Synthesis and Antibacterial, Antioxidant, and Molecular Docking Analysis of Some Novel Quinoline Derivatives

Article abstract of DOI:10.1155/2020/1324096

2-Chloroquinoline-3-carbaldehyde and 2-chloro-8-methylquinoline-3-carbaldehyde derivatives were synthesized through Vilsmeier formulation of acetanilide and N-(o-tolyl)acetamide. Aromatic nucleophilic substitution reaction was used to introduce various nucleophiles in place of chlorine under different reaction conditions. The carbaldehyde group was oxidized by permanganate method and reduced with metallic sodium in methanol and ethanol. The synthesized compounds were characterized by UV-Vis, IR, and NMR. The antibacterial activity of the synthesized compounds was screened against two Gram-positive bacteria (Bacillus subtilis ATCC6633 and Staphylococcus aureus ATCC25923) and two Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). Most of the compounds displayed potent activity against two or more bacterial strains. Among them, compounds 6 and 15 showed maximum activity against Pseudomonas aeruginosa with mean inhibition zones of 9.67 ± 1.11 and 10.00 ± 0.44 mm, respectively, while ciprofloxacin showed mean inhibition zone of 8.33 ± 0.44 mm at similar concentration. On the other hand, compound 8 exhibited maximum activity against Escherichia coli with inhibition zones of about 9.00 ± 0.55 mm at 300 μg/mL and 11.33 ± 1.11 mm at 500 μg/mL. The radical scavenging activity of these compounds was evaluated using 1,1-diphenyl-2-picryl hydrazyl (DPPH), and all of them displayed moderate antioxidant activity, with compound 7 exhibiting the strongest activity. The molecular docking study of the synthesized compounds was conducted to investigate their binding pattern with DNA gyrase, all of them were found to have minimum binding energy ranging from -6.0 to -7.33 kcal/mol, and the best result was achieved with compound 11. The findings of the in vitro antibacterial and molecular docking analysis demonstrated that the synthesized compounds have potential of antibacterial activity and can be further optimized to serve as lead compounds.

Full text of DOI:10.1155/2020/1324096

Hindawi
Journal of Chemistry
Volume 2020, Article ID 1324096, 16 pages
https://doi.org/10.1155/2020/1324096
Research Article
Synthesis and Antibacterial, Antioxidant, and Molecular Docking
Analysis of Some Novel Quinoline Derivatives
Digafie Zeleke,1 Rajalakshmanan Eswaramoorthy ,1 Zerihun Belay,2
1
and Yadessa Melaku
1Department of Applied Chemistry, Adama Science and Technology University, Adama, Ethiopia
2Department of Applied Biology, Adama Science and Technology University, Adama, Ethiopia
Correspondence should be addressed to Yadessa Melaku; yadessamelaku2010@gmail.com
Received 9 March 2020; Revised 8 June 2020; Accepted 19 June 2020; Published 24 July 2020
Academic Editor: Ponnurengam Malliappan Sivakumar
Copyright © 2020 Digafie Zeleke et al. +is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
2-Chloroquinoline-3-carbaldehyde and 2-chloro-8-methylquinoline-3-carbaldehyde derivatives were synthesized through
Vilsmeier formulation of acetanilide and N-(o-tolyl)acetamide. Aromatic nucleophilic substitution reaction was used to introduce
various nucleophiles in place of chlorine under different reaction conditions. +e carbaldehyde group was oxidized by per-
manganate method and reduced with metallic sodium in methanol and ethanol. +e synthesized compounds were characterized
by UV-Vis, IR, and NMR. +e antibacterial activity of the synthesized compounds was screened against two Gram-positive
bacteria (Bacillus subtilis ATCC6633 and Staphylococcus aureus ATCC25923) and two Gram-negative bacteria (Escherichia coli
ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). Most of the compounds displayed potent activity against two or more
bacterial strains. Among them, compounds 6 and 15 showed maximum activity against Pseudomonas aeruginosa with mean
inhibition zones of 9.67 1.11 and 10.00 0.44 mm, respectively, while ciprofloxacin showed mean inhibition zone of
8.33 0.44 mm at similar concentration. On the other hand, compound 8 exhibited maximum activity against Escherichia coli with
inhibition zones of about 9.00 0.55 mm at 300 μg/mL and 11.33 1.11 mm at 500 μg/mL. +e radical scavenging activity of these
compounds was evaluated using 1,1-diphenyl-2-picryl hydrazyl (DPPH), and all of them displayed moderate antioxidant activity,
with compound 7 exhibiting the strongest activity. +e molecular docking study of the synthesized compounds was conducted to
investigate their binding pattern with DNA gyrase, all of them were found to have minimum binding energy ranging from –6.0 to
–7.33 kcal/mol, and the best result was achieved with compound 11. +e findings of the in vitro antibacterial and molecular
docking analysis demonstrated that the synthesized compounds have potential of antibacterial activity and can be further
optimized to serve as lead compounds.
quinoline derivatives are among important compounds
previously reported to have a wide arrays of biological ac-
tivities [2, 3]. +erefore, introduction of different functional
groups on quinoline scaffold is a very good idea for the
development of new drug.
+e discovery of nalidixic acid in 1962, along with its
introduction for clinical use in 1967, marks the beginning of
decades of quinolone development and use [4]. Since then,
various fluoroquinolones have been synthesized and used to
treat various bacterial infections for decades [4]. However,
currently some of them have been removed from market due
1. Introduction
Antibacterial therapy has been challenging because of the
alarming rate in rise of infections caused by bacteria coupled
with their resistance to most of first-line antibiotic agents [1].
+is is a serious threat to human health of the world in the
21st century and urgently calls continuing research to find
out compounds possessing better antimicrobial with broad-
spectrum activities. Hence, designing new drugs to treat
disease and inflammations without causing significant side
effects on patients is very important. In view of this,

2
Journal of Chemistry
to intolerable side effects; in addition, some bacteria have
also developed resistance against them and have narrowed
their spectrum of activities [5].
of crushed ice water. +e solid product was collected by
suction filtration. White crystal; yield 69%, mp 112–113°C
(Lit. mp 114.3°C).
In general, fluoroquinolones underwent four genera-
tions of development and improvement since the discovery
of nalidixic acid, with each subsequent generation exhibiting
broader and stronger bioactivity and less side effects than the
previous one [5, 6]. Oxolinic acid, pipemidic acid, and
nalidixic acid belong to the first generation and were used for
the treatment of urinary tract infection caused by the ma-
jority of Gram-negative bacteria; however, all of them have
short lifetime [6].
Enoxacin, ofloxacin, lomefloxacin, norfloxacin, and
ciprofloxacin are in the second generation, have longer half-
life, and improved activity against Gram-negative bacteria
compared to the first generation [6, 7]. Sparfloxacin, gre-
pafloxacin, and temafloxacin belong to the third generation
[8] and are used as oral broad-spectrum antibacterial agents
in the treatment of acute bacterial exacerbation of chronic
bronchitis and mild-to-moderate pneumonia [9].
Gatifloxacin, clinafloxacin, trovafloxacin, and moxi-
floxacin belong to the fourth generation of fluoroquinolone
drugs, which display extended activity against both Gram-
negative and -positive bacteria strains; additionally, they are
active against anaerobes and atypical bacteria [10].
Besides fluoroquinolone-based drugs, 2-chloroquino-
line-3-carbaldehyde derivatives have also attracted much
attention due to their considerable biological and phar-
macological activities including antimicrobial [8], anti-in-
flammatory [11–13], antimalarial [14, 15], anticancer [16],
antiviral [17, 18], and antifungal activities [19, 20]. Inspired
by these reports, we have designed and synthesized various
quinoline-3-carbaldehyde derivatives and evaluated their
antibacterial and radical scavenging activities. Also incor-
porated herein is the in silico molecular docking analysis of
the synthesized derivatives of quinolines.
2.2.2. Synthesis of 2-Chloroquinoline-3-carbaldehyde (4).
N,N-dimethylformamide (20 mL, 0.26 mol) was added to a
100 mL round-bottom flask guarded with drying tube; it was
cooled to 0°C using ice bath. +en, phosphorus oxychloride
(70 mL, 0.75 mol) was added dropwise to it from dropping
funnel guarded by drying tube while being stirred by magnetic
stirrer. +is addition was done for 30 minutes. +en acet-
amide (13.5 g, 0.1 mol) was added to it. After 5 minutes, the
dropper funnel was replaced by air condenser with guarding
tube at its end, and the mixture was heated for 22 hours on oil
bath at 85–90°C. +en it was cooled to room temperature,
poured into a beaker containing 400 mL crushed ice water,
and stirred for 20 minutes. +e yellow solid product was
collected by suction filtration and washed with 100 mL cold
water. +e crude yield was 11.5 g (60%) and was recrystallized
from ethyl acetate. yellow crystal; mp 146–148°C; yield 48.5%;
Rf � 0.22 (n-hexane : EtOAc � 9 :1); UV-Vis (MeOH)
λmax � 280 nm; IR (ʋ cm−1, KBr): 3035 (CH-arom.), 1693
(C�O aldehyde), 1621 (quinoline C�N str.), 599 (aromatic
1
C�C str.); H NMR (400 MHz, CDCl3) δH 7.65 (1H, m,
H-6), 7.88 (1H, m, H-7), 7.97 (1H, d, J � 8.25 Hz, H-8), 8.07
(1H, d, J � 8.25 Hz, H-5), 8.74 (1H, s, H-4), and 10.54 (1H, s,
H-9); 13C NMR (100 MHz, CDCl3) δC 126.3 (C-1), 126.5
(C-8), 128.2 (C-6), 128.6 (C-4a), 129.7 (C-5), 133.6 (C-7),
140.3 (C-4), 149.6 (C-8a), 150.1 (C-2), and 189.1 (C-9).
2.2.3. Synthesis of 2-Methoxyquinoline-3-carbaldehyde (5).
A 100 mL two-neck round-bottom flask was charged with
methanol (10 mL), N,N-dimethylformamide (10 mL), 2-
chloroquinoline-3-carbaldehyde (0.5 g, 0.0026 mol), and
potassium carbonate (0.67 g, 0.0048 mol); the mixture was
refluxed using water condenser for 6 hours; and the progress
of reaction was monitored with TLC. After completion of the
reaction, methanol was removed by distillation, allowed to
cool to room temperature, and then added to 100 mL ice-
cold water. +e solid product was collected by fractional
distillation and washed with excess ice-cold water. +e
amount of product was 0.44 g. Gray powder; yield 90.2%; mp
106–108°C; Rf � 0.32 (n-hexane:EtOAc � 9 :1; UV-Vis λmax
(MeOH) 295 nm; IR(ʋ cm−1, KBr): 3065.4 (aromatic C-H
str.), 2919.3 (aliphatic C-H str.), 2847 (aliphatic C-H str.),
1673 (aldehyde C�O str.), 1620 (quinoline C�N str.), 1599
2. Materials and Methods
2.1. General. Melting points were determined using open
capillary tubes (+iele) and were uncorrected. Analytical
TLC was run on a 0.2 mm thick layer of silica gel GF254
(Merck) on aluminum plate. Spots were detected using UV
lamp. Column chromatography was performed using silica
gel 60 (250–400 mesh) Merck. +e IR spectra of com-
pounds were recorded using a Perkin-Elmer BX Spec-
trometer (400–4000 cm−1) as KBr pellets. NMR spectra
were recorded using Bruker Avance 400 spectrometer
operating at 400 MHz using CDCl3 and DMSO-d6 as a
solvent. All chemicals were purchased from Loba Chemie
PVT, Ltd.
1
and 1579 (aromatic C�C str.); H NMR (400 MHz, CDCl3)
δH 4.22 (3H, s, H-10), 7.45 (1H, t, J � 7.3 Hz, H-7), 7.76 (1H, t,
J � 7.7 Hz, H-6), 7.85 (2H, m, H-5, H-8), 8.60 (1H, s, H-4), and
10.49 (1H, s, H-9); 13C NMR (100 MHz, CDCl3) δC 55.9 (C-
10), 120.0 (C-3), 124.4 (C-6), 125.1 (C-4a), 127.1 (C-8), 129.8
(C-5), 132.6 (C-7), 140.0 (C-3), 149.0 C-8a), 161.2 (C-2), and
189.4 (C-9).
2.2. Chemistry
2.2.1. Synthesis of Acetanilide (3). In 250 mL round flask,
aniline (20 mL), acetic anhydride (22 mL), zinc powder
(0.2 g), and acetic acid (23 mL) were added. +e mixture was
boiled under reflux using water condenser for an hour. +en,
it was cooled to room temperature and poured into 200 mL
2.2.4. Synthesis of 2-Ethoxyquinoline-3-carbaldehyde (6).
A 100 mL two-neck round-bottom flask was charged
with 2-chloroquinoline-3-carbaldehyde (0.5 g, 0.0026 mol),

Journal of Chemistry
3
potassium carbonate (0.6 g, 0.0044 mol), ethanol (10 mL),
and N,N-dimethylformamide (10 mL), and the necks were
fitted with water condenser and stopper. +e mixture was
refluxed for 5 hours and the progress of the reaction was
monitored with TLC. At the end, the ethanol was removed
by distillation, and the remaining cooled mixture was
poured into 100 mL crushed ice water. +e solid mass was
collected by suction filtration. Yield 67.3%; white powder;
mp 63–65°C, Rf � 0.38 (n-hexane : EtOAc � 9 :1), UV-Vis
λmax (MeOH) 300 nm; IR (ʋ cm−1, KBr) 3429 (OH str.),
3055 (aromatic C-H str.), 2930.9 (aliphatic C-H str.),
2874.45 (aliphatic C-H), 1683 (C�O str.), 1621 (quinoline
Rf � 0.63 (EtOAc: dichloromethane: methanol � (3 : 2 : 3);
UV-Vis λmax (MeOH) 280 nm; IR (ʋ cm−1, KBr)
3440–2483 (broad band, acid CO2-H str), 1725 (C�O str),
1621 (quinoline C�N str.), 1540 and 1496.6 (aromatic C�C
str.); 1H NMR (400 MHz, DMSO-d6), δH 7.72 (1H, t,
J � 7.0 Hz, H-6), 7.92 (1H, t, J � 7.0 Hz, H-7), 7.98 (1H, d,
J � 7.8 Hz, H-8), 8.15 (1H, d, J � 7.8 Hz, H-5), 8.93 (1H, s,
H-4); 13C NMR (100 MHz, DMSO-d6) δC 130.65 (C-3),
131.10 (C-4a), 132.83 (C-8a), 133.21 (C-5), 134.50 (C-6),
137.92 (C-7), 146.93 (C-4), 151.62 (C-8), 152.5 (C-2), and
170.90 (C-9).
1
C�N str.), 1589.6 and 1566 (aromatic C�C str.); H NMR
2.2.7. Synthesis of 4-Nitrophenol (10). Concentrated sul-
furic acid (5.5 mL) was added to a 100 mL beaker con-
taining water (7.5 mL). To the solution, finely powdered
p-nitroaniline (3.5 g, 0.025 mol) and 15 g of finely crushed
ice were added and stirred until the p-nitroaniline con-
verted into a homogeneous paste. It was cooled to 0–5°C
by immersion of the beaker in crushed ice. A cold solution
of sodium nitrite (1.8 g) in 4 mL of water was added to it
dropwise while keeping temperature below 5°C during the
diazotization process. While the diazotization reaction
was in progress, a mixture of 16.5 mL concentrated sul-
furic acid in 15 mL of water was heated to just boiling in
100 mL round flask, and the diazonium solution was
added to it dropwise within 5 minutes. After additional 5
minutes of boiling, the mixture was cooled in ice bath
while being stirred continuously. +e solid mass was
collected by suction filtration and washed with 10 mL of
cold water. +e crude product was recrystallized in 6M
hydrochloric acid. +e yield of yellow crystal product was
2.1 g (60%). +e melting point was 112–113°C (literature
value is 113.8°C). Purity was analyzed with TLC, and its
authenticity was ascertained by comparing its melting
point with literature value.
(400 MHz, CDCl3) δH 1.53 (3H, t, J12 � 7.05 Hz, H-11), 4.89
(2H, q, J12 � 7.05 Hz, H-10), 7.43 (1H, t, J � 7.3 Hz, H-7),
7.72 (1H, t, J � 7.3 Hz, H-6) 7.84 (2H, d, J � 8.37 Hz, H-8,
H-5), 8.59 (1H, s, H-4), and 10.61 (1H, s, H-9); 13C NMR
(100 MHz, CDCl3) δH 14.5 (C-11), 62.4 (C-10) 120.0 (C-3),
124.3 (C-4a), 124.9 (C-6), 127.3 (C-8), 129.8 (C-5), 132.5
(C-7), 139.7 (C-4), 149.1 (C-8a), 161.2 (C-2), and 189.07
(C-9).
2.2.5. Synthesis of 2-2iocyanatoquinoline-3-carbaldehyde
(7). Potassium thiocyanate (0.24 g, 0.0024 mol), 2-chloro-
8-methyl quinoline-3-carbaldehyde (0.5 g, 0.0024 mol),
and potassium carbonate (0.65 g, 0.0047 mol) were added
to 100 mL two-neck round-bottom flask containing N,N-
dimethylformamide (20 mL). A water condenser was
placed on one of its neck, and the other was closed with
glass stopper and then refluxed for 3 hours, and the
progress of the reaction was followed by TLC. +e system
was cooled to room temperature and poured into 50 mL
crushed ice water. +e solid product was collected with
suction filtration and washed with 10 mL cold water. Yield
83.6%; orange powder; mp 134–136°C; Rf � 0.44 (n-hexane:
EtOAc � 2 :1); UV-Vis λmax (MeOH) 255 nm; IR (ʋcm−1,
KBr) 3045 (aromatic C-H str.), 2919.9 (aliphatic C-H str.),
2182 (cyanide S-C≡N str.), 1683 (aldehyde C�O str.), 1610
(quinoline C�N str.), 1572 (aromatic C�C str.), 1512 and
2.2.8. Synthesis of 2-Nitro-12H-chromeno[2,3-b]quinolin-12-
one (11). p-Nitrophenol (0.34 g, 0.0024 mol), 2-chloro-8-
methylquinoline-3-carbaldehyde (0.5 g, 0.0024 mol),
potassium carbonate (0.67 g, 0.0047 mol), and moist
copper powdered (0.1 g, 0.0016) were added to a 100 mL
two-neck round-bottom flask containing N,N-dime-
thylformamide (20 mL). A water condenser was fitted into
one of the necks, and the other one was closed with glass
stopper. +e mixture was refluxed for 5 hours with the
progress followed by TLC. After being cooled to room
temperature, it was added to 100 mL crushed ice water. +e
solid product was separated by suction filtration and washed
with 5% sodium hydroxide solution (50 mL). Yield 0.61 g
(81.3%); yellow powder, mp 177–179°C; Rf � 0.67 (n-hexane :
EtOAc � 2 :1), UV-Vis λmax (MeOH) 285 nm; IR (ʋcm−1,
KBr) 3055 (aromatic C-H str.), 1703 (C�O str.), 1615
(quinoline C�N str.), 1577 (aromatic C�C str.), 1512 and
1
1340 (O�N-O str.); H NMR (400 MHz, CDCl3) δH 7.50
(1H, d, J � 7.8 Hz, H-8), 7.61 (1H, d, J � 8.9 Hz, H6), 7.72
(1H, d, J � 8.8 Hz, H-7), 7.85 (1H, d, J � 8.9 Hz, H-5), 8.74
(1H, s, H-4), 10.65 (1H, s, H-9); 13C NMR (100 MHz,
CDCl3) δC 87.6 (C-10), 121.1 (C-3, C-6), 122.4 (C-6, C-8),
125.8 (C-4), 127.7 (C-5), 129.7 (C-7), 132.8 (C-8a), 135.6
(C-4a), 163.6 (C-2), and 188.9 (C-9).
2.2.6. Synthesis of 2-Chloroquinoline-3-carboxylic Acid (8).
Sodium hydroxide solution (1 mL, 10%) was added to a
suspension of 2-chloroquinoline-3-carbaldehyde (0.5 g,
0.0026 mol) in water (20 mL). +en a saturated solution of
potassium permanganate in water was added dropwise until a
definite purple color remains after shaking the solution. +e
mixture was acidified with 10% sulfuric acid, and a saturated
oxalic acid was added to destroy the excess permanganate
solution. +e carboxylic acid precipitate was isolated by
suction filtration. Yield 59.3%; white powder, mp 202–204°C;
1
1340 (O�N-O str.); H NMR: (400 MHz, CDCl3) δH 6.97
(2H, t, J � 7.4 Hz, H-8, H-9), 7.04 (2H, d, J � 8.4 Hz, H-4,
H-7), 7.55 (2H, t, J � 7.4 Hz, H-1, H-10), 7.96 (2H, d,
J � 8.0 Hz, H-3, H-11); 13C NMR (100 MHz, CDCl3) δC 111.4

4
Journal of Chemistry
1
(C-11a, C-12a), 117.8 (C-1, C-4, C-9), 119.6 (C-7, C-10,
C-10a), 131.0 (C-3, C-8), 137.0 (C-2, C-6a, C-11), 162.2 (C-
4a, C-5a), 175.0 (C-12).
C�N str.), 1558 and 1465 (aromatic C�C str.); H NMR
(400 MHz; CDCl3) δH 2.56 (3H, s, C-10), 7.23 (1H, t,
J � 7.5 Hz, H-6), 7.51 (1H, d, J � 7.32 Hz, H-7) 7.61 (1H, m,
J � 7.7 Hz, H-5), 8.49 (1H, s, H-4) and 10.48 (1H, s, H-9); 13
C
NMR (100 MHz, CDCl3) δC 16.7 (C-10), 117.9 (C-6), 123.3
(C-3, C-8), 129.1 (C-4a, C-7), 135.0 (C-5), 139.1 (C-8a),
144.2 (C-4), 162.7 (C-2), 190.00 (C-9).
2.2.9. Synthesis of 2-Methylacetanilide (13). To a 250 mL
round-bottom flask, o-toluidine (22 mL, 22.2 g, 0.207 mol),
acetic anhydride (23 mL, 24.84 g, 0.24 mol), acetic acid
(23 mL, 24.15 g, 0.40 mol), and zinc powder (0.2 g,
0.003 mol) were added. +e mixture was refluxed for an hour
using water condenser. It was cooled to room temperature
and added to 200 mL crushed ice water. +e product was
collected by suction filtration. Yield 21.2 g (69%); white
powder; mp 108–110°C (Lit. 109–112°C).
2.2.12. Synthesis of (2-Methoxy-8-methylquinolin-3-yl)
methanol (16). A gram of sodium (0.043 mol) was dissolved
in 10 mL methanol, and 2-chloro-8-methylquinoline-3-
carbaldehyde (0.5 g, 0.0024 mol) and 10 mL of N,N-dime-
thylformamide were added to it. +e mixture was refluxed
for 6 hours, at which TLC analysis showed complete dis-
appearance of the aldehyde. After removal of methanol using
distillation, the remaining content was cooled to room
temperature and added to 100 mL ice-cold water. +e
precipitate was collected by fractional distillation. Yield 53%;
gray powder, mp 98–99°C; Rf � 0.51 (n-hexane:EtOAc � 3 :
1), UV-Vis λmax (MeOH) 315 nm; IR (ʋcm−1, KBr): 3470
(br-alcohol CHO-H str.), 3013 (aromatic C-H str.), 2930.9
(aliphatic C-H str.), 1625 (quinoline C�N str.), 1589.6 and
1475.5 (aromatic C�C str.); 1H NMR (400 MHz; CDCl3) δH
2.80 (3H, s, H-10), 4.11 (3H, s, H-9), 4.79 (2H, s, H-1), 7.28
(1H, t, J � 7.58 Hz, H-6), 7.42 (1H, d, J � 7.0 Hz, H-7), 7.58
(2H, d, J � 8.34.Hz, H-5), 7.86 (1H, s, H-4); 13C NMR
(100 MHz, CDCl3) δC 18.1 (C-10), 51.3 (C-9), 61.9 (C-1),
123.8 (C-3), 124.1 (C-6), 124.2 (C-4a), 125.0 C-5), 129.4 (C-
7), 135.1 (C-8), 135.9 (C-4), 144.7 (C-8a), 160.2 (C-2).
2.2.10. Synthesis of 2-Chloro-8-methylquinoline-3-carbalde-
hyde (14). To a 100 mL round-bottom flask equipped with
drying tube, N,N-dimethylformamide (20 mL, 18.88 g,
0.26 mol) was added, and the mixture was cooled to 0°C
using ice bath. +en phosphorus oxychloride (70 mL,
115.15 g, 0.75 mol) was added dropwise from dropping
funnel guarded by drying tube which was fitted to flask with
adaptor while being stirred by magnetic stirrer for 30
minutes. Next, N-(o-tolyl)acetamide (13.5 g, 0.1 mol) was
added to it, the dropper funnel was replaced by air condenser
with guarding tube, and the mixture was heated for 22 hours
on oil bath at 85–90°C. After that, it was cooled to room
temperature and poured into a beaker containing 400 mL
crushed ice water, while being stirred with glass road. +e
yellow solid product was collected by suction filtration and
washed with cold water. +e crude yield was 9.2 g (44.77%),
and it was recrystallized in ethyl acetate. +e final pure
product was 6.8 g (33.09%); pale yellow crystal; mp
136–140°C; Rf � 0.30 (n-hexane:EtOAc � 9 :1), UV-Vis λmax
(MeOH) 295 nm; IR (ʋcm−1, KBr) 3223, 3025 (arom-C-H.),
2956 (alip-C-H), 2837 (alip-C-H), 1683.3 (C�O str.), 1621
2.2.13. Synthesis of (2-Ethoxy-8-methylquinolin-3-yl)metha-
nol (17). Sodium (1 g, 0.043 mol) was dissolved in ethanol
(10 mL), and 0.5 g (0.0024 mol) of 2-chloroquinoline-3-
carbaldehyde and 10 mL of N,N-dimethylformamide were
added to it. +e mixture was refluxed for 5 hours, at which
TLC analysis showed complete disappearance of the alde-
hyde. +e ethanol was removed by distillation, and the
remaining content was cooled to room temperature and
added to 100 ml cold water. +e precipitate was collected by
fractional distillation. Yield 82.7%; dull brown; mp 85–87°C;
Rf � 0.54 (n-hexane:EtOAc � 3 :1); UV-Vis λmax (MeOH)
315 nm; IR (ʋcm−1, KBr) 3502–3148 (OH str.), 3025 (aro-
matic C-H str.), 2930.9 (aliphatic C-H str.), 1625 (quinoline
1
(quinoline C�N str.), 1579 (aromatic C�C str.); H NMR
(400 MHz; CDCl3) δH 2.80 (3H, s, H-10), 7.53 (1H, t, H-6),
7.70 (1H, d, H-7), 7.78 (1H, d, H-5), 8.70 (1H, s, H-4), 10.6
(1H, s, H-9); 13C NMR (100 MHz, CDCl3): δC 17.8 (C-10),
126.0 (C-3), 126.5 (C-6), 127.5 (C-5), 127.8 (C-4a), 133.6 (C-
7), 136.9 (C-8), 140.4 (C-4), 148.7 (C-2), 149.4 (C-8a) and
189.5 (C-1).
1
C�N str.), 1582 (aromatic C�C str.); H NMR (400 MHz;
2.2.11. Synthesis of 8-Methyl-2-oxoquinoline-3-carbaldehyde
(15). 2-Chloro-8-methylquinoline-3-carbaldehyde (0.5 g,
0.0024 mol) was added to a mixture of 6M HCl (10 mL) and
glacial acetic acid (10 mL). +e mixture was refluxed for
3 hours, at which the TLC analysis showed complete dis-
appearance of the starting material. +en the acetic acid
mixture was removed with distillation under reduced
pressure. +e solid residue was washed with cold water and
allowed to dry in wood cupboard. +e amount of the
product was 395 mg. Yield 86.5%; yellow powder; mp
176–178°C; Rf � 0.41 (n-hexane:EtOAc � 1 :1); UV-Vis λmax
(MeOH) 375 nm; IR (ʋcm−1, KBr) 3429 (O-H str.), 3179.5
(NH str.), 3023 (aromatic C-H), 2919.8 (aliphatic CH-str’.),
2837.2 (aliphatic C-H) 1673 (C�O str.), 1610 (quinoline
CDCl3) δH 1.5 (3H, t, J � 7.01 Hz, H-10), 2.74 (3H, s, H-11)
4.63 (2H, q, J � 7.01 Hz, H-9), 4.48 (2H, s, H-1), 7.26 (1H, t,
J � 7.04 Hz, H-6), 7.47 (1H, d, J � 6.89 Hz, H-7), 7.56 (1H, d,
J � 7.80 Hz, H-5), 7.93 (1H, s, H-4); 13C NMR (100 MHz,
CDCl3) δC 13.7 (C-10), 19.3 (C-11), 61.5 (C-1), 61.8 (C-9),
123.0 (C-9), 124.2 (C-6), 124.90 (C-4a), 125.0 (C-5), 130.3
(C-7), 135.0 (C-8), 135.8 (C-4), 144.7 (C-8a), 158.3 (C-2).
2.3. Antibacterial Activity. Antibacterial activities of the
synthesized compounds were tested using the paper disc-
diffusion method. In the process, two Gram-positive
bacteria (Bacillus subtilis ATCC6633 and Staphylococcus
aureus ATCC25923) and two Gram-negative bacteria

Journal of Chemistry
5
O
5
8
4
H
N
9
POCl3
NH2
6
7
Acetic acid
H
O
O
4a
8a
3
2
+
DMF
85-90°C
O
reflux
1 hr
O
N
1
Cl
2
1
3
22 hrs
4
CH3OH
O
5
8
4
9
K2CO3
6
7
H
4a
8a
3
DMF
reflux, 5 hrs
2
N
1
OCH3
10
5
CH3CH2OH
K2CO3
O
5
4
9
6
O
H
4a
8a
3
2
DMF
reflux, 5 hr
7
H
OCH2CH3
N
1
8
11
10
6
7
N
Cl
O
5
4
KSCN
4
9
6
H
4a
8a
3
DMF
reflux 5 hr,
2
7
10
N
1
S
8
N
9
O
5
8
4
Saturated KMnO4
ethanol
6
OH
4a
8a
3
2
7
N
1
Cl
8
O
O
10
11
10a
1
4
K2CO3, DMF
reflux 5 hr
moist Cu
12a
4a
N
–
9
12
O
+
2
3
11a
6a
5a
8
N
6
O
5
7
HO
11
NO2
10
1-NaNO2
con. H2SO4
2. hot 9M H2SO4
NO2
crushed ice
0-5°C
H2N
9
Scheme 1: Synthesis of 2-chloroquinoline-3-carbaldehyde and its derivatives.
(Escherichia coli ATCC 25922 and Pseudomonas aerugi-
nosa ATCC 27853) were used to evaluate the antibacterial
activities. +e medium was prepared from molten nu-
trient and Mu¨eller–Hinton agar. Ciprofloxacin was the
standard drug used as positive control while DMSO was
used as negative control. +e four bacterial strains were
tested with 300 and 500 μg/mL concentration using paper
disc-diffusion method. Each of the ten compounds was
dissolved in DMSO at concentrations of 300 and 500 μg/
mL, 6 mm diameter Whatman filter paper discs were
soaked with 1 mL solution of the above two concentra-
tions for each compound, and then these saturated paper
discs were inoculated at the center of each Petri dish
having bacterial lawn in triplicate. +e plates were in-
cubated at 37°C for 48 h, and the inhibition zone that
appeared around the paper disc in each plate was de-
termined by measuring the diameter of the inhibition
zone.

6
Journal of Chemistry
O
9
5
4
H
N
POCl3
NH2
6
7
O
H
3
Acetic acid
O
4a
8a
2
+
DMF
85-90°C
22 hrs
O
reflux
1 hr
O
N
1
Cl
8
2
13
12
10
14
O
9
5
4
6
7
H
6 M HCl
acetic acid
4a
8a
3
2
N
O
1
8
H
reflux, 3 hr
O
1
10
5
15
H
4
Na, CH3OH
6
7
OH
4a
8a
N
3
2
N
Cl
DMF,
reflux 6 hrs
OCH3
9
8
14
1
16
10
(2-ethoxy-8-methylquinolin-3-yl)methanol
Na, CH3CH2OH
5
4
1
6
7
OH
4a
8a
N
3
2
DMF
refux, 6 hrs
OCH2CH3
8
1
9
10
11
17
Scheme 2: Synthesis of 2-chloro-8-methylquinoline-3-carbaldehyde and its derivatives.
2.4. Radical Scavenging Activity of the Synthesized Compounds.
+e radical scavenging activity of the synthesized com-
pounds was evaluated with 1,1-diphenyl-2-picryl hydrazyl
(DPPH). In the process, 0.04 mg/mL solution of DPPH in
methanol was prepared; 1 mL of this solution was poured
into 4 mL of the synthesized samples in methanol to
furnish four different concentrations (12.5, 25, 50, 100 μg/
mL); and control was made by adding 1 mL of the DPPH
solution to 4 mL of methanol, while 4 mL methanol was
used as a blank. +e mixtures were shaken and allowed to
stand at 37°C for 30 min in dark oven, and absorbance was
recorded at 517 nm using double beam UV-Vis spectro-
photometer. Ascorbic acid was used for reference standard
in similar concentration as above. Percentage inhibition of
DPPH radical was determined using the following
equation:
were drawn using ChemOffice tool (ChemDraw 16.0)
assigned with proper 2D orientation, and energy of each
molecule was minimized using ChemBio3D. +e energy-
minimized ligand molecules were then used as input for
AutoDock Vina, in order to carry out the docking sim-
ulation [22]. +e crystal structures of receptor molecule E.
coli gyrase B (PDB ID : 6F86) and S. aureus gyrase complex
with ciprofloxacin and DNA (PDB ID : 2XCT) were
downloaded from protein data bank. +e protein prepa-
ration was done using the reported standard protocol [23]
by removing the cocrystallized ligand, selected water
molecules, and cofactors; the target protein file was pre-
pared by leaving the associated residue with protein using
Auto Preparation of target protein file AutoDock 4.2
(MGLTools 1.5.6). +e graphical user interface program
was used to set the grid box for docking simulations. +e
grid was set so that it surrounds the region of interest in the
macromolecule. +e docking algorithm provided with
AutoDock Vina was used to search for the best docked
conformation between ligand and protein [22–24]. During
the docking process, a maximum of nine conformers were
considered for each ligand. +e conformations with the
most favorable (least) free binding energy were selected for
analyzing the interactions between the target receptor and
ligands by Discovery Studio Visualizer and PyMOL. +e
ligands are represented in different color; H-bonds and the
interacting residues are represented in ball and stick model
representation.
Ao − A1
% inhibition �
× 100,
(1)
Ao
where Ao is the absorbance of control reaction and A1 is the
absorbance in presence of test or standard sample [21].
2.5. Molecular Docking Analysis of the Synthesized
Compounds. AutoDock Vina with standard protocol was
used to dock the proteins (PDB ID: 6F86; PDB ID: 2XCT)
and synthesized compounds (4–17) into the active site of
proteins [22]. +e chemical structures of compounds 4–17

Journal of Chemistry
7

8
Journal of Chemistry
40
35
30
25
20
15
10
5
0
E. coli
B. subtilis
S. aureus
P. aeruginosa
Bacterial strains
4
5
6
7
8
16
11
14
15
17
Ciprofloxacin
Figure 1: +e inhibition zone of the synthetic compounds in mm (mean SD) at 500 μg/mL.
+e above data shows all synthesized compounds dis-
played medium to good activity against two or more bacterial
strains. +e mean inhibition zones ranged from the lowest
(6 mm at 300 μg/mL) to the highest (11.3 mm at 500 μg/mL).
+ree of the ten compounds, 8, 11, and 16, showed good
activities against Escherichia coli, among which 11 and 8
revealed better activities with mean inhibition zone of
11.00 1.33 and 11.33 1.11 mm diameter at 500 μg/mL,
respectively. Seven of the ten compounds (4, 6, 8, 7, 14, 16,
and 17) (Figure 1) showed antibacterial activity against Ba-
cillus subtilis, but maximum inhibition zone (7.67 0.44 mm)
was observed in compounds 4 and 6. None of the synthetic
compounds demonstrated activity against Staphylococcus
aureus except 4, 5, 8, and 15 which showed slight activity.
Among the synthetic compounds, 4, 5, 6, and 15 displayed
moderate activity against Pseudomonas aeruginosa, and the
maximum inhibition zone was 10.00 0.44 mm for com-
pound 15 but only 8.33 0.44 mm for ciprofloxacin at the
same concentration (500 μg/mL). Compounds 4 and 8 dis-
played moderate to good activity against all tested bacterial
species, while compound 17 showed no activity against all
tested organisms except Bacillus subtilis with inhibition zones
of 6.33 0.44 mm and 7.33 0.44 mm at concentrations of
300 and 500 μg/mL, respectively.
3. Results and Discussion
3.1. Chemistry. In an attempt to generate quinoline deriv-
atives which have antibacterial properties, various quinoline
derivatives were prepared using various reaction conditions.
In the process, N-(o-tolyl)acetamide and acetanilide were
prepared by refluxing the corresponding aniline in acetic
acid and acetic anhydride mixtures. +en 2-chloroquino-
line-3-carbaldehyde and 2-chloro-8-methylquinoline-3-
carbaldehyde were prepared from the acetanilide by
the Vilsmeier approach. +e chlorine in position 2 of
quinolines was substituted by various nucleophiles by
refluxing 2-chloroquinoline-3-carbaldehyde and 2-chloro-
8-methylquinoline-3-carbaldehyde in N,N-dimethylforma-
mide with various nucleophilic reagents in basic medium.
Potassium carbonate was used to induce the basic medium.
Refluxing 2-chloro-8-methylquinoline-3-carbaldehyde in
6M HCl and acetic acid (1 :1) mixture afforded 8-methyl-2-
oxoquinoline-3-carbaldehyde. +e carbaldehyde functional
group of quinoline was oxidized to carboxylic acid by
permanganate method and was subsequently reduced to
alcohol using metallic sodium. +e overall sequence of re-
actions used in the synthesis of various targeted quinoline
derivatives are illustrated in Schemes 1 and 2.
+e structure elucidation of the synthesized compounds
was accomplished using UV-Vis, FTIR, and NMR spec-
troscopic methods.
3.3. Radical Scavenging Activity of the Synthetic Compounds.
DPPH assay was widely used to assess the ability of com-
pounds as scavengers of free radicals and hence evaluate the
antioxidant activity of synthetics compounds or phyto-
chemicals. Compounds exhibiting antioxidant activity re-
duced the absorbance at 517 nm, which is due to DPPH
radical in addition to their ability to turn the purple colored
DPPH to yellow. In this work, the radical scavenging activity
of the synthesized compounds was evaluated using DPPH,
and the findings are depicted in Table 2.
3.2. Antibacterial Activity. Quinolines are pharmacologi-
cally active compounds used to treat various life threatening
diseases. In an attempt to find out lead compounds against
bacteria, a series of quinoline derivatives have been syn-
thesized and subsequently evaluated for their antibacterial
activities against various strains of bacterial pathogens. +e
results obtained are depicted in Table 1 and Figure 1.

Journal of Chemistry
9

10
Journal of Chemistry
100
90
80
70
60
50
40
30
20
10
0
12.5
25
50
100
Concentration
4
5
6
7
8
11
14
Figure 2: Percentage inhibition of DPPH radical by the synthetic compounds.
100
80
60
40
20
0
Ascorbic…
7
100
50
25
12.5
Concentration
7
Figure 3: Comparison of % inhibition of compound 7 with ascorbic acid.
O
O2N
N
O
NO2
NO2
H
H
+
NO2
N
+
NO2
N N
S
N
S
C
N
N
O2N
N
Scheme 3: Proposed mechanism of action of compound 7.
+e DPPH radical scavenging activity of the synthesized
+e data in Table 2 and Figure 2 reveal that nine of the
synthetic compounds showed moderate antioxidant activi-
ties, while compound 7 (Figure 3) exhibited better antiox-
idant activity (67% radical scavenging activity at 100 μg/mL
concentration) among them all. 1,1-Diphenyl-2-picrylhy-
drazyl (DPPH) is a stable free radical accepting hydrogen
compounds was compared with ascorbic acid which is used as
positive control, and the result is presented in Figure 2.
Compound 7, which displayed better radical scavenging
activity in the present work, has been elaborated in com-
parison with ascorbic acid using 3D diagram (Figure 3).

Journal of Chemistry
11
Table 3: Molecular docking value of compounds 4–17 against E. coli DNA gyrase B.
Affinity
(kcal/mol)
Compounds
H-bond
Receptor interactions
4
−6.2
−6.2
−6.4
−6.3
−6.3
−7.3
−6.3
−6.2
−6.0
−6.3
−6.9
Asp-73
Asp-73, +r-165, Gly-77
Gly-77, +r-165
Asn-46, +r-165, Gly-77
Asn-46
Val-43, Val-71, Ile-78, Ala-47
Ile-94, Ile-78
Asp-73, Ile-94, Ile-78, Ala-47
Asp-73, Val-43, Val-167, Ala-47
5
6
7
8
Asp-73, Arg-76, Ala-47, Glu-50, Gly-77, Ile-78, Pro-79, Gly-75, +r-165
Asp-73, Ile-78, Ile-94, Pro-79, Glu-50, Gly-75
Ile-78, Val-167, Val-120
11
Arg-76, Asn-46, Gly-77, +r-165
–
14
15
–
Ala-47, Asn-46, Ile-78, +r-165, Val-167
Ile-78
Ala-47, Glu-50, Ile-78, Pro-79, +r-165
Ala-47, Ile-78, Ile-94, Pro-79, Glu-50, Gly-77
16
Asp-73
17
Asp-73, Gly-77
Asp-73, Arg-76, Asn-46
Ciprofloxacin
Figure 4: +e binding interactions of ciprofloxacin against E. coli DNA gyrase B (PDB ID : 6F86).
from a corresponding donor, which causes it to lose the
characteristic deep purple (λmax 517 nm) color. In com-
pound 7, there is no such easily transferable hydrogen;
however, sulfur of thiocyanate functional group may donate
an electron to lone pair electron on the nitrogen atom to
form bond with sulfur (Scheme 3).
compounds and ciprofloxacin were summarized in Table 3.
Compared to ciprofloxacin, the synthesized compounds
(4–17) showed similar residual interactions profile with
amino acid residues Ile-94, Pro-79 Glu-50, Gly-77, Ile-78,
and Ala-47 and H-bond with Asp-73, Arg-76, and Asn-46.
Compounds 5, 6, and 7 have additional hydrogen bonding
interaction with amino acid residue +r-165. +e com-
pounds 4 (Val-43, Val-71), 7 (Val-167), 14 (Val-120 and
Val-167), and 15 (Val-167) have shown additional hy-
drophobic interaction with amino acid residues. +e re-
sidual amino acid interactions of synthesized ligands
(except 14 and 15) with DNA gyrase (6f86) in this study
were well in agreement with the previously reported
binding modes that include the crucial interactions be-
tween the ligand, Asp-73, and the water molecule [23]. +e
in silico interaction results match the in vitro analysis of the
synthesized compounds; 4 (−6.2 kcal/mol), 11 (−7.3 kcal/
mol), 8 (−6.3 kcal/mol), and 16 (−6.0 kcal/mol) showed
good activities against E. coli, among which compounds 8
(–6.3 kcal/mol) and 11 (−7.3 kcal/mol) revealed better
activity. +e compounds 14 and 15 docking results partially
matched the ciprofloxacin interactions with amino acid
residues. Based on the in silico molecular docking analysis
results, compounds 8 and 11 showed comparable residual
interactions and docking score of ciprofloxacin. +erefore,
compound 11 might have the best antibacterial agents
among the compounds reported herein. +e binding
3.4. In Silico Molecular Docking Evaluation. In general,
antimicrobial agents target the key components of bacterial
metabolism to disable the bacteria such as cell-walls, DNA
gyrase, DNA-directed RNA polymerase, protein synthesis,
and enzymes. DNA gyrase, an enzyme belonging to a
member of bacterial topoisomerase, controls the topology of
DNA during transcription, replication, and recombination
by introducing transient breaks to both DNA strands
[25–27]. In this regard, bacterial DNA gyrase is essential for
bacterial survival and therefore necessary to be exploited as
an antibacterial drug target [28]. +erefore, in the present
study, the molecular docking analysis of the synthesized
compounds was carried out to investigate their binding
pattern with DNA gyrase and compare them with standard
inhibitor (ciprofloxacin). +e synthesized compounds
(4–17) were found to have minimum binding energy
ranging from –6.2 to –7.3 kcal/mol (Table 3), with the best
result achieved using compound 11 (−7.3 kcal/mol). +e
binding affinity, H-bond, and residual interaction of ten

12
Journal of Chemistry
Figure 5: +e binding interactions of compound 6 against E. coli DNA gyrase B (PDB ID : 6F86).
Figure 6: +e binding interactions of compound 7 against E. coli DNA gyrase B (PDB ID : 6F86).

Journal of Chemistry
13
Figure 7: +e binding interactions of compound 8 against E. coli DNA gyrase B (PDB ID : 6F86).
Figure 8: +e binding interactions of compound 11 against E. coli DNA gyrase B (PDB ID : 6F86).

14
Journal of Chemistry
Figure 9: +e binding interactions of compound 17 against E. coli DNA gyrase B (PDB ID : 6F86).
affinity, H-bond, and residual interaction of ten com-
pounds were summarized in Table 3.
study of the synthesized compounds was performed to assess
the binding mode of these compounds against DNA gyrase B
(PDB ID: 6F86), and the result was in good harmony with
antibacterial assay result. Generally, the synthesized com-
pounds have potential of antibacterial activity and can be
further optimized to serve as lead compounds.
+e 3-dimensional binding interaction of compounds 6,
7, 8, 11, 17 and ciprofloxacin against E. coli gyrase B complex
is illustrated in Figures 4–9. +e docking results of com-
pounds 4, 5, 14, 15, and 16 against E. coli gyrase B complex
and compounds 4–17 against S. aureus gyrase B complex are
given as supplementary data.
Data Availability
+e data used to support the findings of this study are in-
cluded within the manuscript and also submitted as Sup-
plementary Materials.
4. Conclusion
+e quinoline heterocycle is a useful scaffold to develop
bioactive molecules. In the present work, we synthesized
series of quinolin derivatives by application of Vils-
meier–Haack reaction. Various nucleophiles were introduced
into 2-chloroquinoline-3-carbaldehyde and 2-chloro-8-
methylquinoline-3-carbaldehyde by substitution of chlorine
using different reaction conditions. +e carbaldehyde func-
tional group was further manipulated to carboxylic acid using
potassium permanganate method and reduced to alcohols
with metallic sodium. All synthesized compounds were
characterized by TLC, melting point, 1H NMR, 13C NMR, and
UV-Vis spectroscopy. +e antibacterial activities of the
synthesized compounds were screened by the disc-diffusion
method against two Gram-negative and two Gram-positive
bacteria, and most of them were found to have moderate
activities against the bacterial strains used for the screening.
Among them, compounds 6 and 15 exhibited maximum
activity against Pseudomonas aeruginosa compared to the
standard drug ciprofloxacin. +e in silico molecular docking
Conflicts of Interest
+e authors assert that there are no conflicts of interest
regarding the publication of this paper.
Acknowledgments
+e authors are thankful to Adama Science and Technology
University for funding this research.
Supplementary Materials
1
+e H NMR and 13C NMR spectra of the synthesized
compounds. Figure 1:1H NMR (400 MHz, CDCl3) spectrum
of 2-chloroquinoline-3-carbaldehyde (4). Figure 2: 13C NMR
(100 MHz, CDCl3) spectrum of 2-chloroquinoline-3-car-
baldehyde (4). Figure 3: 1H NMR (400 MHz, CDCl3)
spectrum of 2-methoxyquinoline-3-carbaldehyde (5).

Journal of Chemistry
15
Figure 4: 13C NMR (100 MHz, CDCl3) spectrum of 2-
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1
methoxyquinoline-3-carbaldehyde (5). Figure 5: H NMR
(400 MHz, CDCl3) spectrum of 2-ethoxyquinoline-3-carbal-
dehyde (6). Figure 6:13C NMR (100 MHz, CDCl3) spectrum of
1
2-ethoxyquinoline-3-carbaldehyde (6). Figure 7: H NMR
(400 MHz, DMSO-d6) spectrum of 2-thiocyanatoquinoline-3-
carbaldehyde. Figure 8: 1H NMR (400 MHz, DMSO-d6)
spectrum of 2-chloroquinoline-3-carboxylic acid (8). Figure 9:
13C NMR (100 MHz, DMSO-d6) spectrum of 2-ethox-
yquinoline-3-carbaldehyde (8). Figure 10: 1H NMR (400 MHz,
CDCl3) spectrum of 2-nitro-12H-chromeno[2,3-b]quinolin-
12-one (11). Figure 11: 13C NMR (100 MHz, CDCl3) spectrum
of 2-nitro-12H-chromeno[2,3-b]quinolin-12-one (11). Fig-
ure 12: 1H NMR (400 MHz; CDCl3) spectrum of 2-chloro-8-
methylquinoline-3-carbaldehyde (14). Figure 13: 13C NMR
(100 MHz; CDCl3) spectrum of 2-chloro-8-methylquinoline-
3-carbaldehyde (14). Figure 14: 1H NMR (400 MHz; CDCl3)
spectrum of 8-methyl-2-oxoquinoline-3-carbaldehyde (15).
Figure 15: 13C NMR (100 MHz; CDCl3) spectrum of 8-methyl-
2-oxoquinoline-3-carbaldehyde (15). Figure 16: 1H NMR
spectrum (400 MHz; CDCl3) of (2-methoxy-8-methyl-
quinolin-3-yl)methanol (16). Figure 17: 13C NMR spectrum
(100 MHz; CDCl3) of (2-methoxy-8-methylquinolin-3-yl)
methanol (16). Figure 18: 1H NMR (400 MHz; CDCl3)
spectrum of (2-ethoxy-8-methylquinolin-3-yl)methanol (17).
Figure 19: 13C NMR (100 MHz; CDCl3) spectrum of (2-eth-
oxy-8-methylquinolin-3-yl)methanol (17). (Supplementary
Materials)
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