Synthesis of some 2-aryl- and 2,3-diaryl-quinolin-4-carboxylic acid derivatives

Article abstract of DOI:10.1080/00397911.2010.486508

Eighteen 2-aryl- and 2,3-diaryl-quinolin-4-carboxlic acid derivatives were synthesized. Basically, the synthetic design of these compounds arose from the appropriate disconnections of the target compounds, which revealed pyruvic acid, aromatic amine, and benzaldehyde or phenyl pyruvic acid, aromatic amine, and benzaldehyde as possible logical precursors for 2-aryl- and 2,3-aryl-quinolin-4- carboxylic acids respectively. The purity and identities of the synthesized compounds were elucidated through chromatographic and spectroscopic techniques (ultraviolet, infrared, mass, ¹H NMR, and ¹³C NMR). The prepared derivatives were screened for their antibacterial activity against the standard bacterial organisms B. subtilis, S. aureus, E. coli, and P. vulgaris. 2,3-Diphenyl-6-sulfanilamido-quinolin-4-carboxylic acid showed the highest activity against the four tested organisms.

Full text of DOI:10.1080/00397911.2010.486508

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Synthesis of Some 2-Aryl- and 2,3-Diaryl-
quinolin-4-carboxylic Acid Derivatives
A. E. M. Saeed a & S. A. Elhadi b
a Chemistry Department, College of Science , Sudan University of
Science and Technology , Khartoum , Sudan
b Chemistry Department, Faculty of Science , University of
Khartoum , Khartoum , Sudan
Published online: 30 Mar 2011.
To cite this article: A. E. M. Saeed & S. A. Elhadi (2011) Synthesis of Some 2-Aryl- and 2,3-
Diaryl-quinolin-4-carboxylic Acid Derivatives, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 41:10, 1435-1443, DOI:
10.1080/00397911.2010.486508
To link to this article: http://dx.doi.org/10.1080/00397911.2010.486508
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Synthetic Communications1, 41: 1435–1443, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.486508
SYNTHESIS OF SOME 2-ARYL- AND
2,3-DIARYL-QUINOLIN-4-CARBOXYLIC ACID
DERIVATIVES
A. E. M. Saeed1 and S. A. Elhadi2
1Chemistry Department, College of Science, Sudan University of Science and
Technology, Khartoum, Sudan
2Chemistry Department, Faculty of Science, University of Khartoum,
Khartoum, Sudan
GRAPHICAL ABSTRACT
Abstract Eighteen 2-aryl- and 2,3-diaryl-quinolin-4-carboxlic acid derivatives were synthe-
sized. Basically, the synthetic design of these compounds arose from the appropriate discon-
nections of the target compounds, which revealed pyruvic acid, aromatic amine, and
benzaldehyde or phenyl pyruvic acid, aromatic amine, and benzaldehyde as possible logical
precursors for 2-aryl- and 2,3-aryl-quinolin-4-carboxylic acids respectively. The purity and
identities of the synthesized compounds were elucidated through chromatographic and spec-
1
troscopic techniques (ultraviolet, infrared, mass, H NMR, and 13C NMR). The prepared
derivatives were screened for their antibacterial activity against the standard bacterial
organisms B. subtilis, S. aureus, E. coli, and P. vulgaris. 2,3-Diphenyl-6-sulfanilamido-
quinolin-4-carboxylic acid showed the highest activity against the four tested organisms.
Keywords Antibacterial activity; heterocycles; quinolin-4-carboxylic acids; spectroscopy;
total synthesis
INTRODUCTION
Quinolines are a group of compounds associated with different biological
activities, such as antiplatelet,[1] antibacterial, antimalarial, and antinuclear inhibi-
tors of immunodeficiency virus.[2] Some derivatives of quinoline-4-carboxylic acid
elicited profound changes in the morphology of typical tips of Botrytis cinerea.[3]
Received December 19, 2009.
Address correspondence to A. E. M. Saeed, Chemistry Department, College of Science, Sudan
University of Science and Technology, P.O. Box 407, Khartoum, Sudan. E-mail: ahmedelsadig@
yahoo.com
1435

1436
A. E. M. SAEED AND S. A. ELHADI
A series of 7-substituted-6-fluoro-1-fluoromethyl 4-oxo-4H-(1,3) thiazeto (3,2-a)
quinoline-3-carboxylic acid derivatives showed excellent in vitro and in vivo anti-
bacterial activity.[4] 4-(Phenylamino)quinoline-3-carboxamides were evaluated for
antisecretory activity against histamine-induced gastric acid secretion in rats. Most
of the compounds inhibited this activity.[5] The 2-phenylquinoline-4-carboxamide
has been found to possess moderate affinity for human neurokinin-3 receptor, and
thiazoloquinolone derivatives were highly cytotoxic against mammalian cells.
The thiazetoquinolone derivatives were less cytotoxic than the thiazoloquinolone
derivatives.[6]
The present work aimed at synthesizing certain substituted 2-aryl-and 2,3-
diaryl-quinolin-4-carboxylic acids. The design of these compounds included the
insertion of certain types of substituents in the homocyclic ring. These substituents
should be to some extent bioisosters to each others. The work aimed to screen the
compounds for antimicrobial activities.
DISCUSSION
Chemistry
The synthetic design in this work depends on the appropriate retrosynthetic
analysis, through disconnection or functional group interchange (FGI) and func-
tional group removal strategies. The total synthesis of any of the quinolines
in this work can be simply linked to benzaldehyde as starting material. The retro-
synthetic analysis of quinoline derivatives exemplifies two important overall
strategies by which the heterocyclic ring can be constructed, as indicated by (I)
and (II):
2-Phenylquinolin-4-carboxylic acid derivatives were prepared by the Doebner
reaction, through the condensation of benzaldehyde, aniline, and pyruvic acid
in absolute ethanol. Similarly, 2,3-diphenylquinolin-4-carboxylic acid derivatives
were prepared through the condensation of a primary aromatic amines with phe-
nylpyruvic acid and benzaldehyde (Schemes 1 and 2). Quinolin-4-carboxylic acids
were obtained through a modified Pfitzinger approach involving the condensation
of a ketone with an isatin derivative.[7] A synthesis of quinolin-4-carboxylic acid
derivatives has been reported by the reaction of 2-methoxy acrylates or acyla-
mides with N-arylbenzaldimines.[8]
The methyl ester derivatives, compounds 14 and 15, were prepared through
direct esterification of compounds 13 and 1 respectively. Compound 1 on treat-
ment with slight excess of thionyl chloride at room temperature followed by
addition of the required amine furnished the carboxamide compounds (16–18)
(Scheme 3).

SYNTHESIS OF QUINOLINCARBOXYLIC ACIDS
1437
Scheme 1. Chemical structures of substituted 2,3-diaryl-quinolin-4-carboxylic acids.
Scheme 2. Chemical structures of substituted 2-aryl-quinolin-4-carboxylic acids.
Scheme 3. Chemical structures of 2,3-diarylquinoline-4-carboxy derivatives.
Antibacterial Activity
As revealed by the results (Table 1), compounds 3, 6, 15, 17, and 18 were inac-
tive against S. aureus while compounds 6, 8, 10, 11, and 15 were inactive against
P. vulgaris. All the tested compounds were active against B. subtilis and E. coli.
Compound 5 showed the highest activity against the four tested organisms. The most

1438
A. E. M. SAEED AND S. A. ELHADI
Table 1. Antibacterial activity of the compounds tested
Mean inhibition zone diameter (mm)
Compound (1 mg=ml)
B. subtilis
S. aureus
E. coli
P. vulgaris
2
17
15
17
15
15
20
3
—
19.5
20
5
23.5
16
22.5
—
19.5
16
6
—
—
8
20
—
16.5
19.5
18
9
10
20.5
21
18.5
15
20
—
—
11
15
18.5
20
14.5
—
16
15
—
17
18
14.5
21
—
—
16.5
17
24.5
22.5
00
Ampicillin in PRG (125 mg=ml)
Ampicillin in PRG (250 mg=ml)
Ampicillin in PRG (500 mg=ml)
11
12
34
36
14
15
00
00
13
41
19
effective compounds, 5, 8, and 10, contain a sulfanilamido moiety in position 6 of the
quinoline ring system. Replacement of this group by methyl, nitro, or carboxyl
groups decreases activity. It seems that the phenyl group at position 3 is not essential
for activity when comparing the pairs of compounds with the same substituents: 3, 9;
5, 10, and 6, 11. Conversion of the carboxyl group into ester and amide functional-
ities results, in improved activity against P. vulgaris. The greater activity of com-
pound 5 compared to compound 10 may be attributed to the large, rigid character
that the additional phenyl group in 5 confers on the molecule. Such molecules can
be inserted into membranes and induce permeability changes leading to leakage
out of the cellular membrane. On the other hand, the greater activity in the other
compounds cannot be explained in terms of cellular differences. It is more likely
due to interaction of the molecules with some intercellular target. The presence of
the powerful electron-withdrawing group (-SONH-) alters the nature of the com-
pound to promote binding to the target.[9]
EXPERIMENTAL
All chemicals and reagents were general purpose reagent grade and were used
without further purification. Melting points were uncorrected. Elemental analyses
for CHNS were within þ0.3%. Infrared (IR) analysis was carried out using IR
satellite Fourier transfrom (FT)–IR spectrometer (Mattson). Ultraviolet=visible
(UV=vis) spectrometry was carried out using an UV=vis spectrophotometer (Jenway
model 6505). Mass spectra analysis was carried out using a GC=MS instrument (GP
5050A Shimadzu GC-17A). 1H and 13C NMR analysis were carried out using a Jeol
ECP 400-MHZ instrument and a Jeol JNMFX 100-MHz instrument. Thin-layer
chromatography (TLC) was carried out with silica-gel 60 GF254 (Merck, Germany)
precoated plates, and different mobile phases were attempted.

SYNTHESIS OF QUINOLINCARBOXYLIC ACIDS
1439
Preparation of 2,3-Diarylquinoline-4-carboxylic Acids (1–8)
A mixture of benzaldehyde (0.6 g, 0.5 ml, 0.236 mol), phenyl pyruvic acid (0.5 g,
0.25 mol), and absolute ethanol (5 ml) was stirred at room temperature. A solution of
the required aromatic amine (0.248 mol) in absolute ethanol (2.0 ml) was added
slowly with shaking. The mixture was refluxed on a water bath for 3 h and allowed
to stand overnight. The crude product was filtered, washed with a little ether, and
recrystallized from ethanol.
Selected Data
2,3-Diphenyl quinoline-4-carboxylic acid (1, C22H15NO2). Yield ¼ 62%;
1
mp ¼ 245–146 ꢀC; H NMR ppm, d ¼ 7.65–7.75 (4, m), 10.64 (1, s), 7.03–7.18 (5,
m), 7.28–7.38 (5, m); 13C NMR ppm, d ¼ 129.0, 128.8, 132.2, 139.2, 138.2, 129.2,
137.5, 166.0, 138.1, 143.6, 122.4, 123.1, 125.1, 127.9, 127.3, 128.3, 128.0; IR (KBr):
;
n ¼ 1670, 1615, 1470, 1400, 1570, 1170, 1210, 730, 700, 3400–2600, 1280 cmꢁ1
UV-vis (ethanol) kmax ¼ 210, 220 nm; MS (70 eV): molecular formula, m=z (% rela-
tive abundance): C22H15NO2, 325, 280, 207 (33), 179 (74), 89 (4), 77 (31), 51 (12).
8-Methyl-2,3-diphenyl quinoline-4-carboxylic acid (2, C23H17NO2).
1
Yield ¼ 78%; mp ¼ 280–282 ꢀC; H NMR ppm, d ¼ 2.51 (3, d), 7.94–8.00 (3, m),
10.67 (1, s), 7.10–7.30 (5, m), 7.43–7.64 (5, m); 13C NMR ppm, d ¼ 129.1, 129.0,
132.0, 138.5, 138.3, 129.8, 131.3, 167.8, 133.4, 147.4, 122.0, 122.6, 126.1, 127.3,
127.5, 128.7, 129.0, 21.9; IR (KBr): n ¼ 1700, 1490, 1420, 1620, 1320, 1210, 3200,
740, 680, 3400–2600, 1280 cmꢁ1; UV-vis (ethanol) kmax ¼ 255 nm; MS (70 eV):
molecular formula, m=z (% relative abundance): C23H17NO2, 339, 294 (1), 263 (8),
220 (10), 193 (4), 179 (100), 89 (38), 77 (79), 51 (53).
6-Methyl-2,3-diphenyl quinoline-4-carboxylic acid (3, C23H17NO2).
1
Yield ¼ 63%; mp ¼ 145–146 ꢀC; H NMR ppm, d ¼ 2.50 (3, s), 7.50–7.73 (3, m),
10.58 (1, s), 7.06–7.24 (5, m), 7.27–7.35 (5, m); 13C NMR ppm, d ¼ 129.1, 134.3,
134.9, 143.7, 138.2, 132.3, 135.9, 165.8, 136.7, 149.3, 121.5, 122.5, 122.8, 127.7,
128.3, 128.8, 129.0, 129.1, 21.2; IR (KBr): n ¼ 1700, 1610, 1450, 1580, 1320, 1210,
3020, 780, 700, 3400–2600, 1250 cmꢁ1; UV-vis (ethanol) kmax ¼ 205, 265 nm; MS
(70 eV): molecular formula, m=z (% relative abundance): C23H17NO2, 339, 263 (4),
219 (1), 194 (100), 179 (3), 89 (14), 77 (9), 51 (13).
7-Methyl-2,3-diphenyl quinoline-4-carboxylic acid (4, C23H17NO2).
1
Yield ¼ 84%; mp ¼ 185–186 ꢀC; H NMR ppm, d ¼ 2.24 (3, s), 7.42–7.73 (3, m),
10.58 (1, s), 7.06–7.20 (5, m), 7.28–7.37 (5, m); 13C NMR ppm, d ¼ 128.9, 128.7,
137.4, 132.2, 138.0, 129.0, 138.2, 165.9, 138.4, 143.6, 119.6, 123.0, 123.1, 125.8,
127.7, 127.9, 128.3, 128.4, 21.7; IR (KBr) n ¼ 1680, 1600, 1450, 1420, 1500, 1300,
1100, 850, 780, 700, 3400–2600, 1200 cmꢁ1; UV-vis (ethanol) kmax ¼ 210, 265 nm;
MS (70 eV): molecular formula, m=z (% relative abundance): C23H17NO2, 339,
322, 294, 263, 218, 194 (5), 179 (100), 89 (9), 77 (12), 51 (2).
6-Sulfanilamido-2,3-diphenyl quinoline-4-carboxylic acid (5, C22H16O4
1
N2S). Yield ¼ 64%; mp ¼ 212–214; H NMR ppm, d ¼ 6.64 (2, s), 7.71–7.98 (3, m),
10.03 (1, s), 7.08–7.22 (5, m), 7.27–7.47 (5, m); 13C NMR ppm, d ¼ 131.9, 133.4,

1440
A. E. M. SAEED AND S. A. ELHADI
136.2, 141.7, 129.2, 128.9, 136.2, 166.7, 137.5, 143.2, 121.6, 121.8, 124.0, 126.9, 127.9,
128.9, 129.2, 129.5; IR (KBr): n ¼ 1690, 1480, 1450, 1580, 1160, 880, 820, 760,
3400–2600, 1200, 3400, 3300, 1410, 1370, 1150, 1600 cmꢁ1; UV-vis (ethanol)
kmax ¼ 205, 265 nm; MS (70 eV): molecular formula, m=z (% relative abundance):
C22H16O4N2S, 404, 327 (35), 282 (3), 260 (100), 179 (61), 89 (10), 77 (29), 51 (12).
6-Nitro-2,3-diphenyl quinoline-4-carboxylic acid (6, C22H14N2O4).
1
Yield ¼ 57%; mp ¼ 145–147 ꢀC; H NMR ppm, d ¼ 7.72–8.20 (3, m), 10.28 (1, s),
7.09–7.23 (5, m), 7.31–7.50 (5, m); 13C NMR ppm, d ¼ 128.6, 128.2, 129.1, 156.0,
143.3, 143.0, 166.3, 141.4, 143.3, 121.2, 121.7, 125.0, 126.9, 127.2, 128.0, 128.2,
129.0; IR (KBr): n ¼ 1690, 1500, 1400, 1490, 1180, 1160, 820, 780, 3400–2600,
1200, 1520, 1350 cmꢁ1; UV-vis (ethanol) kmax ¼ nm; 220, 265 MS (70 eV): molecular
formula, m=z (% relative abundance): C22H14N2O4, 370, 353, 325, 294, 278, 223 (3),
179 (100), 89 (5), 77 (10), 51 (5).
2,3-Diphenyl quinoline-4,6-dicarboxylic acid (7, C23H15NO4). Yield ¼
61%; mp ¼ 272–273 ꢀC; 1H NMR ppm, d ¼ 12.82 (1, s), 7.71–7.92 (3, m), 10.72
(1, s), 7.07–7.24 (5, m), 7.30–7.42 (5, m); 13C NMR ppm, d ¼ 130.5, 131.9, 137.8,
131.9, 130.5, 128.8, 131.8, 166.3, 141.4, 143.3, 121.2, 124.0, 126.9, 127.9, 128.2,
128.6, 128.8, 129.1, 167.3; IR (KBr): n ¼ 1700, 1690, 1600, 1580, 1520, 1290, 1180,
3180, 820, 780, 3300, 1220 cmꢁ1; UV-vis (ethanol) kmax ¼ 205, 265 nm; MS (70 eV):
molecular formula, m=z (% relative abundance): C23H15O4N, 369, 324, 291, 249,
224 (2), 179 (100), 89 (4), 77 (12), 51 (7).
6-(4,6-Dimethyl pyrimid-2-yl sulfanilamido)-2,3-diphenyl quinoline-4-
1
carboxylic acid (8, C28H22O4N4S). Yield ¼ 68%; mp 110–112 ꢀC; H NMR ppm,
d ¼ 3.37 (3, s), 2.50 (3, s), 7.88–8.0 (1, s), 7.61–7.72 (3, m), 10.02 (1, s), 7.03–7.24
(5, m), 7.30–7.42 (5, m); 13C NMR ppm, d ¼ 129.5, 129.7, 130.1, 133.4, 129.8,
129.9, 135.2, 167.9, 136.7, 143.2, 126.9, 127.96, 128.1, 128.3, 128.8, 128.5, 129.0,
129.5; IR (KBr): n ¼ 1700, 1600, 1500, 1520, 1200, 1200, 3060, 750, 700, 3370,
1280, 3300, 1350, 1160, 1600 cmꢁ1; UV-vis (ethanol) kmax ¼ 210, 220 nm; MS
(70 eV): molecular formula, m=z (% relative abundance): C28H22O4N4S, 518, 372
(7), 179 (14), 89 (4), 77 (65), 51 (30).
Preparation of 2-Arylquinoline-4-carboxylic Acids (9–13)
A mixture of benzaldehyde (0.6 g, 0.5 ml, 0.236 mol), freshly distilled pyruvic
acid (1 ml, 0.25 mol), and absolute ethanol (5 ml) were stirred at room temperature.
A solution of the required aromatic amine (0.248 mol) in absolute ethanol (5 ml) was
added slowly with shaking. The mixture was refluxed on a water bath for 3 h and
allowed to stand overnight. The crude product was filtered, washed with a little
ether, and recrystallized from ethanol.
Selected Data
6-Methyl-2-phenyl quinoline-4-carboxylic acid (9, C17H13NO2). Yield ¼
1
66%; mp ¼ 190–192 ꢀC; H NMR ppm, d ¼ 7.96 (1, s), 2.56 (3, s), 8.27 (1, d), 8.57
(1, d), 13.97 (1, s), 8.40 (1, s), 7.50–7.60 (5, m); 13C NMR ppm, d ¼ 129.2, 140.7,

SYNTHESIS OF QUINOLINCARBOXYLIC ACIDS
1441
149.3, 130.4, 130.5, 129.5, 156.2, 168.3, 138.6, 156.3, 118.8, 122.1, 125.6, 127.7; IR
(KBr): n ¼ 1700, 1600, 1420, 1540, 1230, 1200, 2910, 890, 720, 3450, 1340,
1030 cmꢁ1; UV-vis (ethanol) kmax ¼ 205, 265 nm; MS (70 eV): molecular formula,
m=z (% relative abundance): C17H13NO2, 263 (100), 219 (68), 204 (23), 190 (4),
176 (1), 89 (13), 77 (7), 51 (4).
6-Sulfanilamido-2-phenyl quinoline-4-carboxylic acid (10, C16H12N2O4S).
1
Yield ¼ 77%; mp ¼ 244–245 ꢀC; H NMR ppm, d ¼ 7.85 (1, d), 7.76 (1, d), 7.27 (1,
s), 7.83 (1, s), 7.30–7.45 (5, m); 13C NMR 137.7, 135.7, 127.6, 145.4, 167.1, 140.3,
140.0, 113.8, 116.5, 121.5, 126.3; IR (KBr): n ¼ 1700, 1600, 1480, 1530, 1100, 820,
750, 3400–2600, 1330, 1170, 1380, 1160, 1620, 3270, 3250 cmꢁ1; UV-vis (ethanol)
kmax ¼ 210, 265 nm; MS (70 eV): molecular formula, m=z (% relative abundance):
C16H12N2O4S, 328, 311, 285, 205, 172 (82), 156 (100), 92 (66), 89 (1), 77 (5), 51 (6).
6-Nitro-2-phenyl quinoline-4-carboxylic acid (11, C16H10N2O4).
Yield ¼ 62%; mp ¼ 165–167 ꢀC; 1H NMR ppm, d ¼ 7.23 (1, d), 7.41 (1, d), 8.14 (1, s),
9.38 (1, s), 8.13 (1, s), 7.43–7.48 (5, m); 13C NMR ppm, d ¼ 127.4, 126.0, 127.9,
140.4, 136.8, 127.5, 129.4, 170.4, 129.6, 148.7, 116.5, 121.2, 121.8, 125.1; IR (KBr):
n ¼ 1770, 1670, 1520, 1200, 1130, 750, 700, 3350, 1330, 1150, 1520, 1320cmꢁ1; UV-vis
(ethanol) kmax ¼ 205, 265 nm; MS (70 eV): molecular formula, m=z (% relative abun-
dance): C16H10N2O4, 294, 277, 251 (100), 205 (52), 137 (3), 105 (21), 91 (3), 179 (6),
89 (6), 77 (19), 51 (10).
2-Phenyl quinoline-4,6-dicarboxylic acid (12, C17H11NO4). Yield ¼ 68%;
1
mp ¼ 304–306 ꢀC (lit. 305 ꢀC[10]); H NMR ppm, d ¼ 7.70 (1, d), 7.89 (1, d), 10.01
(1, s), 7.89 (1, s), 12.89 (1, s), 8.30 (1, s), 7.40–7.60 (5, m); 13C NMR ppm,
d ¼ 129.5, 130.0, 130.6, 141.4, 129.7, 129.6, 131.4, 167.3, 131.5, 146.6, 116.4, 120.9,
123.4, 127.3, 167.7; IR (KBr): n ¼ 1700, 1600, 1420, 1540, 1190, 1220, 850, 780,
3320, 1380, 1120 cmꢁ1; UV-vis (ethanol) kmax ¼ 205, 255 nm; MS (70 eV): molecular
formula, m=z (% relative abundance): C17H11NO4, 293 (100), 276 (7), 249 (61), 204
(37), 220 (5), 176 (7), 89 (12), 77 (13), 51 (9).
2-Phenyl quinoline-4-carboxylic acid (13, C16H11NO2). Yield ¼ 51%;
1
mp ¼ 209–210; H NMR d ¼ 8.67 (1, d), 8.13–8.35 (3, m), 14.02 (1, s), 8.47 (1, s),
7.53–7.90 (5, m); 13C NMR ppm, d ¼ 138.2, 130.2, 130.5, 130.8, 129.5, 128.3,
138.2, 168.2, 138.5, 148.9, 119.7, 127.8, 124.1, 125.9; IR (KBr): n ¼ 1680, 1600,
1230, 1210, 2820, 760, 720, 1350 cmꢁ1; UV-vis (ethanol) kmax ¼ 205, 265 nm; MS
(70 eV): molecular formula, m=z (% relative abundance): C16H11NO2, 249 (100),
232, 204 (81), 176 (10), 88 (5), 77 (4), 51 (13).
Preparation of Methyl-2-phenylquinoline-4-carboxylate (14,
C17H13NO2) and Methyl-2,3-diphenylquinoline-4-carboxylate (15,
C23H17NO2)
2-Phenylquinoline-4-carboxylic acid (13) or 2,3-diphenylquinoline-4-carboxylic
acid (1) (0.3 mol), methanol (10 ml), and concentrated sulfuric acid (1 ml) were
refluxed for 2 h and cooled to room temperature. Sodium carbonate solution was
added to the mixture and left to stand for 1 h. Pale yellow crystals were collected
and washed with distilled water. Compound 14: Yield ¼ 50%; mp ¼ 58–59 ꢀC;

1442
A. E. M. SAEED AND S. A. ELHADI
1H NMR ppm, d ¼ 8.18–8.57 (4, m), 4.02 (3, s), 8.48 (1, s), 7.50–7.87 (5, m); 13C NMR
ppm, d ¼ 128.6, 130.4, 130.7, 130.9, 148.9, 129.6, 156.9, 166.9, 138.3, 136.1, 119.9,
123.7, 125.7, 127.8, 53.5; IR (KBr): n ¼ 1720, 1570, 1450, 1420, 1530, 1190, 1230,
1320, 2960, 780, 690 cmꢁ1; UV-vis (ethanol) kmax ¼ 215, 265 nm; MS (70 eV): molecu-
lar formula, m=z (% relative abundance): C17H13NO2, 263 (29), 232 (3), 205 (72), 176
1
(8), 89 (5), 77 (8), 51 (14). Compound 15: Yield ¼ 33%; mp ¼ 215–216 ꢀC; H NMR
ppm, d ¼ 8.16–8.57 (4, m), 4.02 (3, s), 7.53–7.88 (10, m); 13C NMR ppm, d ¼ 130.0,
130.4, 130.6, 130.9, 131.0, 136.8, 156.3, 166.8, 138.2, 148.8, 119.9, 123.6, 125.6,
126.0, 127.7, 128.5, 129.5, 129.9, 53.5; IR (KBr): n ¼ 1720, 1570, 1450, 1530, 1120,
1230, 1320, 2960, 780, 690 cmꢁ1; UV-vis (ethanol) kmax ¼ 255 nm; MS (70 eV):
molecular formula, m=z (% relative abundance): C23H17NO2, 339, 205 (97), 263
(100), 176 (8), 88 (4), 75 (5), 51 (9).
Preparation of 2,3-Diarylquinoline-4-carboxamide (16–18)
A mixture of 2,3-diphenylquinoline-4-carboxylic acid (1) (1.0 g, 0.003 mol),
chloroform (25 ml), and thionyl chloride (0.004 mol) were placed. The mixture was
stirred by magnetic stirrer for 30 min. The required amine (0.004 mol) was added
immediately with continuous stirring. Clear crystals occurred.The product was
allowed to stand for several hours, filtered, and dried in air.
Selected Data
2,3-Diarylquinoline-4-carboxamide
(16,
C22H16N2O). Yield ¼ 55%;
1
mp ¼ 240–242 ꢀC; H NMR ppm, d ¼ 7.64–7.74 (4, m), 6.54 (2, s), 7.03–7.19 (5, m),
7.27–7.38 (5, m); 13C NMR ppm, d ¼ 130.0, 128.7, 129.0, 129.1, 132.1, 131.8, 137.4,
165.9, 138.1, 143.5, 122.4, 123.0, 125.0, 126.3, 127.8, 127.8, 128.2, 128.4; IR (KBr):
n ¼ 1680, 1600, 1430, 1510, 1200, 1220, 3050, 790, 700, 1320, 3200 cmꢁ1; UV-vis (etha-
nol) kmax ¼ 215, 260 nm; MS (70 eV): molecular formula, m=z (% relative abundance):
C22H16N2O, 324, 282 (2), 207 (43), 179 (100), 89 (6), 77 (36), 51 (10).
N-Phenyl-2,3-diarylquinoline-4-carboxamide (17, C28H20N2O). Yield ¼
1
75%; mp ¼ 185–186 ꢀC; H NMR ppm, d ¼ 7.46–7.50 (4, m), 6.55 (1, s), 7.38–7.40
(5, m), 7.15–7.18 (5, m), 7.27–7.31 (5, m); IR (KBr): n ¼ 1770, 1600, 1470, 1520,
1500, 1100, 1190, 2900, 740, 1320, 3200, 1570 cmꢁ1; UV-vis (ethanol) kmax ¼ 205,
265 nm; MS (70 eV): molecular formula, m=z (% relative abundance): C28H20N2O,
400, 282 (4), 207 (47), 179 (100), 89 (4), 77 (25), 51 (10).
N-Methyl-2,3-diarylquinoline-4-carboxamide (18, C23H18N2O). Yield ¼
1
66%; mp ¼ 240–242 ꢀC; H NMR ppm, d ¼ 7.66–7.84 (4, m), 6.19 (1, s), 2.39 (3, s),
7.02–7.17 (5, m), 7.23–7.39 (5, m); 13C NMR ppm, d ¼ 129.6, 128.2, 128.3, 128.6,
128.8, 135.0, 135.5, 169.7, 138.3, 140.6, 122.0, 124.2, 124.5, 126.4, 127.7, 128.1,
128.2, 25.81; IR (KBr): n ¼ 1680, 1600, 1450, 1500, 1260, 1170, 3060, 760, 690,
1380, 3060 cmꢁ1; UV-vis (ethanol) kmax ¼ 205, 265 nm; MS (70 eV): molecular
formula, m=z (% relative abundance): C23H18N2O, 338, 282 (4), 207 (29), 179
(100), 89 (2), 77 (16), 51 (6).

SYNTHESIS OF QUINOLINCARBOXYLIC ACIDS
1443
Antibacterial Activity
The standard microbiological two-layer agar diffusion technique was adopted
with some modification. Nutrient agar (Oxoid), which was used as the culture
medium, was reconstituted, sterilized at 121 ꢀC for 15 min, and distributed in
15-ml aliquots into sterile Petri dishes and allowed to set forming the base layer.
The organisms (B. subtilis, S. aureus, E. coli, and P. vulgaris) were grown in nutrient
broth (Oxoid) at 37 ꢀC for 18 h. Each bacterial culture was used to introduce to
inoculate the agar media. The inoculated medium (1 ꢂ 108 cell per ml) was distrib-
uted in 10-ml portions onto the surface of the base layer evenly. Five cups ꢂ 5 mm
in diameter were cut out using sterile cork borer. Each solution (0.2 ml, 1 mg=ml)
of the test compound in propylene glycol (PRG) was added to these cups and
allowed to diffuse at room temperature. The plates were incubated at 37 ꢀC for
18 h. The mean diameters of the inhibition zones were tabulated in Table 1.
REFERENCES
1. Ko, T. C.; Hour, M. J.; Leien, J. Synthesis of 4-alkoxy-2-phnoel aniline derivatives as
potent antiplatelet agents. Bio. Org. Med. Chem. Lett. 2001, 11, 279–282.
2. Baba, M.; Makino, T.; Kimura, Y.; Ikeuchi, T.; Sakaguchi, T.; Okamoto, T. Potent and
selective inhibition of human immunodeficiency virus type I transcription by piperaziny-
loroquinoline derivatives. Antimicrob. Agents Chemother. 1997, 41, 1250–1255.
3. Strigacova, J.; Hudecova, D.; Varecka, L.; Lasikova, A.; Vegh, D. Some biological
properties of new quinoline-4-carboxylic acid derivatives. Folia Microbiol. (Praha)
2000, 45, 305–309.
4. Matsuoka, M.; Seowa, J.; Amimoto, I.; Masdui, Y.; Tomii, Y.; Kitano, M.; Kise, M.
Synthesis and antibacterial activity of novel 7-substituted-6-fluro-1-fluoromethyl-4-oxo-
44-[1,3-thiazeto[3,2-a]-quinoline-3-carboxylic derivatives. Chem. Pharm. Bull. 1999, 47,
1765–1773.
5. Uchida, M.; Matsubara, J.; Ohtani, T.; Morita, S.; Yamasaki, K. Synthesis of
4-(phenyl-amino)-quinoline-3-carboxamides as a novel class of gastric Hþ=kþ-ATpase
inhibitors. Chem. Pharm. Bull. 1995, 43, 693–698.
6. Ozaki, M.; Segawa, J.; Kitano, M.; Tomii, Y.; Honmuura, T.; Matsuda, M.; Kise, M.;
Nishino, T. Structure–antibacterial activity and cytotoxicity relationships of thiazo-10
and thiazetoquinoline derivatives. Biol. Pharm. Bull. 1996, 19, 1457–1462.
7. Lackey, K.; Sternbach, D. D. Synthesis of substituted quinoline-4-carboxylic acids. Syn-
thesis 1993, 993–997.
8. Duvelleroy, D.; Perrio, C.; Parisel, O.; Lasne, M. C. Rapid synthesis of quinoline-4-
carboxylic acid derivatives from aryl imines and 2-substituted acrylates or acryl amides
under indium(III) chloride and microwave activation: Scope and limitations of the
reaction. Org. Biomol. Chem. 2005, 3, 3794–3804.
9. Waring, M. J.; Hadda, T. B.; Kotchevar, A. T.; Ramdani, A.; Touzani, R.; Elkadiri, S.;
Hakkou, A.; Bouakka, M.; Ellis, T. 2,3-Bifunctionalized quinoxalines: Synthesis, DNA
interactions, and evaluation of anticancer, antituberculosis, and antifungal activity. Mole-
cules 2007, 7, 641–656.
10. Di Fonzo, M.; Saracini, C. 2-Phenyl-quinoline-4-6-dicarboxylic acid. Farmaco Sci. 1956,
11, 221–227.