3,3',5,5'-Tetraisopropylbiphenyl-4,4'-diol

Yellow Solid

Compound 32A (2 g, 5.65 mmol) was dissolved in tetrahydrofuran (20 mL).Sodium hydride (0.13 g, 5.33 mmol) was slowly added at 0 °C.The mixture was naturally warmed to room temperature and stirred for 20 min.Bromochloromethane (2.20 g, 17.00 mmol) was added, the temperature was raised to 50 ° C, and the reaction was stirred for 4 h. The solvent was removed under reduced pressure and ethyl acetate (20 mL) was evaporated.After the organic layer is concentrated, The residue was purified by silica gel column chromatography ( petroleum ether / ethyl acetate = (v/v) 400/1 to 100/1).Compound 32B was obtained as a yellow oil (500 mg, yield: 21.96percent).Phosphorus oxychloride (1.54 g, 10 mmol) was dissolved in 100 ml of dichloromethane, protected with nitrogen, cooled to -30 ° C, and 20 g propofol was weighed and dissolved in 100 mL ethyl acetate, 24.75 g silver carbonate and 10 g anhydrous magnesium sulfate were then added thereto, stirred at room temperature for 2 h, and the reaction was checked for completion. Water was added to the reaction solution until no bubble emerged. The solid was filtered and washed with ethyl acetate, and the aqueous phase was removed. The ethyl acetate phase was dried over anhydrous sodium sulfate for 1 h and filtered. The filtrate was evaporated to dryness under reduced pressure and washed with anhydrous methanol to give 12.30 g rosy red crystal. 7 g of the above rosy red solid was dissolved in 100 mL of ethyl acetate. Then, 27.66 g sodium hydrosulfite was dissolved in 1 mol/L NaOH and added to the resultant ethyl acetate solution of the above rosy red solid, the mixture was stirred at room temperature for 1.5 h, and the reaction was checked for completion. The ethyl acetate phase was separated, the aqueous phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate and filtered, and the filtrate was evaporated to dryness under reduced pressure to give 5 g of a light yellow solid which was washed with petroleum ether to give 4.5 g white solid. 1H NMR (300 MHz, CDCl3): delta 7.22 (s, 4H), 4.81 (s, 2H), 3.27-3.20 (m, 4H), 1.37-1.35 (d, 24H).4, 4?-dihydroxy-3, 3?, 5, 5?-tetraisopropylbiphenyl (5.00 g, 14.10 mmol) was dissolved in DMSO (20 mL), and succinic anhydride (1.41 g, 14.09 mmol) was then added thereto and heated at 90° C. for a reaction for 5 h. The reaction solution was cooled to room temperature, into which water was added, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and filtered to remove sodium sulfate. The filtrate was purified with petroleum ether-ethyl acetate eluent to give [4-(4?-hydroxy-3, 3?, 5, 5?-tetraisopropylbiphenyl)oxy]-4-carbonylbutyric acid (3.50 g, 54.59percent) as a white solid. 1H NMR (300 MHz, CDCl3) delta 11.10 (s, 1H), 7.65 (s, 2H), 7.51 (s, 2H), 5.35 (s, 1H), 3.07-3.04 (m, 4H), 2.71 (s, 4H), 1.20-1.18 (d, 24H)4, 4?-dihydroxy-3, 3?, 5, 5?-tetraisopropylbiphenyl (1.0 g, 2.8 mmol) was dissolved in methylene chloride, solid sodium hydroxide (0.112 g, 2.8 mmol) was added thereto under stirring, and then N, N-dimethylformyl chloride (0.3 mL, 2.8 mmol) was added slowly and refluxed for 3 h. The solvent was evaporated to dryness, water was added, and the mixture was extracted with ethyl acetate, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and concentrated to give a yellow oil which was then purified with petroleum ether-ethyl acetate eluent and recrystallized from petroleum ether-ethyl acetate to give 4?-hydroxy-3, 3?, 5, 5?-tetraisopropylbiphenyl-4-dimethyl carbamate (0.36 g, 30.2percent) as a white solid and 3, 3?, 5, 5?-tetraisopropylbiphenyl-4, 4?-bis(dimethylcarbamate) (0.31 g, 22.3percent) as a white solid. (0101) 4?-hydroxy-3, 3?, 5, 5?-tetraisopropylbiphenyl-4-dimethylcarbamate: white solid. 1H NMR (300 MHz, CDCl3) delta 7.16 (s, 2H), 7.12 (s, 2H), 4.82 (s, 1H), 3.11 (s, 6H), 2.98-2.93 (m, 4H), 1.20 (d, 24H). (0102) 3, 3?, 5, 5?-tetraisopropylbiphenyl-4, 4?-bis(dimethylcarbamate): white solid. 1H NMR (300 MHz, CDCl3) delta 7.18 (s, 4H), 3.12 (s, 12H), 2.98-2.94 (m, 4H), 1.22 (d, 24H).(1) 4, 4?-dihydroxy-3, 3?, 5, 5?-tetraisopropylbiphenyl (0.5 g, 1.4 mmol) was dissolved in dry THF (10 mL), solid NaOH (0.224 g, 5.6 mmol) and bromochloromethane (8.185 g, 84 mmol) was added thereto, and then refluxed under N2 for 2 h. The reaction solution was cooled to room temperature, filtered, and concentrated to give a yellow oil as intermediate. (0097) (2) Triethylamine (1.4 mL, 11.03 mmol) and 85percent phosphoric acid (0.5 mL, 8.9 mmol) was added sequentially to 10 mL of anhydrous acetonitrile. The intermediate obtained in (1) was added to the acetonitrile solution under stirring, and then reacted at 65° C. for 2 h. The reaction solution was cooled to room temperature, the solvent was evaporated, and the residue was dissolved in 15 mL of water, adjusted to pH=1.5 with 8 M HCl, and extracted with anhydrous ether. The organic phase was combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and concentrated to give a yellow oil. (0098) (3) 5 mL of water was added to the above oil, adjusted to pH 9 with 20percent sodium hydroxide solution, and extracted twice with toluene. The aqueous phase was concentrated to volume, and 9 mL of isopropanol was added. The mixture was heated at 70° C. until the solution became transparent, and then cooled to 0° C. White solid was precipitated, filtered, and dried under vacuum at 45° C. to give 3, 3?, 5, 5?-tetraisopropylbiphenyl-4, 4?-bis(oxymethylenephosphate) (50 mg, 5percent). 1H NMR (300 MHz, D2O) delta 7.29 (s, 4H), 5.20 (s, 4H), 3.36-3.12 (m, 4H), 1.12 (d, 24H).Preparation procedure: 4, 4?-dihydroxy-3, 3?, 5, 5?-tetraisopropylbiphenyl (5 g, 14.10 mmol) was added to 30 mL acetic anhydride and allowed to reflux for 3 h under nitrogen. The reaction solution was cooled to room temperature and the acetic anhydride was removed under reduced pressure. Water (200 mL) was added to the residue to give a white solid which was washed with 10percent cold ethanol (100 mL) and water (200 mL) and dried to obtain 3, 3?, 5, 5?-tetraisopropylbiphenyl-4?-diacetate (6 g, 95.06percent), as white solid. 1H NMR (300 MHz, CDCl3) delta 7.19 (s, 4H), 2.91-2.89 (m, 4H), 2.32 (s, 6H), 1.19 (d, 24H).4, 4?-dihydroxy-3, 3?, 5, 5?-tetraisopropylbiphenyl (5 g, 14.10 mmol) was added to 30 mL acetic anhydride and allowed to reflux for 3 h under nitrogen. The reaction solution was cooled to room temperature, and the acetic anhydride was removed under reduced pressure. Water (200 mL) was added to the residue to give a white solid which was washed with 10percent cold ethanol (100 mL) and water (200 mL) and dried to afford 3, 3?, 5, 5?-tetraisopropylbiphenyl-4?-diacetate (6 g, 95.06percent) as a white solid. (0091) White solid, 1H NMR (300 MHz, CDCl3) delta 7.19 (s, 4H), 2.91-2.89 (m, 4H), 2.32 (s, 6H), 1.19 (d, 24H).

Dipropofol is a dimeric derivative of Propofol (P829750). Dipropofol is an antibacterial agent with strong activity againts Gram-positive bacteria. Dipropofol also displays antioxidant and radical sca venging activity.

Molecular Weight:354.5
XLogP3:7.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:5
Exact Mass:354.255880323
Monoisotopic Mass:354.255880323
Topological Polar Surface Area:40.5
Heavy Atom Count:26
Complexity:352
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes