Synthesis of new derivatives of 4-quinolinecarboxylic acid [3]

Full text of DOI:10.1023/A:1015363931038

Chemistry of Heterocyclic Compounds, Vol. 38, No. 2, 2002
SYNTHESIS OF NEW DERIVATIVES
OF 4-QUINOLINECARBOXYLIC ACID
M.-G. A. Shvekhgeimer and N. N. Kondrashova
Keywords: 4-aminoacetophenone, 2-(4-aminophenyl)-4-quinolinecarboxylic acids, 5-bromoisatin,
isatin, 5-nitroisatin, Pfitzinger reaction.
The Pfitzinger reaction is the most efficient and simplest method for the synthesis of
4-quinolinecarboxylic acid derivatives [1, 2]. Many isatin derivatives as well as acetophenone and its various
derivatives have been used in this reaction. However, the use of 4-aminoacetophenone (1) in this reaction has not
yet been studied. The use of aminoacetophenone 1 in the Pfitzinger reaction would open a path for the preparation
of derivatives of 2-(4-aminophenyl)-4-quinolinecarboxylic acid, which hold interest as promising synthons.
We have studied the reaction of aminoacetophenone 1 with isatin, 5-bromoisatin, and 5-nitroisatin in
aqueous ethanol in the presence of potassium hydroxide. 2-(4-Aminophenyl)-4-quinolinecarboxylic acids, which
exist as internal salts 2, were obtained in 72-86% yield.
O
O
R
KOH, C2H5OH, H2O
reflux
CH3C
+
NH2
O
N
H
1
–
COO
5
6
4
R
α
α
3
β
β
+
NH3
7
2
N
8
1
2
R = H, Br, NO2
2-(4-Aminophenyl-4-quinolinecarboxylic Acid (2, R = H). Mixture of isatin (10.37 g, 0.075 mol),
aminoacetophenone 1 (9.45 g, 0.07 mol), and solution of potassium hydroxide (11.2 g, 0.2 mol) in ethanol (80
ml) and water (2 ml) was heated at reflux with stirring until starting 1 completely disappeared (20-24 h) as
indicated by periodic monitoring by thin-layer chromatography. The reaction mixture was filtered hot and water
(100 ml) was added to the filtrate. Then, the solution was acidified by adding of 1:1 concentrated hydrochloric
acid–water to pH 6.0-6.5. The precipitate was filtered and washed with three 25 ml water portions, two 5 ml
ethanol portions, and two 10 ml ether portions to give 15.89 g (86%) of compound 2, which was recrystallized
from DMSO–water; mp 174-176°C. IR spectrum (KBr pellet), ν, cm-1: 1595 and 1456 (C=C, arom); 3200 (C–H,
+
-
arom); 816 (1,4-disubstituted benzene ring); 2803 and 1590 (NH3 ); 1540 and 1408 (CO2 ). UV spectrum,
__________________________________________________________________________________________
A. N. Kosygin Moscow State Textile University, 117918 Moscow, Russia; e-mail: office@msta.ac.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 275-276, February, 2002. Original article
submitted June 21, 2001.
0009-3122/02/3802-0253$27.00©2002 Plenum Publishing Corporation
253

1
λmax, nm (log ε): 221.6 (2.01), 282.0 (1.85), 344.8 (1.68). H NMR spectrum (300 MHz, DMSO-d6–CCl4),
ppm: 6.72 (2H, d, α-H); 8.01 (2H, d,
δ,
β-H); 8.32 (1H, s, 3-H); 8.03 (1H, d, 5-H); 7.72 (1H, t, 6-H); 7.52 (1H, t,
7-H); 8.69 (1H, d, 8-H). Found, %: C 73.07, H 4.21; N 10.37. C16H12N2O2. Calculated, %: C 72.71; H 4.58;
N 10.60.
Other compounds 2 were prepared from acetophenone 1 and corresponding isatin derivatives in the
similar way.
2-(4-Aminophenyl)-6-bromo-4-quinolinecarboxylic Acid (2, R = Br) was obtained in 85% yield;
mp 288-290°C (DMSO–water). IR spectrum (KBr pellet), ν, cm-1: 1544 and 1496 (C=C, arom); 3202 (C–H,
+
-
arom); 816 (1,4-disubstituted benzene ring); 2802 and 1580 (NH3 ); 1536 and 1400 (CO2 ). UV spectrum,
1
λmax, nm (log ε): 230.8 (1.94), 266.8 (1.68), 293.2 (1.72), 354.0 (1.60). H NMR spectrum (300 MHz,
, ppm: 7.14 (2H, d, α-H); 8.23 (2H, d,
DMSO-d6–CCl4), δ
β-H); 8.46 (1H, s, 3-H); 8.89 (1H, s, 5-H); 7.93 (1H, d,
7-H); 8.07 (1H, d, 8-H). Found, %: C 55.67; H 3.19; N 7.79. C16H11BrN2O2. Calculated, %: C 55.99; H 3.23;
N 8.16.
2-(4-Aminophenyl)-6-nitro-4-quinolinecarboxylic Acid (2, R = NO2). The reaction mixture after
termination of heating at reflux was not filtered but rather diluted by adding water (100 ml) and treated as
described for acid 2 (R = H). The product yield was 72%; dec. >300°C (DMSO). IR spectrum (KBr pellet),
ν, cm-1: 1592 and 1472 (C=C, arom); 3208 (C–H, arom); 825 (1,4-disubstituted benzene ring); 2802 and
+
-
1592 (NH3 ); 1582 and 1402 (CO2 ); 1560 and 1352 (NO2). UV spectrum, λmax, nm (log ε): 217.6 (1.83),
280.0 (1.72), 352.4 (1.55), 414.8 (1.39). Found, %: C 61.62; H 3.74; N 13.17. C16H11N3O4. Calculated, %:
C 62.13; H 3.58; N 13.58.
REFERENCES
1.
2.
R. Elderfield, Heterocyclic Compounds [Russian translation], Vol. 4, Inostr. Lit., Moscow (1955), p. 36.
G. I. Zhungietu and M. A. Rekhter, Isatin and Isatin Derivatives [in Russian], Shtiintsa, Kishinev
(1977), p. 68.
254