCE (5.0 mL) were added. The Schlenktube was placed in a dark box and illuminated with a 18 W blue LED. The mixture was stirred vigorously under an O2 balloonuntil the reaction was complete (GC). The mixture was thenconcentrated on a rotary evaporator, and the residue was purifiedby column chromatography (silica gel, PE-EtOAc) to give awhite solid; yield: 194 mg (99%); mp 174-175 C.1H NMR (500 MHz, CDCl3): delta = 8.35-8.33 (m, 2 H), 7.73-7.70(m, 2 H), 7.48 (d, J = 8.5 Hz, 2 H), 7.39-7.36 (m, 2 H). 13C NMR(125 MHz, CDCl3): delta = 177.2, 156.2, 134.8, 126.7, 123.9, 121.9,118.0. MS (EI): m/z (%): 196.11 (93) [M]+, 139.10 (100). |
96% | With potassium hexafluorophosphate; iron(III) nitrate monohydrate; oxygen; In acetonitrile; at 80℃; for 2h; | To a 35 mL tube, 1 mmol of oxacanthracene (formula (1-1)), 0.1 mmol of Fe (NO3) 3 · 9H2O, 0.2 mmolOf KPF6 and 3 mL of acetonitrile, with oxygen to replace the tube air,Close the bottle with a rubber stopper, insert the oxygen balloon,The reaction flask was placed in a preheated oil bath and heated to 80 C for 2 h.Filtration, the filtrate vacuum distillation solvent, and then column chromatography separation,A mixture of ethyl acetate / petroleum ether in a volume ratio of 1:50 was used as the eluent,The eluate containing the target compound was collected and the solvent was evaporatedThe product was anoxanthrone and the isolated yield was 95%.; The reaction was carried out in the same manner as in Example 1 except that the amount of KPF6 was changed to 0.3 mmol,The yield of the xanthone was 96%. |
95% | With tert.-butylhydroperoxide; 2.9-dimethyl-1,10-phenanthroline; copper(II) choride dihydrate; In water; at 20℃; for 1h; | General procedure: A stock solution of CuCl2·2H2O in water (0.0171 g/mL) was prepared (by dissolving 0.171 g in 10 mL H2O). To a Teflon screw cap glass tube, catalyst A (100 muL of a stock solution, 0.01 mmol of CuCl2, 2.1mg, 0.01 mmol of neocuproine) was added. Then 0.7 mL of H2O, 0.2 mmol of arylalkanes, and 70 % aq tert-butyl hydroperoxide (200 muL, 1.4 mmol) were added in each case. The mixture was stirred vigorously at room temperature till to its reaction time specified in the Tables 2 and 3. The reaction mixture was then diluted with ethyl acetate and the products dissolved in ethyl acetate layer were analyzed by GC using internal standard 1,4-di-tert-butylbenzene (19.4 mg, 0.1 mol). For product separation, the aqueous phase was extracted with ethyl acetate (3×10 mL). The combined extracts were dried over anhydrous MgSO4 and filtered. The filtrate was concentrated and product isolation was carried out by TLC. The pure products of benzophenone, 9-fluorenone (Table 2, entries 2 and 3) and 4-methoxyacetophenone (Table 3 entry 2) were obtained from drying their ethyl acetate extract without chromatographic workup. Filtration of the reaction mixture afforded pure 9-xanthenone (Table 2, entry 4). |
95% | With tert.-butylhydroperoxide; 1-n-butyl-3-methylimidazolim bromide; In water; at 55℃; for 20h; | General procedure: Charged 0.5 mmol of 3-(9H-fluoren-2-yl)prop-2-yn-1-ol 13a (110 mg, 0.5 mmol), 0.5 mL of [bmim]Br and TBHP (0.5 mL, 3.6 mmol) were taken in a round bottom flask and heated to 55 C until completion of the reaction. The reaction course was monitored by TLC. After completion of the reaction, the reaction mixture was extracted using ethyl acetate (3 * 4 mL). The organic layer was concentrated under vacuum and purified by column chromatography on silica gel to afford the desired product as 2-(3-hydroxyprop-1-yn-1-yl)-9H-fluoren-9-one 13b Yellow Solid; |
93% | With dihydrogen peroxide; trifluoroacetic acid; zinc dibromide; In 1,4-dioxane; water; at 100℃; for 16h; | General procedure: In a 25 mL pressure tube, ZnBr2 (10 mol %) and a stirring bar were added. After the addition of diphenylmethane (1 mmol), trifluoroacetic acid (0.2 mL) and 1,4-dioxane (2 mL) by syringe, H2O2 (4 mmol; 30% aqueous) was added in one pot to the solution and the final solution was kept at 100 C for 16 h. Then hexadecane (100 mg) and ethyl acetate (3 mL) were injected, a part of solution was taken for GC and GC-MS analysis after properly mixed. All the products are commercially available. |
93% | With oxygen; nitric acid; In acetonitrile; at 140℃; under 760.051 Torr; for 3h; | General procedure: After an about 45 mL glass tube was charged with 2 mL acetonitrile, 0.5 mmol substrate and 0.075 mmol HNO3, the system was flushed with oxygen gas three times. Subsequently, the reaction tube was sealed and heated with magnetic stirring at 140 C for 3 h. When the reaction time was reached, the reaction mixture was cooled to room temperature. Finally, evaporation of solvent followed by column chromatography yielded the targeted product. GC yields were obtained by the GC analysisof the mixture from another parallel experiment. |
90% | With 1,2,3-Benzotriazole; 2,2,6,6-tetramethyl-piperidine-N-oxyl; dibenzoyl peroxide; In 1,2-dichloro-ethane; at 80℃; for 6h;Schlenk technique; | A 35-mL Schlenk tube, equipped with a magnetic stirring bar, was charged with 9H-<strong>[92-83-1]xanthene</strong> 1a (137 mg, 0.75 mmol), 1H-benzo[d][1,2,3]triazole 2a (60 mg, 0.5 mmol), and BPO (242 mg, 1.0 mmol), followed by the addition of DCE (5.0 mL). The mixture was stirred at 80 C for 6 h; then it was quenched with saturated aqueous Na2S2O3 (2.0 mL), saturated aqueous K2CO3 (2.0 mL), and water (20.0 mL), and extracted with CH2Cl2 (20.0 mL) three times. The residue obtained after evaporation of the solvent was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 12:1, v/v) to afford 1-(9H-xanthen-9-yl)-1H-benzo[d][1,2,3]triazole 3a as a colorless crystal (144 mg, 96% yield). |
88% | With N-hydroxyphthalimide; 6-((cobalt(II) 4,9,16,23-tetraaminephthalocyanin-4-yl))cellulose; oxygen; potassium hydroxide; In o-xylene; for 9h;Reflux; Green chemistry; | General procedure: N-Hydroxyphthalimide (0.01 g, 0.06 mmol) was added to a two-necked flask equipped with a gas bubbling tube containing colloidal of CoPcCell (0.05 g), tetraline (0.13 g, 1.00 mmol) and KOH (0.25 mmol) in o-xylene (5 mL). The mixture was stirred under reflux conditions in O2 atmosphere provided with a balloon. The reaction temperature was raised to refluxing o-xylene. The progress of the reaction was followed by TLC. Upon completion, CoPcCell was separated by filtration and washed with acetone (5 mL). Tetralone was isolated from the mixture using column chromatography with n-hexane:ethyl acetate (10:1) in 88% yield. |
87% | With oxygen; lithium hexamethyldisilazane; In tetrahydrofuran; at 60℃; under 760.051 Torr; for 12h;Sealed tube; Green chemistry; | General procedure: To an 8 mL oven-dried vial, 4-benzylpyridine (0.1 mmol), dry THF (1 mL), LiHMDS (0.15mmol) were added subsequently. The reaction system was sealed by a rubber septum with a needleconnected with O2 balloon. After stirring at 60 C for 12 h, the reaction mixture was passed througha short pad of silica gel and eluted with ethyl acetate (1 mL × 3). The combined organics wereconcentrated under reduced pressure. The residue was purified by flash chromatography to givethe diarylketone 2a as white solid (15.6 mg, 85% yield). |
83% | With tert.-butylhydroperoxide; In water; at 100℃; for 24h; | General procedure: Caution. tert-Butyl hydroperoxide is an exceptionally dangerous chemical that is highly reactive, flammable, and toxic. It is corrosive to skin and mucous membranes and causes respiratory distress when inhaled. A solution of secondary alcohol (1 mmol) and 70% TBHP (6 or 10 equiv.) was stirred at 100 C for 24 h. The reaction mixture was quenched with the saturated solution of sodium thiosulfate (5 mL) and extracted with dichloromethane (3 x 10 mL). The combined dichloromethane extracts were dried over anhydrous Na2SO4 and filtered, and then the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel with PE or PE/EtOAc as the eluent to obtain the desired products. |
73% | With aluminum(III) nitrate nonahydrate; In acetonitrile; at 0 - 23℃; | General procedure: In a 25 ml dry round-bottom flask was suspended polymeric PhIO (0.25 equivalent) indry acetonitrile at 23C. Then, Al(NO 3 ) 3 (0.35 equivalent) was added and stirred for10 min, afterward, it was cooled to 0C. The benzylic aryl derivative (1 equivalent) wasincorporated in one portion. The reaction was warmed to 23C for a period of 2-4 huntil the starting material was fully consumed judging its advance by TLC. The reactionmixture was quenched by the addition of NH 4 Cl saturated solution (25 mL) and thenextracted with EtOAc (3 10 mL). The organic extracts were collected, dried overanhydrous sodium sulfate, filtered, and concentrated in vacuo to remove the solventand yield the crude of the reaction. The product was purified by flash column chroma-tography on silica gel (100-200 mesh) with EtOAc/hexane system. |
72% | With oxone; cobalt(II) perchlorate; In water; acetonitrile; at 25℃; for 3h;Sealed tube; | General procedure: A mixture of 1 (0.2 mmol), Co(ClO4)2 (0.02 mmol), Oxone (1.2 mmol), CH3CN (2 mL) and H2O (2 mL) was stirred in a sealed tube at 25 C for 3 h. After the reaction was completed (as monitored by TLC), the mixture was placed and allowed to separate into layers. Then the upper organic layer was separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by preparative TLC (petroleum ether/ethyl acetate = 10:1, v/v) to yield 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With ethanol; sodium hydroxide; zinc; at 20℃; for 4.0h;Reflux; | Tonnes (294.3 g, 1.5 mol, 1.0 eq) and ethanol (1800 mL) were added to a 3 L four-necked flask and stirred at room temperatureAfter dissolving, sodium hydroxide solid (480 g, 12.0 mol, 8.0 eq) was added, and then the temperature was raised to 50 C. The reduced Zn(195g, 3.0mol, 2.0eq). After the addition was completed, the mixture was heated to reflux for 4h. The disappearance of the starting material by TLC (VPE / EA = 5: 1)After completion of the reaction, hot filtered to remove the solid, and then concentrated under reduced pressure to remove most of the ethanol, the residue was added 6mol / L dilute hydrochloric acidAdjust the pH = 7, the solid precipitated, filtered, vacuum dried at 50 C to give 279g tyl alcohol, the yield was 94% |
92% | With sodium tetrahydroborate; In ethanol; at 20℃; | To a solution of xanthone (2.00 g, 10.2 mmol) in EtOH(20 ml) was added NaBH4(574 mg, 15.5 mmol) and thesuspension was stirred for overnight at room temperature.H2Owas poured into the solution and stirred for 1 h, and theprecipitated solid was filtered, washed with H2O,and driedto obtain 9-hydroxyxanthene (1.86 g, 9.38 mmol, 92%).To a solution of 9-hydroxyxanthene (1.86 g, 9.38 mmol)in CHCl3/AcOH (1:1, 20 ml) was added NH4OAc(7.23 g,93.8 mmol) and the suspension was stirred for 10 h at roomtemperature. The precipitated solid was filtered, washed withCHCl3,and to the MeOH suspension of the resulting solidwas added Et3Nuntil the solution is clear. The solution wasconcentrated in vacuo. The residue was added to H2OandAcOEt, the organic layer washed with sat. NH4Claq. andbrine, dried over MgSO4,and evaporated in vacuo to give9-aminoxanthene (0.972 g, 4.93 mmol, 53%) as a light yellowsolid. IR (KBr) numax cm-1: 3345, 3327, 3249, 3154,3067, 3039, 2915, 2367, 2335, 1607, 1566, 1475, 1456,1337, 1268, 1210, 1090, 930, 816, 753, 615, 505 cm-1. 1HNMR (600 MHz, DMSO-d6): delta = 4.96 (1H, s), 7.09 (2H, d,J = 8.4 Hz), 7.14 (2H, t, J = 7.8 Hz), 7.28 (2H, td, J = 7.2, 1.2 Hz), 7.62 (2H, d, J = 7.8 Hz) ppm. 13C NMR (150 MHz,DMSO-d6): delta = 45.9, 115.9, 123.2, 126.3, 128.2, 129.5,150.4 ppm. HRMS-ESI: m/z [M - H]+ calcd for C13H10NO:196.0762; found: 196.0782. |
82% | With methanol; sodium tetrahydroborate; | In the first step, 10 g of xanthone was added to 100 ml of methanol, and 20 g of sodium borohydride was added to the solution at room temperature.The reaction process has a hydrogen release,The reaction was monitored by TLC.To the oxygen anthrone finishedAfter the whole reaction,The solvent methanol was distilled off and then dissolved in dichloromethane and the organic phase was washed with deionized water several times until the pH of the aqueous phase was reduced to 7.0. Dispensing The organic phase was collected and concentrated, and the crystals were separated. The reaction and the post-treatment process should be noted in an inert atmosphere to prevent oxidation of the tons of alcohol. The reaction yield was 82%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With pyridine; hydroxylamine hydrochloride at 110℃; for 24h; | 9H-Xanthen-9-one oxime (2a): A 10-mL flame-dried screw-top test tube equipped with a magneticstirring bar was charged with xanthone 4a (100.5 mg, 0.512 mmol), NH2OHHCl (107.1 mg, 1.54 mmol)and anhydrous pyridine (0.51 mL). The resulting mixture was stirred at 110 °C for 24 h. To the resultingmixture was added H2O, and the mixture was extracted with EtOAc three times and CH2Cl2 once. Thecombined organic extracts were washed with brine, dried over anhydrous sodium sulfate, and filtered.The organic solvents were removed under reduced pressure to give crude xanthone oxime 2a. Residualpyridine was azeotropically removed with toluene. The residue was purified by flash silica gel columnchromatography (CHCl3) to afford xanthone oxime 2a (48.0 mg, 0.227 mmol, 44%) as a colorless solidwith recovery of xanthone 4a (56.5 mg, 0.288 mmol, 56%). |
With pyridine; hydroxylamine hydrochloride | ||
With sodium hydroxide; hydroxyammonium sulfate In pyridine; water for 2h; Heating; |
Multi-step reaction with 2 steps 1: thioacetic acid; benzene; thionyl chloride 2: pyridine; hydroxylamine hydrochloride | ||
With pyridine; hydroxylamine hydrochloride at 110℃; for 48h; | 139.139a The mixture of xanthone (1.0 g), hydroxylamine hydrochloride (1.77 g) and pyridine (12 ml) was heated to 110° C. for 2 days. The reaction mixture was concentrated and the residue was extracted with EtOAc. The organic layer was washed with 1% HCl, water, brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography to give desired product.MS (ESI): m/z=212.08 [M+H]. | |
With hydroxylamine hydrochloride In ethanol | ||
Multi-step reaction with 2 steps 1: borane-THF / tetrahydrofuran / 4 h / Reflux 2: tert.-butylnitrite; potassium hexamethylsilazane / tetrahydrofuran / 0.5 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium bis(2-methoxyethoxy)aluminium dihydride; In toluene; at 23 - 60℃; for 3h;Inert atmosphere; | A 50 ml eggplant type flask was charged with a 70 mass% toluene solution of sodium dihydrobis (2-methoxyethoxy) aluminate (Registered trademark: VITRIDE (VITRIDE), manufactured by Bertrass Specialties Incorporated) 3.47 g (12 mmol) Toluene (10 ml) was added to make it under a nitrogen atmosphere, 588 mg (3 mmol) of xanthone (Wako Junyaku reagent grade 1) dissolved in 10 ml of toluene (special grade, Wako Pure Chemical Industries, Ltd.) was added and stirred at room temperature (23 C.). after that, This solution was heated to 60 C. and heated and stirred for 3 hours. After standing to cool, 10 ml of a 2N sodium hydroxide aqueous solution was added under ice cooling to make it alkaline. The organic phase was separated and the organic phase was washed twice with 10 ml of saturated sodium bicarbonate. After washing, the organic phase was dried with magnesium sulfate and then toluene was distilled off. As a result, A solid (crude xanthene) was obtained as a residue. This crude xanthene was purified by silica gel column chromatography to obtain 492 mg (90% yield) of xanthene |
80% | A 50 ml eggplant-shaped flask was placed under a nitrogen atmosphere, and 430 mg (3 mmol) of tri-n-propylamine (Wako pure chemical reagent grade 1: tertiary amine) and 588 mg (3 mmol) of xanthone (Wako Pure Chemical Reagent 1 grade) And the mixture was stirred at room temperature (23 C.). To this solution, 1219 mg (9 mmol) of trichlorosilane was slowly added dropwise using a dropping funnel.After the dropwise addition, the reaction solution was stirred at 60 C. for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, slowly added with 10 ml of a 5% by mass methanol solution of potassium hydroxide and stirred at room temperature for 1 hour (hydrolysis of the silane compound: contacting the reaction mixture with a basic solution). It was confirmed that this mixed solution (reaction mixture) was basic.The resulting mixed solution (reaction mixture) was poured into a separating funnel containing 30 ml of methylene chloride (special grade Wako Pure Chemical Industries, Ltd.), 10 ml of water was added, and the component dissolved in water was extracted into the aqueous phase. After carrying out this operation twice more, the separated methylene chloride solution (organic phase) was dried over magnesium sulfate and methylene chloride was distilled off to obtain a solid (crude xanthene) as a residue. This crude xanthene was purified by silica gel column chromatography to obtain 437 mg (yield: 80%) of xanthene |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With Lawessons reagent for 0.0666667h; microwave irradiation; | |
93% | With Lawessons reagent In toluene for 2h; Inert atmosphere; Schlenk technique; Reflux; | |
92% | With triethylamine; trichlorophosphate In water at 100 - 110℃; for 0.05h; microwave irradiation; |
90% | With Lawessons reagent In toluene at 80℃; for 1h; | |
80% | With Lawessons reagent In benzene for 1h; Heating; | |
80% | With Lawessons reagent In toluene at 75℃; for 12h; | 1.1; 5.1; 6.1 first step The compound 9H-xanthen-9-oneAnd Lawson reagent according to a molar ratio of 1: 0.75 evenly mixed with the sameToluene was placed in a drop-side flask. 75 oil bath reaction 12h. Rotate the organic phase to dryness and provide sufficient saturated sodium hydroxide / hydrogen peroxidePotassium alkali solution, out excessive Lawesson's reagent, stirred and filtered until the filtrate is clear and transparent.Take the product on the filter cake9H-xanthene-9-thione was recrystallized three times and dried at a low temperature in vacuum with a yield of 80%. |
78% | With pyridin-1-ium-1-yl[pyridin-1-ium-1-yl(sulfido)phosphinothioyl]sulfanyl-sulfido-thioxo-phosphane In dimethylsulfone at 165 - 175℃; for 0.25h; | |
74% | With Lawessons reagent In benzene for 2h; Heating; | |
70% | With tetraphosphorus decasulfide; sodium hydrogencarbonate In tetrahydrofuran for 3h; Heating; | |
With diphosphorus pentasulfide at 140 - 150℃; | ||
With oxalyl dichloride unter Feuchtigkeitsausschluss; Behandeln des Reaktionsprodukts mit Thioessigsaeure in Benzol im Kohlendioxydstrom; | ||
With thionyl chloride; tiolacetic acid; benzene | ||
With tetraphosphorus decasulfide | ||
With Lawessons reagent In toluene Heating; | ||
With tetraphosphorus decasulfide In toluene Heating; | ||
With tetraphosphorus decasulfide In toluene at 110℃; for 8h; | ||
With Lawessons reagent In benzene | ||
With Lawessons reagent | ||
With Lawessons reagent In toluene for 4h; Inert atmosphere; Reflux; | ||
With tetraphosphorus decasulfide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dimethyl sulfoxide; potassium hydroxide; In water; for 12h;Reflux; | General procedure: To a solution of xanthone (1 mol equiv) in DMSO, an aqueous solution of 12 N KOH (1.4 mol equiv) is added and the reaction mixture is refluxed in a preheated bath for 12 h. The reaction mixture is then concentrated in vacuo and the residue is treated with ice-water, slowly acidified with concentrated HCl to pH 3 and exhaustively extracted with dichloromethane. The combined extracts are repeatedly washed with water and brine, dried over sodium sulfate, concentrated and the residue is either directly chromatographed (silica, petroleum ether/dichloromethane 6:1) or triturated with an ether/petroleum ether mixture prior to chromatography |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With bromine; acetic acid at 110℃; | |
69% | With bromine; acetic acid for 20h; Reflux; | 10 Synthesis of Compound (17): 9H-xanthen-9-one (5 g, 25 mmol) was dissolved in 50 mL of acetic acid, and 10 mL of Br2 was added dropwise at room temperature and heated to reflux for 20 hours. After that, the mixture was cooled and poured into ice water. The precipitate was washed with saturated solution of NaHCO3, 20% aqueous solution of NaHSO3, and water in sequence. The solid product was dried under vacuum and recrystallized in toluene to give yellow solid 6.1 g with a yield of 69%. Spectral data of compound (17): 1H NMR (400 MHz, CDCl3): δ 8.41 (d, J=1.7 Hz, 2H), 7.79 (d, J=9.0, 1.6 Hz, 2H), 7.38 (dd, J=8.9 Hz, 2H). |
69% | With bromine; acetic acid for 20h; Reflux; | 10 Synthesis of Compound 17 9H-xanthen-9-one (9H-xanthen-9-one) (5g, 25mmol) was dissolved in 50mLOf acetic acid,And 10 mL of Br2 was added dropwise at room temperature.It was further heated to reflux for 20 hours.after that,The mixture was cooled and poured into ice water.Saturated sodium bicarbonate solution,20% aqueous sodium hydrogen sulfite solution,The precipitate is washed with water.Drying the solid crude product under vacuum,And recrystallization in toluene,Yielding 6.1 g of a yellow solid,The yield was 69% |
69% | With bromine; acetic acid at 120℃; Inert atmosphere; | |
52.4% | With bromine; acetic acid Reflux; | 2,7-Dibromoxanthen-9-one (1) Bromination of xanthone was done by the reported method which utilizes the following steps to get the desired product 2,7-Dibromoxanthen-9-one (1). Bromine (10 mL) was added dropwise over 20 min to a solution of xanthone(5 g; 25.5 mmol) in acetic acid (45 mL). The solutionwas stirred continuously and heated at reflux temperature for 20 h, after which half of the solvent was removed by vacuum distillation. The reaction mixture was allowed to cool and then poured over crushed ice toobtain the off-white solid. The resulting solid was filtered and collected and washed with sodium bicarbonate to neutralize the acetic acid and further treated with 20% aqueous solution of sodium bisulfate to remove excess bromine. The obtained solid was then driedunder vacuum and purified using column chromatography(eluent: n-hexane) to afford (6.7 g, 52.4%) pure white crystalline solid desired product (1) M.p.: 211C; Lit. M.p.: 211-212C. |
40% | With bromine; iodine In acetic acid at 100℃; for 24h; | |
With bromine at 180℃; im geschlossenen Rohr; | ||
With bromine; iodine; nitrobenzene bei 20grad oder beim Erhitzen auf 110grad; | ||
With bromine; iodine; acetic acid bei 20grad oder beim Erhitzen auf 110grad; | ||
With bromine; iron(0) | ||
With water monomer; bromine | ||
Multi-step reaction with 2 steps 1: bromine; acetic acid / 4 h / 110 °C 2: bromine; acetic acid | ||
36.4 g | With bromine; iodine; acetic acid at 100℃; for 24h; | 1 Preparation of Compound 3 9H-xanthan-9-one (9H-xanthen-9-one, compound 2, 50 g), a solution of bromine (165 g), iodine (0.5 g) and acetic acid was stirred at 100 °C for 24 h. After cooling to room temperature, the solvent of the filtrate obtained by filtration was removed. This was dissolved again in dichloromethane, sodium bicarbonate solution, sodium thiosulfate solution and water. This was dried with magnesium sulfate, the solvent was removed, and recrystallized from benzene to obtain Compound 3 (36.4 g). |
With bromine; acetic acid at 110℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With trifluoroacetic acid; trifluoroacetic anhydride; at 20℃; for 12h;Inert atmosphere; | General procedure: A 10 mL glass vial with a screw cap was charged with 3-phenoxypropanoic acid 5a (0.75 mmol, 1.0 equiv), TFAA (2.25 mmol, 3 equiv) and TFA (0.8 mL). The reaction mixture was stirred at room temperature for 12 h and monitored by TLC or GC-MS. Upon completion, the solvent was removed under reduced pressure and the residue was subjected to silica gel flash column chromatography (hexanes : AcOEt) to give ketone product 6a. |
17.6 g | In tetrahydrofuran; at 0℃; for 0.5h;Reflux; | In a 150 mL three-neck flask was added 20 g of <strong>[2243-42-7]o-<strong>[2243-42-7]phenoxybenzoic acid</strong></strong> and 80 mL of tetrahydrofuran.Stir mechanically, cool to 0C, add 23 mL of catalyst dropwise, and maintain the temperature at 0C.After the addition is complete, heat to reflux for 30 min, cool to room temperature, add ice water to the reaction solution and extract with dichloromethane. The solvent was rotovapped, a solid precipitated, and recrystallized from a mixture of ethanol and water to give 17.6 g of white crystalline xantone; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: bromobenzene With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 3.5h; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran at -78 - 20℃; for 16h; | 1 Preparation of Compound 1 After adding bromobenzene (60 mmol) and 200 mL of tetrahydrofuran to the reaction vessel,The vessel was cooled to -78 °C under a nitrogen atmosphere.Then n-butyllithium (2.5 M, 60 mmol) was slowly added dropwise to the mixture.After the mixture was stirred at -78 ° C for 30 minutes, it was stirred at room temperature for 3 hours.And cooled to -78 ° C.After that, it will dissolve in 200mLThe xanthone (60 mmol) in tetrahydrofuran was slowly added dropwise to the mixture.After the addition, the reaction temperature was slowly raised to room temperature, and the mixture was stirred for 16 hours.Next, an aqueous ammonium chloride solution is added to the reaction solution to complete the reaction, and acetic acid is used.The ethyl ester extraction reaction solution. The extracted organic layer was then dried using magnesium sulfate, and the solvent was removed using a rotary evaporator. The residue was purified by column chromatography to give Compound 1-1 (13.15 g, yield: 80%, MW: 274.23). |
76.3% | Stage #1: bromobenzene With iodine; magnesium In tetrahydrofuran at 40 - 80℃; for 4h; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran for 15h; Inert atmosphere; Reflux; | 1.a1.1; 1.a1.2 (1) 250mL three-necked flask,In a nitrogen-purged atmosphere,Join 0.05mol raw material U1,0.06molMg powder,Dissolved in 60 ml of dry tetrahydrofuran,Add 0.0004mol elemental I2,Heated to 40 ° C and stirred until the solution changed from yellow to colorless,The above mixed solution was heated to 80 ° C,The reaction was stirred for 4 hours,No magnesium powder remaining, the reaction is complete,Generate format reagent intermediates V1,Without purification, the next step.(2) 250mL three-necked flask,In a nitrogen-purged atmosphere,Join 0.03mol xanthene ketone,Dissolved in 40 ml of dry tetrahydrofuran,Slowly add the above format reagent intermediate V1 solution,Heated to reflux for 15 hours,Generate a lot of white precipitate,Then cooled to room temperature,The addition of saturated NHCl4 converts the salt of form into alcohol;After the reaction was completed, the ether was extracted, dried and swirled through a silica gel column to give a slightly yellow solid tert-butanol intermediate W1. The HPLC purity was 99.5% with a yield of 76.3%. |
76.3% | Stage #1: bromobenzene With iodine; magnesium In tetrahydrofuran at 80℃; for 4h; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran for 15h; Inert atmosphere; Reflux; | 1.a1.1; 1.a1.2 synthesis of intermediate Ml as an example (1) A 250-mL three-necked flask is fed with 0.05 mol of raw material U1 and 0.06 mol of Mg powder in an atmosphere of nitrogen, and dissolved with 60 ml of dry tetrahydrofuran.Add 0.0004π1 to element 12,Heated to 40 ° (stirred until the solution turned from yellow to colorless, the above mixed solution was heated to 80 °C, the reaction was stirred for 4 hours, no magnesium powder remained, and the reaction was complete. Format reagent intermediate VI was produced without purification. Go straight to the next step. (2) 250 mL three-mouth bottle,In a nitrogen atmosphere,Add 0.03mol of tonne ketone,Dissolve in 40 ml of dry tetrahydrofuran, slowly add the above-mentioned reagent Intermediate VI solution, and heat to reflux for 15 hours to generate a large amount of white precipitate, then cool to room temperature and add saturated NHC14 to convert the salt to alcohol; after the reaction is completed, ether is extracted and dried. Swirling, over the silica gel column,Obtained a slightly yellowish solid tertiary alcohol intermediate W1,HPLC purity 99.5%, yield 76.3%. |
74.7% | With magnesium | 9-Phenylxanthen-9-ol (Y=O) (Supplementary Information,S4) Magnesium turnings (0.78 g, 32 mmol), bromobenzene(5.40 g, 34 mmol) and xanthone (5.39 g, 27.5 mmol)afforded 9-hydroxy-9-phenylxanthene (5.12 g, 74.7%) as acream solid, m.p. 160-162 °C (lit., [16] 159 °C); ν(film)/cm-1 3294 (OH) and 1582 (Ar); δH(CDCl3, 400 MHz)/ppm2.67 (s, 1H, OH) and 7.07-7.45 (m, 13H, ArH); δC(CDCl3,400 MHz)/ppm 70.5 (COH), 116.4 (ArC), 123.6 (ArC),126.2 (ArC), 126.8 (ArC), 127.2 (ArC), 128.0 (ArC), 129.0(ArC), 129.1 (ArC), 148.0 (quaternary ArC) and 149.7 (quaternaryArC). |
62% | With magnesium In tetrahydrofuran | 9-Phenylxanthen-9-ol This compound was preparedaccording to a general Grignard addition procedure. Magnesiumturnings (2.4318 g, 0.1001 mol), bromobenzene(15.3602 g, 0.0978 mol) and xanthone (16.0083 g, 0.0816mol) in anhydrous THF yielded a gum which was crystallizedand recrystallized from CH2Cl/petroleum ether toafford 9-phenylxanthen-9-ol (13.8731 g, 62%) as a whitesolid, mp 158-162 °C (lit.,[22] mp 159 °C); vmax (solid)/cm- 1 3548 (OH) and 1600 (Ar C=C); δH(CDCl3)/ppm2.71 (1H, s, OH), 7.09 (2H, t, ArH), 7.23 (3H, d, ArH) and7.30-7.45 (8H, m, ArH); δC(CDCl3)/ppm 70.46 (PhCOH),116.43 (ArC), 123.58 (ArC), 126.25 (ArC), 126.77 (ArC),127.22 (quaternary ArC), 128.00 (ArC), 129.05 (ArC),148.00 (quaternary ArC) and 149.71 (quaternary ArC). |
With magnesium 1)Et2O, 2)Et2O, 2a) reflux, 2 h, 2b) r. t., 2 h; Yield given. Multistep reaction; | ||
Stage #1: bromobenzene With iodine; magnesium In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran at 50℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | In tetrahydrofuran for 0.75h; | |
76.3% | In tetrahydrofuran for 15h; Inert atmosphere; Reflux; | 1.a.2 (2) A 250 mL three-necked flask was charged with 0.03 mol of ketone in an atmosphere of nitrogen gas.Dissolve in 40 ml of dry tetrahydrofuran, slowly add the above reagent intermediate V1 solution,Heating under reflux for 15 hours, a large amount of white precipitate formed, and then cooled to room temperature.Conversion of the format salt to the alcohol by the addition of saturated NHCl4;After the reaction is completed, the ether is extracted, dried and steamed, and passed through a silica gel column.Obtaining a yellowish solid tertiary alcohol intermediate W1,The HPLC purity was 99.5%, and the yield was 76.3%. |
56% | Stage #1: xanth-9-one; phenylmagnesium bromide In tetrahydrofuran at -78 - 20℃; Stage #2: With water; ammonium chloride In tetrahydrofuran |
In tetrahydrofuran at 0 - 50℃; for 12h; Inert atmosphere; | 1 Synthesis of intermediate C-1: The ketone (70 mmol) was dissolved in 100 mL of anhydrous tetrahydrofuran, the reaction solution was cooled to 0 ° C, and the reagent phenylmagnesium bromide (77 mmol) was added dropwise under a nitrogen atmosphere, and the reaction was slowly heated to 50 ° C. 12 hours, a white solid appeared.Use saturated NHCl4Quenching is carried out.It was extracted with diethyl ether, then separated, and the organic phases were combined and concentrated to leave a small solvent.Separation and purification were carried out by column chromatography using petroleum ether and dichloromethane (2:1) as a mobile phase.Compound C-1 (59.5 mmol) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With triphenylphosphine In toluene at 140℃; for 72h; Inert atmosphere; | |
66% | With triphenylphosphine In benzene at 155℃; for 45h; | |
With triphenylphosphine In n-heptane for 48h; Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With cesium fluoride In tetrahydrofuran at 65℃; for 24h; | |
75% | With cesium fluoride In tetrahydrofuran at 65℃; for 24h; | |
With tetrabutyl ammonium fluoride In tetrahydrofuran at 65℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 49% 2: 45% | With tetraazafulvalene In N,N-dimethyl-formamide at 20℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With tert.-butylhydroperoxide; rhodium(III) chloride; triphenylphosphine In chlorobenzene at 160℃; for 24h; Inert atmosphere; | |
89% | With copper; Selectfluor In acetonitrile at 100℃; for 24h; | 1 0.3 mmol of 2-phenoxybenzaldehyde (59.4 mg), 0.03 mmol of Cu powder (1.92 mg), and 0.6 mmol of Selectfluor (212.4 mg) were placed in a 15 mL thick-walled pressure-resistant reaction tube, and then 3 mL of acetonitrile was added as a solvent.Then, magnetic stirring was carried out at 100 ° C for 24 hours.After cooling to room temperature. After completion of the reaction, 10mL of water was added, extracted with dichloromethane (3 * 10mL), the organic phases were combined and dried over anhydrous Na2SO4,After the filtrate was removed by filtration, the filtrate was separated by silica gel column chromatography, eluting with a petroleum ether/ethyl acetate ratio of 20:1 as an eluent, and the eluent containing the product was collected to evaporate the solvent to obtain a xanthone.This material was a white solid with a yield of 89%. |
89% | With water; copper; Selectfluor In acetonitrile at 100℃; for 24h; | 4.3. Typical experimental procedure for the synthesis of xanthones 2 from 1 General procedure: 1 (0.3 mmol), Cu(0) powder (1.92 mg, 10 mol %), Selectfluor (212.6 mg, 0.6 mmol, 2 equiv), and MeCN (water content: 0.05 w/w %, 3 mL) were added to a 25-mL flask. Then the reaction mixture was stirred at 100 °C for 24 h. Upon completion, the resulting mixture was diluted with CH2Cl2 (10 mL) and filtered through Celite. After evaporation of the solvent under vacuum, the residue was purified by column chromatography on silica gel (100-200 mesh) using petroleum ether-EtOAc (20/1, V/V) as eluent to give pure 2. 4.3.1. 9H-xanthen-9-one (2a)[13] Purification by column chromatography (petroleum ether/ EtOAc, 20/1) as a white solid (52.4 mg, 89%); m.p. 180-182 °C (lit. [13]mp179-180 °C); IR (neat): ν = 1654 (C=O) cm-1; 1H NMR (CDCl3, 500 MHz): δ 8.37 (dd, J1 = 8.0 Hz, J2 = 1.5 Hz, 1H), 7.77-7.74 (m, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.41 (t, J = 7.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz): δ 177.3, 156.3, 134.8, 126.8, 123.9, 121.9, 118.0. |
86% | Stage #1: 2-(phenoxy)benzaldehyde With titanium tetrachloride In dichloromethane at 20℃; for 24h; Stage #2: With chromium(VI) oxide; periodic acid In acetonitrile for 1h; | |
65% | With tert.-butylhydroperoxide; tetrabutylammomium bromide In water at 120℃; for 24h; Schlenk technique; Sealed tube; | |
60% | With tert.-butylhydroperoxide; tetrabutylammomium bromide In water at 120℃; Schlenk technique; Sealed tube; | |
60% | With carbon tetrabromide; oxygen In neat (no solvent) at 140℃; for 0.333333h; | |
55% | With tert.-butylhydroperoxide; ferrocene In water; acetonitrile at 20 - 90℃; for 24h; | |
52% | With dipotassium peroxodisulfate; tetraethylammonium bromide In 1,2-dichloro-ethane at 120℃; for 36h; Inert atmosphere; | |
Multi-step reaction with 3 steps 1: MgSO4 / toluene / 100 °C 2: cesium pivalate / Pd(OAc)2; 1,1-bis(diphenylphosphino)methane / dimethylformamide / 24 h / 100 °C 3: aq. HCl / acetone | ||
Multi-step reaction with 3 steps 1: concentrated aqueous KOH / 60 °C 2: thionyl chloride 3: toluene; palladium/barium sulfate / Hydrogenation | ||
Multi-step reaction with 2 steps 1: copper diacetate / toluene / Reflux 2: copper(II) bis(trifluoromethanesulfonate) / toluene / 80 °C | ||
Multi-step reaction with 2 steps 1.1: magnesium sulfate / dichloromethane / 10 h / 20 °C 2.1: [bis(acetoxy)iodo]benzene; boron trifluoride diethyl etherate / 1,2-dichloro-ethane / 26 h / 80 °C 2.2: 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | Stage #1: xanth-9-one; [bis(acetoxy)iodo]benzene With sulfuric acid In acetic anhydride at 0 - 20℃; for 9h; Stage #2: With potassium hexafluorophosphate In water at 20℃; for 2h; | 8 Example 8. Synthesis of 2-(phenyliodonio)xanthene-2-one hexafluorophosphate To 80ml of acetic anhydride were suspended 9.8g (0.05mol) of xanthene-9-one and 16.1g (0.05mol) of iodobenzene diacetate, and 10g (0.1mol) of concentrated sulfuric acid was added dropwise thereto at 0 to 7°C for 1 hour, followed by gradually warming to room temperature and reacting with stirring for 8 hours. After completion of the reaction, the reaction solution was poured in 200ml of ice water, and 150ml of toluene was added thereto to dissolve insoluble substance and fractionation. Then 18.4g (0.1mol) of potassium hexafluorophosphate was added to water layer and stirred at room temperature for 2 hours. The precipitated crystal was filtered off, followed by drying under vacuum at 50°C for 2 hours to obtain 16.1g of objective substance as pale yellow crystal (yield: 59%). m.p.: 222°C (decomposition) 1H NMR (CDCl3) δppm: 7.51-7.58(3H, m, Ar-H), 7.69(2H, t, Ar-H), 7.83(1H, d, Ar-H), 7.93(1H, t, Ar-H), 8.20(1H. d, Ar-H), 8.36(2H, d, Ar-H), 8.62(1H, d, Ar-H), 9.05(1H, s, Ar-H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | Stage #1: xanth-9-one; [bis(acetoxy)iodo]benzene With sulfuric acid In acetic anhydride at 0 - 20℃; for 9h; Stage #2: With potassium tetrafluoroborate In water at 20℃; for 2h; | 6 Comparative Example 6. Synthesis of 2-(phenyliodonio)xanthene-9-one tetrafluoroborate To 80ml of acetic anhydride were suspended 9.8g (0.05mol) of xanthene-9-one and 16.1g (0.05mol) of iodobenzene diacetate, and 10g (0.1mol) of concentrated sulfuric acid was added dropwise thereto at 0 to 7°C for 1 hour, followed by gradually warming to room temperature and reacting with stirring for 8 hours. After completion of the reaction, the obtained reaction solution was poured into 200ml of ice water, and 150ml of toluene was added thereto to dissolve insoluble substance. The solution was fractionated and 12.6g (0.1mol) of potassium tetrafluoroborate was added to the obtained water layer, followed by stirring at room temperature for 2 hours. The precipitated crystal was filtered off and dried at 50°C under vacuum for 2 hours to obtain 11.4g of 2-(phenyliodonio)xanthene-9-one tetrafluoroborate as pale orange crystal (yield: 47%). m.p.: 229-231°C (decomposition) 1H NMR (CDCl3) δppm: 7.51-7.56 (3H, Q, Ar-H), 7.66-7.73 (2H, m, Ar-H), 7.83(1H, d, Ar-H), 7.93(1H, t, Ar-H), 8.20 (1H, d, Ar-H), 8.36(2H, d, Ar-H), 8.62(1H, d, Ar-H), 9.06(1H, s, Ar-H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | Stage #1: xanth-9-one With N-iodo-succinimide; trifluoroacetic acid In dichloromethane at 0℃; for 10h; Stage #2: With sodium thiosulfate In dichloromethane; water; trifluoroacetic acid | 52.52A A solution of xanthen-9-one (1.96 g, 10.0 mmol; Aldrich) in trifluoroacetic acid-CH2Cl2 (1:1, 40 mL) was chilled to 0° C. and treated with N-iodosuccinimide (NIS; 2.25 g, 10.0 mmol; Lancaster), added portionwise over 1 h. After an additional 1 h at 0° C., the ice bath was removed and stirring continued for 8 h. Residual oxidant was quenched with aq. NaS2O3 and the mixture was extracted with CH2Cl2. The organic phase was washed with NaHCO3, dried over MgSO4, and the residue purified by flash chromatography (120 g silica gel, 10-100% CH2Cl2-hexanes) to afford the title compound (1.75 g, 5.43 mmol; 54% yield): 1H NMR (300 MHz, CDCl3) δ ppm 8.66 (d, J=2 Hz, 1H), 8.34 (dd, J=8, 2 Hz, 1H), 7.98 (dd, J=9, 2 Hz, 1H), 7.75 (ddd, J=9, 7, 2 Hz, 1H), 7.50 (dd, J=8, 1 Hz, 1H), 7.40 (ddd, J=8, 7, 1 Hz, 1H), 7.28 (d, J=9 Hz, 1H); MS (DCl/NH3) m/z 323 (M+H)+, 340 (M+NH4)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxygen; ozone; In water; for 0.25 - 2h; | Example A; Degradation of pyrene; This example focuses on an integrated approach for the degradation of pyrene involving chemical oxidation followed by biological treatment. The objectives were to: 1) provide mechanistic details in the degradation of pyrene subject to ozone treatment, 2) test the combined technique of ozone pretreatment followed by biological degradation, and 3) test a pretreatment column to promote efficient use of chemical oxidants and biodegradability. Batch and packed column reactors were used to examine the degradation pathways of pyrene subject to ozonation in the aqueous phase. After different ozonation times, samples containing reaction intermediates and byproducts from both reactors were collected, identified for organic contents, and further biologically inoculated to determine biodegradability. The O3-pretreated samples were incubated for 5, 10, 15, and 20 days, after which biochemical oxygen demand (BOD), chemical oxygen demand (COD), and toxicity tests along with qualitative and quantitative GC/FID and GC/MS analyses of pyrene, intermediates, and products were performed. Intermediates identified at different stages included 4,5-phenanthrenedialdehyde, 2,2',6,6'-biphenyltetraaldehyde, and long-chain aliphatic hydrocarbons, which suggested that the degradation of pyrene was initiated by O3 via ring cleavage at the 4,5- and 9,10-bonds and that further oxidation ensued via reactions with both O3 and OH. until complete mineralization. Intermediates formed during chemical oxidation were biodegradable with a measured first-order rate constant (k0) of 0.243 day-. The integrated chemical-biological system appeared to be feasible for treating recalcitrant compounds, and a chemical pretreatment column was particularly useful in promoting soluble intermediates from otherwise highly insoluble, inaccessible pyrene.Materials and MethodsChemicalsOzone (1% w/w ozone in air) was generated from filtered, dry air by an ozonator (Model T-816, Polymetrics Corp.). Pyrene (99%, Aldrich Chemical Co.) was washed with distilled-deionized (DD) water three times, extracted by dichloromethane (DCM), and the solvent evaporated by a gentle stream of nitrogen gas. Stock and working indigo blue solutions were prepared from potassium indigo trisulfonate (C16H7N2O11S3K3, Aldrich Co.) per Standard Methods (APHA et al., 1992a). Polyseed (Hach Co.) was used in dilution water for biochemical oxygen demand (BOD) measurements per Standard Methods (APHA et al., 1992b). Inoculum for toxicity test was prepared according to a Hach method (HACH, 1988-1995b). COD digestion solutions (0-15,000 mg/L, 0-40 mg/L range, Hach Co.), ToxTrak reagent powder pillows, and ToxTrak accelerator solution (Hach Co.) were purchased and used according to the manufacturer's methods without further processing. Low-organic (<15 ppb as TOC), low-ion (resistivity>18 MOmega-cm), and non-pyrogenic (up to 4-log reduction with reverse osmosis pretreatment) DD water was used in all procedures (4-stage Mill-Q Plus system, Millipore Co.). Dichloromethane (Fisher Scientific) of HPLC grade was used in liquid-liquid extraction procedures. Other chemicals used in this research were of reagent grade.; Results and Discussion; Ozonation of pyrene was carried out in batch and column reactors to study: 1) the effect of reactor on intermediates and products formation, 2) the degradation pathway of pyrene under ozonation, 3) the biodegradability of intermediates, and 4) the feasibility of a combined chemical-biological treatment system for pyrene. Reaction solutions during ozonation and biodegradation processes at different stages were collected and the intermediates and byproducts identified by GC/MS techniques.1. Effects of the Reactor Type on Intermediates and Products FormationTo delineate the influence of reactor configurations on the formation of intermediates and products, ozonation experiments using aqueous and excess pyrene were carried out in batch and packed column reactors. BOD5 and COD were measured for three ozonated, filtered solutions: 1) a saturated aqueous solution of pyrene (0.13 ppm), 2) the solution after ozonation of an excess pyrene suspension (1 g/1.7 L), and 3) the effluent of a column packed with excess pyrene solid (1 g) and glass beads (7.5 in. in bed-length). The saturated pyrene solution was prepared by allowing excess pyrene solid to reach dissolution equilibrium in water overnight followed by removal of the excess solid using a 0.45-mum filter. The ozonated batch solution was obtained after 10 min of ozonation and filtered, while the effluent was collected from the packed column fed with ozonated water over a 4-hr period. Table A-I shows the results of BOD5 and COD measurements. The BOD5 for the saturated pyrene solution approximates over 80% of the COD value, suggesting that pyrene in its dissolved form is amenable to biodegradation, albeit in small quantity. The aqueous phase COD from the ozonated batch reactor increased after ozon... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate In N,N-dimethyl-formamide at 150℃; for 0.5h; Microwave irradiation; Green chemistry; | One-Step Synthesis of Xanthones; General Procedure General procedure: Salicylaldehydes (1 mmol), 1,2-dihaloarenes (2 mmol), K2CO3 (2 mmol), PdNPs/BC (3 mol%), and anhydrous DMF (5 mL) were added to a vessel tube with a magnetic stirring bar. The resulting mixture was heated at 150 °C under microwave irradiation (250 W) for 30 min. The progress of the reaction was monitored by TLC and GC-MS. The crude product was treated with EtOAc. The catalyst was recovered by filtration and washed several times with the same solvent. The filtrate was washed twice with brine and then dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the desired xanthone was purified by column chromatography using silica gel 60 as adsorbent. |
61% | With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In N,N-dimethyl-formamide at 130℃; for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
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80% | With cesium fluoride In tetrahydrofuran at 125℃; | |
80% | With cesium fluoride In tetrahydrofuran at 125℃; for 24h; | 4.2 General procedure for the reaction of carboxylic acids with arynes General procedure: The aryne precursor (1.5 equiv) was added to a mixture of carboxylic acid (0.25 mmol) and CsF (4.0 equiv) in 15 mL of freshly distilled THF, and the reaction mixture was then stirred in a closed vial at 125 °C for 18 h. After the reaction mixture was allowed to cool to room temperature, it was eluted through a plug of silica gel with ethyl acetate and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel using hexanes/EtOAc as the eluent to afford the desired o-hydroxyaryl ketone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With copper(II) bis(trifluoromethanesulfonate) In toluene at 80℃; | 21 Typical procedure for Cu(OTf)2 catalyzed synthesis of 9-aminofluorene derivatives: a dried schenk tube was charged with 1a (33.5 mg, 0.1 mmol), and toluene 2 mL. Cu(OTf)2 (10 mol %) was then added to the mixture and the solution was stirred at 80 °C overnight. The progress of the reaction was monitored by TLC (EtOAc/petroleum ether = 1:7). Upon completion, the solution was concentrated under reduced pressure and the mixture was purified by flash column chromatography (pure petroleum ether, then ethyl acetate/petroleum ether = 1:7) to obtain the product 2a. Yield: 99% (see Table 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41%; 25% | With bromine; iodine; acetic acid; at 100℃; for 5h;Inert atmosphere; | Example 1Synthesis of Example Compound A-7[0143][Chem. 19]C6H5Me/EtOH/Na2C03a<7. A - 7[0144] To a 100 mL round-bottomed flask, the following reagents and solvents were placed.Xanthone : 5.0 g (26 mmol)Bromine: 16 g (102 mmol)Iodine: 50 mg (0.20 mmol)Acetic acid: 20 mL[0145] The resulting reaction solution was refluxed for 5 hours at 100 C under heating and stirring in nitrogen. Upon completion of the reaction, chloroform and a saturated aqueous sodium sulfite solution were added to the reaction solution and stirring was continued until the color of bromine was lost. The organic layer was separated, washed with a saturated aqueous sodium carbonate solution, dried with magnesium sulfate, and filtered. The solvent in the filtrate was distilled away at a reduced pressure. The precipitated solid was purified with a silica gel column (toluene: 100%). As a result, 2.9 g (yield: 41%) of 2- bromoxanthone and 2.2 g (yield: 25%) of 2 , 7-dibromoxanthone were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 78% 2: 15% | With trifluorormethanesulfonic acid; oxygen In ethyl acetate at 20℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: xanth-9-one With thionyl chloride In N,N-dimethyl-formamide Reflux; Stage #2: diisopropyl malonate at 120℃; for 1h; | 13 A conjugated fused tricyclic molecule according to Formula II(f)(2) may be synthesized as follows: Xanthone (49 g, 0.25 mol) and DMF (1.5 mL) was refluxed with SOCl2 (250 mL), and then the excess SOCl2 was distilled. Excess diisopropyl malonate (70 mL, 0.37 mol) was added to the mixture. Then the mixture was stirred at 120° C. for 1 h. The reaction mixture was cooled and added to 1 M NaOH (200 mL) ice water. The red solid was filtered and washed with water. The crude product was purified by recrystallization with ethanol (200 mL). The yield of the final product was 70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With tetrakis[tris(dimethylamino)phosphoranylideneamino]phosphonium chloride; cesium fluoride In o-xylene at 150℃; for 24h; | 2. Carboxylation of aryltrimethylsilanes with CO2 Representative procedure for carboxylation of 2-trimethylsilylthiophene (1a) with CO2 (Table 1, entry2) General procedure: A dried and CO2 (balloon) infused sealed tube, equipped with a magnetic stirrer and a septum, was chargedwith P5Cl (7.8 mg, 0.01 mmol) and CsF (30.4 mg, 0.2 mmol) in o-xylene (0.3 mL). 2-Trimethylsilylthiophene(1a) (15.6 mg, 0.1 mmol) was added to a reaction mixture and the reaction was stirred at 100°C under closed system for 24 h. The reaction mixture was diluted with water (30 mL) and extracted with CH2Cl2 (2 × 10 mL).The aqueous layer was acidified (> pH 1) with aqueous HCl (6 M) at 0°C and then extracted with diethylether (4 × 20 mL). The combined organic layers were dried over Na2SO4. The solvent was removed under vacuum to afford 2a (11.4 mg, 89%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: 2-phenoxyaniline With hydrogenchloride; sodium nitrite In water at -5℃; for 0.25h; Stage #2: With sodium tetrafluoroborate In water Stage #3: carbon monoxide With tetrakis(triphenylphosphine) palladium(0); tetrabutylammomium bromide; potassium carbonate In toluene at 80℃; for 10h; Autoclave; | 9H-xanthen-9-one 2a General procedure: General procedure for the preparation of xanthones from the ortho diazonium salts of diphenylethers using Pd(PPh3)4: An autoclave was charged with the diazonium salts of diaryl ethers (0.5mmol), toluene (5 mL), Pd(PPh3)4 (28 mg, 0.025 mmol) and K2CO3 (69 mg, 0.5 mmol) and catalyticTBAB (16 mg, 0.05 mmol), and the atmosphere was purged with carbon monoxide. The mixturewas stirred at 80°C for 10 hours under a carbon monoxide atmosphere (0.2 MPa). Aftercompletion, the metal precipitate was filtered; the filtrate was diluted with ethyl acetate andwater. The aqueous phase was extracted with ethyl acetate twice and the combined organicphases were washed with brine and dried over MgSO4. Then solvent was evaporated undervacuum and the crude product was purified by column chromatography on silica gel, eluting witha mixture of petroleum ether and ethyl acetate to give xanthones. Yields are listed in Table 2.9H-xanthen-9-one 2a |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8 g | To a vacuum dried 250 ml three-neck round bottom flask was added compound 9-1 (16 g),Anhydrous tetrahydrofuran (120 ml) was added and stirred under argon atmosphereThe temperature of the mixture was lowered to -78.Butyllithium (56.75 ml) was added slowly and stirred at the same temperature for 1 hour.Xanthone (15.18 g) was added at the same temperature and stirred for 12 hours.After concentration under reduced pressure, the residue was extracted with chloroform (320 ml) to obtain 8 g of the title compound. | |
8 g | In a vacuum-dried 250 mL three-neck round bottom flask, 120 mL of anhydrous tetrahydrofuran was added to 16 g of Compound 9-1, stirred under argon atmosphere, and the temperature of the mixture was lowered to -78 C. 56.75 mL of butyllithium was added slowly and stirred at the same temperature for 1 hour. 15.18 g of xanthone was added at the same temperature and stirred for 12 hours. After concentration under reduced pressure, the mixture was extracted with chloroform (320 mL) to obtain 8 g of the title compound. | |
To obtain the D1-DPS, compound 1a of the -OH formationreaction, and compound 2 of the cyclization reactionwere synthesized. Compound 1 (3 g, 12 mmol) was dissolvedin 50 ml of anhydrous tetrahydrofuran (THF) underhigh purity argon in a one neck round bottom flask. It wascooled to -78 C using solid carbon with acetone and then n-butyllithuim (2.5 M in cyclohexane, 24.7 mmol)was added dropwise slowly. Stirring was continued for 1 h before, cooling for 20-30 min. Then a solution of9-fluorenone (2.4 g, 13.3 mmol) in THF was added at-78 C under an argon atmosphere. The mixture wasstirred for 3 h in the same environment. The reaction was completed after the confirmation of compound 1a. Two side products and reactants appeared by TLC with a solutionof hexane and ethyl acetate (10:1). Additional quenching was not required. The mixture was then worked up using water and dichloromethane. The extracted organiclayer was dried by anhydrous MgSO4. For compound 2, compound 1a was placed in a oneneckround bottom flask, to which, chloroform (10 ml)and methane sulfonic acid (MSA, 5 ml) were added whilestirring at room temperature for 15 min. The progress ofthe reaction was monitored by TLC with a solution of hexane and ethyl acetate (5:1). The resulting mixture wasquenched by saturated aqueous NaHCO3 and extractedwith dichloromethane after the reaction completed. Th esolid product was recrystallized using chloroform and hexane.A slightly yellow solid product was obtained, whichwas then purified by column chromatography with hexane and ethyl acetate.Two intermediates, the DPS acceptor and the compound 2 donor, were reacted for D1-DPS by theBuchwald-Hartwig amination. Compound 2 (0.5 g,1.38 mmol), DPS (0.48 g, 1.38 mmol), pd(dba)2 (0.008 g,0.014 mmol), t-BuONa (0.27 g, 2.77 mmol), and triphenylphosphine(0.003 g, 0.011 mmol) showed high purityAr charging. Then toluene (20 ml) was added and refluxedfor 5 h at 115 C. Quenching was not required. The resultingmixture was worked up using ethyl acetate and water.A small amount of water in the extracted organic layerwas removed by MgSO4 and filtered with celite to removethe inorganic materials. Finally, column chromatographywas applied with hexane and dichloromethane.The white solid product was recrystallized byhexane. |
8 g | Synthesis of Intermediate 9-2Anhydrous tetrahydrofuran (120 mL) was added to compound 9-1 (16 g) in a vacuum dried 250 mL three-necked round bottom flask, and the mixture was stirred in an argon atmosphere and the temperature of the mixed solution was lowered to -78 C. Butyl lithium (56.75 mL) was added slowly and stirred at the same temperature for 1 hour. Add Santon (15.18 g) at the same temperature and stir for 12 hours. Concentrated under reduced pressure and extracted with chloroform (320 mL) to give 8 g of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 53% 2: 20% | Stage #1: 1-(4-methoxybenzyloxy)-1,2-dihydroxanthen-9-one With osmium(VIII) oxide; 4-methylmorpholine 4-oxide monohydrate In water; acetone; <i>tert</i>-butyl alcohol at 20℃; for 48h; Inert atmosphere; Stage #2: With sodium metabisulfite In water; acetone; <i>tert</i>-butyl alcohol for 1h; Inert atmosphere; | 4.11 (1R*,3S*,4S*)-1-(4-Methoxybenzyloxy)-1,2,3,4-tetrahydro-3,4-dihydroxyxanthene-9-one (16) To a stirred solution of 15 (1.20g, 3.61mmol) in a mixture of acetone (6mL), H2O (6mL) and tBuOH (2.4mL) at room temperature was added N-methylmorpholine-N-oxide monohydrate (583mg, 4.33mmol) and OsO4 (20μL, 0.02g/mL in tBuOH). The reaction mixture was stirred for 48h, and then treated with sodium metabisulfite (820mg, 4.31mmol). The reaction mixture was stirred for 1h then extracted with EtOAc (3×30mL). The combined organic extracts were washed with 1M HCl (20mL), H2O (3×30mL), brine (3×15mL), dried over MgSO4, filtered and the solvent removed in vacuo. Column chromatography (40% EtOAc in petroleum ether) gave 16 (648mg, 53%) as a yellow solid. Mp 129-131°C; IR (film) 2967, 1608, 1462, 1248, 1095, 755cm-1; δH (300MHz CDCl3) 8.22 (1H, dd, J=1.7, 8.0Hz, ArH), 7.72-7.66 (1H, m, ArH), 7.57 (1H, dd, J=0.8, 8.4Hz), 7.45-7.38 (1H, m, ArH), 7.34-7.26 (2H, m, ArH), 6.89-6.83 (2H, m, ArH), 5.13-5.08 (1H, m, CHOPMB), 4.76 (1H, d, J=10.7Hz, CH2O), 4.72 (1H, d, J=10.7Hz, CH2O), 4.65 (1H, d, J=9.0Hz, OH), 4.58-4.50 (1H, m, CHOH), 4.35-4.26 (1H, m, CHOH), 3.78 (3H, s, OCH3), 3.48 (1H, d, J=10.1Hz, OH), 2.67-2.58 (1H, m, CH2), 1.91-1.81 (1H, m, CH2); δC (125MHz) 176.8 (C), 162.9 (C), 159.5 (C), 156.4 (C), 134.1 (CH), 129.9 (CH), 129.6 (C), 125.9 (CH), 125.3 (CH), 123.5 (C), 118.3 (CH), 118.2 (C), 113.9 (CH), 73.1 (CH2), 69.1 (CH), 68.9 (CH), 67.8 (CH), 55.3 (OCH3), 30.8 (CH2); MS (ES+) m/z 391 ([M+Na]+); HRMS (ES+): calcd for C21H20O6Na [M+Na+]: 391.1152; found: 391.1155. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With palladium diacetate; potassium carbonate; catacxium A In N,N-dimethyl-formamide at 120℃; for 12h; Schlenk technique; Inert atmosphere; | General procedure for the synthesis of xanthone General procedure: To an oven-dried 25 mL Schlenk tube containing a stirring bar was added 4.5 mg Pd(OAc)2 (0.02 mmol), 15.7mg nBuPAd2 (0.44 mmol), 2-bromofluorobenzene (0.50 mmol), salicylaldehyde (0.50 mmol), potassium carbonate (1.0 mmol). The Schlenk tube was vacuumed and then purged with argon before DMF (2.0 mL) was injected using a syringe. Afterwards the Schlenk tube in the ice bath was degassed by evacuation and back fillingwith argon three times. The reaction mixture was then stirred for 12 h at 120 °C. After the reaction was complete,the reaction mixture was diluted with water (5 mL), extracted with ethyl acetate (3 x 10 mL) and dried withanhydrous Na2SO4. After filtration and addition of silica gel into the solution, the organic solvent was reduced evaporated. The crude product was purified by column chromatography using ethyl acetate/n-pentane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With palladium diacetate; potassium carbonate; catacxium A In N,N-dimethyl-formamide at 120℃; for 12h; Schlenk technique; Inert atmosphere; | General procedure for the synthesis of xanthone General procedure: To an oven-dried 25 mL Schlenk tube containing a stirring bar was added 4.5 mg Pd(OAc)2 (0.02 mmol), 15.7mg nBuPAd2 (0.44 mmol), 2-bromofluorobenzene (0.50 mmol), salicylaldehyde (0.50 mmol), potassium carbonate (1.0 mmol). The Schlenk tube was vacuumed and then purged with argon before DMF (2.0 mL) was injected using a syringe. Afterwards the Schlenk tube in the ice bath was degassed by evacuation and back fillingwith argon three times. The reaction mixture was then stirred for 12 h at 120 °C. After the reaction was complete,the reaction mixture was diluted with water (5 mL), extracted with ethyl acetate (3 x 10 mL) and dried withanhydrous Na2SO4. After filtration and addition of silica gel into the solution, the organic solvent was reduced evaporated. The crude product was purified by column chromatography using ethyl acetate/n-pentane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | Stage #1: xanth-9-one; trifluoromethan With tris(trimethylsilyl)amine; phosphazene base-P4-tert-butyl In tetrahydrofuran at 20℃; for 14h; Schlenk technique; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 1h; Schlenk technique; | 12 Example 1 Preparation of 2,2,2-trifluoro-1,1-diphenylethanol (3) A solution of benzophenone (36.4 mg, 0.20 mmol), tris (trimethylsilyl) amine (70.1 mg, 0.30 mmol, 1.5 equiv.) In THF (0.25 ml) was added to a Schlenk tube equipped with a stirrer at room temperature And P4-tBu base(50.0 μL, 0.040 mmol, 0.20 equiv.) Were charged, then trifluoromethane was bubbled through for 1 minute, and the reaction was carried out at the same temperature for 6 hours. After completion of the reaction, a saturated ammonium chloride aqueous solution was added. The mixture was extracted with methylene chloride, and the collected organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and 2 mL of tetrahydrofuran and tetrabutylammonium fluoride (62.6 mg, 0.24 mmol, 1.2 equiv.) (Hereinafter abbreviated as TBAF) were added and stirred at room temperature for 1 hour . Thereafter, the solvent was distilled off under reduced pressure, and the obtained crude product was purified by silica gel column chromatographyTo obtain 2,2,2-trifluoro-1,1-diphenylethanol (3) as a target product in a yield of 84%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With tetrabutylammonium perchlorate; triethylamine In tetrahydrofuran at 25℃; Electrochemical reaction; Inert atmosphere; | 4.2. Typical procedure of electroreductive coupling of 1 with 2 General procedure: A 0.3 M solution of Bu4NClO4 in THF (15 mL) was placed in the cathodic chamber of a divided cell (40 mL beaker, 3 cm diameter, 6 cm height) equipped with a platinum cathode (5 5 cm2 ), a platinum anode (2 1 cm2), and a ceramic cylindrical diaphragm (1.5 cm diameter). A 0.3 M solution of Et4NOTs in DMF (4 mL) was placed in the anodic chamber (inside the diaphragm). Benzophenone (1a) (182 mg, 1.0 mmol), methyl acrylate (2a) (0.45 mL, 5.0 mmol), TMSCl (0.64 mL, 5.0 mmol), and TEA (0.70 mL, 5.0 mmol) were added to the cathodic chamber. After 300 C (3 F/mol for 1a) of electricity was passed at a constant current of200 mA at 25 C under nitrogen atmosphere, the catholyte was evaporated in vacuo. The residue was dissolved in diethyl ether (20 mL) and insoluble solid was filtered off. After removal of the solvent in vacuo, the residue was purified by column chromatography on silica gel (hexanes-EtOAc) to give 3a (325 mg) in 95% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; ethanol at 10 - 40℃; for 1h; | 1 Into a 1000 mL four-necked flask equipped with a stirrer, thermometer and condenser, 19.6 g (0.1 mol, Tokyo Kasei Kogyo) of xanthone, 19.5 g p-toluenesulfonylmethylisocyanide (hereinafter referred to as TosMIC and Sometimes abbreviated, 0.13 mol), 320 mL of 1,2-dimethoxyethane (Wako Special grade, organic solvent (1)),10 mL of ethanol (Wako Special grade, organic solvent (2)) was added and cooled to 10 ° C. or lower in an ice bath. Thereto was added 28 g (0.24 mol, potassium tert-butoxide) of potassium t-butoxide at 10 ° C. or lower, then the ice bath was removed and the mixture was stirred for 30 minutes. And further stirred at 35 to 40 ° C. for 30 minutes. Thereafter, the solution was cooled to 25 ° C., the precipitated potassium p-toluenesulfonate was filtered off, and the salt was washed twice with 20 mL of 1,2-dimethoxyethane (Wako Special Grade). 1,2-Dimethoxyethane was combined and evaporated to dryness. The resultant crude 9-cyanoxanthene was dissolved in 50 mL of heptane (Wako Special grade) and purified with this crude silica gel column chromatography (Wako Gel C-300) to remove the solvent,18.7 g (yield: 90%) of 9-cyanoxanthene was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With magnesium In tetrahydrofuran at 60℃; for 28h; Inert atmosphere; | 1 250ml of four bottles, in the atmosphere of nitrogen,7.9 g of 3-bromopyridine (0.05 mol) and1.44 g Mg powder (0.06 mol),60 ml of tetrahydrofuran,Heated to reflux for 4 hours,The reaction is complete, the formation of reagents;9.8 g of tung ketone (0.05 mol) was dissolved in 50 ml of tetrahydrofuran,The above format reagent was added dropwise,60 ° C for 24 hours,Generate a lot of white precipitate,Finally, saturated NHCl4 was added to convert the format salt to alcohol;After completion of the reaction, the ether was extracted, dried and steamed, and the petroleum ether: dichloromethane mixed solvent (3: 2)A slightly yellow compound C (yield 81%) was obtained; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: 1.4-dibromobenzene With magnesium In tetrahydrofuran for 4h; Reflux; Stage #2: xanth-9-one In tetrahydrofuran at 60℃; for 24h; | 1 Example 1 Synthesis of Compound 1 250 ml of a four-necked flask was charged with 11.8 g of 1,4-dibromobenzene (0.05 mol) and1.44 g Mg powder (0.06 mil), 60 ml of tetrahydrofuran, heated under reflux for 4 hours, the reaction was complete, and the format reagent was generated;9.8g xanthone (0.05 mol)Was dissolved in 50 ml of tetrahydrofuran, and the above-mentioned format reagent was added dropwise, 60 ° C for 24 hours,(3: 2) silica gel column, and then the mixture was extracted with ethyl acetate, and the mixture was extracted with distilled water and petroleum ether: dichloromethane mixed solvent (3: 2)To give a slightly yellow compound C (yield 90%); |
90% | Stage #1: 1.4-dibromobenzene With magnesium In tetrahydrofuran for 4h; Reflux; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran at 60℃; for 24h; Inert atmosphere; | 4 Example 4: Synthesis of intermediate A1: 250ml four-necked bottle, under a nitrogen atmosphere,Add 11.8g 1,4-dibromobenzene (0.05mol) and 1.2g Mg powder (0.05mol), 60ml tetrahydrofuran, heat and reflux for 4 hours, the reaction is complete, and the format reagent is generated;9.81g of xanthone (0.05mol) is dissolved in 50mL of tetrahydrofuran,The reagents in the above format are added dropwise and reacted at 60 ° C for 24 hours to generate a large amount of white format salt precipitates.Saturated NHCl4 solution was added until the precipitation disappeared and the salt was converted to tertiary alcohol;After the reaction is completed, extract with 100ml of ether,The extract is dried over anhydrous sodium sulfate, and the solution is spin-evaporated to remove the solvent to no fraction.A crude tertiary alcohol product was obtained. The crude tertiary alcohol product was purified through a neutral silica gel column using a mixed solvent of petroleum ether and dichloromethane (volume ratio 3: 2) as the eluent.A slightly yellow solid tertiary alcohol was obtained (yield 90%); |
Stage #1: 1.4-dibromobenzene With magnesium In tetrahydrofuran for 4h; Inert atmosphere; Reflux; Stage #2: xanth-9-one In tetrahydrofuran at 60℃; for 24h; Inert atmosphere; | 1 250ml of four bottles, in the atmosphere of nitrogen,11.8 g of 1,4-dibromobenzene (0.05 mol) was added1.33 g Mg powder (0.055 mol),60 ml of tetrahydrofuran, heated under reflux for 4 hours,The reaction is complete, generating the format reagent;10.8 g of t-ketone (0.05 mol) was dissolved in 50 ml of tetrahydrofuran,The above format reagent was added dropwise,60 ° C for 24 hours,Generate a lot of white precipitate,Finally, saturated NHCl4 was added to convert the format salt to alcohol;After completion of the reaction, ether extraction, drying steaming,Petroleum ether: dichloromethane mixed solvent (3: 2) silica gel column,Slightly yellow solid was obtained tertiary alcohol (85% yield); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 43% 2: 5% | Stage #1: xanth-9-one With 2,2,6,6-tetramethyl-piperidine; n-butyllithium; zinc dichloro(N,N,N′,N′-tetramethylethylenediamine) In tetrahydrofuran; hexane at 0℃; for 2h; Inert atmosphere; Stage #2: With iodine In tetrahydrofuran; hexane Inert atmosphere; | 1-Iodo-9-xanthone (1b) and 1,8-Diiodo-9-xanthone (1b′); TypicalProcedure To a stirred, cooled (0 °C) solution of 2,2,6,6-tetramethylpiperidine (0.25 mL, 1.5 mmol) in THF (2-3 mL) were successively added ca. 1.6M BuLi in hexanes (1.5 mmol) and, after 5 min, ZnCl2·TMEDA35 (0.13g, 0.50 mmol). The mixture was stirred for 15 min at 0 °C before introduction of xanthone (1a, 0.20 g, 1.0 mmol). After 2 h at this temperature, a solution of I2 (0.38 g, 1.5 mmol) in THF (4 mL) was added. The mixture was stirred overnight before the addition of aq sat. Na2S2O3 soln (4 mL). The mixture was extracted with EtOAc (3 × 20 mL) and the combined organic layers were dried (MgSO4), filtered, and concentrated under reduced pressure. Purification by chromatography (silica gel, heptane/CH2Cl2 100:0 to 80:20) afforded the products. 1-Iodo-9-xanthone (1b) Pale yellow powder; yield: 0.14 g (43%) ; mp 176 °C (Lit.36 172-173.5°C).IR (ATR): 663, 752, 777, 849, 903, 931, 1108, 1147, 1161, 1234, 1255,1297, 1328, 1346, 1421, 1443, 1466, 1554, 1590, 1612, 1661, 3065cm-1.1H NMR (CDCl3): δ = 7.27 (dd, J = 8.4, 7.8 Hz, 1 H), 7.36 (ddd, J = 8.1,7.2, 0.9 Hz, 1 H), 7.41 (dm, J = 9.0 Hz, 1 H), 7.48 (dd, J = 8.4, 1.2 Hz, 1H), 7.70 (ddd, J = 8.7, 7.2, 1.8 Hz, 1 H), 8.00 (dd, J = 7.6, 1.1 Hz, 1 H),8.31 (ddd, J = 8.1, 1.8, 0.5 Hz, 1 H).13C NMR (CDCl3): δ = 91.3 (C), 117.7 (CH), 119.1 (CH), 120.1 (C), 121.3(C), 124.3 (CH), 127.3 (CH), 134.7 (CH), 135.0 (CH), 138.6 (CH), 154.9(C), 156.8 (C), 175.4 (C).These data are similar to those reported previously.361,8-Diiodo-9-xanthone (1b′) Yellow powder; yield: 22 mg (5%); mp 252 °C.IR (ATR): 658, 777, 804, 868, 906, 1159, 1276, 1354, 1448, 1578, 1659,2927 cm-1.1H NMR (CDCl3): δ = 7.26 (dd, J = 8.1, 7.8 Hz, 2 H), 7.42 (dd, J = 8.3, 1.1Hz, 2 H), 8.01 (dd, J = 7.5, 1.2 Hz, 2 H).13C NMR (CDCl3): δ = 92.1 (C), 118.7 (CH), 120.3 (C), 124.8 (C), 134.6(CH), 138.9 (CH), 155.6 (C). Crystal data for 1b′: 2(C13H6I2O2), M = 895.96, triclinic, P -1, a =8.2003(2), b = 10.2204(2), c = 15.1904(3) Å, α = 86.8230(10), β =74.5930(10), γ = 75.9650(10)°, V = 1190.67(4) Å3, Z = 2, d = 2.499 g cm-3, μ = 5.267 mm-1. A final refinement on F2 with 5418 unique intensitiesand 307 parameters converged at ωR(F2) = 0.0725 (R(F) =0.0402) for 4325 observed reflections with I > 2σ(I). CCDC 1544822. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With N,N,N',N'',N'''-pentamethyldiethylenetriamine; copper; copper(I) bromide In toluene at 65℃; for 48h; Inert atmosphere; | 5.2 The second step coupling reaction reaction steps: 1st step will be to make the resultant of 9 H - xanthene -9 - thione with 2 - methyl butyrate [...], Cu powder/CuBr, PMDETA in accordance with the molar ratio of 1:2: 2:2 uniformly mixed, using toluene as the solvent is placed in the branch pipe flask, nitrogen atmosphere sealing thaw 3 degas. Then in the 65 °C oil bath reaction 48 h. After the reaction taken out, alumina column chromatography out metal and salt, silica gel column chromatography to remove organic impurities, there will be phase turns on lathe does, get the pure target product VI, and the yield is 70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With N,N,N',N'',N'''-pentamethyldiethylenetriamine; copper; copper(I) bromide In toluene at 65℃; for 48h; Inert atmosphere; | 6.2 The second step coupling reaction reaction steps: 1st step will be to make the resultant of 9 H - xanthene -9 - thione with 2 - [...] ethyl butyrate, Cu powder/CuBr, PMDETA in accordance with the molar ratio of 1:2: 2:2 uniformly mixed, using toluene as the solvent is placed in the branch pipe flask, nitrogen atmosphere sealing thaw 3 degas. Then in the 65 °C oil bath reaction 48 h. After the reaction taken out, alumina column chromatography to remove the metal and salt, silica gel column chromatography to remove organic impurities, there will be phase turns on lathe does, get the pure target product VII, and the yield is 70%. |
Yield | Reaction Conditions | Operation in experiment |
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100% | With trifluorormethanesulfonic acid In 1,2-dichloro-ethane at 130℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
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61% | Stage #1: C12H6Br3IO With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Stage #2: xanth-9-one In tetrahydrofuran at 20℃; for 2h; | 2 (2) Synthesis of Intermediate-2 In a dry 1 L three-necked flask, 22.4 g (42.3 mmol, 1.0 eq.) of intermediate-1 was charged., dissolved in 200 ml of dry tetrahydrofuran, and cooled to -78 ° C.20 ml of 2.5 M (50.8 mmol, 1.2 eq.) of n-BuLi was added dropwise, after the dropwise addition,Stirring was continued for 1 hour at this temperature.8.3 g (42.3 mmol, 1.0 eq.) of a ton of ketone dissolved in 200 ml of dry tetrahydrofuran was added dropwise, and after the completion of the dropwise addition, the mixture was naturally warmed to room temperature for 2 hours.After the reaction was completed, 100 ml of 1 M hydrochloric acid was added dropwise to quench the reaction.Add 300 ml of water and stir for 1 hour, let stand for stratification, and wash the upper layer solution with saturated saline for 3 times.The lower layer was extracted with dichloromethane and washed with water, the organic phases were combined and dried.Dissolve the solvent, dissolve the solid in 400 ml of acetic acid, add 10 ml of concentrated HCl.The temperature was raised to 110 ° C and the reaction was carried out for 18 hours. After the reaction is over, cool down, suction filtration,The filter cake was washed with water and ethanol in turn, and beaten with ethanol three times to finally obtain 15.0 g of intermediate-2.The yield was 61%. |
Yield | Reaction Conditions | Operation in experiment |
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65% | Stage #1: 1-(furan-2-yl)cyclobutan-1-ol With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran at -78 - 20℃; Inert atmosphere; | 4.1. General procedure for the synthesis of 5 General procedure: To a solution of 1-furan-2-yl-cyclobutanol (6 mmol), TMEDA (12 mmol, 1.39 g) in anhydrous THF (6 mL), at 0 °C under nitrogen atmosphere, was added dropwise a solution of n-BuLi (7.44 mL,1.6 M in hexane, 12 mmol). The solution was stirred for 2 h at room temperature and then a solution of diphenyl-methanone (12 mmol) in anhydrous THF (2 mL) was added at 78 °C. After stirring at the same temperature for 4 h and then stirring overnight at room temperature, the mixture was quenched with saturated aq. NH4Cl (5 mL). The organic solvent was evaporated under reduced pressure and the aqueous layer was extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with saturated brine, dried over sodium sulfate, concentrated under reduced pressure to provide the crude product, which was purified by flash chromatography on a silica gel (using petroleum ether/ethyl acetate 4:1 as the eluent) to give product 5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(II) 2-ethylhexanoate; chlorobis(ethylene)rhodium(I) dimer; silver sulfate In cyclohexane at 140℃; for 24h; Inert atmosphere; Overall yield = 48 %; | 2-1. General procedure for Rh-catalyzed non-directed alkenylation (Scheme 1 and 2) General procedure: A screw-top glass tube was charged with aromatic compound 1 (1.25 mmol, 5.0 eq.), alkene 2 (0.25 mmol, 1.0 eq.), [RhCl(C2H2)2]2 (2.5 mol %), Cu(eh)2 (0.5 mmol, 2.0 eq.), and Ag2SO4 (0.5mmol, 2.0 eq.). Cyclohexane (3.0 mL) was added via syringe, and the resulting mixture was stirred at 140 °C for 24 h. After cooling to room temperature, the reaction mixture was extracted with EtOAc several times. The combined organic layers was washed with H2O containing ethylenediamine (ca. 1.0 mL), dried over Na2SO4, and concentrated in vacuo. The residue was subjected to silica gel column chromatography to give the corresponding product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With tris(trimethylsilyl)amine; tetramethylammonium fluoride In N,N-dimethyl-formamide at 80℃; for 24h; Inert atmosphere; Glovebox; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
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47% | Stage #1: piperidine-2,6-dione; xanth-9-one With titanium tetrachloride; zinc In tetrahydrofuran at 0℃; for 12h; Stage #2: With hydrogenchloride In tetrahydrofuran; water at 25℃; for 0.25h; Stage #3: With toluene-4-sulfonic acid In toluene for 2h; Reflux; Dean-Stark; | 4.3. Typical procedure for the reductive coupling of 1a with 2a(Table 1, run 1) General procedure: To a solution of 1a (113 mg, 1 mmol), 2a (384 mg, 2 mmol), and zinc powder (0.26 g, 4 mmol) in THF (10 mL) was added TiCl4 (0.22 mL, 2 mmol) dropwise at 0 °C and then the dark blue suspension was stirred for 12 h at this temperature. To the mixture was added 1M HCl (20 mL) and the mixture was stirred for 15 min at 25 °C. The clear solution was extracted with ethyl acetate three times. The organic layer was washed with aqueous NaCl and dried over MgSO4. After the solvent was removed in vacuo, the residuewas dissolved in benzene (10 mL). The solution was refluxed in the presence of cat. p-TsOH for 30 min using Dean-Stark apparatus.After the solvent was removed in vacuo, the residue was purified by column chromatography on silica gel to give 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Stage #1: piperidine-2,6-dione; xanth-9-one With titanium tetrachloride; zinc In tetrahydrofuran at 30℃; Stage #2: With hydrogenchloride In tetrahydrofuran; water at 25℃; for 0.25h; Stage #3: With toluene-4-sulfonic acid In toluene for 2h; Reflux; Dean-Stark; | 4.3. Typical procedure for the reductive coupling of 1a with 2a(Table 1, run 1) General procedure: To a solution of 1a (113 mg, 1 mmol), 2a (384 mg, 2 mmol), and zinc powder (0.26 g, 4 mmol) in THF (10 mL) was added TiCl4 (0.22 mL, 2 mmol) dropwise at 0 °C and then the dark blue suspension was stirred for 12 h at this temperature. To the mixture was added 1M HCl (20 mL) and the mixture was stirred for 15 min at 25 °C. The clear solution was extracted with ethyl acetate three times. The organic layer was washed with aqueous NaCl and dried over MgSO4. After the solvent was removed in vacuo, the residuewas dissolved in benzene (10 mL). The solution was refluxed in the presence of cat. p-TsOH for 30 min using Dean-Stark apparatus.After the solvent was removed in vacuo, the residue was purified by column chromatography on silica gel to give 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | Stage #1: Succinimide; xanth-9-one With titanium tetrachloride; zinc In tetrahydrofuran at -10℃; for 12h; Stage #2: With hydrogenchloride In tetrahydrofuran; water at 25℃; for 0.25h; Enzymatic reaction; Stage #3: With toluene-4-sulfonic acid In toluene for 1h; Reflux; Dean-Stark; | 4.3. Typical procedure for the reductive coupling of 1a with 2a(Table 1, run 1) General procedure: To a solution of 1a (113 mg, 1 mmol), 2a (384 mg, 2 mmol), and zinc powder (0.26 g, 4 mmol) in THF (10 mL) was added TiCl4 (0.22 mL, 2 mmol) dropwise at 0 °C and then the dark blue suspension was stirred for 12 h at this temperature. To the mixture was added 1M HCl (20 mL) and the mixture was stirred for 15 min at 25 °C. The clear solution was extracted with ethyl acetate three times. The organic layer was washed with aqueous NaCl and dried over MgSO4. After the solvent was removed in vacuo, the residuewas dissolved in benzene (10 mL). The solution was refluxed in the presence of cat. p-TsOH for 30 min using Dean-Stark apparatus.After the solvent was removed in vacuo, the residue was purified by column chromatography on silica gel to give 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: 1-(2-bromophenyl)naphthalene With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Stage #2: xanth-9-one In tetrahydrofuran at -78 - 20℃; for 14h; | 1.1-2 [Reaction 1-2] Synthesis of Intermediate 1-b Intermediate 1-a (3.5 g, 12.2 mmol) was added to 50 mL of tetrahydrofuran and n-butyllithium (5.8 mL, 14.6 mmol) was added dropwise thereto at -78° C. The mixture was stirred for about 1 h. To the mixture was slowly added dropwise a solution of 9-xanthone (2.1 g, 10.8 mmol) in 10 mL of tetrahydrofuran at the same temperature. The resulting mixture was stirred for 2 h. Stirring was continued at room temperature for 12 h. The reaction mixture was extracted with ethyl acetate and recrystallized from diethyl ether, affording 3.2 g (yield 75%) of Intermediate 1-b. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: 9-(2-bromo-5-chlorophenyl)-9H-carbazole With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran for 1h; Inert atmosphere; | 1 9- (2-Bromo-5-chlorophenyl) -9H-carbazole (30 g, 84.1 mmol) was dissolved in 300 mL of anhydrous tetrahydrofuran (THF) solution and stirred under a nitrogen atmosphere of -78 ° C. 2.5M n-butyllithium (n-BuLi) (37 mL, 93 mmol) was slowly added dropwise to the reaction solution. After 1 hour, 9H-xanthene-9-one (18.2 g 93 mmol) was dissolved in 100 mL of anhydrous tetrahydrofuran (THF) and slowly added dropwise thereto.After 1 hour, the reaction solution was heated to room temperature, and then 200 mL of water was added thereto and stirred. THF layer was distilled to give compound P1 (32.3 g, 81% yield). |
With n-butyllithium In tetrahydrofuran at -78℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | 4'-Bromo-N,N-diphenyl-[1,10-biphenyl]-4-amine 8 (1.00 g,2.50 mmol) was dissolved in 20 mL of anhydrous THF in an oven dried round bottom flask. The solution was cooled to 78 C in a dry ice/acetone bath and sparged with Ar for 20 min. 1.6 M n-BuLi in hexane (1.88 mL, 3.00 mmol) was added dropwise via syringe and the reaction was stirred for 1 h at 78 C. During this time xanthone 18 (490 mg, 2.50 mmol) was dissolved in 30 mL of anhydrous THF in a separate oven dried round bottom flask. The solution was cooled to 78 C in a dry ice/acetone bath and sparged with Ar for 30 min. The aryllithium solution was transferred to the solution containing 18 at 78 C via cannula under Ar pressure. The cooling bath was removed, and the reaction stirred for 4 h. The reaction was quenched by the addition of 75 mL of sat. NH4Cl and the mixture was subsequently extracted 3x with 50 mL of EtOAc. The combined organics were washed with water and brine, dried with Na2SO4, filtered, and concentrated under reduced pressure to yield a crude solid. The crude product was purified with column chromatography under gradient elution (10:90 CH2Cl2:hexane /80:20 CH2Cl2:hexane) to yield 26a as a light-yellow powder (789 mg, 61%) which was not characterized further. 300 mg (0.580 mmol) of 16a was dissolved in 20 mL of CH2Cl2 in a graduated cylinder and 0.1 mL of 1:1 HBF4 diethyl ether complex and 0.5 mL of Ac2O was carefully added resulting in a green solution. Diethyl ether (30 mL) was layered on top of the solution and was allowed to sit for 48 h as a ppt formed. The ppt was filtered to achieve a green solid (293 mg, 86%). The product was acid sensitive and was therefore analyzed via NMR spectroscopy dissolved in CD2Cl2 as a solvent with no added CF3CO2D, which reduced its solubility. mp 234e235 C. 1H NMR (400 MHz, CD2Cl2): d 8.57 (t,J 7.8 Hz, 2H), 8.41 (d, J 8.8 Hz, 2H), 8.35 (d, J 8.6 Hz, 2H), 8.05(d, J 7.8 Hz, 2H), 8.01 (t, J 7.8 Hz, 2H), 7.79 (d, J 7.8 Hz, 2H), 7.69(d, J 8.6 Hz, 2H), 7.34 (t, J 7.8 Hz, 4H), 7.21-7.17 (m, 6H), 7.13 (t,J 7.8 Hz, 2H). 13C NMR (100 MHz, CD2Cl2): d 175.3, 158.5, 149.7, 147.7,146.3,144.7,132.9,132.7,131.9,130.0,129.3,128.6,127.7,125.8,124.0,123.2,120.6. IR (ATR) nmax: 1598,1483,1053 cm1. HRMS (ESI)m/z calcd for C37H26NO [M] 500.2014, found 500.2007. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | Stage #1: 4-bromo-4'-methoxylbiphenyl With magnesium; ethylene dibromide In tetrahydrofuran Reflux; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere; Stage #3: With perchloric acid; acetic anhydride In diethyl ether; water at 0℃; for 0.5h; | 4.10. 9-(40methoxy-[1,10-biphenyl]-4-yl)xanthylium perchlorate (24) Magnesium (0.132 g, 5.42 mmol) was placed into an oven-dried round bottom flask and flushed with Ar for 30 min while stirring. 4-Bromo-4'-methoxybiphenyl 6 (1.43 g, 5.42 mmol), anhydrous THF(8 mL), and 2 drops of 1,2-dibromoethane were then added. The reaction was heated to reflux, stirred for 30 min under Ar, and allowed to cool back to rt over 1 h. During this time xanthone 18 (0.532 g, 2.71 mmol) was dissolved in 16 mL of anhydrous THF in a separate oven dried round bottom flask. The flask was cooled to0 C with an ice bath and sparged for 30 min with Ar. The arylmagnesium bromide solution was transferred to the solution containing 18 at 0 C via cannula under Ar pressure. The cooling bath was removed, and the reaction was stirred for 2 h. 50 mL of sat. NaHCO3 was added to the reaction and subsequently extracted 3x with 100 mL of CH2Cl2. The combined organics were washed dried with Na2SO4, filtered, and concentrated under reduced pressure. The crude intermediate was purified via column chromatography using gradient elution (5% EtOAc in hexane/50% EtOAc in hexane) but not characterized further. The purified intermediate was dissolved in 10 mL of diethyl ether and 70% aq. HClO4 was added dropwise at rt until a colored precipitate formed. The reaction was allowed to stir for 30 min and filtered to yield a red solid. The solid was recrystallized in glacial acetic acid to yield small red needles (0.595 g, 47%). mp 230e231 C. 1H NMR (400 MHz, CDCl3/CF3CO2D): d 8.51 (ddd, J 8.6 Hz, J 7.0 Hz, J 1.2 Hz, 2H), 8.37 (d,J 8.8 Hz, 2H) 8.33 (dd, J 8.7 Hz, J 1.3 Hz, 2H), 8.01-7.94 (m, 4H),7.78 (d, J 8.1 Hz, 2H), 7.73 (d, J 8.8 Hz, 2H), 7.10 (d, J 8.8 Hz, 2H)3.94 (s, 3H). 13C NMR (100 MHz, CDCl3/CF3CO2D): d 174.9, 160.2,158.3, 145.7, 144.0, 132.0, 131.9, 131.4, 129.4, 128.7, 128.6, 127.3,123.5,120.0,114.8, 55.6. IR (ATR) nmax: 1596,1578,1083 cm1. HRMS(ESI) m/z calcd for C26H19O2 [M] 363.1385, found 363.1382. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Stage #1: bromobenzene With iodine; magnesium In tetrahydrofuran Inert atmosphere; Reflux; Stage #2: xanth-9-one In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere; | 9-phenylxanthylium perchlorate (19) Magnesium (0.389 g, 16.2 mmol) was placed into an oven-dried round bottom flask and flushed with Ar for 30 minutes while stirring. Bromobenzene 1 (1.70 mL, 16.2 mmol), anhydrous THF (20 mL), and 1 crystal of iodine were then added. The reaction was heated to reflux, stirred for 30 min under Ar, and allowed to cool back to rt over 1 h. During this time xanthone 18 (1.54 g, 7.85 mmol) was dissolved in 50 mL of anhydrous THF in a separate oven dried round bottom flask. The flask was cooled to 0 °C with an ice bath and sparged for 30 min with Ar. The arylmagnesium bromide solution was transferred to the solution containing 18 at 0 °C via cannula under Ar pressure. The cooling bath was removed, and the reaction was stirred for 2 h. 50 mL of sat. NaHCO3 was added to the reaction and subsequently extracted 3x with 100 mL of CH2Cl2. The combined organics were washed dried with Na2SO4, filtered, and concentrated under reduced pressure. The crude intermediate was dissolved in 10 mL of acetone and 70% aq. HClO4 was added dropwise at rt until a colored precipitate formed. The reaction was allowed to stir for 1 h and filtered to yield a yellow solid. The solid was recrystallized in glacial acetic acid to yield yellow needles (1.88 g, 67%). mp 280-281 °C. 1H NMR (400 MHz, CDCl3/CF3CO2D): δ 8.58 (t, J = 8.8 Hz, 2H), 8.40 (d, J =8.8 Hz, 2H), 8.24 (d, J = 8.6 Hz, 2H), 8.01 (t, J = 7.8 Hz, 2H), 7.92 (t, J = 7.6 Hz, 1H), 7.84 (t, J = 7.8 Hz, 2H), 7.65 (d, J = 8.6 Hz, 2H).13C NMR (100 MHz, CDCl3/CF3CO2D): δ 175.4, 161.5, 158.5, 144.4, 132.9, 131.9, 130.6, 129.6, 129.4, 123.7, 120.1. IR (ATR) νmax: 1595, 1578, 1068 cm-1. HRMS (ESI) m/z calcd for C19H13O [M+] 257.0966, found 257.0959. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | Stage #1: 1-bromo-4-methoxy-benzene With magnesium; ethylene dibromide In tetrahydrofuran Inert atmosphere; Reflux; Stage #2: xanth-9-one In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere; Stage #3: With perchloric acid In diethyl ether; water at 20℃; for 1h; | 9-phenylxanthylium perchlorate (19) Magnesium (0.389 g, 16.2 mmol) was placed into an oven-dried round bottom flask and flushed with Ar for 30 minutes while stirring. Bromobenzene 1 (1.70 mL, 16.2 mmol), anhydrous THF (20 mL), and 1 crystal of iodine were then added. The reaction was heated to reflux, stirred for 30 min under Ar, and allowed to cool back to rt over 1 h. During this time xanthone 18 (1.54 g, 7.85 mmol) was dissolved in 50 mL of anhydrous THF in a separate oven dried round bottom flask. The flask was cooled to 0 °C with an ice bath and sparged for 30 min with Ar. The arylmagnesium bromide solution was transferred to the solution containing 18 at 0 °C via cannula under Ar pressure. The cooling bath was removed, and the reaction was stirred for 2 h. 50 mL of sat. NaHCO3 was added to the reaction and subsequently extracted 3x with 100 mL of CH2Cl2. The combined organics were washed dried with Na2SO4, filtered, and concentrated under reduced pressure. The crude intermediate was dissolved in 10 mL of acetone and 70% aq. HClO4 was added dropwise at rt until a colored precipitate formed. The reaction was allowed to stir for 1 h and filtered to yield a yellow solid. The solid was recrystallized in glacial acetic acid to yield yellow needles (1.88 g, 67%). mp 280-281 °C. 1H NMR (400 MHz, CDCl3/CF3CO2D): δ 8.58 (t, J = 8.8 Hz, 2H), 8.40 (d, J =8.8 Hz, 2H), 8.24 (d, J = 8.6 Hz, 2H), 8.01 (t, J = 7.8 Hz, 2H), 7.92 (t, J = 7.6 Hz, 1H), 7.84 (t, J = 7.8 Hz, 2H), 7.65 (d, J = 8.6 Hz, 2H).13C NMR (100 MHz, CDCl3/CF3CO2D): δ 175.4, 161.5, 158.5, 144.4, 132.9, 131.9, 130.6, 129.6, 129.4, 123.7, 120.1. IR (ATR) νmax: 1595, 1578, 1068 cm-1. HRMS (ESI) m/z calcd for C19H13O [M+] 257.0966, found 257.0959. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: C16H10BrCl With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: xanth-9-one In tetrahydrofuran; hexane at 20℃; for 2h; | 1.1 1) Preparation of E1-P1 The formula1- (2-Bromophenyl) naphthalene compound (20 g, 63.0 mmol) was added to 200 mL of tetrahydrofuran, and 2.5 M n-butyllithium in Hexane (22.7 mL, 56.7 mmol) was added dropwise at -78 ° C for about 1 hour. While stirring.After 2-bromo-9H-xanthen-9-one compound (9.9 g, 50.4 mmol) was added, the mixture was stirred at room temperature for 2 hours. After extraction with ethyl acetate, it was concentrated to prepare a compound represented by Formula E1-P1 (19.7 g, yield 90%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: tetrafluoroboric acid diethyl ether; xanth-9-one; 2,3,7,8-tetrafluorothianthrene-S-oxide With trifluoroacetic anhydride In acetonitrile at 0 - 25℃; for 3h; Sealed tube; Stage #2: sodium tetrafluoroborate In dichloromethane; water | Xanthone-derived thianthrenium salt 23-TFT Under ambient atmosphere, a 20 mL borosilicate vial was charged with xanthone (392 mg,2.00 mmol, 1 .00 equiv.), tetrafluorothianthrene-S-oxide (628 mg, 2.00 mmol, 1 .00 equiv.) and dry MeCN (2.0 mL, c = 0.25 M). After cooling to 0 °C, trifluoroacetic anhydride (840 pL, 1.27 g, 6.00 mmol, 3.00 equiv.) addition at 0 °C in one portion, followed by HBF4OEt2(348 pL,2.40 mmol, 1 .20 equiv.) was added in one portion at 0 °C. The vial was sealed with a screw- cap, and the mixture was stirred at 0 °C for 1 h, followed by warming the reaction mixture to 25 °C over a period of 1 h. After stirring at 25 °C for 1 h further, the reaction mixture was concentrated under reduced pressure, and diluted with 10 mL CH2CI2. The CH2CI2solution was poured onto a saturated aqueous NaHC03solution (ca. 10 mL). The mixture was poured into a separatory funnel, and the layers were separated. The CH2CI2layer was collected, and the aqueous layer was further extracted with CH2CI2(2 x ca. 10 mL). The combined CH2CI2solution was washed with aqueous NaBF4solution (2 x ca. 10 mL, 5 % w/w). The CH2CI2layer was dried over Na2S04, filtered, and the solvent was removed under reduced pressure. The residue was purified by chromatography on silica gel eluting with CH2CI2//-PrOH (50:1 , v/v). The product was dissolved in 2 mL CH2CI2, and precipitated with 10 mL Et20. The suspension was decanted, and the solid was dried in vacuo to afford 23-TFT (890 mg, 1 .56 mmol, 78 %) as a colorless solid.Rf= 0.35 (CH2CI2/MeOH, 15:1 , v/v).NMR Spectroscopy:1H NMR (500 MHz, DMSO -cfe, 298 K, d): 8.93 (dd, J = 9.7, 7.3 Hz, 2H), 8.44 (dd, J = 10.2, 7.2 Hz, 2H), 8.20 (d, J = 2.7 Hz, 1 H), 8.16 (dd, J = 8.0, 1.7 Hz, 1 H), 7.93 (ddd, J = 8.7, 7.1 , 1 .7 Hz, 1 H), 7.83 (d, J = 9.2 Hz, 1 H), 7.73-7.69 (m, 2H), 7.54 (ddd, J = 8.1 , 7.1 , 1 .0 Hz, 1 H) ppm.13C NMR (126 MHz, DMSO-cfe, 298 K, d): 174.7, 157.5, 155.4, 152.7 (dd, J = 260.2, 13.0 Hz), 149.3 (dd, J = 253.3, 13.4 Hz), 136.5, 134.3, 133.3 (dd, J = 8.7, 3.4 Hz), 127.8, 126.1 , 125.4 (d, J = 22.2 Hz), 125.4, 122.0, 121.0, 120.8, 1 19.9 (d, J = 21 .8 Hz), 1 19.7, 1 18.4,1 15.8 (dd, J = 7.5, 3.0 Hz) ppm.19F NMR (471 MHz, DMSO -cfe, 298 K, d): -125.40 (dt, J = 23.6, 8.7 Hz), -133.87 (dt, J = 23.1 , 8.6 Hz)), -148.22 (bs), -148.28 (bs) ppm.HRMS-ESI (m/z) calculated for C^HuF^S [M-BF4]+, 483.0131 14; found, 483.013440;deviation: -0.67 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 2-bromodiphenylamine With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran Inert atmosphere; | 1.4 (4) Synthesis of Intermediate D2 (4) Synthesis of Intermediate D2 7.5 g of intermediate D1 was added into 80 mL of THF under nitrogen atmosphere, and then the solution was cooled down to -78° C. using dry ice. 24 mL of 2.5 M n-BuLi was added into the solution drop wisely and then the solution was stirred for 1 hour. 5.88 g of xanthone dissolved in 50 mL of THF was added into the solution. After removing solvents, 100 mL of acetic acid/HCl (1:10 v/v) was added to give 8.35 g of Intermediate D2 (yield: 80%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; silver(l) oxide In 1,2-dichloro-ethane at 80℃; for 10h; | 5 Synthesis of 2,3-diphenylpyrano[4,3,2-kl]anthracen-1-ium hexafluoroantimonate (V-a) (1) Combine xanthone (39.2mg, 0.20mmol), diphenylacetylene (71.2mg, 0.40mmol), [Cp*RhCl2]2 (3.1mg, 5μmol, 2.5mol%), Ag2O (46.4mg, 0.20 mmol, 1.0equiv), AgSbF6 (13.7mg, 40μmol, 20mol%), NaSbF6 (51.7mg, 0.20mmol) and dichloroethane (1.0mL) were added to the reaction tube, stirred uniformly under anhydrous and oxygen-free conditions and heated to 80°C, react for 10 hours;(2) After the reaction is completed, cool the reaction tube to room temperature, add 10 mL of dichloromethane to dilute the reaction system,Then filter through diatomaceous earth and wash with 10-20 mL of dichloromethane, combine the filtrate,The solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (dichloromethane/ethyl acetate=15:1, v/v),After vacuum drying, 97.4 mg of the target product 2,3-diphenylpyrano[4,3,2-kl]anthracen-1-ium hexafluoroantimonate (V-a) was obtained as a light yellow solid, and the yield was 80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Stage #1: isopropyl bromide With magnesium In diethyl ether at 0℃; for 1h; Inert atmosphere; Stage #2: xanth-9-one In diethyl ether for 1h; Inert atmosphere; Reflux; | Preparation of compound L1 (Scheme 2) Mg turnings (2.2 g, 89.2 mmol) were carefully added in small portions under positive Ar pressure to a solution of 2-bromopropane (8.4 mL, 89.2 mmol) in dry Et2O (25 mL) at 0 °C. After 30 min the solution turned murky white, and once all Mg turnings were added the reaction was left to stir for 30 min at 0 °C. Xanthone (3.5 g, 17.8 mmol) in Et2O (25 mL) was added portion wise to the chilled reaction mixture. The reaction was warmed and refluxed for 1 h. The reaction was cooled to room temperature, diluted with Et2O (40 mL), and the solution cooled to 0 °C. The reaction was quenched by dropwise addition of a saturated NH4Cl solution, filtered, washed with Et2O and the organic layer extracted with Et2O (3 x 20 mL). After drying over anhydrous MgSO4, filtration and evaporation, the yellow viscous oil was purified by column chromatography on silica gel (hexane/EtOAc, 9:1, Rf = 0.5). The product was dried under vacuum to give compound L1 as white microcrystals: yield: 3.5 g (68%); 1H NMR (CDCl3, 400 MHz) δ/ppm: 7.66 (dd, J 7.8, 1.6 Hz, 2H), 7.29 (ddd, J 8.1, 7.3, 1.7 Hz, 2H), 7.18 - 7.07 (m, 4H), 2.22 (s, 1H), 2.10 (m, 1H), 0.71 (d, J 6.8 Hz, 6H); 13C NMR (CDCl3,101 MHz) δ/ppm: 151.0 (CO), 128.6 (C), 126.9 (CH), 126.7 (CH), 123.0 (CH), 115.8 (CH), 72.1 (C), 42.6 (CH), 16.8 (CH3); IR (neat) ν/cm-1 3331, 2981, 2960, 2932, 2874, 1601, 1575, 1473, 1447, 1020, 1285, 743; HR-MS (ESI): [M - OH]+ m/z = 223.1117, calcd. for C16H15O 223.1117. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | Stage #1: N-(9,9'-spirobis-9H-fluorene-2-yl)-2-bromoaniline With n-butyllithium In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran at -78 - 20℃; Inert atmosphere; Further stages; | 1.2 Under a nitrogen atmosphere, compound B1 (1 mmol) was added to anhydrous tetrahydrofuran THF, stirred at -78°C to cool the reaction solution, and 1.6 mol/L n-BuLi (1 mmol) was added dropwise, and Keep the reaction at -78° C. for 2 hours; slowly add compound b1 (1 mmol) to the low-temperature reaction solution dropwise. After the dropwise addition is complete, continue the reaction at low temperature for 2 hours, and then warm up to room temperature and react overnight. After the reaction is over, add a small amount of water to quench, add DCM/H2O for extraction, collect the organic phase and dry with anhydrous Na2SO4, collect the filtrate by suction and spin off the solvent to obtain the crude product;The above crude product was added to 20 mL of AcOH acetic acid under nitrogen, stirred and heated, and reacted at 120° C. for 2 h, then 2 mL of hydrochloric acid was added, and the reaction was heated at this temperature for 12 h. After the reaction is complete, cool and extract, collect the organic phase and spin off the solvent, and purify by column chromatography to obtain the intermediate compound C1 (yield 66%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With n-butyllithium In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; | 1 Synthesis of compound A-2 Compound A-1 (39 g, 90 mmol) and 350 mL of THF were added to the flask under a nitrogen atmosphere, and the mixture was cooled to -78°C. Next, n-butyllithium (40 mL, 99 mmol) was slowly added dropwise to the mixture. Then xanthone (16 g, 81 mmol) was added dropwise, and the mixture was allowed to react for 2 hours. After the reaction was completed, water was added to the mixture to terminate the reaction, the organic layer was extracted with ethyl acetate, and residual moisture was removed by using magnesium sulfate. The residue was dried and separated by column chromatography to obtain compound A-2 (40 g, yield: 80%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Stage #1: (benzofuryl-2) methane phosphonate de diethyle With n-butyllithium In tetrahydrofuran; hexane at -40 - 0℃; for 1.5h; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran; hexane at 60℃; for 9h; Inert atmosphere; | Preparation of compound A1: General procedure: 20.8g (60.0mmol) of (5-bromo-benzofuran-2-methylene) diethyl phosphate was dissolved in 100.0mL of dry THF, and the temperature was cooled to -40°C with liquid nitrogen,26.5mL of 2.5M n-butyllithium n-hexane solution was added dropwise, stirred and reacted for 30 minutes,The temperature was raised to 0°C and the reaction was stirred for 1 hour, and 11.0 g (50.0 mmol) was added dropwise10,10-Dimethylanthrone was dissolved in 25.0mL dry THF solution, stirred and reacted for 1 hour,The temperature was raised to 60°C and the reaction was stirred for 8 hours, then cooled to room temperature,Add 200 mL of 2N dilute hydrochloric acid aqueous solution, extract with ethyl acetate,The organic phase was collected and dried, filtered, and the filtrate was concentrated under reduced pressure to dryness, and separated and purified by a silica gel column.Compound A1 was obtained with a yield of 96%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: diethyl(benzo<b>thiophene-2-ylmethyl)phosphonate With n-butyllithium In tetrahydrofuran; hexane at -40 - 0℃; for 1.5h; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran; hexane at 60℃; for 9h; Inert atmosphere; | Preparation of compound A1: General procedure: 20.8g (60.0mmol) of (5-bromo-benzofuran-2-methylene) diethyl phosphate was dissolved in 100.0mL of dry THF, and the temperature was cooled to -40°C with liquid nitrogen,26.5mL of 2.5M n-butyllithium n-hexane solution was added dropwise, stirred and reacted for 30 minutes,The temperature was raised to 0°C and the reaction was stirred for 1 hour, and 11.0 g (50.0 mmol) was added dropwise10,10-Dimethylanthrone was dissolved in 25.0mL dry THF solution, stirred and reacted for 1 hour,The temperature was raised to 60°C and the reaction was stirred for 8 hours, then cooled to room temperature,Add 200 mL of 2N dilute hydrochloric acid aqueous solution, extract with ethyl acetate,The organic phase was collected and dried, filtered, and the filtrate was concentrated under reduced pressure to dryness, and separated and purified by a silica gel column.Compound A1 was obtained with a yield of 96%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.1% | Stage #1: C37H36ClN With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 2h; Inert atmosphere; Stage #2: xanth-9-one In tetrahydrofuran; hexane at 20℃; for 8h; Inert atmosphere; | 5 Synthesis of compound 162-5 Dissolve compound 162-3 (15g, 28.3mmol) in 70mL of anhydrous tetrahydrofuran, cool to -78°C and stir under a nitrogen atmosphere, and slowly add 12mL (30mmol) of 2.5M normal The butyl lithium n-hexane solution was stirred at -78°C under a nitrogen atmosphere for 2 hours, and compound 162-4 (5.5 g, 28 mmol) dissolved in 20 mL of anhydrous tetrahydrofuran was added dropwise to it, and the mixture was stirred at room temperature under a nitrogen atmosphere. Hour.The reaction solution was cooled to 0°C, 70 mL of 1.0 M ammonium chloride aqueous solution was added to it, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solution was concentrated under reduced pressure with ethyl acetate: n-hexane as 20 80 (V/V) washing liquid was subjected to silica gel column chromatography, concentrated and dried to obtain solid compound 162-5 (12 g, 62.1%). |
[ 6320-42-9 ]
7-Hydroxy-2-methyl-4H-chromen-4-one
Similarity: 0.96
[ 26964-24-9 ]
6-Methoxy-2-phenyl-4H-chromen-4-one
Similarity: 0.91
[ 6320-42-9 ]
7-Hydroxy-2-methyl-4H-chromen-4-one
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[ 26964-24-9 ]
6-Methoxy-2-phenyl-4H-chromen-4-one
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