Synthesis, characterization, and antimicrobial studies of some quinolines containing 1,3-thiazines

Article abstract of DOI:10.1080/10426500802561450

6/8-Substituted-2-chloroquinoline-3-carboxylic acids, upon reaction with 3-(p-substituted aryl)-4H-5-mercapto-1,2,4-triazoles in the presence of sodium acetate and an acetic anhydride medium, afforded a novel series of 2-(p-substituted aryl)-s-triazolo[5,

Full text of DOI:10.1080/10426500802561450

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Synthesis, Characterization,
and Antimicrobial Studies of
Some Quinolines Containing
1,3-Thiazines
Janardhana Nayak a b , K. S. Girisha a , Balakrishna
Kalluraya a & Shalini Shenoy c
a Department of Studies in Chemistry , Mangalore
University , Karnataka, India
b Department of Chemistry , NMAM Institute of
Technology , Karnataka, India
c Department of Microbiology , Kasturba Medical
College , Mangalore, India
Published online: 21 Sep 2009.
To cite this article: Janardhana Nayak , K. S. Girisha , Balakrishna Kalluraya &
Shalini Shenoy (2009) Synthesis, Characterization, and Antimicrobial Studies of Some
Quinolines Containing 1,3-Thiazines, Phosphorus, Sulfur, and Silicon and the Related
Elements, 184:10, 2697-2703, DOI: 10.1080/10426500802561450
To link to this article: http://dx.doi.org/10.1080/10426500802561450
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Phosphorus, Sulfur, and Silicon, 184:2697–2703, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802561450
Synthesis, Characterization, and Antimicrobial Studies
of Some Quinolines Containing 1,3-Thiazines
Janardhana Nayak,1,2 K. S. Girisha,1 Balakrishna
Kalluraya,1 and Shalini Shenoy3
1Department of Studies in Chemistry, Mangalore University,
Karnataka, India
2 Department of Chemistry, NMAM Institute of Technology, Karnataka,
India
3Department of Microbiology, Kasturba Medical College, Mangalore,
India
6/8-Substituted-2-chloroquinoline-3-carboxylic acids, upon reaction with 3-(p-
substituted aryl)-4H-5-mercapto-1,2,4-triazoles in the presence of sodium acetate
and an acetic anhydride medium, afforded a novel series of 2-(p-substituted aryl)-s-
triazolo[5,1-b]-6/8-substituted quinolino [1,3] thiazin-9(H)-ones. The structures of
the new compounds were elucidated by IR, 1H NMR, and mass spectral studies. All
the newly synthesized compounds have been screened for their antibacterial and
antifungal activities. Most of them showed significant activity comparable with
that of the standards Furacin and Flucanazol.
Keywords Antibacterial activity; antifungal activity; mercapto-s-triazoles; quinoline
carboxylic acids; 1,3-thiazine
INTRODUCTION
Thiazines are found to show a number of biological activities such as an-
ticancer,1 antileukemic,2 and antibacterial3 properties. Some thiazines
also show antihypertensive4 activity. Quinolines are the traditional an-
timalarial drugs.5 Many of them also exhibit potent anti-inflammatory
and antipyretic action.6,7 Various 1,2,4-triazole derivatives are found to
associated with diverse pharmacological activities such as antiviral,8
antitubercular,9 antibacterial,10 and antifungal10 properties. Quinoline
Received 14 May 2008; accepted 16 October 2008.
The authors are thankful to the Head, SAIF, RSIC, Punjab University; Head, SAIF,
CDRI, Lucknow; and Raghunadana K. Bhakta for spectral and analytical data.
Address correspondence to Balakrishna Kalluraya, Department of Studies in Chem-
istry, Mangalore University, Mangalagangothri-574 199, Karnataka, India. E-mail:
bkalluraya@gmail.com
2697

2698
J. Nayak et al.
SCHEME 1
moiety flanked with a thiazole ring has been found to possess an-
tibacterial activity.11 Prompted by these observations and also in
continuation of our research work12,13 on quinoline-containing biolog-
ically active compounds, we studied the reactions of 3-substituted-
4H-5-mercapto-1,2,4-triazoles with 6/8-substituted-2-chloroquinoline-
3-carboxylic acid. Such reactions resulted in the formation of a novel
series of 2-aryl-s-triazolo[5,1-b]-6/8-substituted quinolino[1,3]thiazine-
9(H)-ones 3.
The synthetic route followed for obtaining the title compounds
is outlined in Scheme 1. Thus 3-substituted aryl-4H-5-mercapto-
1,2,4-triazoles 1 on reaction with 6/8-substituted-2-choroquinoline-3-
carboxylic acid 2 in acetic anhydride in the presence of sodium ac-
etate afforded a series of the title compounds 2-(p-substituted aryl)-s-
triazolo[5,1-b]-6/8-substituted quinolino[1, 3] thiazine-9H-ones 3. The
1,2,4-triazole 1 and quinolino carboxylic acids 2 were synthesized ac-
cording to the procedures in the literature.14,15
RESULTS AND DISCUSSION
The structure of newly synthesized thiazines 3 were established on
the basis of their analytical and spectral data. The IR spectra of com-
pounds 3 showed absorption bands in the region 1700–1720 cm−1
,

Quinolines Containing 1,3-Thiazines
2699
characteristic of carbonyl stretching, and 1622–1640 cm−1 character-
1
istic of carbon nitrogen stretching. In a typical example, the H NMR
spectra of 3b showed a singlet at δ 2.62, integrating for three pro-
tons of the methyl group. The quinoline 4-H proton appeared as a
singlet at δ 9.43, integrating for one proton, while the signals due
to the quinoline 8-H appeared as a doublet at δ 8.01, integrating
for one proton. The signals due to the remaining quinoline protons
and aromatic protons merged together and appeared as a multiplet
in the region of δ 7.42–8.32, integrating for 7 protons. Similarly in
the mass spectrum of compound 3b, the molecular ion peak was ob-
served at m/z, 344 (M.F. C19H12N4OS) in agreement with the proposed
structure.
Characterization data of the new compounds are given in Table I, and
the spectral data of other compounds are presented in the Experimental
section.
Antibacterial and Antifungal Activities
The antibacterial and antifungal activity of the newly synthesized com-
pounds was assessed by minimum inhibitory concentration (MIC) by
the serial dilution method.16 The antibacterial activity of the newly
synthesized thiazines 3 were carried out against four different microor-
ganisms, namely Staphylococcus aureus, Bacillus subtilis, Escherichia
coli, and Pseudomonas aeruginosa. Furacin was used as the standard.
Antifungal activity was carried out on the fungus Candida albicans.
Flucanazol was employed as the standard.
Among the compounds tested, most of them showed significant an-
tibacterial and antifungal activity comparable with that of the stan-
dard. Particularly compound 3f carrying p-hydroxyphenyl group at
position 3 of the triazole moiety and methyl group at position 6 of
quinoline moiety showed highest activity against P. aeruginosa. Also
compounds 3i, 3j, 3k, and 3l carrying p-chlorophenyl group at postion
3 of the triazole moiety showed significant antibacterial activities such
as 3i against P. aeruginosa, 3j against S. aureus, 3k against E. coli and
P. aeruginosa, and 3l against S. aureus. Similarly, the compounds 3d,
3i, and 3l showed significant antifungal activity against C. albicans
(Table II).
EXPERIMENTAL
Melting points were determined by capillary method and are un-
corrected. IR spectra were recorded on a Nicolet Avatar 330 FT IR

2700

Quinolines Containing 1,3-Thiazines
2701
TABLE II Antibacterial and Antifungal Activity Data of Compounds
3a–l
Antifungal
activity(MIC in
Antibacterial activity(MIC in µg/mL)
µg/mL)
Compd
E. coli S. aureus P. aeruginosa B. subtilis
C. Albicans
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
6.25
6.25
6.25
6.25
6.25
12.5
6.25
12.5
6.25
6.25
6.25
6.25
6.25
6.25
6.25
6.25
3.125
6.25
6.25
3.125
6.25
3.125
6.25
6.25
—
12.5
6.25
6.25
6.25
6.25
6.25
6.25
3.125
6.25
6.25
6.25
6.25
3.125
6.25
6.25
3.125
—
12.5
25
6.25
6.25
25
6.25
12.5
6.25
6.25
—
12.5
6.25
6.25
6.25
6.25
3.125
6.25
6.25
—
12.5
6.25
6.25
3.125
6.25
3.125
6.25
—
Furacin
Flucanazol
DMF (Control)
6.25
—
—
—
—
—
Index for biological activity: disc size: 5.5 mm; duration: 24 h; E. coli: Escherichia coli;
S. aureus: Staphylloococcus aureus; P. aeruginosa: Pseudomonas aeruginosa; B. subtilis:
Bacillus subtilis; C. albicans: Candida albicans.
1
spectrophotometer (νmax. in cm−1) using KBr pellets. H NMR spectra
were recorded on a Bruker Avance II 400 NMR spectrometer using
DMSO-d6 or CDCl3 as solvent (chemical shift in δ, ppm) and TMS as
internal standard. Mass spectra were recorded on a JEOL-SX 102/DA-
6000 mass spectrometer using Argon/Xenon (6kV, 10 mA) as the FAB
gas operating at 10 KV. The purity of compounds were checked by
TLC.
General Procedure for the Preparation of 2-(p-Substituted
aryl)-s-triazolo[5,1-b]-6/8-substituted Quinolino[1,3]
thiazin-9(H)-ones 3
A mixture of 3-substituted aryl-4H-5-mercpto-1,2,4-triazole 1 (0.01
mol), 6/8-substituted-2-chloroquinoline-3-carboxylic acid 2 (1.64 g, 0.01
mol), and fused sodium acetate (0.02 mol) in acetic anhydride (20 mL)
was refluxed on an oil bath (120–125 ◦C) for 6 h. It was allowed to cool
to room temperature and diluted with water. The solid, thus separated,

2702
J. Nayak et al.
was filtered, washed with water, and recrystallized from dimethylfor-
mamide.
Spectral data for other compounds are presented here: 3a: 1H
NMR (CDCl3+DMSO-d6): δ, 9.41 (s,1H, quinoline-4H), 7.12–8.51 (m,
9H, Ar-H & Quinoline protons). Mass: m/z, 331(M++1 Peak) (M.F.:
1
C18H10N4SO). 3c: H NMR (DMSO-d6): δ, 2.68 (s, 3H, CH3), 9.38
(s,1H, quinoline-4H), 7.28–8.46 (m, 8H, Ar-H & quinoline pro-
1
tons). Mass: m/z, 344 (M.F.: C19H12N4SO). 3d: H NMR (CDCl3 +
DMSO-d6): δ, 3.91 (s, 3H, OCH3), 9.35 (s, 1H, quinoline-4H), 7.31–8.22
(m, 8H, Ar-H & quinoline protons). Mass: m/z, 361 (M++1 peak)
1
(M.F.: C19H12N4SO2). 3e: H NMR (CDCl3 + DMSO-d6): δ, 9.51, (s,
1H, OH), 9.38 (s, 1H, quinoline-4H), 6.81 (d, 2H, ortho protons of
p-hydroxyphenyl), 7.91 (d, 2H, meta protons of p-hydroxyphenyl),
7.48–8.21 (m, 4H, quinoline-5H, 6H, 7H & 8H). Mass: m/z, 346 (M.F.:
C18H10N4SO2). 3f: 1H NMR (DMSO-d6): δ, 2.64, (s, 3H,CH3), 9.46,
(s, 1H, OH), 9.36 (s, 1H, quinoline-4H), 6.76 (d, 2H, ortho protons
of p-hydroxyphenyl), 8.01 (d, 2H, meta protons of p-hydroxyphenyl),
7.41–8.21 (m, 3H, quinoline-5H, 7H & 8H).Mass: m/z, 360(M++1Peak)
1
(M.F.: C18H10N4SO2). 3g: H NMR (DMSO-d6): δ, 2.80 (s, 3H, CH3),
9.46 (s, 1H, OH), 9.44 (s, 1H, quinoline-4H), 6.92 (d, 2H, ortho protons
of p-hydroxyphenyl), 8.10 (d, 2H, meta protons of p-hydroxyphenyl),
1
7.57–8.32 (m, 3H, quinoline-5H, 6H and 7H). 3h: H NMR (CDCl3
+ DMSO-d6): δ, 3.82, (s, 3H, OCH3), 9.48 (s, 1H, OH), 9.36 (s, 1H,
Quinoline-4H), 6.84 (d, 2H, ortho protons of p-hydroxyphenyl), 8.19 (d,
2H, meta protons of p-hydroxyphenyl), 7.38–8.191 (m, 3H, quinoline-
5H, 7H & 8H). Mass: m/z, 376 (M.F.: C19H12N4SO3). 3i: 1H NMR (CDCl3
+ DMSO-d6): δ, 9.34 (s, 1H, Quinoline-4H), 6.81 (d, 2H, ortho pro-
tons of p-chloroyphenyl), 7.81 (d, 2H, meta protons of p-chlorophenyl),
7.43–8.11 (m, 4H, quinoline-5H,6H, 7H & 8H). Mass: m/z, 365/367
(M++1&M++3 peak) (M.F.: C19H12N4SO3). 3j: 1H NMR (CDCl3
+
DMSO-d6): δ, 2.38, (s, 3H, CH3), 9.28 (s, 1H, quinoline-4H), 7.31 (d,
2H, ortho protons of p-chloroyphenyl), 7.84 (d, 2H, meta protons of
p-chlorophenyl), 7.81–8.19 (m, 3H, Quinoline-5H, 7H & 8H). Mass:
1
m/z, 378/380 (M.F.: C19H11ClN4SO). 3k: H NMR (CDCl3 + DMSO-
d6): δ, 2.39, (s, 3H, CH3), 9.18 (s, 1H, quinoline-4H), 7.29 (d, 2H,
ortho protons of p-chloroyphenyl), 7.91 (d, 2H, meta protons of p-
chlorophenyl), 7.43–8.08 (m, 3H, quinoline-5H, 6H & 7H). Mass: m/z,
1
378/380 (M.F.: C19H11ClN4SO). 3l: H NMR (CDCl3 + DMSO-d6): δ,
3.81, (s, 3H, OCH3), 9.21 (s, 1H, quinoline-4H), 7.36 (d, 2H, ortho pro-
tons of p-chloroyphenyl), 8.01 (d, 2H, meta protons of p-chlorophenyl),
7.43–8.18 (m, 3H, Quinoline-5H, 7H & 8H). Mass: m/z, 394/396 (M.F.:
C19H11ClN4SO2).

Quinolines Containing 1,3-Thiazines
2703
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