Aziridines as templates: A general strategy for the stereospecific synthesis of 2-azetidinones

Article abstract of DOI:10.1002/jhet.5570430103

Various routes to a variety of azridine-2-carboxylates have been described and the stereochemistry of these compounds has been determined by spectroscopic methods. Further, greater diversity of β-lactams via ring expansion of these azridines-2-carboxylates were obtained by a general, efficient and direct stereospecific approach.

Full text of DOI:10.1002/jhet.5570430103

Jan-Feb 2006
11
Aziridines as Templates: A General Strategy for the
Stereospecific Synthesis of 2-Azetidinones
S. D. Sharma* Seema Kanwar and Shivani Rajpoot
Department of Chemistry, Panjab University, Chandigarh 160 014 India
E mail: sdsharmapu@yahoo.com ; Phone: 91-172-2541435; Fax : 91-172-2545074
Received March 29, 2005
Various routes to a variety of azridine-2-carboxylates have been described and the stereochemistry of these
compounds has been determined by spectroscopic methods. Further, greater diversity of β-lactams via ring expan-
sion of these azridines-2-carboxylates were obtained by a general, efficient and direct stereospecific approach.
J. Heterocyclic Chem., 43, 11 (2006).
Aziridines represent a valuable class of useful and highly
stereoselective synthesis of such class of compounds.
Among them a notable example is the use of 3-chloroaze-
tidin-2-ones for the preparation of β-lactamase inhibitors as
well as the β-lactam antibiotic, carpetimycin. Although 3-
haloazetidin-2-ones have been generally prepared by the
ketene-imine cycloaddition methods [12-16], few reports
deals with the preparation by the enolate-imine condensation
reaction [17-21] as well. Though the classical methods have
been successfully employed for the preparation of a variety
of β-lactams, it should be noted that these routes are often
limited as regards to the stereochemical outcome. Direct
stereospecific approach, therefore, could provide a general
route to a greater diversity of β-lactams and would reduce the
dependence on other known non-stereospecific methods.
One such approach to β-lactams is through ring expansion of
aziridines.
versatile synthetic intermediates [1]. In fact, they can be pre-
pared by several stereo specific methods [2-3] and, due to
the intrinsic high strain of the aziridine ring, they are capable
of undergoing stereo controlled nucleophilic ring opening
reactions leading to a wide variety of nitrogen-containing
compounds bearing the most different functionalities [4-5].
By selecting suitable substitutents at the ring nitrogen or car-
bon atoms, aziridines can also be converted into less
strained heterocycles, often in a single-step sequence.
The relief or ring strain represents the driving force also in
another ring expansion of fame, namely the nucleophilic
attack of chloride ion on to azridine-2-carboxylates, whereby
the three-membered cycle is expanded to a β-lactam ring.
The reaction has proved to be an efficient tool for the stere-
oselective synthesis of substituted β-lactams. Due to signifi-
cant attention on the chemistry of β-lactamase inhibitors
such as 6-halopenicillanic acids [6-8], 3-halo-2-azetidinone
has been employed as synthetic intermediates [9-11] for the
In this paper, we disclose the synthesis of β-lactams by
making elegant use of aziridines. The initial target in our syn-
thesis was aziridine-2-carboxylates which serve as the repre-

12
S. D. Sharma S. Kanwar and S. Rajpoot
Vol. 43
tion of three-membered ring 8 (Scheme 2). Again both iso-
mers, cis and trans, were obtained in 85 % yield, and the
mixture was chromatographed to obtain the major cis isomer.
Finally aziridines of the type 10 [23] were prepared from
Schiff's bases 9 through carbene addition, which were gen-
erated from chloroform using potassium t-butoxide as a
base (Scheme 3).
We also synthesized cis ethyl aziridine-2-carboxylate 11
[24] via carbenoid addition on Schiff's base 9a, generated
using dichloromethane and butyl lithium (Scheme 4).
sentatives for β-lactam ring formation. This is due to the fact
that carboxylate group acts as a handle for enlargement of 3-
membered ring to 4-membered 2-azetidinone structure. We
adopted the following three methods to obtain the desired
aziridines. The first involves [22] synthesis of aziridine-2-
carboxylates from α,β-unsaturated esters 1, as outlined in
Scheme 1. In particular, addition of bromine to α,β-unsatu-
rated esters 1 in carbon tetrachloride at reflux smoothly pro-
vided dibromo derivatives 2, which were subjected to amina-
tive cyclization with variety of amines in anhydrous ethanol
at room temperature affording N-substituted aziridine car-
boxyltaes 3 as 75:25 mixture of cis/trans isomers in 95%
total yield. The two isomers were separated by column chro-
matography and the ring stereochemistry was assigned on
1
3
3
6
the basis of H NMR spectral analysis ( J > J ) the cis
cis
trans
stereochemistry was unambiguously assigned to aziridines 3
3
3
cis ( J 6.6 Hz) and trans stereochemistry to 3 trans ( J
2,3
2,3
2.7 Hz). The two isomers were separated by flash chro-
matography and the major cis isomer was taken for its further
elaboration to the β-lactam.
After successful formation of various cis aziridine-2-car-
boxylates 12, the three-membered ring was enlarged stere-
ospecifically to yield cis 2-azetidinones 14 using inexpensive
and easily available starting materials (Scheme 5) [25]. The
purified aziridine-2-carboxylates were first converted to their
sodium salts 13 by reaction with sodium hydroxide. The iso-
lated sodium salts were made to react with acid activating
agent either oxalyl chloride or thionyl chloride in presence of
base at room temperature to furnish cis 3-chloro-2-azetidi-
nones 14. The β-lactams were fully characterized by elemen-
tal and spectral analysis and it was observed that conversion of
aziridine-2-carboxylates to 2-azetidinones was stereospecific
as only cis β-lactams were isolated and no trans isomer were
detected within the limits of nmr spectral detection. A variety
of β-lactams have been prepared via this route (Table 1).
The second route to aziridine involves the use of Schiff's
bases as the starting material. Two different types of Schiff's
bases were used in three different methodologies to get aziri-
dine-2-carboxylates. Aiming to explore the feasibility of
intramolecular ring closure on Schiff's bases, the imines of
type 7 were prepared by the reaction of appropriate aldehyde
and glycine ethyl ester hydrochloride in presence of base in
dichloromethane at reflux temperature. After Schiff's base
formation, it was then cyclized to aziridine by the generation
of a carbanion at the α-carbon. Subsequent intramolecular
attack at the electrophilic imine carbon, results in the forma-
The ring enlargement involves initial conversion of
aziridine-2-carboxylate to sodium salt (13) using
saponification with aqueous sodium hydroxide. Further
reaction with oxalyl chloride or thionyl chloride fur-
nished the corresponding β-lactams 14 as shown in
Scheme 6 [27]. The ring expansion reactions were car-
ried out at ambient temperature. Although sensitive to
structural change, it is significant that changes in the
carboxylate activating reagent and proton scavenger
had relatively little effect on the yield. We thus con-

Jan-Feb 2006
A General Strategy for the Stereospecific Synthesis of 2-Azetidinones
13
Table 1
Various cis 3-Chloro-2-azetidinones Prepared from Aziridnes
1
2
S. No.
R
R
Yield (%)
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
H
H
H
CH C H
6 5
56
55
65
63
67
62
65
68
62
61
60
63
64
69
62
60
60
2
(CH ) CH
2 3 3
CH CH(CH )
2
3 2
H
CH CH C H
2 2 6 5
CH
CH
CH
CH
CH C H
2 6 5
3
3
3
3
(CH ) CH
2 3
3
CH CH(CH )
2 3 2
CH CH C H
2
2
6
5
C H
CH C H
6
5
5
5
5
2 6 5
C H
(CH ) CH
2 3 3
6
C H
CH CH C H
6
2 2 6
5
C H
H
6
C H OCH (p)
H
H
H
H
H
6
4
3
C H Cl(o)
6
4
C H OH(p)
6
4
Piperonyl
C H
6
5
clude that the mechanism for ring expansion does not
involve acid-catalyzed nucleophilic ring opening of the
aziridine ring and that the activating reagent plays no
role other than to foster acyl-oxygen cleavage. Since
formation of the β-lactam is totally stereo specific as
substituted aziridines. Further, several cis α-chloro-β-
alkyl/aryl azetidin-2-ones have been synthesized effi-
ciently by ring enlargement of cis aziridine-2-carboxy-
lates, which can serve as suitable precursors for other hete-
rocyclic systems especially the antibiotic drugs.
1
determined by H NMR spectra, it is therefore unlikely
that "free" carbonium ions intervene in the expansion
process. The mechanism shown in Scheme 6 fits the
experimental data and is also in agreement with
observed stereochemistry of products 14 by virtue of
EXPERIMENTAL
All melting points (m.p., °C) are uncorrected. The FT-IR spec-
tra were recorded on a Perkin-Elmer Model 1430 spectropho-
tometer and were calibrated against polystyrene. Only the princi-
the back side attack on the C -N bond.
3
1
-1 1
pal peaks of interest are reported and expressed in cm . H NMR
spectra were recorded on a 300 MHz Bruker AC 300F spectrom-
eter. Chemical shifts are expressed as δ values (ppm) downfield
from tetramethylsilane. Elemental analysis (C, H, N) was
recorded using a Perkin Elmer 2400 (C, H, N) elemental ana-
lyzer. Thin layer chromatography was performed using tlc grade
Silica gel (G) and was developed in an atmosphere of iodine
vapours.
General Procedure for the Preparation of 2,3-Dibromopropionic
Acid Ethyl Ester 2a.
To a stirred solution of acrylic acid ethyl ester (0.1 mmole) in
carbon tetrachloride, bromine (0.101 mmole) was added drop-
wise at room temperature. After the contents were gently
refluxed for 24 hour, the solution was cooled and solvent was
1
removed under reduced pressure to get 2a in 88% yield. H nmr
(deuteriochloroform): δ 1.36 (t, J = 7.1 Hz, 3H, CH CH ), 4.32
2
3
(q, J = 7.1 Hz, 2H, CH CH ), 4.36 (m, 1H, CHBrCO ), 4.48 (m,
2
3
2
-1
2H, CH Br); IR (chloroform): 1744 cm .
All attempts to convert the dichloro aziridine-2-carbox-
ylates 10a, 10b and monochloroazridine-2-carboxylate 11
to the corresponding β-lactam structures were not success-
ful. The reason may be attributed to the unstable nature of
these type of aziridines under the reaction conditions used.
2
Anal. Calcd. for C H O Br : C 23.08, H 3.08. Found:
22.97, H 3.15.
C
5
8
2
2
2,3-Dibromobutyric Acid Ethyl Ester (2b).
1
This compound was obtained in 78 % yield; H nmr (deuteri-
ochloroform): δ 1.37 (t, J = 7.1 Hz, 3H, CH CH ), 1.93 (d, J = 6.3
2
3
Conclusion.
Hz, 3H, CH CHBr,), 4.32 (q, J = 7.1 Hz, 2H, CH CH ,), 4.36 (d,
3
2
3
n the course of our study, we have amply demonstrated
I
J = 7.0 Hz, 1H, CHBrCO ), 4.48 (m, 1H, CH CHBr); IR (chloro-
2
3
-1
the use of a large no. of convenient routes to a variety of
form): 1745 cm .

14
S. D. Sharma S. Kanwar and S. Rajpoot
Vol. 43
1
Anal. Calcd. for C H O Br : C 26.27, H 3.65. Found:
C
This compound was obtained in 77 % yield; H nmr (deuterio-
6
10
2
2
26.11, H 3.54.
chloroform): δ 0.82-1.83 (m, 10H, CH (CH ) , CH CH ), 1.79
3
2 2
2
3
(dd, J = 5.8 Hz & 6.6 Hz, 1H, C H,), 2.18 (dd, J = 6.2 Hz & 6.6
3
2,3-Dibromo-3-phenylpropionic Acid Ethyl Ester (2c).
Hz, 1H, C H,), 2.92 (t, 2H, NCH ), 3.43 (dd, J = 5.8 Hz & 6.7 Hz,
3
2
1
This compound was obtained in 78 % yield; H nmr (deuteri-
-1
1H, C H), 4.21 (q, 2H, CH CH ); IR (chloroform): 1732 cm .
2
2
3
ochloroform): δ 1.37 (t, 3H, CH CH ), 4.34 (q, J = 7.2 Hz, 2H,
2
3
Anal. Calcd. for C H NO : C 63.16, H 9.94, N 8.18. Found:
9
17
2
CH CH ), 4.76 (d, J = 7.3 Hz, 1H, CHPh), 5.06 (d, J = 7.3 Hz,
2
3
C 63.01, H 9.91, N 8.21.
-1
1H, CHBrCO ), 7.34 (s, 5H, C H ); IR (chloroform): 1743 cm .
2
6 5
1-Butyl-3-methylaziridine-2-carboxylic Acid Ethyl Ester (4b).
Anal. Calcd. for C H O Br : C 37.07, H 3.37. Found: C
11 12
2
2
36.99, H 3.21.
1
This compound was obtained in 74 % yield; H nmr (deuteri-
ochloroform): δ 0.81-1.82 (m, 7H, (CH ) CH ,), 1.28 (d, J = 5.6
1-Benzyl-Aziridine-2-Carboxylic Acid Ethyl Ester (3a).
2 2
3
Hz, 3H, CH ), 1.31 (t, J = 7.2 Hz, 3H, CH CH ), 1.96-2.05 (m,
3
2
3
To the stirred solution of benzyl amine (0.1 mmole) in anhy-
drous ethanol maintained at 0° was slowly added a solution of 2a
(0.03 mmole) in absolute ethanol. The reaction mixture was
allowed to warm to room temperature and stirred overnight. The
solvent was removed under vacuum to get a solid which was dis-
solved in ether and washed with water. The aqueous layer was
extracted with ether. The combined organic extract was dried
over anhydrous magnesium sulphate and concentrated to afford
dark yellow oil, which was purified by chromatography over sil-
ica gel using petroleum ether: ethyl ether to get pure 3a. Yield
1H, C H), 2.22 (d, J = 6.6 Hz, 1H, C H), 2.84 (t, 2H, NCH ),
3
2
2
-1
4.25 (q, J = 7.2 Hz, 2H, CH CH ); IR (chloroform): 1730 cm .
2
3
Anal. Calcd. for C
H NO : C 63.16, H 10.27, N 7.57.
10 19 2
Found: C 64.55, H 10.00, N 7.46.
1-Butyl-3-phenylaziridine-2-carboxylic Acid Ethyl Ester (4c).
1
This compound was obtained in 70 % yield; H nmr (deuteri-
ochloroform): δ 0.78-1.79 (m, 7H, CH (CH ) CH , CH CH ),
2
2 2
3
2
3
1.32 (t, J = 7.2 Hz, 3H, CH CH ), 2.51 (d, J = 6.8 Hz, 1H, C H),
2
3
2
2.89 (t, 2H, NCH ), 2.92 (d, J = 6.8 Hz, 1H, C H), 4.21 (q, J = 7.2
2
3
1
79%. H nmr (deuteriochloroform): δ 1.3 (t, 3H, CH CH ), 1.8
2
3
Hz, 2H, CH CH ), 7.21-7.31 (s, 5H, C H ); IR (chloroform):
2
3
6 5
(dd, J = 6.2 Hz & 6.6 Hz, 1H, C H), 2.2 (dd, J = 5.8 Hz & 6.6 Hz,
3
-1
1727 cm .
Anal. Calcd. for C
1H, C H), 3.51 (dd, J = 6.2 Hz, & 5.8 Hz, 1H, C H), 3.56 (d, J =
3
2
H
NO : C 72.87, H 8.50, N 5.67. Found:
2
15 21
13.9 Hz, 1H, CH Ph,), 3.63 (d, J = 13.9 Hz, 1H, CH Ph), 4.2 (q,
2
2
C 72.71, H 8.49, N 5.79.
-1
2H, CH CH ), 7.45 (s, 5H, C H ); IR (chloroform): 1731.8 cm .
2
3
6 5
1-Isobutylaziridine-2-carboxylic Acid Ethyl Ester (5a).
Anal. Calcd. for C
H NO : C 70.24, H 7.31, N 6.82. Found:
12 15 2
C 69.98, H 7.15, N 6.90.
1
This compound was obtained in yield 70 %; H nmr (deuteri-
ochloroform): δ 1.21 (d, 6H, CH(CH ) ), 1.31 (t, 3H, CH CH ),
Cis 1-Benzyl-3-methylaziridine-2-carboxylic Acid Ethyl Ester (3b).
3 2
2
3
1.42 (m, 1H, CH(CH ) ), 1.80 (d, J = 6.1 Hz, 2H, NCH ) 1.89
3 2
2
1
This compound was obtained in 72 % yield; H nmr (deuterio-
(dd, J = 6.2 Hz & 6.8 Hz, 1H, C H), 2.25 (dd, J = 5.9 Hz & 6.8
3
chloroform): δ 1.27 (t, J = 7.2 Hz, 3H, CH CH ), 1.31 (d, J = 5.6
2
3
Hz, 1H, C H), 3.42 (dd, J = 6.2 Hz & 5.9 Hz, 1H, C H), 4.21 (q,
3
2
Hz, 3H, CHCH ), 2.01 (m, 1H, C H), 2.22 (d, J = 5.3 Hz, 1H,
3
3
-1
2H, CH CH ); IR (chloroform): 1732 cm .
2
3
C H), 3.56 (d, J = 13.9 Hz, 1H, CH Ph), 3.65 (d, J = 13.9 Hz, 1H,
2
2
Anal. Calcd. for C H NO : C 63.16, H 9.94, N 8.18. Found:
9
17
2
CH Ph), 4.21(q, J = 7.2 Hz, 2H, CH CH ), 7.42-7.84 (s, 5H,
2
2
3
C 62.99, H 9.89, N 8.30.
-1
C H ); IR (chloroform): 1732 cm .
6
5
1-Isobutyl-3-methylaziridine-2-carboxylic Acid Ethyl Ester (5b).
Anal. Calcd. for C
H NO : C 71.23, H 7.76, N 6.39. Found:
13 17 2
C 69.99, H 7.49, N 6.59.
1
This compound was obtained in 73 % yield; H nmr (deuteri-
ochloroform): δ 1.26 (d, 6H, CH(CH ) ), 1.29 (d, J = 5.6 Hz, 3H,
Trans 1-Benzyl-3-methylaziridine-2-carboxylic Acid Ethyl Ester
(3b).
3 2
CHCH ), 1.31 (t, J = 7.1 Hz, 3H, CH CH ), 1.43 (m, 1H,
3
2
3
CH(CH ) ), 1.81 (d, 2H, NCH ), 1.96-2.04 (1H, m, C H), 2.19
3 2
2
3
1
This compound was obtained in 27 % yield; H nmr (deuterio-
(d, J = 6.8 Hz, 1H, C H,), 4.22 (q, J = 7.1 Hz, 2H, CH CH ); IR
2
2
3
chloroform): δ 1.25 (t, J = 7.2 Hz, 3H, CH CH ), 1.35 (d, J = 5.6
2
3
-1
(chloroform): 1729 cm .
Anal. Calcd. for C
Hz, 3H, CHCH ), 2.13 (d, J = 2.4 Hz, 1H, C H), 2.46 (m, 1H,
3
2
H
NO : C 64.88, H 10.27, N 7.57.
2
10 19
C H), 3.56 (d, J = 13.9 Hz, 1H, CH Ph), 3.65 (d, J = 13.9 Hz, 1H,
3
2
Found: C 64.71, H 10.01, N 7.61.
CH Ph), 4.20(q, J = 7.2 Hz, 2H, CH CH ), 7.40-7.80 (s, 5H,
2
2
3
-1
C H ); IR (chloroform): 1732 cm .
1-Isobutyl-3-phenylaziridine-2-carboxylic Acid Ethyl Ester (5c).
6
5
Anal. Calcd. for C
C 69.99, H 7.49, N 6.59.
H NO : C 71.23, H 7.76, N 6.39. Found:
13 17 2
1
This compound was obtained in 68 % yield; H nmr (deuteri-
ochloroform): δ 1.24 (d, 6H, CH(CH ) ), 1.44 (m, 1H,
3 2
CH(CH ) ), 1.31 (t, J = 7.1 Hz, 3H, CH CH ), 1.90 (d, 2H,
1-Benzyl-3-phenylaziridine-2-carboxylic Acid Ethyl Ester (3c).
3 2
2
3
NCH ), 2.90 (1H, J = 6.8 Hz, d, C H), 3.45 (1H, J = 6.8 Hz, d,
1
2
2
This compound was obtained in 70 % yield; H nmr (deuterio-
C H), 4.32 (q, J = 7.1 Hz, 2H, CH CH ), 6.98-7.56 (m, 5H,
3
2
3
chloroform): δ 1.32 (t, J = 7.1 Hz, 3H, CH CH ), 2.66 (d, J = 6.8
2
3
-1
ArH); IR (chloroform): 1725 cm .
Anal. Calcd. for C NO : C 72.87, H 8.50, N 5.67. Found:
Hz, 1H, C H), 3.07 (d, J = 6.8 Hz, 1H, C H,), 3.84 (d, J = 13.9
2
3
H
15 21
2
Hz, 1H, CH C H ), 3.93 (d, J = 13.9 Hz, 1H, CH C H ), 4.20 (q,
J = 7.1 Hz, 2H, CH CH ), 7.2-7.5 (m, 10H, ArH); IR (chloro-
2
6
5
2 6 5
C 72.59, H 8.30, N 5.77.
2
3
-1
form): 1725 cm .
Anal. Calcd. for C
1-Phenylethylaziridine-2-carboxylic Acid Ethyl Ester (6a).
H
NO : C 64.86, H 10.27, N 7.57.
2
18 19
1
This compound was obtained in 75 % yield; H nmr (deuteri-
Found: C 64.61, H 10.11, N 7.72.
ochloroform): δ 1.33 (t, 3H, CH CH ), 2.00 (dd, J = 6.0 Hz &
2
3
1-Butylaziridine-2-carboxylic Acid Ethyl Ester (4a).
6.59 Hz, 1H, C H,), 2.21 (dd, J = 5.7 Hz & 6.59 Hz, 1H, C H),
3
3

Jan-Feb 2006
A General Strategy for the Stereospecific Synthesis of 2-Azetidinones
15
1
3.50 (m, 2H, CH C H ), 3.62 (m, 2H, NCH ), 3.65 (dd, J = 6.0
This compound has the following properties: H nmr (deuteri-
2
6
5
2
Hz & 5.7 Hz, 1H, C H), 4.29 (q, 2H, CH CH ), 7.1-7.53 (m, 5H,
ArH); IR (chloroform): 1735 cm .
ochloroform): δ 1.43 (t, 3H, CH CH ), 4.11 (d, J = 15 Hz, 1H,
2
2
3
2
3
-1
NCH ), 4.20 (d, J = 15 Hz, 1H, NCH ), 4.31 (q, 2H, CH CH ),
2
2
2
3
Anal. Calcd. for C NO : C 71.23, H 7.76, N 6.39. Found:
C 70.05, H 7.52, N 6.69.
H
6.12 (s, 2H, OCH O), 6.85-7.67 (m, 3H, ArH), 8.32 (s, 1H,
HCN); IR (chloroform): 1741, 1688, 1645 cm .
13 17
2
2
-1
Anal. Calcd. for C
C 61.11, H 5.36, N 5.46.
H NO : C 61.27, H 5.53, N 5.95. Found:
12 13 4
1-Phenylethyl-3-methylaziridine-2-carboxylic Acid Ethyl Ester (6b).
1
This compound was obtained in 75 % yield; H nmr (deuteri-
[(Benzylidene)amino]acetic Acid Ethyl Ester (7e).
ochloroform): δ 1.29 (t, 3H, CH CH ), 1.32 (d, J = 5.6 Hz, 3H,
2
3
CHCH ), 2.15 (m, 1H, C H), 2.35 (d, J = 6.8 Hz, 1H, C H), 3.62
1
3
3
2
This compound has the following properties: H nmr (deuteri-
(m, 2H, CH C H ), 4.29 (q, 2H, CH CH ), 6.89-7.56 (m, 10H,
2
6
5
2
3
ochloroform): δ 1.32 (t, 3H, CH CH ), 3.89 (m, 2H, NCH ), 4.23
2
3
2
-1
ArH); IR (chloroform): 1730 cm .
Anal. Calcd. for C NO : C 72.10, H 8.15, N 6.01. Found:
(q, 2H, CH CH ), 6.89-7.12 (m, 5H, ArH), 8.23 (s, 1H, HCN); IR
2
3
H
-1
14 19
2
(chloroform): 1743, 1686 cm .
C 71.99, H 7.98, N 5.96.
Anal. Calcd. for C H NO : C 69.10, H 6.81, N 7.33. Found:
11 13
2
1-Phenylethyl-3-phenylaziridine-2-carboxylic Acid Ethyl Ester
C 69.00, H 6.52, N 7.01.
(6c).
3-(4-Methoxyphenyl)aziridine-2-carboxylic Acid Ethyl Ester
(8a).
1
This compound was obtained in 74 % yield; H nmr (deuteri-
ochloroform): δ 1.32 (t, 3H, CH CH ), 2.56 (m, 2H, CH C H ),
3.41 (m, 2H, NCH ), 3.21 (d, J = 6.7 Hz, 1H, C H), 3.52 (d, J =
6.8 Hz, 1H, C H), 4.22 (q, 2H, CH CH ), 7.01-7.53 (m, 10H,
ArH); IR (chloroform): 1730 cm .
Anal. Calcd. for C NO : C 77.29, H 7.11, N 4.75. Found:
2
3
2 6 5
Sodium hydride (0.81 mmole) was washed with dry hexane
and to this 7a (0.1 mmole) in dry benzene was added dropwise
under stirring. The reaction mixture was heated to reflux for 5-6
hour, cooled to room temperature and poured over crushed ice
slowly taking care of froth formation. The organic layer was sep-
arated and dried over anhydrous sodium sulphate, filtered and
concentrated under vacuum to get 8a, which was purified using
column chromatography (ethyl acetate:hexane 2:3) to obtain only
2
2
3
2
3
-1
H
19 21
2
C 76.97, H 6.93, N 4.83.
[(4-Methoxybenzylidene)amino]acetic Acid Ethyl Ester (7a).
p-Anisaldehyde (0.1 mmole) and carbethoxymethyl amine
hydrochloride (0.1 mmole) were stirred in dry dichloromethane
while a solution of triethylamine (0.1 mmole) in dry
dichloromethane was added dropwise at room temperature. After
the complete addition, the solution was refluxed for 2 hour and
then stirred overnight at room temperature. The resulting solution
was washed with water and dried over sodium sulphate. Removal
of the solvent afforded 7a, as an oil in 76 % yield, which was
1
the major cis isomer in 65 % yield. H nmr (deuteriochloroform):
δ 1.21 (t, 3H, CH CH ), 1.65 (s, 1H, NH), 3.25 (d, J = 6.1 Hz,
2
3
1H, C H), 3.45 (d, J = 6.3 Hz, 1H, C H), 3.82 (s, 3H, OCH ),
2
3
3
4.21 (q, 2H, CH CH ), 6.9-7.51 (m, 4H, ArH); IR (chloroform):
2
3
-1
3250, 1721 cm .
Anal. Calcd. for C
H NO : C 65.16, H 6.79, N 6.33. Found:
12 15 3
C 64.99, H 6.65, N 6.45.
1
used as such in the next reaction. H nmr (deuteriochloroform): δ
1.45 (t, 3H, CH CH ), 3.35 (d, J = 14.9 Hz, 1H, NCH ,), 3.98 (s,
3H, OCH ), 4.19 (d, J = 14.9 Hz, 1H, NCH ), 4.32 (q, 2H,
3-(2-Chlorophenyl)aziridine-2-carboxylic acid ethyl ester (8b).
2
3
2
1
This compound was obtained in 60 % yield; H nmr (deuteri-
3
2,
ochloroform): δ 1.35 (t, 3H, CH CH ), 1.71 (s, 1H, NH), 3.12 (d,
CH CH ), 7.21 (d, 2H, ArH), 8.05 (d, 2H, ArH), 8.45 (s, 1H,
2
3
2
3
-1
J = 6.1 Hz, 1H, C H), 3.31 (d, J = 6.1 Hz, 1H, C H), 4.32 (q, 2H,
HCN); IR (chloroform): 1736, 1686 cm .
Anal. Calcd. for C NO : C 65.16, H 6.79, N 6.33. Found:
C 64.89, H 6.61, N 6.45.
2
3
CH CH ), 6.95-7.32 (m, 4H, ArH); IR (chloroform): 3250, 1720,
H
2
3
12 15
3
-1
1225 cm .
Anal. Calcd. for C
Found: C 58.35, H 5.12, N 6.19.
H NO C: C 58.54, H 5.32, N 6.20.
11 12 2
[(2-Chlorobenzylidene)amino]acetic Acid Ethyl Ester (7b).
1
This compound has the following properties: H nmr (deuteri-
3-(4-Hydroxyphenyl)aziridine-2-carboxylic Acid Ethyl Ester
(8c).
ochloroform): δ 1.72 (t, 3H, CH CH ), 4.12 (q, 2H, CH CH ),
2
3
2
3
4.51 (d, J = 15.0 Hz, 1H, NCH ,), 4.72 (d, J = 15.0 Hz, 1H,
2
1
NCH ,), 7.81 (s, 4H, ArH), 8.71 (s, 1H, HCN); IR (chloroform):
1736, 1641 cm .
This compound was obtained in 62 % yield; H nmr (deuteri-
2
-1
ochloroform): δ 1.31 (t, 3H, CH CH ), 1.52 (s, 1H, NH), 3.23 (d,
2
3
Anal. Calcd. for C
H NO CI: C 58.54, H 5.32, N 6.21.
11 12 2
J = 6.2 Hz, 1H, C H), 3.41 (d, J = 6.2 Hz, 1H, C H), 4.32 (q, 2H,
2
3
Found: C 58.41, H 5.10, N 5.94.
CH CH ), 6.95-7.32 (m, 4H, ArH); IR (chloroform): 3230, 1725
2
3
-1
cm .
[(4-Hydroxybenzylidene)amino]acetic Acid Ethyl Ester (7c).
Anal. Calcd. for C H NO : C 63.77, H 6.28, N 6.76. Found:
11 13
3
1
This compound has the following properties: H nmr (deuteri-
C 63.42, H 6.11, N 6.52.
ochloroform): δ 1.31 (t, 3H, CH CH ), 3.91 (d, J = 15.2 Hz, 1H,
2
3
3-Benzo[1,3]dioxol-5-yl-aziridine-2-carboxylic Acid Ethyl Ester
NCH ), 4.09 (d, J = 15.2 Hz, 1H, NCH), 4.21 (q, 2H, CH CH ),
2
2
3
(8d).
6.71-7.51 (m, 4H, ArH), 8.45 (s, 1H, HCN); IR (chloroform):
3316, 1744 cm .
-1
1
This compound was obtained in 63 % yield; H nmr (deuteri-
Anal. Calcd. for C H NO : C 63.77, H 6.28, N 6.76. Found:
C 63.45, H 5.96, N 6.52.
11 13
3
ochloroform): δ 1.33 (t, 3H, CH CH ), 1.62 (s, 1H, NH), 3.25 (d,
2
3
J = 6.0 Hz, 1H, C H), 3.59 (d, J = 6.0 Hz, 1H, C H), 4.28 (q, 2H,
2
3
[(Benzo[1,3]dioxol-5-ylmethylene)amino]acetic Acid Ethyl
Ester (7d).
CH CH ), 6.12 (s, 2H, OCH O), 6.85-7.41 (m, 3H, ArH); IR
(chloroform): 3240, 1721 cm .
2
3
2
-1

16
S. D. Sharma S. Kanwar and S. Rajpoot
Vol. 43
Anal. Calcd. for C
C 61.00, H 5.21, N 5.99.
H
NO : C 61.28, H 5.53, N 5.96. Found:
(0.05 mmole) was added dropwise with stirring to the above
cooled solution. The reaction temperature was maintained below
–90° at all times. The resulting opaque solution was stirred for 5
minutes at –100° and 9a (0.013 mmole) in dry ether was added
dropwise. After the addition (upon which the temperature was
maintained below -90°) was complete, the reaction temperature
was allowed to rise to –75° and the resulting homogenous
orange-yellow solution was stirred at –75° for 5-10 minutes and
then allowed to warm up slowly. At room temperature the reac-
tion mixture was poured into water and the organic layer sepa-
rated and washed with three portions of water, dried over sodium
sulphate and evaporated in vacuo to leave the product 11 in 50%
12 13
4
3-Phenylaziridine-2-carboxylic Acid Ethyl Ester (8e).
1
This compound was obtained in 65 % yield; H nmr (deu-
teriochloroform): δ 1.35 (t, 3H, CH CH ), 1.58 (s, 1H, NH),
3.31 (d, J = 5.9 Hz, 1H, C H), 3.66 (d, J = 5.9 Hz, 1H, C H),
2
3
2
3
4.23 (q, 2H, CH CH ), 6.90-7.20 (m, 5H, ArH); IR (chloro-
2
3
-1
form): 3245, 1723 cm .
Anal. Calcd. for C H NO : C 69.11, H 6.81, N 7.32. Found:
C 69.00, H 6.79, N 7.45.
11 13
2
(4-Methoxyphenylimino)acetic Acid Ethyl Ester (9a).
1
yield. H nmr (deuteriochloroform): δ 1.32 (t, 3H, CH CH ),
2
3
Ethyl glyoxalate (50 % solution in toluene, 0.2 mmole) and p-
anisidine (0.1 mmole) were stirred in dichloromethane over mol-
ecular sieves at room temperature. When the reaction was over
(reaction monitored by tlc), molecular sieves were filtered and
washed with dichloromethane and the filtrate concentrated under
vacuum to get a brown coloured liquid in 87% yield, which was
3.52 (d, 1H, C H), 3.85 (s, 3H, OCH ), 4.22 (d, 1H, C H), 4.31
2
3
3
(q, 2H, CH CH ), 6.89-7.12 (m, 4H, ArH); IR (chloroform):
2
3
-1
1730 cm .
Anal. Calcd. for C
H
NO Cl: C 56.36, H 5.48, N 5.48.
3
12 14
Found: C 56.01, H 5.26, N 5.61.
1
General Procedure for the Synthesis of Sodium Aziridine-2-car-
boxylates (13a-q).
used as such for the next operation. H nmr (deuteriochloro-
form): δ 1.35 (t, 3H, CH CH ), 3.71 (s, 3H, OCH ), 4.23 (q, 2H,
2
3
3
CH CH ), 6.89-7.32 (m, 4H, ArH), 8.45 (s, 1H, HCN); IR (chlo-
2
3
Ethyl aziridine-2-carboxylate (0.1 mmole) and sodium
hydroxide (0.1 mmole) were stirred together in water (0.2 ml) at
room temperature overnight. The resulting solution was evapo-
rated to dryness to yield sodium salt of aziridine. Analytical data
of some of the representatives are given below.
-1
roform): 1740, 1645 cm .
Anal. Calcd. for C H NO : C 63.77, H 6.28, N 6.76. Found:
C 63.57, H 6.17, N 6.97.
11 13
3
Phenyliminoacetic Acid Ethyl Ester (9b).
1
Sodium 1-Benzylaziridine-2-carboxylate (13a).
This compound has the following properties; H nmr (deuteri-
ochloroform): δ 1.30 (t, 3H, CH CH ), 4.20 (q, 2H, CH CH ),
1
2
3
2
3
This compound has the following properties: H nmr (deuteri-
6.99-7.42 (m, 4H, ArH), 8.35 (s, 1H, HCN); IR (chloroform):
ochloroform): δ 3.18 (dd, J = 2.1 Hz & 14.4 Hz, 1H, C H), 3.78
(dd, J = 5.1 Hz & 14.4 Hz, 1H, C H), 4.10 (d, J = 15.3 Hz, 1H,
CH C H ), 4.59 (d, J = 15.3 Hz, 1H, CH C H ), 4.57 (dd, J = 2.1
3
-1
1742, 1665cm .
3
Anal. Calcd. for C H NO : C 67.80, H 6.21, N 7.91. Found:
10 11
2
2
6
5
2 6 5
C 67.70, H 6.10, N 7.99.
Hz & 5.1 Hz, 1H, C H), 7.25-7.38 (m, 5H, C H ); IR (chloro-
2
6 5
-1
form): 1766 cm .
Anal. Calcd. for C
3,3-Dichloro-1-(4-methoxyphenyl)aziridine-2-carboxylic Acid
Ethyl Ester (10a).
H
NO Na: C 60.30, H 5.03, N 7.04.
2
10 10
Found: C 59.99, H 4.89, N 7.32.
To a stirred slurry of 9a (0.10 mmole) and potassium t-butox-
ide (0.20 mmole) in n-hexane, chloroform (0.20 mmole) was
slowly added at –20° to –30°. The reaction mixture was stirred
for 3 hour at this temperature and then for 5 hour at room temper-
ature. The mixture was suction filtered and the residue was
washed three times with n-hexane, and the solvent was removed
in vacuum from the combined filtrates, yielding 56 % of oily
Sodium 1-Butylaziridine-2-carboxylate (13b).
1
This compound has the following properties: H nmr (deuteri-
ochloroform): δ 1.61-1.92 (m, 7H, CH CH & CH ), 3.10 (t, 2H,
2
2
3
NCH ), 3.20 (dd, J = 3.1 Hz & 13.8 Hz, 1H, C H), 3.71 (dd, J =
2
3
5.0 Hz & 13.8 Hz, 1H, C H), 4.49 (dd, J = 3.1 Hz & 5.0 Hz 1H,
3
-1
C H); IR (chloroform): 1757 cm .
1
2
material. H nmr (deuteriochloroform): δ 1.30 (t, 3H, CH CH ),
2
3
Anal. Calcd. for C H NO Na: C 50.91, H 7.27, N 8.49.
7
12
2
3.06 (s, 1H, NCH), 3.85 (s, 3H, OCH ), 4.23 (q, 2H, CH CH ),
3
2
3
Found: C 50.61, H 7.10, N 8.53.
-1
6.59-7.10 (m, 4H, ArH); IR (chloroform): 1732 cm .
Anal. Calcd. for C NO Cl : C 49.83, H 4.50, N 4.84.
H
Sodium 1-Isobutylaziridine-2-carboxylate (13c).
12 13
3
2
Found: C 49.52, H 4.26, N 4.95.
1
This compound has the following properties: H nmr (deuteri-
3,3-Dichloro-1-phenyl-aziridine-2-carboxylic Acid Ethyl Ester
(10b).
ochloroform): δ 1.32 (d, J = 6.2 Hz, 6H, CH(CH ) ), 1.92 (d,
3 2
J = 6.0 Hz, 2H, CH CH(CH ) ), 3.01 (dd, J = 3.2 Hz & 13.8 Hz,
2
3 2
1H, C H), 3.69 (dd, J = 5.1 Hz & 13.8 Hz, 1H, C H), 4.51 (dd, J
1
3
3
This compound was obtained in 50 % yield; H nmr (deuteri-
-1
= 3.2 Hz & 5.1 Hz, 1H, C H); IR (chloroform): 1765 cm .
ochloroform): δ 1.35 (t, 3H, CH CH ), 3.21 (s, 1H, C H), 4.19 (q,
2H, CH CH ), 6.99-7.20 (m, 5H, ArH); IR (chloroform): 1729 cm .
2
2
3
2
-1
Anal. Calcd. for C H NO Na: C 50.91, H 7.27, N 8.49.
7
12
2
2
3
Found: C 50.75, H 7.07, N 8.53.
Anal. Calcd. for C
H NO Cl : C 50.97, H 4.25, N 5.41.
11 11 2 2
Found: C 50.47, H 4.11, N 5.53.
Sodium 1-Phenethylaziridine-2-carboxylate (13d).
3-Chloro-1-(4-methoxyphenyl)aziridine-2-carboxylic Acid Ethyl
Ester (11).
1
This compound has the following properties: H nmr (deuteri-
ochloroform): 1.32 (d, J = 6.2 Hz, 6H, CH(CH ) ), 1.92 (d, J =
3 2
6.0 Hz, 2H, CH CH(CH ) ), 3.01 (dd, J = 3.2 Hz & 13.8 Hz, 1H,
A solution of dry tetrahydrofuran, dry ether and methylene
chloride (0.1 mmole) was cooled in ether-liquid nitrogen bath
under nitrogen atmosphere. A hexane solution of n-butyl lithium
2
3 2
C H), 3.69 (dd, J = 5.1 Hz & 13.8 Hz, 1H, C H), 4.51 (dd, J = 3.2
3
3
-1
Hz & 5.1 Hz, 1H, C H); IR (chloroform): 1600 cm .
2

Jan-Feb 2006
A General Strategy for the Stereospecific Synthesis of 2-Azetidinones
17
Anal. Calcd. for C
H
NO Na: C 61.97, H 5.63, N 6.57.
Anal. Calcd. for C H NOCl: C 52.01, H 7.43, N 8.66. Found:
7 12
11 12
2
Found: C 61.82, H 5.51, N 6.48.
C 51.88, H 7.29, N 8.75.
3-Chloro-1-isobutylazetidin-2-one (14c).
Sodium 3-(4-Methoxyphenyl) aziridine-2-carboxylate (13m).
1
1
This compound has the following properties: H nmr (deuterio-
This compound has the following properties: H nmr (deuterio-
chloroform): δ 1.32 (d, J = 6.1 Hz, 6H, CH(CH ) ), 1.92 (d, 2H,
chloroform): δ 3.39 (d, J = 6 Hz, 1H, C H), 3.52 (d, J = 6 Hz, 1H,
3 2
2
CH CH(CH ) ), 3.01 (dd, J = 3.2 Hz & 13.8 Hz, 1H, C H), 3.69
C H), 3.86 (s, 3H, OCH ), 6.81-7.32 (m, 4H, ArH); IR (chloro-
2
3 2
4
3
3
-1
(dd, J = 5.1 Hz & 13.8 Hz, 1H, C H), 4.51 (dd, J = 3.2 Hz & 5.1
form): 3245, 1600 cm .
4
13
Hz, 1H, C H); C nmr (deuteriochloroform): δ 20.33,24.79,
56.41, 57.24, 57.84, 170.04; IR (chloroform): 1765 cm .
Anal. Calcd. for C
H
NO Na: C 55.81, H 4.65, N 6.51.
3
10 10
3
-1
Found: C 55.65, H 4.39, N 6.85.
Anal. Calcd. for C H NOCl: C 52.01, H 7.43, N 8.66. Found:
C 51.79, H 7.34, N 8.72.
7
12
Sodium 3-Benzo[1,3]dioxol-4-yl-aziridine-2-carboxylate (13p).
1
This compound has the following properties: H nmr (deuteri-
3-Chloro-1-phenethylazetidin-2-one (14d).
ochloroform): δ 3.25 (d, J = 6 Hz, 1H, C H), 2.56 (d, J = 6 Hz,
2
1
1H, C H), 6.31 (s, 2H, OCH O), 6.81-7.25 (m, 3H, ArH); IR
This compound has the following properties: H nmr
3
2
-1
(chloroform): 3345, 1600 cm .
Anal. Calcd. for C H NO Na: C 52.40, H 3.49, N 6.11.
(deuteriochloroform): δ 2.79 (t, 2H, CH C H ), 3.32 (t, 2H,
2
6 5
NCH ), 3.44 (dd, J = 3.0 Hz & 14.2 Hz, 1H, C H), 3.59 (dd, J =
10
8
4
2
4
5.3 Hz & 14.2 Hz, 1H, C H), 4.89 (dd, J = 3.0 Hz & 5.3 Hz, 1H,
Found: C 52.00, H 3.31, N 6.32.
4
13
C H), 7.02-7.53 (br, 5H, ArH); C nmr (deuteriochloroform): δ
3
General Procedure for the Synthesis of 3-Chloro-2-Azetidinone
(14a-q).
33.13, 47.55, 55.83, 56.23, 126.09, 128.71, 128.92, 140.33,
-1
169.80; IR (chloroform): 1752, 1754 cm .
Using Oxalyl Chloride.
Anal. Calcd. for C
H NOCl: C 63.00, H 5.72, N 6.68.
11 12
Found: C 62.81, H 5.60, N 6.81.
The sodium salt (13, 0.1 mmole) was slowly added to a mix-
ture of oxalyl chloride (0.12 mmole) and triethylamine (0.12
mmole) in benzene (1 ml). The dark brown slurry was stirred at
room temperature for 45 minutes, washed with 5% hydrochloric
acid, sodium carbonate, and water, dried over anhydrous magne-
sium sulphate, and evaporated to obtain the corresponding
3-chloro-2-azetidinone 14.
1-Benzyl-3-chloro-4-methylazetidin-2-one (14e).
1
This compound has the following properties: H nmr (deuterio-
chloroform): δ 1.22 (d, J = 6.4 Hz, 3H, CHCH ), 3.57-3.60 (m, 1H,
3
C H), 4.58 (d, J = 5.2 Hz, 1H, C H), 4.12 (d, J = 15.3 Hz, 1H,
4
3
CH C H ), 4.60 (d, J = 15.3 Hz, 1H, CH C H ), 7.38 (br s, 5H,
2
6
5
2 6 5
13
C H ); C nmr (deuteriochloroform): δ 14.79, 43.34, 59.18, 62.27,
6
5
-1
Using Thionyl Chloride.
127.43, 128.93, 129.58, 137.97, 170.10; IR (chloroform): 1748 cm .
Anal. Calcd. for C NOCI: C 63.00, H 5.72, N 6.68.
H
A sodium hydride suspension (0.1 mmole), washed three times
with cyclohexane, was added to tetrahydrofuran (1 ml) under
nitrogen to form slurry; sodium aziridine-2-carboxylate 13 (0.34
mmole) was added to the slurry followed by dropwise addition of
thionyl chloride (0.5 mmole). The resulting mixture was stirred at
room temperature for 1.25 hour. Solvent was removed by evapo-
ration and cyclohexane (2 ml) was added followed by careful
addition of water to destroy the sodium hydride present. The
organic layer was separated and washed with water, dried over
magnesium sulphate, and, evaporation of solvent afforded 3-
chloro-2-azetidinones 14.
11 12
Found: C 62.89, H 5.64, N 6.75.
1-Butyl-3-chloro-4-methylazetidin-2-one (14f).
1
This compound has the following properties: H nmr
(deuteriochloroform): δ 1.23 (d, J = 6.6 Hz, 3H, CHCH ), 1.62-
3
1.89 (m, 7H, CH CH CH ), 3.15 (t, 2H, CH (CH ) CH ), 3.55-
2
2
3
2
2 2
13
3
3.59 (m, 1H, C H), 4.55 (d, J = 5.2 Hz, 1H, C H); C nmr (deu-
4
3
teriochloroform): δ 13.78, 14.00, 20.35, 29.99, 53.06, 59.52,
60.73, 169.77; IR (chloroform): 1748 cm .
-1
Anal. Calcd. for C H NOCI: C 54.70, H 7.98, N 7.98. Found:
8
14
C 54.45, H 7.75, N 7.99.
1-Benzyl-3-chloroazetidin-2-one (14a).
3-Chloro-1-isobutyl-4-methylazetidin-2-one (14g).
1
This compound has the following properties: H nmr (deuteri-
1
This compound has the following properties: H nmr
ochloroform): δ 3.18 (dd, J = 2.1 Hz & 14.4 Hz, 1H, C H), 3.78
4
(deuteriochloroform): δ 1.19 (d, J = 6.6 Hz, 3H, CHCH ), 1.30
(dd, J = 5.1 Hz & 14.4 Hz, 1H, C H), 4.10 (d, J = 15.3 Hz, 1H,
3
4
(d, J = 6.0 Hz, 6H, CH(CH ) ), 1.53 (m, 1H, CH(CH ) ), 1.95 (d,
CH C H ), 4.59 (d, J = 15.3 Hz, 1H, CH C H ), 4.57 (dd, J = 2.1
3 2
3 2
2
6
5
2 6 5
13
2H, CH CH(CH ) ), 3.52-3.61 (m, 1H, C H), 4.60 (d, J = 5.4 Hz,
Hz & 5.1 Hz, 1H, C H), 7.25-7.38 (m, 5H, C H ); C nmr (deu-
2
3 2
4
3
6 5
13
1H, C H); C nmr (deuteriochloroform): δ 15.98, 20.29, 26.14,
55.63, 60.12, 62.01, 170.38; IR (chloroform): 1763 cm .
teriochloroform): δ 49.94, 56.65, 56.83, 127.46, 128.97, 129.98,
3
-1
-1
137.27, 169.76; IR (chloroform): 1766 cm .
Anal. Calcd. for C H NOCI: C 54.70, H 7.98, N 7.98. Found:
C 54.53, H 7.81, N 8.80.
Anal. Calcd. for C
Found: C 61.01, H 5.10, N 7.21.
H NOCl: C 61.38, H 5.11, N 7.16.
8
14
10 10
3-Chloro-4-methyl-1-phenethylazetidin-2-one (14h).
1-Butyl-3-chloroazetidin-2-one (14b.
1
1
This compound has the following properties: H nmr (deuteri-
This compound has the following properties: H nmr (deuterio-
ochloroform): δ 1.61-1.92 (m, 7H, CH CH CH ), 3.10 (t, 2H,
chloroform): δ 1.30 (d, J = 6.8 Hz, 3H, CHCH ), 2.78 (t, 2H,
2
2
3
3
NCH CH ), 3.20 (dd, J = 3.1 Hz &13.8 Hz, 1H, C H), 3.71 (dd,
CH CH C H ), 3.49 (t, 2H, CH CH C H ), 3.68 (m, 1H, C H),
2
2
4
2
2
6
5
2
2
6
5
4
13
J = 5.0 Hz & 13.8 Hz, 1H, C H), 4.49 (dd, J =3.1 Hz & 5.0 Hz,
4.79 (d, J = 4.5 Hz, 1H, C H), 7.01-7.23 (br, 5H, ArH); C nmr
4
3
13
1H, C H); C nmr (deuteriochloroform): δ 14.06, 20.36, 29.09,
47.20, 56.01, 56.99, 169.21; IR (chloroform): 1757 cm .
(deuteriochloroform): δ 14.23, 35.12, 47.95, 56.25, 60.05, 126.09,
3
-1
-1
128.75, 128.95, 140.89, 169.85; IR (chloroform): 1763 cm .

18
S. D. Sharma S. Kanwar and S. Rajpoot
Vol. 43
Anal. Calcd. for C
H
NOCl: C 64.43, H 6.26, N 6.26.
Anal. Calcd. for C H NOCI : C 50.23, H 3.26, N 6.51. Found:
9 7 2
12 14
C 49.99, H 3.16, N 6.61.
Found: C 64.17, H 6.01, N 6.35.
3-Chloro-4-(4-hydroxyphenyl)azetidin-2-one (14o).
1-Benzyl-3-chloro-4-phenylazetidin-2-one (14i).
1
1
This compound has the following properties: H nmr (deuteri-
This compound has the following properties: H nmr (deuterio-
ochloroform): δ 4.25 (d, J = 6.70 Hz, 1H, C H), 4.68 (d, J = 6.70
chloroform): δ 3.10 (d, J = 5.1 Hz, 1H, C H), 3.25 (d, J = 5.1 Hz,
3
4
13
Hz, 1H, C H), 6.91-7.51 (m, 4H, ArH); C nmr (deuteriochloro-
1H, C H), 3.95 (d, J = 15.1 Hz, 1H, CH C H ), 4.05 (d, J = 15.1 Hz,
4
3
2 6 5
13
form): δ 59.12m 65.26, 117.49, 125.49, 130.95, 158.02, 165.29;
1H, CH C H ), 7.35-7.48 (m, 5H, C H ), 7.58 (s, 5H, C H );
C
2
6
5
6
5
6 5
-1
IR (chloroform): 1776 cm .
nmr (deuteriochloroform): δ 43.79, 59.03, 70.39, 125.56, 127.69,
Anal. Calcd. for C H NO CI: C 54.68, H 4.05, N 7.09. Found:
128.00, 128.79, 130.09, 138.95, 139.05, 169.75; IR (chloroform):
9
8
2
-1
C 54.49, H 3.89, N 7.32.
1766 cm .
Anal. Calcd. for C
Found: C 70.53, H 5.00, N 5.30.
H NOCI: C 70.71, H 5.16, N 5.16.
16 14
4-Benzo[1,3]dioxol-5-yl-3-chloroazetidin-2-one (14p).
1
This compound has the following properties: H nmr (deuteri-
1-Butyl-3-chloro-4-phenylazetidin-2-one (14j).
ochloroform): δ 4.32 (d, J = 6.5 Hz, 1H, C H), 4.87 (d, J = 66.5
3
1
Hz, 1H, C H), 6.36 (s, 2H, OCH O), 6.95-7.31 (m, 3H, ArH);
This compound has the following properties: H nmr (deuteri-
4
2
13
C nmr (deuteriochloroform): δ 58.89, 63.59, 101.59, 104.59,
110.99, 119.35, 132.59, 148.29, 148.99, 165.50; IR (chloroform):
1777 cm .
ochloroform): δ 1.64-1.89 (m, 7H, CH CH CH ), 3.13 (d, J = 5.2
2
2
3
Hz, 1H, C H), 3.20 (t, 2H, NCH CH ), 3.35 (d, J = 5.2 Hz, 1H,
4
2
2
-1
13
C H), 7.23-7.58 (m, 5H, C H ); C nmr (deuteriochloroform): δ
3
6 5
Anal. Calcd. for C H NO CI: C 53.22, H 3.55, N 6.21.
14.52, 20.95, 29.65, 54.79, 59.48, 68.83, 124.89, 127.69, 128.59,
10
8
3
-1
Found: C 53.01, H 3.47, N 6.44.
138.32, 169.91; IR (chloroform): 1766 cm .
Anal. Calcd. for C
Found: C 65.52, H 6.51, N 5.90.
H NOCI: C 65.68, H 6.74, N 5.89.
13 16
3-Chloro-4-phenylazetidin-2-one (14q).
1
This compound has the following properties: H nmr (deuteri-
3-Chloro-1-isobutyl-4-phenylazetidin-2-one (14k).
ochloroform): δ 4.26 (d, J = 6.70 Hz, 1H, C H), 4.71 (d, J = 6.70
3
13
1
Hz, 1H, C H), 7.11 (s, 5H, ArH); C nmr (deuteriochloroform):
This compound has the following properties: H nmr (deuteri-
4
δ 59.12, 62.59, 126.56, 127.80, 128.59, 139.54, 165.69; IR (chlo-
ochloroform): δ 1.35 (d, J = 6.3 Hz, 6H, (CH ) ),1.48 (m, 1H,
3 2
-1
roform): 1777 cm .
CH(CH ) ), 1.89 (d, 2H, NCH CH(CH ) ), 3.20 (d, J = 5.3 Hz,
3 2
2
3 2
Anal. Calcd. for C H NOCI: C 59.50, H 4.40, N 7.71. Found:
C 59.46, H 4.35, N 7.68.
1H, C H), 3.39 (d, J = 5.3 Hz, 1H, C H), 6.89-7.23 (m, 5H, ArH);
9
8
4
3
13
C nmr (deuteriochloroform): δ 21.29, 26.59, 57.39, 59.68,
68.59, 124.98, 127.59, 127.99, 138.79, 170.05; IR (chloroform):
Acknowledgements.
-1
1774 cm .
Anal. Calcd. for C
Found: C 65.29, H 6.49, N 5.93.
H NOCI: C 65.68, H 6.74, N 5.89.
13 16
Authors are grateful to CSIR and UGC (New Delhi, India) for
financial assistance.
3-Chloro-1-phenethyl-4-phenylazetidin-2-one (14l).
REFERENCES AND NOTES
1
This compound has the following properties: H nmr (deuteri-
ochloroform): δ 2.81 (t, 2H, CH C H ), 3.53 (t, 2H, NCH ), 4.80
2
6
5
2
[1] J. B. Sweeney, Chem. Soc. Rev. 31, 347 (2002).
[2] W. McCoull, F. A. Davis, Synthesis, 1347 (2000).
[3] H. M. I. Osborn, J. Sweeney, Tetrahedron Asymmetry, 8, 1693
(1997).
[4] X. E. Hu, Tetraherdon, 60, 2701, (2004).
[5] V. H. Dahanukar, I. A. Zavialov, Current Opinion in Drug
Discovery and Development, 5, 918 (2002).
(d, J = 5.6 Hz, 1H, C H), 5.18 (d, J = 5.6 Hz, 1H, C H), 6.99-7.23
4
3
13
(m, 10H, ArH); C nmr (deuteriochloroform): δ 35.01, 46.99,
58.69, 69.79, 125.49, 126.09, 127.69, 128.17, 128.99, 140.99,
169.78; IR (chloroform): 1754 cm .
-1
Anal. Calcd. for C
H NOCl: C 71.45, H 5.60, N 4.90.
17 16
Found: C 71.19, H 5.43, N 5.12.
[6] M. J. Loosemore, R. F. Pratt, J. Org. Chem., 43, 3611 (1978).
[7] J. E. G. Kemp, M. D. Closier, S. Narayanaswami, M. H. stefa-
niak, Tetrahedron Lett., 21, 2991 (1980).
[8] R. A. Volkmann, R. D. Caroll, R. B. Droleu, M. L. Elliot, B. S.
Moore, J. Org. Chem. 47, 3344 (1982).
[9] J. A. Aimetti, E. S. Hamanaka, D. A. Johnson, M. S. Kellogg,
Tetrahedron Lett., 20, 4621 (1979).
[10] E. G. Mata, O. A. Mascaretti, Tetrahedron Lett., 30, 3905
(1989).
3-Chloro-4-(4-methoxyphenyl)azetidin-2-one (14m).
1
This compound has the following properties: H nmr (deuteri-
ochloroform): δ 3.79 (s, 3H, OCH ), 4.27 (d, J = 6.98 Hz, 1H,
3
C H), 4.73 (d, J = 6.98 Hz, 1H, C H), 6.86 (d, J = 9.08 Hz, 2H,
3
4
13
ArH), 7.51 (d, J = 9.08 Hz, 2H, ArH); C nmr (deuteriochloro-
form): δ 55.11, 59.12, 62.24, 114.59, 126.06, 131.59, 159.89,
165.58; IR (chloroform): 1775 cm .
-1
Anal. Calcd. for C
H NO CI: C 56.74, H 4.73, N 6.62.
10 10 2
[11] F. DiNinno, T. R. Beatti, B. G. Christensen, J. Org. Chem. 42,
2960 (1977).
Found: C 56.45, H 4.45, N 6.85.
[12] K. Araki, J. A. Wichtowski, J. T. Welch, Tetrahedron Lett., 32,
5461 (1991).
[13] D. A. Nelson, Tetrahedron Lett., 12, 2543 (1971).
[14] F. Duran, L. Ghosez, Tetrahedron Lett., 11, 245 (1970).
[15] A. K. Bose, M. S. Manhas, J. S. Chib, H. P. S. Chawla, B.
Dayal, J. Org. Chem., 39, 2877 (1974).
3-Chloro-4-(2-chlorophenyl)azetidin-2-one (14n).
1
This compound has the following properties: H nmr (deuteri-
ochloroform): δ 4.31 (d, J = 6.25 Hz, 1H, C H), 4.71 (d, J = 6.25
3
13
Hz, 1H, C H), 6.80-7.51 (m, 4H, ArH); C nmr (deuteriochloro-
4
form): δ 59.26, 60.39, 125.34, 126.49, 128.09, 128.99, 131.65,
-1
[16] I. Ojima, H. –J. C. Chen, X. Qui, Tetrahedron, 44, 5307
157.02, 165.59; IR (chloroform): 1776 cm .

Jan-Feb 2006
A General Strategy for the Stereospecific Synthesis of 2-Azetidinones
19
(1988).
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