Synthesis and antimicrobial evaluation of new monocyclic β-lactams

Article abstract of DOI:10.1002/jhet.973

A simple, practical, and efficient approach to synthesize new series of 2-(3-(2,4-dichlorophenoxy)-2-(4-(dimethylamino)phenyl)-4-oxoazetidin-1-ylamino) -N-arylacetamide by Staudinger [2 + 2] cycloaddition reaction. The titled compounds were evaluated for

Full text of DOI:10.1002/jhet.973

September 2012
Synthesis and Antimicrobial Evaluation of New
1151
Monocyclic β-Lactams
a
a
a
*
Ramakanth Pagadala, Jyotsna S. Meshram, Himani N. Chopde,
Venkateshwarlu Jetti,a Praveen Chidurala,a and Uppalaiah Kusampallyb
aDepartment of Chemistry, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur-440 033,
Maharashtra, India
bDepartment of Chemistry, Osmania University, Hyderabad-500 007, Andhrapradesh, India
*
E-mail: drjsmeshram@rediffmail.com
Received December 11, 2010
DOI 10.1002/jhet.973
Published online 26 October 2012 in Wiley Online Library (wileyonlinelibrary.com).
A simple, practical, and efficient approach to synthesize new series of 2-(3-(2,4-dichlorophenoxy)-2-
(4-(dimethylamino)phenyl)-4-oxoazetidin-1-ylamino)-N-arylacetamide by Staudinger [2 + 2] cycloaddi-
tion reaction. The titled compounds were evaluated for their antibacterial and antifungal activity against
eight microorganisms. All the newly synthesized compounds are characterized by IR, 1H-NMR, and
mass spectroscopic data.
J. Heterocyclic Chem., 49, 1151 (2012).
INTRODUCTION
azetidin-2-one, has gained enormous attention [10], so
functionalization of the azetidin-2-one framework is piv-
otal for the development of new β-lactam antibiotics
[11]. Researchers have shown some other useful biologi-
cal activities of such compounds, for example, cholesterol
absorption inhibition, enzymes inhibition, hypoglycemic,
and anticancer activity [12]. Ezetimibe, a monocyclic 2-
azetidinone, is clinically used as a cholesterol absorption
inhibitor [13]. Because of such a versatile applications, these
moieties always attracted the interest of synthetic and
medicinal organic chemists [14]. Hence, with these observa-
tion, we examined the feasibility and efficiency of an
approach to synthesize 2, 4-dichlorophenoxy and N,N-
dimethylamino group coupled with azetidinone nucleus,
which turns to exhibit significant antimicrobial activities.
In the past few years, there is an increasing interest in the
research area of four-membered heterocycles, the effective-
ness of β-lactam heterocycle in various important areas,
within many fields of Science, including medicine, biol-
ogy, and chemistry have been clearly demonstrated [1–7].
In addition to its use in the synthesis of variety of β-lactam
antibiotics, the β-lactam skeleton has been recognized as
a useful building block by exploiting its strain energy
associated with four-member ring [8]. An interesting
group of β-lactams are the monocyclic β-lactams, which
are molecules that do not contain another ring fused to
the β-lactam one. Natural and synthetic azetidinone deri-
vatives occupy a central place among medicinally impor-
tant compounds due to their diverse and interesting
antibiotic activities [9]. Even though they have a long
history of development starting from the discovery of
Penicillin in 1928, the quest for new synthetic methods
and refinement of those already known remains appeal-
ing, as does the research into the application of these
methods in synthesizing novel biologically active azetidi-
none derivatives.
RESULTS AND DISCUSSION
Chemistry. Preparation of new compounds 4a–j is
depicted on Scheme 1. Reaction course and formation
of products were monitored by thin layer chromatography
(TLC). 2-Chloro-N-arylacetamides (1) were synthesized by
various aromatic amines with chloroacetyl chloride. The
model reaction was carried out simply treatment of various
aromatic amines with chloroacetyl chloride yielded 2-
chloro-N-arylacetamide (1). These compounds, on amination
with hydrazine hydrate afforded 2-hydrazinyl-N-arylacetamides
The chemistry of small-ring nitrogen heterocycles are of
considerable interest not only because of their wide use
as important synthetic intermediates but also because of
their biological activities such as antibiotic properties.
Among them, the four-membered azetidine series, especially
© 2012 HeteroCorporation

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R. Pagadala, J. S. Meshram, H. N. Chopde, V. Jetti, P. Chidurala, and U. Kusampally
Vol 49
Scheme 1. Synthetic route for 2‐(3‐(2,4‐dichlorophenoxy)‐2‐(4‐(dimethylamino)phenyl)‐4‐oxoazetidin‐1‐ylamino)‐N‐arylacetamide.
(2). The condensation reaction of compound 2 with N,N-
dimethylaminobenzaldehyde yielded 2-(2-(4-(dimethylamino)
benzylidene)hydrazinyl)-N-arylacetamide (3a–j). Compounds
3a–j, on reaction with 2,4-dichlorophenoxy acetic acid in the
presence of POCl3 and triethylamine afforded azetidinone
(4a–j). These reactions are summarized in Scheme 1. The
required for a complete inhibition of the fungal and bacterial
growth after incubation time. For antifungal activity, each
fungus was spread on Sabouraud’s dextrose agar plates. For
antibacterial activity, Muller Hinton agar was used. The wells
of 6 mm diameter were filled with 0.1 mL of each compound
is diluted separately for each test of bacteria and fungi
strain. The antibiotic ampicillin and nystatin are used as
reference antibacterial and antifungal agents, respectively, for
comparison. Inoculated plates were then incubated at 37°C for
antibacterial activity for 24 h and 48 h at 28°C for antifungal
activity. After incubation, the antimicrobial activity was
measured in terms of the zone of inhibition in mm as shown
in Table 1. Biological screening results were mentioned in
mm, that is, showing diameter of inhibition zone, and these
are categorized, as 0–5 mm for mild, 6–12 mm for moderate,
end of the reaction was monitored by TLC.
Biological activity. Biological screening. The synthesized
compounds were screened by agar diffusion method [15,
16]. All human pathogenic bacteria viz. Bacillus subtilis,
Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris,
Staphylococcus aureus and fungi viz. Aspergillus flavus
and Aspergillus niger, Trichoderma viridae were obtained
from the Osmania University, Hyderabad, India. Stock
solutions of compounds were diluted in dimethyl sulfoxide
(DMSO) to give a final concentration for determining the
minimum inhibitory concentration (MIC) value. MIC was
defined as the lowest concentration of compound is
and 13–17 mm for efficacy, respectively.
Antibacterial studies. From Table 1, the investigation of
antibacterial screening data revealed that all the tested
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Synthesis and Antimicrobial Evaluation of New Monocyclic β-Lactams
1153
Table 1
Antimicrobial activities of synthesized compounds.
Bacteria (MIC at 100 μg/mL)
Gram positive
B
Gram negative
Fungi (MIC at 250 μg/mL)
Compd.
A
C
D
E
F
G
H
4a
4b
4c
4d
4e
4f
4g
4h
+++
+
++
+++
++
+
+++
−
+++
−
+++
++
++
++
+
++
+
+
++
+
+++
−
+
++
++
−
++
+++
−
−
+++
++
+
++
++
+++
+
+++
++
+
−
++
−
+++
+
+
++
+++
−
+
++
+
+++
−
++
−
++
+
++
−
++
+++
+
++
+++
++
++
+++
++
+++
+
++
++
+++
−
+++
+++
++
−
4i
4j
+
+++
+++
++
+++
++
Ampicillin
Nystatin
+++
+++
+++
Gram positive Bacteria: (A) Bacillus subtilis; (B) Proteus vulgaris; (C) Staphylococcus aureus; Gram negative Bacteria: (D) Escherichia coli; (E)
Klebsiella pneumonia; Fungi: (F) Aspergillus flavus; (G) Aspergillus niger; (H) Trichoderma viridae; inactive = − (inhibition zone < 5 mm); slightly
active = + (inhibition zone 5–12 mm); moderately active = ++ (inhibition zone 13–17 mm); highly active = +++ (inhibition zone > 17 mm).
General procedure for the synthesis of Schiff base (3a-j). A
quantity of 0.008 mol of N,N-dimethylaminobenzaldehyde, 0.008 mol
of 2-hydrazinyl-N-arylacetamide (2), and two to three drops of
glacial acetic acid in 20 mL of ethanol was refluxed for ∼1 h. The
reaction was monitored by TLC. After completion of the reaction,
the residue was stirred with ice-cold water, filtered, and dried. The
air which separates was induced to crystallize by rubbing with
glass rod. Solid deposit was collected by filtration and the crude
product obtained was purified by n-hexane and EtOAc.
compounds showed moderate to good bacterial inhibition.
Compounds 4a and 4h active against B. subtilis, 4c, 4f,
4h, and 4j for Proteus vulgaris, 4e, 4f, and 4j for S.
aureus, 4e and 4j for E. coli, and 4d for K. pneumonia
showed very good activity almost equivalent to that of
standard against all the bacterial strains. The rest of the
compounds were found to be moderately active, slightly
active or inactive against the tested microorganisms.
2-(2-(4-(Dimethylamino)benzylidene)hydrazinyl)-N-
phenylacetamide (3a). Yield 70%; IR (KBr, cmÀ1): 3198 (NH),
1608 (CONH), 1552 (—CH═N—); 1H-NMR (300 MHz,
CDCl3) δ (ppm) = 2.49 (s, 1H, NH), 2.9 (s, 6H, —N(CH3)2), 3.7
(s, 2H, CH2), 6.5–7.8 (m, 9H, Ar-H), 8.5 (s, 1H, CONH), 8.8 (s, 1H,
—CH═N—); Elemental analysis: Calcd. (found): C, 68.89 (68.82);
H, 6.80 (6.69); N, 18.90 (18.85); Mass spectra, m/z = 296 (100%).
N-(3-Chlorophenyl)-2-(2-(4-(dimethylamino) benzylidene)-
hydrazinyl)acetamide (3b). Yield 75%; IR (KBr, cmÀ1): 3379
(NH), 1647 (CONH), 1549 (—CH═N—); 1H-NMR (300 MHz,
CDCl3) δ (ppm) = 2.4 (s, 1H, NH), 2.94 (s, 6H, —N(CH3)2), 3.6
(s, 2H, CH2), 6.5–7.6 (m, 8H, Ar-H), 8.2 (s, 1H, CONH), 8.5 (s, 1H,
—CH═N—); Elemental analysis: Calcd. (found): C, 61.72 (61.75);
H, 5.79 (5.67); N, 16.94 (16.91); Mass spectra, m/z = 330 (100%).
2-(2-(4-(Dimethylamino)benzylidene)hydrazinyl)-N-(2-
nitrophenyl)acetamide (3c). Yield 77%; IR (KBr, cmÀ1): 3317
(NH), 1678 (CONH), 1541 (—CH═N—); 1H-NMR (300 MHz,
CDCl3) δ (ppm) ═ 2.43 (s, 1H, NH), 2.89 (s, 6H, —N(CH3)2), 3.8
(s, 2H, CH2), 6.7–7.9 (m, 8H, Ar-H), 8.0 (s, 1H, CONH), 8.4 (s, 1H,
—CH═N—); Elemental analysis: Calcd. (found): C, 59.81 (59.72);
H, 5.61 (5.49); N, 20.52 (20.45); Mass spectra, m/z = 341 (100%).
N-(4-Chlorophenyl)-2-(2-(4-(dimethylamino) benzylidene)-
hydrazinyl)acetamide (3d). Yield 79%; IR (KBr, cmÀ1): 3365
(NH), 1637 (CONH), 1521 (—CH═N—); 1H-NMR (300 MHz,
CDCl3) δ (ppm) = 2.41 (s, 1H, NH), 2.93 (s, 6H, —N(CH3)2), 3.4
(s, 2H, CH2), 6.5–7.6 (m, 8H, Ar-H), 8.2 (s, 1H, CONH), 8.5 (s, 1H,
—CH═N—); Elemental analysis: Calcd. (found): C, 61.72 (61.67);
H, 5.79 (5.72); N, 16.94 (16.98); Mass spectra, m/z = 330 (100%).
Antifungal studies. The antifungal activity of the
compounds was studied with three pathogenic fungi. The
results are summarized in Table 1. Nystatin has been used as
reference for inhibitory activity against fungi. Compounds 4c
and 4h for Aspergillus flavus, 4a, 4g, and 4j for Aspergillus
niger, 4c and 4h for Trichoderma viridae exhibited very
good activity almost equivalent to that of standard drug. The
rest of the compounds were found to be moderately active,
slightly active or inactive against all the fungal strains.
EXPERIMENTAL
General. All the chemicals and solvents were used analytical
reagent (AR) grade without further purification. Melting points
were taken in an open capillary tube. IR spectra were recorded
on a Shimadzu Dr-8031 instrument. 1H-NMR spectra of the
titled compounds were recorded on a Bruker-Avance (300 MHz)
spectrophotometer using DMSO solvent and tetra methyl silane
(TMS) as the internal standard. Elemental analyses were carried
out using a PerkinElmer, CHN elemental analyzer model 2400.
Electron impact mass spectrometer (EI-MS) spectra were
determined on a liquid chromatography quadrupole (LCQ) ion
trap mass spectrometer (Thermo Fisher, San Jose, CA), equipped
with an electron ionization (EI) source. The reactions were
monitored and the purity of products was checked out on
precoated TLC plates (Silica gel 60 F254, Merck), visualized the
spots under ultraviolet light and iodine chamber.
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2-(2-(4-(Dimethylamino)benzylidene)hydrazinyl)-N-(4-
CONH); Elemental analysis: Calcd. (found): C, 56.25 (56.18); H,
4.34 (4.28); N, 10.50 (10.49); Mass spectra, m/z = 532 (100%).
2-(3-(2,4-Dichlorophenoxy)-2-(4-(dimethylamino) phenyl)-
4-oxoazetidin-1-ylamino)-N-(2-nitrophenyl) acetamide (4c). Yield
65%; m.p. (°C): 168; IR (KBr, cmÀ1): 3263 (NH), 1670
nitrophenyl)acetamide (3e). Yield 68%; IR (KBr, cmÀ1): 3329
1
(NH), 1667 (CONH), 1545 (—CH═N—); H-NMR (300 MHz,
CDCl3) δ (ppm) = 2.43 (s, 1H, NH), 2.9 (s, 6H, —N(CH3)2), 3.7
(s, 2H, CH2), 6.6–7.9 (m, 8H, Ar-H), 8.1 (s, 1H, CONH), 8.3 (s,
1H, —CH═N—); Mass spectra, m/z = 341 (100%).
1
(CONH), 1734 (CO, β-lactam); H-NMR (300 MHz, CDCl3) δ
N-(2-Chlorophenyl)-2-(2-(4-(dimethylamino) benzylidene)-
hydrazinyl)acetamide (3f). Yield 72%; IR (KBr, cmÀ1): 3372
(NH), 1644 (CONH), 1532 (—CH═N—); 1H-NMR (300 MHz,
CDCl3) δ (ppm) = 2.3 (s, 1H, NH), 2.92 (s, 6H, —N(CH3)2), 3.8
(s, 2H, CH2), 6.5–7.6 (m, 8H, Ar-H), 8.4 (s, 1H, CONH), 8.7 (s,
1H, —CH═N—); Mass spectra, m/z = 330 (100%).
(ppm) = 2.82 (s, 6H, —N(CH3)2), 3.3 (s, 1H, NH), 3.62 (s, 2H,
CH2), 5.2 (d, 1H, J = 5.5 Hz, CH-Ar), 5.78 (d, 1H, J = 5.2 Hz,
CH-OAr), 6.5–8.0 (m, 11H, Ar-H), 8.6 (s, 1H, CONH);
Elemental analysis: Calcd. (found): C, 55.16 (55.22); H, 4.26
(4.19); N, 12.86 (12.68); Mass spectra, m/z = 543 (100%).
N-(4-Chlorophenyl)-2-(3-(2,4-dichlorophenoxy)-2-(4-
(dimethylamino)phenyl)-4-oxoazetidin-1-ylamino) acetamide
(4d). Yield 69%; m.p. (°C): 132; IR (KBr, cmÀ1): 3198
(NH), 1680 (CONH), 1732 (CO, β-lactam); 1H-NMR (300
MHz, CDCl3) δ (ppm) = 2.87 (s, 6H, —N(CH3)2), 3.1 (s,
1H, NH), 3.59 (s, 2H, CH2), 5.4 (d, 1H, J = 5.4 Hz, CH-
Ar), 5.8 (d, 1H, J = 5.1 Hz, CH-OAr), 6.5–7.6 (m, 11H,
Ar-H), 8.1 (s, 1H, CONH); Elemental analysis: Calcd.
(found): C, 56.25 (56.12); H, 4.34 (4.38); N, 10.50
(10.43); Mass spectra, m/z = 532 (100%).
2-(2-(4-(Dimethylamino)benzylidene)hydrazinyl)-N-(3-
nitrophenyl)acetamide (3g). Yield 70%; IR (KBr, cmÀ1): 3324
(NH), 1656 (CONH), 1549 (—CH═N—); 1H-NMR (300 MHz,
CDCl3) δ (ppm) = 2.46 (s, 1H, NH), 2.87 (s, 6H, —N(CH3)2),
3.75 (s, 2H, CH2), 6.5–7.9 (m, 8H, Ar-H), 8.1 (s, 1H, CONH),
8.4 (s, 1H, —CH═N—); Mass spectra, m/z = 341 (100%).
2-(2-(4-(Dimethylamino)benzylidene)hydrazinyl)-N-(4-
hydroxyphenyl)acetamide (3h). Yield 75%; IR (KBr, cmÀ1): 3368
(NH), 1666 (CONH), 1558 (—CH═N—); 1H-NMR (300 MHz,
CDCl3) δ (ppm) = 2.1 (s, 1H, NH), 2.85 (s, 6H, —N(CH3)2), 3.6
(s, 2H, CH2), 6.5–7.5 (m, 8H, Ar-H), 8.2 (s, 1H, CONH), 8.3 (s, 1H,
—CH═N—), 12.8 (s, 1H, —OH); Mass spectra, m/z = 312 (100%).
2-(2-(4-(Dimethylamino)benzylidene)hydrazinyl)-N-p-
tolylacetamide (3i). Yield 75%; IR (KBr, cmÀ1): 3342 (NH),
2-(3-(2,4-Dichlorophenoxy)-2-(4-(dimethylamino) phenyl)-
4-oxoazetidin-1-ylamino)-N-(4-nitrophenyl) acetamide (4e). Yield
66%; m.p. (°C): 156; IR (KBr, cmÀ1): 3248 (NH), 1675 (CONH),
1
1738 (CO, β-lactam); H-NMR (300 MHz, CDCl3) δ (ppm) = 2.85
(s, 6H, —N(CH3)2), 3.4 (s, 1H, NH), 3.65 (s, 2H, CH2), 5.2 (d, 1H,
J = 5.4 Hz, CH-Ar), 5.76 (d, 1H, J = 5.2 Hz, CH-OAr), 6.5–8.0
(m, 11H, Ar-H), 8.4 (s, 1H, CONH); Mass spectra, m/z = 543 (100%).
N-(2-Chlorophenyl)-2-(3-(2,4-dichlorophenoxy)-2-(4-
(dimethylamino)phenyl)-4-oxoazetidin-1-ylamino) acetamide
(4f). Yield 70%; m.p. (°C): 140; IR (KBr, cmÀ1): 3221 (NH),
1669 (CONH), 1742 (CO, β-lactam); 1H-NMR (300 MHz,
CDCl3) δ (ppm) = 2.86 (s, 6H, —N(CH3)2), 3.2 (s, 1H, NH),
3.56 (s, 2H, CH2), 5.43 (d, 1H, J = 5.5 Hz, CH-Ar), 5.84 (d, 1H,
J = 5.3 Hz, CH-OAr), 6.5–7.6 (m, 11H, Ar-H), 8.2 (s, 1H,
CONH); Mass spectra, m/z = 532 (100%).
1
1652 (CONH), 1566 (—CH═N—); H-NMR (300 MHz, CDCl3)
δ (ppm) = 2.2 (s, 1H, NH), 2.54 (s, 3H, —CH3), 2.88 (s, 6H, —N
(CH3)2), 3.65 (s, 2H, CH2), 6.5–7.6 (m, 8H, Ar-H), 7.9 (s, 1H,
CONH), 8.5 (s, 1H, —CH═N—); Mass spectra, m/z = 310 (100%).
2-(2-(4-(Dimethylamino)benzylidene)hydrazinyl)-N-(4-
methoxyphenyl)acetamide (3j). Yield 78%; IR (KBr, cmÀ1): 3364
(NH), 1661 (CONH), 1558 (—CH═N—); 1H-NMR (300 MHz,
CDCl3) δ (ppm) = 2.26 (s, 1H, NH), 2.87 (s, 6H, —N(CH3)2), 3.63
(s, 2H, CH2), 3.87 (s, 3H, —OCH3), 6.5–7.6 (m, 8H, Ar-H), 8.2 (s,
1H, CONH), 8.5 (s, 1H, —CH═N—); Mass spectra, m/z = 326 (100%).
General procedure for the synthesis of 2-(3-(2,4-
dichlorophenoxy)-2-(4-(dimethylamino)phenyl)-4-oxoazetidin-
1-ylamino)-N-phenylacetamide (4a–j). The appropriate Schiff
base (0.02 mol), 2,4-dichlorophenoxy acetic acid (0.02 mol),
and triethylamine (0.05 mol) were stirred in anhydrous
dichloromethane, while a solution of POCl3 (0.02 mol) in dry
dichloromethane was added dropwise. The reaction mixture was
stirred for ∼14 h. The completion of the reaction was monitored by
TLC. The reaction mixture was washed with water and dried over
sodium sulphate. The products that were obtained after removing
the solvent were purified from ethyl acetate and n-hexane.
2-(3-(2,4-Dichlorophenoxy)-2-(4-(dimethylamino) phenyl)-
4-oxoazetidin-1-ylamino)-N-(3-nitrophenyl) acetamide (4g). Yield
64%; m.p. (°C): 160; IR (KBr, cmÀ1): 3236 (NH), 1672 (CONH),
1
1733 (CO, β-lactam); H-NMR (300 MHz, CDCl3) δ (ppm) = 2.87
(s, 6H, —N(CH3)2), 3.4 (s, 1H, NH), 3.63 (s, 2H, CH2), 5.32 (d, 1H,
J = 5.4 Hz, CH-Ar), 5.74 (d, 1H, J = 5.2 Hz, CH-OAr), 6.5–8.0
(m, 11H, Ar-H), 8.1 (s, 1H, CONH); Mass spectra, m/z = 543 (100%).
2-(3-(2,4-Dichlorophenoxy)-2-(4-(dimethylamino) phenyl)-
4-oxoazetidin-1-ylamino)-N-(4-hydroxyphenyl) acetamide
(4h). Yield 69%; m.p. (°C): 126; IR (KBr, cmÀ1): 3262 (NH),
1
1655 (CONH), 1750 (CO, β-lactam); H-NMR (300 MHz, CDCl3)
2-(3-(2,4-Dichlorophenoxy)-2-(4-(dimethylamino) phenyl)-
4-oxoazetidin-1-ylamino)-N-phenylacetamide (4a). Yield 68%; m.p.
(°C): 145; IR (KBr, cmÀ1): 3080 (NH), 1602 (CONH), 1732 (CO,
δ (ppm) = 2.85 (s, 6H, —N(CH3)2), 3.2 (s, 1H, NH), 3.6 (s, 2H, CH2),
5.4 (d, 1H, J = 5.3 Hz, CH-Ar), 5.8 (d, 1H, J = 5.2 Hz, CH-OAr),
6.5–7.5 (m, 11H, Ar-H), 8.3 (s, 1H, CONH), 12.5 (s, 1H, —OH); Mass
spectra, m/z = 514 (100%).
1
β-lactam); H-NMR (300 MHz, CDCl3) δ (ppm) = 2.8 (s, 6H, —N
(CH3)2), 3.2 (s, 1H, NH), 3.6 (s, 2H, CH2), 5.3 (d, 1H, J = 5.4 Hz,
CH-Ar), 5.85 (d, 1H, J = 5.2 Hz, CH-OAr), 6.5–7.7 (m, 12H, Ar-H),
8.51 (s, 1H, CONH); Elemental analysis: Calcd. (found): C, 60.13
(60.05); H, 4.84 (4.69); N, 11.22 (11.30); Mass spectra, m/z = 498 (100%).
N-(3-Chlorophenyl)-2-(3-(2,4-dichlorophenoxy)-2-(4-
(dimethylamino)phenyl)-4-oxoazetidin-1-ylamino) acetamide
(4b). Yield 69%; m.p. (°C): 138; IR (KBr, cmÀ1): 3184 (NH),
1662 (CONH), 1741 (CO, β-lactam); 1H-NMR (300 MHz,
CDCl3) δ (ppm) = 2.85 (s, 6H, —N(CH3)2), 3.1 (s, 1H, NH),
3.54 (s, 2H, CH2), 5.5 (d, 1H, J = 5.5 Hz, CH-Ar), 5.83 (d, 1H,
J = 5.2 Hz, CH-OAr), 6.5–7.8 (m, 11H, Ar-H), 8.4 (s, 1H,
2-(3-(2,4-Dichlorophenoxy)-2-(4-(dimethylamino) phenyl)-
4-oxoazetidin-1-ylamino)-N-p-tolylacetamide (4i). Yield 65%;
m.p. (°C): 130; IR (KBr, cmÀ1): 3259 (NH), 1669 (CONH),
1
1748 (CO, β-lactam); H-NMR (300 MHz, CDCl3) δ (ppm) =
2.48 (s, 3H, —CH3), 2.86 (s, 6H, —N(CH3)2), 3.1 (s, 1H,
NH), 3.72 (s, 2H, CH2), 5.5 (d, 1H, J = 5.5 Hz, CH-Ar), 5.73
(d, 1H, J = 5.2 Hz, CH-OAr), 6.5–7.6 (m, 11H, Ar-H), 8.1 (s,
1H, CONH); Mass spectra, m/z = 512 (100%).
2-(3-(2,4-Dichlorophenoxy)-2-(4-(dimethylamino) phenyl)-
4-oxoazetidin-1-ylamino)-N-(4-methoxyphenyl) acetamide
(4j). Yield 66%; m.p. (°C): 150; IR (KBr, cmÀ1): 3260 (NH),
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1654 (CONH), 1740 (CO, β-lactam); 1H-NMR (300 MHz, CDCl3)
δ (ppm) = 2.82 (s, 6H, —N(CH3)2), 3.4 (s, 1H, NH), 3.69 (s, 2H,
CH2), 3.83 (s, 3H, —OCH3), 5.28 (d, 1H, J = 5.4 Hz, CH-Ar), 5.68
(d, 1H, J = 5.2 Hz, CH-OAr), 6.4–7.7 (m, 11H, Ar-H), 8.0 (s, 1H,
CONH); Mass spectra, m/z = 528 (100%).
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for providing the necessary research facilities. And also grateful
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet