A simple and highly efficient procedure for one-pot synthesis of 2-azetidinones using 3,5-dinitrobenzoyl chloride

Article abstract of DOI:10.2174/15701786113109990037

One-pot synthesis of 2-azetidinones has efficiently been carried out in excellent yields by treatment of imines and substituted acetic acids with 3,5-dinitrobenzoyl chloride in the presence of triethylamine. The method is remarkably convenient and pure pr

Full text of DOI:10.2174/15701786113109990037

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Letters in Organic Chemistry, 2013, 10, 645-650
645
A Simple and Highly Efficient Procedure for One-Pot Synthesis of 2-
Azetidinones Using 3,5-Dinitrobenzoyl Chloride
Alireza Darvishia, Maaroof Zarei b* and Mohammad Reza Akhgara
aDepartment of Chemistry, Faculty of Science, Kerman Branch, Islamic Azad University, Kerman, Iran; bDepartment of
Chemistry, College of Sciences, Hormozgan University, Bandar Abbas 71961, Iran
Received May 25, 2013: Revised July 09, 2013: Accepted July 12, 2013
Abstract: One-pot synthesis of 2-azetidinones has efficiently been carried out in excellent yields by treatment of imines
and substituted acetic acids with 3,5-dinitrobenzoyl chloride in the presence of triethylamine. The method is remarkably
convenient and pure products were obtained by simple crystallization.
Keywords: ꢀ-Lactam, 2-Azetidinone, Staudinger reaction, 3,5-Dinitrobenzoyl chloride, Ketene, Imine.
INTRODUCTION
The objective of this work was to investigate the applica-
tion of 3,5-dinitrobenzoyl chloride for the one-pot synthesis
of 2-azetidinones from imines and carboxylic acids.
2-Azetidinone (ꢀ-lactam) ring is present in several widely
used families of antibiotics such as penicillins, cepha-
losporins, carbapenems, and other ꢀ-lactam antibiotics [1].
Ezetimibe is a new clinical drug which has 2-azetidinone
ring and it is used as a cholesterol absorption inhibitor [2]. In
addition, literature survey reveals that 2-azetidinones shown
to possess other relevant biological activities [3]. Besides its
fundamental importance in medicinal and pharmaceutical
chemistry, the 2-azetidinone ring is a useful intermediate in
organic synthesis (ꢀ-lactam synthon method) [4] and in the
semi-synthesis of Taxol and Taxotere derivatives [5].
RESULTS AND DISCUSSION
Imines were synthesized by reaction of corresponding
amines and aldehydes in refluxing ethanol or by stirring
overnight in the presence of anhydrous Na2SO4 in dry
CH2Cl2. Reaction of imine 1a, phenoxyacetic acid 2a and
3,5-dinitrobenzoyl chloride in the presence of triethylamine
in dry dichloromethane at room temperature gave pure cis ꢀ-
lactam 3a after purification by crystallization from 95%
ethanol. Simple aqueous work-up removes the by-product of
3,5-dinitrobenzoyl chloride and any resulting salts. The
stereochemistry of ꢀ-lactams were assigned by comparison
of the coupling constant H-3 and H-4 (J3,4> 4.0 Hz) for the
cis stereoisomer and (J3,4ꢁ 3.0 Hz) for the trans stereoisomer
[16]. The conditions were optimized using this reaction. The
effect of solvent, temperature and quantity of reagent were
investigated. In all reactions, 1.0 mmol of imine 1a and three
times the equivalents of phenoxyacetic acid 2a with respect
to the amount of 3,5-dinitrobenzoyl chloride were used. As it
is shown in (Table 1), dichloromethane gave the best results
among the dry solvents tested. High decrease in the yield of
ꢀ-lactam 3a was observed when reaction was performed in
cold media. The highest yield was obtained when 1.3 mmol
phenoxyacetic acid and 1.3 mmol 3,5-dinitrobenzoyl chlo-
ride were reacted with 1.0 mmol of imine 1a (Table 1, entry
6). Therefore reactions of 1.0 mmol imine, 1.3 mmol acid
and 1.3 mmol 3,5-dinitrobenzoyl chloride in the presence of
triethylamine in dry dichloromethane at room temperature
were used for next reactions.
Because of these applications, synthesis of 2-azetidinones
has received considerable attention over recent years and
several methods have been reported for preparation of 2-
azetidinones [6]. The most widely used and simple method
for the synthesis of 2-azetidinones is the Staudinger reaction
(ketene-imine cycloaddition) [7]. Generally, the ketene com-
ponents are produced in situ by the reaction of an acyl chlo-
ride and a tertiary amine as a base [8]. Due to instability,
commercial unavailability and difficulty in the preparation of
acyl chloride, a variety of acid-activating agents have been
used for in situ generation of ketenes from carboxylic acids
in the modified Staudinger [2+2] cycloaddition [9]. Some of
these acid activators have disadvantages such as unavailabil-
ity, pollution, low or high temperature requirements tedious
purification and low yields of products.
3,5-Dinitrobenzoyl chloride is a colored and active acyl
chloride which is used for evaluation of biogenic amines in
fish sauce [10], the recognition of chiral carboxylate anions
[11], determination of residual amines used in bulk drug syn-
thesis [12], derivatization of alcohols at dilute levels [13],
determination of naphazoline in pharmaceuticals [14] and
determination of putrescine and tyramine in fish [15].
According to the above results, 2-azetidinones 3a-p were
synthesized by treatment of 1.0 mmol of corresponding
Schiff basis 1, 1.3 mmol of acetic acid derivative 2 and 1.3
mmol 3,5-dinitrobenzoyl chloride in the presence of triethy-
lamine in dry CH2Cl2 at room temperature (Scheme 1, Table
2). Purification of ꢀ-lactams 3a-p were performed by simple
*Address correrspondence to these authors at the Department of Chemistry,
Faculty of Science, Kerman Branch, Islamic Azad University, Kerman, Iran;
and Department of Chemistry, College of Sciences, Hormozgan University,
Bandar Abbas 71961, Iran; Tel: +98 761 766 0063; Fax: +98 761 667 0714;
E-mails: maaroof1357@yahoo.com, mzarei@hormozgan.ac.ir
1875-6255/13 $58.00+.00
© 2013 Bentham Science Publishers

646 Letters in Organic Chemistry, 2013, Vol. 10, No. 9
Zarei et al.
Table 1. Optimization of the Reaction Conditions for the Synthesis of ꢀ-lactam 3a
Me
PhO
O
3,5-dinitrobenzoyl
chloride
PhOCH2CO2H
+
MeO
N=CH
Me
N
Et3N,CH2Cl2
1a
2a
3a
OMe
Entry
Solvent
Temp.
3,5-dinitrobenzoyl Chloride (Equiv)
Yield %
1
2
3
4
5
6
7
DMF
THF
rt
rt
1.0
1.0
1.0
1.0
1.0
1.3
1.5
46
51
77
65
33
90
88
CH2Cl2
toluene
CH2Cl2
CH2Cl2
CH2Cl2
rt
rt
0 oC
rt
rt
COCl
R2
R1
R3
O
O2N
NO2
N
R1N=CHR2 + R3CH2COOH
Et3N, CH2Cl2
rt
3a-p
1
2
Scheme 1. Synthesis of 2-azetidinones 3a-p.
Table 2. Synthesis of 2-azetidinones 3a-p using 3,5-dinitrobenzoyl Chloride
Entry
R1
R2
R3
Product
Isolated Yield (%)
1
2
4-MeONaphth-1-yl
4-EtC6H4
4-MeC6H4
4-ClC6H4
PhO
4-ClC6H4O
PhthN
3a
3b
3c
3d
3e
3f
90
86
92
93
88
91
90
82
91
86
90
3
4-EtC6H4
4-ClC6H4
4
4-EtC6H4
4-ClC6H4
PhO
5
4-EtC6H4
4-(Me2N)C6H4
4-(Me2N)C6H4
4-(Me2N)C6H4
4-(Me2CH)C6H4
4-(Me2CH)C6H4
4-(Me2CH)C6H4
4-(Me2N)C6H4
4-ClC6H4O
PhthN
6
4-EtC6H4
7
4-EtC6H4
PhO
3g
3h
3i
8
4-EtC6H4
4-ClC6H4O
PhthN
9
4-EtC6H4
10
11
4-EtC6H4
PhO
3j
4-MeOC6H4
4-ClC6H4O
3k

A Simple and Highly Efficient Procedure for One-Pot Synthesis of 2-Azetidinones
Letters in Organic Chemistry, 2013, Vol. 10, No. 9 647
Table 2. Contd…..
Entry
R1
R2
R3
Product
Isolated Yield (%)
12
13
14
15
16
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-(Me2N)C6H4
4-(Me2N)C6H4
4-(Me2CH)C6H4
4-(Me2CH)C6H4
4-(Me2CH)C6H4
PhthN
PhO
3l
3m
3n
3o
3p
88
82
84
83
87
4-ClC6H4O
PhthN
PhO
crystallization from 95% ethanol. All products were charac-
terized by spectroscopic data and elemental analyses.
ethanol to give pure imine. Except 1d, other imines have
been reported previously [18c,20].
The mechanism of [2+2] cycloaddition of the imine and
ketene has been previously investigated. It is actually a two-
step process. In the first step, nitrogen atom of the imine, the
nucleophile, attacks the lowest unoccupied molecular orbital
(LUMO) of the ketene carbonyl group giving rise to a zwit-
terionic intermediate and a subsequent the second step, a
four-electron conrotatory ring closure of the zwitterionic
intermediate produced the ꢀ-lactam. This intermediate was
detected and characterized by IR spectroscopy. Many differ-
ent experimental factors, such as reaction temperature, sol-
vent, electronic effects, and the steric hindrance of the ketene
and imine substituents may affect the stereochemistry of ꢀ-
lactams in the Staudinger reaction [17]. Then, it is assumed
that the reaction proceeds via a [2+2] cycloaddition of the
imine and ketene by formation of an activated ester [18].
This activated ester generates, in situ, the corresponding
ketene in the presence of triethylamine.
4-Ethyl-N-(4-isopropylbenzylidene)aniline (1d)
Light-yellow oil. IR (KBr) cm-1: 1625 (C=N, imine);
Anal. Calcd for C18H21N: C, 86.01; H, 8.42; N, 5.57; Found:
C, 86.13; H, 8.56; N, 5.65.
General Procedure for the Synthesis of 2-azetidinones 3a-
p
A 3,5-dinitrobenzoyl chloride (1.3 mmol) was added to a
solution of the substituted acetic acid (1.3 mmol), the imine
(1.0 mmol) and Et3N (4.0 mmol) in dry CH2Cl2 (12 mL) at
room temperature and the mixture was stirred overnight. The
mixture was washed successively with saturated NaHCO3
(12 mL) and brine (12 mL). The organic layer was dried
(Na2SO4), filtered and the solvent was removed under re-
duced pressure to give the crude products. 2-azetidinones 3a-
p were purified by crystallization from 95% ethanol.
O
C
O
3-(4-Chlorophenoxy)-4-(4-chlorophenyl)-1-(4-
ethylphenyl)azetidin-2-one (3b)
NO2
R3H2C
O
o
White solid. mp: 159-161 C IR (KBr) cm-1: 1750 (CO,
ꢀ-lactam); 1H NMR (CDCl3) ꢁ 1.27 (Me, t, 3H, J = 7.0), 2.59
(CH2, q, 2H, J = 7.0), 5.43 (H-4, d, 1H, J = 4.9), 5.56 (H-3,
d, 1H, J = 4.9), 6.78-7.33 (ArH, m, 12H); 13C NMR (CDCl3)
ꢁ 14.7 (Me), 33.6 (CH2), 62.8 (C-4), 80.9 (C-3), 115.9-156.9
(aromatic carbons), 161.7 (CO, ꢀ-lactam); Anal. Calcd for
C23H19Cl2NO2: C, 67.00; H, 4.64; N, 3.40; Found: C, 67.11;
H, 4.74; N, 3.34.
NO2
activated ester
EXPERIMENTAL
General Procedures
All required chemicals were purchased from Merck,
Fluka or Acros chemical companies. The melting points
were determined on a Buchi 535 apparatus and are uncor-
rected. IR spectra were measured on a galaxy series FT-IR
5000 spectrometer. NMR spectra were recorded in CDCl3
using a Bruker spectrophotometer (1H NMR 250 MHz, 13C
NMR 62.9 MHz) using tetramethylsilane as an internal stan-
dard and coupling constants were given in cycles per second
(Hz). Elemental analyses were run on a Vario EL III elemen-
tal analyzer. Thin-layer chromatography was carried out on
silica gel 254 analytical sheets obtained from Fluka. Spectral
data for 3a has been previously reported [19].
2-(2-(4-Chlorophenyl)-1-(4-ethylphenyl)-4-oxoazetidin-3-
yl)isoindoline-1,3-dione (3c)
o
White solid. mp: 175-177 C IR (KBr) cm-1:1735, 1775
1
(CO, phth), 1786 (CO, ꢀ-lactam); H NMR (CDCl3) ꢁ 1.33
(Me, t, 3H, J =7.0 ), 2.57 (CH2, q, 2H, J = 7.0), 5.23 (H-4, d,
1H, J =5.0 ), 5.33 (H-3, d, 1H, J = 5.0), 6.78-7.33 (ArH, m,
12H); 13C NMR (CDCl3) ꢁ 14.6 (Me), 34.8 (CH2), 62.3 (C-
4), 63.8 (C-3), 116.1-156.2 (aromatic carbons), 161.5 (CO,
phth ), 166.3 (CO, ꢀ-lactam); Anal. Calcd for C25H19ClN2O3:
C, 69.69; H, 4.44; N, 6.50; Found: C, 69.77; H, 4.57; N,
6.44.
4-(4-Chlorophenyl)-1-(4-ethylphenyl)-3-phenoxyazetidin-2-
one (3d)
General Procedure for the Synthesis of Imines
o
White solid. mp: 182-184 C IR (KBr) cm-1: 1739 (CO,
A mixture of amine (10.0 mmol) and aldehyde (10.0
mmol) was refluxed in ethanol for 3-4 hours. After cooling
of the solution, the precipitate was filtered and washed with
ꢀ-lactam); 1H NMR (CDCl3) ꢁ 1.31 (Me, t, 3H, J = 7.0), 2.83
(CH2, q, 2H, J =7.0), 5.24 (H-4, d, 1H, J = 4.8), 5.45 (H-3, d,

648 Letters in Organic Chemistry, 2013, Vol. 10, No. 9
Zarei et al.
1H, J = 4.8), 6.68-7.23 (ArH, m, 13H); 13C NMR (CDCl3) ꢀ
14.6 (Me), 33.2 (CH2), 63.8 (C-4), 82.0 (C-3), 115.0-156.8
(aromatic carbons), 163.7 (CO, ꢁ-lactam); Anal. Calcd for
C23H20ClNO2: C, 73.11; H, 5.33; N, 3.71; Found: C, 73.03;
H, 5.45; N, 3.78.
bons), 167.3 (CO, ꢁ-lactam); Anal. Calcd for C28H26N2O3: C,
76.69; H, 5.98; N, 6.39; Found: C, 76.81; H, 6.09; N, 6.31.
1-(4-Ethylphenyl)-4-(4-isopropylphenyl)-3-
phenoxyazetidin-2-one (3j)
o
White solid. Yield: (0.40 g, 86%), mp: 166-168 C IR
3-(4-Chlorophenoxy)-4-(4-(dimethylamino)phenyl)-1-(4-
ethylphenyl)azetidin-2-one (3e)
1
(KBr) cm-1: 1755 (CO, ꢁ-lactam); H NMR (CDCl3) ꢀ 1.06
(2Me, d, 6H, J = 7.0), 1.10 (Me, t, 3H, J = 7.0), 2.56 (CH2, q,
2H, J =7.0), 2.73 (CH, sept, 1H, J = 7.0), 5.25 (H-4,d, 1H, J
= 4.8), 5.45 (H-3, d, 1H, J =4.8), 6.52-7.28 (ArH, m, 13H);
13C NMR (CDCl3) ꢀ 12.5 (Me), 23.5 (Me), 34.2 (CH2), 38.4
(CH), 61.3 (C-4), 81.0 (C-3), 112.0-156.9 (aromatic car-
bons), 161.7 (CO, ꢁ-lactam); Anal. Calcd for C26H27NO2: C,
81.01; H, 7.06; N, 3.63; Found: C, 81.13; H, 7.16; N, 3.71.
o
White solid. mp: 150-152 C IR (KBr) cm-1: 1750 (CO,
ꢁ-lactam); 1H NMR (CDCl3) ꢀ 1.36 (Me, t, 3H, J =7.0 ), 2.35
(CH2, q, 2H, J =7.0 ), 2.99 (2Me, s, 6H), 5.32 (H-4, d, 1H, J
= 4.9), 5.45 (H-3, d, 1H, J = 4.9), 6.77-7.33 (ArH, m, 12H);
13C NMR (CDCl3) ꢀ 14.8 (Me), 32.3 (CH2), 41.3 (Me-N),
63.7 (C-4), 81.7 (C-3), 113.9-160.1 (aromatic carbons),
161.7 (CO, ꢁ-lactam); Anal. Calcd for C25H25ClN2O2: C,
71.33; H, 5.99; N, 6.66; Found: C, 71.41; H, 6.12; N, 6.72.
3-(4-Chlorophenoxy)-4-(4-(dimethylamino)phenyl)-1-(4-
methoxyphenyl)azetidin-2-one (3k)
2-(2-(4-(Dimethylamino)phenyl)-1-(4-ethylphenyl)-4-
oxoazetidin-3-yl)isoindoline-1,3-dione (3f)
o
White solid. mp: 209-211 C IR (KBr) cm-1: 1734 (CO,
o
White solid. mp: 153-155 C IR (KBr) cm-1:1735, 1775
1
ꢁ-lactam); H NMR (CDCl3) ꢀ 2.84 (2Me, s, 6H), 3.82
1
(CO, phth), 1790 (CO, ꢁ-lactam); H NMR (CDCl3) ꢀ 1.35
(MeO, s, 3H), 5.20 (H-4, d, 1H, J = 4.7), 5.41 (H-3, d, 1H, J
=4.7 ), 6.68-7.23 (ArH, m, 12H); 13C NMR (CDCl3) ꢀ 41.8
(Me), 55.2 (Me), 63.6 (C-4), 81.2 (C-3), 113.8-159.8 (aro-
matic carbons), 162.6 (CO, ꢁ-lactam); Anal. Calcd for
C24H23Cl N2O3: C, 68.16; H, 5.48; N, 6.62; Found: C, 68.08;
H, 5.60; N, 6.66.
(Me, t, 3H, J = 6.9 ), 2.44 (CH2, q, 2H, J = 6.9), 2.91 (2Me,
s, 6H), 5.35 (H-4, d, 1H, J =5.0), 5.43 (H-3, d, 1H, J =5.0),
6.59-7.85 (ArH, m, 12H); 13C NMR (CDCl3) ꢀ 14.3 (Me),
32.7 (CH2), 40.7 (Me-N), 62.3 (C-4), 63.1 (C-3), 114.4-
155.3 (aromatic carbons), 161.1 (CO, phth), 166.3 (CO, ꢁ-
lactam); Anal. Calcd for C27H25N3O3: C, 73.78; H, 5.73; N,
9.56; Found: C, 73.88; H, 5.87; N, 9.49.
2-(2-(4-(Dimethylamino)phenyl)-1-(4-methoxyphenyl)-4-
oxoazetidin-3-yl)isoindoline-1,3-dione(3l)
4-(4-(Dimethylamino)phenyl)-1-(4-ethylphenyl)-3-
phenoxyazetidin-2-one (3g)
o
White solid. mp: 209-211 C IR (KBr) cm-1:1724, 1772
1
o
White solid. mp: 177-179 C IR (KBr) cm-1: 1744 (CO,
(CO, phth), 1785 (CO, ꢁ-lactam); H NMR (CDCl3) ꢀ 2.58
ꢁ-lactam); 1H NMR (CDCl3) ꢀ 1.32 (Me, t, 3H, J = 7.0), 2.56
(CH2, q, 2H, J = 7.0), 2.90 (2Me, s, 6H), 5.28 (H-4, d, 1H, J
=4.8), 5.47 (H-3, d, 1H, J =4.8), 6.74-7.30 (ArH, m, 13H);
13C NMR (CDCl3) ꢀ 14.8 (Me), 32.2 (CH2), 40.4 (Me-N),
63.8 (C-4), 81.4 (C-3), 114.3-157.1 (aromatic carbons),
162.1 (CO, ꢁ-lactam); Anal. Calcd for C25H26N2O2: C, 77.69;
H, 6.78; N, 7.25; Found: C, 77.76; H, 6.90; N, 7.33.
(2Me, s, 6H), 3.72 (MeO, s, 3H), 5.37 (H-4, d, 1H, J =5.5),
5.61 (H-3, d, 1H, J =5.5), 6.78-7.78 (ArH, m, 12H); 13C
NMR (CDCl3) ꢀ 41.78 (Me), 55.5 (Me), 58.8 (C-4), 60.3 (C-
3), 114.5-156.5 (aromatic carbons), 160.1 (CO, Phth), 166.7
(CO, ꢁ-lactam); Anal. Calcd for C26H23N3O4: C, 70.73; H,
5.25; N, 9.52; Found: C, C, 70.78; H, 5.32; N, 9.48.
4-(4-(Dimethylamino)phenyl)-1-(4-methoxyphenyl)-3-
phenoxyazetidin-2-one (3m)
3-(4-Chlorophenoxy)-1-(4-ethylphenyl)-4-(4-
isopropylphenyl)azetidin-2-one (3h)
o
White solid. mp: 222-224 C IR (KBr) cm-1: 1731 (CO,
o
White solid. mp: 111-113 C IR (KBr) cm-1: 1759 (CO,
1
ꢁ-lactam); H NMR (CDCl3) ꢀ 2.86 (2Me, s, 6H), 3.73
1
ꢁ-lactam); H NMR (CDCl3) ꢀ 1.29 (2Me, d, 6H, J = 6.9 ),
(MeO, s, 3H), 5.27 (H-4, d, 1H, J = 4.7), 5.48 (H-3, d, 1H, J
=4.7), 6.59-7.31 (ArH, m, 13H); 13C NMR (CDCl3) ꢀ 40.7
(Me), 55.2 (Me), 61.7 (C-4), 81.1 (C-3), 112.8-159.7 (aro-
matic carbons), 162.2 (CO, ꢁ-lactam); Anal. Calcd for
C24H24N2O3: C, 74.21; H, 6.23; N, 7.21; Found: C, 74.33; H,
6.37; N, 7.30.
1.37(Me, t, 3H, J = 7.0), 3.17 (CH2, q, 2H, J = 7.0 ), 3.46
(CH, sept, 1H, J = 6.9), 5.35 (H-4, d, 1H, J =5.0 ), 5.48 (H-3,
d, 1H, J =5.0), 6.78-7.33 (ArH, m, 12H); 13C NMR (CDCl3)
ꢀ 14.8 (Me), 25.1 (Me), 34.7 (CH2), 37.9 (CH), 63.7 (C-4),
81.7 (C-3), 115.1-156.2 (aromatic carbons), 161.5 (CO, ꢁ-
lactam); Anal. Calcd for C26H26Cl NO2: C, 74.36; H, 6.24; N,
3.34; Found: C, 74.30; H, 6.34; N, 3.25.
3-(4-Chlorophenoxy)-4-(4-isopropylphenyl)-1-(4-
methoxyphenyl)azetidin-2-one (3n)
2-(1-(4-Ethylphenyl)-2-(4-isopropylphenyl)-4-oxoazetidin-
3-yl)isoindoline-1,3-dione (3i)
o
White solid. mp: 169-171 C IR (KBr) cm-1: 1731 (CO,
1
o
White solid. mp: 224-226 C IR (KBr) cm-1: 1735, 1770
ꢁ-lactam); H NMR (CDCl3) ꢀ 1.27 (2Me, d, 6H, J =7.0),
1
2.79 (CH, sept, 1H, J = 7.0), 3.9 (Me, s, 3H), 5.45 (H-4,d,
1H, J =4.8 ), 5.62 (H-3, d, 1H, J =4.8 ), 6.80-7.90 (ArH, m,
12H); 13C NMR (CDCl3) ꢀ 23.8 (Me), 36.8 (CH), 56.2 (Me),
61.6 (C-4), 81.3 (C-3), 115.6-160.5 (aromatic carbons),
166.2 (CO, ꢁ-lactam); Anal. Calcd for C25H24ClNO3: C,
71.17; H, 5.73; N, 3.32; Found: C, 71.09; H, 5.85; N, 3.26.
(CO, phth), 1778 (CO, ꢁ-lactam); H NMR (CDCl3) ꢀ 1.17
(2Me, d, 6H, J = 7.0), 1.31 (Me, t, 3H, J = 6.8), 2.74 (CH2, q,
2H, J =6.8), 3.00 (CH, sept, 1H, J = 7.0) 5.37 (H-4, d, 1H, J
=4.7), 5.76 (H-3, d, 1H, J =4.7), 6.90-8.37 (ArH, m, 12H);
13C NMR (CDCl3) ꢀ 14.8 (Me), 24.2 (Me), 33.0 (CH2), 37.7
(CH), 61.04 (C-4), 63.7 (C-3), 114.9-160.6 (aromatic car-

A Simple and Highly Efficient Procedure for One-Pot Synthesis of 2-Azetidinones
Letters in Organic Chemistry, 2013, Vol. 10, No. 9 649
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2-(2-(4-Isopropylphenyl)-1-(4-methoxyphenyl)-4-
oxoazetidin-3-yl)isoindoline-1,3-dione (3o)
o
White solid. mp: 261-263 C IR (KBr) cm-1: 1735, 1775
1
(CO, phth), 1785 (CO, ꢀ-lactam); H NMR (CDCl3) ꢁ 1.17
(2Me, d, 6H, J = 6.9), 2.73 (CH, sept, 1H, J = 6.9), 3.74
(MeO, s, 3H), 5.26 (H-4, d, 1H, J = 5.1), 5.36 (H-3, d, 1H, J
= 5.1), 6.86-7.82 (ArH, m, 12H); 13C NMR (CDCl3) ꢁ 24.1
(Me), 35.2 (CH), 55.3 (OMe), 60.8 (C-4), 62.8 (C-3), 114.8-
160.1 (aromatic carbons), 162.2 (CO, phth), 166.8 (CO, ꢀ-
lactam); Anal. Calcd for C27H24N2O4: C, 73.62; H, 5.49; N,
6.36; Found: C, 73.69; H, 5.59; N, 6.28.
[4]
4-(4-Isopropylphenyl)-1-(4-methoxyphenyl)-3-
phenoxyazetidin-2-one (3p)
o
White solid. mp: 254-256 C IR (KBr) cm-1: 1740 (CO,
1
ꢀ-lactam); H NMR (250 MHz, CDCl3) ꢁ 1.34 (2Me, d, 6H,
J =7.0), 2.82 (CH, sept, 1H, J = 7.0), 3.62 (MeO, s, 3H), 5.29
(H-4, d, 1H, J =4.6 ), 5.56 (H-3, d, 1H, J =4.6), 6.69-7.69
(ArH, m, 13H); 13C NMR (CDCl3) ꢁ 24.5 (Me), 37.2 (CH),
55.1 (Me), 63.7 (C-4), 81.1 (C-3), 113.9-159.9 (aromatic
carbons), 162.5 (CO, ꢀ-lactam); Anal. Calcd for C25H25NO3:
C, 77.49; H, 6.50; N, 3.61; Found: C, 77.60; H, 6.64; N,
3.68.
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CONCLUSION
In conclusion, 3,5-dinitrobenzoyl chloride is an efficient
reagent for the one-pot synthesis 2-azetidinones (ꢀ-lactams)
from imines and carboxylic acids under mild conditions.
Simple aqueous work-up removes the by-product of 3,5-
dinitrobenzoyl chloride and any resulting salts. Pure products
were obtained by crystallization from 95% ethanol with ex-
cellent yields. This method is remarkably simple and con-
venient for the synthesis of 2-azetidinones.
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CONFLICT OF INTEREST
The author(s) confirm that this article content has no con-
flict of interest.
ACKNOWLEDGEMENTS
[7]
Support for this work by the Kerman Branch of Islamic
Azad University, is gratefully acknowledged.
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