Abstract: Herein, we describe 39 novel quinolone compounds bearing a hydrophilic amine chain and varied substituted benzyloxy units. These compounds demonstrate broad-spectrum activities against acid-fast bacterium, Gram-pos. and -neg. bacteria, fungi, and leishmania parasite. Compound 30 maintained antitubercular activity against moxifloxacin-, isoniazid-, and rifampicin-resistant Mycobacterium tuberculosis, while 37 exhibited low micromolar activities (<1 μg/mL) against World Health Organization (WHO) critical pathogens: Cryptococcus neoformans, Acinetobacter baumannii, and Pseudomonas aeruginosa. Compounds in this study are metabolically robust, demonstrating % remnant of >98% after 30 min in the presence of human, rat, and mouse liver microsomes. Several compounds thus reported here are promising leads for the treatment of diseases caused by infectious agents.
* 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] Journal of Fluorine Chemistry, 1995, vol. 70, # 2, p. 201 - 206
2
[ 654-76-2 ]
[ 1548-61-4 ]
Yield
Reaction Conditions
Operation in experiment
83%
With hydrogen bromide In water; acetic acid for 96 h; Heating / reflux
A solution of 6-methoxy-5-nitrobenzotrifluoride (24.73 g, 110.7 mmol) in acetic acid (260 ml) and aqueous HBr solution (62percent, 130 ml) was heated to reflux for 96 h, cooled, evaporated and taken up in aqueous saturated NaHCO3 solution/Et2O (3x). The organic phases were washed with aqueous 10percent NaCl, dried over Na2SO4 and evaporated to yield 19.27 g (83percent) of 4-nitro-2-trifluoromethyl-phenol as yellow solid, MS: 207 (M+), MP: 103-104 C.
65%
With lithium chloride In N,N-dimethyl-formamide for 6.5 h; Heating / reflux
A mixture of l-methoxy-4-nitro-2- (trifluoromethyl) benzene (10.29 g, 46.5 mmol) , lithium chloride (5.92 g, 140 mmol) and N, N-dimethylformamide (46.5 mL) was heated under reflux for 6.5 hr. After cooling to room temperature, 10percent aqueous sodium hydroxide solution (230 mL) was added, and the mixture was washed with ethylether (χ2) . The aqueous solution was acidified with 10percent hydrochloric acid, and extracted with ether (χ2) . The- extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was purified by column chromatography (silica gel, hexane/ethyl acetate=80/20) to give the title compound (6.20 g, 65percent) .1H-NMR (CDCl3, 300 MHz) δ V.08 (IH, d, J = 9.0 Hz), 8.32 (IH, dd, J = 9.0, 2.7 Hz) , 8.48 (IH, d, J = 2.7 Hz) .
3.5 g
at 160℃; for 5 h;
Lithium chloride (2.30 g) was added to a solution of 1-methoxy-4-nitro-2-(trifluoromethyl)benzene (4 g) in N,N-dimethylformamide (40 ml) at room temperature. The reaction mixture was stirred at 160 °C for 5 h. After cooling to rt, the solution was diluted with EtOAc (300 ml). The mixture was washed with water (100 ml * 2) and brine (100 ml), dried and concentrated to give 4-nitro-2-(trifluoromethyl)phenol (3.5 g) as a yellow solid.
Reference：
[1] Journal of Materials Chemistry, 2009, vol. 19, # 39, p. 7208 - 7215
[2] Patent: US2004/248951, 2004, A1, . Location in patent: Page 16
[3] Patent: WO2007/4749, 2007, A1, . Location in patent: Page/Page column 150
[4] Journal of Organic Chemistry, 1962, vol. 27, p. 4660 - 4662
[5] Patent: WO2005/80340, 2005, A1, . Location in patent: Page/Page column 50
[6] Patent: WO2012/100734, 2012, A1, . Location in patent: Page/Page column 28
[7] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 17, p. 5293 - 5302
3
[ 367-67-9 ]
[ 1548-61-4 ]
Reference：
[1] Angewandte Chemie - International Edition, 2009, vol. 48, # 46, p. 8729 - 8732
[2] Journal of Medicinal Chemistry, 2017, vol. 60, # 7, p. 3082 - 3093
4
[ 777-37-7 ]
[ 1548-61-4 ]
Yield
Reaction Conditions
Operation in experiment
67%
With sodium hydroxide In dimethyl sulfoxide at 25℃; for 8 h;
1-Chloro-4-nitro-2-(trifluoromethyl)benzene (2.0 mL, 13.3 mmole) was dissolved in dimethyl sulfoxide (DMSO, 12 mL), NaOH (1.6 g) was batchwise added at a temperature lower than 25° C., and the reaction solution was reacted at room temperature (RT) for 8 hours. After the reaction was terminated, the pH of the reaction solution was adjusted to 1.0 using concentrated HCl, and then the reaction solution was poured into the separatory funnel and extracted with CH2Cl2 for five times (each for 20 ml). The obtained CH2Cl2 solution was hydrated over MgSO4 and concentrated under vacuum. The obtained concentrate was subjected to the purification of silica gel column (50 g) and eluted with the system of CHCl3/n-hexane (2:1) to afford compound 1 (1.85 g), yield of about 67percent. [0030] Compound 1: 1H NMR (400 MHz, CDCl3): δ 8.48 (1H, d, J=2.4 Hz), 8.32 (1H, dd, J=8.8, 2.4 Hz), 7.14 (1H, d, J=8.8 Hz).
Reference：
[1] Patent: US2014/11882, 2014, A1, . Location in patent: Paragraph 0009; 0029
[2] Journal of Organic Chemistry, 1971, vol. 36, # 1, p. 242 - 243
[3] Journal of Organic Chemistry, 2005, vol. 70, # 12, p. 4659 - 4666
[4] Journal of Organic Chemistry, 2005, vol. 70, # 12, p. 4659 - 4666
[5] Tetrahedron Letters, 1993, vol. 34, # 24, p. 3901 - 3902
5
[ 98-46-4 ]
[ 1548-61-4 ]
Reference：
[1] Journal of Organic Chemistry, 1990, vol. 55, # 17, p. 4979 - 4981
[2] Journal of Organic Chemistry, 1998, vol. 63, # 13, p. 4199 - 4208
6
[ 1426689-52-2 ]
[ 4110-33-2 ]
[ 1548-61-4 ]
Yield
Reaction Conditions
Operation in experiment
96%
With triethylamine In water; acetonitrile at 25℃; for 7 h;
General procedure: A solution of 0.50 g (1.51 mmol) of 1a and an excess amount of base a in the appropriate base (10 mL) was stirred for 7 h at room temperature. The solvent was removed invacuo and the residue was extracted with CH2Cl2 and washed thoroughly with water until all of the amine, ammonium salt, and aryloxide were completely removed. The product was 2,4-dinitrobenzonitrile with mp 104-106 °C (lit.23 mp 104-105 °C). The yield of 2,4-dinitrobenzonitrile was 96percent. For all reactions, the yields of aryloxides as determined by comparing the absorbance of the infinity absorbance of the samples from the kinetic studies with those for the authentic aryloxides were in the range of 96-98percent.
Reference：
[1] Bulletin of the Korean Chemical Society, 2013, vol. 34, # 4, p. 1030 - 1034
With hydrogen bromide; In water; acetic acid; for 96h;Heating / reflux;
A solution of 6-methoxy-5-nitrobenzotrifluoride (24.73 g, 110.7 mmol) in acetic acid (260 ml) and aqueous HBr solution (62%, 130 ml) was heated to reflux for 96 h, cooled, evaporated and taken up in aqueous saturated NaHCO3 solution/Et2O (3x). The organic phases were washed with aqueous 10% NaCl, dried over Na2SO4 and evaporated to yield 19.27 g (83%) of 4-nitro-2-trifluoromethyl-phenol as yellow solid, MS: 207 (M+), MP: 103-104 C.
65%
With lithium chloride; In N,N-dimethyl-formamide; for 6.5h;Heating / reflux;
A mixture of l-methoxy-4-nitro-2- (trifluoromethyl) benzene (10.29 g, 46.5 mmol) , lithium chloride (5.92 g, 140 mmol) and N, N-dimethylformamide (46.5 mL) was heated under reflux for 6.5 hr. After cooling to room temperature, 10% aqueous sodium hydroxide solution (230 mL) was added, and the mixture was washed with ethylether (chi2) . The aqueous solution was acidified with 10% hydrochloric acid, and extracted with ether (chi2) . The- extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was purified by column chromatography (silica gel, hexane/ethyl acetate=80/20) to give the title compound (6.20 g, 65%) .1H-NMR (CDCl3, 300 MHz) delta V.08 (IH, d, J = 9.0 Hz), 8.32 (IH, dd, J = 9.0, 2.7 Hz) , 8.48 (IH, d, J = 2.7 Hz) .
With boron tribromide; In dichloromethane; at -78℃;
[0184] 1-Fluoro-4-nitro-2-trifluoromethylbenzene 67 (0.1 mol), was dissolved in tetrahydrofuran (100 mL). The solution was cooled to 0C and sodium methoxide (0.1 mol) was added. The reaction was warmed to room temperature over 2 hours. Water and ethyl acetate were added. The organic phase was dried and concentrated to afford l-methoxy-4- nitro-2-trifluoromethylbenzene 68. This material was dissolved in methylene chloride (100 mL) and the solution was cooled to-78C. Boron tribromide (0.1 mol) was added. The mixture was warmed to room temperature. Water was added, and the organic phase was dried and concentrated. Chromatography then afforded the title compound 69.
Example 19; Ar-(5-(4-chloro-2-(trifluoromethyl)phenoxy)-4-(3-cyanophenyl)thiazol-2-yl)-2-(4- (ethylsulfonyl)phenyl)acetamide; Step 1:; Lithium chloride (2.30 g) was added to a solution of l-methoxy-4-nitro-2- (trifluoromethyl)benzene (4 g) in NN-dimethylformamide (40 mL) at room temperature. The reaction mixture was stirred at 160 C for 5 hours. After cooling to RT, the solution was diluted with EtOAc (300 mL). The mixture was washed with water (100 mL x 2) and brine (100 mL), dried and concentrated to give 4-nitro-2-(trifluoromethyl)phenol (3.5 g) as a yellow solid.
3.5 g
With N,N-dimethyl-formamide; lithium chloride; at 160℃; for 5h;
Lithium chloride (2.30 g) was added to a solution of <strong>[654-76-2]1-methoxy-4-nitro-2-(trifluoromethyl)benzene</strong> (4 g) in N,N-dimethylformamide (40 ml) at room temperature. The reaction mixture was stirred at 160 C for 5 h. After cooling to rt, the solution was diluted with EtOAc (300 ml). The mixture was washed with water (100 ml * 2) and brine (100 ml), dried and concentrated to give 4-nitro-2-(trifluoromethyl)phenol (3.5 g) as a yellow solid.
With ammonium formate; zinc; In methanol; water; at 80℃; for 3h;
Step 2:; Zinc (4.42 g) was added to a solution of <strong>[1548-61-4]4-nitro-2-(trifluoromethyl)phenol</strong> (3.5 g) and ammonium formate (8.52 g) in methanol (5 mL) and water (5 mL) at room temperature. The reaction mixture was stirred at 80 C for 3 hours. After cooling to room temperature, the mixture was filtered and EtOAc (80 mL) was added to the filtrate. The organic layer was washed with water (30 mL) and brine (40 mL), dried, and concentrated to afford 4-amino-2-(trifluoromethyl)phenol (2.8 g) as a yellow solid.
2.8 g
With ammonium formate; zinc; In methanol; water; at 80℃; for 3h;
Zinc (4.42 g) was added to a solution of <strong>[1548-61-4]4-nitro-2-(trifluoromethyl)phenol</strong> (3.5 g) and ammonium formate (8.52 g) in methanol (5 ml) and water (5 ml) at room temperature. The reaction mixture was stirred at 80 C for 3 h. After cooling to room temperature, the mixture was filtered and EtOAc (80 ml) was added to the filtrate. The organic layer was washed with water (30 ml) and brine (40 ml), dried, and concentrated to afford 4-amino-2-(trifluoromethyl)phenol (2.8 g) as a yellow solid.
With sodium hydroxide; In dimethyl sulfoxide; at 25℃; for 8h;
1-Chloro-4-nitro-2-(trifluoromethyl)benzene (2.0 mL, 13.3 mmole) was dissolved in dimethyl sulfoxide (DMSO, 12 mL), NaOH (1.6 g) was batchwise added at a temperature lower than 25 C., and the reaction solution was reacted at room temperature (RT) for 8 hours. After the reaction was terminated, the pH of the reaction solution was adjusted to 1.0 using concentrated HCl, and then the reaction solution was poured into the separatory funnel and extracted with CH2Cl2 for five times (each for 20 ml). The obtained CH2Cl2 solution was hydrated over MgSO4 and concentrated under vacuum. The obtained concentrate was subjected to the purification of silica gel column (50 g) and eluted with the system of CHCl3/n-hexane (2:1) to afford compound 1 (1.85 g), yield of about 67%. [0030] Compound 1: 1H NMR (400 MHz, CDCl3): delta 8.48 (1H, d, J=2.4 Hz), 8.32 (1H, dd, J=8.8, 2.4 Hz), 7.14 (1H, d, J=8.8 Hz).
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 1.5h;
A mixture of 4-nitro-2- (trifluoromethyl) phenol (6.20 g, 29.9 mmol), benzyl bromide (7.68 g, 44.9 mmol), potassium carbonate (8.26 g, 59.8 mmol) and N, N-dimethylformamide (50 mL) was stirred at 600C for 1.5 hr. The reaction mixture was diluted with ethyl acetate, washed with water (chi2) and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was purified by column chromatography (silica gel, hexane/ethyl acetate=100/0-»75/25) to give 1- (benzyloxy) -4-nitro-2- (trifluoromethyl) benzene (8.44 g) . A mixture of the thus-obtained 1- (benzyloxy) -4-nitro-2- (trifluoromethyl) benzene (8.44 g) , calcium chloride (1.58 g, EPO <DP n="152"/>14.2 mmol) , ethanol (280 itiL) and water (28 mL) was stirred at 900C for 5 min and reduced iron (9.52 g, 170 mmol) was added. The mixture was stirred at 9O0C for 6.5 hr, cooled to room temperature and filtered through celite. The filtrate was concentrated under reduced pressure, and the residue was diluted with ethyl acetate and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was purified by column 'chromatography (silica gel, hexane/ethyl acetate=90/10->70/30) to give the title compound (4.80 g, 63%) .1H-NMR (CDCl3, 300 MHz ) 5 3 . 54 ( 2H, br s) , . 5. 08 ( 2H, s) , 6. 75 ( IH, dd, J = 9 . 0, 2 . 7 Hz) , 6. 86 ( IH, . d, J = 9. 0 Hz ) , 6. 92 ( IH, d, J = 2. 7 Hz) , 7 . 25 - 7 . 44 ( 5H, m) .
With potassium carbonate; In butanone; for 10h;Heating / reflux;
A mixture of <strong>[1548-61-4]2-trifluoromethyl-4-nitrophenol</strong> (73.4 g, 0.354 mol), ethyl bromoacetate (65.2 g, 0.39 mol), potassium carbonate (58.7 g, 0.425 mol) and 2-butanone (400 mL) was REFLUXED under stirring for 10 h. The solid was filtered off, the filtrate was evaporated and the residue was fractionated yielding 97.8 g (95 %) of 2-trifluromethyl-4-nitrophenoxyacetic acid ethyl ester, b. p. 126C/40 Pa.
With triphenylphosphine; diethylazodicarboxylate; In dichloromethane; at 0 - 20℃;
To a solution of 1-t-butoxycarbonyl-4-hydroxypiperidine (1.45 g), <strong>[1548-61-4]2-trifluoromethyl-4-nitrophenol</strong> (1.38 g), which was prepared from 3-trifluoromethylnitrobenzene according to the method described in J. Org. Chem., 63, 4199 (1998), and triphenylphosphine (2.27 g) in dichloromethane (65 ml), diethyl azodicarboxylate (1.4 ml) was added dropwise with stirring under ice-cooling, and the resulting mixture was stirred at room temperature overnight and then evaporated in vacuo.. The residue obtained was purified by chromatography on a silica gel column using dichloromethane as the eluent to afford the title compound (2.28 g, yield: 88 %) as a pale yellow oil. 1H NMR (500MHz, CDCl3) delta ppm: 1.49 (9H, s), 1.88-1.99 (4H, m), 3.51 (2H, m), 3.64 (2H, m), 4.83 (1H, m), 7.09 (1H, d, J=9.0), 8.41 (1H, dd, J=9.0, 3.0), 8.53 (1H, d, J=3.0).
With hydrogen bromide; In water; acetic acid; for 96h;Heating / reflux;
A] 4-Nitro-2-trifluoromethyl-phenol A solution of 24.73 g (110.7 mmol) 6-methoxy-5-nitrobenzotrifluoride in 260 ml acetic acid and 130 ml of aqueous HBr solution (62%) was heated to reflux for 96 h, cooled down, evaporated and taken up in aqueous saturated NaHCO3 solution/Et2O (3*). The organic phases were washed with aqueous 10% NaCl, dried over sodium sulfate, and evaporated to dryness to yield 19.27 g of the title compound as yellow solid of mp. 103-104 C. MS: 207 (M+).
Reference Example 30 4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3-trifluoromethylnitrobenzene To a solution of 1-t-butoxycarbonyl-4-hydroxypiperidine (1.45 g), 2-trifluoromethyl-4-nitrophenol (1.38 g) [which was prepared from 3-trifluoromethylnitrobenzene according to the method described in J. Org. Chem., 63 4199 (1998)] and triphenylphosphine (2.27 g) in dichloromethane (65 ml) was added dropwise diethyl azodicarboxylate (1.4 ml) in an ice bath and the mixture was stirred at room temperature for 24 hours. The reaction mixture was concentrated in vacuo. The residue was purified by chromatography on a silica gel column using dichloromethane as an eluant to give the desired compound (2.28 g, yield 88%) as a pale yellow oil. 1H NMR (500 MHz, CDCl3) delta ppm: 1.49 (9H, s), 1.88-1.99 (4H, m), 3.51 (2H, m), 3.64 (2H, m), 4.83 (1H, m), 7.09 (1H, d, J=9.0), 8.41 (1H, dd, J=9.0, 3.0), 8.53 (1H, d, J=3.0).
With aqueous nitric acid; In water; ethyl acetate; Petroleum ether;
1) 2-Trifluoromethyl-4-nitrophenol 20 ml. (0.18 mole) 40% aqueous nitric acid are added to a suspension of 10 g. (0.06 mole) 2-trifluoromethylphenol in 30 ml. water with ice cooling and within the course of 1 hour. Stirring is continued for 2 hours at 20 C., followed by shaking out with 100 ml. ethyl acetate. After drying the organic phase over anhydrous sodium sulphate, the solvent is stripped off on a rotary evaporator and the product obtained purified by means of column chromatography over silica gel (silica gel 60; elution agent ethyl acetate/petroleum ether: 1:3 v/v). TLC (silica gel 60; ethyl acetate/toluene 1:2 v/v): RF=0.44. The fractions are collected and evaporated under vacuum on a rotary evaporator. For further purification and crystallisation, the product is dissolved in 100 ml. water and the pH adjusted to 2 with 1N hydrochloric acid. After 24 hours at 4 C., the precipitated crystals are filtered off, washed with a little cold water and dried in a vacuum at 40 C. Yield 2.3 g. (19% of theory). TLC: (silica gel 60: ethyl acetate): RF=0.11.
2) 2-Trifluoromethyl-4-nitrophenyl-2,3,4,6-tetra-O-acetyl-beta-D-galactopyranoside The preparation takes place from 2 g. (9.7 mmole) <strong>[1548-61-4]2-trifluoromethyl-4-nitrophenol</strong>, 4.11 g. (10 mmole) acetobromogalactose and 2.32 g. (10 mmole) silver oxide analogously to Example 1.2. Yield 2 g. (38% of theory). TLC (silica el 60; toluene/ethyl acetate 2:1 v/v): RF=0.35
EXAMPLE 18 Preparation of 1,2-bis-[2-(trifluoromethyl)-4-nitrophenoxy]-3,3,4,4,5,5-hexafluorocyclopent-1-ene 70 g (0.33 mol) of perfluorocyclopentene were added dropwise at 0 C. to 5 C. with stirring in the course of 30 minutes from a cooled dropping funnel to 138 g (0.66 mol) of <strong>[1548-61-4]2-trifluoromethyl-4-nitrophenol</strong> and 66.7 g of triethylamine (0.66 mol) in 300 ml of methylene chloride. After 30 minutes, the mixture was slowly warmed to room temperature and subsequently stirred at room temperature for 3 hours. The reaction mixture was successively washed twice with 200 ml each of water, once with 100 ml of 5% strength hydrochloric acid and then again with 100 ml of water and dried over sodium sulphate. After stripping off the solvent, a whitish-brown crude product remained in an amount of 135 g (=70% of theory) having a melting point of 95 to 110 C. Recrystallization from petroleum ether gave back 85% of this product having a melting point of 118 to 120 C. The mass spectrum gave a value for m/e of 586 for the molecular ion. The 19 F NMR spectrum showed bands at delta=+16.1 ppm (CF3), -35.2 ppm, measured against trifluoroacetic acid as external standard.
Step 1 A mixture of <strong>[1548-61-4]2-trifluoromethyl-4-nitrophenol</strong> (73.4 g, 0.354 mol), ethyl bromoacetate (65.2 g, 0.39 mol), potassium carbonate (58.7 g, 0.425 mol) and 2-butanone (400 mL) was refluxed under stirring for 10 h. The solid was filtered off, the filtrate was evaporated and the residue was fractionated yielding 97.8 g (95%) of 2-trifluromethyl-4-nitrophenoxyacetic acid ethyl ester, b.p. 126 C./40 Pa.
With triethylamine; In water; acetonitrile; at 25℃; for 7h;Kinetics;
General procedure: A solution of 0.50 g (1.51 mmol) of 1a and an excess amount of base a in the appropriate base (10 mL) was stirred for 7 h at room temperature. The solvent was removed invacuo and the residue was extracted with CH2Cl2 and washed thoroughly with water until all of the amine, ammonium salt, and aryloxide were completely removed. The product was 2,4-dinitrobenzonitrile with mp 104-106 C (lit.23 mp 104-105 C). The yield of 2,4-dinitrobenzonitrile was 96%. For all reactions, the yields of aryloxides as determined by comparing the absorbance of the infinity absorbance of the samples from the kinetic studies with those for the authentic aryloxides were in the range of 96-98%.
With water; sodium hydroxide; In 1,4-dioxane; at 100℃; for 24h;
Next, compound 1 (500 mg, 2.4 mmole) and tert-butyl 2-aminoethylcarbamate (769 mg, 4.8 mmole) were transferred in a reaction bottle, 1 M aqueous NaOH solution (7.2 mmole) and dioxane (10 mL) were added, and then the mixture solution were heated to 100 C. and reacted for 24 hours. After the reaction was terminated, the pH of the reaction solution was adjusted to 1.0 using 1 N HCl solution, and then the reaction solution was poured into the separatory funnel and extracted with CH2Cl2 for five times (each for 20 ml). The obtained CH2Cl2 solution was hydrated over MgSO4 and concentrated under vacuum. The obtained concentrate was subjected to the purification of silica gel column (50 g) and eluted with the system of CHCl3/n-hexane (19:1) to afford compound 2 (600.0 mg), yield of about 77%. [0033] Compound 2: 1H NMR (400 MHz, Acetone-d6): delta 8.96 (1H, s), 8.74 (1H, d, J=2.4 Hz), 8.30 (1H, dd, J=8.8, 2.4 Hz), 7.10 (1H, d, J=8.8, 2.4 Hz), 6.32 (1H, s), 3.58 (2H, m), 3.39 (2H, m).
2,6-bis(2-trifluoromethyl-4-nitrophenoxy)pyrazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
at 20℃; under 760.051 Torr; for 7.5h;Inert atmosphere; Ionic liquid;
Under normal temperature and pressure,100 mmol of 2,6-dichloroquinoline,218mmol <strong>[1548-61-4]2-hydroxy-5-nitrobenzotrifluoride</strong>,2380 mmol of basic ionic liquid [bmin] OH was transferred to a three-necked flask.The reaction was carried out for 7.5 hours under stirring and nitrogen protection.Obtaining a product system;Pour the resulting product system into deionized water,Recovery of alkaline ionic liquid [bmin]OH,The precipitated solid is suction filtered,Wash 5 times with deionized water,Dry at 80 C for 12 hours,Recrystallized from methanol,Obtaining 2,6-bis(2-trifluoromethyl-4-nitrophenoxy)pyrazine,The yield was 90%.
With dmap; dicyclohexyl-carbodiimide In dimethyl sulfoxide at 20℃;
1 Embodiment 1: Synthetic diamine compound BA-COOH
In a 500mL flask, 2-trifluoromethyl-4-nitrophenol (16.56g, 80mmol), 3,3',4,4'-biphenyltetracarboxylic acid (13.22g, 40mmol), 4- Dimethylaminopyridine (DMAP, 0.20 g, 1.6 mmol) and dicyclohexylcarbodiimide (DCC, 16.51 g, 80 mmol) were dissolved in 300 mL of dimethyl sulfoxide (DMSO), and stirred at room temperature for 12 h.After the reaction, the reaction liquid system was filtered, and the filtrate was introduced into a large amount of water to obtain a crude product (yellow solid). The crude product was further separated and processed by silica gel column chromatography to obtain a nitro-containing intermediate compound.
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