* 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] Russian Journal of Organic Chemistry, 1997, vol. 33, # 3, p. 348 - 352
2
[ 603-87-2 ]
[ 81282-60-2 ]
Reference：
[1] Patent: US2014/309208, 2014, A1,
3
[ 573-56-8 ]
[ 603-87-2 ]
Yield
Reaction Conditions
Operation in experiment
95%
With hydrogen In ethyl acetate for 5 h;
To a nitrogen flushed solution of 2, 6-dinitrophenol (10 g, 54.3 mmol) in ethyl acetate (100 ml) was added 10percent palladium on carbon (0.5 g) and the resulting mixture stirred under a balloon of hydrogen for 5 hours. The catalyst was removed by filtration and the filtrate evaporated to give the title compound (8.0 g, 95percent). 1H NMR (400 MHz, CDC13) 8 3.95 (2H, br s), 6.78 (1H, t, J 8. 4 and 8.0), 6.95 (1H, dd, J7. 6 and 1.2), 7.46 (1H, DD, J 8. 6 AND 1.2).
92%
With palladium 10% on activated carbon; hydrogen In methanol for 1 h;
To a of solution of 2,6-dinitrophenol (5.43 mmol, 1.00 g) in methanol (100 mL), 10percent palladium on activated carbon (10 wtpercent of 2,6-dinitrophenol, 0.10 g) was added. The reaction was flushed with argon followed by hydrogen for fifteen minutes each with constant magnetic stirring. The reaction was then maintained under hydrogen atmosphere at ordinary pressure (balloon) for one hour. The reaction was monitored closely by thin layer chromatography to avoid over reduction.1 Argon was again flushed through the reaction vessel for 15 minutes. Then the reaction contents were filtered over a thin pad of celite which was then washed with methanol (50 mL). The filtrate was concentrated in vacuo yielding a brown solid. Silica gel column chromatography (10:1 hexanes/ethyl acetate) provided a crystalline red solid in a 92percent yield.
60%
Stage #1: With sodium sulfide; ammonia; ammonium chloride In water at 70℃; for 2 h; Stage #2: With hydrogenchloride In water
2-Amino-6-nitrophenol: A suspension of 2,6-dinitrophenol 5.0 g (27 mmol), ammonium hydroxide (3 ml) and ammonium chloridel4. 3 g (270 mmol) in 30 ml of water was heated to 70°C. A solution of sodium sulfide nonahydrate (24.19 g, 100 mmol) in water was added and the resulting mixture stirred at 70°C for 2h. The reaction was cooled to room temperature, acidified (pH 3.2) with 2N HC1, and the brown precipitate separated by filtration. The filtrate was extracted with chloroform (6 x 75 ml), the organic extracts combined with the precipitate, and evaporated in-vacuo to yield 2.5 g (60 percent) of product as a dark brown solid. 1H NMR (CDC13) 5 4.09 (s, 2H), 6.78 (t, 1H, J = 8. 2 Hz), 6.95 (d, 1H, J = 7.8 Hz), 7.47 (d, 1H, J = 8.6 Hz), 10.73 (s, 3H).
48%
With palladium 10% on activated carbon; hydrogen In ethyl acetate at 20℃; for 144 h;
Step 1 2-Amino-6-nitrophenol 8.6 g of 2,6-dinitrophenol (46.71 mmol) were dissolved in 95 ml of ethyl acetate. The solution was degassed and then 0.86 g (10percent by weight) of palladium on carbon at 10percent was added. The reaction medium was stirred under a hydrogen atmosphere for 6 days at ambient temperature. The reaction medium was filtered through celite and concentrated to dryness. The residue obtained was chromatographed on a cartridge of silica gel eluted with 100percent dichloromethane to 80/20 dichloromethane/ethyl acetate. 3.43 g of product were obtained in the form of a dark copper solid. Yield=48percent.
2.41 g
With palladium 10% on activated carbon; hydrogen In ethyl acetate for 5 h;
(1) A solution of 2,6-dinitrophenol (6.31 g, 27.4 mmol) in ethyl acetate (50 mL) was cooled to 0°C, 10percent palladium activated carbon (250 mg) was added thereto, and the mixture was stirred under a hydrogen atmosphere for 5 hr. The reaction mixture was filtered through Celite (registered trademark) and the filtrate was concentrated under reduced pressure. The resulting residue was diluted with chloroform, anhydrous sodium sulfate was added thereto, and the mixture was stirred for 15 min. Anhydrous sodium sulfate was filtered off, followed by concentration under reduced pressure. The resulting residue was powdered with hexane and collected by filtration to afford 2-amino-6-nitrophenol as a brown amorphous substance (2.41 g).
Reference：
[1] Patent: WO2005/28445, 2005, A2, . Location in patent: Page/Page column 38
[2] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 15, p. 3521 - 3525
[3] Journal of Medicinal Chemistry, 2004, vol. 47, # 6, p. 1319 - 1321
[4] Patent: WO2005/44793, 2005, A2, . Location in patent: Page/Page column 135
[5] Patent: US2014/309208, 2014, A1, . Location in patent: Paragraph 0237; 0238
[6] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 8, p. 2512 - 2515
[7] Justus Liebigs Annalen der Chemie, 1880, vol. 205, p. 72
[8] Chemische Berichte, 1959, vol. 92, p. 407,410
[9] Patent: US5496853, 1996, A,
[10] Patent: US2006/264631, 2006, A1, . Location in patent: Page/Page column 27; 39
[11] Patent: EP2687507, 2014, A1, . Location in patent: Paragraph 0347
4
[ 95-55-6 ]
[ 603-87-2 ]
[ 99-57-0 ]
Reference：
[1] Russian Journal of Organic Chemistry, 1997, vol. 33, # 3, p. 348 - 352
5
[ 74255-39-3 ]
[ 603-87-2 ]
Reference：
[1] Journal of the Chemical Society, 1927, p. 1057
6
[ 614-80-2 ]
[ 603-87-2 ]
Reference：
[1] Journal of the Chemical Society, 1927, p. 1057
7
[ 7664-93-9 ]
[ 860728-40-1 ]
[ 603-87-2 ]
Reference：
[1] Chemische Berichte, 1914, vol. 47, p. 1007
8
[ 7664-93-9 ]
[ 861528-05-4 ]
[ 603-87-2 ]
Reference：
[1] Chemische Berichte, 1914, vol. 47, p. 1007
9
[ 7647-01-0 ]
[ 860728-44-5 ]
[ 603-87-2 ]
Reference：
[1] Journal of the Chemical Society, 1928, p. 3070
With hydrogen;palladium 10% on activated carbon; In ethyl acetate; for 5h;
To a nitrogen flushed solution of 2, 6-dinitrophenol (10 g, 54.3 mmol) in ethyl acetate (100 ml) was added 10% palladium on carbon (0.5 g) and the resulting mixture stirred under a balloon of hydrogen for 5 hours. The catalyst was removed by filtration and the filtrate evaporated to give the title compound (8.0 g, 95%). 1H NMR (400 MHz, CDC13) 8 3.95 (2H, br s), 6.78 (1H, t, J 8. 4 and 8.0), 6.95 (1H, dd, J7. 6 and 1.2), 7.46 (1H, DD, J 8. 6 AND 1.2).
92%
With palladium 10% on activated carbon; hydrogen; In methanol; for 1h;
To a of solution of 2,6-dinitrophenol (5.43 mmol, 1.00 g) in methanol (100 mL), 10% palladium on activated carbon (10 wt% of 2,6-dinitrophenol, 0.10 g) was added. The reaction was flushed with argon followed by hydrogen for fifteen minutes each with constant magnetic stirring. The reaction was then maintained under hydrogen atmosphere at ordinary pressure (balloon) for one hour. The reaction was monitored closely by thin layer chromatography to avoid over reduction.1 Argon was again flushed through the reaction vessel for 15 minutes. Then the reaction contents were filtered over a thin pad of celite which was then washed with methanol (50 mL). The filtrate was concentrated in vacuo yielding a brown solid. Silica gel column chromatography (10:1 hexanes/ethyl acetate) provided a crystalline red solid in a 92% yield.
60%
2-Amino-6-nitrophenol: A suspension of 2,6-dinitrophenol 5.0 g (27 mmol), ammonium hydroxide (3 ml) and ammonium chloridel4. 3 g (270 mmol) in 30 ml of water was heated to 70C. A solution of sodium sulfide nonahydrate (24.19 g, 100 mmol) in water was added and the resulting mixture stirred at 70C for 2h. The reaction was cooled to room temperature, acidified (pH 3.2) with 2N HC1, and the brown precipitate separated by filtration. The filtrate was extracted with chloroform (6 x 75 ml), the organic extracts combined with the precipitate, and evaporated in-vacuo to yield 2.5 g (60 %) of product as a dark brown solid. 1H NMR (CDC13) 5 4.09 (s, 2H), 6.78 (t, 1H, J = 8. 2 Hz), 6.95 (d, 1H, J = 7.8 Hz), 7.47 (d, 1H, J = 8.6 Hz), 10.73 (s, 3H).
48%
With palladium 10% on activated carbon; hydrogen; In ethyl acetate; at 20℃; for 144h;
Step 1 2-Amino-6-nitrophenol 8.6 g of 2,6-dinitrophenol (46.71 mmol) were dissolved in 95 ml of ethyl acetate. The solution was degassed and then 0.86 g (10% by weight) of palladium on carbon at 10% was added. The reaction medium was stirred under a hydrogen atmosphere for 6 days at ambient temperature. The reaction medium was filtered through celite and concentrated to dryness. The residue obtained was chromatographed on a cartridge of silica gel eluted with 100% dichloromethane to 80/20 dichloromethane/ethyl acetate. 3.43 g of product were obtained in the form of a dark copper solid. Yield=48%.
palladium-carbon; In methanol;
REFERENCE EXAMPLE 1 Synthesis of 2-amino-6-nitrophenol 100 ml of methanol was added to 5.0 g of 2,6-dinitrophenol in a vessel. The inside of the vessel was purged with argon. About 1.5 g of 10% palladium-carbon was added thereto, the inside of the vessel was purged with argon and then with hydrogen, and the reaction mixture was stirred at room temperature overnight. After the completion of the reaction, the palladium-carbon was removed by filtration with Celite, and the filtrate was concentrated to provide 4.1 g of the title compound, that is, 2-amino-6-nitrophenol. 1 H NMR (CDCl3) delta (ppm): 10.70 (s, 1H, OH), 7.46(dd, J=2.0Hz, 8.2Hz, 1H, ArH), 6.94(dd, J=2.0Hz, 7.7Hz, 1H, ArH), 6.76(dd, J=8.2Hz, 7.7Hz, 1H, ArH), 3.70-4.50(br, 2H, NH2)
Example 14 2-Amino-6-nitro phenol: Ref.: WO 96/11917. A slurry of 2,6-dinitro phenol (20% in H2O, 5 g, 0.0271 mol), NH4Cl (14.30 g, 0.267 mol), and ammonium hydroxide solution (3 mL) was heated in a 70 C. bath. A warm solution of Na2S-9H2O (24.19 g, 0.1 mol) in H2O (23 mL) was added to the slurry and the resulting orange suspension was heated with stirring for 3 h, then allowed to cool to room temperature. The mixture was cooled in an ice bath and slowly acidified with 6 N HCl to pH 2. The mixture was filtered and the filtrate was extracted with CHCl3 (3*75 mL). The combined organic extracts were concentrated in vacuo and the crude material was adsorbed onto silica gel. Purification by silica gel chromatography, eluding with 25% hexane/CH2Cl2 then CH2Cl2, afforded the title compound (1.47 g) as a brick red powder. MS (ESI-POS): [M+H]+=155.
2.41 g
With palladium 10% on activated carbon; hydrogen; In ethyl acetate; for 5h;
(1) A solution of 2,6-dinitrophenol (6.31 g, 27.4 mmol) in ethyl acetate (50 mL) was cooled to 0C, 10% palladium activated carbon (250 mg) was added thereto, and the mixture was stirred under a hydrogen atmosphere for 5 hr. The reaction mixture was filtered through Celite (registered trademark) and the filtrate was concentrated under reduced pressure. The resulting residue was diluted with chloroform, anhydrous sodium sulfate was added thereto, and the mixture was stirred for 15 min. Anhydrous sodium sulfate was filtered off, followed by concentration under reduced pressure. The resulting residue was powdered with hexane and collected by filtration to afford 2-amino-6-nitrophenol as a brown amorphous substance (2.41 g).
With palladium on activated charcoal; hydrogen; In 1,2-dichloro-ethane; at 35 - 40℃; under 1500.15 - 4500.45 Torr;Large scale;
Mixing 2,6-dinitrophenol (II)-1,2-dichloroethane solution obtained in step 1), 15 kg of palladium carbon, venting with nitrogen, stirring, and introducing at 35-40 C 0.2 to 0.6 MPa of hydrogen, stirred to the end of the reaction; the catalyst was recovered by filtration, and allowed to stand for separation to obtain a 2-amino-6-nitrophenol (III)-dichloroethane solution.
With sodium hydrogencarbonate; In water; ethyl acetate; at 20℃; for 1.5h;Cooling with ice;
2) Sodium hydrogen carbonate (6.30 g, 75.0 mmol) and water (75 mL) were added to a solution of <strong>[603-87-2]2-amino-6-nitrophenol</strong> obtained (5.77 g, 37.5 mmol) in ethyl acetate (75 mL) while cooling in ice, and chloroacetic acid chloride (3.58 mL, 45.0 mmol) was added dropwise thereto. After stirring at room temperature for 1.5 hr, the reaction mixture was cooled in ice, saturated aqueous ammonium chloride solution was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The desiccant was filtered off, followed by concentration under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 9:1 ? 1:1) to afford 2-chloro-N-(2-hydroxy-3-nitrophenyl)acetamide as a pale yellow powder (5.70 g).
With sodium carbonate; In ethanol;Heating / reflux;
To a mixture containing 0.10 g (0.65 mmol) of 2-amino- 6-nitrophenol and 0.14 g (1.3 mmol) of sodium carbonate in ethanol was added 0.14 g (0.78 mmol) of 2-isothiocyanato- 1,3, 5-trimethylbenzene. The reaction was heated at reflux overnight. The reaction was cooled to room temperature, filtered and concentrated under reduced pressure. Purification of the residue via Biotage chromatography eluting with 20% ethyl acetate/dichloromethane gave 0.17 g (80 %) of product. MS Calcd.: 331 ; Found: 332 (M+H).
With Montmorillonite KSF clay; In toluene;Heating / reflux;
To a solution of <strong>[603-87-2]2-amino-6-nitrophenol</strong> (Description 34,8 g, 51.9 mmol) in anhydrous toluene (150 ml) was added triethyl orthoacetate (9.51 ml, 51.9 mmol) and Montmorillonite KSF clay (2 g). The resulting mixture was then heated at reflux overnight. The cooled reaction mixture was filtered through CELITE AND the filtrate evaporated to dryness. The residue was triturated with diethyl ether and the solid collected by filtration and dried to give the title compound (2. 96 g, 32%). 1H NMR (400 MHz, CDC13) 8 2.77 (3H, s), 7.45 (1H, T, J8. 1), 7.98 (1H, dd, J7. 9 and 0.9), 8.14 (1 H, dd, J 8. 4 and 0.9).
REFERENCE EXAMPLE 3 Synthesis of 7-nitro-2-(3-pyridyl)benzoxazole 15 ml of the trimethylsilyl polyphosphate solution prepared in Reference Example 2 was placed in a vessel purged with argon, and 1.06 g of <strong>[603-87-2]2-amino-6-nitrophenol</strong> prepared in Reference Example 1 and 0.62 g of nicotinic acid. The mixture was allowed to react under reflux for 3 hr. After the completion of the reaction, 50 ml of a 1N aqueous sodium hydroxide solution was added to the reaction mixture. The intended product was extracted with dichloromethane (50 ml*3), and the organic layer was washed with water and then dried. The organic solvent was removed by evaporation, and the resultant concentrate was purified by silica gel column chromatography (hexane:ethyl acetate=6:4) to provide 0.49 g of the title compound. 1 H NMR (CDCl3) delta (ppm): 9.40(d, J=1.5Hz, 1H, ArH), 8.87(dd, J=4.8Hz, 1.5Hz, 1H, ArH), 8.58(ddd, J=1.8Hz, 2.2Hz, 7.9Hz, 1H, ArH), 8.34 (dd, J=2.2Hz, 1.1Hz, 1H, ArH), 8.27 (d, J=1.1Hz, 1H, ArH), 7.58-8.24(m, 2H, ArH)
EXAMPLE 2B This Example gives a general process for the preparation of 2-mercaptobenzoxazoles from the corresponding 2-aminophenol or a salt thereof, as illustrated by the procedure for preparing 2-mercapto-7-nitrobenzoxazole. Carbon disulphide (0.6 cm3) was added to a solution of potassium hydroxide (0.652 g) in methanol (16.5 cm3) and water (3 cm3). The resulting solution containing potassium methyl xanthate was added to <strong>[603-87-2]2-amino-6nitrophenol</strong> (1.4 g) and the mixture heated and stirred under reflux for 18 hours. The resulting solution was cooled, acidified to pH 3 with concentrated hydrochloric acid, and the dark orange solid which precipitated was recoved by filtration and dried by suction. This gave 2-mercapto-7-nitrobenzoxazole (1.25 g). M+ =196; 1 H NMR (DMSO): delta7.6(1H,t); 7.75(1H,d); 8.1(1H,d).
Example 15 4-tert-butyl-N-(2-hydroxy-3-nitrophenyl)benzamide: Ref.: WO 96/11917. To a solution of 4-tert-butyl benzoic acid (0.81 g, 4.57 mmol) in CH2Cl2 (10 mL) cooled in an ice bath was added 1,1'-carbonyldiimidazole (0.94 g, 5.80 mmol). The solution was stirred for 5 min., then the bath was removed and the reaction was stirred at room temperature for 1.5 h. To a solution of <strong>[603-87-2]2-amino-6-nitro phenol</strong> (0.829 g, 5.38 mmol) in CH2Cl2 (40 mL) cooled in an ice bath was added the activated acid solution dropwise. The reaction was allowed to stir and gradually come to room temperature overnight. To the solution was added CH2Cl2 (50 mL) and H2O (25 mL) and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2*30 mL). The combined organic layers were washed with H2O (25 mL), 1 N HCl (25 mL), and brine (25 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude material was adsorbed onto silica gel and purified by silica gel chromatography, eluding with 66% CH2Cl2/hexane to 75% CH2Cl2/hexane to afford the title compound (0.579 g) as a golden solid. MS (ESI-POS): [M+H]+=315; Anal. Calc'd for C17H18N2O4: C, 64.96; H, 5.77; N, 8.91. Found: C, 64.98; H, 5.78; N, 8.89.
Bl 2-Hydroxy-3-nitro-benzenesulfonyl chloride; 2.30 g (14.9 mMol) of <strong>[603-87-2]2-amino-6-nitro-phenol</strong> [PCT Int. Appl. WO 9611917 Al] was suspended in 7.8 rnL aq. HCl (37%) and 3.2 rnL of acetic acid and the mixture was cooled down to - 5 0C; then, a solution of 1.13 g (1.1 eq.) of sodium nitrite in 1.8 mL water was added drop by drop. After stirring at 0 0C for 45 min, this reaction mixture was dropped into a saturated solution of sulfur dioxide in acetic acid at 0 0C, which contained 0.46 g (0.3 eq.) of copper(I) -chloride. Afterwards, the reaction mixture was warmed up to RT. 1 hour later, the mixture was poured into crashed ice and extracted three times with AcOEt; the organic phases were washed with water, dried over MgSO4, filtered and evaporated i.V. to yield 2.81 g of the title compound as brown oil.MS: 237.0 (M)+, 1 Cl.
To a solution of <strong>[603-87-2]2-amino-6-nitrophenol</strong> (KR-401) (6.49 mmol, 1.00 g) in acetonitrile (50 mL), di(imidazole-1-yl)methanimine (16.22 mmol, 2.61 g) was added with constant magnetic stirring. The reaction was then placed under argon atmosphere and refluxed for six hours. The reaction was concentrated under reduced pressure and silica gel column chromatography (10:1 hexanes/ethyl acetate) provided a crystalline white solid in a 79% yield.
Step 2 7-Nitro-3H-benzooxazol-2-one 2.27 g of N,N'-carbonyldiimidazole (14 mmol, 1.4 eq) in a homogeneous suspension in 6 ml of ethyl acetate were added to 1.54 g of <strong>[603-87-2]2-amino-6-nitrophenol</strong> (10 mmol, 1 eq) in solution in 10 ml of ethyl acetate. The reaction medium was vigorously stirred for 3 hours, and then 10 ml of water were added. The stirring was continued for 15 minutes, before evaporating off approximately 3/4 of the ethyl acetate. The reaction medium was brought to 0 C. and then 2 ml of 37% hydrochloric acid were added. The stirring was again continued for 15 minutes. The reaction medium was filtered. The solid obtained was washed with a 1 N hydrochloric acid solution, with water and with a water-ethanol (4:1) mixture, and then oven-dried. 1.3 g of product were obtained in the form of a pale yellow solid. Yield=73%.
With triethylamine; In 1,2-dichloro-ethane; at 65 - 75℃;Large scale;
The <strong>[603-87-2]2-amino-6-nitrophenol</strong> (III)-dichloroethane solution obtained by the second step of step 2), 1338.1 kg of triphosgene, 1369.0 kg of triethylamine was mixed, and the reaction was stirred at 65 to 75 C. To the end, a solution of 4-nitro-2-benzoxazolone (IV)-dichloroethane was obtained.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
