Synthesis and characterization of new 2-oxo-azetidine derivatives

Article abstract of DOI:10.1080/00397911.2010.515328

Several new N-[(4-aryl-3-chloro-2-oxo-azetidine)acetamidyl]-5- nitroindazoles 4a-l were synthesized from N-(arylidene amino acetamidyl)-5-nitroindazoles 3a-l. The structures of all these compounds were confirmed by infrared, ¹H NMR, ¹³

Full text of DOI:10.1080/00397911.2010.515328

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Synthesis and Characterization of New 2-
Oxo-azetidine Derivatives
Apoorva Upadhyay a , S. K. Srivastava a & S. D. Srivastava a
a Synthetic Organic Chemistry Laboratory, Department of
Chemistry , Dr. H. S. Gour University , Sagar , India
Published online: 29 Jun 2011.
To cite this article: Apoorva Upadhyay , S. K. Srivastava & S. D. Srivastava (2011) Synthesis and
Characterization of New 2-Oxo-azetidine Derivatives, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 41:17, 2544-2556, DOI:
10.1080/00397911.2010.515328
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Synthetic Communications1, 41: 2544–2556, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.515328
SYNTHESIS AND CHARACTERIZATION OF NEW
2-OXO-AZETIDINE DERIVATIVES
Apoorva Upadhyay, S. K. Srivastava, and S. D. Srivastava
Synthetic Organic Chemistry Laboratory, Department of Chemistry, Dr. H. S.
Gour University, Sagar, India
GRAPHICAL ABSTRACT
Abstract Several new N-[(4-aryl-3-chloro-2-oxo-azetidine)acetamidyl]-5-nitroindazoles
4a–l were synthesized from N-(arylidene amino acetamidyl)-5-nitroindazoles 3a–l. The
structures of all these compounds were confirmed by infrared, 1H NMR, 13C NMR, and
fast atom bombardment–mass spectra and also by microanalytical data.
Keywords Arylidene; azetidinones; 5-nitroindazole
INTRODUCTION
Heterocycles constitute one of the biggest classical divisions of organic
chemistry and are of immense importance biologically, to the pharmaceutical and
agronomic based industries, and indeed to the development of human beings.
Heterocycles and medicines have been interconnected recently. Most life-saving
modern drugs contain the heterocyclic nucleus. The biological properties of hetero-
cycles in general make them of prime interest to the pharmaceutical, biotechnologi-
cal, and electronic industries. Organic synthesis is a principal way to produce
chemical products of practical applications. The indazole nucleus is a pharmaceuti-
cally important and emerging heterocycle with a broad spectrum of activities includ-
ing anti-inflammatory,[1] antitumor,[2] anti-HIV[3] and antimicrobial activities.[4]
Particularly 5-nitroindazole and its derivatives have been found to possess a wide
spectrum of activities such as antiprotozoal,[5] antimalarial,[6] and cytotoxic.[7]
Received January 6, 2010.
Address correspondence to Apoorva Upadhyay, Synthetic Organic Chemistry Laboratory,
Department of Chemistry, Dr. H. S. Gour University, Sagar, M.P. 470 003, India. E-mail:
upadhyay.apoorva@gmail.com
2544

NEW 2-OXO-AZETIDINE DERIVATIVES
2545
2-Oxo-azetidine derivatives also exhibit antimicrobial,[8–11] antitubercular,[12]
anticonvulsant[13,14] and anti-inflammatory properties.[15–17] The incorporation of
the 2-oxo-azetidine moiety in 5-nitroindazole through the acetamidyl framework
has been found to enhance the activity. Hence, in the present study, position 1 in
the 5-nitroindazole moiety having an imino group was used as the target for chemi-
cal modification. In view of these, we have synthesized some new N-(arylidene amino
acetamidyl)-5-nitroindazoles 3a–l and N-[(4-aryl-3-chloro-2-oxo-azetidine)acet
amidyl]-5-nitroindazoles 4a–l.
RESULTS AND DISCUSSION
5-Nitroindazole on reaction with ethyl chloroacetate yielded N-(ethyl
ethanoate)-5-nitroindazole 1. In the infrared (IR) spectrum of compound 1, the
=
absorption band characteristic for the >C O ester group was identified at
1
1730 cmꢀ1 and in the H NMR spectrum the peaks at d 1.25 ppm and d 4.25 ppm
were due to CH3 and CH2 respectively in –COOCH2CH3 (J ¼ 7 Hz). Furthermore,
13
=
in the C NMR spectrum, a peak at d 168.9 ppm appeared due to >C O of ester,
and the peaks at d 61.1 ppm (COOCH2CH3) and d 14.5 ppm (COOCH2CH3) con-
firmed the formation of compound 1. The compound 1 on amination with hydrazine
hydrate yielded N-(acetyl hydrazino)-5-nitroindazole 2. In the IR spectrum of the
compound 2, the bands at 1678 cmꢀ1 for –CONH and 3252, 3378 cmꢀ1 for –NHNH2
were observed. In the 1H NMR spectrum, the peak at d 8.20 ppm was due to
–CONH, and a peak at d 4.45 ppm was observed due to –NH2. Furthermore in
the 13CNMR spectrum a peak at d 168.0 ppm (-CONH) confirmed the formation
of compound 2. The compound 2 on condensation with various aromatic aldehydes
yielded N-(arylidene amino acetamidyl)-5-nitroindazoles 3a–l. Formation of com-
pounds 3a–l was evidenced by the appearance of peaks at d 8.62–8.73 ppm due to
ꢀ1
=
=
N CH and IR bands at 1635–1647 cm for –N CH of arylidenes. Furthermore,
in the 13C NMR spectra, peaks were observed in the range of d 143.0–144.1 ppm
=
due to a –N CH group, which confirmed the formation of compounds 3a–l. The
compounds 3a–l on reaction with chloroacetyl chloride in the presence of triethyla-
mine yielded N-[(4-aryl-3-chloro-2-oxo-azetidine)acetamidyl]-5-nitroindazoles 4a–l
(Scheme 1). Formation of compounds 4a–l was confirmed by the appearance of
peaks at d 5.01–5.12 ppm due to CH-Cl. In the IR spectra, the bands at
738–749 cmꢀ1 for CH-Cl and 1730–1741 cmꢀ1 for >C O, cyclic were observed. Fur-
=
thermore, in the 13CNMR spectra, peaks at d 132.1–133.3 ppm appeared due to
=
CH-Cl, and peaks at d 171.2–172.5 ppm were observed due to >C O, cyclic which
confirmed the formation of compounds 4a–l.
EXPERIMENTAL
General Methods and Materials
All the melting points were taken in open capillary tubes. Formation of the
compounds was routinely checked by thin-layer chromatography (TLC) using silica
gel G, and the spots were exposed to iodine vapors for visualization. IR spectra were
recorded in Shimadzu 8201 PC spectrophotometer. The 1H NMR spectra were

2546
A. UPADHYAY, S. K. SRIVASTAVA, AND S. D. SRIVASTAVA
Scheme 1. Synthesis of new 2-oxo-azetidine derivatives 4a–l.
recorded at 400 MHz, and 13C NMR spectra were recorded at 100 MHz on Bruker
DRX-300 in CDCl3 using tetramethylsilane (TMS) as an internal standard on d
scale. The fast atom bombardment (FAB)–mass spectra were recorded on a Jeol
SX102 mass spectrometer. All the compounds gave satisfactory C, H, and N
percentages within the experimental limits.
Synthesis of N-(Ethyl ethanoate)-5-nitroindazole (1)
Equimolar solution of 5-nitroindazole (30 g, 0.18 mol) and ethyl chloroacetate
(22.55 g, 0.18 mol) in acetone (100 ml) was stirred for about 2 h. The solvent was
removed in vacuo, and the residue thus obtained was purified over the column of
silica-gel and recrystalliꢀze1d from acetone to furnish compound 1. Yield 78%; mp
264–266 ꢁC; IR (n, cm , KBr): 3046 (C-H, Ar-H), 1730 (>C O, ester), 1601
=
(N CHꢀ, cyclic), 1530, 1338 (ArNO2), 1430 (NꢀCH2); 1H NMR (400 MHz,
=
=
CDCl3): d 7.90 (s, 1H, N CHꢀ, cyclic), 7.26–7.60 (m, 3H, Ar-H), 4.25 (q, 2H,
13
J ¼ 7 Hz, COOCH2CH3), 2.51 (s, 2H, NꢀCH2), 1.25 (t, 3H, J ¼ 7 Hz,
=
COOCH2CH3); C NMR (100 MHz, CDCl3): d 168.9 (>C O of ester), 142.0
=
(C-NO2, aromatic), 135.0 (N CHꢀ, cyclic), 110.9–122.2 (C of aromatic ring), 61.1
(COOCH2CH3), 33.3 (NꢀCH2), 14.5 (COOCH2CH3). Mass (m=z): 249 [Mþ], 204,
203, 176, 162, 134, 88. Anal. (%) for C11H11N3O4, calcd. C, 53.01; H, 4.42; N,
16.87. Found: C, 52.98; H, 4.39; N, 16.83.
Synthesis of N-(Acetyl hydrazino)-5-nitroindazole (2)
Equimolar solution of the compound 1 (27 g, 0.11 mol) and hydrazine hydrate
(5.43 g, 0.11 mol) in dioxane (90 ml) was stirred for about 8 h. The solvent was
removed in vacuo, and the residue thus obtained was purified over the column of

NEW 2-OXO-AZETIDINE DERIVATIVES
2547
Melting point (ꢁC)
197–198
Table 1. Synthesized new 2-oxo-azetidine derivatives (4a–l)
Entry
Ar
Product
Yield (%)
1
C6H5
72
2
2-OHC6H4
70
215–216
3
4
5
2-ClC6H4
4-ClC6H4
2-BrC6H4
68
73
69
175–176
177–178
185–186
6
7
3-BrC6H4
71
74
76
72
75
180–181
205–206
201–202
210–211
2-NO2C6H4
3-NO2C6H4
2-CH3OC6H4
4-CH3OC6H4
8
9
10
207–208
(Continued )

2548
Entry
11
A. UPADHYAY, S. K. SRIVASTAVA, AND S. D. SRIVASTAVA
Table 1. Continued
Ar
Product
Yield (%)
Melting point (ꢁC)
4-CH3C6H4
70
192–193
12
4-N(CH3)2C6H4
65
195–196
silica gel and recrystallized from acetone to furnish compound 2. Yield 80%; mp
210–211 ꢁC; IR (n, cmꢀ1, KBr]: 3252, 3378 (ꢀNHNH2), 3045 (C-H, Ar-H), 1678
1
=
=
(>C O, amide), 1600 (N CHꢀ, cyclic), 1527, 1333 (ArNO2), 1427 (NꢀCH2); H
=
NMR (400 MHz, CDCl3): d 8.20 (s, 1H, CONH), 7.89 (s, 1H, N CHꢀ, cyclic),
7.25–7.61 (m, 3H, Ar-H), 4.45 (s, 2H, NH2), 2.49 (s, 2H, NꢀCH2); 13C NMR
=
(100 MHz, CDCl3): d 168.0 (CONH), 142.2 (C-NO2, aromatic), 135.2 (N CHꢀ,
cyclic), 111.9–122.0 (C of aromatic ring), 33.5 (NꢀCH2). Mass (m=z): 235 [Mþ],
204, 189, 176, 162, 134, 88. Anal. (%) for C9H9N5O3: calcd. C, 45.96; H, 3.83; N,
29.79. Found: C, 45.90; H, 3.79; N, 29.76.
Synthesis of N-(Benzylidene amino acetamidyl)-5-nitroindazole (3a)
Equimolar solution of the compound 2 (1.8 g, 0.008 mol) and benzaldehyde
(0.81 g, 0.008 mol) in dioxane (30 ml) was stirred for about 1 h. The solvent was
removed in vacuo, and the residue thus obtained was purified over the column of sil-
ica gel and recrystallized from chloroform to furnish compound 3a. Yield 80%; mp
ꢀ1
200–202 ꢁC; IR (n, cm , KBr): 3043 (C-H, Ar-H), 1674 (>C O, amide), 1635
=
=
=
(N CHꢀ, acyclic), 1604 (N CHꢀ, cyclic), 1524, 1329 (ArNO2), 1428 (NꢀCH2);
1
=
H NMR (400 MHz, CDCl3): d 8.21 (s, 1H, CONH), 8.70 (s, 1H, N CHꢀ, acyclic),
7.86 (s, 1H, N CHꢀ, cyclic), 7.27–7.63 (m, 8H, Ar-H), 2.52 (s, 2H, NꢀCH2); 13C
=
=
NMR (100 MHz, CDCl3): d 168.1 (CONH), 143.2 (N CH, acyclic), 142.3
=
(C-NO2, aromatic), 135.6 (N CHꢀ, cyclic), 112.1–122.2 (C of aromatic ring), 33.4
(NꢀCH2). Mass (m=z): 323 [Mþ], 277, 219, 204, 176, 162, 161, 147, 134, 119, 104,
88. Anal. (%) for C16H13N5O3: calcd. C, 59.44; H, 4.02; N, 21.67. Found: C,
59.40; H, 3.98; N, 21.63.
Other compounds 3b–l were prepared similarly by treating 2 with various
aromatic aldehydes.
N-(2-Hydroxybenzylidene amino acetamidyl)-5-nitroindazole (3b)
Yield 81%; mp 260–261 ꢁC; IR [n, cmꢀ1, KBr): 3246 (Ar-OH), 3047 (C-H,
=
=
=
Ar-H), 1672 (>C O, amide), 1637 (N CHꢀ, acyclic), 1602 (N CHꢀ, cyclic),

NEW 2-OXO-AZETIDINE DERIVATIVES
2549
1
1520, 1324 (ArNO2), 1431 (NꢀCH2); H NMR (400 MHz, CDCl3): d 11.95 (s, 1H,
=
Ar-OH), 8.71 (s, 1H, ꢀN CHꢀ, acyclic), 8.22 (s, 1H, CONH), 7.84 (s, 1H,
N CHꢀ, cyclic), 7.23–7.59 (m, 7H, Ar-H), 2.50 (s, 2H, NꢀCH2); 13C NMR
=
=
(100 MHz, CDCl3): d 167.9 (CONH), 165.1 (C-OH, aromatic), 143.1 (N CHꢀ,
=
acyclic), 142.4 (C-NO2, aromatic), 135.4 (N CHꢀ, cyclic), 112.3–122.6 (C of aro-
matic ring), 33.6 (NꢀCH2). Mass (m=z): 339 [Mþ], 293, 219, 204, 177, 176, 163,
162, 135, 134, 120, 88. Anal. (%) for C16H13N5O4: calcd. C, 56.64; H, 3.83; N,
20.65. Found: C, 56.59; H, 3.79; N, 20.61.
N-(2-Chlorobenzylidene amino acetamidyl)-5-nitroindazole (3c)
Yield 72%; mp 152–155 ꢁC; IR (n, cmꢀ1, KBr): 3042 (C-H, Ar-H), 1669
=
=
=
(>C O, amide), 1639 (N CHꢀ, acyclic), 1605 (N CHꢀ, cyclic), 1523, 1327
(ArNO2), 1432 (NꢀCH2), 754 (Ar-Cl); 1H NMR (400 MHz, CDCl3): d 8.73 (s,
=
=
1H, N CHꢀ, acyclic), 8.18 (s, 1H, CONH), 7.87 (s, 1H, N CHꢀ, cyclic),
7.20–7.55 (m, 7H, Ar-H), 2.54 (s, 2H, NꢀCH2); 13C NMR (100 MHz, CDCl3): d
=
167.7 (CONH), 143.0 (N CHꢀ, acyclic), 142.7 (C-NO2, aromatic), 135.8
=
(N CHꢀ, cyclic), 134.3 (C-Cl, aromatic), 112.8–122.3 (C of aromatic ring), 33.8
(NꢀCH2). Mass (m=z): 357.5 [Mþ], 311, 219, 204, 195, 181, 176, 162, 153, 138,
134, 88. Anal. (%) for C16H12N5O3Cl: calcd. C, 53.71; H, 3.36; N, 19.58. Found:
C, 53.67; H, 3.31; N, 19.52.
N-(4-Chlorobenzylidene amino acetamidyl)-5-nitroindazole (3d)
Yield 78%; mp 156–158 ꢁC; IR [n, cmꢀ1, KBr]: 3041 (C-H, Ar-H), 1671
=
=
=
(>C O, amide), 1636 (N CHꢀ, acyclic), 1603 (N CHꢀ, cyclic), 1528, 1325
(ArNO2), 1434 (NꢀCH2), 757 (Ar-Cl); 1H NMR (400 MHz, CDCl3): d 8.72 (s,
=
=
1H, -N CHꢀ, acyclic), 8.16 (s, 1H, CONH), 7.85 (s, 1H, N CHꢀ, cyclic),
7.21–7.57 (m, 7H, Ar-H), 2.55 (s, 2H, NꢀCH2); 13C NMR (100 MHz, CDCl3): d
=
167.5 (CONH), 143.3 (N CHꢀ, acyclic), 142.5 (C-NO2, aromatic), 135.3
=
(N CHꢀ, cyclic), 134.0 (C-Cl, aromatic), 112.0–122.1 (C of aromatic ring), 33.7
(NꢀCH2). Mass (m=z): 357.5 [Mþ], 311, 219, 204, 195, 181, 176, 162, 153, 138,
134, 88. Anal. (%) for C16H12N5O3Cl: calcd. C, 53.71; H, 3.36; N, 19.58. Found:
C, 53.68; H, 3.34; N, 19.54.
N-(2-Bromobenzylidene amino acetamidyl)-5-nitroindazole (3e)
Yield 74%; mp 190–192 ꢁC; IR (n, cmꢀ1, KBr): 3040 CꢀH, Ar-H), 1666
=
=
=
(>C O, amide), 1638 (N CHꢀ, acyclic), 1607 (N CHꢀ, cyclic), 1526, 1323
1
(ArNO2), 1436 (NꢀCH2), 618 (Ar-Br); H NMR (400 MHz, CDCl3): d 8.69 (s,
=
=
1H, -N CHꢀ, acyclic), 8.14 (s, 1H, CONH), 7.88 (s, 1H, N CHꢀ, cyclic),
7.22–7.58 (m, 7H, Ar-H), 2.53 (s, 2H, NꢀCH2); 13C NMR (100 MHz, CDCl3): d
=
167.8 (CONH), 143.6 (N CHꢀ, acyclic), 141.9 (C-NO2, aromatic), 135.1
=
(N CHꢀ, cyclic), 118.2 (C-Br, aromatic), 111.7–122.4 (C of aromatic ring), 33.9
(NꢀCH2). Mass (m=z): 401.9 [Mþ], 356, 240, 226, 219, 208, 198, 183, 176, 162,
134, 88. Anal. (%) for C16H12N5O3Br; calcd. C, 47.76; H, 2.98; N, 17.41. Found:
C, 47.71; H, 2.93; N, 17.37.

2550
A. UPADHYAY, S. K. SRIVASTAVA, AND S. D. SRIVASTAVA
N-(3-Bromobenzylidene amino acetamidyl)-5-nitroindazole (3f)
Yield 72%; mp 188–190 ꢁC; IR (n, cmꢀ1, KBr): 3044 (CꢀH, Ar-H), 1661
=
=
=
(>C O, amide), 1640 (N CHꢀ, acyclic), 1606 (N CHꢀ, cyclic), 1522, 1326
1
(ArNO2), 1433 (NꢀCH2), 620 (Ar-Br). H NMR (400 MHz, CDCl3): d 8.65 (s,
=
=
1H, ꢀN CHꢀ, acyclic), 8.11 (s, 1H, CONH), 7.91 (s, 1H, N CHꢀ, cyclic),
7.24–7.56 (m, 7H, Ar-H), 2.56 (s, 2H, NꢀCH2); 13C NMR (100 MHz, CDCl3): d
=
168.2 (CONH), 143.4 (N CHꢀ, acyclic), 141.7 (C-NO2, aromatic), 135.5
=
(N CHꢀ, cyclic), 118.4 (C-Br, aromatic), 111.5–122.8 (C of aromatic ring), 34.0
(NꢀCH2). Mass (m=z): 401.9 [Mþ], 356, 240, 226, 219, 208, 198, 183, 176, 162,
134, 88. Anal. (%) for C16H12N5O3Br: calcd. C, 47.76; H, 2.98; N, 17.41. Found:
C, 47.73; H, 2.94; N, 17.38.
N-(2-Nitrobenzylidene amino acetamidyl)-5-nitroindazole (3g)
Yield 83%; mp 210–212 ꢁC; IR (n, cmꢀ1, KBr): 3048 (CꢀH, Ar-H), 1662
=
=
1
=
(>C O, amide), 1642 (N CHꢀ, acyclic), 1609 (N CHꢀ, cyclic), 1525, 1328
=
(ArNO2), 1429 (NꢀCH2); H NMR (400 MHz, CDCl3): d 8.68 (s, 1H, ꢀN CHꢀ,
=
acyclic), 8.13 (s, 1H, CONH), 7.93 (s, 1H, N CHꢀ, cyclic), 7.28–7.62 (m, 7H,
Ar-H), 2.60 (s, 2H, NꢀCH2); 13C NMR (100 MHz, CDCl3): d 168.5 (CONH),
=
=
143.5 (N CHꢀ, acyclic), 141.6 (C-NO2, aromatic), 135.7 (N CHꢀ, cyclic),
111.2–122.5 (C of aromatic ring), 34.1 (NꢀCH2). Mass (m=z): 368 [Mþ], 322, 219,
206, 204, 192, 176, 164, 149, 134, 88. Anal. (%) for C16H12N6O5: calcd. C, 52.17;
H, 3.26; N, 22.82. Found: C, 52.13; H, 3.21; N, 22.80.
N-(3-Nitrobenzylidene amino acetamidyl)-5-nitroindazole (3h)
Yield 85%; mp 214–215 ꢁC; IR (n, cmꢀ1, KBr): 3050 (CꢀH, Ar-H), 1664
=
=
=
(>C O, amide), 1641 (N CHꢀ, acyclic), 1608 (N CHꢀ, cyclic), 1529, 1332
1
=
(ArNO2), 1435 (NꢀCH2), H NMR (400 MHz, CDCl3): d 8.66 (s, 1H, ꢀN CHꢀ,
=
acyclic), 8.12 (s, 1H, CONH), 7.92 (s, 1H, N CHꢀ, cyclic), 7.31–7.65 (m, 7H,
Ar-H), 2.59 (s, 2H, NꢀCH2); 13C NMR (100 MHz, CDCl3): d 168.3 (CONH),
=
=
143.7 (N CHꢀ, acyclic), 141.8 (C-NO2, aromatic), 135.9 (N CHꢀ, cyclic),
111.3–122.7 (C of aromatic ring), 34.3 (NꢀCH2). Mass (m=z): 368 [Mþ], 322, 219,
206, 204, 192, 176, 164, 149, 134, 88. Anal. (%) for C16Hꢀ12N6O5: calcd. C, 52.17;
H, 3.26; N, 22.82. Found: C, 52.14; H, 3.23; N, 22.83.
N-(2-Methoxybenzylidene amino acetamidyl)-5-nitroindazole (3i)
Yield 72%; mp 220–222 ꢁC; IR [n, cmꢀ1, KBr]: 3049 (CꢀH, Ar-H), 2825
=
=
=
(Ar-OCH3), 1663 (>C O, amide), 1644 (N CHꢀ, acyclic), 1610 (N CHꢀ, cyclic),
1
1533, 1331 (ArNO2), 1437 (NꢀCH2); H NMR (400 MHz, CDCl3): d 8.67 (s, 1H,
=
=
ꢀN CHꢀ, acyclic), 8.15 (s, 1H, CONH), 7.94 (s, 1H, N CHꢀ, cyclic), 7.30–7.67
(m, 7H, Ar-H), 3.96 (s, 3H, OCH3), 2.58 (s, 2H, NꢀCH2); 13C NMR (100 MHz,
=
CDCl3): d 168.4 (CONH), 144.0 (N CHꢀ, acyclic), 142.6 (C-NO2, aromatic), 136.1
=
(N CHꢀ, cyclic), 110.5–122.9 (C of aromatic ring), 55.8 (OCH3), 34.5 (NꢀCH2).
Mass (m=z): 353 [Mþ], 219, 204, 191, 177, 176, 162, 149, 134, 88. Anal. (%) for
C17H15N5O4: calcd. C, 57.79; H, 4.25; N, 19.83. Found: C, 57.73; H, 4.21; N, 19.79.

NEW 2-OXO-AZETIDINE DERIVATIVES
2551
N-(4-Methoxybenzylidene amino acetamidyl)-5-nitroindazole (3j)
Yield 80%; mp 224–225 ꢁC; IR (n, cmꢀ1, KBr): 3053 (CꢀH, Ar-H), 2828
=
=
=
(Ar-OCH3), 1665 (>C O, amide), 1643 (N CHꢀ, acyclic), 1613 (N CHꢀ, cyclic),
1
1532, 1335 (ArNO2), 1439 (NꢀCH2); H NMR (400 MHz, CDCl3): d 8.64 (s, 1H,
=
=
ꢀN CHꢀ, acyclic), 8.17 (s, 1H, CONH), 7.95 (s, 1H, N CHꢀ, cyclic), 7.29–7.66
(m, 7H, Ar-H), 3.95 (s, 3H, OCH3), 2.57 (s, H, NꢀCH2); 13C NMR (100 MHz,
=
CDCl3): d 168.6 (CONH), 143.8 (N CHꢀ, acyclic), 143.1 (C-NO2, aromatic),
=
136.3 (N CH, cyclic), 110.4–123.0 (C of aromatic ring), 55.5 (OCH3), 34.2
(NꢀCH2). Mass (m=z): 353 [Mþ], 219, 204, 191, 177, 176, 162, 149, 134, 88. Anal.
(%) for C17H15N5O4: calcd. C, 57.79; H, 4.25; N, 19.83. Found: C, 57.76; H, 4.22;
N, 19.78.
N-(4-Methylbenzylidene amino acetamidyl)-5-nitroindazole (3k)
Yield 70%; mp 200–201 ꢁC; IR (n, cmꢀ1, KBr): 3051 (CꢀH, Ar-H), 2920
=
=
=
(Ar-CH3), 1667 (>C O, amide), 1645 (N CHꢀ, acyclic), 1611 (N CHꢀ, cyclic),
1
1534, 1337 (ArNO2), 1440 (NꢀCH2), H NMR (400 MHz, CDCl3): d 8.62 (s, 1H,
=
=
ꢀN CHꢀ, acyclic), 8.19 (s, 1H, CONH), 7.96 (s, 1H, N CHꢀ, cyclic), 7.32–7.68
(m, 7H, Ar-H), 2.61 (s, 2H, NꢀCH2), 2.37 (s, 3H, Ar-CH3); 13C NMR (100 MHz,
=
CDCl3): d 168.8 (CONH), 143.9 (N CHꢀ, acyclic), 142.8 (C-NO2, aromatic),
=
136.0 (N CHꢀ, cyclic), 110.0–123.2 (C of aromatic ring), 34.4 (NꢀCH2), 22.5
(CH3). Mass (m=z): 337 [Mþ], 291, 219, 204, 190, 176, 162, 147, 134, 88. Anal. (%)
for C17H15N5O3: calcd. C, 60.53; H, 4.45; N, 20.77. Found: C, 60.51; H, 4.41; N,
20.72.
N-(4-Dimethylaminobenzylidene amino acetamidyl)-5-
nitroindazole (3l)
Yield 73%; mp 205–206 ꢁC; IR (n, cmꢀ1, KBr): 3054 (CꢀH, Ar-H), 2910, 2852
=
=
=
(NꢀCH3), 1668 (>C O, amide), 1647 (N CHꢀ, acyclic), 1612 (N CHꢀ, cyclic),
1
1536, 1336 (ArNO2), 1438 (NꢀCH2); H NMR [400 MHz, CDCl3]: 8.63 (s, 1H,
=
=
ꢀN CHꢀ, acyclic), 8.23 (s, 1H, CONH), 7.98 (s, 1H, N CHꢀ, cyclic), 7.34–7.64
(m, 7H, Ar-H), 3.12 (s, 6H, 2 ꢂ CH3), 2.63 (s, 2H, NꢀCH2); 13C NMR (100 MHz,
=
CDCl3): d 168.7 (CONH), 144.1 (N CHꢀ, acyclic), 143.0 (C-NO2, aromatic),
=
136.4 (N CHꢀ, cyclic), 110.3–123.1 (C of aromatic ring), 34.7 (NꢀCH2), 23.7
(NCH3). Mass (m=z): 366 [Mþ], 320, 219, 204, 190, 176, 162, 147, 134, 88. Anal.
(%) for C18H18N6O3: calcd. C, 59.02; H, 4.92; N, 22.95. Found: C, 58.97; H, 4.88;
N, 22.90.
Synthesis of N-[(4-Phenyl-3-chloro-2-oxo-azetidine)
acetamidyl]-5-nitroindazole (4a)
An equimolar solution of the compound 3a (1 g, 0.003 mol) and chloroacetyl
chloride (0.35 g, 0.003 mol) with triethylamine (0.31 g, 0.003 mol) in acetone (25 ml)
was stirred for about 5 h. The solvent was removed in vacuo, and the residue thus
obtained was purified over a column of silica gel and recrystallized from chloroform

2552
A. UPADHYAY, S. K. SRIVASTAVA, AND S. D. SRIVASTAVA
to furnish compound 4a. Yield 72%; mp 197–198 ꢁC; IR (n, cmꢀ1, KBr): 3055 (CꢀH,
=
=
=
Ar-H), 1730 (>C O, cyclic), 1672 (>C O, amide), 1613 (N CHꢀ, cyclic), 1535,
1
1339 (ArNO2), 1442 (NꢀCH2), 738 (CH-Cl); H NMR (400 MHz, CDCl3): d 8.27
=
(s, 1H, CONH), 8.01 (s, 1H, N CHꢀ, cyclic), 7.38–7.71 (m, 8H, Ar-H), 5.01 (d,
1H, J ¼ 5 Hz, CHCl), 4.19 (d, 1H, J ¼ 5 Hz, ꢀNꢀCHꢀ), 2.66 (s, 2H, NꢀCH2); 13C
=
NMR (100 MHz, CDCl3): d 171.2 (>C O, cyclic), 167.5 (CONH), 143.7 (C-NO2,
=
aromatic), 137.1 (N CHꢀ, cyclic), 132.1 (CH-Cl), 112.2–124.3 (C of aromatic ring),
39.1 (NꢀCH-), 35.1 (NꢀCH2). Mass (m=z): 399 [Mþ], 371, 353, 325, 237, 223, 219,
209, 204, 195, 180, 176, 167, 162, 152, 134, 88. Anal. (%) for C18H14N5O4Cl: calcd.
C, 54.07; H, 3.50; N, 17.52. Found: C, 54.04; H, 3.46; N, 17.48.
Other compounds 4b–l were prepared similarly by using 3b–l respectively.
N-[f4-(2-Hydroxyphenyl)-3-chloro-2-oxo-
azetidinegacetamidyl]-5-nitroindazole (4b)
IR [n, cmꢀ1, KBr]: 3244 (Ar-OH), 3057 (CꢀH, Ar-H), 1733 (>C O, cyclic),
=
=
=
1674 (>C O, amide), 1615 (N CHꢀ, cyclic), 1537,1340 (ArNO2), 1444 (NꢀCH2),
1
739 (CH-Cl); H NMR (400 MHz, CDCl3): d 11.96 (s, 1H, Ar-OH), 8.28 (s, 1H,
=
CONH), 8.03 (s, 1H, N CHꢀ, cyclic), 7.40–7.70 (m, 7H, Ar-H), 5.03 (d, 1H,
J ¼ 5 Hz, CHCl), 4.22 (d, 1H, J ¼ 5 Hz, ꢀNꢀCHꢀ), 2.67 (s, 2H, NꢀCH2); 13C
=
NMR (100 MHz, CDCl3): d 171.3 (>C O, cyclic), 167.8 (CONH), 165.3 (C-OH,
=
aromatic), 143.5 (C-NO2, aromatic), 137.3 (N CHꢀ, cyclic), 132.2 (CH-Cl),
112.5–124.1 (C of aromatic ring), 39.3 (NꢀCH-), 35.3 (NꢀCH2). Mass (m=z): 415
[Mþ], 387, 369, 341, 253, 239, 225, 219, 211, 204, 196, 183, 176, 168, 162, 134, 88.
Anal. (%) for C18H14N5O5Cl; calcd. C, 51.98; H, 3.37; N, 16.85. Found: C, 51.95;
H, 3.33; N, 16.81.
N-[f4-(2-Chlorophenyl)-3-chloro-2-oxo-
azetidinegacetamidyl]-5-nitroindazole (4c)
IR (n, cmꢀ1, KBr): 3059 (CꢀH, Ar-H), 1731 (>C O, cyclic), 1673 (>C O,
=
=
=
amide), 1614 (N CHꢀ, cyclic), 1536, 1338 (ArNO2), 1443 (NꢀCH2), 755 (Ar-Cl),
1
740 (CH-Cl); H NMR (400 MHz, CDCl3): d 8.30 (s, 1H, CONH), 8.02 (s, 1H,
=
N CHꢀ, cyclic), 7.41–7.72 (m, 7H, Ar-H), 5.02 (d, 1H, J ¼ 5 Hz, CHCl), 4.21 (d,
1H, J ¼ 5 Hz, -NꢀCH-), 2.69 (s, 2H, NꢀCH2); 13C NMR (100 MHz, CDCl3): d
=
=
171.4 (>C O, cyclic), 167.6 (CONH), 143.6 (C-NO2, aromatic), 137.6 (N CHꢀ,
cyclic), 134.1 (C-Cl, aromatic), 132.4 (CH-Cl), 112.3–124.2 (C of aromatic ring),
39.2 (NꢀCH-), 35.2 (NꢀCH2). Mass (m=z): 434 [Mþ], 406, 388, 360, 272, 258,
244, 230, 219, 215, 204, 202, 187, 176, 162, 134, 88. Anal. (%) for C18H13N5O4Cl2:
calcd. C, 49.77; H, 2.99; N, 16.13. Found: C, 49.74; H, 2.95; N, 16.10.
N-[f4-(4-Chlorophenyl)-3-chloro-2-oxo-
azetidinegacetamidyl]-5-nitroindazole (4d)
IR (n, cmꢀ1, KBr): 3061 (CꢀH, Ar-H), 1734 (>C O, cyclic), 1671 (>C O,
=
=
=
amide), 1616 (N CHꢀ, cyclic), 1538, 1341 (ArNO2), 1445 (NꢀCH2), 756 (Ar-Cl),
1
741 (CH-Cl); H NMR (400 MHz, CDCl3): d 8.29 (s, 1H, CONH), 8.04 (s, 1H,

NEW 2-OXO-AZETIDINE DERIVATIVES
2553
=
N CHꢀ, cyclic), 7.43–7.73 (m, 7H, Ar-H), 5.04 (d, 1H, J ¼ 5 Hz, CHCl), 4.23 (d,
1H, J ¼ 5 Hz, -NꢀCH-), 2.68 (s, 2H, NꢀCH2); 13C NMR (100 MHz, CDCl3): d
=
=
171.6 (>C O, cyclic), 167.7 (CONH), 143.3 (C-NO2, aromatic), 137.4 (N CHꢀ,
cyclic), 134.1 (C-Cl, aromatic), 132.3 (CH-Cl), 112.4–124.4 (C of aromatic ring),
39.4 (NꢀCH-), 35.4 (NꢀCH2). Mass (m=z): 434 [Mþ], 406, 388, 360, 272, 258,
244, 230, 219, 215, 204, 202, 187, 176, 162, 134, 88. Anal. (%) for C18H13N5O4Cl2:
calcd. C, 49.77; H, 2.99; N, 16.13. Found: C, 49.75; H, 2.96; N, 16.11.
N-[f4-(2-Bromophenyl)-3-chloro-2-oxo-
azetidinegacetamidyl]-5-nitroindazole (4e)
IR (n, cmꢀ1, KBr): 3060 (CꢀH, Ar-H), 1732 (>C O, cyclic), 1675 (>C O,
=
=
=
amide), 1618 (N CHꢀ, cyclic), 1539, 1342 (ArNO2), 1446 (NꢀCH2), 743 (CH-Cl),
1
623 (Ar-Br); H NMR (400 MHz, CDCl3): d 8.32 (s, 1H, CONH), 8.06 (s, 1H,
=
N CHꢀ, cyclic), 7.45–7.69 (m, 7H, Ar-H), 5.06 (d, 1H, J ¼ 5 Hz, CHCl), 4.25 (d,
1H, J ¼ 5 Hz, -NꢀCH-), 2.70 (s, 2H, NꢀCH2); 13C NMR (100 MHz, CDCl3): d
=
=
171.7 (>C O, cyclic), 168.1 (CONH), 143.1 (C-NO2, aromatic), 137.5 (N CHꢀ,
cyclic), 132.5 (CH-Cl), 118.1 (C-Br, aromatic), 112.6–124.6 (C of aromatic ring),
39.6 (NꢀCH-), 35.5 (NꢀCH2). Mass (m=z): 478 [Mþ], 450, 432, 404, 316, 302,
288, 274, 259, 246, 231, 219, 204, 176, 162, 134, 88. Anal. (%) for C18H13N5O4ClBr:
calcd. C, 45.14; H, 2.72; N, 14.63. Found: C, 45.11; H, 2.69; N, 14.58.
N-[f4-(3-Bromophenyl)-3-chloro-2-oxo-
azetidinegacetamidyl]-5-nitroindazole (4f)
IR (n, cmꢀ1, KBr): 3062 (CꢀH, Ar-H), 1735 (>C O, cyclic), 1676 (>C O,
=
=
=
amide), 1617 (N CHꢀ, cyclic), 1541, 1343 (ArNO2), 1448 (NꢀCH2), 742 (CH-Cl),
1
619 (Ar-Br); H NMR (400 MHz, CDCl3): d 8.31 (s, 1H, CONH), 8.08 (s, 1H,
=
N CHꢀ, cyclic), 7.42–7.74 (m, 7H, Ar-H), 5.05 (d, 1H, J ¼ 5 Hz, CHCl), 4.24 (d,
1H, J ¼ 5 Hz, -NꢀCH-), 2.72 (s, 2H, NꢀCH2); 13C NMR (100 MHz, CDCl3): d
=
=
171.9 (>C O, cyclic), 168.3 (CONH), 143.2 (C-NO2, aromatic), 137.7 (N CHꢀ,
cyclic), 132.6 (CH-Cl), 118.3 (C-Br, aromatic), 112.7–124.7 (C of aromatic ring),
39.7 (NꢀCH-), 35.7 (NꢀCH2). Mass (m=z): 478 [Mþ], 450, 432, 404, 316, 302,
288, 274, 259, 246, 231, 219, 204, 176, 162, 134, 88. Anal. (%) for C18H13N5O4ClBr:
calcd. C, 45.14; H, 2.72; N, 14.63. Found: C, 45.10; H, 2.68; N, 14.60.
N-[f4-(2-Nitrophenyl)-3-chloro-2-oxo-
azetidinegacetamidyl]-5-nitroindazole (4g)
IR (n, cmꢀ1, KBr): 3065 (CꢀH, Ar-H), 1736 (>C O, cyclic), 1678 (>C O,
=
=
=
amide), 1619 (N CHꢀ, cyclic), 1540, 1344 (ArNO2), 1447 (NꢀCH2), 744 (CH-Cl);
1
=
H NMR (400 MHz, CDCl3): d 8.33 (s, 1H, CONH), 8.10 (s, 1H, N CHꢀ, cyclic),
13
7.46–7.76 (m, 7H, Ar-H), 5.07 (d, 1H, J ¼ 5 Hz, CHCl), 4.26 (d, 1H, J ¼ 5 Hz,
=
ꢀNꢀCHꢀ), 2.71 (s, 2H, NꢀCH2); C NMR (100 MHz, CDCl3): d 172.2 (>C O,
=
cyclic), 168.2 (CONH), 143.4 (C-NO2, aromatic), 137.8 (N CHꢀ, cyclic), 132.7
(CH-Cl), 112.9–124.8 (C of aromatic ring), 39.5 (NꢀCH-), 35.6 (NꢀCH2). Mass
(m=z): 444 [Mþ], 416, 398, 376, 282, 268, 254, 240, 225, 219, 212, 204, 197, 176,

2554
A. UPADHYAY, S. K. SRIVASTAVA, AND S. D. SRIVASTAVA
162, 134, 88. Anal. (%) for C18H13N6O6Cl: calcd. C, 48.59; H, 2.92; N, 18.90. Found:
C, 48.55; H, 2.88; N, 18.86.
N-[f4-(3-Nitrophenyl)-3-chloro-2-oxo-
azetidinegacetamidyl]-5-nitroindazole (4h)
IR (n, cmꢀ1, KBr): 3064 (CꢀH, Ar-H), 1738 (>C O, cyclic), 1677 (>C O,
=
=
=
amide), 1620 (N CHꢀ, cyclic), 1542, 1346 (ArNO2), 1449 (NꢀCH2), 745 (CH-Cl);
1
=
H NMR (400 MHz, CDCl3): d 8.35 (s, 1H, CONH), 8.09 (s, 1H, N CHꢀ, cyclic),
13
7.47–7.78 (m, 7H, Ar-H), 5.09 (d, 1H, J ¼ 5 Hz, CHCl), 4.27 (d, 1H, J ¼ 5 Hz,
=
ꢀNꢀCHꢀ), 2.73 (s, 2H, NꢀCH2); CNMR (100 MHz, CDCl3): d 172.1 (>C O,
=
cyclic), 168.4 (CONH), 143.8 (C-NO2, aromatic), 137.9 (N CHꢀ, cyclic), 132.9
(CH-Cl), 112.8–125.1 (C of aromatic ring), 39.8 (NꢀCH-), 35.8 (NꢀCH2). Mass
(m=z): 444 [Mþ], 416, 398, 376, 282, 268, 254, 240, 225, 219, 212, 204, 197, 176,
162, 134, 88. Anal. (%) for C18H13N6O6Cl: calcd. C, 48.59; H, 2.92; N, 18.90. Found:
C, 48.56; H, 2.89; N, 18.87.
N-[f4-(2-Methoxyphenyl)-3-chloro-2-oxo-
azetidinegacetamidyl]-5-nitroindazole (4i)
IR (n, cmꢀ1, KBr): 3063 (CꢀH, Ar-H), 2823 (Ar-OCH3), 1737 (>C O, cyclic),
=
=
=
1680 (>C O, amide), 1622 (N CHꢀ, cyclic), 1544, 1348 (ArNO2), 1450 (NꢀCH2),
1
747 (CH-Cl); H NMR (400 MHz, CDCl3): d 8.34 (s, 1H, CONH), 8.07 (s, 1H,
=
N CHꢀ, cyclic), 7.48–7.77 (m, 7H, Ar-H), 5.08 (d, 1H, J ¼ 5 Hz, CHCl), 4.29 (d,
1H, J ¼ 5 Hz, ꢀNꢀCHꢀ), 3.94 (s, 3H, OCH3), 2.75 (s, 2H, NꢀCH2); 13C NMR
=
(100 MHz, CDCl3): d 172.3 (>C O, cyclic), 168.5 (CONH), 144.1 (C-NO2,
=
aromatic), 138.1 (N CHꢀ, cyclic), 132.8 (CH-Cl), 113.1–125.2 (C of aromatic ring),
55.7 (OCH3), 39.9 (NꢀCH-), 35.9 (NꢀCH2). Mass (m=z): 429 [Mþ], 401, 383,
355, 267, 253, 239, 225, 219, 210, 204, 197, 182, 176, 162, 134, 88. Anal. (%)
for C19H16N5O5Cl: calcd. C, 53.08; H, 3.72; N, 16.30. Found: C, 53.05; H, 3.69;
N, 16.26.
N-[f4-(4-Methoxyphenyl)-3-chloro-2-oxo-
azetidinegacetamidyl]-5-nitroindazole (4j)
IR (n, cmꢀ1, KBr]: 3066 (CꢀH, Ar-H), 2824 (Ar-OCH3), 1739 (>C O, cyclic),
=
=
=
1682 (>C O, amide), 1621 (N CHꢀ, cyclic), 1543, 1347 (ArNO2), 1452 (NꢀCH2),
1
746 (CH-Cl); H NMR (400 MHz, CDCl3): d 8.36 (s, 1H, CONH), 8.11 (s, 1H,
=
N CHꢀ, cyclic), 7.50–7.80 (m, 7H, Ar-H), 5.10 (d, 1H, J ¼ 5 Hz, CHCl), 4.28 (d,
1H, J ¼ 5 Hz, -NꢀCH-), 3.97 (s, 3H, OCH3), 2.74 (s, 2H, NꢀCH2); 13C NMR
=
(100 MHz, CDCl3): d 172.4 (>C O, cyclic), 168.7 (CONH), 143.9 (C-NO2,
=
aromatic), 138.3 (N CHꢀ, cyclic), 133.1 (CH-Cl), 113.2–125.4 (C of aromatic
ring), 55.9 (OCH3), 40.0 (NꢀCH-), 36.1 (NꢀCH2). Mass (m=z): 429 [Mþ], 401,
383, 355, 267, 253, 239, 225, 219, 210, 204, 197, 182, 176, 162, 134, 88. Anal. (%)
for C19H16N5O5Cl: calcd. C, 53.08; H, 3.72; N, 16.30. Found: C, 53.04; H, 3.68;
N, 16.27.

NEW 2-OXO-AZETIDINE DERIVATIVES
2555
N-[f4-(4-Methylphenyl)-3-chloro-2-oxo-
azetidinegacetamidyl]-5-nitroindazole (4k)
IR [n, cmꢀ1, KBr]: 3067 (CꢀH, Ar-H), 2921 (Ar-CH3), 1740 (>C O, cyclic),
=
=
=
1681 (>C O, amide), 1623 (N CHꢀ, cyclic), 1545, 1349 (ArNO2), 1451 (NꢀCH2),
1
748 (CH-Cl); H NMR (400 MHz, CDCl3): d 8.37 (s, 1H, CONH), 8.12 (s, 1H,
=
N CHꢀ, cyclic), 7.49–7.79 (m, 7H, Ar-H), 5.11 (d, 1H, J ¼ 5 Hz, CHCl), 4.30 (d,
1H, J ¼ 5 Hz, ꢀNꢀCHꢀ), 2.76 (s, 2H, NꢀCH2), 2.36 (s, 3H, Ar-CH3); 13C NMR
=
(100 MHz, CDCl3): d 172.5 (>C O, cyclic), 168.6 (CONH), 144.2 (C-NO2,
=
aromatic), 138.2 (N CHꢀ, cyclic), 133.2 (CH-Cl), 113.3–125.3 (C of aromatic
ring), 40.1 (NꢀCH-), 36.2 (NꢀCH2), 22.7 (CH3). Mass (m=z): 413 [Mþ], 385, 367,
339, 251, 237, 223, 219, 209, 204, 194, 181, 176, 166, 162, 134, 88. Anal. (%)
for C19H16N5O4Cl: calcd. C, 55.14; H, 3.87; N, 16.93. Found: C, 55.11; H, 3.83;
N, 16.89.
N-[f4-(4-Dimethylaminophenyl)-3-chloro-2-oxo-
azetidinegacetamidyl]-5-nitroindazole (4l)
IR (n, cmꢀ1, KBr): 3068 (CꢀH, Ar-H), 2911, 2851 (NꢀCH3), 1741 (>C O,
=
=
=
cyclic), 1683 (>C O, amide), 1624 (N CHꢀ, cyclic), 1546, 1350 (ArNO2), 1453
1
(NꢀCH2), 749 (CH-Cl); H NMR (400 MHz, CDCl3): d 8.38 (s, 1H, CONH), 8.13
=
(s, 1H, N CHꢀ, cyclic), 7.51–7.81 (m, 8H, Ar-H), 5.12 (d, 1H, J ¼ 5 Hz, CHCl),
13
4.31 (d, 1H, J ¼ 5 Hz, ꢀNꢀCHꢀ), 3.15 (s, 6H, 2 ꢂ CH3), 2.77 (s, 2H, NꢀCH2);
=
C NMR (100 MHz, CDCl3): d 172.6 (>C O, cyclic), 168.8 (CONH), 144.3
=
(C-NO2, aromatic), 138.4 (N CHꢀ, cyclic), 133.3 (CH-Cl), 113.4–125.5 (C of aro-
matic ring), 40.2 (NꢀCH-), 36.3 (NꢀCH2), 23.8 (NCH3). Mass (m=z): 442 [Mþ],
414, 396, 374, 280, 266, 252, 238, 223, 219, 210, 204, 195, 176, 162, 134, 88. Anal.
(%) for C20H19N6O4Cl; calcd. C, 54.24; H, 4.29; N, 18.98. Found: C, 54.20; H,
4.26; N, 18.94.
ACKNOWLEDGMENTS
The authors are thankful to SAIF, CDRI Lucknow (India) for providing the
spectral and analytical data of the compounds. Authors are also thankful to the head,
Department of Chemistry, for providing the laboratory facility. One of the authors
(A. Upadhyay) is also grateful to the University Grants Commission, New Delhi,
India, for the award of a UGC Meritorious Research Fellowship.
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