SYNTHESIS OF SUBSTITUTED 1,2,3,4-TETRAHYDROQUINOLINE-4-CARBOXYLIC ACIDS
611
20% hydrochloric acid. The precipitate was filtered off
from the hot mixture and washed with hot water. Yield
5.6 g (81%), yellow crystals, mp 340–342°C (from
EtOH). IR spectrum, ν, cm–1: 3421 (OH), 1735 (C=O).
1H NMR spectrum, δ, ppm: 2.36 s (3H, CH3), 6.83 s
(1H, 3-H), 7.3 d (1H, 8-H), 7.4 d (1H, 7-H), 7.85 s
(1H, 5-H). Found, %: C 65.10; H 4.50; N 6.46.
C11H9NO3. Calculated, %: C 65.02; H 4.46; N 6.89.
The reduction of 2-cyclopropylquinoline-4-carbox-
ylic acid [14] was performed according to the proce-
dure described above for the synthesis of compound I.
Overall yield of acid mixture 0.78 g (78%).
2-Propyl-1,2,3,4-tetrahydroquinoline-4-carbox-
1
ylic acid. H NMR spectrum, δ, ppm: 0.89–1.00 m
(3H, CH3), 1.30–1.55 m (2H, CH2), 1.69 q (1H, CH2),
1.89 q (1H, CH2), 3.70 d.d (1H, 4-H), 6.00 s (1H, NH).
Mass spectrum, m/z (Irel, %): 233 (10) [M]+, 190 (22),
174 (10), 131 (12), 130 (100), 128 (4), 103 (6), 77 (8).
2-Methyl-1,2,3,4-tetrahydroquinoline-4-carbox-
ylic acid (I). Raney nickel, 2 g, was added in small
portions over a period of 1 h under stirring to a solu-
tion of 2 g (0.01 mol) of 2-methyl-4-quinolinecarbox-
ylic acid [13] in 10 ml of 10% aqueous sodium hy-
droxide, and the mixture was stirred for 1 h at room
temperature. The precipitate was filtered off and
washed with hot water, the filtrate was acidified to
pH 3 with formic acid and extracted with chloroform,
the extract was dried over anhydrous sodium sulfate
and evaporated, and the residue was recrystallized
from 50% ethanol. Yield 1.6 g (80%), colorless crys-
tals, mp 131–134°C. IR spectrum, ν, cm–1: 3278 (NH),
2-Cyclopropyl-1,2,3,4-tetrahydroquinoline-4-
1
carboxylic acid. H NMR spectrum, δ, ppm: 0.15–
0.35 m (2H, CH2), 0.40–0.65 m (2H, CH2), 1.15–
1.30 m (1H, CH), 2.15 d.d (1H, 3-Hax), 2.45 d.d.d (1H,
3-Heq), 6.00 s (1H, NH). Mass spectrum, m/z (Irel, %):
231 (26) [M]+, 216 (14), 203 (8), 190 (14), 173 (6),
172 (48), 170 (16), 157 (12), 144 (18), 130 (100), 128
(10), 103 (9), 102 (4), 77 (17).
2-Oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic
acid (III) was synthesized according to the procedure
reported in [10]. Yield 0.8 g (80%), mp 218–220°C
(from water); published data [11]: mp 218°C. IR spec-
trum, ν, cm–1: 3384 (NH); 1708 (C=O, acid), 1647
(C=O, lactam). 1H NMR spectrum, δ, ppm: 2.71 q (2H,
CH2), 4.05 t (1H, 4-H), 6.9 d (1H, 8-H), 6.95 t (1H,
6-H), 7.2 t (1H, 7-H), 7.25 s (1H, 5-H). Mass spec-
trum, m/z (Irel, %): 205 (36) [M]+, 147 (6), 146 (100),
128 (52), 117 (20), 89 (10), 77 (8), 51 (6). Found, %:
C 62.50; H 4.46; N 7.52. C10H9NO3. Calculated, %:
C 62.82; H 4.74; N 7.33. M 191.19.
1
2966 (CH3), 1701 (C=O). H NMR spectrum, δ, ppm:
1.29 d (3H, CH3, J = 6.11 Hz), 2.01 d.d (1H, 3-Hax,
J = 12.21, 10.98 Hz), 2.26 d.d.d (1H, 3-Heq, J = 10.98,
6.11, 2.44 Hz), 3.45 d.d.d (1H, 2-Hax, J = 10.98, 6.11,
2.44 Hz), 4.01 d.d (1H, 4-Hax, J = 12.21, 6.11 Hz),
6.56 d (1H, 8-H, J = 7.33 Hz), 6.71 t (1H, 6-H, J =
7.33 Hz), 7.07 t (1H, 7-H, J = 7.33 Hz), 7.14 d (1H,
5-H, J = 3.33 Hz). Mass spectrum,* m/z (Irel, %): 205
(44) [M]+, 190 (28), 146 (91), 130 (100), 118 (9.5), 103
(4), 77 (19), 65 (8). Found, %: C 69.00; H 6.87;
N 7.40. C11H13NO2. Calculated, %: C 69.09; H 6.85;
N 7.32. M 191.23.
6-Methyl-2-oxo-1,2,3,4-tetrahydroquinoline-4-
carboxylic acid (IV). A solution of 1 g (5 mmol) of
2-hydroxy-6-methylquinoline-4-carboxylic acid in
15 ml of acetic acid was heated to 80°C on a water
bath, 4 g (0.06 mol) of zinc dust was added in portions
over a period of 1 h under stirring, and the mixture was
stirred for 1.5 h. The mixture was then filtered, the
filtrate was diluted with 10 ml of water and left over-
night, and the colorless needles were filtered off. Yield
0.75 g (75%), mp 223–225°C. IR spectrum, ν, cm–1:
3452 (NH), 1708 (C=O, acid), 1643 (C=O, lactam).
1H NMR spectrum, δ, ppm: 2.25 s (3H, CH3), 2.65 q
(2H, CH2), 3.80 t (1H, 4-H), 6.75 d (1H, 8-H), 7.0 d
(1H, 7-H), 7.1 s (1H, 5-H). Mass spectrum, m/z
(Irel, %): 219 (24) [M]+, 161 (11), 160 (100), 142 (56),
130 (19), 117 (13), 115 (10), 103 (5), 77 (8), 65 (7).
Found, %: C 64.10; H 5.30; N 6.96. C11H11NO3. Cal-
culated, %: C 64.38; H 5.40; N 6.83. M 205.21.
2,6-Dimethyl-1,2,3,4-tetrahydroquinoline-4-car-
boxylic acid (II) was synthesized in a similar way.
Yield 85%, mp 136–140°C (from 50% ethanol). IR
spectrum, ν, cm–1: 3382 (NH); 2950, 2854 (CH3); 1716
1
(C=O). H NMR spectrum, δ, ppm: 1.29 d (3H, CH3,
J = 6.3 Hz), 1.8 d.d (1H, 3-Hax, J = 12.3, 11.1 Hz),
2.11 s (3H, CH3), 2.2 d.d.d (1H, 3-Heq, J = 11.3, 7.11,
2.6 Hz), 3.35 d.d.d (1H, 2-Hax, J = 11.11, 6.58, 2.4 Hz),
3.85 d.d (1H, 4-Hax, J = 12.5, 6.6 Hz), 6.4 d (1H, 8-H,
J = 8.1 Hz), 6.8 d (1H, 7-H, J = 8.33 Hz), 7.4 s (1H,
5-H). Mass spectrum, m/z (Irel, %): 219 (45) [M]+, 204
(25), 160 (78), 144 (100), 143 (9.5), 103 (3), 91 (9.5),
71 (8), 65 (6). Found, %: C 70.10; H 7.30; N 6.85.
C12H15NO2. Calculated, %: C 70.22; H 7.37; N 6.82.
M 205.26.
Reduction of 1,2,3,4-tetrahydroacridine-9-car-
boxylic acid. Raney nickel, 3 g, was added in small
* Hereinafter, the mass spectra of the corresponding methyl esters
are given.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009