A facile synthesis of novel 9-methyl[1,2,3]selenadiazoles[4,5-b]quinoline and 9-methyl[1,2,3]thiadiazole[4,5-b]quinoline as a new class of antimicrobial agents

Article abstract of DOI:10.1080/10426500500267590

2-chloro-4-methyl quinoline 2 on condensation with semicarbazide hydrochloride gave its semicarbazone. This on reaction with SeO₂ and SOCl₂ yielded a new class of novel selenadiazoles 4 and thiadiazoles 5, respectively. The structure of all the compounds were elucidated on the basis of elemental analysis, IR, ¹H NMR, and the mass spectral data. Some derivatives of 9-methyl[1,2,3]selenadiazole[4,5-b] quinoline and 9-methyl[1,2,3]thiadiazole [4,5-b]quinoline have been screened for antimicrobial activities. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500500267590

This article was downloaded by: [University Of South Australia Library]
On: 11 August 2014, At: 02:24
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
A Facile Synthesis of
Novel 9-Methyl[1, 2,
3]Selenadiazoles[4,
5-b]Quinoline and 9-
Methyl[1, 2, 3]Thiadiazole[4,
5-b]Quinoline as a New Class of
Antimicrobial Agents
Halehatty S. Bhojya Naik a , Machenahalli S.
Ramesha a , Boovanahalli V. Swetha a & Thopenahalli
R. Roopa a
a Department of Studies and Research in Industrial
Chemistry , Kuvempu University , Shankarghatta,
Shimoga, India
Published online: 01 Feb 2007.
To cite this article: Halehatty S. Bhojya Naik , Machenahalli S. Ramesha ,
Boovanahalli V. Swetha & Thopenahalli R. Roopa (2006) A Facile Synthesis of Novel
9-Methyl[1, 2, 3]Selenadiazoles[4, 5-b]Quinoline and 9-Methyl[1, 2, 3]Thiadiazole[4,
5-b]Quinoline as a New Class of Antimicrobial Agents, Phosphorus, Sulfur, and Silicon
and the Related Elements, 181:3, 533-541, DOI: 10.1080/10426500500267590
To link to this article: http://dx.doi.org/10.1080/10426500500267590
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no

representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 181:533–541, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500267590
A Facile Synthesis of Novel
9-Methyl[1,2,3]Selenadiazoles[4,5-b]Quinoline and
9-Methyl[1,2,3]Thiadiazole[4,5-b]Quinoline as a New
Class of Antimicrobial Agents
Halehatty S. Bhojya Naik
Machenahalli S. Ramesha
Boovanahalli V. Swetha
Thopenahalli R. Roopa
Department of Studies and Research in Industrial Chemistry, Kuvempu
University, Shankarghatta, Shimoga, India
2-chloro-4-methyl quinoline 2 on condensation with semicarbazide hydrochloride
gave its semicarbazone. This on reaction with SeO and SOCl yielded a new class
2
2
of novel selenadiazoles 4 and thiadiazoles 5, respectively. The structure of all the
1
compounds were elucidated on the basis of elemental analysis, IR, H NMR, and the
mass spectral data. Some derivatives of 9-methyl[1,2,3]selenadiazole[4,5-b] quino-
line and 9-methyl[1,2,3]thiadiazole [4,5-b]quinoline have been screened for antimi-
crobial activities.
Keywords 2-Chloro-4-methyl quinoline; microbial activities; semicarbazones; selenadi-
azoles; thiadiazoles
INTRODUCTION
The quinoline ring has been the subject of continued interest as sev-
eral derivatives of this exhibited a wide range of biological activities
including antitumour,1 hypoglycemic properties,2 antihistamine,3 and
anticarcinorgic,4 activities etc. They have been used to synthesize var-
ious fused heterocyclic ring systems and they show a wide range of
pharmacological activities.5−8 Further, it is well known that a number
of heterocyclic compounds containing N and S exhibit a wide variety
Received April 14, 2005; accepted May 16, 2005.
One of the authors, M. S. Ramesha, thanks Kuvempu University for providing a re-
search fellowship.
Address correspondence to Halehatty S. Bhojya Naik, Kuvempu University, Depart-
ment of Studies and Research in Industrial Chemistry, Shankarghatta, 577 451, Shimoga,
India. E-mail: hsb-naik@rediff.com
533

534
H. S. B. Naik et al.
of biological activities.9−12 Even though sulphur and selenium are con-
sidered to be isosteric as defined by Langmiur13 and Erlenmeyer,14 the
reports about selenium-containing heterocyclics are relatively few.5−17
However, the medicinal application of isosterism has been reviewed by
Klayman and Gunther.18 Recently, the synthesis of some fused selena-
diazoles and thiodiazoles has been reported.19−25 Therefore, in contin-
uation of our work on the synthesis of quinoline derivatives23,24 and in
view of the biological importance of selenium and sulphur, here we wish
to report a facile synthesis of quinoline derivatives of [1,2,3]selenadia-
zoles and [1,2,3]thiadiazoles.
RESULTS AND DISCUSSION
2-hydroxy-4-methyl quinolines la–d was prepared by using microwave
irradiation.24 It reacts with phosphorus oxychloride and affords the cor-
responding 2-chloro-4-methyl quinoline 2a–d (Scheme 1). The spectral
data of the compounds la–d and 2a–d are in agreement with the the-
oretical data. The IR (cm−1) spectrum of all the compounds exhibited
absorption bands in the region of 1432–1440, 1320–1325, and 2010–
2015 for (N C), (C C), and (C H), respectively.
SCHEME 1
The microwave irradiation of compound 2a–d with semicarbazide
hydrochloride in sodium ethoxide leads to the formation of substituted
semicarbazone 3a–d. The absence of chlorine was confirmed by Beil-
stein’s test. The IR (cm−1) spectrum of 3a shows the bands for (C N) at
1432, (NHCO, CONH2) at 34460, 3246, (N N) at 1585, and (CONH2)
at 1721. Some important spectral data are presented in Table I.

9-Methyl[1,2,3]Selenadiazoles[4,5-b]Quinoline
535
TABLE I Some Important Spectral Data of Synthesized Compounds
Compound
no.
IR (cm−1
)
1H NMR (δ ppm)
2a–d
3a
1432–1440 (C N, 3449 (N H)
1432 (C N), 3446–3246
(NHCO CONH2), 1585 (N N),
1721 (CONH2)
8.4 (s, 9H), 2.31 (3H, CH3)
2.31(s, 3H), 9.2 (s, 9H),
(N CH), 2.31 (3H, CH3)
4a
5a
685 (C Se N), 1487 (N N),
1430 (C N)
7.4 (s, 7H), 2.5 (s, 3H, CH3)
7.2 (m, 7H), 2.6 (s, 3H, CH3)
700 (C
S N), 1485 (N N),
1434 (C N)
The formation of 9-methyl[1,2,3] selenadiazole[4,5-b] quinoline 4a–d
was assumed to proceed via the addition of selenium dioxide, followed
by the intermolecular cyclization (Scheme 2). Elemental analyses and
spectral data confirmed the structures of 4a–d. The IR (cm−1) spectra
SCHEME 2

536
H. S. B. Naik et al.
of the molecule 4a shows absorption bands at 685, 1487, and 1430,
which are assigned for (C Se N), (N N), and (C N), respectively. The
’HNMR spectra of the molecule 4a showed signals at δ = 7.4 (s, 7H) and
δ = 2.5 (s, 3H, CH3). The mass spectrum of the compound 4a was found
to be 248 (M+).
On the other hand, 3a–d on treatment with thionylchloride
at −10–0◦C yielded 9-methyl[1,2,3]thiadiazole[4,5-b]quinoline 5a–d
(Scheme 2). The analytical and spectral data were consistent with the
assigned structure of the compounds 5a–d. The IR (cm−1) spectra of 5b
revealed absorption bands at 700, 1485, and 1434 for (C S N), (N N),
1
and (C N), respectively. The HNMR spectrum in DMSO-d6 showed
signals at δ = 7.9 (m, 7H) and δ = 2.6 (s, 3H,CH3). The mass spectra of
the compound 5a were found to be 201 (M+).
EXPERIMENTAL
Melting points were determined in open capillaries and were uncor-
rected. The IR spectra were measured in KBr pellets on Shimadzu FT-
IR 200-spectrophotometer. ’H NMR spectra were recorded in DMSO-d6
on 200 MHz on a Perkin Elmer instrument and chemical shifts are ex-
pressed in δ units using TMS as an internal reference. Mass spectra
were recorded on a Jeol JMS-D 300 instrument at 70 eV. Elemental
analyses were carried out at the Department of Chemistry, University
of Mysore, Mysore, India. The characteristic data of synthesised com-
pounds are given in Table II some and important spectral data are
presented in Table I
Synthesis of 2-Hydroxyl-4-Methyl Quinoline 1(a–d)
A mixture of distilled aniline (Ig, 0.01 mol) and ethylacetoacetate (1.3 g,
0.013 mol) was irradiated in microwave oven for 4 min, and 2 to 4 drops
of H2SO4 were added and again irradiated for 5 min. The solid product
obtained was filtered and recrystalized from ethanol to give 1a. The
same procedure was adopted for the synthesis of Ib–d.
General Procedure for the Synthesis of 2-Chloro-4-Methyl
Quinoline 2(a–d)
A mixture of 1a–d (1.6 g, 0.01 mol) and POCl3 was mixed and refluxed
separately for 10 h on a water bath. The product that produced 2a–d
was isolated, filtered, and recrystalized from a suitable solvent (Tables I
and II).

9-Methyl[1,2,3]Selenadiazoles[4,5-b]Quinoline
537
TABLE II Analytical Data of the Synthesized Compounds
Elemental analysis
calcd./found [%]
Yield
(%)
colour
Molecular
formula
[mol. wt.]
M.P
[◦C]
Compound no.
C%
H%
N%
2a
82
66
220
208
177
168
170
173
210
195
198
203
C10H8NCl
177.5
C11H12N4O
215
67.58
67.48
61.37
61.30
68.70
68.54
30.65
30.58
43.00
42.93
47.32
46.91
58.44
58.40
42.28
42.01
48.66
48.49
56.05
55.02
4.51
4.49
5.48
5.46
2.15
2.08
1.50
1.41
2.01
2.00
3.23
3.20
3.03
3.00
2.01
1.94
2.36
2.33
4.25
4.23
7.79
7.75
3a
4a
4b
4c
4d
5a
5b
5c
5d
26.04
26.00
13.36
13.01
10.67
10.28
20.10
20.00
15.06
15.05
20.5
20.00
14.68
14.41
22.68
22.42
17.83
16.92
Pale yellow
88
Brown
86
Deep brown
82
Yellow
85
Pale yellow
73
Dark brown
70
Yellow
76
Yellow
74
C
10H7N3Se
310
C
10H6N3SeBr
388.9
C
10H4NO2Se
277.9
C
11H9N3OSe
278.9
C10H7N3S
204.5
C
10H6N3SBr
283.4
C
10H6N4SO2
246.06
C11H10N3OS
235.5
Black
General Synthesis of 2-Chloro-4-Methyl Quinoline 3(a–d)
A mixture of 2a–d (0.18 g, 0.001 mol) and semicarbazide hydrochloride
(0.11 g, 0.001 mol) in sodium ethoxide was irradiated in microwave oven
for about 30 min. The obtained solid product was isolated, filtered, and
recrystalized from a suitable solvent to give 3a. The same procedure was
used for the preparation of 3b–d. The elemental analysis and spectral
data are presented in Tables I and II.
Synthesis of 9-Methyl[1,2,3]Selenadiazoles (4a)
The compound 3a (1.075 g, 0.005 mol) was dissolved in 15–20 mL of
acetic acid and kept in an oil bath at 60◦C with constant mechanical
stirring. Then SeO2 (0.05 g, 0.005 mol) was added portionwise with
stirring, maintaining the temperature 60◦C until the entire SeO2 got
transferred. Then the reaction mixture was stirred for about 1 h, main-
taining the same temperature. After, the mixture was cooled to f. t. and
poured on crushed ice. The precipitate 4a thus obtained was filtered,
dried, and recrystalized (Tables I and II).

538
H. S. B. Naik et al.
Synthesis of 11-Bromo-9-Methyl[1,2,3]Selenadiazoles (4b)
A solution of 3b (1.470 g, 0.005 mol) and selenium dioxide (0.5 g,
0.005 mol) was added portionwise to an acetic acid medium with con-
stant stirring, maintaining the temperature at 60◦C. It was refluxed for
10 h until a clear solution was obtained. The completion of the reaction
was monitored by TLC. The solution mixture was cooled and poured
into crushed ice with stirring. The bromo compound 4b thus formed
was collected and crystallized from chloroform.
Synthesis of 11-Nitro 4-Methyl [1,2,3]Selenadiazoles
Quinoline (4c)
A mixture of compound 3c (1.470 g, 0.005 mol) and selenium dioxide
(0.5 g, 0.005 mol) was added portionwise to an acetic acid medium with
stirring and refluxed for 9 h. Again the reaction mixture was placed on
a water bath for 5 min, cooled, and poured into crashed ice with stirring.
4c was collected and recrystalized from ethanol.
Synthesis of 11-Methoxy 9-Methyl [1,2,3]Selenadiazoles
Quinoline (4d)
Compound 3d (1.225 g, 0.005 mol) and selenium dioxide (0.5 g,
0.005 mol) were added to a round-bottom flask in an acetic acid medium.
The reaction mixture was refluxed for 7 h, and the mixture was kept
on a water bath for 5 min and poured into crushed ice. The comple-
tion of the reaction was confirmed by TLC. The resulting solid 4d was
collected, washed, and recrystalized from ethanol.
Synthesis of 9-Methyl[1,2,3]Thiadiazole Quinoline (5a)
Redistilled thionylchloride (4 mL, 0.05 mol) was added to a clean dry
250-mL round-bottom flask kept in a salt ice bath and the tempera-
ture was allowed to drop to −10◦C. The compound 3a (1.075 g 0.005
mol) was added to it with constant magnetic stirring, maintaining the
temperature below 0◦C. After the complete addition, the temperature
was allowed to rise to r.t. and 30 mL of dichloromethane was added.
The mixture was stirred for a further 2 h. Excess thionylchloride was
removed using a saturated NaHCO3 solution. The product 5a was iso-
lated using an extractive isolation technique, then recrystalized (Tables
as I and II).

9-Methyl[1,2,3]Selenadiazoles[4,5-b]Quinoline
539
Synthesis of 11-Bromo-9-Methyl[1,2,3]Thiadiazole
Quinoline (5b)
The compound 5b was synthesized by using the same procedure as de-
scribed for 5a. The isolated compound 5b was washed and recrystalized
in ethanol.
Synthesis of 11-Nitro-9-Methyl[1,2,3]Thiadiazole
Quinoline (5c)
The compound 5c was synthesized by varying the reaction temperature
using the procedure used for the preparation of 5a. The compound 5c
was isolated, washed, and recrystalized in ethanol.
Synthesis of 11-Methoxy-9-Methyl[1,2,3]Thiadiazole
Quinoline (5d)
The compound 5d was synthesized by using the same procedure as de-
scribed for 5a. The solid compound 5d was isolated by using extractive
isolation technique and was washed and recrystalized in ethanol.
BIOLOGICAL SCREENING
The antimicrobial activity of the newly synthesized compounds
was screened with in vitro for Euro strains of bacteria Staphy-
lococcus aureus and Escherichia coli using the cup plate method.
The antimicrobial activity was carried out against 24-hour-old cul-
tures of two bacteria. The compounds were tested at a concentra-
tion (0.001 mol/mL) in dimethylformamide against both organisms.
Ciprofloxacines (0.001 mol/mL) were used as a standard for comparison
of antimicrobial activities. The plates were inoculated with a 24-hour-
old culture of bacteria. The zone of inhibition was compared with the
standard drug after 24 hours of inoculation at 37◦C for antimicrobial
activity. The results are presented in Table III. The results reveal that
the compound 4b shows higher activity with respect to Staphylococcus
aureus and Escherichia coli compared to other compounds. This may
be due to the compound having a bromo group besides a selenium atom
in its structure. Compounds 5b and 5c exhibited the same activities
with respect to Escherichia coli and Staphylococcus aureus. Most of the
synthesised compounds showed moderate microbial activity against the
tested organisms.

540
H. S. B. Naik et al.
TABLE III Antibacterial Activity of the
Synthesized Compounds. +: (0.2–0.5 cm) less
active; ++: (0.6–1.4 cm) moderately active; +++:
(1.5–3 cm) highly active. Standard: Ciproflaxacin
(25 µg mL−1
Compound no.
Staphylococcus aureus
Escherichia coli
4a
4b
4c
4d
5a
5b
5c
5d
+
++
+++
++
++
++
+++
+
+++
++
++
++
++
+++
++
+
REFERENCES
[1] A. Padwa, Angew. Chem. Int. Ed. Engl., 15, 123 (1976).
[2] R. Huisgen, R. Sustmann, and G. Wallbillich, Chem. Ber., 100, 1786 (1976).
[3] A. O. Abdelhamid and F. A. Atlaby, J. Heterocycl. Chem., 28, 41 (1991).
[4] D. I. Kornis, Comprensive Heterocyclic Chemistry, Vol 4, Eds. A. R. Kartritzky, C.
W. Rees, and E. F. V. Scriven (Pergamon, Oxford, 1996).
[5] A. P. Abbott, V. R. Bonnert, V. M. Caffrey, A. P. Cage, J. A. Cooke, K. D. Donald, M.
Furber, S. Hill, and J. Withnall, Tetrahedron, 58, 3185 (2002).
[6] C. B. Ranu, A. Hajra, S. S. Dey, and U. Jana, Tetrahedron, 59, 813 (2003).
[7] O. V. Singh, P. K. Amancharla, and G. Venkateshwar, Indian J. Chem., 4213, 1456
(2003).
[8] P. Helissey, S. Desbene-Finck, and S. Giorgi Renault, Eur. J. Org. Chem., 410 (2005).
[9] Swati, A. K. Sharma, and L. Prakash, Indian. J. Chem., 35B, 1221 (1996).
[10] A. O. Abdelhamid, N. M. Rateb, and K. M. Dawood, Phosphorus, Sulfur, and Silicon,
167, 251 (2000).
[11] T. I. El-Emary, A. Khalia, G. A. M. El-Hag Ali, and A. A. A. M. El-Adasy, Phosphorus,
Sulfur, and Silicon, 180, 19 (2005).
[12] A. O. A. Mohammed and A. M. Alkhodshi, Phosphorus, Sulfur, and Silicon, 180, 149
(2005).
[13] I. Langmiur, J. Am. Chem. Soc., 4, 1543 (1919).
[14] H. Erlenmeyer, Bull. So. Chem. Bio., 30, 792 (1948).
[15] R. N. kumar, S. T. Selvi, T. Suresh, and P. S. Mohan, Indian. J. Chem., 42B, 187
(2003).
[16] I. Lalezari, A. Shafiee, and S. Yazdani, J. Pharm Sci., 63, 628 (1974).
[17] K. S. Sharma and S. P. Singh., Indian. J. Chem., 31B, 396 (1992).
[18] D. L. Klayman and W. H. H. Gunther, Organic Selenium Compounds Their Chem-
istry, and Biology (Washington, New York, 1972).
[19] S. K. Nandeeshaiah, Ph.D. Thesis, University of Mysore, Mysore, India (1994).
[20] M. S. Gaikwad, A. S. Mane, R. V. Hangarge, V. P. Chavan, and M. S. Shingare,
Indian. J. Chem., 42B, 189 (2003).

9-Methyl[1,2,3]Selenadiazoles[4,5-b]Quinoline
541
[21] D. B. Reddy, A. S. Reddy, and V. Padmavathi, Indian. J. Chem., 37B, 1194
(1998).
[22] V. Padmavathi, A. Padmaja, and D. B. Reddy, Indian. J. Chem., 38B, 308
(1999).
[23] B. P. Nandeshwarappa, D. B. Aruna Kumara, M. N. Kumaraswamy. H. S. B. Naik,
and K. M. Mahadevan, Indian. J. Chem., 580B (2004).
[24] B. P. Nandeshwarappa, D. B. A. Kumara, H. S. B. Naik, V. P. Vaidya, and K. M.
Mahadevan, Indian. J. Chem., 302B (2004).