Green and Efficient Synthesis of 4-Heteryl-Quinolines and Their Antibacterial Evaluations

Article abstract of DOI:10.1002/jhet.2698

A green and efficient synthesis of 4-heteryl-quinolines (9a, 9b, 9c, 9d), (10a, 10b, 10c, 10d) and (11a, 11b, 11c, 11d) has been described using PEG-600 as a green solvent. Initially, 4-chloro-2-methylquinolines (5a, 5b, 5c, 5d) on reaction with aromatic heterocyclic thiols (6), (7), and (8) using PEG-600 at 100°C for 30–40 min resulted in (9), (10), and (11) in good yields. Alternatively, (9), (10), and (11) could also be prepared in dimethylformamide using K2CO3 as base and tetrabutylammonium bromide as phase transfer catalyst at 100°C for 1–2 h. All the compounds were synthesized and characterized by IR, NMR, mass spectroscopy, and 13C NMR analysis. All synthesized compounds were screened for their antibacterial activity against clinical strains that include Gram-positive (Bacillus subtilis MTCC 121, staphylococcus aureus MLS-16 MTCC 2940, Micrococcus lutes MTCC 2470, and Staphylococcus aureus MTCC 96) and Gram-negative bacteria (Candida albicans MTCC 3017, Klebsiella planticola MTCC 530, Escherichia coli MTCC 739, and Pseudomonas aeruginosa MTCC 2453). The results revealed that compounds (9a, 9d, 10a, 10c, 11b, and 11d) exhibited significant antibacterial activity almost equal to the standard drug, that is, Ciprofloxacin.

Full text of DOI:10.1002/jhet.2698

Month 2016
Green and Efficient Synthesis of 4-Heteryl-Quinolines and Their
Antibacterial Evaluations
*
Venkata Ramana Reddy Ch., B. Rama Devi, and P.K. Dubey
a
a,b
a
a
a
*
Raja S. Bhupathi, Madhu Bandi,
aDepartment of Chemistry, College of Engineering, Jawaharlal Nehru Technological University Hyderabad, Kukatpally,
Hyderabad, Telangana 500 085, India
bJawaharlal Nehru Technological University, Kakinada, Andhra Pradesh, India
*
E-mail: madhubandi2@gmail.com; rs.bhupathi@gmail.com
Received March 1, 2016
DOI 10.1002/jhet.2698
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
A green and efficient synthesis of 4-heteryl-quinolines (9a–9d), (10a–10d) and (11a–11d) has been
described using PEG-600 as a green solvent. Initially, 4-chloro-2-methylquinolines (5a–5d) on reaction with
aromatic heterocyclic thiols (6), (7), and (8) using PEG-600 at 100°C for 30–40 min resulted in (9), (10), and
(11) in good yields. Alternatively, (9), (10), and (11) could also be prepared in dimethylformamide using
K2CO3 as base and tetrabutylammonium bromide as phase transfer catalyst at 100°C for 1–2 h. All the
compounds were synthesized and characterized by IR, NMR, mass spectroscopy, and 13C NMR analysis.
All synthesized compounds were screened for their antibacterial activity against clinical strains that include
Gram-positive (Bacillus subtilis MTCC 121, staphylococcus aureus MLS-16 MTCC 2940, Micrococcus
lutes MTCC 2470, and Staphylococcus aureus MTCC 96) and Gram-negative bacteria (Candida albicans
MTCC 3017, Klebsiella planticola MTCC 530, Escherichia coli MTCC 739, and Pseudomonas aeruginosa
MTCC 2453). The results revealed that compounds (9a, 9d, 10a, 10c, 11b, and 11d) exhibited significant
antibacterial activity almost equal to the standard drug, that is, Ciprofloxacin.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
chloroquine. After the worldwide development of drug
resistance to chloroquine, focused chemistry and screening
efforts produced mefloquine, another quinoline-containing
compound that was highly active against the chloroquine-
resistant strains of Plasmodium falciparum [2]. Since the
development of mefloquine, there have been several
reports of new potent quinoline compounds [3,4]. The
quinoline moiety has found broad application in drug
development for the treatment of melanin-concentrating
hormone receptor-related disorders [5]; cell proliferative
diseases [6]; transmissible spongiform encephalopathies
[7]; malignant tumors (such as stomach cancer, brain
tumor, and large intestine cancer) [8]; and bacterial infec-
tions in mammals [9].
Quinolines and its related compounds are used as very
good antibiotics in developing countries, because synthesis
and isolation of quinolone drugs are economically cheap
and have easy synthetic procedures. Especially quinolines
are used in treating malarial and urinary tract infections.
Malaria is one of the most devastating infectious diseases
in the world, affecting 200 to 500 million people and kill-
ing one to two million annually [1]. Since the discovery
of cinchona alkaloids and synthesis of anti-malarial agents
such as chloroquine, this has created a demand for the
development of new anti-malarial agents. The heterocyclic
systems containing a quinoline nucleus have long been
used for the treatment of malaria, beginning with
quinine (Fig. 1). Systematic modifications of quinine lead
to the potent and inexpensive 4-aminoquinoline drug
Reducing or eliminating the use of volatile organic
solvents can minimize the generation of waste, which is
essential in one of the principles of green chemistry [10].
© 2016 Wiley Periodicals, Inc.

R. S. Bhupathi, M. Bandi, V. R. R. Ch., B. Rama Devi, and P. K. Dubey
Vol 000
Table 1
Synthesis of compounds (9a–9d) from (5a–5d) and 6 at 100°C.
Synthesis
number
Product
(R)
Solvent
Time
(min)
Yield
(%)a
1
2
3
4
5
6
7
8
-OCH3
-CH3
-F
PEG-600
PEG-600
PEG-600
PEG-600
DMF
DMF
DMF
DMF
30
30
40
40
60
60
90
90
92
85
90
88
78
75
80
75
- Cl
-OCH3
-CH3
-F
-Cl
DMF, dimethylformamide.
aReference to yields of crude products only.
they are inexpensive, biodegradable, non-halogenated,
and low toxicity.
Hence, we explored the possibilities of exploiting the
versatile features of this green solvent PEG-600 [12]. In
this connection, here, we report a simple, efficient,
and green protocol for the synthesis of 4-thioquinolines
as antimicrobial agents from substituted 4-chloro-2-
methylquinolines and various heterocyclic thiols.
Figure 1. Quinoline anti-malarial drugs with diverse substitutions around
the quinoline ring.
Liquid polymers have been used as green reaction media
with unique properties such as thermal stability,
commercial availability, non-volatility, immiscibility with
organic solvents, and recyclability. Polyethylene glycol
(PEG) stands as one of the best in comparison with other
currently favored systems such as ionic liquids, super-
critical carbon dioxide, and micellar systems [11]. PEGs
systems were selected instead of other polymers because
RESULTS AND DISCUSSION
The starting materials were prepared according to the
literature method (Scheme 1) [13,14]. Anilines (1a–1d)
Scheme 1
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Green Synthesis of 4-Heteryl-Quinolines and Their Antibacterial Evaluations
Scheme 3
were condensed with ethyl acetoacetate 2 in ethanol to
obtain (3a–3d), which were subsequently cyclized to
2-methyl-4-quinolones (4a–4d) in diphenyl ether. The
latter on treatment with POCl3 at 100°C for 3–4 h resulted
in 4-chloro-2-methylquinolines (5a–5d), which were used
for substitution (SNAr) with heterocyclic thiols under green
conditions.
Compounds (5a–5d) on reaction with different
heterocyclic thiols such as 2-mercapto-benzimidazole
using PEG-600 as a solvent at 100°C for 30–40min
without additional usage of any base resulted in the
methoxy-2-methylquinolines (9a–9d). PEG-600 is a very
effective solvent that dissolves both the substrate and the
reagent, bringing them together and thereby providing
an effective means for chemical reaction to occur. Further,
PEG-600 is able to extract the proton from the -SH of
2-mercaptobenzimidazole and is able to retain it by
chelation through several lone pairs of electrons in its
oxygen-containing chain. This role of PEG-600 is
very similar to that of proton sponge (i.e., 1, 8
dimethylaminonaphthalene), which is a very strong base
because of its ability to extract proton from an acidic sub-
strate and then retain it in its claws by chelation through
lone pair of electrons on the two nitrogen atoms of proton
sponge. In an alternative approach, compounds (9a–9d)
were also prepared by refluxing (9a–9d) with 2-
mercaptobenzimidazole 6 in dimethylformamide (DMF)
using K2CO3 as a base and tetrabutylammonium bromide
(TBAB) for 1–2 h (Scheme 2), and the results were
summarized in Table 1.
formation
of
4-(1H-benzo[d]imidazol-2-ylthio)-6-
Table 2
Synthesis of compounds (10a–10d) from (5a–5d) and 7 at 100 °C.
Synthesis
number
Product
(R)
Solvent
Time
(min)
Yield
(%)a
Compound (5a–5d) on reaction with 2-methyl-6-thio-4-
pyrimidinones 7 heating with PEG-600 as a solvent at 100°C
for 30–50min resulted in the formation of 6-(6-methoxy-2-
methylquinolin-4-ylthio)-2-methylpyrimidin-4-ol (10a–10d).
In an alternative approach, compounds (10a–10d)
were also prepared by refluxing 2-methyl-6-thiolo-4-
pyrimidinones 7 with (5a–5d) in DMF using K2CO3 as a
base and TBAB for 1–2 h (Scheme 3). But the yields of
(10a–10d) were reasonably more in PEG-600 when
1
2
3
4
5
6
7
8
-OCH3
-CH3
-F
PEG-600
PEG-600
PEG-600
PEG-600
DMF
DMF
DMF
DMF
30
30
45
45
60
60
100
100
90
88
90
85
80
75
74
76
-Cl
-OCH3
-CH3
-F
-Cl
DMF, dimethylformamide.
aReference to yields of crude products only.
Scheme 4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. S. Bhupathi, M. Bandi, V. R. R. Ch., B. Rama Devi, and P. K. Dubey
Vol 000
Table 3
Synthesis of compounds (11a–11d) from (5a–5d) and 8 at 100°C.
Synthesis
number
Product
(R)
Solvent
Time
(min)
Yield
(%)a
1
2
3
4
5
6.
7
8
-OCH3
-CH3
-F
PEG-600
PEG-600
PEG-600
PEG-600
DMF
DMF
DMF
DMF
30
30
40
40
60
60
90
90
91
88
90
88
78
74
76
72
-Cl
-OCH3
-CH3
-F
-Cl
DMF, dimethylformamide.
aReference to yields of crude products only.
compared with DMF, and the results were summarized in
Table 2.
Similarly, compounds (5a–5d) on reaction with
2-thioquinazolinones 8 heating with PEG-600 at 100°C
for 30–40min resulted in the formation 2-(6-methoxy-2-
methylquinolin-4-ylthio) quinazolin-4(3H)-one (11a–11d).
In an alternative approach, compounds (9a–9d) were also
prepared by refluxing 2-thioquinazolinones 8 with (5a–5d)
in DMF using K2CO3 as a base and TBAB for 1–2h
(Scheme 4), and the reaction was smoothly carried out in
PEG-600 and gave high yields of products when compared
with DMF, and all the results were summarized in Table 3.
Antibacterial assay. The antibacterial activity of all the
synthesized quinolone compounds (9a–9d), (10a–10d) and
(11a–11d) was determined using the well diffusion method
(Amsterdam et al., 1996) against different Gram-positive
and Gram-negative microbial strains, which were
produced from the Microbial Culture Collection CSIR–
Indian Institute of Chemical Technology, Hyderabad,
India. The clinical strains were seeded on the surface of
the media Petri plates, containing Muller–Hinton agar
with 0.1mL of prepared microbial suspensions, which
individually contains 1.5 × 108 cfu mLÀ1. 6.0 mm wells
were prepared in media plates by using a cork borer. And
the synthesized compounds dissolved in 10 % DMSO at
a dose range of 250À0.97 μg were added to each well,
under sterile conditions in a laminar air flow chamber,
Standard antibiotic solutions of ciprofloxacin (bacterial
strains) and miconazole (Candida albicans) at a dose
range of 250À0.97 μg. The plates were incubated for
28h at 32°C, and the well containing the least
concentration showing the inhibition zone is considered
as the minimum inhibitory concentration. All experiments
were carried out in duplicates, and mean values are
represented. All the results were summarized in Table 4.
It is clear that all the compounds possess good activity
against both Gram-positive and Gram-negative bacteria,
especially compounds 9a, 9d, 10a, 10c, 11b, and 11d
that showed promising antibacterial activity without any
cytotoxicity against the tested cell lines.
Journal of Heterocyclic Chemistry
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Green Synthesis of 4-Heteryl-Quinolines and Their Antibacterial Evaluations
CONCLUSION was filtered and washed with water and dried to obtain pure
9, 10, and 11.
In summary, we have synthesized a new series of
substituted 4-heteryl-thioquinolines (9, 10, and 11) by
using PEG-600 as solvent without adding any base.
Compounds 9,10, and 11 could also be prepared by
another method by using DMF and K2CO3/TBAB. But
when compared in both methods, PEG-600 gave reasonably
high yield and reaction time was also very less. This method
shows simplicity, avoiding usage of base and phase transfer
catalyst. All the synthesized compounds were evaluated for
their biological activity; compounds 9a, 9d, 10a, 10c, 11b,
and 11d showed good activity against Gram-positive and
Gram-negative bacteria.
4-((1H-benzo[d]imidazol-2-yl)thio)-6-methoxy-2-methylquinoline
(9a). IR (KBr): 3461–3250cmÀ1 (broad, medium, -NH);
1H-NMR: δ 2.3 (s, 3H, -CH3), 3.7 (s, 3H, -OCH3), δ 6.3–
8.4 (m, 8H, Ar-H), 10.2 (s, 1H, -NH, D2O exchangeable).
13C NMR (DMSO-d6, 100MHz): 26.3, 40.4, 121.1, 122.4,
123.1, 123.3, 124.5, 132.1, 132.5, 132.8, 132.9, 141.1,
145.4, 147.5, 147.8, 148.2, 149.5, 160.3. ms: m/z= 337
(M+. +1). Anal. Calcd for C19H18N3OS (336.43): C, 67.83;
H, 5.39; N, 12.49; Found: C, 67.80; H, 5.32; N, 12.46.
4-((1H-benzo[d]imidazol-2-yl)thio)-2,6-dimethylquinoline (9b). IR
(KBr): 3462–3253 cmÀ1 (broad, medium, -NH); 1H-NMR:
δ 2.3 (s, 3H, -CH3), 2.5 (s, 3H, -CH3), δ 6.3–8.4 (m, 8H,
Ar-H), 10.2 (s, 1H, -NH, D2O exchangeable). 13C NMR
(DMSO-d6, 100 MHz): 26.3, 26.9, 121.3, 122.2, 123.2,
123.5, 125.7, 132.2, 132.4, 132.6, 132.9, 141.3, 145.6,
147.8, 147.9, 148.3, 149.7, 160.2. ms: m/z = 321
(M+. + 1). Anal. Calcd for C19H18N3S (320.43): C, 71.22;
H, 5.66; N, 13.11; Found: C, 71.24; H, 5.69; N, 13.10.
4-((1H-benzo[d]imidazol-2-yl)thio)-6-fluoro-2-methylquinoline
(9c). IR (KBr): 3461–3255 cmÀ1 (broad, medium, -NH);
1H-NMR: δ 2.4 (s, 3H, -CH3), δ 6.3–8.4 (m, 8H, Ar-H),
10.2 (s, 1H, -NH, D2O exchangeable). 13C NMR
(DMSO-d6, 100MHz): 26.5, 121.2, 122.4, 123.1, 123.6,
125.8, 132.3, 132.5, 132.7, 132.9, 141.2, 145.4, 147.6,
147.7, 148.4, 149.9, 160.1. ms: m/z=325 (M+. +1). Anal.
Calcd for C18H15FN3S (324.40): C, 66.64; H, 4.66; N,
12.95; Found: C, 66.62; H, 4.64; N, 12.93.
4-((1H-benzo[d]imidazol-2-yl)thio)-6-chloro-2-methylquinoline
(9d). IR (KBr): 3463–3252cmÀ1 (broad, medium, -NH);
1H-NMR: δ 2.2 (s, 3H, -CH3), δ 6.1–8.3 (m, 8H, Ar-H),
10.3 (s, 1H, -NH, D2O exchangeable). 13C NMR
(DMSO-d6, 100 MHz): 26.2, 121.3, 122.4, 123.2, 123.4,
125.6, 132.2, 132.4, 132.8, 132.9, 141.1, 145.3, 147.5,
147.8, 148.7, 149.6, 160.2. ms: m/z =342 (M+. +1). Anal.
Calcd for C18H15ClN3S (341.07): C, 63.43; H, 4.44; N,
12.33; Found: C, 63.41; H, 4.42; N, 12.30.
2-((6-methoxy-2-methylquinolin-4-yl)thio)-6-methylpyrimidin-
4-ol (10a). IR (KBr): 3570–3325cmÀ1 (broad, medium, -OH);
1H-NMR: δ 2.2 (s, 3H, -CH3), 2.4 (s, 3H, -CH3) 3.8
(s, 3H, -OCH3), δ 6.4–8.4 (m, 5H, Ar-H and 1H, -OH).
13C NMR (DMSO-d6, 100 MHz): 25.1, 26.2, 45.6,
122.1, 122.8, 123.3, 123.7, 132.4, 132.6, 132.8, 132.9,
136.4, 141.3, 145.8, 150.2, 155.0. ms: m/z = 314
(M+. + 1). Anal. Calcd for C16H15N3O2S (313.37): C,
61.32; H, 4.82; N, 13.41; Found: C, 61.33; H, 4.80; N,
13.43.
2-((2,6-dimethylquinolin-4-yl)thio)-6-methylpyrimidin-4-ol (10b). IR
(KBr): 3572–3324 cmÀ1 (broad, medium, -OH); 1H-NMR:
δ 2.3 (s, 3H, -CH3), 2.4 (s, 3H, -CH3) 2.6 (s, 3H, -CH3),
δ 6.6–8.5 (m, 5H, Ar-H and 1H, -OH). 13C NMR
(DMSO-d6, 100MHz): 25.4, 26.7, 27.5, 122.3, 122.9,
123.6, 123.8, 132.5, 132.7, 132.9, 132.9, 136.7, 141.4,
EXPERIMENTAL
General information. All the reagents used in this work
were obtained from commercial suppliers. Solvents were
freshly distilled before being used. Melting points were
determined using a Buchi melting point apparatus
(Sigma-Aldrich, India) and are uncorrected. The progress
of the reaction was monitored by thin-layer
chromatography (TLC) performed on silica gel
G
(Merck), and spots were exposed to iodine vapor and UV
light (Medical Equipment India, Delhi, India). IR spectra
were recorded by using KBr disc on a Perkin-Elmer 240c
analyzer (Perkin-Elmer, UK). 1H NMR spectra were
recorded on Brucker DPX-400 (Bruker, USA) at
400MHz (chemical shifts in δ, ppm) and mass spectra on
an Agilent LC-MS instrument (Agilent, Santa Clara, CA)
giving only M+ values in Q+ 1 mode.
Chemistry
General procedure for the synthesis of 4-thioquinolines (9, 10, 11)
Using PEG-600.
A mixture of (5a–5d) (1 mmol),
heterocyclic thiols 6, 7, and 8 (1 mmol) were added to
PEG-600 (10 mL) in a round bottom flask and is allowed
to heat at 100°C on a water bath for 30–40 min. The
reaction was monitored by checking TLC for the disap-
pearance of the starting material. At the end of this period,
the reaction mixture is poured into ice-cold water (25 mL);
the precipitated solid was filtered and washed with excess
water to obtain the crude 9, 10, and 11. The latter was
recrystallized from ethanol to obtain pure products.
Using DMF and K2CO3.
A mixture of (5a–5d)
(1 mmol), heterocyclic thiols 6, 7, and 8 (1 mmol) were
added to DMF (10 mL) followed by the addition of
K2CO3 (3 mmol) and catalytic amount of TBAB in a round
bottom flask and is allowed to heat at 100°C in an oil bath
for 1–2h. The reaction is monitored by checking TLC for
the disappearance of the starting material. At the end, the
reaction mixture was poured on ice-cold water (25 mL),
adjusted pH aq.HCl solution, and the precipitated solid
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. S. Bhupathi, M. Bandi, V. R. R. Ch., B. Rama Devi, and P. K. Dubey
Vol 000
145.9, 150.7, 155.3. ms: m/z = 298 (M+. + 1). Anal. Calcd
for C16H15N3OS (297.09): C, 64.62; H, 5.08; N, 14.13;
Found: C, 64.64; H, 5.04; N, 14.11.
(s, 1H, -NH, D2O exchangeable). 13C NMR (DMSO-d6,
100MHz): 25.2, 121.4, 122.4, 123.3, 125.1, 131.2, 131.3,
131.3, 132.4, 140.2, 146.1, 147.2, 160.3. ms: m/z=338
(M+. +1). Anal. Calcd for C18H12N3FOS (337.37): C,
64.08; H, 3.59; N, 12.46; Found: C, 64.06; H, 3.57; N, 12.44.
2-((6-chloro-2-methylquinolin-4-yl)thio)quinazolin-4(3H)-one
(11d). IR (KBr): 3465–3263cmÀ1 (broad, medium, -NH),
1693cmÀ1 (sharp, strong, -CO- of amide group); 1H-NMR:
δ 2.4 (s, 3H, -CH3), δ 6.4–8.1 (m, 8H, Ar-H), 10.2 (s, 1H,
-NH, D2O exchangeable). 13C NMR (DMSO-d6,
100MHz): 25.1, 122.6, 122.9, 123.5, 125.2, 131.3, 131.5,
131.6, 132.2, 140.4, 146.5, 147.0, 160.4. ms: m/z=354
(M+. +1). Anal. Calcd for C18H12N3ClOS (353.83): C,
61.10; H, 3.42; N, 11.88; Found: C, 61.12; H, 3.40; N,
11.86.
2-((6-fluoro-2-methylquinolin-4-yl)thio)-6-methylpyrimidin-
4-ol (10c). IR (KBr): 3574–3325 cmÀ1 (broad, medium, -OH);
1H-NMR: δ 2.3 (s, 3H, -CH3), 2.4 (s, 3H, -CH3), δ 6.6–8.5
(m, 5H, Ar-H and 1H, -OH). 13C NMR (DMSO-d6,
100MHz): 25.2, 26.5, 122.2, 122.6, 123.6, 123.9, 132.6,
132.6, 132.8, 132.9, 136.4, 141.3, 145.9, 150.4, 155.1.
ms: m/z =302 (M+. + 1). Anal. Calcd for C15H12FN3OS
(297.09): C, 59.79; H, 4.01; N, 13.94; Found: C, 59.77;
H, 4.03; N, 13.92.
2-((6-chloro-2-methylquinolin-4-yl)thio)-6-methylpyrimidin-
4-ol (10d). IR (KBr): 3573–3326 cmÀ1 (broad, medium, -OH);
1H-NMR: δ 2.1 (s, 3H, -CH3), 2.2 (s, 3H, -CH3), δ 6.4–8.3
(m, 5H, Ar-H and 1H, -OH). 13C NMR (DMSO-d6,
100MHz): 25.1, 26.3, 122.2, 122.5, 123.6, 123.7, 132.5,
132.6, 132.7, 132.8, 136.2, 141.4, 145.8, 150.3, 155.3.
ms: m/z =318 (M+. + 1). Anal. Calcd for C15H12FN3OS
(297.09): C, 56.69; H, 3.81; N, 13.22; Found: C, 56.67;
H, 3.83; N, 13.20.
Acknowledgments. The authors are indebted to the authorities of
Jawaharlal Nehru Technological University Hyderabad for
providing laboratory facilities.
REFERENCES AND NOTES
2-((6-methoxy-2-methylquinolin-4-yl)thio)quinazolin-4(3H)-one
(11a). IR (KBr): 3462–3252cmÀ1 (broad, medium, -NH),
[1] Muentener, P.; Schlagenhauf, P.; Steffen, R. Bull World
Health Organ 1999, 77, 560.
1
1693 cmÀ1 (sharp, strong, -CO- of amide group); H-NMR:
δ 2.2 (s, 3H, -CH3), 3.8 (s, 3H, -OCH3), δ 6.4–8.2 (m, 8H,
Ar-H), 10.1 (s, 1H, -NH, D2O exchangeable). 13C NMR
(DMSO-d6, 100 MHz): 26.5, 40.3, 121.2, 122.4, 123.5,
123.1, 132.2, 132.6, 132.9, 132.9, 141.0, 145.2, 147.5,
160.3. ms: m/z= 350 (M+. +1). Anal. Calcd for
C19H15N3O2S (349.41): C, 65.31; H, 4.33; N, 12.03;
Found: C, 65.33; H, 4.30; N, 12.01.
2-((2,6-dimethylquinolin-4-yl)thio)quinazolin-4(3H)-one (11b). IR
(KBr): 3463–3272 cmÀ1 (broad, medium, -NH),
1696 cmÀ1 (sharp, strong, -CO- of amide group);
1H-NMR: δ 2.3 (s, 3H, -CH3), 2.5 (s, 3H, -CH3), δ 6.2–8.6
(m, 8H, Ar-H), 10.1 (s, 1H, -NH, D2O exchangeable). 13C
NMR (DMSO-d6, 100MHz): 24.1, 26.5, 120.2, 123.1,
123.4, 124.0, 132.3, 132.4, 132.4, 132.6, 141.3, 145.1,
147.1, 160.2. ms: m/z=334 (M+. +1). Anal. Calcd for
C19H15N3OS (333.41): C, 68.45; H, 4.53; N, 12.60;
Found: C, 68.43; H, 4.51; N, 12.62.
[2] Rieckmann, K. H.; Trenholme, G. M.; Williams, R. L.;
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2-((6-fluoro-2-methylquinolin-4-yl)thio)quinazolin-4(3H)-one
(11c). IR (KBr): 3464–3273cmÀ1 (broad, medium, -NH),
1690cmÀ1 (sharp, strong, -CO- of amide group); 1H-NMR:
δ 2.3 (s, 3H, -CH3), δ 6.3–8.2 (m, 8H, Ar-H), 10.3
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet