Synthesis of novel derivatives of 2-phenylquinoline-4-carboxylic acid

Full text of DOI:10.1023/A:1014783307934

Doklady Chemistry, Vol. 383, Nos. 1–3, 2002, pp. 72–74. Translated from Doklady Akademii Nauk, Vol. 383, No. 2, 2002, pp. 221–223.
Original Russian Text Copyright © 2002 by Shvekhgeimer, Kondrashova.
CHEMISTRY
Synthesis of Novel Derivatives
of 2-Phenylquinoline-4-carboxylic Acid
M.-G. A. Shvekhgeimer and N. N. Kondrashova
Presented by Academician N.K. Kochetkov December 6, 2001
Received December 21, 2001
Among the compounds of a quinoline series, quino- potassium hydroxide in water and an aqueous alcohol
line-4-carboxylic acid derivatives attract the attention medium and found that the yields of 2-(4-aminophe-
of researchers due to their close structural resemblance nyl)quinoline-4-carboxylic acids (2) are higher (72–
to alkaloids.
The most general and simple method for preparing
quinoline-4-carboxylic acids is the Pfitzinger reaction:
the condensation of compounds of an isatin series with
ketones of the general formula R1CH2COR2 in the pres-
ence of NaOH or KOH [1, 2]:
86%) when the reaction is run in an aqueous alcohol
medium. According to spectral data, the resulting com-
pounds exist as bipolar ions 2:
R
O
O
+
CH3CO
NH2
N
H
O
O
R
+ R1CH2COR2
N
H
COOH
R
KOH, C2H5OH, H2O
COOH
R1
reflux
NH2
N
NaOH or KOH
alcohol, water
R
R2
COO–
4
N
5
It follows from the literature data that both ace-
tophenone and a wide variety of its derivatives were
involved in the reaction with numerous compounds of
isatin series. Before our work, however, no information
on the use of 4-aminoacetophenone (1) in the Pfitzinger
reaction was available. At the same time, the reaction of
ketone 1 with isatin and its derivatives opens the way to
the preparation of 2-(4-aminophenyl)quinoline-4-car-
boxylic acids, initial compounds for the synthesis of
numerous derivatives of 2-phenylquinoline-4-carboxy-
lic acid.
6
β
α
α
R
3
+
7
NH2 ,
2
N
8
1
β
2
R = H, Br, NO2.
The diazotization of compound 2 was found to
readily occur under standard conditions to produce dia-
zonium salts 3. Diazonium salts 3 were involved in situ
into the coupling reaction with the derivatives of 1-aryl-
We studied the reaction of ketone 1 with isatin, 3-methylpyrazol-5-one (4) to form coupling products
5-bromoisatin, and 5-nitroisatin in the presence of (5), usually in high yield.
CH3
COOH
N
COOH
O
N
R
CH3
4
NaNO2, HCl (H2O)
0°C, 0.5–1 h
Ar
NHN
2
R
N
+
–
N
NCl
O
N
N
3
5
Ar
R = H, Br, NO2; Ar = C6H5–, 4-CH3C6H4–, 4-
HO3SC6H4–.
Kosygin State Textile University, Moscow,
ul. Malaya Kaluzhskaya 1, Moscow, 117918 Russia
0012-5008/02/0003-0072$27.00 © 2002 åÄIä “Nauka /Interperiodica”

SYNTHESIS OF NOVEL DERIVATIVES
73
zene ring), 2802 and 1592 (NH+3 ), 1582 and 1402
(COO–), 1560 and 1352 (NO2). UV (λmax, nm (logε)):
EXPERIMENTAL
IR spectra were recorded on a Specord M-80 spec-
trophotometer (as pressed KBr pellets). UV spectra
were recorded on a Uvidek-610 spectrophotometer in a
1
228.0 (4.25), 272.8 (4.22), 368.0 (4.09). H NMR
(300 MHz, DMSO-d6-CCl4, δ, ppm): 6.74 (d, 2H,
CαH), 8.09 (d, 2H, CβH), 8.46 (s, 1H, C3H), 8.85 (s, 1H,
C5H), 7.86 (d, 1H, C7H), 8.66 (d, 1H, C8H).
1
1% aqueous solution of sodium hydroxide. H NMR
spectra were recorded on Bruker AC-300 or WM-250
spectrometers in DMSO-d6–CCl4 solutions.
For C16H11N3O4 anal. calcd. (%): C, 62.13; H, 3.58;
N, 13.58.
2-(4-Aminophenyl)quinoline-4-carboxylic acid
(2) (R = H). A mixture of 10.37 g (0.075 mol) of isatin,
9.45 g (0.07 mol) of ketone 1, and a solution of 11.2 g
(0.2 mol) of potassium hydroxide in 80 mL of alcohol
and 2 mL of water was heated under reflux with stirring
until compound 1 was exhausted (monitoring with the
use of thin layer chromatography), which required 20–
24 h. The hot reaction mixture was filtered, 100 mL of
water was added to the filtrate, and hydrochloric acid
(1 : 1) was added with stirring to pH 6–6.5. The mixture
was stirred for 15 min and filtered. The precipitate was
washed on the filter with water (3 × 25 mL), alcohol
(2 × 5 mL), and ether (2 × 10 mL). The yield was 15.89 g
(85.9%); mp 174–176°C (DMF–H2O). IR (KBr, ν,
Found (%): C, 61.62; H, 3.74; N, 13.17.
Hydrazone 5 (R = H, Ar = C6H5). A. A mixture of
1.32 g (0.005 mol) of compound 2 (R = H), 25 mL of
water and 5.4 mL of 27.5% hydrochloric acid was
heated to reflux with stirring and cooled to 0°C. Then,
3.5 mL of an aqueous solution of NaNO2 (concentra-
tion 200 g/L) was added, and the mixture was stirred at
0°C for 1 h. B. Water (4.5 mL) and a solution of 0.2 g
of NaOH in 2 mL of H2O were added to 0.86 g
(0.005 mol) of 1-phenyl-3-methylpyrazol-5-one (4)
(Ar = C6H5) with stirring. The mixture was heated to
60°C, and 0.5 mL of a 10% aqueous solution of NaOH
and a solution of 0.5 g of Na2CO3 in 6.5 mL of H2O
were added with stirring. The resulting solution was
cooled to 5–8°C and added to mixture A over 10 min.
During the mixing of mixtures A and B, the pH 8.5 of
the medium was maintained by periodically adding a
10% aqueous NaOH solution. The reaction mixture
was stirred at 5–8°C to the complete disappearance of
diazonium salt, allowed to stand overnight, and acidi-
fied to pH 7 with acetic acid. The precipitate was col-
lected by filtration, washed on the filter with water, and
dried in air. The yield was 2.25 g (88.9%); mp 226–
228°C. IR (KBr, ν, cm–1): 1548 (C=C arom.), 3216 (C–
H arom.), 829 (1,4-disubstituted benzene ring), 1636
cm−1): 1544 and 1496 (C=C arom.), 3202 (C–H arom.),
816 (1,4-disubstituted benzene ring), 2802 and 588
(NH+3 ), 1536 and 1400 (COO–). UV (λmax, nm (logε)):
1
227.2 (4.26), 282.4 (4.17), 345.6 (4.01). H NMR
(300 MHz, DMSO-d6-CCl4, δ, ppm): 6.72 (d, 2H,
CαH), 8.01 (d, 2H, CβH), 8.32 (s, 1H, C3H), 8.03 (d, 1H,
C5H), 7.72 (m, 1H, C6H), 7.52 (m, 1H, C7H), 8.69 (d,
1H, C8H).
For C16H12N2O2 anal. calcd. (%): C, 72.71; H, 4.58;
N, 10.60.
Found (%): C, 73.07; H, 4.21; N, 10.37.
2-(4-Aminophenyl)-6-bromoquinoline-4-carbox-
ylic acid (2) (R = Br) was obtained similarly to com-
pound 2 (R = H). The yield was 85%; mp 288–290°C
(from DMF–H2O). IR (KBr, ν, cm–1): 1592 and 1472
(C=C arom.), 3208 (C–H arom.), 825 (1,4-disubstituted
benzene ring), 2802 and 1592 (NH+3 ), 1582 and 1402
(COO–). UV (λmax, nm (logε)): 232.0 (4.46), 265.6
(4.22), 293.6 (4.25), 353.6 (4.14). 1H NMR (300 MHz,
DMSO-d6-CCl4, δ, ppm): 7.14 (d, 2H, CαH), 8.23 (d,
2H, CβH), 8.46 (s, 1H, C3H), 8.89 (s, 1H, C5H), 7.93 (d,
1H, C7H), 8.07 (d, 1H, C8H).
( C=NNH–), 1664 (>C=O). UV (λmax, nm (logε)):
1
336.8 (4.37), 375.2 (4.41). H NMR (250 MHz, δ,
ppm): 2.32 (s, 3H, CH3), 8.22 (s, 1H, C3H), 8.06 (d, 1H,
C5H), 7.53 (m, 1H, C6H), 7.22 (m, 1H, C7H), 8.68 (d,
1H, C8H), 7.94 (d, 2H, CαH), 8.33 (d, 2H, CβH), 7.46–
7.74 (6H, C6H5, NH).
For C26H19N5O3 anal. calcd. (%): C, 69.48; H, 4.26;
N, 15.58.
Found (%): C, 69.12; H, 4.48; N, 15.17.
Other hydrazones 5 were obtained in a similar way
from the corresponding compounds 2 and 4.
For C16H11BrN2O2 anal. calcd. (%): C, 55.99; H,
3.23; N, 8.16.
Hydrazone 5 (R = Br, Ar = C6H5). Yield, 87.0%;
mp 159–161°C. IR (KBr, ν, cm–1): 1552 (C=C arom.),
3216 (C–H arom.), 836 (1,4-disubstituted benzene
ring), 1640 (>C=NNH–), 1664 (>C=O). UV (λmax, nm
(logε)): 207.2 (4.35), 221.6 (4.5), 237.2 (4.46), 354.4
(4.22), 428.8 (4.35).
Found (%): C, 55.67; H, 3.19; N, 7.79.
2-(4-Aminophenyl)-6-nitroquinoline-4-carboxy-
lic acid (2) (R = NO2) was obtained similarly to com-
pound 2 (R = H, Br) with the difference that the reaction
mixture after refluxing was not filtered but diluted with
100 mL of water and treated as described above. The
yield was 72.1%; decomposition temperature >300°C
(from DMF). IR (KBr, ν, cm–1): 1592 and 1472 (C=C
For C26H18BrN5O3 anal. calcd. (%): C, 59.09; H,
3.43; N, 13.26.
Found (%): C, 58.68; H, 3.54; N, 12.91.
Hydrazone 5 (R = NO2, Ar = C6H5). Yield, 77.2%;
arom.), 3208 (C–H arom.), 825 (1,4-disubstituted ben- decomposition temperature > 250°C. IR (KBr, ν, cm–1):
DOKLADY CHEMISTRY Vol. 383 Nos. 1–3 2002

74
SHVEKHGEIMER, KONDRASHOVA
1512 (C=C arom.), 3408 (C–H arom.), 840 (1,4-disub- ν, cm–1): 1483 (C=C arom.), 3412 (C–H arom.), 818
stituted benzene ring), 1636 (>C=NNH–), 1660 (1,4-disubstituted benzene ring), 1662 (>C=NNH–),
(>C=O), 1544 and 1356 (NO2). UV (λmax, nm (logε)): 1554 (>C=O), 1384 and 1165 (SO3H). UV (λmax, nm
207.2 (4.41), 220.8 (4.49), 246.4 (4.43), 374.4 (4.33), (logε)): 214.2 (4.29), 236.8 (4.26), 336.0 (4.02), 383.2
456.0 (4.48).
(4.20), 424.0 (4.27).
For C26H18N6O5 anal. calcd. (%): C, 63.15; H, 3.41;
N, 17.00.
For C26H19N5O5S anal. calcd. (%): C, 60.81; H,
3.73; N, 13.64.
Found (%): C, 63.25; H, 3.41; N, 16.52.
Found (%): C, 61.27; H, 3.64; N, 13.21.
Hydrazone 5 (R = H, Ar = 4-CH3C6H4). Yield,
87.0%; mp 156–158°C. IR (KBr, ν, cm–1): 1524 (C=C
arom.), 3404 (C–H arom.), 816 (1,4-disubstituted ben-
Hydrazone 5 (R = Br, Ar = 4-HO3SC6H4). Yield,
82.2%; decomposition temperature >280°C. IR (KBr,
ν, cm–1): 1552 (C=C arom.), 3380 (C–H arom.), 832
(1,4-disubstituted benzene ring), 1572 (>C=NNH–),
1596 (>C=O), 1356 and 1176 (SO3H). UV (λmax, nm
(logε)): 202.4 (4.29), 219.2 (4.35), 231.2 (4.31), 253.6
(4.20), 296.8 (4.04), 360.8 (4.07), 443.0 (3.96).
zene ring), 1628 (>C=NNH–), 1664 (>C=O). UV (λmax
,
nm (logε)): 330.4 (4.44), 376.0 (4.49).
For C27H21N5O3 anal. calcd. (%): C, 69.96; H, 4.57;
N, 14.16.
For C26H18BrN5O5S anal. calcd. (%): C, 52.71; H,
3.06; N, 11.82.
Found (%): C, 69.62; H, 4.28; N, 15.81.
Hydrazone 5 (R = Br, Ar = 4-CH3C6H4). Yield,
70.1%; mp 154–156°C. IR (KBr, ν, cm–1): 1512 (C=C
arom.), 3416 (C–H arom.), 810 (1,4-disubstituted ben-
Found (%): C, 52.38; H, 3.16; N, 12.21.
Hydrazone 5 (R = NO2, Ar = 4-HO3SC6H4).Yield,
38.3%; decomposition temperature >280°C. IR (KBr,
ν, cm–1): 1544 (C=C arom.), 3408 (C–H arom.), 840
(1,4-disubstituted benzene ring), 1545 (>C=NNH–),
1600 (>C=O), 1500 and 1352 (NO2), 1336 and 1180
(SO3H). UV (λmax, nm (logε)): 203.2 (4.37), 218.4
(4.44), 252.8 (4.33), 280.0 (4.26), 440.8 (4.32).
zene ring), 1640 (>C=NNH–), 1656 (>C=O). UV (λmax
,
nm (logε)): 207.2 (4.58), 238.4 (4.67), 385.6 (4.4),
433.6 (4.4).
For C27H20BrN5O3 anal. calcd. (%): C, 59.78; H,
3.72; N, 12.91.
Found (%): C, 59.31; H, 3.46; N, 12.56.
For C26H18N6O7S anal. calcd. (%): C, 55.91; H,
3.25; N, 15.05.
Hydrazone 5 (R = NO2, Ar = 4-CH3C6H4). Yield,
78.7%; decomposition temperature >250°C. IR (KBr,
ν, cm–1): 1544 (C=C arom.), 3392 (C–H arom.), 816
(1,4-disubstituted benzene ring), 1642 (>C=NNH–),
1558 (>C=O), 1544 and 1356 (NO2). UV (λmax, nm
(logε)): 206.4 (4.39), 246.4 (4.44), 272.8 (4.3), 380.0
(4.26), 449.6 (4.36).
For C27H20N6O5 anal. calcd. (%): C, 63.77; H, 3.96;
N, 16.53.
Found (%): C, 64.13; H, 3.78; N, 16.14.
Hydrazone 5 (R = H, Ar = 4-HO3SC6H4). Yield,
96.2%; decomposition temperature >280°C. IR (KBr,
Found (%): C, 56.31; H, 3.46; N, 14.68.
REFERENCES
1. Heterocyclic Compounds, Elderfield, R., Ed., NewYork,
1952, vol. 4. Translated under the title Geterotsikli-
cheskie soedineniya, Moscow: Inostrannaya Literatura,
1955, vol. 4.
2. Zhungietu, G.I. and Rekhter, M.A., Izatin i ego proizvod-
nye (Isatin and Its Derivatives), Chisinau: Shtiintsa,
1977, pp. 68–78.
DOKLADY CHEMISTRY Vol. 383 Nos. 1–3 2002