E. Leyva et al. / Journal of Fluorine Chemistry 94 (1999) 7±10
9
®ltered and washed with hexane to remove the excess of
diphenylether. The corresponding ester 7a±7e was obtained
as a white solid.
7.46 (1H, m, JH±F 10 Hz, JH±H 5 Hz, aromatic H), 7.58
(1H, m, JH±H 8 Hz, JH±F 5 Hz, aromatic H), 8.26 (1H,
dd, JH±F 10 Hz, JH±H 5 Hz), 8.8 (1H, S, aromatic H),
13.6 (1H, broad S, COOH); 19F NMR (DMSO-D6) ꢀ 44.2
(m, aromatic F); MS (EI, 70 eV) m/z: 207 (34%), 189 (59%),
161 (5%), 133 (28%), 107 (28%), 94 (10%); exact mass for
C10H6NO3F 207.0331. Found: 207.0332.
3.1.3. Hydrolysis
Each ¯uoroester 7a±7e was re¯uxed with an aqueous
solution of NaOH (10%) for 1 h. The mixture was cooled to
room temperature and was acidi®ed with a solution of HCl
(10%) to give the corresponding acid 8a±8e as a white
precipitate.
3.4. Preparation of 6-fluoro-4-hydroxyquinoline-3-
carboxylic acid (8c)
3.2. Preparation of 8-fluoro-4-hydroxyquinoline-3-
carboxylic acid (8a)
Following the general procedure, 6c was obtained as a
crystalline solid (75%) with m.p. 69±708C; IR (KBr)
1
1
1685 cm (ester); H NMR (CD3COCD3) ꢀ 1.22 (3H, t,
CH3), 1.26 (3H, t, CH3), 4.20 (2H, C, CH2), 4.24 (2H, C,
CH2), 7.24 (2H, m, aromatic H), 7.74 (2H, m, aromatic H),
8.44 (1H, d, vinyl H), 10.86 (1H, d, NH); MS (EI, 70 eV)
m/z: 281 (100%), 235 (82%), 207 (10%), 190 (26%), 162
(53%), 122 (31%), 95 (33%).
Following the general procedure, 6a was obtained as a
crystalline white solid (92%) with m.p. 80±818C, IR (KBr)
1
1
1686 cm (ester); H NMR (CD3COCD3) ꢀ (ppm): 1.24
(3H, t, CH3), 1.30 (3H, t, CH3), 4.20 (2H, C, CH2), 4.24 (2H,
C, CH2), 7.26 (3H, m, aromatic H), 7.60 (1H, m, aromatic
H), 8.55 (1H, d, vinyl H), 11.02 (1H, d, NH); MS (EI, 70 eV)
m/z: 281 (100%); 235 (87%), 207 (15%), 190 (26%), 162
(27%), 122 (31%), 95 (18%).
Re¯uxing 6c with diphenylether gave 7c as a white solid
1
(60%) with m.p. 273±2758C; IR (KBr) 1728 cm (ester).
The solid was washed with hexane and used in the next
reaction. 7c was hydrolyzed with NaOH and the resulting
solution was precipitated with HCl to give the correspond-
ing acid 8c as a white solid (70%) with m.p. 2878C; IR
Re¯uxing 6a with diphenylether gave 7a as a white solid
1
(65%) with m.p. 202±2038C; IR (KBr) 1719 cm (ester).
The solid was washed with hexane and used in the next
reaction. 7a was hydrolyzed with NaOH and the resulting
solution was precipitated with HCl to give the correspond-
ing acid 8a as a white solid (96%) with m.p. 2638C; IR
1
(KBr) 1680 cm (COOH); 1H NMR (DMSO-D6), 7.91
(3H, m, aromatic H). 8.9 (1H, S, aromatic H), 15 (1H, broad
S, COOH); 19F NMR (DMSO-D6) ꢀ 34.8 (m, aromatic F);
MS (EI, 70 eV), m/z: 207 (40%), 189 (100%), 161 (12%).
133 (38%), 107 (24%), 94 (10%); exact mass for
C10H6NO3F 207.0331. Found: 207.0332.
1
(KBr) 1714 cm (COOH); 1H NMR (DMSO-D6) ꢀ (ppm):
7.59 (1H, m, JH±F 13 Hz, JH±H 7 Hz , JH±H 3 Hz,
aromatic H), 7.84 (1H, m, JH±H 9 Hz, JH±F 5 Hz, aro-
matic H), 8.10 (1H, m, JH±H 5 Hz,, JH±H 8 Hz, aro-
matic H), 8.66 (1H, S, aromatic H), 15 (1H, broad S,
COOH); 19F NMR (DMSO-D6) ꢀ (ppm): 49.7 (m, aro-
matic F); MS (EI, 70 eV) m/z: 207 (40%), 189 (100%), 161
(12%), 133 (38%), 107 (24%), 94 (10%); exact mass for
C10H6NO3F 207.0331 . Found: 207.0332.
3.5. Preparation of 6,7-difluoro-4-hydroxyquinoline-3-
carboxylic acid (8d)
Following the general procedure, 6d was obtained as a
crystalline slightly pink solid (85%) with m. p. 76±778C; IR
1
1
(KBr) 1739 cm
(ester), 1688 cm
(ester); 1H NMR
3.3. Preparation of 7-fluoro-4-hydroxyquinoline-3-
carboxylic acid (8b)
(CD3COCD3) ꢀ (ppm): 1.2 (3H, t, CH3), 1.26 (3H, t,
CH3), 4.18 (2H, C, CH2), 4.24 (2H, C, CH2), 7.26 (1H,
m, aromatic H), 7.40 (1H, m, aromatic H), 7.44 (1H, m,
aromatic H), 8.40 (1H, d, vinyl H), 10.82 (1H, d, NH); MS
(EI, 70 eV) m/z: 299 (100%), 253 (76%), 225 (13%), 208
(14%), 180 (53%), 140 (23%), 113 (19%).
Following the general procedure, 6b was obtained as a
crystalline white solid (65%) with mp 44±458C; IR (KBr)
1
1
1689 cm (ester); H NMR (CD3COCD3) ꢀ (ppm): 1.22
(3H, t, CH3), 1.26 (3H, t, CH3), 4.18 (2H, C, CH2), 4.22 (2H,
C, CH2), 6.86 (1H, m, aromatic H), 7.22 (2H, m, aromatic
H), 7.42 (1H, m, aromatic H), 8.47 (1H, d, vinyl H), 10.82
(1H, d, NH); MS (EI, 70 eV) m/z: 281 (100%), 235 (78%),
207 (13%), 190 (23%), 162 (34%), 122 (35%), 95 (33%).
Re¯uxing 6b with diphenylether gave 7b as a white solid
Re¯uxing 6d with diphenylether gave 7d as a white solid
1
(80%) with m.p. 238±2398C; IR (KBr) 1698 cm (ester).
The solid was washed with hexane and used in the next
reaction. 7d was hydrolyzed with NaOH and the resulting
solution was precipitated with HCl to give the correspond-
ing acid 8d as a white solid (95%) with m.p. 276±2788C; IR
1
1
(60%) with mp 263±2658C; IR (KBr) 1738 cm (ester).
(KBr) 1712 cm (COOH); 1H NMR (DMSO-D6), ꢀ (ppm):
The solid was washed with hexane and used in the next
reaction. 7b was hydrolyzed with NaOH and the resulting
solution was precipitated with HCl to give the correspond-
ing acid 8b as a white solid (90%) with m. p. 245±2468C; IR
7.88 (1H, m, JH±H 11 Hz, JH±F 6, JH±F 3 Hz, aro-
matic H), 8.17 (1H, m, JH±H Hz, JH±F 10 Hz, JH±F
2 Hz, aromatic H), 8.9 (1H, S, aromatic H), 13.75 (H, broad
S, COOH); 19F NMR (DMSO-D6) ꢀ (ppm): 48.44 (1F,m,
aromatic F), 58.78 (1F,m,aromatic F); MS (EI, 70 eV) m/z:
1
(KBr) 1706 cm (COOH); 1H NMR (DMSO-D6) ꢀ (ppm):