6-Fluoro-8-quinolinol
1441
Additional NCS was added equal to unreacted 1. Heating and stirring were continued for 1 h and then
brought to boiling. This may have to be repeated until the gas chromatogram indicates the absence of
1. The solution was poured into 1200 cm3 H2O with stirring, and the product was removed by filtration
and air dried. Yield 12 g (82%); mp 158ꢁC (aq alc, Darco G-60); 1H NMR (300MHz, ꢀ, DMSO-d6):
8.97 (d, J24 ¼ 2.3 Hz, H-2), 8.86 (d, H-4), 8.40 (dd, J57 ¼ 2.8 Hz, J6F7H ¼ 8.8 Hz, H-7), 8.07 (dd,
J5H6F ¼ 7.9 Hz, H-5), ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 158.3 (JCF ¼ 250.5 Hz, C-6), 150.9
(JCF ¼ 2.7 Hz, C-2), 148.2 (JCF ¼ 10.4Hz, C-8), 134.2 (JCF ¼ 5.3 Hz, C-4), 133.7 (JCF ¼ 15.9 Hz, C-
8a), 130.5 (JCF ¼ <1 Hz, C-3), 129.5 (JCF ¼ 10.7Hz, C-4a), 114.9 (JCF ¼ 14.9 Hz, C-5), 114.6
(JCF ¼ 24.1Hz, C-7) ppm.
3-Bromo-6-fluoro-8-nitroquinoline (4b, C9H4BrFN2O2)
Compound 4b was prepared from 1 in the same manner as 4a was from 1. NBS was the haloge-
nating agent in place of NCS, and the reaction was based on a 0.1mol run. Yield: 26 g (96%);
1
mp 165–166ꢁC (95% alc, Darco G-60); H NMR (300 MHz, ꢀ, DMSO-d6): 9.08 (d, J24 ¼ 1.8 Hz,
H-2), 8.87 (d, H-4), 8.53 (dd, J57 ¼ 2.6 Hz, J7H6F ¼ 8.0 Hz, H-7), 8.10 (dd, J5H6F ¼ 8.8 Hz,
H-5), ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 158.1 (JCF ¼ 250.1Hz, C-6), 152.7 (JCF ¼ 2.6 Hz,
C-2), 148.4 (JCF ¼ 10.5Hz, C-8), 137.4 (JCF ¼ 5.4 Hz, C-4), 133.9 (JCF ¼ <1 Hz, C-8a),
130.0 (JCF ¼ 10.8Hz, C-4a), 119.7 (JCF ¼ <1 Hz, C-3), 114.72 (JCF ¼ 32.0Hz, C-7), 114.65
(JCF ¼ 22.1Hz, C-5) ppm.
8-Amino-3-chloro-6-fluoroquinoline (5a, C9H6ClFN2)
To a solution of 9.1 g 4a (0.04 mol) in 250cm3 ethanol was added 8.4 g Fe powder (0.14 mol) and
0.8 cm3 HCl. The suspension was stirred under reflux for 3 h. The solids were filtered off, and the
solvent evaporated under a stream of air to yield 5a. Yield 7.9 g (100%); mp 127–128ꢁC (sublimation);
1H NMR (300 MHz, ꢀ, DMSO-d6): 8.63 (d, J24 ¼ 2.3 Hz, H-2), 8.32 (d, H-4), 6.78 (dd, J7H6F ¼ 9.7 Hz,
H-7), 6.70 (dd, J57 ¼ 2.7 Hz, J6F5H ¼ 11.5Hz, H-5) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 162.1
(JCF ¼ 242.6 Hz, C-6), 148.0 (JCF ¼ 14.4Hz, C-8), 144.6 (JCF ¼ 2.6 Hz, C-2), 133.5 (JCF ¼ 5.8 Hz, C-
4), 132.9 (JCF ¼ <1 Hz, C-8a), 129.8 (JCF ¼ 13.8Hz, C-4a), 128.9 (JCF ¼ <1 Hz, C-3), 97.5
(JCF ¼ 29.1Hz, C-7), 95.7 (JCF ¼ 23.7Hz, C-5) ppm.
8-Amino-3-bromo-6-fluoroquinoline (5b, C9H6BrFN2)
Compound 5a was reduced to 5b in the same manner as 4a was converted to 5a. The reaction was
carried out on 0.08 mol of 4b. Yield 17 g (88%); mp 145ꢁC (aq alc); 1H NMR (300MHz, ꢀ, DMSO-d6):
8.71 (s, H-2), 8.49 (s, H-4) 6.68–6.78 (m, H-5 and H-7), 6.45 (s, NH2) ppm; 13C NMR (75 MHz, ꢀ,
DMSO-d6): 161.9 (JCF ¼ 242.5 Hz, C-6), 148.1 (JCF ¼ 14.34 Hz, C-8), 146.3 (JCF ¼ <1 Hz, C-2),
136.7 (JCF ¼ 5.5 Hz, C-4), 133.0 (JCF ¼ <1 Hz, C-8a), 130.5 (JCF ¼ 13.9Hz, C-4a), 118.1
(JCF ¼ <1 Hz, C-3), 97.5 (JCF ¼ 29.0Hz, C-5), 95.6 (JCF ¼ 23.6 Hz, C-7) ppm.
3-Chloro-6,8-dihydroxyquinoline (6a)
Compound 5a (3.9g, 0.02mol) was hydrolyzed in the presence of 70% aq H2SO4 (w=w) in the same
way as 3 was formed from 2. Upon steam distillation of the mixture, no solid material volatilized. The
residual aqueous solution was cooled to room temperature, and 6a crystals formed which were
recovered by filtration. Yield 3.5 g (90%); mp 182–183ꢁC (aq alc, Darco G-60) (Ref. [6]: mp
182–184ꢁC); NMR data in Ref. [6].