Abstract: In this study, we developed a metal-free and highly chemoselective method for the reduction of aromatic nitro compounds. This reduction was performed using tetrahydroxydiboron [B2(OH)4] as the reductant and 4,4'-bipyridine as the organocatalyst and could be completed within 5 min at room temperature. Under optimal conditions, nitroarenes with sensitive functional groups, such as vinyl, ethynyl, carbonyl, and halogen, were converted into the corresponding anilines with excellent selectivity while avoiding the undesirable reduction of the sensitive functional groups.
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To a solution of 3-nitro-2-chloropyridine (4.0 g, 25.2 mmol) in 15 mL 2-methoxyethanol was added methylamine (2.0 M in THF, 32 mL). The reactionwas stirred for 8 hr at 80 °C in a sealed tube. After cooling to rt, the reaction mixture was evaporated to afford 15 quantitatively (3.6 g, 23.2 mmol). 1H NMR (500 MHz, CDCl3) δ 8.47 – 8.37 (m, 2H), 8.20 (s, 1H), 6.64 (dd, J = 8.3, 4.4 Hz, 1H), 3.17 (d, J = 4.8 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 156.0, 153.5, 135.4, 111.7, 28.4. HRMS (ESI+) m/z calcd for C6H8N3O2+ 154.0617, found 154.0610.
98.5%
at 0 - 20℃; for 3 h;
Methylamine (33percent in EtOH) (1 10 mL, 883 mmol) was placed in a 500 mL three necked round bottom flask. It was cooled to 0 °C using ice bath. 2-chloro-3-nitropyridine (20 g, 126 mmol) was added to the above solution in portions as this is an exothermic reaction. After the addition was complete the reaction mixture was stirred for 2 h at 0 °C and later 1 h at room temperature. Solvent was concentrated and residue was taken in 500 mL of water and extracted with EtOAc 3 x 150 mL. Combine organic layer was dried over Na2SC"4, filtered and concentrated to give a bright orangish yellow solid(19 g , 98.5percent).
95.76%
With triethylamine In dichloromethane at 20℃; for 5 h;
24 mL of methylamine, 39.5 mL of triethylamine was added to 240 mL of dichloromethane, and 30 g(0.18 mol) of 2-chloro-3-nitropyridine, and the reaction was completed at room temperature for 5 h. After completion of the reaction, the reaction solution was washed three times with waterInto anhydrous sodium sulfate in addition to water, suction filtration, steaming, yellow crystalline solid product 44.8g (yield 95.76percent).
86%
With sodium acetate In water; acetonitrile at 20℃; Heating / reflux
2-chloro-3-nitropyridine 70.0 g, 0.44 mol) was dissolved in recently distilled acetonitrile (400 mL) under stirring. Sodium acetate (55.2 g, 0.67 mol) and 30percent aqueous solution of methylamine (111 mL) were added under vigorous stirring. The obtained suspension was stirred at room temperature for 30 min, refluxed for 1 h, and kept overnight at room temperature. The yellow reaction mixture was concentrated under reduced pressure to remove approximately 300 mL of the solvent. The residue was diluted with 20percent aqueous solution of K2CO3 (1 L) under stirring. The yellow precipitate was filtered off, washed with water (3° * 200 mL), and dried to afford W-Methyl-3-nitropyridin-2-amine in 86percent (58.14 g, 0.38 mol) yield as bright yellow crystals.
Reference：
[1] Tetrahedron Letters, 2015, vol. 56, # 44, p. 6097 - 6099
[2] Patent: WO2012/121936, 2012, A2, . Location in patent: Page/Page column 93
[3] Patent: CN106831776, 2017, A, . Location in patent: Paragraph 0097; 0098; 0099
[4] European Journal of Organic Chemistry, 2009, # 22, p. 3753 - 3764
[5] Acta Chemica Scandinavica, 1993, vol. 47, # 8, p. 805 - 812
[6] Patent: WO2008/12622, 2008, A2, . Location in patent: Page/Page column 57
[7] Open Medicinal Chemistry Journal, 2018, vol. 12, # 1, p. 74 - 83
[8] Chemistry - A European Journal, 2017, vol. 23, # 57, p. 14173 - 14176
[9] Patent: US4520196, 1985, A,
[10] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 5, p. 1696 - 1701
[11] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 20, p. 5493 - 5496
2
[ 5470-18-8 ]
[ 4093-88-3 ]
Yield
Reaction Conditions
Operation in experiment
98.5%
With methylamine In ethanol; water
Synthesis of N-methyl-3-nitropyridin-2-amine Methylamine (33percent in EtOH) (110 mL, 883 mmol) was placed in a 500 mL three necked round bottom flask. It was cooled to 0° C. using ice bath. 2-chloro-3-nitropyridine (20 g, 126 mmol) was added to the above solution in portions as this is an exothermic reaction. After the addition was complete the reaction mixture was stirred for 2 h at 0° C. and later 1 h at room temperature. Solvent was concentrated and residue was taken in 500 mL of water and extracted with EtOAc 3*150 mL. Combine organic layer was dried over Na2SO4, filtered and concentrated to give a bright orangish yellow solid (19 g, 98.5percent).
Reference：
[1] Patent: US2012/228583, 2012, A1,
3
[ 5470-18-8 ]
[ 4093-88-3 ]
[ 33742-70-0 ]
Reference：
[1] Patent: US5624935, 1997, A,
4
[ 5470-18-8 ]
[ 74-89-5 ]
[ 4093-88-3 ]
[ 73895-39-3 ]
Reference：
[1] Advanced Synthesis and Catalysis, 1999, vol. 341, # 1, p. 75 - 78
5
[ 123-39-7 ]
[ 5470-18-8 ]
[ 4093-88-3 ]
Reference：
[1] Journal of the Brazilian Chemical Society, 2010, vol. 21, # 8, p. 1439 - 1445
6
[ 79-16-3 ]
[ 5470-18-8 ]
[ 4093-88-3 ]
Reference：
[1] Journal of the Brazilian Chemical Society, 2010, vol. 21, # 8, p. 1439 - 1445
A suspension of sodium methoxide (40.5 g, 0.750 mol) in 200 mL of methanol was slowly added to a solution of 2-chloro-3- nitro-pyridine (79.3 g, 0.500 mol) in 800 mL of methanol at 0 °C. The reaction mixture was stirred for 4 hours and then poured into 1000 g of ice. The resulting precipitate was filtered, washed with water, and dried to give 2-methoxy-3-nitro-pyridine (70. g, 0.45 mmol, 90 percent) as a white solid.
EXAMPLE 12 Synthesis of 2-methoxy-3-nitropyridine STR27 2-Chloro-3-nitropyridine (25 g, 0.157 mol) was suspended in methanol (300 ml) and sodium methoxide (17 g, 0.315 mol) was added. The mixture was refluxed for 2 hr and part of the solvent removed under reduced pressure. The reaction mixture was diluted with water (1 litre) and the precipitate collected by filtration. The white solid obtained was washed with more water and dried under vacuum to give the title compound (18.2 g, 75percent). 1 H NMR (CDCl3): 8.42 (dd, J=5, 2 Hz, 1H); 8.28 (dd, J=8, 2 Hz, 1H); 7.06 (dd, J=8, 5 Hz, 1H); 4.13 (s, 3H)
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