Conventional and microwave assisted synthesis of 2-oxo-4-substituted aryl-azetidine derivatives of benzotriazole: A new class of biological compounds

Article abstract of DOI:10.1016/j.bmcl.2010.10.057

We report herein the synthesis and biological activity of a new kind of azetidinone derivatives of benzotriazole. The reaction was carried out by both conventional and microwave methods. The chemical structures of all the synthesized compounds were deduce

Full text of DOI:10.1016/j.bmcl.2010.10.057

Bioorganic & Medicinal Chemistry Letters 21 (2011) 569–573
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Conventional and microwave assisted synthesis of 2-oxo-4-substituted
aryl-azetidine derivatives of benzotriazole: A new class of biological compounds
⇑
Adesh Dubey , S. K. Srivastava, S. D. Srivastava
Synthetic Organic Chemistry Laboratory, Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (MP) 470 003, India
a r t i c l e i n f o
a b s t r a c t
Article history:
We report herein the synthesis and biological activity of a new kind of azetidinone derivatives of
benzotriazole. The reaction was carried out by both conventional and microwave methods. The chemical
structures of all the synthesized compounds were deduced according to FTIR, 1H NMR, 13C NMR and
FAB-mass spectral along with microanalytical data. All the synthesized compounds of series 5a–i were
evaluated for their antitubercular activity against Mycobacterium tuberculosis H37RV and antimicrobial
activity against some selected microorganism. Unexpectedly, some azetidinone derivatives of benzotria-
zole displayed better activities.
Received 3 August 2010
Revised 22 September 2010
Accepted 13 October 2010
Available online 30 October 2010
Keywords:
Antimicrobial
Antitubercular
Ó 2010 Published by Elsevier Ltd.
Azetidinone
Conventional and microwave irradiation
Tuberculosis (TB) remains the major cause of death all over the
world. Up to 4% of all TB cases worldwide are resistant to more than
one antitubercular because of incomplete or partial therapy. So now
a day it is very essential demand for a new class of antitubercular
agent with a different mode of action. Benzotriazole and its deriva-
tives have captured the imagination of organic chemists for more
than a century. Literature survey reveals that benzotriazole and its
derivatives possess broad spectrum of biological activities which
include antimicrobial,1 antiviral,2 anti-inflammatory, ANTICON-
VULSANT,3 DNA cleavage,4 herbicidal,5 antitubercular,6,7 etc. 2-aze-
tidinones, known as b-lactams, serve as synthones for much
biologically important class of organic compounds. 2-Azetidinones
and its derivatives are important compounds due to their broad
range of biological activities such as CNS depressant,8 anti-inflam-
matory,9 anticancer,10,11 antimicrobial,12–17 antitubercular,18
cholesterol absorption inhibitor19 and antibiotic.20 Microwave
reactions under solvent free conditions are attractive offering
reduced pollution, low cost and offer high yields together with
simplicity in processing and handling.21,22 The salient features of
microwave approach are shorter reaction times, simple reaction
conditions and enhancements in yields.
study we report the synthesis and antimicrobial screening of
2-oxo-4-substituted aryl- azetidinone derivatives of benzotriazole.
Our synthesis strategy was based on to synthesize a highly
biologically active heterocycle containing benzotriazole and
azetidinone moieties. As the results, we obtained a mixture of
the 1- and 2-substituted isomers of benzotriazole derivatives in
all steps by Scheme 1. Generally the compounds bearing the sub-
stituent in 1-position were obtained in higher yields. So we were
mentioned here only major products (1-substituted). Separation
of the compounds was performed by column chromatography.
The spectroscopic data supported the formation of the products
in end step. Comparative study results obtained by microwave as-
sisted synthesis; versus conventional heating method is that some
reactions which required 5.5–8 h by conventional method, was
completed within 2–5 min by the microwave irradiation technique
and yields have been improved from 60–72% to 84–92%.The
comparison study data are given in Table 3.
All the synthesized compounds of series (5a–i) were screened
against Mycobacterium tuberculosis for their antitubercular activity
and against some microorganisms for their antimicrobial activities.
Generally compounds possessing electron withdrawing groups
showed good antibacterial and antitubercular activity. Some
derivatives (5b, 5c, 5d, 5f, 5g) containing electron withdrawing
groups (–Cl, –Br, –NO2) have shown promising activity against
M. tuberculosis and some bacteria. Compounds possessing electron
donating groups (5h, 5i) have shown good antifungal activity.
Activity data are given in Tables 1 and 2. We have also done cyto-
toxicity analysis of the synthesized compounds. From the study
of cytotoxicity, none of them were found toxic. Hence the activities
The biological significances of these class of heterocycles and
important features of microwave assisted synthesis impelled us
to synthesize some new azetidinone derivatives having benzotria-
zole moiety by conventional and microwave irradiation. In this
⇑
Corresponding author.
E-mail address: adeshdubey1985@yahoo.com (A. Dubey).
0960-894X/$ - see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.bmcl.2010.10.057

570
A. Dubey et al. / Bioorg. Med. Chem. Lett. 21 (2011) 569–573
N
N
NH2NH2.H2O
BrCH2CH2CH2Cl
N
N
N
H
N
(2)
CH2CH2CH2Cl
(1)
N
N
ClCH2COCl/Et3N
Ar-CHO
N
N
N
N
R
CH2CH2CH2NHN=CH
CH2CH2CH2NHNH2
(3)
(4)
N
N
H
N
R
CH2CH2CH2NHN
(5)
Cl
O
R= -H, 2-Cl, 4-Cl, 2-Br, 3-Br, 2-NO2, 4-NO2, 2-OCH3, 4-OCH3,
Scheme 1.
Table 3
Table 1
Comparative yields of the compounds, 2, 3, 4a–i and 5a–i
Antitubercular activity of selected compounds of series 5a–i (MIC
lg/ml)
Compd
No.
Molecular
formula
R
Concentional
Microwave
Yield Rea. T.
No.
Compounds
MIC (lg/ml) H37Rv
Yield
(%)
Rea. T.
(h)
1
2
3
4
5
6
7
8
9
5a
5b
5c
5d
5e
5f
5g
5h
>12.5
3.125
>3.125
>3.125
6.25
>3.125
>1.56
>6.25
>12.5
4.0
(%)
(min)
2
3
C9H10N3Cl
C9H13N3
—
—
—
2-Cl
4-Cl
2-Br
3-Br
2-NO2
4-NO2
2-OCH3
4-OCH3
–H
2-Cl
4-Cl
2-Br
3-Br
72
65
68
62
63
65
67
63
62
65
64
68
63
71
72
70
69
67
66
64
6.0
7.0
5.0
4.0
4.0
5.0
5.0
3.5
4.0
5.5
5.5
6.0
4.0
4.5
5.5
5.0
4.0
4.0
7.0
6.0
84
86
86
89
86
90
91
88
87
90
86
92
89
86
84
86
85
86
84
87
2.5
3.0
4.0
3.5
3.5
4.0
3.5
3.0
2.5
5.0
4.5
3.0
3.5
4.0
4.5
4.5
2.5
3.0
5.0
4.5
4a
4b
4c
4d
4e
4f
4g
4h
4i
5a
5b
5c
5d
5e
5f
5g
5h
5i
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
16H17N5
16H16N5Cl
16H16N5Cl
16H16N5Br
16H16N5Br
16H16N6O2
16H16N6O2
17H19N5O
5i
10
11
Streptomycin
Ethambutol
1.0
17H19N5O
18H17N5Cl
18H17N5OCl2
18H17N5OCl2
18H17N5OBrCl
18H17N5OBrCl
18H17N6O3Cl
18H17N6O3Cl
19H20N5O2Cl
19H20N5O2Cl
Table 2
Antibacterial and antifungal activity of compounds 5a–i (MIC
lg/ml)
No.
S. aures E. coli S. pneumoe C. albicas A. fumigats A. niger
2-NO2
4-NO2
2-OCH3
4-OCH3
5a
5b
5c
5d
5e
5f
5g
5h
1.0
0.5
0.1
0.1
0.1
0.5
0.1
1.0
1.0
0.1
1.0
0.1
0.1
0.1
0.1
0.5
0.5
2.0
1.0
0.1
0.5
0.1
0.5
0.5
0.1
0.1
0.5
0.5
0.5
0.1
1.0
1.0
0.5
1.0
0.5
0.1
0.1
0.1
0.1
1.0
0.5
0.5
0.5
0.1
0.1
0.5
0.1
0.1
1.0
0.5
1.0
0.5
0.1
0.1
0.5
0.1
0.1
activity. Drug susceptibility and determination of MIC of the test
compounds/drugs against M. tuberculosis H37Rv was performed
by agar microdilution method where twofold dilutions of each test
compound were added into 7H10 agars supplemented with OADC
and organism. A culture of M. tuberculosis H37Rv growing on L-J
medium23 was harvested in 0.85% saline with 0.05% Tween-80. A
suspension of compounds was prepared in DMSO. This suspension
was added to (in tubes) 7H10 middle brook’s medium (containing
1.7 ml medium and 0.2 ml OADC supplement) at different concen-
tration of compound keeping the volume constant, that is, 0.1 ml.
Medium was allowed to cool keeping the tubes in slanting posi-
tion. These tubes were then incubated at 37 °C for 24 h followed
by streaking of M. tuberculosis H37Rv (5 Â 104 bacilli per tube).
5i
Oflaxacin
Miconazole
0.1
0.1
0.1
of the above synthesized compounds were not due to cytotoxicity
of the compounds. It is thus concluded that new synthesized aze-
tidinones are good antitubercular and antimicrobial compounds
for therapeutic uses.
Evaluation of antimycobacterial screening: All the synthesized
compounds of series (5a–i) were evaluated for their antitubercular

A. Dubey et al. / Bioorg. Med. Chem. Lett. 21 (2011) 569–573
571
These tubes were then incubated at 37 °C. Growth of bacilli was
seen after 30 days of incubation. Tubes having the compounds
were compared with control tubes where medium alone was
incubated with H37Rv. The concentration at which complete
inhibition of colonies occurred was taken as active concentration
of test compound. Streptomycin and ethambutol were used as
standard drug. The MIC levels of some active compounds (5a–i)
against these organisms are given in Table 1.
to give compound 3. Mp 98–99 °C; IR: 3361 (–NH2), 3316 (–NH),
3072 (C–H), 1318 (N–CH2). 1H NMR: 8.76 (s, 1H, NH), 8.05–7.29
(m, 4H, Ar), 4.23 (s, 1H, NH2), 3.14 (t, 2H, J = 7.05, CH2CH2CH2),
2.62 (t1, 2H, J = 7.05, CH2CH2CH2), 1.59 (m, 2H, J = 7.05,
CH2CH2CH2). 13C NMR: 113.42–148.16 (Ar), 42.24 (CH2CH2CH2),
36.92 (CH2CH2CH2), 32.32 (CH2CH2CH2). MS, m/z: 191(M)+, 175,
160, 146, 132, 118. Anal. Calcd for C9H13N5: C, 56.52; H, 6.85; N,
36.62. Found: C, 56.48; H, 6.80; N, 36.58.
Evaluation of antimicrobial screening: All the synthesized com-
pounds of series (5a–i) were tested for their antimicrobial activity.
For antibacterial screening a gram-positive bacterium Staphylococ-
cus aureus and two gram-negative bacteria, Escherichia coli and
Streptococcus pneumoniae were used. For antifungal activity
Candida albicans, Aspergillus pumigatus and Aspergillus niger was
taken. Antibacterial and antifungal screenings were performed by
dilution method using nutrient agar media. MIC was determined
Microwave irradiation method: An equimolar mixture of com-
pound 2 (14 g, 0.072 mol) and hydrazine hydrate (3.6 g, 0.072 mol)
was placed in a microwave oven for 3 min. The crude product was
readily purified by passing it through a chromatographic column
packed with silica gel using acetone: methanol (6:4 v/v) as eluant
to obtain pure derivative. The resulting purified product was recrys-
tallized by ethanol to give compounds 3.
Synthesis of N-[(benzylidenehydrazino)-propyl]-benzotriazole (4a).
Conventional method: A mixture of compound 3 (2 g, 0.01 mol) and
benzaldehyde (1.11 g, 0.01 mol) in methanol (20 ml) in the presence
of catalytic amountof glacial acetic acid was refluxed for 5 h. The sol-
vent was removed under reduced pressure to and the resulting
crude product was purified by passing it through a chromatographic
column packed with silica gel using chloroform/methanol (8:2 v/v)
as eluant. Resulting purified product was recrystallized by chloro-
form to give compounds, 4a. Mp 113–114 °C: IR: 3358 (N–H),
3081 (C–H), 1581 (CH@N, azomet.), 1319 (N–CH2). 1H NMR: 8.74
(s, 1H, N@CH, azomet.), 8.32 (s, 1H, N–H), 8.06–7.22 (m, 9H, Ar.),
3.12 (t, 2H, J = 7.08, CH2CH2CH2), 2.59 (t, 2H, J = 7.08, CH2CH2CH2),
1.58 (m, 2H, J = 7.08, CH2CH2CH2). 13C NMR: 114.20–149.16 (Ar.),
132.13 (N@CH, azomet.), 42.16 (CH2CH2CH2), 36.92 (CH2CH2CH2),
32.46 (CH2CH2CH2). M/S, m/z: 279(M)+, 175, 160, 146, 132, 118,
104, 77. Anal. Calcd for C16H17N5: C, 68.81; H, 6.13; N, 25.08. Found:
C, 68.78; H, 6.11; N, 25.04.
at five concentrations (in
lg/ml) ranging from 0.5
lg, 1.0 lg,
5.0 g, 10.0 g, 25.0 g and 50.0 l
l
l
l
g of each compounds. The tubes
were incubated at 37 °C for 48 h. DMSO was used as solvent. The
lowest concentration, which showed no visible growth, was taken
as an end point for minimum inhibitory concentration (MIC).
Oflaxacin was used as standard drug for antibacterial screening
in a concentration 0.1
standard drug for antifungal screening in a concentration 0.1
l
g/ml/disc and miconazole was used as
g/
l
ml/disc. The MIC level of some active compounds (5a–i) against
these organisms is given in Table 2.
Cytotoxicity analysis: All the synthesized products were ana-
lysed for cytotoxicity using neutral red uptake by using vero-c-
1008 cell line at various concentrations ranging from 0.01 to
0.1 lg/ml, none of them were found toxic. Hence the activities of
the above synthesized compounds were not due to cytotoxicity
of the compounds.
General procedure of the synthesis. Synthetic protocol for the syn-
thesis of N-(chloropropyl)-benzotriazole (2): Conventional method:
Microwave irradiation method: An equimolar mixture of com-
pound 3 (2 g, 0.01 mol) and benzaldehyde (1.11 g, 0.01 mol) in
the presence of a catalytic amount of glacial acetic acid was placed
in a microwave oven for 4.0 min. The resulting crude product was
purified by passing it through a chromatographic column packed
with silica gel using chloroform/methanol (8:2 v/v) as eluant.
Resulting purified product was recrystallized by chloroform to give
compounds, 4a.
Benzotriazole
1 (25 g, 0.21 mol) was dissolved in methanol
(50 ml) and 1-bromo-3-chloropropane (33.58 g, 0.21 mol) was
added. The mixture was refluxed for about 6 h, filtered and the sol-
vent was evaporated to dryness in vacuo. The crude product was
readily purified by passing it through a chromatographic column
packed with silica gel using chloroform/methanol (7:3 v/v) as elu-
ant to obtain pure derivative. The resulting purified product was
recrystallized by chloroform to give compounds 2. Mp 84–85 °C;
IR: 3080 (C–H), 1316 (N–CH2), 734 (C–Cl). 1H NMR: 8.01–7.30
(m, 4H, Ar.), 3.10 (t, 2H, J = 7.03, CH2CH2CH2), 2.57 (t1, 2H, J =
7.03, CH2CH2CH2), 1.65 (m, 2H, J = 7.03, CH2CH2CH2). 13C NMR:
114.81–146.12 (Ar.), 42.40 (CH2CH2CH2), 36.29 (CH2CH2CH2),
31.19 (CH2CH2CH2). MS, m/z: 196 (M)+, 160, 146, 132, 118. Anal.
Calcd for C9H10N3Cl: C, 55.25; H, 5.15; N, 21.47. Found: C, 55.23;
H, 5.11; N, 21.44.
Microwave irradiation method: An equimolar mixture of benzotri-
azole 1 (25 g, 0.21 mol) and 1-bromo-3-chloropropane (33.58 g,
0.21 mol) was subjected to microwave irradiation for 2.5 min. The
crude product was readily purified by passing it through a
chromatographic column packed with silica gel using chloroform/
methanol (7:3 v/v) as eluant to obtain pure derivative. The resulting
purified product was recrystallized by chloroform to give com-
pounds 2.
Synthesis of N-(hydrazino propyl)-benzotriazole (3): Conventional
method: Compound 2 (14 g, 0.072 mol) was dissolved in acetone
(35 ml) and hydrazine hydrate (3.6 g, 0.072 mol) was added. The
well stirred (2 h) mixture was refluxed for 7 h. After cooling and fil-
tration the solvent was evaporated under in vacuo to obtain a solid
crude product. This resulting crude product was purified by pass-
ing it through a chromatographic column packed with silica gel
using acetone/methanol (6:4 v/v) as eluant to obtain pure deriva-
tive. The resulting purified product was recrystallized by ethanol
Other compounds 4b–i was synthesized in the similar manner by
treating compound 3 with selected aromatic aldehydes (Scheme 1).
Synthesis of N-[(2-oxo-3-chloro-4-phenyl–azetidineimino)-pro-
pyl]-benzotriazole (5a). Conventional method: A mixture of com-
pound 4a (0.01 mol) and Et3N (0.01 mol) in methanol, ClCH2COCl
(0.01 mol) was added drop wise. The well stirred (2 h) reaction
mixture was refluxed on a steam bath for 5 h. The reaction mixture
was cooled and excess of solvent was evaporated under reduced
pressure. The solid obtained was purified by passing it through a
chromatographic column packed with Silica gel using chloro-
form/methanol (6:4 v/v) as eluant and recrystallised from ethanol
to give compounds 5a. Mp 102–103 °C: IR: 3362 (N–H), 3068
(C–H), 1731 (C@O), 1318 (N–CH2). 1H NMR: 8.52 (s, 1H, N–H),
8.11–7.56 (m, 9H, Ar.), 5.32 (d, 1H, J = 4.21, N–CH–Ar), 5.51 (d,
1H, J = 4.21, CH–Cl), 3.20 (t, 2H, J = 7.15, CH2CH2CH2), 2.61 (t, 2H,
J = 7.15, CH2CH2CH2), 1.57 (m, 2H, J = 7.15, CH2CH2CH2). 13C NMR:
166.22 (C@O), 113.31–152.19 (Ar.), 63.63 (CH–Cl), 57.57 (N–CH–
Ar), 42.61 (CH2CH2CH2), 37.62 (CH2CH2CH2), 32.43 (CH2CH2CH2).
MS, m/z: 356(M)+, 181, 175, 160, 153, 146, 132, 118. Anal. Calcd
for C18H18N5OCl: C, 60.75; H, 5.09; N, 19.68. Found: C, 60.71; H,
5.07; N, 19.64.
Microwave irradiation method: A mixture of compound 4a
(0.01 mol) and Et3N (0.01 mol) in methanol, ClCH2COCl
(0.01 mol) was added drop wise. The well stirred (2 h) reaction
mixture was refluxed on a steam bath for 5 h. The reaction mixture
was cooled and excess of solvent was evaporated under reduced

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A. Dubey et al. / Bioorg. Med. Chem. Lett. 21 (2011) 569–573
pressure. The solid obtained was purified by passing it through a
chromatographic column packed with Silica gel using chloro-
form/methanol (6:4 v/v) as eluant and recrystallised from ethanol
to give compounds 5a.
Other compounds 5b–i was synthesized in the similar manner
using compounds 4b–i. Characterisation data are presented in
Table 2.
37.82 (CH2CH2CH2), 32.24 (CH2CH2CH2). MS, m/z: 401(M)+, 226,
175, 148, 160, 153, 146, 132, 118. Anal. Calcd for C18H17N6O3Cl:
C, 53.93; H, 4.27; N, 20.96. Found: C, 53.89; H, 4.21; N, 20.93.
N-[{4-(2-Methoxyphenyl)-3-chloro-2-oxo-azetidineimino}-pro-
pyl]-benzotriazole (5h): Mp 97–98 °C: IR: 3362 (N–H), 3073
(C–H), 1747 (C@O), 1328 (N–CH2), 1235 (Ar–OCH3). 1H NMR: 8.32
(s, 1H, N–H), 5.44 (d, 1H, J = 4.35, CH–Cl), 5.25 (d, 1H, J = 4.35,
N–CH–Ar), 3.74 (s, 1H, –OCH3), 3.11 (t, 2H, J = 7.10, CH2CH2CH2),
2.67 (t, 2H, J = 7.10, CH2CH2CH2), 1.64 (m, 2H, J = 7.10, CH2CH2CH2).
13C NMR: 113.92–152.81 (Ar.), 168.48 (C@O), 63.91 (CH–Cl), 56.22
(N–CH), 43.73 (CH2CH2CH2), 38.28 (CH2CH2CH2), 31.83 (CH2CH2-
CH2), 55.42 (O–CH3). MS, m/z: 386(M)+, 211, 183, 175, 160, 153,
146, 132, 118. Anal. Calcd for C19H20N5O2Cl: C, 59.14; H, 5.22, N,
18.15. Found: C, 59.10; H, 5.18, N, 18.10.
N-[{4-(4-Methoxyphenyl)-3-chloro-2-oxo-azetidineimino}-pro-
pyl]-benzotriazole (5i): Mp 92–93 °C: IR: 3366 (N–H), 3097 (C–H),
1741 (C@O), 1331 (N–CH2), 1244 (Ar–OCH3). 1H NMR: 8.40 (s,
1H, N–H), 5.45 (d, 1H, J = 4.22, CH–Cl), 5.16 (d, 1H, J = 4.22,
N–CH–Ar), 3.71 (s, 1H, –OCH3), 3.08 (t, 2H, J = 7.06, CH2CH2CH2),
2.65 (t, 2H, J = 7.06, CH2CH2CH2), 1.63 (m, 2H, J = 7.09, CH2CH2CH2).
13C NMR: 165.59 (C@O), 112.08–150.96 (Ar.), 64.39 (CH–Cl), 61.07
(N–CH), 43.82 (CH2CH2CH2), 37.46 (CH2CH2CH2), 31.63 (CH2CH2-
CH2), 57.32 (O–CH3). MS, m/z: 386(M)+, 211, 183, 175, 160, 153,
146, 132, 118. Anal. Calcd for C19H20N5O2Cl: C, 59.14; H, 5.22, N,
18.15. Found: C, 59.11; H, 5.17, N, 18.12.
N-[{4-(2-Chlorophenyl)-3-chloro-2-oxo-azetidineimino}-propyl]-
benzotriazole (5b): Mp 109–110 °C: IR: 3362 (N–H), 3071 (C–H),
1739 (C@O), 1321 (N–CH2), 748 (Ar–Cl). 1H NMR: 8.53 (s, 1H,
N–H), 5.29 (d, 1H, J = 4.19, N–CH–Ar), 5.54 (d, 1H, J = 4.19, CH–Cl),
3.07 (t, 2H, J = 7.13, CH2CH2CH2), 2.62 (t, 2H, J = 7.13, CH2CH2CH2),
1.62 (m, 2H, J = 7.13, CH2CH2CH2). 13C NMR: 166.35 (C@O), 114.41–
153.23 (Ar.), 65.23 (CH–Cl), 57.64 (N–CH–Ar), 43.32 (CH2CH2CH2),
37.85 (CH2CH2CH2), 31.82 (CH2CH2CH2). MS, m/z: 390(M)+, 215,
187, 175, 160, 153, 146, 132, 118. Anal. Calcd for C18H17N5OCl2:
C, 55.39; H, 4.39; N, 17.94. Found: C, 55.36; H, 4.34; N, 17.90.
N-[{4-(3-Chlorophenyl)-3-chloro-2-oxo-azetidineimino}-propyl]-
benzotriazole (5c): Mp 102–103 °C: IR: 3363 (N–H), 3077 (C–H),
1740 (C@O), 1323 (N–CH2), 749 (Ar–Cl). 1H NMR: 8.57 (s, 1H,
N–H), 5.27 (d, 1H, J = 4.11, N–CH–Ar), 5.56 (d, 1H, J = 4.11, CH–Cl),
3.19 (t, 2H, J = 7.10, CH2CH2CH2), 2.55 (t, 2H, J = 7.10, CH2CH2CH2),
1.51 (m, 2H, J = 7.10, CH2CH2CH2). 13C NMR: 165.87 (C@O), 114.61–
149.35 (Ar.), 65.29 (CH–Cl), 56.64 (N–CH–Ar), 44.99 (CH2CH2CH2),
37.12 (CH2CH2CH2), 31.88 (CH2CH2CH2). MS, m/z: 390(M)+, 215,
187, 175, 160, 153, 146, 132, 118. Anal. Calcd for C18H17N5OCl2:
C, 55.39; H, 4.39; N, 17.94. Found: C, 55.35; H, 4.35; N, 17.91.
N-[{4-(2-Bromophenyl)-3-chloro-2-oxo-azetidineimino}-propyl]-
benzotriazole (5d): Mp 98–99 °C: IR: 3366 (N–H), 3091 (C–H),
1735 (C@O), 1334 (N–CH2), 644 (Ar–Br). 1H NMR: 8.46 (s, 1H,
NH), 5.52 (d, 1H, J = 4.26, CH–Cl), 5.28 (d, 1H, J = 4.26, N–CH–Ar),
3.09 (t, 2H, J = 7.16, CH2CH2CH2), 2.64 (t, 2H, J = 7.16, CH2CH2CH2),
1.55 (m, 2H, J = 7.16, CH2CH2CH2). 13C NMR: 168.51 (C@O), 112.89–
154.34 (Ar.), 63.82 (CH–Cl), 58.91 (N–CH), 43.51 (CH2CH2CH2),
37.84 (CH2CH2CH2), 31.62 (CH2CH2CH2). MS, m/z: 435(M)+, 260,
232, 175, 160, 153, 146, 132, 118. Anal. Calcd for C18H17N5OClBr:
C, 49.73; H, 3.94; N, 16.11. Found: C, 49.69; H, 3.90; N, 16.07.
N-[{4-(3-Bromophenyl)-3-chloro-2-oxo-azetidineimino}-propyl]-
benzotriazole (5e): Mp 93–94 °C IR: 3361 (N–H), 3094 (C–H),
1741 (C@O), 1339 (N–CH2), 636 (Ar–Br). 1H NMR: 8.43 (s, 1H,
N–H), 5.49 (d, 1H, J = 4.27, CH–Cl), 5.18 (d, 1H, J = 4.27, N–CH–
Ar), 3.07 (t, 2H, J = 7.18, CH2CH2CH2), 2.60 (t, 2H, J = 7.18,
CH2CH2CH2), 1.56 (m, 2H, J = 7.18, CH2CH2CH2). 13C NMR: 167.44
(C@O), 112.15–149.21 (Ar.), 64.13 (CH–Cl), 56.72 (N–CH), 43.34
(CH2CH2CH2), 36.57 (CH2CH2CH2), 31.57 (CH2CH2CH2). M/S, m/z:
435(M)+, 260, 232, 175, 160, 153, 146, 132, 118. Anal. Calcd for
Acknowledgements
The authors thank to SAIF, CDRI Lucknow for providing FTIR, 1H
NMR, 13C NMR and FAB-mass spectral analysis data of the com-
pounds. We are also grateful to Head, Department of Biotechnol-
ogy, Dr. H. S. Gour University, Sagar (MP) for providing help in
carrying out the antimicrobial screening and microcare laboratory
and tuberculosis research center, Surat for antitubercular activity.
Thanks are also due to the Head, Department of Chemistry,
Dr. H. S. Gour University, Sagar (MP) for laboratories facilities to
carry out the work.
References and notes
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C
18H17N5OClBr: C, 49.73; H, 3.94; N, 16.11. Found: C, 49.68; H,
3.91; N, 16.08.
N-[{4-(2-Nitrophenyl)-3-chloro-2-oxo-azetidineimino}-propyl]-
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benzotriazole (5f): Mp 111–112 °C: IR: 3384 (N–H), 3098 (C–H),
1743 (C@O), 1332 (N–CH2), 1358 (Ar–NO2). 1H NMR: 8.54 (s, 1H,
N–H), 5.64 (d, 1H, J = 4.35, CH–Cl), 5.32 (d, 1H, J = 4.35, N–CH–
Ar), 3.16 (t, 2H, J = 7.18, CH2CH2CH2), 2.65 (t, 2H, J = 7.18,
CH2CH2CH2), 1.76 (m, 2H, J = 7.18, CH2CH2CH2). 13C NMR: 166.83
(C@O), 111.83–154.76 (Ar.), 64.88 (CH–Cl), 60.29 (N–CH), 44.41
(CH2CH2CH2), 38.21 (CH2CH2CH2), 32.33 (CH2CH2CH2). MS, m/z:
401(M)+, 226, 175, 148, 160, 153, 146, 132, 118. Anal. Calcd for
13. Chavan, A. A.; Pai, N. R. Molecules 2007, 12, 2467.
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C
18H17N6O3Cl: C, 53.93; H, 4.27; N, 20.96. Found: C, 53.90; H,
4.22; N, 20.92.
N-[{4-(4-Nitrophenyl)-3-chloro-2-oxo-azetidineimino}-propyl]-
benzotriazole (5g): Mp 109–110 °C: IR: 3380 (N–H), 3081 (C–H),
1748 (C@O), 1332 (N–CH2), 1351 (Ar–NO2). 1H NMR: 8.52 (s, 1H,
NH), 5.60 (d, 1H, J = 4.34, CH–Cl), 5.29 (d, 1H, J = 4.34, N–CH–Ar),
3.13 (t, 2H, J = 7.17, CH2CH2CH2), 2.63 (t, 2H, J = 7.17, CH2CH2CH2),
1.76 (m, 2H, J = 7.17, CH2CH2CH2). 13C NMR: 169.58 (C@O), 112.91–
151.53 (Ar.), 64.92 (CH–Cl), 60.37 (N–CH), 44.36 (CH2CH2CH2),
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Experimental section: All the melting points were determined by open capillary
method. All reagents were obtained from Sigma–Aldrich chemicals Pvt. Ltd.
Solvents were commercially obtained as laboratory grade. The progress of

A. Dubey et al. / Bioorg. Med. Chem. Lett. 21 (2011) 569–573
573
reactions and the purity of the compounds were controlled by thin layer
chromatography (TLC). The purification of the compounds was crried out by
column chromatography using 100–200 mesh Silica gel. 1H NMR spectra were
recorded on a Bruker DRX 300 instrument at 300 MHz in CDCl3 on d scale in
ppm using TMS as a reference. 13C NMR spectra were recorded on a Varian
AMX 400 spectrophotometer at 50 MHz using CDCl3. The FTIR spectra were
recorded on a Perkin–Elmer IR spectrophotometer using KBr disc of the sample
in cmÀ1. Mass spectra of the synthesized compounds have been recorded on a
JEOL SX 102/DA-6000 spectrometer. The microwave assisted synthesis was
performed in modified microwave oven ETC 2100 (2450 MHz and 800 W)
using microwave irradiation at 50% power levels and under controlled
temperature ranging between 81 and 90 °C. The reactions took place in an
open vessel and in solvent free media and the progress of the reactions
monitored by TLC.