Synthesis and transformations of 2- and 4-(2-methylquinolin-4-ylamino) benzoic acids and ethyl 4-(2-methylquinolin-4-ylamino)benzoates and their fluorescent properties

Article abstract of DOI:10.1134/S1070428007070196

2- and 4-(2-Methylquinolin-4-ylamino)benzoic acids and ethyl 4-(2-methylquinolin-4-ylamino)-benzoates having a substituent in the 6(8)-position of the quinoline ring were synthesized by reaction of the corresponding substituted 4-chloro-2-methylquinolines

Full text of DOI:10.1134/S1070428007070196

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 7, pp. 1052–1057. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © A.A. Avetisyan, I.L. Aleksanyan, L.P. Ambartsumyan, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 7,
pp. 1058–1062.
Synthesis and Transformations of 2- and 4-(2-Methylquinolin-
4-ylamino)benzoic Acids and Ethyl 4-(2-Methylquinolin-
4-ylamino)benzoates and Their Fluorescent Properties
A. A. Avetisyan, I. L. Aleksanyan, and L. P. Ambartsumyan
Erevan State University, ul. A. Manukyana 1, Erevan, 375025 Armenia
e-mail: organkim@sun.ysu.am
Received April 23, 2006; revised October 10, 2006
Abstract—2- and 4-(2-Methylquinolin-4-ylamino)benzoic acids and ethyl 4-(2-methylquinolin-4-ylamino)-
benzoates having a substituent in the 6(8)-position of the quinoline ring were synthesized by reaction of the
corresponding substituted 4-chloro-2-methylquinolines with 2- and 4-aminobenzoic acids and ethyl 4-amino-
benzoate. Intramolecular cyclization of 2-(2-methylquinolin-4-ylamino)benzoic acids in concentrated sulfuric
acid gave 7-hydroxy-6-methyldibenzo[b,h][1,6]naphthyridines, and ethyl 4-(2-methylquinolin-4-ylamino)ben-
zoates were converted into 4-(2-methylquinolin-4-ylamino)benzoic acids by alkaline hydrolysis.
DOI: 10.1134/S1070428007070196
With a view to obtain new 4-phenylaminoquinoline
derivatives, we examined reactions of compounds Ia–
If with ethyl 4-aminobenzoate. Under the optimal con-
ditions (reactant ratio 1:1.1, ethanol–hydrochloric acid,
15 h) we obtained in high yields the corresponding
ethyl 4-(2-methylquinolin-4-ylamino)benzoates Va–
Vf. Their alkaline hydrolysis gave 4-(2-methylquino-
lin-4-ylamino)benzoic acids VIa–VIf in quantitative
yield (Scheme 2). Compounds VIa–VIf were also
synthesized by direct reaction of substituted quinolines
Ia–If with 4-aminobenzoic acid. Samples of acids
VIa–VIf obtained by the two methods were identical
in physical properties and spectral parameters.
The present article reports on reactions of
6(8)-substituted 4-chloro-2-methylquinolines with 2-
and 4-aminobenzoic acids and ethyl 4-aminobenzoate.
Optimal conditions for these reactions were found. By
heating substituted 4-chloro-2-methylquinolines Ia–If
with 2-aminobenzoic acid at a ratio of 1:1.1 in ethanol
in the presence of hydrochloric acid for 15 h we ob-
tained in high yields the corresponding 2-(2-methyl-
quinolin-4-ylamino)benzoic acids IIa–IIf. The latter
underwent intramolecular cyclization in concentrated
sulfuric acid, which involved the 3-position of the
quinoline ring and led to the corresponding 7-hydroxy-
6-methylquinolino[3,2-c]quinolines IIIa–IIIf in high
yields (Scheme 1). No intramolecular cyclization was
observed when polyphosphoric acid (PPA) was used as
condensing agent; presumably, the reason is lower
protonating power of PPA compared to sulfuric acid.
We also examined electronic absorption, fluores-
cence, and fluorescence excitation spectra of com-
pounds IIIa, Vb, Vc, and VIe and previously syn-
thesized 6-methyldibenzo[b,h][1,6]naphthyridin-7-ol
Scheme 1.
NH2
Cl
N
HN
N
COOH
Me
OH
COOH
R
R
R
Me
N
N
Me
Ia–If
IIa–IIf
IIIa–IIIf
R = 6-Me (a), 8-Me (b), 6-MeO (c), 8-MeO (d), 6-Br (e), 8-Cl (f).
1052

SYNTHESIS AND TRANSFORMATIONS OF 4-(4-ETHOXYCARBONYLPHENYLAMINO)- ...
1053
Scheme 2.
COOEt
COOEt
COOEt
HN
N
HN
N
H2N
·2HCl
R
R
Me
Me
Va–Vf
IVa–IVf
Ia–If
COOH
COOH
HN
N
H2N
R
Me
VIa–VIf
R = 6-Me (a), 8-Me (b), 6-MeO (c), 8-MeO (d), 6-Br (e), 8-Cl (f).
(VII) [1] (Figs. 1–3; see table). Compound VIe
showed no fluorescence properties. The long-wave
region of the electronic absorption spectra of com-
pounds VII and IIIa is characterized by vibrational
structure (Fig. 1). Analogous vibrational structure was
also observed in the emission spectra of VII and Vb
(Figs. 2, 3), while it was absent in the spectra of IIIa
and Vc. Presumably, the observed pattern is deter-
mined by different conformations of these compounds
in the ground and excited states.
50 ml of ethanol was heated for 14–15 h on a water
bath. The solvent was distilled off, the residue was
treated with water, and the precipitate was filtered off.
It was dissolved in dilute alkali, the solution was
filtered, the filtrate was acidified to pH 1–2, and the
precipitate was filtered off.
2-(2,6-Dimethylquinolin-4-ylamino)benzoic acid
dihydrochloride (IIa). Yield 3.48 g (95%), mp 206–
208°C, Rf 0.54 (EtOH). IR spectrum, ν, cm–1: 1700
1
(C=O), 3250–3420 (OH). H NMR spectrum, δ, ppm:
2.50 s (3H, 6-CH3), 2.70 s (3H, 2-CH3), 6.80–8.70 m
(8H, Harom), 10.10 s (1H, OH) 10.50 s (1H, NH).
EXPERIMENTAL
The IR spectra were recorded on a UR-20 spec-
trometer from samples dispersed in mineral oil. The
1H NMR spectra were obtained on a Varian Mercury-
300 instrument using DMSO-d6 as solvent. The purity
of the products was checked by TLC on Silufol UV-
254 plates (development with iodine vapor). Photo-
and fluorimetric measurements were performed in
2-methyltetrahydrofuran (from Sigma) at 20–25°C at
a concentration of (1.3–5)×10–4 M. The electronic ab-
sorption spectra were measured on a Specord 50-PC
spectrophotometer. The fluorescence spectra were
recorded on a Cary Eclipse Varian Fluorescence fluo-
rimeter.
I, arb. units
1.0
0.8
1
0.6
2
0.4
0.2
2-(2-Methylquinolin-4-ylamino)benzoic acid di-
hydrochlorides IIa–IIf (general procedure). A mix-
ture of 0.01 mol of substituted 4-chloro-2-methylquin-
oline Ia–If [2], 1.507 g (0.011 mol) of 2-aminobenzoic
acid, and 1 ml of concentrated hydrochloric acid in
0.0
360
420
480
540
λ, nm
Fig. 1. Electronic absorption spectra of (1) 6-methyldibenzo-
[b,h][1,6]naphthyridin-7-ol (VII) [1] and (2) 2,6-dimethyldi-
benzo[b,h][1,6]naphthyridin-7-ol (IIIa).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

AVETISYAN et al.
1054
I, arb. units
D
3.0
2.5
2.0
1.5
1.0
0.5
0.0
1.0
0.8
0.6
0.4
0.2
0.0
1
1
2
2
400
450
500
550
600 λ, nm
200
250
300
350
400
λ, nm
Fig. 2. Fluorescence spectra of (1) ethyl 4-(2,8-dimethyl-
quinolin-4-ylamino)benzoate (Vb) and (2) ethyl 4-(6-meth-
oxy-2-methylquinolin-4-ylamino)benzoate (Vc).
Fig. 3. Fluorescence excitation spectra of (1) 6-methyldi-
benzo[b,h][1,6]naphthyridin-7-ol (VII) [1] and (2) 2,6-di-
methyldibenzo[b,h][1,6]naphthyridin-7-ol (IIIa).
Found, %: C 59.26; H 4.84; N 7.84. C18H18Cl2N2O2.
Calculated, %: C 59.18; H 4.93; N 7.67.
C18H18Cl2N2O3. Calculated, %: C 56.69; H 4.72;
N 7.35.
2-(8-Methoxy-2-methylquinolin-4-ylamino)ben-
zoic acid (IId). Yield 3.26 g (86%), mp 222–224°C
(decomp.), Rf 0.49 (EtOH–hexane, 2:1). IR spectrum,
ν, cm–1: 1720 (C=O), 3000–3300 (OH). 1H NMR spec-
trum, δ, ppm: 2.75 s (3H, 2-CH3), 4.00 s (3H, OCH3),
6.80–8.80 m (8H, Harom), 10.0 s (1H, OH), 10.50 s
(1H, NH). Found, %: C 56.75; H 4.63; N 7.48.
C18H18Cl2N2O3. Calculated, %: C 56.69; H 4.72;
N 7.35.
2-(2,8-Dimethylquinolin-4-ylamino)benzoic acid
dihydrochloride (IIb). Yield 3.03 g (83%), mp 200°C,
Rf 0.51 (EtOH). IR spectrum, ν, cm–1: 1720 (C=O),
1
3200–3400 (OH). H NMR spectrum, δ, ppm: 2.30 s
(3H, 8-CH3), 2.70 s (3H, 2-CH3), 6.80–8.75 m (8H,
Harom), 10.20 s (1H, OH), 10.70 s (1H, NH). Found, %:
C 59.05; H 4.99; N 7.76. C18H18Cl2N2O2. Calculated,
%: C 59.18; H 4.93; N 7.67.
2-(6-Methoxy-2-methylquinolin-4-ylamino)ben-
zoic acid dihydrochloride (IIc). Yield 3.59 g (94%),
mp 283–285°C (decomp.), Rf 0.54 (EtOH). IR spec-
trum, ν, cm–1: 1730 (C=O), 3100–3300 (OH). 1H NMR
spectrum, δ, ppm: 2.70 s (3H, 2-CH3), 3.70 s (3H,
OCH3), 6.70–8.60 m (8H, Harom), 10.0 s (1H, OH),
10.30 s (1H, NH). Found, %: C 56.54; H 4.89; N 7.42.
2-(6-Bromo-2-methylquinolin-4-ylamino)benzoic
acid dihydrochloride (IIe). Yield 3.23 g (75%),
mp 316–319°C (decomp.), Rf 0.50 (EtOH). IR spec-
trum, ν, cm–1: 1730 (C=O), 2800–3000 (OH). 1H NMR
spectrum, δ, ppm: 2.70 s (3H, CH3), 6.80–8.70 m (8H,
Harom), 10.10 s (1H, OH), 10.30 s (1H, NH). Found, %:
C 47.31; H 3.62; N 6.43. C17H15BrCl2N2O2. Calculat-
ed, %: C 47.44; H 3.49; N 6.51.
Electronic absorption and fluorescence spectra of com-
pounds IIIa, Vb, Vc, VIe, and VII
2-(8-Chloro-2-methylquinolin-4-ylamino)benzoic
acid dihydrochloride (IIf). Yield 2.76 g (72%),
mp 198–200°C (decomp.), Rf 0.50 (EtOH). IR spec-
trum, ν, cm–1: 1730 (C=O), 2700–3000 (OH). 1H NMR
spectrum, δ, ppm: 2.52 s (3H, CH3), 6.70–8.50 m (8H,
Compound
no.
Absorption spectrum,
Fluorescence
spectrum, λmax, nm.
λmax, nm (logε)
VIIa
329 (4.34), 351 (3.78),
368 (3.58)
384, 399
Harom), 10.00 s (1H, OH), 10.20 s (1H, NH). Found, %:
334 (3.63), 363 (3.46),
381 (3.50)
423
IIIa
C 52.84; H 4.01; N 7.37. C17H15Cl3N2O2. Calculated,
%: C 52.92; H 3.89; N 7.26.
350 (4.15)
359 (3.66)
353 (2.82)
415
403
–
Vb
Vc
Substituted 6-methyldibenzo[b,h][1,6]naphthyri-
din-7-ols IIIa–IIIf (general procedure). A mixture of
0.005 mol of compound IIa–IIf and 10 ml of concen-
trated sulfuric acid was heated for 2 h on a water bath.
VIe
a
Data of [1].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

SYNTHESIS AND TRANSFORMATIONS OF 4-(4-ETHOXYCARBONYLPHENYLAMINO)- ...
1055
The mixture was cooled and poured onto 50 g of
crushed ice. The precipitate was filtered off and dis-
solved in dilute alkali, the solution was filtered and
neutralized, and the precipitate was filtered off and
recrystallized from alcohol.
distilled off, the residue was treated with water, and the
precipitate was filtered off.
Ethyl 4-(2,6-dimethylquinolin-4-ylamino)ben-
zoate dihydrochloride (IVa). Yield 3.36 g (86%),
mp 232–235°C, Rf 0.60 (EtOH–hexane, 1:1). Found,
%: C 61.15; H 5.51; N 7.20. C20H22Cl2N2O2. Calculat-
ed, %: C 61.07; H 5.60; N 7.12.
2,6-Dimethyldibenzo[b,h][1,6]naphthyridin-7-ol
(IIIa). Yield 1.09 g (80%), mp 310°C, Rf 0.68 (EtOH).
1H NMR spectrum, δ, ppm: 2.70 s (3H, 2-CH3), 3.00 s
(3H, 6-CH3), 7.2–8.7 m (7H, Harom), 11.5 s (1H, OH).
Found, %: C 78.71; H 5.22; N 10.34. C18H14N2O. Cal-
culated, %: C 78.83; H 5.11; N 10.22.
Ethyl 4-(2,8-dimethylquinolin-4-ylamino)ben-
zoate dihydrochloride (IVb). Yield 3.40 g (87%),
mp 216–218°C, Rf 0.68 (EtOH). Found, %: C 59.94;
H 5.69; N 7.03. C20H22Cl2N2O2. Calculated, %:
C 61.07; H 5.60; N 7.12.
4,6-Dimethyldibenzo[b,h][1,6]naphthyridin-7-ol
(IIIb). Yield 1.16 g (85%), mp 300°C, Rf 0.68 (EtOH).
1H NMR spectrum, δ, ppm: 2.50 s (3H, 4-CH3), 2.90 s
(3H, 6-CH3), 7.3–8.6 m (7H, Harom), 11.6 s (1H, OH).
Found, %: C 78.79; H 5.28; N 10.38. C18H14N2O. Cal-
culated, %: C 78.83; H 5.11; N 10.22.
Ethyl 4-(6-methoxy-2-methylquinolin-4-yl-
amino)benzoate dihydrochloride (IVc). Yield 3.80 g
(93%), mp 263–265°C, Rf 0.50 (EtOH–hexane, 1:1).
Found, %: C 58.75; H 5.29; N 6.70. C20H22Cl2N2O3.
Calculated, %: C 58.68; H 5.38; N 6.85.
2-Methoxy-6-methyldibenzo[b,h][1,6]naphthyri-
din-7-ol (IIIc). Yield 1.30 g (92%), mp 296–300°C
(decomp.), Rf 0.51 (EtOH–hexane, 2:1). H NMR spec-
trum, δ, ppm: 2.75 s (3H, 6-CH3), 4.00 s (3H, OCH3),
7.2–8.6 m (7H, Harom), 11.2 s (1H, OH). Found, %:
C 74.35; H 4.96; N 9.58. C18H14N2O2. Calculated, %:
C 78.48; H 4.83; N 9.66.
Ethyl 4-(8-methoxy-2-methylquinolin-4-yl-
amino)benzoate dihydrochloride (IVd). Yield 3.51 g
(86%), mp 255–257°C, Rf 0.42 (EtOH–water, 1:1).
Found, %: C 58.60; H 5.45; N 6.92. C20H22Cl2N2O3.
Calculated, %: C 58.68; H 5.38; N 6.85.
1
Ethyl 4-(6-bromo-2-methylquinolin-4-ylamino)-
benzoate dihydrochloride (IVe). Yield 3.91 g (85%),
mp 256–258°C, Rf 0.69 (EtOH–hexane, 1:1). Found,
%: C 49.69; H 4.26; N 6.03. C19H19BrCl2N2O2. Calcu-
lated, %: C 49.78; H 4.15; N 6.11.
4-Methoxy-6-methyldibenzo[b,h][1,6]naphthyri-
din-7-ol (IIId). Yield 1.31 g (90%), mp 271–274°C
(decomp.), Rf 0.6 (EtOH). 1H NMR spectrum, δ, ppm:
2.70 s (3H, 6-CH3), 3.95 s (3H, OCH3), 7.3–8.8 m
(7H, Harom), 11.6 s (1H, OH). Found, %: C 74.56;
H 4.75; N 9.74. C18H14N2O2. Calculated, %: C 74.48;
H 4.83; N 9.66.
Ethyl 4-(8-chloro-2-methylquinolin-4-ylamino)-
benzoate dihydrochloride (IVf). Yield 3.90 g (94%),
mp 207–209°C, Rf 0.65 (EtOH). Found, %: C 55.26;
H 4.52; N 6.89. C19H19Cl3N2O2. Calculated, %:
C 55.14; H 4.59; N 6.77.
2-Bromo-6-methyldibenzo[b,h][1,6]naphthyri-
din-7-ol (IIIe). Yield 1.15 g (68%), mp 306–310°C
1
Ethyl 4-(2-methylquinolin-4-ylamino)benzoates
Va–Vf (general procedure). Dihydrochloride IVa–IVf
was dissolved in water, the solution was filtered and
adjusted to pH 8 by adding alkali, and the precipitate
was filtered off.
(decomp.), Rf 0.52 (EtOH–hexane, 1:1). H NMR spec-
trum, δ, ppm: 2.70 s (3H, CH3), 7.3–8.7 m (7H, Harom),
11.5 s (1H, OH). Found, %: C 60.26; H 3.17; N 8.39.
C17H11BrN2O. Calculated, %: C 60.18; H 3.24; N 8.26.
4-Chloro-6-methyldibenzo[b,h][1,6]naphthyri-
din-7-ol (IIIf). Yield 1.20 g (82%), mp 352–354°C,
Ethyl 4-(2,6-dimethylquinolin-4-ylamino)ben-
zoate (Va). Yield 2.54 g (93%), mp 126–128°C,
Rf 0.65 (chloroform–hexane, 1:6). IR spectrum, ν,
cm–1: 1730 (C=O), 1110 (COC). 1H NMR spectrum, δ,
ppm: 1.14 t (3H, CH2CH3), 2.50 s (3H, 6-CH3), 2.70 s
(3H, 2-CH3), 3.95 q (2H, CH2CH3), 6.50–8.20 m (8H,
1
Rf 0.60 (EtOH–hexane, 2:1). H NMR spectrum, δ,
ppm: 2.72 s (3H, CH3), 7.2–8.6 m (7H, Harom), 11.3 s
(1H, OH). Found, %: C 69.39; H 3.67; N 9.63.
C17H11ClN2O. Calculated, %: C 69.27; H 3.74; N 9.51.
Ethyl 4-(2-methylquinolin-4-ylamino)benzoate
dihydrochlorides IVa–IVf (general procedure).
A mixture of 0.01 mol of compound Ia–If, 1.82 g
(0.011 mol) of ethyl 4-aminobenzoate, and 1 ml of
concentrated hydrochloric acid in 50 ml of ethanol was
heated for 15–20 h on a water bath. The solvent was
Harom), 10.70 s (1H, NH). Found, %: C 75.09; H 6.17;
N 8.89. C20H20N2O2. Calculated, %: C 75.00; H 6.25;
N 8.75.
Ethyl 4-(2,8-dimethylquinolin-4-ylamino)ben-
zoate (Vb). Yield 2.55 g (92%), mp 62–65°C, Rf 0.67
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

AVETISYAN et al.
1056
(chloroform–hexane, 1:7). IR spectrum, ν, cm–1: 1700
(C=O), 1100 (COC). 1H NMR spectrum, δ, ppm: 1.03 t
(3H, CH2CH3), 2.40 s (3H, 8-CH3), 2.65 s (3H, 2-CH3),
3.90 q (2H, CH2CH3), 6.60–8.30 m (8H, Harom),
10.60 s (1H, NH). Found, %: C 74.91; H 6.34; N 8.61.
C20H20N2O2. Calculated, %: C 75.00; H 6.25; N 8.75.
was acidified with hydrochloric acid to pH 1–2, and
the precipitate was filtered off.
b. A mixture of 0.01 mol of 4-chloro-2-methyl-
quinoline Ia–If [2], 1.507 g (1.1 mmol) of 4-amino-
benzoic acid, and 1 ml of concentrated hydrochloric
acid in 50 ml of alcohol was heated for 14–15 h on
a water bath. The solvent was distilled off, the residue
was treated with water, the precipitate was filtered off
and dissolved in dilute alkali, the solution was filtered,
the filtrate was acidified to pH 1–2, and the precipitate
was filtered off.
Ethyl 4-(6-methoxy-2-methylquinolin-4-yl-
amino)benzoate (Vc). Yield 2.97 g (95%), mp 120–
121°C, Rf 0.62 (chloroform–hexane, 1:6). IR spec-
1
trum, ν, cm–1: 1710 (C=O), 1090 (COC). H NMR
spectrum, δ, ppm: 1.10 t (3H, CH2CH3), 2.60 s (3H,
2-CH3), 3.90 s (3H, OCH3), 4.00 q (2H, CH2CH3),
6.55–8.30 m (8H, Harom), 10.70 s (1H, NH). Found, %:
C 71.52; H 5.87; N 8.48. C20H20N2O3. Calculated, %:
C 71.43; H 5.95; N 8.33.
4-(2,6-Dimethylquinolin-4-ylamino)benzoic acid
dihydrochloride (VIa). Yield 1.50 g (82%) (a), 3.36 g
(92%) (b); mp 242–244°C (decomp.), Rf 0.67 (EtOH).
IR spectrum, ν, cm–1: 1730 (C=O), 2700–3000 (OH).
1H NMR spectrum, δ, ppm: 2.50 s (3H, 6-CH3), 2.70 s
(3H, 2-CH3), 6.60–8.80 m (8H, Harom), 10.0 s (1H, OH)
10.60 s (1H, NH). Found, %: C 59.25; H 4.82; N 7.75.
C18H18Cl2N2O2. Calculated, %: C 59.18; H 4.93;
N 7.67.
Ethyl 4-(8-methoxy-2-methylquinolin-4-yl-
amino)benzoate (Vd). Yield 2.62 g (91%), mp 55–
56°C, Rf 0.66 (chloroform–hexane, 1:7). IR spectrum,
ν, cm–1: 1720 (C=O), 1100 (COC). 1H NMR spectrum,
δ, ppm: 1.05 t (3H, CH2CH3), 2.65 s (3H, 2-CH3),
3.93 s (3H, OCH3), 4.05 q (2H, CH2CH3), 6.60–8.30 m
(8H, Harom), 11.00 s (1H, NH). Found, %: C 71.37;
H 6.04; N 8.20. C20H20N2O3. Calculated, %: C 71.43;
H 5.95; N 8.33.
4-(2,8-Dimethylquinolin-4-ylamino)benzoic acid
dihydrochloride (VIb). Yield 1.66 g (91%) (a), 3.21 g
(88%) (b); mp 291–293°C (decomp.), Rf 0.62 (EtOH).
IR spectrum, ν, cm–1: 1720 (C=O), 2800–3100 (OH).
1H NMR spectrum, δ, ppm: 2.55 s (3H, 8-CH3), 2.75 s
(3H, 2-CH3), 6.60–8.50 m (8H, Harom), 10.15 s (1H,
OH), 10.70 s (1H, NH). Found, %: C 59.26; H 4.82;
N 7.78. C18H18Cl2N2O2. Calculated, %: C 59.18;
H 4.93; N 7.67.
Ethyl 4-(6-bromo-2-methylquinolin-4-ylamino)-
benzoate (Ve). Yield 3.15 g (96%), mp 114–116°C,
Rf 0.60 (chloroform–hexane, 1:6). IR spectrum, ν,
cm–1: 1700 (C=O), 1090 (COC). 1H NMR spectrum, δ,
ppm: 1.03 t (3H, CH2CH3), 2.70 s (3H, 2-CH3), 3.95 q
(2H, CH2CH3), 6.65–8.40 m (8H, Harom), 10.60 s
(1H, NH). Found, %: C 59.33; H 4.38; N 7.35.
C19H17BrN2O2. Calculated, %: C 59.22; H 4.42;
N 7.27.
4-(6-Methoxy-2-methylquinolin-4-ylamino)ben-
zoic acid dihydrochloride (VIc). Yield 1.80 g (97%)
(a), 3.47 g (91%) (b); mp 253–255°C (decomp.),
Rf 0.53 (EtOH). IR spectrum, ν, cm–1: 1730 (C=O),
1
2700–3000 (OH). H NMR spectrum, δ, ppm: 2.70 s
Ethyl 4-(8-chloro-2-methylquinolin-4-ylamino)-
benzoate (Vf). Yield 3.00 g (93%), mp 121–123°C,
Rf 0.64 (chloroform–hexane, 1:7). IR spectrum, ν,
cm–1: 1710 (C=O), 1100 (COC). 1H NMR spectrum, δ,
ppm: 1.10 t (3H, CH2CH3), 2.70 s (3H, 2-CH3), 4.00 q
(2H, CH2CH3), 6.60–8.40 m (8H, Harom), 11.00 s
(1H, NH). Found, %: C 67.03; H 4.87; N 8.40.
C19H17ClN2O2. Calculated, %: C 66.96; H 4.99; N 8.22.
(3H, 2-CH3), 3.93 s (3H, OCH3), 6.50–8.60 m (8H,
Harom), 10.20 s (1H, OH), 10.65 s (1H, NH). Found, %:
C 56.77; H 4.61; N 7.47. C18H18Cl2N2O3. Calculated,
%: C 56.69; H 4.72; N 7.35.
4-(8-Methoxy-2-methylquinolin-4-ylamino)ben-
zoic acid dihydrochloride (VId). Yield 1.80 g (94%)
(a), 3.39 g (89%) (b); mp 251–253°C (decomp.),
Rf 0.55 (EtOH). IR spectrum, ν, cm–1: 1690 (C=O),
4-(2-Methylquinolin-4-ylamino)benzoic acid
dihydrochlorides VIa–VIf (general procedure).
a. Compound IVa–IVf, 0.005 mol, was dissolved in
40 ml of ethanol, a solution of 0.6 g (0.015 mol) of
sodium hydroxide in 20 ml of water was added, and
the mixture was heated for 4 h on a water bath. The
solvent was distilled off, the residue was treated with
50 ml of water, the mixture was filtered, the filtrate
1
3000–3300 (OH). H NMR spectrum, δ, ppm: 2.75 s
(3H, 2-CH3), 3.95 s (3H, OCH3), 6.60–8.40 m (8H,
Harom), 10.50 s (1H, OH), 11.00 s (1H, NH). Found, %:
C 56.80; H 4.64; N 7.47. C18H18Cl2N2O3. Calculated,
%: C 56.69; H 4.72; N 7.35.
4-(6-Bromo-2-methylquinolin-4-ylamino)benzoic
acid dihydrochloride (VIe). Yield 2.00 g (93%) (a),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

SYNTHESIS AND TRANSFORMATIONS OF 4-(4-ETHOXYCARBONYLPHENYLAMINO)- ...
1057
1
3.87 g (90%) (b); mp 237–239°C (decomp.), Rf 0.56
(EtOH). IR spectrum, ν, cm–1: 1700 (C=O), 3100–3450
(OH). H NMR spectrum, δ, ppm: 2.72 s (3H, CH3),
6.60–8.70 m (8H, Harom), 10.00 s (1H, OH), 10.30 s
(1H, NH). Found, %: C 47.53; H 3.57; N 6.63.
C17H15BrCl2N2O2. Calculated, %: C 47.44; H 3.49;
N 6.51.
(OH). H NMR spectrum, δ, ppm: 2.75 s (3H, CH3),
6.50–8.70 m (8H, Harom), 10.10 s (1H, OH), 10.40 s
(1H, NH). Found, %: C 53.01; H 3.80; N 7.37.
C17H15Cl3N2O2. Calculated, %: C 52.92; H 3.89;
N 7.26.
1
REFERENCES
4-(8-Chloro-2-methylquinolin-4-ylamino)benzoic
acid dihydrochloride (VIf). Yield 1.70 g (88%) (a),
3.28 g (85%) (b); mp 286–288°C (decomp.), Rf 0.61
(EtOH). IR spectrum, ν, cm–1: 1690 (C=O), 2900–3250
1. Avetisyan, A.A., Aleksanyan, I.L., and Ambartsu-
myan, L.P., Russ. J. Org. Chem., 2005, vol. 41, p. 769.
2. Beilsteins Handbuch der organischen Chemie, H, vol. 20,
p. 392.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007