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Structure of 101-81-5 * Storage: {[proInfo.prStorage]}
* 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.
Reference：
[1] American Chemical Journal, 1903, vol. 30, p. 465
2
[ 101-81-5 ]
[ 90-90-4 ]
[ 34699-28-0 ]
Yield
Reaction Conditions
Operation in experiment
89%
Stage #1: With n-butyllithium In tetrahydrofuran for 1.33333 h; Inert atmosphere; Cooling with ice Stage #2: at 20℃; for 12 h;
16.7 mL (0.1 mol) of diphenylmethane and 300 ml of tetrahydrofuran (THF) were added to a solution of500ml three-necked flask, magnetic stirring and argon, ice salt bath 40min, to the three bottles by adding 54.5mL (0.12mol) n-butyl lithium solution, continue ice salt bath 40min, add 13.0555g4-bromobenzophenone(Bis (4-bromophenyl) methanone, 0.05),After the reaction was carried out at room temperature for 12 h, 250 ml of saturated ammonium chloride (NH4Cl) solution was added to the three-necked flask. After stirring for 10 min, the reaction solution was poured into a separatory funnel, the supernatant was taken and the water in the solution was adsorbed with 300 g of anhydrous sodium sulfate. And then heated to 110 ° C. After adding 5 g of p-toluenesulfonic acid, the mixture was refluxed for 12 hours. After the reaction was stopped, the reaction solution was dried and dried. The reaction mixture was heated to 110 ° C, The product was spin dried to dry the powder and the powder was dried in vacuo at 60 ° C for 24 h to give the white intermediate Si-Br in 89percent yield.
73.03%
Stage #1: With n-butyllithium In tetrahydrofuran at 0℃; for 1 h; Inert atmosphere Stage #2: at 20℃; for 6 h; Stage #3: With toluene-4-sulfonic acid In tolueneReflux
1, under the conditions of a temperature of 0 ° C, the 100ml three-necked flask was evacuated and filled with N2 three times,12 mmol of diphenylmethane and 50 ml of dehydrated tetrahydrofuran were evacuated, and 10 mmol of n-butyllithium was gradually introduced into the flask. While maintaining the atmosphere of nitrogen at 0 ° C, n-butyllithium was subjected to dehydrogenation for 1 hour. To the solution was added 9.5 mmolBromobenzophenone, the reaction was allowed to return to room temperature and stirred for 6 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride. The organic phase was extracted with CH 2 Cl 2, washed three times with saturated brine and dried over anhydrous Na 2 SO 4. The organic solvent , The residue,Toluenesulfonic acid and 60 ml of toluene were added to a 100 ml two-necked flask, and the mixture was refluxed for 6-8 hours. The mixture was cooled to room temperature and the organic layer was washed with 10percent aqueous NaHCO 3 solution Three times, the combined organic phases were dried over anhydrous Na2SO4 and the solvent toluene was evaporated under reduced pressure. The residue was purified by column chromatography to give a white solid Product 1-1. Yield: 73.03percent. 1-1
66%
Stage #1: With n-butyllithium In tetrahydrofuran at 0℃; for 0.5 h; Stage #2: at 20℃; for 6 h; Stage #3: With toluene-4-sulfonic acid In toluene at 110℃;
In a 250 mL three-necked flask,Diphenylmethane (10.0 g, 59.5 mmol) was dissolved in 150 mL of re-distilled tetrahydrofuran,At 0 slowly added dropwise n-BuLi (25mL, 2.5M),After reaction for 30 min, 4-bromobenzoylbenzene (5.2 g, 20.0 mmol) was slowly added dropwise.Then, the temperature was raised to room temperature for 6 h, quenched with ammonium chloride,The reaction was extracted with CH2Cl2 (3 x 20 mL) and the extract was washed with water (3 x 20 mL)Dried over anhydrous MgSO4 and the solvent was removed under reduced pressure to give an alcohol.The above alcohol solution was dissolved with toluene,P-toluenesulfonic acid (1.7 g, 0.01 mol) was added,The reaction was carried out at 110 ° C for 3-4 h with a water distilling apparatus.The reaction was extracted with sodium bicarbonate. The extract was washed with water (3 x 20 mL) and dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the column was separated (PE) to give 5.3 g of product (yield: 66percent) as a white solid.
64%
Stage #1: With n-butyllithium In tetrahydrofuran; cyclohexane at 0℃; for 0.5 h; Inert atmosphere Stage #2: at 20℃; for 10 h; Stage #3: With toluene-4-sulfonic acid In toluene for 5 h; Reflux
1. Add 10.09 g (0.06 mol) of diphenylmethane to a 500 mL three-necked flask.And 250 mL of dry tetrahydrofuran, vacuum replacement, cooling to 0 ° C,Maintain mixing,Slowly add to the mixture with a syringe under nitrogen protection24.0 mL of 2.5 mol/L (0.06 mol) n-butyllithium in cyclohexane solution,Stirring was continued for 30 min after the addition, and then 40 mL of a dry tetrahydrofuran solution containing 15.14 g (0.058 mol) of 4-bromobenzophenone was added dropwise.After stirring at room temperature for 10 h, the reaction mixture was quenched with aqueous ammonium chloride, and extracted with dichloromethane (300 mL×3×),Rinse alternately with saturated aqueous sodium chloride solution and deionized water (300 mL × 3 times).Dry with anhydrous magnesium sulfate, filter, and distill off the solvent.The intermediate 2-(4-bromophenyl)-1,1,2-triphenylethanol was obtained.The obtained intermediate was dissolved in 300 mL of toluene with 1.0 g of anhydrous p-toluenesulfonic acid.After refluxing for 5 h, toluene was distilled off, and the obtained solid was dissolved in 300 mL of dichloromethane.Then alternately wash with saturated aqueous sodium chloride solution and deionized water (300mL×3 times).Drying anhydrous magnesium sulfate, filtering, and distilling off the solvent to obtain a crude product;Taking cyclohexane/dichloromethane (v/v=5:1) as the eluent,The crude product was separated by silica gel column chromatography.15.27g of white solid 1-(4-bromophenyl)-1,2,2-triphenylethylene,The yield was 64percent.
37%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.5 h; Inert atmosphere Stage #2: at 0 - 20℃; for 6 h; Stage #3: With toluene-4-sulfonic acid In toluene for 16 h; Reflux
Step 1, synthesis of bromotetraphenylethene (TPE-Br) The benzylbenzene (2.0g, 11.9mmol) was dissolved in 20mL of anhydrous tetrahydrofuran, was stirred at 0°C under nitrogen atmosphere, 1.6M n-hexane solution of n-butyllithium (7.4mL, 11.9mmol) was slowly added, reacted for 30 minutes; and then 4-bromo-benzophenone (3.1g, 11.9mmol) was added, slowly warmed to room temperature and the reaction mixture was stirred for 6 hours, followed by addition of a small amount of water to the reaction solution for the reaction to stop, the reaction solution was extracted twice with dichloromethane, the organic layer was dried over anhydrous magnesium sulfate and was filtered. The solvent was distilled off under reduced pressure. The resulting solid was dissolved in 80mL of toluene, p-toluenesulfonic acid monohydrate (500mg, 2.6mmol, catalyst) was added, and refluxed for 16 hours, the reaction was cooled to room temperature and extracted twice with dichloromethane, the organic layer was dried over anhydrous magnesium sulfate and was filtered. The solvent was distilled off under reduced pressure. The crude product with hexane as a mobile phase and the silica gel as the stationary phase was pass through column chromatography, obtaining a white solid 1.8g, 37percent yield;
Reference：
[1] Patent: CN104341311, 2016, B, . Location in patent: Paragraph 0057; 0058; 0059
[2] Patent: CN107082753, 2017, A, . Location in patent: Paragraph 0030; 0031; 0032; 0033; 0034; 0035
[3] Angewandte Chemie - International Edition, 2018, vol. 57, # 29, p. 8947 - 8952[4] Angew. Chem., 2018, vol. 130, # 29, p. 9085 - 9090,6
[5] Patent: CN106565595, 2017, A, . Location in patent: Paragraph 0028; 0033; 0034; 0035
[6] Patent: CN108727277, 2018, A, . Location in patent: Paragraph 0008; 0030-0031
[7] Patent: CN103274965, 2016, B, . Location in patent: Paragraph 0058; 0059; 0060; 0061; 062
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[9] ChemPlusChem, 2012, vol. 77, # 10, p. 949 - 958
[10] Science China Chemistry, 2013, vol. 56, # 9, p. 1213 - 1220
[11] Dyes and Pigments, 2014, vol. 106, p. 87 - 93
[12] Chemistry - A European Journal, 2015, vol. 21, # 3, p. 1149 - 1155
[13] Journal of Materials Chemistry C, 2015, vol. 3, # 47, p. 12328 - 12334
[14] Journal of Materials Chemistry C, 2017, vol. 5, # 10, p. 2552 - 2558
[15] Patent: CN108250205, 2018, A, . Location in patent: Paragraph 0043; 0044; 0045; 0052; 0059
3
[ 101-81-5 ]
[ 34699-28-0 ]
Reference：
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[11] Chemical Communications, 2012, vol. 48, # 62, p. 7711 - 7713
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[15] Patent: US2013/59392, 2013, A1,
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With hydrogen;palladium 10% on activated carbon; In methanol; ethyl acetate;
(b) Title compoundA solution of the compound obtained in section a) (6.06 g, 16.5 mmol) in 60 ml_ of MeOH and 15 ml_ of EtOAc was purged with argon. Then, Pd/C (10%) (814 mg) was added and the solution was purged again with argon and was stirred under H2 overnight. The reaction was filtered through Celite and the filter was washed with EtOAc and MeOH. The solvent was concentrated to dryness, to afford 4.55 g of a mixture of the title compound together with one equivalent of diphenylmethane, that was used as such.1H NMR (300 MHz, CDCI3) delta: 1.45 (s, 12H), 2.67 (s, 3H), 3.28 (m, 1 H), 3.61 (m, 1 H), 3.87 (m, 1 H), 4.00 (m, 1 H)
With hydrogen;palladium 10% on activated carbon; In methanol; ethyl acetate; for 18.0h;
(b) Title compound; A solution of the compound obtained in section a) (6.06 g, 16.5 mmol) in 60 ml_ of MeOH and 15 ml_ of EtOAc was purged with argon. Pd/C (10%) (814 mg) was added and the mixture was then purged again with argon and stirred overnight in an H2 atmosphere. The reaction was filtered through Celite and the filter cake was washed with EtOAc and MeOH. The solvent was evaporated to dryness, providing 4.55 g of a mixture of the title compound together with one equivalent of diphenylmethane that was used as such in the following steps.1H NMR (300 MHz, CDCI3) delta: 1.45 (s, 12H), 2.67 (s, 3H), 3.28 (m, 1 H), 3.61 (m, 1 H), 3.87 (m, 1 H), 4.00 (m, 1 H)
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In 1,4-dioxane; acetonitrile; at 90.0℃; for 48.0h;
EXAMPLE 15; 2-lsobutyl-6-(3-methyl-3-(methylamino)azetidin-1-yl)pyrimidin-4-amine; a) terf-Butyl 1 -(6-amino-2-isobutylpyrimidin-4-yl)-3-methylazetidin-3- yl(methyl)carbamate; The compound obtained in reference example 31 (0.15 g, 0.90 mmol), the amine obtained in reference example 30 (0.57 g of a 1 :1 mixture with diphenylmethane, equivalent to 0.29 g 100%, 1.4 mmol) and PyBOP (0.52 g, 0.99 mmol) in a mixture of TEA (6 ml_), acetonitrile (6 ml_) and 1 ,4-dioxane (6 ml_) were heated at 90 0C for 2 days. The reaction mixture was concentrated to dryness. The crude product obtained was purified by chromatography over silica gel using mixtures of hexane/EtOAc of increasing polarity as eluent, providing 229 mg of the desired compound (yield: 73%) LC-MS (Method 2): tR = 2.15 min; m/z 350 (MH+).
With di-tert-butyl peroxide; acetic acid; cobalt(II) bromide In 1,1,2-trichloroethane at 120℃; for 28h;
4.2. General procedure for amination of benzylic hydrocarbons
General procedure: Ethylbenzene (1 mL), or a solution of diphenylmethane (1 mmol) in trichloroethane (1 mL), was added to a mixture of amide (0.5 mmol), CoBr2 (0.1 mmol) and AcOH (0.05 mmol) at room temperature, and DTBP (1 mmol) was then added. The resulting mixture was stirred at 120 °C for 28 h under air. After cooling to room temperature, the mixture was diluted with ethyl acetate (50 mL) and washed with water. The organic phase was dried over MgSO4 and removed under reduced vacuum. The residue was purified by column chromatography eluting with ethyl acetate and hexane to afford the desired product.
With di-tert-butyl peroxide; acetic acid; cobalt(II) bromide; In 1,1,2-trichloroethane; at 120℃; for 28h;
General procedure: Ethylbenzene (1 mL), or a solution of diphenylmethane (1 mmol) in trichloroethane (1 mL), was added to a mixture of amide (0.5 mmol), CoBr2 (0.1 mmol) and AcOH (0.05 mmol) at room temperature, and DTBP (1 mmol) was then added. The resulting mixture was stirred at 120 C for 28 h under air. After cooling to room temperature, the mixture was diluted with ethyl acetate (50 mL) and washed with water. The organic phase was dried over MgSO4 and removed under reduced vacuum. The residue was purified by column chromatography eluting with ethyl acetate and hexane to afford the desired product.
80%
With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In 1,2-dichloro-ethane; at 100℃; for 24h;Schlenk technique; Molecular sieve; Inert atmosphere;
General procedure: A 20 mL Schlenk tube equipped with a stir-bar was charged with substituted diphenylmethanes (0.5 mmol), TsNH2 (1.0 mmol), DDQ (0.6 mmol) and 200.0 mg 3 A molecular sieve. The reaction tube was purged with nitrogen. 4 mL 1,2-dichloroethane (DCE) was then added to the reaction tube via a syringe. The Schlenk tube was placed in an oil-bath and heated to 100C for 24 h. The reaction mixture was then cooled to room temperature and filtered with ethyl acetate (2×10 mL) to remove the solid residue. The combined solution was concentrated by the rotary evaporator, and then purified by column chromatography on silica gel using petroleum ether/ethyl acetate as eluent to give the desired product.
With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In 1,2-dichloro-ethane; at 100℃; for 24h;Schlenk technique; Molecular sieve; Inert atmosphere;
General procedure: A 20 mL Schlenk tube equipped with a stir-bar was charged with substituted diphenylmethanes (0.5 mmol), TsNH2 (1.0 mmol), DDQ (0.6 mmol) and 200.0 mg 3 A molecular sieve. The reaction tube was purged with nitrogen. 4 mL 1,2-dichloroethane (DCE) was then added to the reaction tube via a syringe. The Schlenk tube was placed in an oil-bath and heated to 100C for 24 h. The reaction mixture was then cooled to room temperature and filtered with ethyl acetate (2×10 mL) to remove the solid residue. The combined solution was concentrated by the rotary evaporator, and then purified by column chromatography on silica gel using petroleum ether/ethyl acetate as eluent to give the desired product.
60%
With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In nitromethane; at 80℃; for 4h;
General procedure: To a solution of amide 2 (0.3 mmol), allylic or benzylic sp3 C-H compound 1 (1.5 mmol) in CH3NO2 (3 mL) was added DDQ (0.36 mmol). The resulting mixture was heated at 80 C while stirring for indicated time. After completion of the reaction as evidenced by TLC, the reaction mixture was cooled to room temperature and filtered. Filtrate was diluted with water (10 mL) and extracted into ethyl acetate (3 × 10 mL). The combined organic layer was washed with saturated NaHCO3 solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give crude residue, which was purified on silica gel column chromatography using hexane and ethyl acetate as the eluent to give the pure product. All products were characterized by 1H, 13C, IR, and mass spectral data.
57%
With di-tert-butyl peroxide; acetic acid; cobalt(II) bromide; In 1,1,2-trichloroethane; at 120℃; for 28h;
General procedure: Ethylbenzene (1 mL), or a solution of diphenylmethane (1 mmol) in trichloroethane (1 mL), was added to a mixture of amide (0.5 mmol), CoBr2 (0.1 mmol) and AcOH (0.05 mmol) at room temperature, and DTBP (1 mmol) was then added. The resulting mixture was stirred at 120 C for 28 h under air. After cooling to room temperature, the mixture was diluted with ethyl acetate (50 mL) and washed with water. The organic phase was dried over MgSO4 and removed under reduced vacuum. The residue was purified by column chromatography eluting with ethyl acetate and hexane to afford the desired product.
With tert.-butylhydroperoxide; iodine; In neat (no solvent); at 100℃; for 8h;
General procedure: All reactions were performed on a 0.50mmol scale relative to azoles. The benzotriazole(1a) (0.50 mmol), toluene (2a) (1.50 mmol), I2 (0.050 mmol) and TBHP (2 eq) weretaken in a round bottom flask equipped with stirrer. The resulting mixture was stirred for8 h at 100 oC. After cooling to room temperature, to the reaction mixture was addedwater (2 mL), and extracted with ester (3×10 mL). The combined organic phases werewashed with brine (2×5 mL), dried over anhydrous MgSO4 and concentrated in vacuo.The residue was subjected to flash column chromatography with hexanes/EtOAc (10/1)as eluent to obtain the desired 3aa a light yellow solid( 90% yield). The identity andpurity of the products was confirmed by 1H and 13C NMR spectroscopic analysis.
16.7 mL (0.1 mol) of diphenylmethane and 300 ml of tetrahydrofuran (THF) were added to a solution of500ml three-necked flask, magnetic stirring and argon, ice salt bath 40min, to the three bottles by adding 54.5mL (0.12mol) n-butyl lithium solution, continue ice salt bath 40min, add 13.0555g4-bromobenzophenone(Bis (4-bromophenyl) methanone, 0.05),After the reaction was carried out at room temperature for 12 h, 250 ml of saturated ammonium chloride (NH4Cl) solution was added to the three-necked flask. After stirring for 10 min, the reaction solution was poured into a separatory funnel, the supernatant was taken and the water in the solution was adsorbed with 300 g of anhydrous sodium sulfate. And then heated to 110 C. After adding 5 g of p-toluenesulfonic acid, the mixture was refluxed for 12 hours. After the reaction was stopped, the reaction solution was dried and dried. The reaction mixture was heated to 110 C, The product was spin dried to dry the powder and the powder was dried in vacuo at 60 C for 24 h to give the white intermediate Si-Br in 89% yield.
73.03%
1, under the conditions of a temperature of 0 C, the 100ml three-necked flask was evacuated and filled with N2 three times,12 mmol of diphenylmethane and 50 ml of dehydrated tetrahydrofuran were evacuated, and 10 mmol of n-butyllithium was gradually introduced into the flask. While maintaining the atmosphere of nitrogen at 0 C, n-butyllithium was subjected to dehydrogenation for 1 hour. To the solution was added 9.5 mmolBromobenzophenone, the reaction was allowed to return to room temperature and stirred for 6 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride. The organic phase was extracted with CH 2 Cl 2, washed three times with saturated brine and dried over anhydrous Na 2 SO 4. The organic solvent , The residue,Toluenesulfonic acid and 60 ml of toluene were added to a 100 ml two-necked flask, and the mixture was refluxed for 6-8 hours. The mixture was cooled to room temperature and the organic layer was washed with 10% aqueous NaHCO 3 solution Three times, the combined organic phases were dried over anhydrous Na2SO4 and the solvent toluene was evaporated under reduced pressure. The residue was purified by column chromatography to give a white solid Product 1-1. Yield: 73.03%. 1-1
66%
In a 250 mL three-necked flask,Diphenylmethane (10.0 g, 59.5 mmol) was dissolved in 150 mL of re-distilled tetrahydrofuran,At 0 slowly added dropwise n-BuLi (25mL, 2.5M),After reaction for 30 min, 4-bromobenzoylbenzene (5.2 g, 20.0 mmol) was slowly added dropwise.Then, the temperature was raised to room temperature for 6 h, quenched with ammonium chloride,The reaction was extracted with CH2Cl2 (3 x 20 mL) and the extract was washed with water (3 x 20 mL)Dried over anhydrous MgSO4 and the solvent was removed under reduced pressure to give an alcohol.The above alcohol solution was dissolved with toluene,P-toluenesulfonic acid (1.7 g, 0.01 mol) was added,The reaction was carried out at 110 C for 3-4 h with a water distilling apparatus.The reaction was extracted with sodium bicarbonate. The extract was washed with water (3 x 20 mL) and dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the column was separated (PE) to give 5.3 g of product (yield: 66%) as a white solid.
64%
1. Add 10.09 g (0.06 mol) of diphenylmethane to a 500 mL three-necked flask.And 250 mL of dry tetrahydrofuran, vacuum replacement, cooling to 0 C,Maintain mixing,Slowly add to the mixture with a syringe under nitrogen protection24.0 mL of 2.5 mol/L (0.06 mol) n-butyllithium in cyclohexane solution,Stirring was continued for 30 min after the addition, and then 40 mL of a dry tetrahydrofuran solution containing 15.14 g (0.058 mol) of 4-bromobenzophenone was added dropwise.After stirring at room temperature for 10 h, the reaction mixture was quenched with aqueous ammonium chloride, and extracted with dichloromethane (300 mL×3×),Rinse alternately with saturated aqueous sodium chloride solution and deionized water (300 mL × 3 times).Dry with anhydrous magnesium sulfate, filter, and distill off the solvent.The intermediate 2-(4-bromophenyl)-1,1,2-triphenylethanol was obtained.The obtained intermediate was dissolved in 300 mL of toluene with 1.0 g of anhydrous p-toluenesulfonic acid.After refluxing for 5 h, toluene was distilled off, and the obtained solid was dissolved in 300 mL of dichloromethane.Then alternately wash with saturated aqueous sodium chloride solution and deionized water (300mL×3 times).Drying anhydrous magnesium sulfate, filtering, and distilling off the solvent to obtain a crude product;Taking cyclohexane/dichloromethane (v/v=5:1) as the eluent,The crude product was separated by silica gel column chromatography.15.27g of white solid 1-(4-bromophenyl)-1,2,2-triphenylethylene,The yield was 64%.
37%
Step 1, synthesis of bromotetraphenylethene (TPE-Br) The benzylbenzene (2.0g, 11.9mmol) was dissolved in 20mL of anhydrous tetrahydrofuran, was stirred at 0C under nitrogen atmosphere, 1.6M n-hexane solution of n-butyllithium (7.4mL, 11.9mmol) was slowly added, reacted for 30 minutes; and then 4-bromo-benzophenone (3.1g, 11.9mmol) was added, slowly warmed to room temperature and the reaction mixture was stirred for 6 hours, followed by addition of a small amount of water to the reaction solution for the reaction to stop, the reaction solution was extracted twice with dichloromethane, the organic layer was dried over anhydrous magnesium sulfate and was filtered. The solvent was distilled off under reduced pressure. The resulting solid was dissolved in 80mL of toluene, p-toluenesulfonic acid monohydrate (500mg, 2.6mmol, catalyst) was added, and refluxed for 16 hours, the reaction was cooled to room temperature and extracted twice with dichloromethane, the organic layer was dried over anhydrous magnesium sulfate and was filtered. The solvent was distilled off under reduced pressure. The crude product with hexane as a mobile phase and the silica gel as the stationary phase was pass through column chromatography, obtaining a white solid 1.8g, 37% yield;
10 g of diphenylmethane was placed in a two-neck reaction flask, nitrogen was distilled off three times, and 50 mL of tetrahydrofuran was added under a nitrogen atmosphere.25 mL of 2.5 M n-butyllithium was slowly injected under ice bath at 0 C. After one hour of activation, a solution of 12.2 g of 4-bromobenzophenone in 20 mL of tetrahydrofuran was added thereto, and the mixture was reacted at room temperature for 8 hours.The reaction was quenched with saturated ammonium chloride solution, extracted with dichloromethane. The organic phase was collected and concentrated in vacuo. The obtained solid was washed with n-hexane and methanol to remove excess diphenylmethane, and the remaining solid residue was poured into a reaction flask, and 30 mL of toluene was added. With 20 mg of p-toluenesulfonic acid, refluxed overnight to obtain a crude product using n-hexane over silica gel column.The white solid product 2-(4-bromophenyl)-1,1,2-triphenylethylene was obtained.
With tert.-butylhydroperoxide; iodine; In neat (no solvent); at 100℃; for 8h;
General procedure: All reactions were performed on a 0.50mmol scale relative to azoles. The benzotriazole(1a) (0.50 mmol), toluene (2a) (1.50 mmol), I2 (0.050 mmol) and TBHP (2 eq) weretaken in a round bottom flask equipped with stirrer. The resulting mixture was stirred for8 h at 100 oC. After cooling to room temperature, to the reaction mixture was addedwater (2 mL), and extracted with ester (3×10 mL). The combined organic phases werewashed with brine (2×5 mL), dried over anhydrous MgSO4 and concentrated in vacuo.The residue was subjected to flash column chromatography with hexanes/EtOAc (10/1)as eluent to obtain the desired 3aa a light yellow solid( 90% yield). The identity andpurity of the products was confirmed by 1H and 13C NMR spectroscopic analysis.
Diphenylmethane (3.36 g, 20 mmol, 1.25 eq) was added to a 250 mL oblique vial.Add 80 mL of freshly steamed anhydrous THF under argon.Stir at 0 C for 30 min.Slowly add n-BuLi (1.6M, 12.5mL, 1.25eq),Stirring was continued for 1 h, then 1,4-dibromobenzophenone (5.44 g, 16 mmol, 1 eq) was added.The reaction was continued for 2 h, then allowed to warm to room temperature and allowed to react overnight.The reaction was quenched by the addition of aq.The solvent was removed and the crude product was taken without further purification.Used directly in the next step. Add p-toluenesulfonic acid to the reaction flask(0.34 g, 1.8 mmol), toluene 80 mL, refluxed at 110 C overnight.Cool to room temperature, spin off the toluene and extract three times with DCM.Dry over anhydrous sodium sulfate, filter and spin dry.The crude product was purified by silica gel chromatography (eluent: PE).6.6g of white solid,The yield was 75%.
With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In 1,2-dichloro-ethane; at 100℃; for 24h;Schlenk technique; Molecular sieve; Inert atmosphere;
General procedure: A 20 mL Schlenk tube equipped with a stir-bar was charged with substituted diphenylmethanes (0.5 mmol), TsNH2 (1.0 mmol), DDQ (0.6 mmol) and 200.0 mg 3 A molecular sieve. The reaction tube was purged with nitrogen. 4 mL 1,2-dichloroethane (DCE) was then added to the reaction tube via a syringe. The Schlenk tube was placed in an oil-bath and heated to 100C for 24 h. The reaction mixture was then cooled to room temperature and filtered with ethyl acetate (2×10 mL) to remove the solid residue. The combined solution was concentrated by the rotary evaporator, and then purified by column chromatography on silica gel using petroleum ether/ethyl acetate as eluent to give the desired product.
With n-butyllithium; In tetrahydrofuran; at -20℃; for 3h;Inert atmosphere;
Diphenylmethane (12 mmol, 2.02 g)Dissolved in 50ml of tetrahydrofuran, minus 20 ,Under nitrogen, 2.5 M n-butyllithium (10 mmol, 4 ml) was added dropwise,4-Methoxybenzophenone (12 mmol, 3.03 g)Warmed to room temperature, stirred for 3 hours,Quenched with water, extracted with methylene chloride,Unscrew the solvent, add toluene,P-toluenesulfonic acid (1.8 mmol, 0.342 g),Reflux for 6 hours,Cool at room temperature, washed with 5% sodium bicarbonate twice, anhydrous magnesium sulfate dare to spin out the solvent to give a yellow crude product,Recrystallization gave white solid product Compound A, 80%.
74%
The diphenylmethane 4’ (3 g, 18 mmol) and the THF (20 mL) were added into the 100 mL flask. Replacing the gas in the flask 3 times under argon atmosphere, and the n-BuLi (7.5 mL, 18 mmol) was added at 0 oC dropwise, and the solution was stirred for 1 h. After that, the mixture was added into the 4-methoxylbenzophenone 5’ (3.4 g, 16 mmol) solution of THF (30 mL) at 0 oC. The solution was stirred at 30 oC for 6 h after 15 min. The mixture was poured into the solution of NH4Cl and was extracted with EA. The organic layer was washed with NaCl saturated aqueous solution, and dried with anhydrous sodium sulfate. The residue was evaporated and was added into the p-toluene sulfonic acid (0.69 g, 4 mmol) solution of toluene (120 mL). The solution was stirred at 120 oC for 6 h. The mixture was washed with saturated NaCl aqueous solution, dried, concentrated and purified by column chromatography on silica gel (SiO2, PE : DCM = 10:1, V/V) to give white solid (4.29 g, 74.0%). 1H NMR (400 MHz, CDCl3, ppm): δ = 7.10 - 6.98 (m, 15 H), 6.93 (d, J = 8.8 Hz, 2 H), 6.60 (d, J = 8.8 Hz, 2 H), 3.65 (s, 3 H).
5.93 g
(1) Under a nitrogen atmosphere,In SchlenkTube added dibenzyl burn(3.16 g, 20 mmol) and 80 mL of dry tetrahydrofuran. 2.2 M n-butyllithium in hexane (9. lmL, 20 mmo 1) was added dropwise at 0 C and the reaction was carried out at 0 C for 0.5 h.4-methoxybenzoylbenzene (3.40 g, 16 mmol) was added and the temperature was allowed to warm to room temperature and stirring was continued for 6 hours. After completion of the reaction, the reaction was quenched by the addition of saturated aqueous ammonium chloride solution, extracted with dichloromethane, the organic phase was collected, dried over anhydrous Na2S04,The solvent was evaporated to give the crude product as an intermediate. The intermediate was dissolved in 80 mL of dry toluene in a 250 mL round bottom flask,A catalytic amount of hydrated p-toluenesulfonic acid was added(570 mg, 3.0 mmol) and refluxed for 12 hours. After completion of the reaction, the mixture was cooled to room temperature, and the toluene solution was washed with 10 wt% aqueous NaHC03 solution. The organic phase was collected, the organic phase was collected, dried over anhydrous Na2S04, and the product was chromatographed on silica gel using petroleum ether as eluant. And the residue was dried in vacuo to give a white solid (5.93 g, yield 90.1%). The structure was characterized by Guru NMR. It was confirmed that the white solid was Compound 1,
With iron(II) chloride tetrahydrate; ethanol at 400℃; for 3h;
Catalytic activity measurements
General procedure: All the experiments were performed in stainless-steel batchreactors with an internal volume of 13 mL. Reactions were carriedout in the temperature range of 300-400C with a reaction time of3 h. The reactors were filled with either 8 mL of water or 6.5 mL ofanhydrous ethanol. The reactant and catalyst concentrations were0.1 mol/L and 0.025 mol/L, respectively. Reactions at 300C and350C were carried out by placing the autoclaves in the oven of agas chromatograph. Reactions at 400C were done in a pre-heatedfluidized sand bath. After reaction, the reactors were quenched inan ice bath. The organic compounds were extracted from the watersolvent by ethyl acetate in 1:1 volume ratio with water. In case ofethanol as solvent, this extraction step was not needed.
With manganese(II) acetate dihydrate; trifluoroacetic acid; 2,3-dicyano-5,6-dichloro-p-benzoquinone; In 1,2-dichloro-ethane; at 90℃; for 12h;Inert atmosphere;
To the reactor was added 0.2 mmol of diphenylmethane, 0.04 mmol of manganese acetate dihydrate, 0.4 mmol of DDQ, 0.5 mL of cyclopropionitrile, 0.15 mL of TFA,0.35mL DCE mixed, heated to 90 under nitrogen, stirring for 12h, stop the reaction, cooling to room temperature, adding potassium carbonate to neutral, extracted with ethyl acetate,Dried, and the solvent was removed by distillation under reduced pressure. The crude product was separated by column chromatography to obtain the desired product,Yield 94%.
With 5 mol% Pd/C; In cyclohexane; at 130℃; for 24h;Inert atmosphere; Molecular sieve; Sealed tube;
General procedure: Dry glass reaction tube purged with argon and equipped with a magnetic stir bar was chargedwith molecular sieves (3-4 A, 100 mg), aldehyde 1a (50 muL, 0.38 mmol), Pd/C (20 mg, 5 mol%Pd), and cyclohexane (1 mL) and the sealed tube was heated at 130 C for 24 h. The reaction mixture was cooled to room temperature, filtered through a pad of Celite, and washed withCH2Cl2 (15 - 20 mL). Compound 2a was obtained, GC-MS yield: 67%, based on naphthalene asa standard.
With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In 1,2-dichloro-ethane; at 100℃; for 8h;Inert atmosphere; Sealed tube;
General procedure: An oven-dried pressure tube (10 mL) was charged with diphenylmethane (1a, 33.4 L, 0.2 mmol),benzoic acid (2a, 36.6 mg, 0.3 mmol), DDQ (54.5 mg, 0.24 mmol), and DCE (0.6 mL). The reaction vesselwas flushed with argon and sealed. The resulting solution was heated to 100 C for 8 h. After coolingto room temperature, the volatiles were removed under vacuum and the residue was purified bycolumn chromatography (silica gel, petroleum ether/ethyl acetate = 9:1) to give 3a as white solid; yield:46.1 mg (80%). (NMR spectra for all compounds shown in the Supplementary Materials).
benzhydryl 3-methylthiophene-2-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88%
With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In 1,2-dichloro-ethane; at 100℃; for 8h;Inert atmosphere; Sealed tube;
General procedure: An oven-dried pressure tube (10 mL) was charged with diphenylmethane (1a, 33.4 L, 0.2 mmol),benzoic acid (2a, 36.6 mg, 0.3 mmol), DDQ (54.5 mg, 0.24 mmol), and DCE (0.6 mL). The reaction vesselwas flushed with argon and sealed. The resulting solution was heated to 100 C for 8 h. After coolingto room temperature, the volatiles were removed under vacuum and the residue was purified bycolumn chromatography (silica gel, petroleum ether/ethyl acetate = 9:1) to give 3a as white solid; yield:46.1 mg (80%). (NMR spectra for all compounds shown in the Supplementary Materials).
With (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; potassium carbonate; In acetonitrile; at 20.0℃; for 12.0h;Inert atmosphere; Irradiation;
Weigh first (74.1mg, 0.3mmol), 4CzIPN (3.2mg, 0.004mmol),K2CO3 (5.52mg, 0.04mmol), added to the reaction tube,Pumped through the vacuum line three times, under an argon atmosphere,Add 4mL of anhydrous acetonitrile, then carefully add (purchased from Nanjing Chemical Reagent Co., Ltd; 33.7mg, 0.2mmol),Then placed under the irradiation of two 45W blue light lamps, the reaction at room temperature for 12h.Dry loading, column chromatography (300-400 mesh chromatography silica gel, the same below) to obtain 44.5mg of product,(Eluent: n-hexane), yield 83%,
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