On-column N-dearylation of 2-azetidinones by silica-supported ceric ammonium nitrate

Article abstract of DOI:10.1016/j.tet.2012.04.088

A modified traditional preparative chromatographic column can be used to achieve quantitative N-dearylation of N-(alkoxyphenyl), N-(alkoxynaphthyl), and N-(alkoxybenzyl)-2-azetidinones under mild conditions. Starting materials are charged on top of the co

Full text of DOI:10.1016/j.tet.2012.04.088

Tetrahedron 68 (2012) 5505e5512
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On-column N-dearylation of 2-azetidinones by silica-supported ceric ammonium
nitrate
,
b
b
b
Maaroof Zarei a, Aliasghar Jarrahpour b , Edris Ebrahimi , Malihe Aye , Seid Ali Torabi Badrabady
*
a Department of Chemistry, College of Sciences, Hormozgan University, Bandar Abbas 71961, Iran
b Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A modified traditional preparative chromatographic column can be used to achieve quantitative N-
dearylation of N-(alkoxyphenyl), N-(alkoxynaphthyl), and N-(alkoxybenzyl)-2-azetidinones under mild
conditions. Starting materials are charged on top of the column and the pure N-unsubstituted 2-
azetidinones leave the column minutes later without need for other purifications. The yields are good-
to-excellent and the reaction condition is mild, easy, efficient, and cheap.
Received 13 February 2012
Received in revised form 5 April 2012
Accepted 23 April 2012
Available online 30 April 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
On-column reaction
N-Dearylation
N-Unsubstituted 2-azetidinone
b
-Lactam
Ceric ammonium nitrate
Silica-supported
1. Introduction
synthetase inhibitor, tabtoxin.9 Application of N-unsubstituted 2-
azetidinones in the semi-synthesis of the anticancer agents Taxol
Ceric ammonium nitrate (CAN) is a one-electron oxidant with
advantages, such as low toxicity, ease of handling, and solubility in
a number of organic solvents.1 Ceric ammonium nitrate has proved
to be very useful to synthetic organic chemists for several decades.
The enormous growth in the use of this reagent is evidenced by the
publication of a large number of research papers and several re-
views concerning CAN-mediated reactions.1,2
and Taxotere has been also reported.10
Routes to N-unsubstituted 2-azetidinones involve the reaction
of N-trimethylsilyl imines with the corresponding compounds,11
reaction of chlorosulfonyl isocyanate with alkenes12 and N-
deprotection of N-functionalized
often used for N-protection of -lactams and can be deprotected
in different methods to give N-unsubstituted
-lactams.13 With
b-lactams. Several groups are
b
b
2-Azetidinones, commonly known as
b
-lactams, are heterocy-
few exceptions the yields are poor. Furthermore some methods
need expensive and unavailable materials. Toxic and non-safe
byproducts obtained in some cases together with difficulties of
the purification of main products are other problems of these
methods. Among these methods, oxidative cleavage by ceric
ammonium nitrate of p-alkoxyphenyl moiety attached to the ni-
clic compounds well known to organic and medicinal chemists.3
The activities of widely used antibiotics, such as penicillins, ceph-
alosporins, carbapenems, monobactams, and nocardicins are at-
tributed to the presence of 2-azetidinone ring.4 Ezetimibe is a new
drug, which has the 2-azetidinone skeleton and selectively inhibits
the absorption of cholesterol.5 Besides the antibacterial and cho-
trogen of the -lactam ring offers the most direct synthesis of N-
b
lesterol absorption inhibitory activities,
b
-lactams possess various
unsubstituted b
-lactams.14 This reaction commonly is performed
other biological activities.6
b-Lactams are not only useful in me-
in aqueous acetonitrile and involves oxidation of the aromatic
ring to benzoquinone with the release of 1 mol equiv of corre-
sponding alcohol and 1 mol equiv of the cyclic amide (Scheme 1).
The mechanism of this reaction has been reported by several
groups.14g,15
dicinal applications, but are also used as intermediates and synthon
for the production of several organic compounds.7 Several syn-
thetic methods have been developed for the preparation of the
lactam ring.8
b-
N-Unsubstituted 2-azetidinones offer major synthetic opportu-
nities in the synthesis of -lactam antibiotics and the glutamine
Alumina, silica, and clays are of the most widely employed
supports, where surface hydroxyl groups play a major role in these
reactions. Amongst them silica is widely used as a supporting
material since it presents desirable properties and silica gel plays an
important role in fine organic synthesis.14g,16
b
* Corresponding author. Tel.: þ98 711 228 4822; fax: þ98 711 228 0926; e-mail
addresses: jarrah@susc.ac.ir, aliasghar6683@yahoo.com (A. Jarrahpour).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.04.088

5506
M. Zarei et al. / Tetrahedron 68 (2012) 5505e5512
R2
R2
dichloromethane and the solvent was allowed to percolate down to
the surface of silica gel. Then the column was eluted with THF/H2O
(19:1).
R3
O
R3
O
O
O
CAN
+ R1OH
+
N
NH
After the addition of eluent the yellowish reaction zone turned
to red. The resulting solution was collected in fractions (10e15 mL)
and checked by TLC. At first p-benzoquinone eluted from the col-
umn and then, N-unsubstituted 2-azetidinones 2aei were isolated
in excellent yields with high purities. The yields were comparable
to those obtained in the solution phase reaction (Table 1).
Successful results obtained from type A on-column reaction and
removal of p-benzoquinone by Na2SO3 solution by the general
procedure, promoted us to create a type B on-column reaction. The
type B column was packed from the bottom: a little silica gel
(w1 cm), 10% SiO2eNa2SO3, 10% CANeSiO2, and a little silica gel
(Fig. 2).
OR1
Scheme 1. Deprotection of b-lactams with CAN.
Ceric ammonium nitrate on silica gel (CANeSiO2) has been used
for the removal of trityl and silyl groups,17 oxidation of oxygenated
aromatic compounds to quinones,18 regeneration of carbonyl
compounds from oximes, semicarbazones, phenylhydrazones,19
nitration of aromatics, and heteroaromatics,20 in the synthesis of
2,2-bis(N-methyl-30-indolyl)-N-methylindoxyl21 and oxidative
deprotection of benzylic tetrahydropyranyl ethers.22 High applica-
tions of ceric ammonium nitrate on silica gel (CANeSiO2) have
made it commercially available.23 In industry, reaction columns
have been used for large-scale synthesis for quite some time;
however, much of the technology is proprietary.24
In our recently reported letter,25 we described the use of
CANeSiO2 as an efficient reagent for N-dearylation of N-(p-
methoxyphenyl) and N-(p-ethoxyphenyl) groups on
b-lactams in
solutions and on column reactions. The versatility and efficiency of
the on column N-dearylation of several types of
demonstrated in this paper.
b-lactams is
2. Results and discussion
Ceric ammonium nitrate on silica gel was prepared as a yel-
lowish solid by a reported method.17 Based on earlier successful N-
Fig. 2. Type B column.
dearylations,25,26 we decided to carry out these
b-lactam N-dear-
b
-Lactams 1aei were charged onto the type B column and in the
N-dearylation zone, they were converted to N-unsubstituted
lactams 2aei and the benzoquinone byproduct was trapped in the
trapping zone (Na2SO3eSiO2). A clear and colorless solution was
eluted from the column, which contained only N-unsubstituted
ylation reactions on a CANeSiO2 column. Also purification of the
products was performed at the same time. The 10% CANeSiO2
column was chosen due to better filling height of the reaction zone.
Our type A column was filled with silica gel and was topped with
a band of 10% CANeSiO2, which conducted the reaction ‘on-col-
b
-
b-
lactam. The pure NH- -lactams 2aei were obtained in excellent
b
umn’, followed by ‘in situ’ purification of the products (Fig. 1). cis-b-
yields after removal of solvent under reduced pressure. A change of
color from yellow to red in the N-dearylation zone and from white
to dark-brown in the trapping zone was indicative of the depro-
tection and the trapping of benzoquinone, respectively.
Lactams 1aei were charged carefully onto the column in a little
On the basis of these successful results, the N-dearylation of
lactams 3aen with ‘on column type B’ was performed and N-
unsubstituted -lactams 4aen were obtained in good-to-excellent
yields without any further purification (Scheme 2, Table 2). -Lac-
b-
b
b
tams 3hen containing electron withdrawing substituents on po-
sition 3 also resulted in excellent yields. Especially N-dearylation of
3-chloro b-lactams 3hei using ‘on column type B’ showed better
results than AgO13q and CoF3.13p
Encouraged by above successful results, we next investigated
the oxidative N-dearylation of other types of N-alkoxyphenyl-b-
Fig. 1. Type A column.
Table 1
Solution phase and ‘on-column’ synthesis of deprotected cis-
b-lactams 2aei
Substrate
R1
R2
R3
Product
Isolated yield (%) by 10% CANeSiO2
Isolated yield
(%) by CAN
CH3CN/H2O
CH2Cl2/H2O
On column A
On column B
1a
1b
1c
1d
1e
1f
1g
1h
1i
Me
Me
Me
Et
Et
Et
Et
Et
Et
3,4-DiMeOC6H3
2,3-DiMeOC6H3
3,4-DiMeOC6H3
CH]CHPh
4-MeOC6H4
CH]CHPh
4-NO2C6H4
4-NO2C6H4
4-MeC6H4
PhO
PhO
3-NO2PhthN
PhthN
PhO
PhO
2-NaphthO
2,4-DiClC6H3O
MeO
2a
2b
2c
2d
2e
2f
2g
2h
2i
94
86
88
91
85
93
82
91
84
81
73
68
74
74
79
71
80
75
91
83
90
87
85
91
88
90
86
94
88
87
93
89
90
92
94
87
83
77
79
71
85
78
80
74
85

M. Zarei et al. / Tetrahedron 68 (2012) 5505e5512
5507
R2
R3
O
R2
NH
O
R3
O
O
on column
type B
on column
type A
MeO
O
MeO
O
OMe
N
O
N
N
OR1
4a-n
3a-n
MeO
O
Scheme 2. N-Dearylation of b-lactams 3aen with ‘on column type B’.
9
8
Scheme 4. Reaction of b-lactam 8 with ‘on column type A’.
Table 2
N-Dearylation of
b
-lactams 3aen with ‘on column type B’
R3
Stereochemistry Products Isolated
It is noteworthy that Alcaide and co-workers have synthesized
-lactams bearing a quinone moiety at N1, C3 or C4 positions from
Substrate R1 R2
b
yield (%)
2,5-dimethoxyphenyl substituted
b-lactams using ceric ammo-
nium nitrate (CAN) in aqueous acetonitrile.27
3a
3b
3c
3d
Me 3-NO2C6H4 2,4-DiClC6H3O Cis
Et 4-ClC6H4 2,4-DiClC6H3O Cis
Et 4-NO2C6H4 MeO
4a
4b
4c
4d
80
86
88
81
It is reasonable to assume that 4-methoxynaphthyl group re-
sembles the 4-methoxyphenyl group. Therefore 2-azetidinones
10aec containing the 4-methoxynaphthyl group on N1-position
were prepared using [2þ2] keteneeimine cycloaddition. When 2-
azetidinones 10aec were treated with ‘on column type B’, only
the corresponding NH-2-azetidinones were obtained from the
column. But treatment of 2-azetidinones 10aec with ‘on column
type A’ resulted in both the corresponding NH-2-azetidinones and
naphthoquinone (compared with authentic sample) (Scheme 5).
The resulted naphthoquinone was trapped in the trapping zone
(Na2SO3eSiO2) of ‘on column type B’. The 4-methoxynaphthyl
group was oxidized better than the p-methoxyphenyl group
(compare R¼MeO in Scheme 3 and compound 1i in Table 1).
Cis
Cis
Me 4-NO2C6H4 4-ClC6H4O
3e
3f
Me 4-MeOC6H4
Et 4-NO2C6H4
Trans
Trans
4e
4f
78
80
O
3g
Me 4-ClC6H4
Trans
4g
74
N
O
3h
3i
Me 4-MeOC6H4 Cl
Me C6H5
Cis
Cis
Cis
Cis
Cis
Cis
Cis
4h
4i
4j
4k
4l
4m
4n
82
84
85
79
81
80
77
Cl
Cl
3j
Et 4-ClC6H4
3k
3l
3m
3n
Et 4-MeC6H4 N3
Me 4-ClC6H4 N3
Me 4-MeOC6H4 MeSO2
Me 4-ClC6H4 MeSO2
Me
Me
O
on column
type B
R
O
R
O
lactams. Treatment of N-(2,4-dimethoxyphenyl)-
and N-(3,4-dimethoxyphenyl)- -lactams 6aee with ‘on column
type B’ afforded the pure corresponding NH- -lactams in excellent
yields (Scheme 3, Table 3). The mechanism is similar to 4-
(methoxyphenyl)- -lactams and the resulted benzoquinone de-
rivatives were trapped in the trapping zone (Na2SO3eSiO2).
b-lactams 5aee
+
N
NH
b
b
O
OMe
11a, R = PhO 89%
2i, R = MeO 91%
11b, R = PhthN 86%
Naphthoquinone
b
10a-c
R2
R3
O
R2
NH
R3
O
on column
type B
Scheme 5. Removal of 4-methoxynaphthyl group from N1-position of
‘on column type B’.
b-lactams by
N
R1
5a-e
6a-e
products
Treatment of Schiff bases derived from anthracene-9-
carbaldehyde or 9H-fluoren-9-one with 9H-xanthene-9-
carboxylic acid in the presence of triethylamine and tosyl chlo-
Scheme 3. N-Dearylation of b-lactams 5aee and 6aee with ‘on column type B’.
ride afforded polycyclic aromatic spiro-
dispiro-
-lactams 13a,b,29 respectively.
The crystal structure of
-lactam 12a30a (Fig. 3) and 12b30b have
been reported previously. Using the ‘on column type B’, spiro-
lactams 12aec and dispiro- -lactams 13a,b were converted into the
-lactams 14 and 15, in good-to-excellent yields
b
-lactams 12aec28 and
b
Treatment of N-(2,5-dimethoxyphenyl)-
column type A’ produced -lactam 9 bearing a quinone moiety at
N1-position and no NH-2-azetidinones were found (Scheme 4). ‘On
column type B’ is not useful for -lactams like 8 because the
b-lactam 8 with ‘on
b
b
b
-
b
b
corresponding NH-
b
products will be trapped in the trapping zone (Na2SO3eSiO2).
(Scheme 6).
Table 3
N-Dearylation of
b-lactams 5aee and 6aee with ‘on column type B’
Substrate
R1
R2
R3
Stereochemistry
Product
Isolated yield (%)
5a
5b
5c
5d
5e
6a
6b
6c
6d
6e
2,4-DiMeOC6H3
2,4-DiMeOC6H3
2,4-DiMeOC6H3
2,4-DiMeOC6H3
2,4-DiMeOC6H3
3,4-DiMeOC6H3
3,4-DiMeOC6H3
3,4-DiMeOC6H3
3,4-DiMeOC6H3
3,4-DiMeOC6H3
3,4-DiMeOC6H3
2-NO2C6H4
3-MeOC6H4
3-NO2C6H4
3-MeOC6H4
4-NO2C6H4
4-MeOC6H4
3,4-DiMeOC6H3
4-NO2C6H4
PhO
PhO
PhO
PhthN
PhthN
PhO
PhO
PhO
Cis
Cis
Cis
Trans
Trans
Cis
Cis
Cis
2a
7a
7b
7c
7d
7e
2e
2a
7f
84
78
81
80
83
85
80
84
78
82
PhthN
PhthN
Trans
Trans
4-MeOC6H4
7g

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M. Zarei et al. / Tetrahedron 68 (2012) 5505e5512
Bisulfite addition products are formed from aldehydes upon
treatment with sodium bisulfite. The reaction is reversible (by
treatment of the addition product with either acid or base) and is
useful for the purification of the starting compounds.32 Treatment
of
b
-lactams 16aed with ‘on column type B’ afforded a mixture of
2-azetidinones 17aed and p-methox-
N-unsubstituted
ybenzaldehyde. The pure N-unsubstituted 2-azetidinones 17aed
were obtained after evaporation of solvents and crystallization
from Et2O. The acidic property of silica gel is the cause of re-
versibility of bisulfite addition reaction. The above facts encouraged
us to create ‘on column type C’ for the N-dearylation of N-(p-
methoxybenzyl)-b-lactams 16aed without need to further purifi-
cation. ‘On column type C’ was packed like ‘on column type B’, but
the trapping zone is NaHSO3 supported on neutral alumina (NaH-
SO3eAl2O3) for the trapping of p-methoxybenzaldehyde (Fig. 4).
The pure NH-b-lactams 17aed were obtained from N-(p-methox-
ybenzyl)- -lactams 16aed in excellent yields using ‘on column
b
type C’ after removal of solvent under reduced pressure (Table 4).
All products were characterized by spectral data and elemental
analyses.
Fig. 3. ORTEP diagram of
b-lactam 12a.
Fig. 4. Type C column.
O
O
on column
type B
O
on column
type B
O
N
N
N
NH
O
R
O
O
O
R
H
15
14
84%
13a, R = 4-MeOC6H4
13b, R = 4-EtOC6H4
88%
12a, R = 4-MeOC6H4
89%
79%
82%
12b, R = 2,4-diMeOC6H3
12c, R = 3,4-diMeOC6H3
Scheme 6. N-Dearylation of spiro-
b
-lactams 12aec and dispiro-
b
-lactams 13a,b using the ‘on column type B’.
This method was also extended to the N-dearylation of N-(p-
methoxybenzyl)- -lactams. N-Dearylation of N-(p-methox-
ybenzyl)- -lactams using ceric ammonium nitrate in aqueous
acetonitrile has been reported.31 p-Methoxybenzaldehyde is the
byproduct of this reaction (Scheme 7). -Lactams 16aed were
synthesized by the [2þ2] keteneeimine cycloaddition reaction and
then charged to ‘on column type A’. First p-methoxybenzaldehyde
was eluted from the column and then N-unsubstituted 2-
azetidinones 17aed were eluted with THF/H2O (19:1).
Table 4
b
On-column N-dearylation of N-(p-methoxybenzyl)-b-lactams 16aed
b
Substrate R1
R2
Product Isolated yield (%) by 10% CAN-SiO2
On column On column On column
b
A
B
C
16a
16b
16c
16d
4-NO2C6H4 PhO
4-NO2C6H4 PhthN
4-ClC6H4 MeO
17a
17b
17c
77
80
78
85
69
78
71
76
75
84
80
88
4-ClC6H4 2-NaphthO 17d
R1
R2
R1
R2
CAN
+
CHO
MeO
OMe
3. Conclusion
N
NH
O
O
In summary, silica-supported ceric ammonium nitrate
(CANeSiO2) serves as a convenient and effective reagent for on
column N-dearylation of b-lactams. ‘On column type A’ provides N-
16a-d
17a-d
Scheme 7. N-Dearylation of N-(p-methoxybenzyl)-b-lactams 16aed.

M. Zarei et al. / Tetrahedron 68 (2012) 5505e5512
5509
dearylation and subsequent in situ separation to give NH-
b-lac-
C15H10Cl2N2O4: C, 51.01; H, 2.85; N, 7.93. Found: C, 51.10; H, 2.94; N,
tams. In addition, ‘on column type B’ and ‘on column type C’ con-
7.86.
taining the trapping zone for the removal of byproducts provide
easy and efficient methods for obtaining pure NH-
good-to-excellent yields.
b
-lactams in
4.2.2. cis-3-(4-Chlorophenoxy)-4-(4-nitrophenyl)azetidin-2-one
(4d). Light-yellow solid (0.26 g, 81%). Mp: 149e151 ꢁC. Rf¼0.34 (3:7
hexane/EtOAc); IR (KBr) cmꢂ1: 1338, 1529 (NO2), 1770 (CO,
b
-lac-
5.29 (H-3, d, 1H,
J¼5.0), 5.69 (H-4, dd, 1H, J¼5.0, 2.6), 7.05e8.11 (ArH, m, 8H), 9.10
(NH, br s, 1H); 13C NMR (62.9 MHz, DMSO-d6)
56.2 (C-4), 82.6 (C-
3), 116.3, 125.5, 127.3, 130.0, 134.9, 141.1, 145.8, 159.5 (aromatic
carbons), 161.3 (CO, -lactam); Anal. Calcd for C15H11ClN2O4: C,
56.53; H, 3.48; N, 8.79. Found: C, 56.61; H, 3.60; N, 8.84.
tam), 3375 (NH); 1H NMR (250 MHz, DMSO-d6)
d
4. Experimental section
4.1. Chemical reagents
d
b
All needed chemicals were purchased from Merck, Fluka, and
Acros chemical companies. IR spectra were run on a Shimadzu FT-IR
8300 spectrophotometer or galaxy series FT-IR 5000 spectrometer.
1H NMR and 13C NMR spectra were recorded in DMSO-d6 and CDCl3
using a Bruker Avance DPX instrument (1H NMR 250 MHz, 13C NMR
62.9 MHz) or Bruker spectrophotometer (1H NMR 300 MHz, 13C
NMR 75 MHz). Chemical shifts were reported in parts per million
4.2.3. trans-4-(4-Nitrophenyl)-3-vinylazetidin-2-one
(4f). White
solid (0.17 g, 80%). Mp: 56e58 ꢁC. Rf¼0.45 (3:7 hexane/EtOAc); IR
(KBr) cmꢂ1: 1346, 1518 (NO2), 1761 (CO, -lactam), 3370 (NH); 1H
b
NMR (300 MHz, DMSO-d6)
d
3.75 (H-3, dd, 1H, J¼7.7, 2.4), 4.80 (H-4,
dd, 1H, J¼3.1, 2.4), 5.18e5.30 (vinilic H, m, 2H), 5.88e6.00 (vinilic H,
(d) downfield from TMS. All of the coupling constants (J) are in
m, 1H), 6.75e8.07 (ArH, m, 4H), 9.14 (NH, br s, 1H); 13C NMR
Hertz. Elemental analyses were run on a Thermo Finnigan Flash EA-
1112 series or on a Vario EL III elemental analyzer. Melting points
were determined in open capillaries with Buchi 510 melting point
apparatus. Thin-layer chromatography was carried out on silica gel
254 analytical sheets obtained from Fluka. Column chromatogra-
phy was performed on Merck Kiesel gel (230e270 mesh). [2þ2]
(75 MHz, DMSO-d6)
141.8, 159.2 (C]C, aromatic carbons), 162.4 (CO,
Calcd for C11H10N2O3: C, 60.55; H, 4.62; N, 12.84. Found: C, 60.47; H,
4.72; N, 12.76.
d
66.1 (C-3), 67.9 (C-4), 114.6, 117.5, 127.0, 139.3,
-lactam); Anal.
b
4.2.4. cis-3-Chloro-4-(4-chlorophenyl)azetidin-2-one
(4j). White
Keteneeimine cycloaddition was chosen for preparation of
b-lac-
solid (0.18 g, 85%). Mp: 78e80 ꢁC. Rf¼0.48 (4:6 hexane/EtOAc); IR
tams and spectral data for 1aei, 3aen, 12aec, and 13a,b have been
previously reported.28,29,33 Spectral data for the NH-2-azetidinones
2aei, 4b,c, 4e,gei, 7eeg, 11a, 17a,b, and 17d have been previously
reported.13e,p,q,14eeh,25
(KBr) cmꢂ1: 1761 (CO, -lactam), 3436 (NH); 1H NMR (300 MHz,
b
DMSO-d6)
6.84e7.35 (ArH, m, 4H), 9.13 (NH, br s, 1H); 13C NMR (75 MHz,
DMSO-d6) 60.9 (C-4), 67.1 (C-3), 112.7, 122.0, 130.3, 152.8 (aro-
matic carbons), 163.5 (CO, -lactam); Anal. Calcd for C9H7Cl2NO: C,
d
4.60 (H-4, dd, 1H, J¼4.8, 2.3), 5.08 (H-3, d, 1H, J¼4.8),
d
b
50.03; H, 3.27; N, 6.48. Found: C, 50.14; H, 3.42; N, 6.55.
4.2. General procedure for on-column N-dearylation
reactions
4.2.5. cis-3-Azido-4-p-tolylazetidin-2-one (4k). Pale-yellow solid
(0.16 g, 79%). Mp: 97e99 ꢁC. Rf¼0.44 (3:7 hexane/EtOAc); IR (KBr)
(a) ‘On column type A’. A 48ꢀ2 cm2 glass column was packed
with silica gel (4.5 g, w 4.0 cm) and was topped up with 10%
CANeSiO2 (12.0 g, w11.5 cm). Then 2-azetidinone (1.0 mmol) in
a little dichloromethane was charged onto the column and was
allowed to stand at room temperature for 10e15 min. The column
was then eluted with 19:1 THFewater to afford firstly p-benzo-
cmꢂ1: 2129 (N3), 1762 (CO, -lactam), 3414 (NH); 1H NMR
b
(300 MHz, DMSO-d6)
2.8), 5.47 (H-3, d, 1H, J¼5.0), 6.93e7.41 (ArH, m, 4H), 9.03 (NH, br s,
1H); 13C NMR (75 MHz, DMSO-d6)
24.6 (Me), 61.8 (C-3), 67.5 (C-4),
120.5, 128.3, 140.9, 146.2 (aromatic carbons), 164.4 (CO, -lactam).
d
2.30 (Me, s, 3H), 4.96 (H-4, dd, 1H, J¼5.0,
d
b
Anal. Calcd for C10H10N4O: C, 59.40; H, 4.98; N, 27.71. Found: C,
59.47; H, 5.09; N, 27.63.
quinone followed by pure N-unsubstituted b-lactam.
(b) ‘On column type B’. A 48ꢀ2 cm2 glass column was packed
from the bottom: a little silica gel (w1 cm), 10% Na2SO3eSiO2 (6.0 g,
w4.5 cm), 10% CANeSiO2 (12.0 g, w11.5 cm), and a little of silica gel
4.2.6. cis-3-Azido-4-(4-chlorophenyl)azetidin-2-one (4l). Pale-yel-
low solid (0.18 g, 81%). Mp: 86e88 ꢁC. Rf¼0.42 (3:7 hexane/EtOAc);
on top.
b
-Lactam (1.0 mmol) in dichloromethane (1.0e1.5 mL) was
IR (KBr) cmꢂ1: 2118 (N3), 1758 (CO, -lactam), 3402 (NH); 1H NMR
b
then charged onto the column. After 15 min the column was eluted
(300 MHz, DMSO-d6)
d
4.84 (H-4, dd, 1H, J¼4.7, 3.1), 5.39 (H-3, d,
with 19:1 THFewater to afford pure N-unsubstituted
p-benzoquinone was trapped in the column.
b
-lactam and
1H, J¼4.7), 6.90e7.37 (ArH, m, 4H), 8.94 (NH, br s, 1H); 13C NMR
(75 MHz, DMSO-d6) d 63.6 (C-3), 66.2 (C-4),122.4, 127.0,138.6,147.4
(aromatic carbons), 162.5 (CO, b-lactam). Anal. Calcd for
C9H7ClN4O: C, 48.55; H, 3.17; N, 25.17. Found: C, 48.51; H, 3.26; N,
25.12.
(c) ‘On column type C’. A 48ꢀ2 cm2 glass column was packed
from the bottom: a little silica gel (w1 cm), 10% NaHSO3eneutral
Al2O3 (7.5 g, w5.5 cm), 10% CANeSiO2 (12.0 g, w11.5 cm), and a lit-
tle of silica gel on top. b-Lactam (1.0 mmol) in dichloromethane
(1.0e1.5 mL) was then charged onto the column. After 15 min the
column was eluted with 19:1 THFewater to afford pure N-unsub-
4.2.7. cis-4-(4-Methoxyphenyl)-3-(methylsulfonyl)azetidin-2-one
(4m). White solid (0.20 g, 80%). Mp: 103e105 ꢁC. Rf¼0.39 (2:8
stituted
column.
b
-lactam and p-methoxybenzaldehyde was trapped in the
hexane/EtOAc); IR (KBr) cmꢂ1: 1154, 1322 (SO2), 1768 (CO,
b
-lac-
tam), 3357 (NH); 1H NMR (300 MHz, DMSO-d6)
d 3.21 (SO2eMe, s,
3H), 3.58 (OMe, s, 3H), 4.40 (H-4, dd,1H, J¼4.5, 2.8), 5.38 (H-3, d,1H,
4.2.1. cis-3-(2,4-Dichlorophenoxy)-4-(3-nitrophenyl)azetidin-2-one
J¼4.5), 6.88e7.55 (ArH, m, 4H), 9.05 (NH, br s, 1H); 13C NMR
(4a). Light-yellow solid (0.28 g, 80%). Mp: 156e158 ꢁC. Rf¼0.38 (3:7
(75 MHz, DMSO-d6) d 35.1 (SO2eMe), 55.9 (OMe), 65.1 (C-4), 81.7
(C-3), 113.4, 126.4, 137.9, 155.7 (aromatic carbons), 161.6 (CO, b-
lactam). Anal. Calcd for C11H13NO4S: C, 51.75; H, 5.13; N, 5.49.
Found: C, 51.87; H, 5.31; N, 5.56.
hexane/EtOAc); IR (KBr) cmꢂ1: 1344, 1515 (NO2), 1773 (CO,
b
-lac-
5.48 (H-3, d, 1H,
J¼4.7), 5.69 (H-4, dd, 1H, J¼4.7, 2.8), 7.19e8.09 (ArH, m, 7H), 9.04
(NH, br s, 1H); 13C NMR (62.9 MHz, DMSO-d6)
58.3 (C-4), 80.7 (C-
3), 118.1, 120.3, 122.8, 126.0, 128.1, 129.0, 132.8, 133.5, 135.9, 143.7,
147.1, 158.3 (aromatic carbons), 163.8 (CO, -lactam); Anal. Calcd for
tam), 3388 (NH); 1H NMR (250 MHz, DMSO-d6)
d
d
4.2.8. cis-4-(4-Chlorophenyl)-3-(methylsulfonyl)azetidin-2-one
(4n). White solid (0.20 g, 77%). Mp: 109e111 ꢁC. Rf¼0.38 (2:8
b

5510
M. Zarei et al. / Tetrahedron 68 (2012) 5505e5512
hexane/EtOAc); IR (KBr) cmꢂ1: 1149, 1330 (SO2), 1764 (CO,
tam), 3344 (NH); 1H NMR (300 MHz, DMSO-d6)
3.29 (SO2eMe, s,
3H), 4.35 (H-4, dd, 1H, J¼4.7, 2.5), 5.28 (H-3, d, 1H, J¼4.7), 6.93e7.36
(ArH, m, 4H), 9.11 (NH, br s,1H); 13C NMR (75 MHz, DMSO-d6)
34.0
(SO2-Me), 66.6 (C-4), 80.9 (C-3), 116.1, 127.7, 141.3, 153.9 (aromatic
carbons), 162.8 (CO, -lactam). Anal. Calcd for C10H10ClNO3S: C,
b
-lac-
NMR (300 MHz, CDCl3)
(H-4, d,1H, J¼4.8), 5.57 (H-3, d,1H, J¼4.8), 6.75e8.03 (ArH, m,15H);
13C NMR (75 MHz, CDCl3)
22.5 (Me), 55.6 (OMe), 61.4 (C-4), 83.3
(C-3), 107.4, 109.7, 111.0, 112.8, 113.3, 115.9, 117.4, 118.5, 119.1, 122.4,
130.8, 131.5, 132.2, 137.9, 147.4, 150.8, 152.7, 157.5 (aromatic car-
d 2.44 (Me, s, 3H), 3.62 (OMe, s, 3H), 5.27
d
d
d
b
bons), 163.4 (CO, b-lactam); Anal. Calcd for C27H23NO3: C, 79.20; H,
46.25; H, 3.88; N, 5.39. Found: C, 46.38; H, 4.02; N, 5.31.
5.66; N, 3.42. Found: C, 79.31; H, 5.80; N, 3.49.
4.2.9. cis-(2,4-Dimethoxyphenyl)-4-(3,4-dimethoxyphenyl)-3-
phenoxyazetidin-2-one (5a). White solid (0.40 g, 91%). Mp:
116e118 ꢁC. Rf¼0.51 (7:3 hexane/EtOAc); IR (KBr) cmꢂ1: 1758 (CO,
4.2.15. cis-3-Methoxy-1-(4-methoxynaphthalen-1-yl)-4-p-tolyl-aze-
tidin-2-one (10b). White solid (0.29 g, 84%). Mp: 135e137 ꢁC.
Rf¼0.48 (7:3 hexane/EtOAc); IR (KBr) cmꢂ1: 1745 (CO,
b
-lactam); 1H
b
-lactam); 1H NMR (250 MHz, CDCl3)
d
3.64e3.70 (4OMe, 4s, 12H),
NMR (300 MHz, CDCl3) d 2.48 (Me, s, 3H), 3.29, 3.62 (2OMe, s, 6H),
5.51 (H-3, 4s, 2H, J¼4.4), 6.30e7.59 (ArH, m, 11H); 13C NMR
4.84 (H-4, d, 1H, J¼4.5), 5.26 (H-3, d, 1H, J¼4.6), 6.72e7.85 (ArH, m,
(62.9 MHz, CDCl3)
d
55.48, 55.55, 55.68, 55.86 (4OMe), 64.94 (C-4),
10H); 13C NMR (75 MHz, CDCl3)
d
23.7 (Me), 56.3, 57.1 (OMe), 63.7
82.01 (C-3), 99.64, 104.46, 110.44, 111.22, 115.51, 117.75, 121.19,
121.88,125.30,126.44,128.78,129.20,130.89,148.47,148.90, 153.00,
(C-4), 82.8 (C-3), 108.8, 110.6, 112.3, 112.8, 118.0, 119.1, 123.9, 124.5,
131.9, 133.4, 136.2, 143.9, 151.6, 154.6 (aromatic carbons), 162.1 (CO,
157.02, 158.89 (aromatic carbons), 164.58 (CO,
b-lactam); Anal.
b-lactam); Anal. Calcd for C22H21NO3: C, 76.06; H, 6.09; N, 4.03.
Calcd for C25H25NO6: C, 68.95; H, 5.79; N, 3.22. Found: C, 68.47; H,
5.93; N, 3.73.
Found: C, 76.14; H, 6.17; N, 3.95.
4.2.16. cis-2-(1-(4-Methoxynaphthalen-1-yl)-2-oxo-4-p-tolylazeti-
din-3-yl)-isoindoline-1,3-dione (10c). White solid (0.40 g, 87%). Mp:
201e203 ꢁC. Rf¼0.43 (7:3 hexane/EtOAc); IR (KBr) cmꢂ1: 1738, 1776
4.2.10. cis-4-(2-Nitrophenyl)-3-phenoxyazetidin-2-one (7a). Light-
yellow solid (0.22 g, 78%). Mp: 127e129 ꢁC. Rf¼0.40 (3:7 hexane/
EtOAc); IR (KBr) cmꢂ1: 1355, 1532 (NO2), 1771 (CO), 3240 (NH); 1H
(CO, phth), 1781 (CO, b d 2.44
-lactam); 1H NMR (300 MHz, CDCl3)
NMR (250 MHz, DMSO-d6)
d
5.12 (H-3, d, 1H, J¼5.1), 5.40 (H-4, dd,
(Me, s, 3H), 3.58 (OMe, s, 3H), 5.26 (H-4, d, 1H, J¼4.7), 5.39 (H-3, d,
1H, J¼5.1, 2.6), 6.81e8.06 (ArH, m, 9H), 9.10 (NH, br s, 1H); 13C NMR
1H, J¼4.7), 6.77e7.94 (ArH, m, 14H); 13C NMR (75 MHz, CDCl3)
(62.9 MHz, DMSO-d6)
d
55.2 (C-4), 84.6 (C-3), 114.6, 119.1, 122.8,
d 24.2 (Me), 56.7 (OMe), 61.2 (C-4), 64.2 (C-3), 106.4, 109.2, 111.4,
125.9, 127.3, 137.0, 139.4, 142.6, 146.3, 159.5 (aromatic carbons),
161.6 (CO, -lactam); Anal. Calcd for C15H12N2O4: C, 63.38; H, 4.25;
113.1, 113.6,113.9, 120.3, 122.4, 122.9, 123.5, 124.1, 127.9, 132.3, 134.6,
139.7, 140.3, 149.4, 153.7 (aromatic carbons), 160.9 (CO, phth), 163.5
b
N, 9.85. Found: C, 63.30; H, 4.31; N, 9.79.
(CO, b-lactam); Anal. Calcd for C29H22N2O4: C, 75.31; H, 4.79; N,
6.06. Found: C, 75.40; H, 4.93; N, 6.13.
4.2.11. cis-4-(3-Methoxyphenyl)-3-phenoxyazetidin-2-one
(7b).
White solid (0.22 g, 81%). Mp: 137e139 ꢁC. Rf¼0.47 (4:6 hexane/
4.2.17. cis-2-(2-Oxo-4-p-tolylazetidin-3-yl)isoindoline-1,3-dione
EtOAc); IR (KBr) cmꢂ1: 1771 (CO), 3414 (NH); 1H NMR (250 MHz,
(11b). White solid (0.26 g, 86%). Mp: 193e195 ꢁC. Rf¼0.44 (2:8
DMSO-d6)
d
3.46 (MeO, s, 3H), 5.00 (H-3, d,1H, J¼4.3), 5.38 (H-4, dd,
hexane/EtOAc); IR (KBr) cmꢂ1: 1736, 1772 (CO, phth), 1781 (CO,
b-
1H, J¼4.3, 1.7), 6.82e7.24 (ArH, m, 9H), 9.05 (NH, br s, 1H); 13C NMR
lactam), 3486 (NH); 1H NMR (300 MHz, DMSO-d6)
d 2.32 (Me, s,
(62.9 MHz, DMSO-d6)
110.5, 113.8, 126.3, 127.5, 133.8, 135.0, 139.3, 144.1, 158.1 (aromatic
carbons), 161.6 (CO, -lactam); Anal. Calcd for C16H15NO3: C, 71.36;
d
55.3 (OMe), 56.6 (C-4), 82.1 (C-3), 107.3,
3H), 4.86 (H-4, dd, 1H, J¼3.3, 4.9), 5.13 (H-3, d, 1H, J¼4.9), 7.17e8.01
(ArH, m, 8H), 9.09 (NH, br s, 1H); 13C NMR (75 MHz, DMSO-d6)
b
d
22.0 (Me), 56.2 (C-4), 61.7 (C-3), 120.1, 125.6, 126.2, 129.8, 137.2,
H, 5.61; N, 5.20. Found: C, 71.44; H, 5.73; N, 5.14.
139.5, 147.4 (aromatic carbons), 163.7 (CO, phth), 165.2 (CO, -lac-
b
tam); Anal. Calcd for C18H14N2O3: C, 70.58; H, 4.61; N, 9.15. Found:
C, 70.48; H, 4.73; N, 9.24.
4.2.12. trans-2-(2-(3-Nitrophenyl)-4-oxoazetidin-3-yl)isoindoline-
1,3-dione (7c). Light-yellow solid (0.27 g, 80%). Mp: 188e190 ꢁC.
Rf¼0.35 (2:8 hexane/EtOAc); IR (CHCl3) cmꢂ1: 1353, 1547 (NO2),
4.2.18. 2-(Anthracen-9-yl)spiro[azetidine-3,90-xanthen]-4-one (14).
Light-yellow solid (0.36 g, 88%). Mp: 211e213 ꢁC. Rf¼0.47 (5:5
1739, 1771 (CO, phth), 1783 (CO, b
-lactam), 3367 (NH); 1H NMR
(250 MHz, DMSO-d6)
d
4.81 (H-3, d, 1H, J¼2.3), 5.62 (H-4, dd, 1H,
hexane/EtOAc); IR (KBr) cmꢂ1: 1769 (CO, -lactam), 3447 (NH); 1H
b
J¼2.3, 1.5), 7.02e8.00 (ArH, m, 8H), 9.04 (NH, br s, 1H); 13C NMR
NMR (300 MHz, DMSO-d6)
(ArH, m, 17H), 9.17 (NH, br s, 1H); 13C NMR (75 MHz, DMSO-d6)
68.4 (C-4), 84.7 (C-3), 114.9, 116.1, 121.2, 123.5, 124.2, 128.9, 129.3,
131.7,132.0,137.7,139.3,141.2,145.9,155.6 (aromatic carbons),166.1
(CO, -lactam); Anal. Calcd for C29H19NO2: C, 84.24; H, 4.63; N, 3.39.
d
6.11 (H-4, d, 1H, J¼3.8), 6.73e8.29
(62.9 MHz, DMSO-d6)
d 56.7 (C-4), 63.8 (C-3), 117.1, 119.5, 125.3,
128.1, 130.6, 132.3, 141.4, 145.9, 150.4 (aromatic carbons), 161.5 (CO,
phth), 165.8 (CO, -lactam); Anal. Calcd for C17H11N3O5: C, 60.54; H,
d
b
3.29; N, 12.46. Found: C, 60.46; H, 3.39; N, 12.41.
b
Found: C, 84.32; H, 4.79; N, 3.44.
4.2.13. trans-2-(2-(3-Methoxyphenyl)-4-oxoazetidin-3-yl)isoindo-
line-1,3-dione (7d). White crystalline solid (0.27 g, 83%). Mp:
171e173 ꢁC. Rf¼0.42 (2:8 hexane/EtOAc); IR (CHCl3) cmꢂ1: 1731,
4.2.19. Dispiro[azetidine((2,90-fluoren)(3,90-xanthen))]-4-one (15).
Light-yellow solid (0.34 g, 89%). Mp >235 ꢁC. Rf¼0.45 (5:5 hexane/
1772 (CO, phth), 1784 (CO,
(250 MHz, DMSO-d6)
5.14 (H-4, dd, 1H, J¼2.4, 1.8), 7.16e8.19 (ArH, m, 8H), 9.06 (NH, br s,
1H); 13C NMR (62.9 MHz, DMSO-d6)
56.4 (OMe), 57.9 (C-4), 63.5
(C-3), 109.8, 115.3, 123.8, 128.5, 133.1, 137.7, 142.9, 144.0, 157.3 (ar-
omatic carbons), 165.7 (CO, phth), 166.5 (CO, -lactam); Anal. Calcd
b
-lactam), 3342 (NH); 1H NMR
EtOAc); IR (KBr) cmꢂ1: 1762 (CO, -lactam), 3432 (NH); 1H NMR
b
d
3.68 (OMe, s, 3H), 5.08 (H-3, d, 1H, J¼2.4),
(300 MHz, DMSO-d6)
13C NMR (75 MHz, DMSO-d6)
122.5, 125.7, 126.1, 127.9, 129.2, 134.6, 136.0, 140.4, 143.5, 158.2
(aromatic carbons), 165.8 (CO, -lactam); Anal. Calcd for
d
6.64e8.18 (ArH, m, 16H), 9.02 (NH, br s, 1H);
d
72.8 (C-3), 80.3 (C-4), 116.8, 118.2,
d
b
b
C27H17NO2: C, 83.70; H, 4.42; N, 3.62. Found: C, 83.78; H, 4.57; N,
3.54.
for C18H14N2O4: C, 67.07; H, 4.38; N, 8.69. Found: C, 67.14; H, 4.47; N,
8.71.
4.2.20. cis-1-(4-Methoxybenzyl)-4-(4-nitrophenyl)-3-phenoxy-aze-
tidin-2-one (16a). Light-yellow crystalline solid (0.37 g, 92%). Mp:
94e96 ꢁC. Rf¼0.42 (7:3 hexane/EtOAc); IR (KBr) cmꢂ1: 1335, 1538
4.2.14. cis-1-(4-Methoxynaphthalen-1-yl)-3-phenoxy-4-p-tolyl-aze-
tidin-2-one (10a). White solid (0.38 g, 92%). Mp: 182e184 ꢁC.
Rf¼0.53 (7:3 hexane/EtOAc); IR (KBr) cmꢂ1: 1751 (CO,
b
-lactam); 1H
(NO2), 1748 (CO, b d 3.78 (OMe,
-lactam); 1H NMR (300 MHz, CDCl3)

M. Zarei et al. / Tetrahedron 68 (2012) 5505e5512
5511
4. (a) Long, T. E.; Turos, E. Curr. Med. Chem.: Anti-Infect. Agents 2002, 1, 251e268;
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J¼4.5), 5.46 (H-3, d, 1H, J¼4.5), 6.68e8.11 (ArH, m, 13H); 13C NMR
(75 MHz, CDCl3)
d 44.3 (CH2), 55.3 (OMe), 60.5 (C-3), 82.0 (C-4),
114.1, 115.2, 122.1, 123.3, 126.1, 128.9, 129.1, 129.4, 140.8, 147.9, 156.4,
159.5 (aromatic carbons), 164.9 (CO, -lactam); Anal. Calcd for
b
C23H20N2O5: C, 68.31; H, 4.98; N, 6.93. Found: C, 68.24; H, 5.08; N,
6.98.
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4.2.21. cis-2-(1-(4-Methoxybenzyl)-2-(4-nitrophenyl)-4-
oxoazetidin-3-yl)-isoindoline-1,3-dione (16b). White solid (0.39 g,
85%). Mp: 124e126 ꢁC. Rf¼0.36 (7:3 hexane/EtOAc); IR (KBr) cmꢂ1
:
1337, 1530 (NO2), 1735, 1772 (CO, phth), 1788 (CO, b
-lactam); 1H
NMR (300 MHz, CDCl3)
2d, 2H, J¼14.5), 5.22 (H-4, d, 1H, J¼4.6), 5.64 (H-3, d, 1H, J¼4.6),
6.81e8.25 (ArH, m, 12H); 13C NMR (75 MHz, CDCl3)
45.1 (CH2),
d 3.70 (OMe, s, 3H), 3.89, 4.84 (CH2ebenzyl,
d
55.7 (OMe), 60.2 (C-4), 62.7 (C-3), 110.7, 114.5, 115.4, 127.7, 128.2,
128.5, 129.9, 144.6, 146.2, 148.5, 158.8 (aromatic carbons), 161.1 (CO,
phth), 163.6 (CO, b-lactam); Anal. Calcd for C25H19N3O6: C, 65.64; H,
4.19; N, 9.19. Found: C, 65.72; H, 4.31; N, 9.27.
4.2.22. cis-1-(4-Methoxybenzyl)-4-(4-chlorophenyl)-3-methoxy-
azetidin-2-one (16c). White solid (0.30 g, 90%). Mp: 65e67 ꢁC.
Rf¼0.49 (7:3 hexane/EtOAc); IR (KBr) cmꢂ1: 1752 (CO,
b
-lactam); 1H
d 3.30, 3.78 (2OMe, 2s, 6H), 3.88, 4.63
NMR (300 MHz, CDCl3)
(CH2ebenzyl, 2d, 2H, J¼15.0), 4.80 (H-4, d, 1H, J¼4.9), 5.19 (H-3, d,
1H, J¼4.9), 6.81e7.44 (ArH, m, 8H); 13C NMR (75 MHz, CDCl3)
d 43.1
(CH2), 55.3, 56.5 (2OMe), 63.7 (C-3), 83.9 (C-4), 115.7, 122.9, 123.1,
126.3, 128.0, 135.1, 144.9, 150.6 (aromatic carbons), 162.4 (CO, b-
lactam); Anal. Calcd for C18H18ClNO3: C, 65.16; H, 5.47; N, 4.22.
Found: C, 65.11; H, 5.59; N, 4.27.
4.2.23. cis-1-(4-Methoxybenzyl)-4-(4-chlorophenyl)-3-(naphthalen-
2-yloxy)azetidin-2-one (16d). Light-yellow crystalline solid (0.41 g,
93%). Mp: 137e139 ꢁC. Rf¼0.53 (7:3 hexane/EtOAc); IR (KBr) cmꢂ1
:
1744 (CO, b d 3.70 (OMe, s, 3H),
-lactam); 1H NMR (300 MHz, CDCl3)
3.92, 4.73 (CH2ebenzyl, 2d, 2H, J¼14.9), 4.88 (H-4, d, 1H, J¼4.4),
5.53 (H-3, d, 1H, J¼4.4), 6.75e7.74 (ArH, m, 15H); 13C NMR (75 MHz,
CDCl3)
d 45.5 (CH2), 56.2 (OMe), 59.9 (C-3), 83.7 (C-4), 110.5, 112.7,
118.8,119.3,122.6,124.0,127.3,127.5,127.9,128.5,129.0,129.6,130.1,
134.5, 135.8, 142.2, 144.9, 147.3 (aromatic carbons), 163.1 (CO,
b
-
lactam); Anal. Calcd for C27H22ClNO3: C, 73.05; H, 5.00; N, 3.16.
Found: C, 73.16; H, 5.14; N, 3.22.
4.2.24. cis-4-(4-Chlorophenyl)-3-methoxyazetidin-2-one
(17c). White solid (0.17 g, 80%). Mp: 74e76 ꢁC. Rf¼0.38 (3:7 hex-
ane/EtOAc); IR (KBr) cmꢂ1: 1769 (CO), 3426 (NH); 1H NMR
(300 MHz, DMSO-d6)
2.9), 4.71 (H-3, d, 1H, J¼4.5), 6.73e7.25 (ArH, m, 4H), 8.94 (NH, br s,
1H); 13C NMR (75 MHz, DMSO-d6)
55.9 (OMe), 59.7 (C-4), 83.3 (C-
3), 125.1, 128.4, 140.2, 142.5 (aromatic carbons), 165.9 (CO, -lac-
d
3.32 (OMe, s, 3H), 4.56 (H-4, dd, 1H, J¼4.5,
d
b
tam); Anal. Calcd for C10H10ClNO2: C, 56.75; H, 4.76; N, 6.62. Found:
C, 56.83; H, 4.90; N, 6.55.
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Acknowledgements
The authors thank the Shiraz University Research Council (Grant
No. 90-GR-SC-23) and the Hormozgan University Research Council
for financial support of this work.
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