Facile radical mediated synthesis of azetidin-2,3-diones: Potential synthons for biologically active compounds

Article abstract of DOI:10.1007/s00706-010-0346-9

An operationally simple and efficient approach for the synthesis of azetidin-2,3-diones is described. The starting substrate 2-(2-bromobenzyloxy) ethanoyl chloride was treated with appropriate Schiff's bases in triethylamine and dichloromethane to afford

Full text of DOI:10.1007/s00706-010-0346-9

Monatsh Chem (2010) 141:987–991
DOI 10.1007/s00706-010-0346-9
ORIGINAL PAPER
Facile radical mediated synthesis of azetidin-2,3-diones:
potential synthons for biologically active compounds
•
Shamsher S. Bari Mehmood S. Magtoof
•
Aman Bhalla
Received: 1 October 2009 / Accepted: 10 June 2010 / Published online: 28 July 2010
Ó Springer-Verlag 2010
Abstract An operationally simple and efficient approach
for the synthesis of azetidin-2,3-diones is described. The
starting substrate 2-(2-bromobenzyloxy)ethanoyl chloride
was treated with appropriate Schiff’s bases in triethylamine
and dichloromethane to afford 3-(2-bromobenzyloxy)az-
etidin-2-ones. The synthesis of azetidin-2,3-diones was
successfully achieved via radical mediated rearrangement
of appropriately substituted 3-(2-bromobenzyloxy)azeti-
din-2-ones using n-tributyltin hydride and AIBN in
refluxing dry benzene.
Several research groups have shown that azetidin-2,3-
diones are useful synthetic targets for the construction of
b-lactams with the cephamycin, asparenomycin, and
noncardican type side chains [8]. In addition, azetidin-2,3-
diones are important synthons for 3-alkyl/aryl/allyl-b-lac-
tams, 3-alkylidene-b-lactams, and bicyclic b-lactams [9].
Moreover, azetidin-2,3-diones with known configuration
serve as the precursors to a-hydroxy-b-amino acids [10],
peptides [11, 12], taxol, taxotere (highly promising anti-
cancer drugs) [13–15], and bestatin, a peptide enzyme
inhibitor with antimicrobial, anticancer, and immunomod-
ifier properties [16].
Keywords Azetidin-2,3-diones Á
3-(2-Bromobenzyloxy)azetidin-2-ones Á b-Lactams Á
Radical mediated rearrangement
Over the past few decades, many synthetic methods,
such as oxidation of 3-hydroxyazetidin-2-ones [8], reaction
of 3-hydroxy-b-lactam with diisopropyl carbodiimide and
methyl sulfoxide [17, 18], treatment of 3-amino-b-lactam
with mercuric chloride [19], reactions of bis(3-ethyl-
thio)azetidin-2-ones with excess of N-bromosuccinimide in
acetonitrile/water [20], ozonolysis of a-ethylidene-b-lac-
tams [21], and hydrolysis of 3-chloro-3-mercaptoazetidin-
2-ones with moist silica gel and catalytic amount of zinc
chloride [22], have been developed for the synthesis of
azetidin-2,3-diones. Recently, a convenient access to
enantiopure azetidin-2,3-diones using L-(?)-diethyl tar-
Introduction
Since the discovery of new b-lactam antibiotics such as
monobactams and nocardicins, a lot of interest has been
aroused in the study of monocyclic b-lactams [1, 2]. The
synthesis of functionalized monocyclic b-lactams is an
important area of research. Recently, monocyclic b-lac-
tams have been shown to be biologically active as
cholesterol acyl transferase inhibitors [2–4], thrombin
inhibitors [5], and apoptosis inductors [6, 7].
trate derived ketenes and imines in
cycloaddition has been listed [9].
a Staudinger
The application of free-radical reactions in organic
synthesis has grown enormously during the past decade
providing a wealth of useful new chemistry [23, 24]. Very
recently, the stereoselective synthesis of bi- and tricyclic b-
lactams by radical cyclization has been established as an
efficient methodology in organic chemistry [25, 26]. In
connection with our earlier studies aimed towards the
synthesis of novel b-lactams and their functionalization
[27–31], we report herein full details of a facile synthetic
S. S. Bari (&) Á A. Bhalla
Department of Chemistry, Centre of Advanced Studies
in Chemistry, Panjab University, Chandigarh, India
e-mail: ssbari@pu.ac.in
M. S. Magtoof
Department of Chemistry, Science College,
Thiqar University, Nashyria, Thiqar, Iraq
123

988
S. S. Bari et al.
route to azetidin-2,3-diones through radical mediated
rearrangement of appropriately substituted 3-(2-bromo-
benzyloxy)azetidin-2-ones.
Table 1 Synthesis of cis-3-(2-bromobenzyloxy)-b-lactams 5a–5f
from substrates 3 and 4a–4f
Entry
Product
R1
R2
Yielda (%)
1
2
3
4
5
6
a
5a
5b
5c
5d
5e
5f
C6H5
4-MeO-C6H4
4-MeO-C6H4
4-MeO-C6H4
4-Me-C6H4
4-Me-C6H4
C6H5
79
72
76
69
65
70
4-Br-C6H4
4-MeO-C6H4
4-MeO-C6H4
4-Cl-C6H4
C6H5
Results and discussion
2-(2-Bromobenzyloxy)ethanoic acid (2) required for these
studies was prepared by treating 2-bromobenzyl alcohol (1)
with ethyl 2-chloroethanoate using sodium hydride in re-
fluxing dry toluene, followed by subsequent acidification
with 20% hydrochloride (Scheme 1) according to the
reported procedure [32–35]. The starting substrate, 2-(2-
bromobenzyloxy)ethanoyl chloride (3), was conveniently
prepared by reaction of acid 2 and phosphorus trichloride
(Scheme 1) using a literature method [36].
Isolated yield
The exclusive formation of cis-3-(2-bromobenzyloxy)-
b-lactams 5 in this case can be rationalized on the basis
of the similar mechanism as discussed in our recent
publication [28] and through the previous experimental
classification as proposed by George and Ravikumar [37].
The synthesis of azetidin-2,3-diones 6a–6f, serving as
potential synthons for biologically active compounds, was
successfully achieved through radical mediated rearrange-
ment of appropriately substituted 3-(2-bromobenzyloxy)
azetidin-2-ones 5a–5f. Initially, the reaction of 5a with 1.1
equiv of n-tributyltin hydride and a catalytic amount of
AIBN in refluxing dry benzene afforded azetidin-2,3-dione
6a in good yield. Similar results were obtained for free
radical intramolecular rearrangements of b-lactams 5b–5f
(Scheme 3; Table 2).
2-(2-Bromobenzyloxy)ethanoyl chloride (3) was further
used as a ketene precursor in a Staudinger cycloaddition
reaction. Initially, reaction of 3 with Schiff base 4a in the
presence of triethylamine and dichloromethane exclusively
afforded cis-3-(2-bromobenzyloxy)-b-lactam 5a in good
yield according to the procedure reported for synthesis of
3-phenylthio/benzylthio-b-lactams [27, 28]. This reaction
was performed with different Schiff’s bases 4b–4f under
similar conditions and furnished cis-3-(2-bromobenzyl-
oxy)-b-lactams 5b–5f in good yields (Scheme 2; Table 1).
b-lactams 5a–5f were characterized by FT-IR, 1H NMR,
13C NMR, 13C DEPT-135 NMR spectroscopic studies, and
CHN analysis. The stereochemistry at C3-H and C4-H of
b-lactams 5a–5f was assigned cis on the basis of coupling
The structures of azetidin-2,3-diones 6a–6f were estab-
lished on the basis of their spectral data such as UV-vis,
FT-IR, H NMR, 13C NMR, 13C DEPT-135 NMR, and
1
1
constants (J = 4.8–5.1 Hz, C3-H and C4-H) in H NMR
spectra [28].
CHN analysis. The azetidin-2,3-diones 6a, 6d, 6f are
Br
H H
N
H
N
R1
R2
R1
R2
O
O
1. NaH, ClCH2COOC2H5
Toluene, Reflux
Br
n-Bu3SnH, AIBN
Benzene, 50 oC
Br
O
O
OH
OH
Cl
O
O
2. 20% HCl
1
2
5a-5f
6a-6f
PCl3
Scheme 3
Br
O
O
Table 2 Synthesis of azetidin-2,3-diones 6 through radical mediated
rearrangement of 5 using n-Bu3SnH and AIBN
3
Scheme 1
Entry Substrate R1
R2
Product Yielda (%)
1
2
3
4
5
6
a
5a
5b
5c
5d
5e
5f
C6H5
4-MeO-C6H4 6a
4-MeO-C6H4 6b
76
73
69
71
64
68
Br
4-Br-C6H4
H H
N
R1
O
Br
R1
R2
O
4-MeO-C6H4 4-MeO-C6H4 6c
Et3N
CH2Cl2, 0oC
+
O
4-MeO-C6H4 4-Me-C6H4
6d
6e
6f
Cl
N
O
R2
4a-4f
4-Cl-C6H4
C6H5
4-Me-C6H4
C6H5
3
5a-5f
Scheme 2
Isolated yield
123

Facile radical mediated synthesis of azetidin-2,3-diones
989
Br
with iodine vapors. The reactions for the synthesis of cis-3-
(2-bromobenzyloxy)-b-lactams 5a–5f and azetidin-2,3-di-
ones 6a–6f were carried out under dry and deoxygenated
nitrogen atmosphere. Sodium hydride (Qualigen), ethyl 2-
chloroethanoate (Alfa Aesar), n-tributyltin hydride (Fluka),
AIBN (Himedia), and all other commercially available
compounds/reagents were of analytical grade and used
without further purification. Dichloromethane distilled over
P2O5 was redistilled over CaH2 before use. Benzene and
toluene were distilled from sodium-benzophenone imme-
diately before use.
H
H
H
N
H
N
R1
R2
R1
R2
O
H
H
N
O
R1
R2
n-Bu3SnH
O
AIBN
O
O
O
5
7
8
H
N
6
1
O
R
H
R2
O
CH3
CH2
Scheme 4
2-(2-Bromobenzyloxy)ethanoic acid (2, C9H9BrO3)
The starting acid
known, and they were identified by comparison of their
data with those in [22]. However, the unreported data of 6a,
6d, 6f have been given in the ‘‘Experimental’’.
2 was prepared from 1.87 g 1
(10.0 mmol), 0.50 g sodium hydride (20.8 mmol), and
1.22 g ethyl 2-chloroethanoate (10.0 mmol) in 55 cm3
toluene according to [32–35]. Colorless crystalline solid
(1.81 g, 74%); m.p.: 67–68 °C (Ref. [32] 70 °C); FT-IR
A plausible mechanism for radical mediated rearrange-
ment of cis-3-(2-bromobenzyloxy)azetidin-2-ones 5 has
been depicted in Scheme 4. Homolytic cleavage of the
C–Br bond of b-lactam 5 by n-tributyltin hydride and the
radical initiator AIBN afforded phenyl radical 7, which
further on C3-H abstraction generated C-3 radical b-lactam
8. The radical intermediates 8 undergo rearrangement
involving benzylic carbon–oxygen (C–O) bond cleavage to
furnish azetidin-2,3-dione 6 in good yields.
(CHCl3): vꢀ = 1,757 (C=O) cm-1 1H NMR (300 MHz,
;
CDCl3): d = 3.90 (s, 2H, PhCH2O), 4.40 (s, 2H, CH2CO),
7.00–7.90 (m, 4H Ar–H), 8.89 (s, 1H, COOH) ppm; 13C
NMR (75 MHz, CDCl3): d = 174.7 (C=O), 136.6, 130.0,
128.2, 127.7 (Ar–C), 72.9 (PhCH2O), 66.2 (CH2CO) ppm.
2-(2-Bromobenzyloxy)ethanoyl chloride
(3, C9H8BrClO2)
In conclusion, we described a convenient route to
azetidin-2,3-diones 6a–6f, employing radical mediated
rearrangements of cis-3-(2-bromobenzyloxy)azetidin-2-
ones 5a–5f using n-tributyltin hydride and AIBN in re-
fluxing dry benzene. Due to the operational simplicity and
efficiency, this synthetic procedure represents an interest-
ing alternative to existing methodologies.
Compound 3 was prepared from 2.00 g 2 (8.16 mmol) and
1.12 g PCl3 (8.16 mmol, 0.71 cm3) according to [36].
Yellow oil (1.80 g, 83%); FT-IR (CHCl3): vꢀ = 1,753
(C=O) cm-1; 1H NMR (300 MHz, CDCl3): d = 3.60–3.65
(m, 4H, 2CH2), 7.05–7.80 (m, 4H, Ar–H) ppm; 13C NMR
(75 MHz, CDCl3): d = 171.4 (C=O), 139.3, 132.7, 128.5,
126.1, 120.3 (Ar–C), 79.3 (PhCH2O), 65.7 (CH2CO) ppm.
General procedure for the preparation of compounds
5a–5f
Experimental
Melting points were determined in open glass capillaries on
a melting point apparatus and are corrected. FT-IR spectra
were recorded on a Perkin-Elmer 1430 FT-IR spectro-
photometer (vꢀ in cm-1). 1H NMR (300 MHz) and 13C
NMR (75 MHz) spectra were recorded on a JEOL AL 300
(300 MHz) spectrometer. The chemical shifts are given in
d (ppm) relative to tetramethylsilane as an internal standard
(d = 0 ppm) for 1H NMR and CDCl3 (d = 77.0 ppm)
for 13C NMR spectra. Ultraviolet spectra were recorded on
a JASCO V-530 UV-vis spectrophotometer. Elemental
analysis data were performed with a Perkin-Elmer 2400
elemental analyzer. Their results agreed favorably with the
calculated values. For purification, column chromatogra-
phy was carried out using silica gel (60–120 mesh, Merck)
with n-hexane:EtOAc (9:1) as an eluent system. Analytical
thin layer chromatography (TLC) was performed using
silica gel G (Merck) with n-hexane:EtOAc (8:2) as an
eluent system. For visualization, TLC plates were stained
Compounds 5a–5f were prepared from 1.1 mmol 3,
1.0 mmol 4a–4f, and 3.0 mmol Et3N in 50 cm3 CH2Cl2 by
the procedure reported earlier for the synthesis of 3-phenyl/
benzylthio-b-lactams [27, 28].
cis-3-(2-Bromobenzyloxy)-1-(4-methoxyphenyl)-4-phenyl-
azetidin-2-one (5a, C23H20BrNO3)
Starting from 1.37 g 3 (5.19 mmol), 1.0 g 4a (4.73 mmol)
and 1.43 g Et3N (1.97 cm3, 14.15 mmol). Colorless crys-
talline solid (1.72 g, 79%); m.p.: 142–144 °C; FT-IR
(KBr): vꢀ = 1,748 (C=O) cm-1 1H NMR (300 MHz,
;
CDCl3): d = 3.70 (s, 3H, OMe), 4.31 (d, 1H,
J = 13.2 Hz, PhCH2O), 4.58 (d, 1H, J = 13.2 Hz,
PhCH2O), 4.90 (d, 1H, J = 4.8 Hz, C4-H), 5.10 (d, 1H,
J = 4.8 Hz, C3-H), 6.70–7.40 (m, 13H, Ar–H) ppm; 13C
NMR (75 MHz, CDCl3): d = 163.4 (C=O), 129.3, 129.1,
128.0, 127.8, 127.6, 117.2, 113.8 (Ar–C), 82.1 (C–3), 72.0
(PhCH2O), 61.2 (C–4), 54.8 (OCH3) ppm.
123

990
S. S. Bari et al.
cis-3-(2-Bromobenzyloxy)-4-(4-bromophenyl)-1-(4-
methoxyphenyl)azetidin-2-one (5b, C23H19Br2NO3)
Starting from 0.99 g 3 (3.75 mmol), 1.0 g 4b (3.44 mmol)
and 1.04 g Et3N (1.44 cm3, 10.29 mmol). Colorless
crystalline solid (1.33 g, 72%); m.p.: 139–141 °C; FT-IR
6.92–7.34 (m, 12H, Ar–H) ppm; 13C NMR (75 MHz,
CDCl3): d = 163.0 (C=O), 136.2, 134.6, 133.3, 132.3,
129.4, 129.2, 128.6, 128.1, 127.8, 117.0 (Ar–C), 82.1, 72.2
(PhCH2O), 60.8 (C–4), 20.9 (CH3) ppm.
cis-3-(2-Bromobenzyloxy)-1,4-diphenylazetidin-2-one
(5f, C22H18BrNO2)
(KBr): vꢀ = 1,753 (C=O) cm-1 1H NMR (300 MHz,
;
CDCl3): d = 3.69 (s, 3H, OMe), 4.40 (d, 1H,
J = 12.9 Hz, PhCH2O), 4.60 (d, 1H, J = 13.2 Hz,
PhCH2O), 4.96 (d, 1H, J = 4.8 Hz, C4-H), 5.00 (d, 1H,
J = 5.1 Hz, C3-H), 6.67–7.38 (m, 12H, Ar–H) ppm; 13C
NMR (75 MHz, CDCl3): d = 156.5 (C=O), 132.6, 132.3,
131.7, 129.6, 129.3, 127.7, 127.4, 122.7, 118.7, 114.5
(Ar–C), 83.3 (C–3), 71.9 (PhCH2O), 61.5 (C–4), 55.4
(OCH3) ppm.
Starting from 1.59 g 3 (6.03 mmol), 1.0 g 4f (5.51 mmol)
and 1.67 g Et3N (2.31 cm3, 16.53 mmol). Colorless crys-
talline solid (1.65 g, 70%); m.p.: 139–140 °C; FT-IR
(KBr): vꢀ = 1,750 (C=O) cm-1 1H NMR (300 MHz,
;
CDCl3): d = 4.30 (d, 1H, J = 12.9 Hz, PhCH2O), 4.52
(d, 1H, J = 11.7 Hz, PhCH2O), 4.90 (d, 1H, J = 5.1 Hz,
C4-H), 5.14 (d, 1H, J = 4.8 Hz, C3-H), 6.95–7.48 (m,
14H, Ar–H) ppm; 13C NMR (75 MHz, CDCl3): d = 163.6
(C=O), 137.5, 137.1, 136.7, 132.7, 132.2, 129.2, 129.0,
128.9, 128.7, 128.6, 128.5, 128.2, 128.1, 128.0, 126.0,
124.1, 117.4 (Ar–C), 89.8 (C–3), 72.8 (PhCH2O), 63.6
(C–4) ppm.
cis-3-(2-Bromobenzyloxy)-1,4-bis(4-methoxyphenyl)-
azetidin-2-one (5c, C24H22BrNO4)
Starting from 1.19 g 3 (4.51 mmol), 1.0 g 4c (4.14 mmol)
and 1.25 g Et3N (1.72 cm3, 12.37 mmol). Colorless crys-
talline solid (1.54 g, 76%); m.p.: 138–140 °C; FT-IR
(KBr): vꢀ = 1,749 (C=O) cm-1 1H NMR (300 MHz,
;
General procedure for the preparation of compounds
6a–6f
CDCl3): d = 3.73 (s, 3H, OMe), 3.79 (s, 3H, OMe), 4.50
(d, 1H, J = 4.8 Hz, C4-H), 4.62 (d, 1H, J = 13.1 Hz,
PhCH2O), 4.70 (d, 1H, J = 4.8 Hz, C3-H), 4.81 (d, 1H,
J = 13.1 Hz, PhCH2O), 6.71–7.33 (m, 12H, Ar–H) ppm;
13C NMR (75 MHz, CDCl3): d = 163.1 (C=O), 159.8,
156.2, 137.2, 130.9, 129.2, 128.5, 128.2, 128.0, 127.4,
127.3, 118.7, 114.5, 114.3 (Ar–C), 89.8 (C–3), 73.0
(PhCH2O), 63.3 (C–4), 55.3 (OCH3), 55.0 (OCH3).
Compounds 6a–6f were prepared from 1.0 mmol 5a–5f,
1.1 mmol n-Bu3SnH, and a catalytic amount of AIBN in
10 cm3 C6H6 using the protocol previously described for
the n-Bu3SnH reduction of 3-alkoxy-3-phenyl/benzylthio-
b-lactams [28].
1-(4-Methoxyphenyl)-4-phenylazetidin-2,3-dione
(6a, C16H13NO3)
cis-3-(2-Bromobenzyloxy)-4-(4-methoxyphenyl)-1-(4-meth-
ylphenyl)azetidin-2-one (5d, C24H22BrNO3)
Starting from 0.10 g 5a (0.22 mmol) and 0.073 g n-
Bu3SnH (0.067 cm3, 0.25 mmol). Yellowish-white crys-
1
talline solid (0.034 g, 56%); FT-IR, H NMR, m.p., and
Starting from 1.28 g 3 (4.85 mmol), 1.0 g 4d (4.43 mmol)
and 1.34 g Et3N (1.85 cm3, 13.26 mmol). Colorless crys-
talline solid (1.51 g, 69%); m.p.: 145–146 °C; FT-IR
CHN analysis of compound 6a were found to be identical
with the one described in Ref. [22]; UV-vis: kmax (e) = 350
(9,000) nm; 13C NMR (75 MHz): d = 189.8 (C=O), 154.4
(C=O), 131.8, 130.3, 129.5, 129.3, 126.3, 119.7, 114.8
(Ar–C), 74.6 (C–4), 55.2 (OCH3) ppm.
(KBr): vꢀ = 1,752 (C=O) cm-1 1H NMR (300 MHz,
;
CDCl3): d = 2.26 (s, 3H, Me), 3.72 (s, 3H, OMe), 4.34
(d, 1H, J = 13.2 Hz, PhCH2O), 4.90 (d, 1H, J = 12.9 Hz,
PhCH2O), 4.96 (d, 1H, J = 4.8 Hz, C4-H), 5.11 (d, 1H,
J = 4.8 Hz, C3-H), 6.81–7.42 (m, 12H, Ar–H) ppm; 13C
NMR (75 MHz, CDCl3): d = 163.7 (C=O), 132.5, 130.0,
129.8, 129.6, 129.3, 129.1, 128.9, 127.5, 127.4, 126.3,
121.9, 117.5, 115.2, 114.1 (Ar–C), 83.3 (C–3), 71.5
(PhCH2O, 64.8 (C–4), 55.0 (OCH3), 21.1 (CH3) ppm.
4-(4-Bromophenyl)-1-(4-methoxyphenyl)azetidin-2,3-dione
(6b, C16H12BrNO3)
Starting from 0.10 g 5b (0.19 mmol) and 0.061 g
n-Bu3SnH (0.056 cm3, 0.20 mmol). White solid (0.044 g,
66%); m.p.: 187–188 °C; FT-IR (KBr): vꢀ = 1,769 (ketone
C=O), 1,830 (amide C=O) cm-1 1H NMR (300 MHz,
;
cis-3-(2-Bromobenzyloxy)-4-(4-chlorophenyl)-1-
CDCl3): d = 3.72 (s, 3H, OMe), 5.55 (s, 1H, C4-H), 6.74–
7.39 (m, 8H, Ar–H) ppm; 13C NMR (75 MHz, CDCl3):
d = 189.0 (C=O), 150.6 (C=O), 143.9, 143.4, 129.6, 129.4,
126.3, 119.5, 114.6 (Ar–C), 74.5 (C–4), 55.1 (OCH3) ppm.
(4-methylphenyl)azetidin-2-one (5e, C23H19BrClNO2)
Starting from 1.26 g 3 (4.78 mmol), 1.0 g 4e (4.35 mmol)
and 1.31 g Et3N (1.81 cm3, 12.97 mmol). Colorless crys-
talline solid (1.35 g, 65%); m.p.: 144–145 °C; FT-IR
(KBr): vꢀ = 1,754 (C=O) cm-1 1H NMR (300 MHz,
;
1,4-Bis(4-methoxyphenyl)azetidin-2,3-dione
(6c, C17H15NO4)
CDCl3): d = 2.21 (s, 3H, Me), 4.43 (d, 1H, J = 11.7 Hz,
PhCH2O), 4.54 (d, 1H, J = 11.7 Hz, PhCH2O), 4.82 (d,
1H, J = 4.8 Hz, C4-H), 5.01 (d, 1H, J = 5.1 Hz, C3-H),
Starting from 0.10 g 5c (0.21 mmol) and 0.068 g n-
Bu3SnH (0.062 cm3, 0.23 mmol). White solid (0.032 g,
123

Facile radical mediated synthesis of azetidin-2,3-diones
991
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;
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15. Denis J-N, Correa A, Greene AE (1990) J Org Chem 55:1975,
and references therein
4-(4-Methoxyphenyl)-1-(4-methylphenyl)azetidin-2,3-dione
(6d)
Starting from 0.10 g 5d (0.22 mmol) and 0.070 g
n-Bu3SnH (0.064 cm3, 0.24 mmol). White crystalline solid
1
(0.029 g, 47%); FT-IR, H NMR, m.p., and CHN analysis
of compound 6d were found to be identical with the one
described in Ref. [22]; 13C NMR (75 MHz, CDCl3):
d = 191.0 (C=O), 153.7 (C=O), 143.3, 142.9, 129.5, 129.1,
126.3, 118.5, 113.8 (Ar–C), 73.9 (C–4), 55.0 (OCH3), 21.4
(CH3) ppm.
4-(4-Chlorophenyl)-1-(4-methylphenyl)azetidin-2,3-dione
(6e, C16H12ClNO2)
16. Herranz R, Castro-Pichel J, Vinuesa S, Garcia-Lopaz MT (1990)
J Org Chem 55:2232, and references therein
Starting from 0.10 g 5e (0.21 mmol) and 0.070 g
n-Bu3SnH (0.064 cm3, 0.24 mmol). White solid (0.040 g,
64%); m.p.: 186–188 °C; FT-IR (KBr): vꢀ = 1,770 (ketone
17. Lo YS, Sheehan JC (1972) J Am Chem Soc 94:8253
18. Sheehan JC, Lo YS (1973) J Org Chem 38:3227
19. Jen T, Frazee J, Hoover JR (1973) J Org Chem 38:2857
20. Bates GS, Ramaswany S (1980) Can J Chem 58:116
21. Tufariello JJ, Pinto DJ, Milowsky AS, Reinhardt DV (1987)
Tetrahedron Lett 28:5481
C=O), 1,820 (amide C=O) cm-1 1H NMR (300 MHz,
;
CDCl3): d = 2.24 (s, 3H, Me), 5.23 (s, 1H, C4-H), 6.92–
7.44 (m, 8H, Ar–H) ppm; 13C NMR (75 MHz, CDCl3):
d = 190.6 (C=O), 151.8 (C=O), 143.9, 143.8, 130.2, 129.4,
126.5, 119.7, 114.8 (Ar–C), 74.7 (C–4), 21.6 (CH3) ppm.
22. Van der Veen JM, Bari SS, Krishnan L, Manhas MS, Bose AK
(1989) J Org Chem 54:5758
23. Giese B (1989) Angew Chem Int Ed 28:969
24. Giese B (1986) Radicals in organic synthesis: formation of
Carbon-Carbon bonds. Pergamon Press, Oxford
25. Alcaide B, Almendros P, Aragoncillo C, Redono MC (2007)
J Org Chem 72:1604
26. Leemans E, D’hooghe M, Dejaegher Y, Tornroos KW, Kimpe
ND (2008) J Org Chem 73:1422
27. Bhalla A, Madan S, Venugopalan P, Bari SS (2006) Tetrahedron
62:5054
1,4-Diphenylazetidin-2,3-dione (6f)
Starting from 0.10 g 5f (0.24 mmol) and 0.078 g
n-Bu3SnH (0.072 cm3, 0.26 mmol). White solid (0.030 g,
52%); FT-IR, 1H NMR, m.p., and CHN analysis of
compound 6f were found to be identical with the one
described in Ref. [22]; UV-vis: kmax (e) = 352 (9,100) nm.
28. Bhalla A, Venugopalan P, Bari SS (2006) Tetrahedron 62:8291
29. Bhalla A, Rathee S, Madan S, Venugopalan P, Bari SS (2006)
Tetrahedron Lett 47:5255
30. Bhalla A, Venugopalan P, Bari SS (2006) Eur J Org Chem 4943
31. Bhalla A, Venugopalan P, Bhasin KK, Bari SS (2007) Tetrahe-
dron 63:3195
Acknowledgments We gratefully acknowledge the financial sup-
port for this work from the Indian Council of Cultural Relations, New
Delhi, Government of India, under ICCR (Indo-Iraqi, CEP Schme),
TF/OCF grant and Department of Science and Technology (DST),
New Delhi, Government of India, project no. SR/FTP/CS-135/2006
dated 13-03-2007.
32. Viout A, Gault H (1953) Compt Rend 237:1162
33. Abraham DJ, Mehanna AS, Williams FL (1982) J Med Chem
25:1015
34. Abraham DJ, Kennedy PE, Mehanna AS, Patwa DC, Williams
FL (1984) J Med Chem 27:967
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123