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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
1,4-Dimethoxybenzene is an endogenous metabolite.
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CAS No. : | 150-78-7 |
Formula : | C8H10O2 |
M.W : | 138.16 |
SMILES Code : | COC1=CC=C(OC)C=C1 |
MDL No. : | MFCD00008401 |
InChI Key : | OHBQPCCCRFSCAX-UHFFFAOYSA-N |
Pubchem ID : | 9016 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
92% | Stage #1: With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 2 h; Stage #2: at 0℃; for 2 h; Stage #3: With ammonia; iodine In tetrahydrofuran; hexane; water at 0 - 20℃; for 2 h; |
General procedure: n-Butyllithium (1.67 M solution in hexane, 2.9 mL, 4.8 mmol) was added dropwise into a solution of 1,3-dimethoxybenzene (0.55 g, 4.0 mmol) in THF (5 mL) at 0 °C and the mixture was stirred for 2 h at the same temperature. Then, DMF (0.34 mL, 4.4 mmol) was added to the mixture and the obtained mixture was stirred at 0 °C. After 2 h at the same temperature, aq NH3 (8 mL, 120 mmol) and I2 (1.12 g, 4.4 mmol) were added and stirred for 2 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (15 mL) and was extracted with Et2O (3.x.20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide 2,6-dimethoxybenzonitrile in over 80percent purity. The product was purified by a short column chromatography on silica gel (Hexane/EtOAc=3:1) to give pure 2,6-dimethoxybenzonitrile in 91percent yield as a colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Stage #1: at 0℃; for 0.5 h; Stage #2: at 100℃; for 10 h; Stage #3: With ammonia; iodine In tetrahydrofuran; water; N,N-dimethyl-formamide at 20℃; for 3 h; |
General procedure: To an ice cooled solution of N-methylformanilide (2.2 mmol) was added dropwise diphosphoryl chloride (2.2 mmol). The solution was stirred for 30 min at 0 °C, and then 1,2-dimethoxybenzene (276.3 mg, 2 mmol) in DMF (1.0 mL) was added dropwise. After being stirred for 10 h at 100 °C, I2 (1015.2 mg, 4 mmol), aq NH3 (4 mL, 28-30percent) and THF (1 mL) were added to the reaction mixture. The obtained mixture was stirred for 3 h at rt. After the reaction, the mixture was poured into aq satd Na2SO3 solution and extracted with CHCl3 (3.x.20 mL). The organic layer was dried over Na2SO4, filtered, and evaporated. The product was purified by flash short column chromatography (Hexane:AcOEt=3:1) to afford 3,4-dimethoxybenzonitrile as a white solid in 92percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | A three-necked reactor equipped with a thermometer was charged with 7.0 g (50.67 mmol) of 1,4-dimethoxybenzene, 29.44 g (253.33 mmol) of N,N,N?,N?-tetramethylethylenediamine, and 280 ml of diethyl ether under a nitrogen stream to prepare a homogeneous solution. After cooling the solution to 0 C., 97.4 ml (253.33 mmol) of 2.6 M n-butyllithium (n-hexane solution) was added dropwise to the solution over 30 minutes. After the dropwise addition, the reaction mixture was reacted for 5 hours under reflux, and then cooled to -78 C. After the addition of 18.52 g (253.33 mmol) of N,N-dimethylformamide, the mixture was stirred at -78 C. for 1 hour. After the addition of 350 ml of a 3 N hydrochloric acid aqueous solution to the reaction mixture at -78 C., the mixture was heated to 25 C., and 300 ml of distilled water and 200 ml of a saturated sodium chloride solution were added to the mixture, followed by extraction with 700 ml of chloroform. The chloroform layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. The solvent was evaporated from the filtrate under reduced pressure using a rotary evaporator. The resulting solid was added to 100 ml of toluene. After stirring the mixture for 5 minutes, the resulting crystals were filtered off to obtain 6.1 g of an intermediate A as yellow crystals (yield: 62%). (0225) The structure of the target product was identified by 1H-NMR. (0226) 1H-NMR (500 MHz, CDCl3, TMS, delta ppm): 10.51 (s, 2H), 7.46 (s, 2H), 3.95 (s, 6H). | |
at 20℃; | (4) C product was added N, N-dimethylformamide 220mmol, stirred overnight at room temperature; (5) D product is added with 100ml water, extracted with chloroform (3x100ml), the organic phase is dried over anhydrous magnesium sulfate, and the solvent is removed under reduced pressure.Silica gel column chromatography, the eluent was 6/4 volume ratio of n-hexane / toluene, yellow solid intermediate c, that is, E product; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride;aluminium trichloride; | EXAMPLE 4 Synthesis of 5,6,7,8-tetrafluoroquinizarin Into a molten mixture (130 to 135 C.) of 7 g of common salt and 70 g of aluminum chloride, 11.0 g (0.050 mol) of tetrafluorophthalic anhydride and 10.3 g (0.075 mol) of 1,4-dimethoxybenzene were added piecemeal. After completion of the addition, the resultant mixture was heated and stirred at 200 C. for 30 minutes. Then, the resultant reaction mixture was poured into ice water. Subsequently, the cooled reaction mixture and 200 ml of concentrated hydrochloric acid added thereto were heated and stirred. The crystals which were consequently precipitated were separated by filtration, washed with cold water, and then dried. Consequently, there was obtained 11.1 g of 5,6,7,8-tetrafluoroquinizarin (in a yield of 71.1 mol% based on tetrafluorophthalic anhydride) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33%; 10% | 1,4-Dimethoxybenzene (11.96 g, 86.56 mmol) and<strong>[5471-84-1]1,4-bis(bromoethoxy)benzene</strong> (1.75 g, 5.41 mmol) weredissolved in dry CH2Cl2 (350 mL). Paraformaldehyde(7.80 g, 259.68 mmol) was added and the mixture sirredunder a nitrogen atmosphere. After cooling to 0 C, FeCl3(2.19 g, 13.53 mmol) was added with stirring. The temperaturewas maintained at 0 C for a further 30 min, duringwhich time the solution turned light green, before beingallowed to warm to room temperature, whereupon it wasstirred for a further 3 h, turning dark green in the process.After completion of the reaction, distilled water (100 mL)was added. The organic layer was isolated, washed withdistilled water (100 mL), saturated brine (100 mL) anddried over Na2SO4. After filtration the solvent was removedunder vacuum and purified by column chromatography(silica, 230-400 mesh, 3.0 cm × 25.5 cm column), using amixture of petroleum ether and CH2Cl2 (initially 2:1 thendecreasing to 1:1) as the eluent. Two products (2 and 3)were obtained as white solids.1,4-Bis(bromoethyoxy)copillar[4+1]arene (2): yield1.56 g (33%); Rf: 0.66 (petroleum ether:CH2Cl2 1:1; silica40-70 Å); m.p.: 127.5 C; 1H NMR (400 MHz, CDCl3) δ (ppm):6.79 (d, J = 5.6 Hz, 4H, -ArH), 6.77 (s, 4H, -ArH), 6.73 (s, 2H,-ArH), 4.06 (t, J = 6.2 Hz, 4H, CH2O), 3.79 (s, 4H, ArCH2Ar),3.78 (s, 6H, ArCH2Ar), 3.69 (s, 18H, OCH3), 3.74 (s, 6H, OCH3), 3.55 (t, 4H, -CH2Br); 13C NMR (90 MHz, CDCl3) δ (ppm):150.85, 150.78, 150.74, 149.74, 129.11, 128.57, 128.24,128.15, 127.82, 115.83, 114.39, 114.03, 113.93, 68.74, 56.05,55.82, 55.79, 55.76, 34.00, 29.88, 29.80, 29.56; IR (ν, cm-1):2929.4, 2100.2, 1721.4, 852.2, 696.4; HRMS (m/z): calcd forC47H52Br2NaO10, 959.1804; found, 959.2048. Data are inagreement with literature values (36).1,4-Bis(bromoethyoxy)copillar[3+2]arene (3): yield:607 mg (10%); Rf: 0.80 (petroleum ether:CH2Cl2 1:1; silica40-70 Å); m.p.: 140.24 C; 1H NMR (400 MHz, CDCl3)δ (ppm): 6.90-6.91 (m, 6H, -ArH), 6.85 (d, 4H, -ArH),3.93-3.97 (m, 8H, ArCH2Ar), 3.78-3.81 (m, 28H, ArCH2Ar+-OCH3), 3.49-3.52 (m, 8H, -CH2Br); 13C NMR (90 MHz,CDCl3) δ (ppm): 150.82, 150.80, 150.73, 149.73, 129.26,128.55, 127.95, 115.78, 115.73, 114.34, 113.92, 68.83, 68.74,56.05, 55.79, 39.7, 31.84, 31.53, 29.95, 29.67, 29.59, 28.97;IR (ν, cm-1): 2932.1, 1910.2, 1781.2, 1730.3, 850.1, 692.3;HRMS (m/z): calcd for C49H54Br4NaO10, 1145.0308; found,1144.9071. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | To a solution of 1-1 1 ,4-dimethoxybenzene (11.5 g, 83.26 mmol, 1 eq) in distilled Et20(276 mL) was added TMEDA (37,4 mL, 249.78 mmol, 3 eq). At 000, nBuLi at 2.5 M inhexane (100 mL, 249.78 mmol, 3 eq) was added dropwise. The mixture was stirred atreflux overnight under inert atmosphere. At 000, 1-formylpiperidine (27.74 mL, 249.78mmol, 3 eq). was added dropwise. The mixture was stirred at room temperature for 1 h.Following the addition of distilled water (300 mL) and HCI 3 M (57.5 mL), the mixture was extracted with hot CHCI3 (300 mLx4). The organic phase was dried over an hydrous Na2SO4 and filtered. After removing the solvent, the remaining residue was purified by recrystallization in CHCI3 to give an orange solid (9.51 g, 51 %).1H NMR (300 MHz, ODd3) 6 ppm = 10.51 (s, 2 H, CHO), 7.46 (s, 2 H, Ar), 3.95 (s, 6 H,OH3) data matched with literature reference |
Tags: 1,4-Dimethoxybenzene | Benzene Compounds | Aryls | Ethers | Organic Building Blocks | 150-78-7
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