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With potassium permanganate; In water; tert-butyl alcohol; for 16.0h;Reflux; |
Arene 8 (6.46 g, 28.4 mmol) was dissolved in t-BuOH (50 mL) and H2O (50 mL). KMnO4 (9.2 g, 58 mmol) and Celite (10 g) were added and the reaction mixture was refluxed for 16 h. The reaction mixture was cooled to rt and filtered through a pad of Celite. The filtrate was acidified with concd HCl and extracted with MTBE (3*75 mL). The combined organics were extracted with 5% aq NaOH (3*50 mL). The combined aqueous layers were acidified with concd HCl and extracted with MTBE (3*75 mL). The combined organics were dried with MgSO4. The solvents were removed under vacuum to achieve a crude white solid (5.25 g, 72% crude yield), which was not purified further. 1H NMR (CDCl3): delta 7.98 (d, J=8.3 Hz, 1H), 7.72 (d, J=1.5 Hz, 1H), 7.42 (dd, J=8.3, 1.5 Hz, 1H), 1.35 (s, 9H). The crude 2-bromo-4-tert-butylbenzoic acid (5.25 g, 20.4 mmol) was dissolved in MeOH (75 mL), concd H2SO4 (1 mL) was added, and refluxed for 3 h. The reaction mixture was cooled to rt and 75 mL of H2O was added. The reaction mixture was extracted with MTBE (3*50 mL). The combined organics were washed with 50 mL of satd NaHCO3, 50 mL of H2O, and 50 mL of brine. The organics were dried with MgSO4, filtered, and the solvents were removed under reduced pressure to achieve the product (9) as a crude yellow oil (4.6 g, 84% crude yield), which was not purified further. 1H NMR (CDCl3): delta 7.77 (d, J=8.0 Hz, 1H), 7.67 (d, J=1.8 Hz, 1H), 7.37 (dd, J=8.3, 1.8 Hz, 1H), 3.93 (s, 3H), 1.33 (s, 9H). Crude 9 (2.0 g, 7.3 mmol) was dissolved in 1,4-dioxane (75 mL). KOAc (2.20 g, 22.4 mmol) and bis(pinacolato)diboron (2.63 g, 10.4 mmol) were added and the reaction mixture was sparged with Ar for 1 h. Pd(dppf)Cl2 (270 mg, 0.37 mmol) was added, the mixture was sparged with Ar for an additional 15 min, and then heated at 90 C for 16 h. The reaction mixture was cooled to rt and 50 mL of satd NH4Cl and 25 mL of H2O were added. The reaction mixture was extracted with MTBE (3*75 mL). The combined organics were washed with 50 mL of H2O and 50 mL of brine, dried with MgSO4, treated with activated charcoal, and filtered through a pad of Celite. The solvent was removed under vacuum and the product was isolated with column chromatography to afford a white/light green solid (1.74 g, 74%), mp 55-57 C. 1H NMR (CDCl3): delta 7.87 (d, J=8.3 Hz, 1H), 7.47 (d, J=2.0 Hz, 1H), 7.43 (dd, J=8.3 Hz, 2.0 Hz, 1H), 3.90 (s, 3H), 1.44 (s, 12H), 1.33 (s, 9H). 13C NMR (CDCl3): delta 167.4, 154.0, 129.7, 121.7, 121.7, 125.2, 82.9, 51.1, 33.9, 30.1, 23.9. FTIR (cm-1): 1709.55. Anal. Calcd for C18H27BO4: C, 67.94; H, 8.55. Found: C, 67.94; H, 8.72. |
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With potassium permanganate; In water; tert-butyl alcohol; for 16.0h;Reflux; |
p-tert-butyltoluene (5.0 mL, 29 mmol) was dissolved in 60 mL of CH3CN. NaBrO3 (13.2 g, 87.0 mmol) dissolved in H2O (45 mL) was added, followed by addition of NaHSO3 (9.0 g, 87.0 mmol) dissolved in H2O (90 mL) over 15 minutes. The reaction was stirred for 16 hours. The reaction mixture was extracted with Et2O. The combined organic layer was washed with sat. Na2S2O3, brine and water in sequence, and finally dried over Na2SO4. The crude product was obtained by removal of all solvents. Then, it was dissolved in t-BuOH (50 mL) and H2O (50 mL). KMnO4 (13.8 g, 87 mmol) was added and the mixture was refluxed for 16 hours. The mixture was cooled to room temperature and filtered through a pad of Celite. The filtrate was acidified with 2M HCl and extracted with ethyl acetate. The organic layer was washed with brine and water, and finally dried over Na2SO4. The white crude product can be obtained by removal of all solvents. Finally, it was dissolved in EtOH (100 mL), H2SO4 (1.5 mL) was next added, and refluxed for 12 hours. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with NaHCO3, brine and water in sequence, and dried over Na2SO4. The pure white product was obtained (4.8 g) by column chromatography using hexane:EA=30:1 as the eluent in a yield of 58%. (0089) Spectral data of compound (4): 1H NMR (400 MHz, CDCl3): delta 7.73 (d, J=8.2 Hz, 1H), 7.63 (d, J=1.9 Hz, 1H), 7.35 (dd, J=7.3, 2.8 Hz, 1H), 4.37 (q, J=7.2 Hz, 2H), 1.38 (t, J=7.1 Hz, 3H), 1.30 (s, 9H). |
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With potassium permanganate; water; In tert-butyl alcohol; for 16.0h;Reflux; |
P-tert-butyltoluene (5.0 mL, 29 mmol) was dissolved in 60 mL of acetonitrile.Sodium bromate (13.2 g, 87.0 mmol) dissolved in water (45 mL) was added.Sodium bisulfite (9.0 g, 87.0 mmol) dissolved in water (90 mL) was then added over 15 min.The reaction was stirred for 16 hours.And extracted with diethyl ether.Use saturated sodium thiosulfate,brine,Wash the combined organic layer with water,It was dried using sodium sulfate.The crude product was obtained by removing all the solvent.then,Dissolved in tert-butanol (50 mL) and water (50 mL).Potassium permanganate (13.8 g, 87 mmol) was added and the mixture was refluxed for 16 h.The mixture was returned to room temperature and filtered through celite. The filtrate was acidified with 2M hydrochloric acid.It was extracted with ethyl acetate.Use salt water,Wash the organic layer with water,It was dried using sodium sulfate.White crude product by removing all solventsAnd get.2-bromobenzoic acid (2.0 g, 10 mmol) was dissolved in ethanol (100 mL).Add sulfuric acid (1.5mL),Reflux for 12 hours.Pour the mixture into the water,It was extracted with ethyl acetate.Sodium bicarbonate,brine,Wash the organic layer with water,It was dried using sodium sulfate.The pure white product (4.8 g) was obtained by column chromatography.Use n-hexane: ethyl acetate = 30:1 as the extract,The yield in the three stages was 58%. |