2-Chloro-8-nitroquinoline

Pure HGeneral procedure: HA solution of nitric acid (16 mL) and sulfuric acid (8 mL) was added over period of 20 min to a solution of 2-chloroquinoline (61.1 mmol) in sulfuric acid (150 mL) at 0 °C. The reaction mixture was heated at 40 °C for 30 min and was quenched with ice water (800 mL). The precipitated solids were collected by filtration and purified by Flash chromatography (20/1 petroleum ether/ethyl acetate) to provide 2-chloro-8-nitroquinoline in 64percent yield as a yellow solid.Intermediate 23: Synthesis of 2-oxo-l, 2-dihydroquinoline-8-sulfonyl chloride.1. Synthesis of 2-chloro-8-nitroquinoline.A solution of nitric acid (16 mL) and sulfuric acid (8 mL) was added over period of 20 min to a solution of 2-chloroquinoline (61.1 mmol) in sulfuric acid (150 mL) at 0 Intermediate 23: Synthesis of 2-oxo-l, 2-dihydroquinoline-8-suIfonyl chloride. 1. Synthesis of 2-chloro-8-nitroquinoline.A solution of nitric acid (16 mL) and sulfuric acid (8 mL) was added over period of 20 min to a solution of 2-chloroquinoline (61.1 mmol) in sulfuric acid (150 mL) at 0 General Procedure 15: 2-Chloro-8-nitroquinoline (Intermediate 24)Conc. HA solution of nitric acid (16 mL) and sulfuric acid (8 mL) was added over period of 20 min to a solution of 2-chloroquinoline (61.1 mmol) in sulfuric acid (150 mL) at 0 C. The reaction mixture was heated at 40 C for 30 min and was quenched with ice water (800 mL). The precipitated solids were collected by filtration and purified by Flash chromatography (20/1 petroleum ether/ethyl acetate) to provide Intermediate 23: Synthesis of 2-oxo-l, 2-dihydroquinoline-8-sulfonyl chloride.1. Synthesis of Intermediate 23: Synthesis of 2-oxo-l, 2-dihydroquinoline-8-suIfonyl chloride. 1. Synthesis of In a 2 L three-necked flask2-chloroquinoline Was dissolved 30 g (183.3 mmol) in 450 ml of sulfuric acid was cooled to 0 .A mixed solution of 48 ml of nitric acid and 24 ml of sulfuric acid was added over 20 minutes. The reaction mixture was heated at 40 for 30 minutes. When the reaction was completed, the mixture was quenched with 2500 ml of ice water. The precipitated solid was collected by filtration and purified by column chromatography to give 20 g (52.3%) of intermediate A.General Procedure 15: 2-Chloro-8-nitroquinoline (Intermediate 24)Conc. H2SO4 was added slowly to 2-chloroquinoline (1.0 g, 6.13 mmol), followed by portionwise addition of potassium nitrate (800 mg, 7.97 mmol) at 0 C. The mixture was allowed to warm to room temperature overnight. After completion of the reaction (monitored by TLC and HPLCMS), the solution was poured slowly over ice, and the precipitate was extracted with EtOAc. The organic phase was washed with brine and concentrated in vacuo. The crude residue was purified by column chromatography with n-hexane/EtOAC (17:3) as the eluent to give the title compound (450 mg, 38%).MW: 208.61HPLCMS (4.5 min): [m/z]: 209A solution of 2-chloroquinoline B18 (2.00 g, 12.2 mmol) in H2S04 (20 mL) was cooled to 0C. HNO3 (3.55 g, 36.7 mmol) was added dropwise. The reaction solution was stirred at 25C for 1 hour to give a black brown solution. TLC showed the reaction was completed. The reaction solution was poured into water (50 mL), neutralized to pH = 7-8 with saturated Na2C03. The resulting mixture was extracted with DCM (200 mL x 2). The combined organic layer was washed with brine (200 mL), dried over anhydrous Na2S04 and concentrated under reduced pressure. The residue was purified by Combi Flash to give compound B19 (1.30 g) as a yellow solid.Pure H2SO4 was added onto 1 equiv of 29 at 0 C. 3 equiv of 65% HNO3 were then added dropwise and the reaction mixture was stirred at rt for 1 h. After the reaction mixture was poured into water, the solution was neutralized with Na2CO3 and extracted twice with dichloromethane. The organic layer was washed with water, dried over anhydrous Na2SO4 and evaporated in vacuo.Compound 30 was obtained, after purification by column chromatography (eluent: cyclohexane-ethyl acetate 8:2), as a white solid in 54% yield; mp 152 C, Lit: 149 C [40]. 1H NMR (200 MHz, CDCl3) delta: 7.52-7.56 (d, J = 8.6 Hz, 1H), 7.60-7.68 (m, 1H), 8.02-8.11 (m, 2H), 8.20 (d, J = 8.6 Hz, 1H). 13C NMR (50 MHz, CDCl3) delta: 124.6 (CH), 124.9 (CH), 125.8 (CH), 127.6 (C), 131.8 (CH), 138.6 (CH), 139.0 (C), 147.3 (C), 153.6 (C).Compound 31 was obtained, after purification by column chromatography (eluent: cyclohexane-ethyl acetate 8:2), as a pale yellow solid in 14% yield; mp 134 C, Lit: 133-134 C [41]. 1H NMR (200 MHz, CDCl3) delta: 7.63 (d, J = 9.2 Hz, 1H), 7.80-7.88 (m, 1H), 8.34 (d, J = 8.5 Hz, 1H), 8.40 (dd, J = 1.1 and 7.7 Hz, 1H), 8.99 (d, J = 9.2 Hz, 1H). 13C NMR (50 MHz, CDCl3) delta: 119.9 (C), 124.9 (CH), 125.4 (CH), 128.8 (CH), 134.9 (CH), 135.5 (CH), 145.4 (C), 148.0 (C), 152.5 (C).General procedure: H2SO4 (98%) was added onto 1 equiv. of the quinoline derivatives, cooled with an ice bath. 5 equiv. of 65% HNO3 were then added dropwise at 0 C and the reaction mixture was stirred at rt for 1-4 h. The reaction mixture was successively poured into ice, neutralized with NaOH and extracted three times with dichloromethane. The organic layer was washed with water, dried over anhydrous Na2SO4 and evaporated in vacuo. The crude residue was purified by chromatography on silica gel using adapted eluent and recrystallized if necessary to give compounds 1, 4, 6, 12, 15, 17 and 18. 8-nitroquinoline 1 (C9H6N2O2) was purified by chromatography on silica gel using dichloromethane as an eluent, separated from its 5-nitro isomer and isolated to yield a pale yellow solid (35%, 2.7 mmol, 470 mg).General procedure: Acetonitrile (25'mL) and 70% perchloric acid solution (25'mL) were added onto 1 equiv. of the quinoline derivatives. The reaction mixture was stirred at 100'C overnight. The reaction mixture was then poured into ice, neutralized with KOH and extracted twice with dichloromethane. The organic layer was washed with water, dried over anhydrous MgSO4 and evaporated in vacuo. The crude residues were purified by chromatography on silica gel using adapted eluent and recrystallized if necessary to give compounds 7, 14, 19, 20. 4-methyl-8-nitroquinolin-2(1H)-one 7 (C10H8N2O3) was isolated and recrystallized in acetonitrile to yield a yellow solid (92%, 11'mmol, 2.2'g).A solution of 2. Synthesis of 8-nitroquinolin-2(lH)-one.A solution of 2. Synthesis of 8-nitroquinolin-2(lHVone. A solution of To a solution of compound B19 (2.7 g, 12.9 mmol, 1 eq) and compound 32 (3.15 g, 12.9 mmol, 1.0 eq) in dioxane (50 mL) and H20 (10 mL) were added Na2C03 (2.74 g, 25.9 mmol, 2 eq) and Pd(PPh3)4 (748 mg, 0.65 mmol, 0.05 eq) under N2. The resulting mixture was heated at 80C and stirred for 12 hrs to give yellow suspension. TLC showed the reaction was completed. The reaction mixture was filtered to give a residue as a light yellow solid. Then the residue was dissolved in DCM (200 mL) and H20 (200 mL), and extracted with DCM (200 mL). The combined organic layers were washed with brine (100 mL), dried over Na2S04, filtered and concentrated under reduced pressure to give compound B33 (3.25 g) as a light yellow solid.

Molecular Weight:208.60
XLogP3:2.4
Hydrogen Bond Acceptor Count:3
Exact Mass:208.0039551
Monoisotopic Mass:208.0039551
Topological Polar Surface Area:58.7
Heavy Atom Count:14
Complexity:231
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes