Ceric ammonium nitrate on silica gel for solid-solid phase N-dearylation of -lactams

Article abstract of DOI:10.1080/10426500802336630

Silica gel-supported ceric ammonium nitrate (CAN-SiO2) has been found to be an effective reagent for the solid-solid phase and solvent-free N-dearylation of -lactams. The results have been compared with CAN alone in solution and solid-solid phase.

Full text of DOI:10.1080/10426500802336630

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Phosphorus, Sulfur, and Silicon
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Ceric Ammonium Nitrate on
Silica Gel for Solid–Solid Phase
N-Dearylation of β -Lactams
a
a
Aliasghar Jarrahpour & Maaroof Zarei
a
Department of Chemistry, College of Sciences ,
Shiraz University , Shiraz, Iran
Published online: 22 Jun 2009.
To cite this article: Aliasghar Jarrahpour & Maaroof Zarei (2009) Ceric Ammonium
Nitrate on Silica Gel for Solid–Solid Phase N-Dearylation of β -Lactams,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:7, 1738-1749, DOI:
10.1080/10426500802336630
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Phosphorus, Sulfur, and Silicon, 184:1738–1749, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802336630
Ceric Ammonium Nitrate on Silica Gel for Solid–Solid
Phase N-Dearylation of β-Lactams
Aliasghar Jarrahpour and Maaroof Zarei
Department of Chemistry, College of Sciences, Shiraz University,
Shiraz, Iran
Silica gel–supported ceric ammonium nitrate (CAN-SiO ) has been found to be
2
an effective reagent for the solid–solid phase and solvent-free N-dearylation of
β-lactams. The results have been compared with CAN alone in solution and solid–
solid phase.
Keywords 2-Azetidinones; ceric ammonium nitrate; N-dearylation; solid–solid phase;
solvent-free; N-unsubstituted β-lactam
INTRODUCTION
The introduction of supported reagents for bringing about various
chemical transformations has provided an attractive option for organic
1
synthesis. Supported reagents offer advantages such as simple work-
up, purification of product, and enhanced or reduced reactivity of
2
functional groups. Silica gel plays an important role in fine organic
3
4
5
synthesis. Solid-state or solvent-free reactions have many advan-
tages, such as reduced pollution, low costs, and simplicity in process and
handling. These factors are especially important in industry. Further-
more, in many cases, solid-state reactions proceed much faster than re-
actions in solution, probably because the solid state reaction has a very
6
high concentration reaction. Among the various heterocyclic ring sys-
tems, β-lactams are possibly some of the best-known and most widely
7
8
investigated. This is primarily due to their antibacterial activity and
9
other new biological activities. Also, this four-membered cyclic amide
Received 13 April 2008; accepted 1 July 2008.
The authors thank the Shiraz University Research Council for financial support
(Grant No. 86-GR-SC-23).
Address correspondence to A. Jarrahpour, Department of Chemistry, College
of Sciences, Shiraz University, Shiraz 71454, Iran. E-mail: jarrah@susc.ac.ir or
aliasghar6683@yahoo.com
1738

CAN on Silica Gel
1739
1
0
has been extensively used for the synthesis of several compounds and
in the semi-synthesis of Taxol derivatives.11
Some of the β-lactam antibiotics and tabtoxin, the glutamine syn-
1
2
thase inhibitor, can be synthesized from N-unsubstituted β-lactams.
N-unsubstituted β-lactams have been obtained from the reaction of N-
1
3
trimethylsilylimine with corresponding compounds, N-deprotection of
1
4
N-aryl or alkyl β-lactams, and reaction of chlorosulfonyl isocyanate
1
5
with alkenes. N-Deprotection of N-alkoxyphenyl-β-lactams by several
methods is an established method in β-lactam chemistry.1
6
Ceric ammonium nitrate (CAN) is one of the reagents that has been
previously utilized for this purpose.17 Commonly N-(4-alkoxyphenyl)-
β-lactams are converted to NH-β-lactams with CAN in aqueous ace-
tonitrile or THF.18 Toxicity, high cost, and tedious work-up are some
drawbacks of these methods, and environmentally benign processes
try to minimize the use of hazardous solvents such as acetonitrile.
1
9
Silica-supported CAN has been used in some reactions. In our labo-
ratory, we have successfully developed N-dearylation of 2-azetidinones
with CAN-SiO2 in solution phase and on column reactions in which
the columns were packed with CAN-SiO2 (as the N-dearylation zone)
and silica gel (as the purification zone).20 Recently, we reported the
solvent-free and solid–solid phase N-dearylation of β-lactams by CAN.2
Here, a remarkably simple, effective, solvent-free, and solid–solid
phase method for N-dearylation of N-(4-methoxy or 4-ethoxyphenyl)-
β-lactams with CAN-SiO2 is described. No solvents are utilized, and no
further purifications are required.
1
RESULTS AND DISCUSSION
Ceric ammonium nitrate on silica gel (CAN-SiO2) was prepared as a
yellowish solid by a reported method.1 The [2+2] ketene-imine cy-
cloaddition (Staudinger reaction) was chosen for the generation of the
9a
2
2
β-lactam ring. 2-Azetidinones 1a–j were synthesized, and the cis or
trans stereochemistry was assigned by measuring coupling constants
1
of H-3 and H-4 in their H NMR spectra. Then the finely powdered
β-lactam 1a was ground with 40% CAN-SiO2 (3.0 eq CAN) in a mortar
for 1 min to afford the N-unsubstituted β-lactam 2a. The color changed
from yellow to orange.
Experiments were performed to find the optimized reaction condi-
tion. It was found to be 2.5 eq of CAN-SiO2 using 20 min reaction time
(
Table I).
In view of this, β-lactams 1a–j were converted to N-unsubstituted
β-lactams 2a–j by grinding with wet 40% CAN-SiO2 (2.5 eq CAN)

1740
A. Jarrahpour and M. Zarei
TABLE I N-Dearylation of 1a by Grinding with 40%
CAN-SiO
2
Molar eq. of CAN
Time (min)
30
Isolated yield (%)
3.0
2.5
2.0
82
84
76
84
83
79
2
1
0
5
30
2
1
0
5
a
45
51
48
46
33
a
30
20
15
a
a
aBased on unreacted starting material.
for 20 min in high yields (Scheme 1, Table II). After completion of
the reaction (TLC monitoring), the reaction mixture was poured into
dichloromethane, and the silica gel was filtered off. The resulting solu-
tion contained the corresponding NH-β-lactams and p-benzoquinone
(
compared with authentic samples). p-Benzoquinone was easily re-
2
3
moved by washing with 10% NaHSO3 solution.
R3
O
R2
R3
O
R2
O
wet CAN-SiO2
grinding
1
+
+ R OH
N
NH
OR1
O
1a-j
2a-j
SCHEME 1
According to Table II, compared to the solution reaction, use of CAN-
SiO2 has the following merits: easy separation and purification, simple
instruments, mild conditions, and no hazardous solvents.
Although the solid–solid phase N-dearylation by CAN alone is a
good method, a larger amount of the reagent (3.5 eq) is needed to
complete the reaction. In addition, CAN-SiO2 is more convenient to
2
4
handle than CAN alone, as the latter is hygroscopic. The structures of
N-unsubstituted β-lactams 2a–j were confirmed by spectroscopic data
and elemental analyses.

1741

1742
A. Jarrahpour and M. Zarei
CONCLUSION
We found that CAN-SiO2 is a rapid, easy, efficient reagent for solvent-
free N-dearylation of β-lactams with high yields. This reagent can easily
be prepared and handled. Use of silica gel–supported CAN allowed the
N-dearylation reactions to proceed using less reagent than the other
methods.
EXPERIMENTAL
All needed chemicals were purchased from Merck, Fluka, and Acros
chemical companies. Dichloromethane and triethylamine were dried
by distillation over CaH2 and then stored over molecular sieve 4Å.
1
IR spectra were run on a Shimadzu FT-IR 8300 spectrophotometer. H
1
3
NMR and C NMR spectra were recorded in DMSO-d6 and CDCl3 using
1
13
a Bruker Avance DPX instrument ( H NMR 250 MHz, C NMR 62.9
MHz). Chemical shifts were reported in ppm (δ) downfield from TMS.
All of the coupling constants (J) are in Hertz. The mass spectra were
recorded on a Shimadzu GC-MS QP 1000 EX instrument. Elemental
analyses were run on a Thermo Finnigan Flash EA-1112 series. Melting
points were determined in open capillaries with Buchi 510 melting
point apparatus and are not corrected. Thin-layer chromatography was
carried out on silica gel 254 analytical sheets obtained from Fluka.
Preparation of Silica Gel–Supported Ceric Ammonium Nitrate
1
9a
(CAN-SiO2)
Silica gel (6.0 g, Merck Kieselgel 70–230 mesh) was mixed with a so-
lution of CAN (4.0 g) in water (4.0 mL). Evaporation of water under
reduced pressure gave a yellowish powder, which contained 40% (by
weight) of CAN. This reagent was found to be active for at least 6
months if stored in a well-capped bottle.
General Procedure for the Solvent-Free N-Dearylation
of β-Lactams 1a–j by CAN-SiO2
β−Lactams 1a–i (1 mmol) were mixed thoroughly with wet 40% CAN-
SiO2 (contained 2.5 eq of CAN) in a mortar. Then the mixture was
ground together for 1 min and was kept for the mentioned times. After
completion of the reaction (TLC monitoring), the mixture was poured
into dichloromethane, and the solid was filtered off. The resulting so-
lution was washed with 10% NaHSO3 (2 × 20 mL) and brine, and

CAN on Silica Gel
1743
then dried (Na2SO4). Filtration and removal of solvent under reduced
pressure afforded the N-unsubstituted β-lactams 2a–j.
4
-(3,4-Dimethoxyphenyl)-1-(4-ethoxyphenyl)-3-
phenoxyazetidin-2-one (1a)
Mp 186–188 C IR (KBr) cm :1758.2 (CO, β-lactam); 1H NMR
◦
−1
(CDCl3) δ 1.36 (Me, t, 3H), 3.75, 3.81 (2OMe, 2s, 6H), 3.95 (OCH2,
q, 2H), 5.28 (H-4, d, 1H, J = 4.2), 5.52 (H-3, d, 1H, J = 4.2), 6.74–
7
6
1
.33 (ArH, m, 12H); 13C NMR (CDCl3) δ 14.8 (Me), 55.8, 55.9 (2OMe),
2.0 (OCH2), 63.6 (C-4), 81.1 (C-3), 110.8, 110.9, 114.9, 115.6, 118.9,
20.9, 122.1, 125.0, 129.2, 130.4, 148.9, 149.3, 155.8, 156.9 (aromatic
+
carbons), 162.5 (CO, β-lactam); GC-MS m/z = 419 [M ]; Anal. Calcd for
C25H25NO5: C, 71.58; H, 6.01; N, 3.34. Found: C, 71.63; H, 5.98, N, 3.38.
1
-(4-Methoxyphenyl)-4-(4-methoxyphenyl)-3-phenoxyazetidin-
-one (1b)
2
Mp 168–170 C IR (KBr) cm :1753.5 (CO, β-lactam); 1H NMR
◦
−1
(
CDCl3) δ 3.64, 3.71 (2OMe, 2s, 6H), 5.27 (H-4, d, 1H, J = 4.5), 5.46 (H-
1
3
3
5
1
, d, 1H, J = 4.5), 6.60–7.32 (ArH, m, 13H); C NMR (CDCl3) δ 55.2,
6.9 (2OMe), 61.4 (C-4), 81.6 (C-3), 113.2, 114.9, 115,7, 118.9, 122.1,
24.5, 129.3, 129.5, 130.4, 155.8, 157.1, 159.5 (aromatic carbons), 163.6
+
(
7
CO, β-lactam); GC-MS m/z = 375 [M ]; Anal. Calcd for C23H21NO4: C,
3.58; H, 5.64; N, 3.73. Found: C, 73.65; H, 5.77; N, 3.72.
2
-(1-(4-Ethoxyphenyl)-2-oxo-4-p-tolylazetidin-3-yl)-isoindoline-
,3-dione (1c)
1
◦
−1
Mp 202–204 C IR (KBr) cm : 1744.2, 1776.2 (CO, phth), 1788.7 (CO,
1
β-lactam); H NMR (CDCl3) δ 1.35 (Me, t, 3H), 2.33 (Me, s, 3H), 3.94
OCH2, q, 2H), 5.25 (H-4, d, 1H, J = 2.5), 5.32 (H-3, d, 1H, J = 2.5),
.68–7.85 (ArH, m, 12H); 13C NMR (CDCl3) δ 14.3, 20.7 (2Me), 60.7
OCH2), 62.3 (C-4), 63.1 (C-3), 114.4, 118.6, 123.2, 125.7, 128.6, 129.5,
(
6
(
1
30.1, 131.2, 132.4, 133.6, 134.0, 138.5, 155.3 (aromatic carbons), 161.1
+
(
CO, phth), 166.3 (CO, β-lactam); GC-MS m/z = 426 [M ]; Anal. Calcd
for C26H22N2O4: C, 70.58; H, 5.01; N, 6.33. Found: C, 70.64; H, 5.05; N,
.37.
6
2
-[2-(3,4-Dimethoxyphenyl)-1-(4-methoxyphenyl)-4-oxo-
azetidin-3-yl]-4-nitroisoindole-1,3-dione (1d)
◦
1
−1
Mp 198–200 C. IR (KBr) cm : 1735.0, 1770.0 (CO, phth), 1778.0
(
CO, β-lactam). H NMR (CDCl3) δ 3.65, 3.74, 3.78 (3 OMe, 3 s, 9H),
5
.33 (H-4, d, 1H, J = 5.2), 5.53 (H-3, d, 1H, J = 5.2), 6.64–8.01 (ArH, m,
13
10H); C NMR (CDCl3) δ 55.8, 56.1, 56.4 (OMe), 61.2 (C-4), 63.3 (C-3),

1744
A. Jarrahpour and M. Zarei
1
09.1, 115.3, 117.8, 118.0, 123.1, 124.6, 126.2, 127.2, 128.7, 129.3, 129.9,
1
35.5, 142.8, 148.7, 153.6, 157.0 (aromatic carbons), 161.2 (CO), 163.5
CO, β-lactam); GC-MS m/z = 503 [M ]; Anal. Calcd for C26H21N3O8:
+
(
C, 62.03; H, 4.20; N, 8.35; found: C, 62.12; H, 4.38; N, 8.40.
1
-(4-Ethoxyphenyl)-3-(naphthalen-2-yloxy)-4-(4-nitrophenyl)-
azetidin-2-one (1e)
Mp 174–176 C IR (KBr) cm :1750.6 (CO, β-lactam); 1H NMR
◦
−1
(
CDCl3) δ 1.39 (Me, t, 3H), 3.95 (OCH2, q, 2H), 5.51 (H-4, d, 1H,
1
3
J = 4.8), 5.74 (H-3, d, 1H, J = 4.8), 6.79–8.11 (ArH, m, 15H);
C
NMR (CDCl3) δ 14.8 (Me), 61.1 (OCH2), 63.7 (C-4), 81.2 (C-3), 109.0,
1
15.2, 118.1, 118.7, 123.6, 124.5, 126.7, 126.9, 127.7, 128.9, 129.6, 129.7,
1
29.8, 133.8, 140.5, 148.1, 154.4, 156.3 (aromatic carbons), 161.7 (CO,
β-lactam); GC-MS m/z = 454 [M ]; Anal. Calcd for C27H22N2O5: C,
+
71.35; H, 4.88; N, 6.16. Found: C, 71.41; H, 4.92; N, 6.20.
4
-(4-Chlorophenyl)-1-(4-ethoxyphenyl)-3-(naphthalen-2-yloxy)-
azetidin-2-one (1f)
Mp 140–142 C IR (KBr) cm :1747.6 (CO, β-lactam); 1H NMR
◦
−1
(
CDCl3) δ 1.35 (Me, t, 3H), 3.90 (OCH2, q, 2H), 5.35 (H-4, d, 1H,
1
3
J = 4.5), 5.64 (H-3, d, 1H, J = 4.5), 6.67–8.08 (ArH, m, 15H);
C
NMR (CDCl3) δ 14.9 (Me), 61.4 (OCH2), 64.6 (C-4), 81.0 (C-3), 109.1,
1
14.7, 115.1, 118.3, 123.9, 124.3, 126.6, 126.9, 127.7, 128.1, 128.7, 129.4,
29.6, 131.4, 133.9, 134.6, 154.7, 156.1 (aromatic carbons), 162.2 (CO,
1
+
37
+
35
β-lactam); GC-MS m/z = 445 [M , Cl], 443 [M , Cl]; Anal. Calcd for
C27H22ClNO3: C, 73.05; H, 5.00; N, 3.16. Found: C, 73.13; H, 5.09; N,
3.11.
3
-(2,4-Dichlorophenoxy)-1-(4-methoxyphenyl)-4-(4-
nitrophenyl)-azetidin-2-one (1g)
Mp 177–189 C IR (KBr) cm :1751.1(CO, β-lactam); 1H NMR
◦
−1
(
CDCl3) δ 3.89 (OMe, s, 3H), 5.56 (H-4, d, 1H, J = 4.5), 5.64 (H-3,
1
3
d, 1H, J = 4.5), 6.72–8.04 (ArH, m, 11H); C NMR (CDCl3) δ 57.9
(OMe), 64.4 (C-4), 82.7 (C-3), 113.4, 116. 3, 118.9, 123.1, 124.7, 127.0,
1
27.9, 129.1, 129.5, 130.1, 140.2, 148.2, 151.5, 155.8 (aromatic carbons),
+
37
+
35
1
63.6 (CO, β-lactam); GC-MS m/z = 463 [M , Cl], 461, 459 [M , Cl];
Anal. Calcd for C22H16Cl2N2O5: C, 57.53; H, 3.51; N, 6.10. Found: C,
7.48; H, 3.63; N, 6.12.
5

CAN on Silica Gel
1745
4
-(4-Chlorophenyl)-3-(2,4-dichlorophenoxy)-1-(4-
ethoxyphenyl)-azetidin-2-one (1h)
Mp 182–184 C IR (KBr) cm :1745.7 (CO, β-lactam); 1H NMR
◦
−1
(
CDCl3) δ 1.38 (Me, t, 3H), 3.96 (OCH2, q, 2H), 5.35 (H-4, d, 1H,
1
3
J = 5.0), 5.48 (H-3, d, 1H, J = 5.0), 6.78–7.33 (ArH, m, 11H); C NMR
(CDCl3) δ 14.8 (Me), 60.9 (OCH2), 63.7 (C-4), 81.7 (C-3), 115.1, 116.7,
1
18.8, 124.3, 127.5, 127.7, 128.8, 129.5, 129.8, 130.1, 131.0, 134.9, 151.4,
+
156.2 (aromatic carbons), 161.5 (CO, β-lactam); GC-MS m/z = 468 [M ,
3
7
+
35
Cl], 466, 464, 462 [M , Cl]; Anal. Calcd for C23H18Cl3NO3: C, 59.70;
H, 3.92; N, 3.03. Found: C, 59.65; H, 4.01; N, 3.06.
1
-(4-Methoxyphenyl)-3-methoxy-4-p-tolylazetidin-2-one (1i)
◦
−1
1
Mp 151–153 C IR (KBr) cm :1748.4 (CO, β-lactam); H NMR
CDCl3) δ 2.34 (Me, s, 3H), 3.25, 3.91 (2OMe, 2s, 6H), 4.63 (H-4, d, 1H,
(
1
3
J = 5.1), 4.81 (H-3, d, 1H, J = 5.1), 6.68–7.42 (ArH, m, 8H); C NMR
(CDCl3) δ 20.4 (Me), 56.7, 58.1 (2OMe), 61.9 (C-4), 83.5 (C-3), 111.7,
13.6, 125.7, 127.3, 129.6, 130.4, 138.9, 156.7 (aromatic carbons), 164.1
+
1
-(4-Ethoxyphenyl)-3-methoxy-4-(4-nitrophenyl)-azetidin-2-
one (1j)
Mp 118–120 C IR (KBr) cm :1748.7 (CO, β-lactam); 1H NMR
◦
−1
(
4
CDCl3) δ 1.41 (Me, t, 3H), 3.26 (OMe, s, 3H), 4.19 (OCH2, q, 2H),
.60 (H-4, d, 1H, J = 4.4), 5.04 (H-3, d, 1H, J = 4.4), 6.61-7.85 (ArH,
13
m, 8H); C NMR (CDCl3) δ 15.7 (Me), 57.8 (OMe), 62.6 (OCH2), 64.8
(
C-4), 85.5 (C-3), 117.5, 119.3, 121.5, 127.8, 133.1, 145.0, 151.2, 158.36
+
(aromatic carbons), 165.6 (CO, β-lactam); GC-MS m/z = 342 [M ]; Anal.
Calcd for C18H18N2O5: C, 63.15; H, 5.30; N, 8.18. Found: C, 63.18; H,
5.37; N, 8.20.
4
-(3,4-Dimethoxyphenyl)-3-phenoxyazetidin-2-one (2a)
◦
−1
1
Mp 140–142 C IR (KBr) cm :1777.7 (CO), 3418.9 (NH); H NMR
(
DMSO-d6) δ 3.58, 3.66 (2MeO, 2s, 6H), 5.03 (H-3, d, 1H, J = 4.0),
5
1
3
.58 (H-4, dd, 1H, J = 2.2, 4.0), 6.64–7.26 (ArH, m, 8H), 8.83 (NH, brs,
13
H); C NMR (DMSO-d6) δ 55.2, 55.23 (2OMe), 56.4 (C-4), 81.1 (C-
), 111.0, 111.4, 115.0, 119.7, 121.4, 128.5, 129.2, 147.9, 148.3, 156.6
+
(
aromatic carbons), 166.0 (CO, β-lactam); GC-MS m/z = 299 [M ]; Anal.
Calcd for C17H17NO4: C, 68.21; H, 5.72; N, 4.68. Found: C, 68.31; H, 5.79;
N, 4.73.

1746
A. Jarrahpour and M. Zarei
4
-(4-Methoxyphenyl)-3-phenoxyazetidin-2-one (2b)
◦
−1
1
Mp 157–159 C IR (CHCl3) cm :1776.3 (CO), 3409.9 (NH); H NMR
(
DMSO-d6) δ 3.66 (MeO, s, 3H), 5.02 (H-3, d, 1H, J = 4.3), 5.52 (H-4,
13
dd, 1H, J = 1.8, 4.3), 6.55–7.35 (ArH, m, 9H), 9.08 (NH, brs, 1H);
C
NMR (DMSO-d6) δ 54.83 (OMe), 56.4 (C-4), 81.8 (C-3), 113.19, 114.8,
1
21.7, 127.5, 128.8, 129.3, 156.2, 158.7 (aromatic carbons), 166.9 (CO,
+
β-lactam); GC-MS m/z = 269 [M ]; Anal. Calcd for C16H15NO3: C, 71.36;
H, 5.61; N, 5.20. Found: C, 71.42; H, 5.66; N, 5.24.
2
-(2-Oxo-4-p-tolylazetidin-3-yl)-isoindoline-1,3-dione (2c)
◦
−1
Mp 197–199 C IR (CHCl3) cm : 1740.0, 1775.0 (CO, phth), 1785.0
1
(
CO, β-lactam), 3480.5 (NH); H NMR (DMSO-d6) δ 2.35 (Me, s, 3H),
.94 (H-4, dd, 1H, J = 2.5, 3.5), 5.04 (H-3, d, 1H, J = 2.5), 7.23–8.03
4
1
3
(ArH, m, 8H), 9.02 (NH, brs, 1H); C NMR (DMSO-d6) δ 20.7 (Me),
5
5.4 (C-4), 62.6 (C-3), 123.4, 125.8, 129.1, 131.3, 134.8, 136.0, 137.3
(aromatic carbons), 164.6 (CO, phth), 166.7 (CO, β-lactam); GC-MS m/z
+
=
306 [M ]; Anal. Calcd for C18H14N2O3: C, 70.58; H, 4.61; N, 9.15.
Found: C, 70.62; H, 4.58; N, 9.21.
2
-[2-(3,4-Dimethoxyphenyl)-4-oxo-azetidin-3-yl]-4-
nitroisoindole-1,3-dione (2d)
◦
−1
Mp 117–119 C. IR (KBr, cm ) 1735.0, 1770.2 (phth., CO), 1785.0
1
(
CO, β-lactam), 3380.5 (NH); H NMR (DMSO-d6) δ 3.61, 3.75 (2 OMe,
2
(
s, 6H), 5.04 (H-4, dd, 1H, J = 2.2, 5.5), 5.53 (H-3, d, 1H, J = 5.5), 6.55
NH, br s, 1H), 6.97–8.63 (ArH, m, 6H); 1 C NMR (DMSO-d6) δ 55.4,
3
5
5.9 (OMe), 60.8 (C-4), 63.2 (C-3), 110.1, 114.6, 118.7, 122.5, 124.1,
1
26.4, 128.3, 129.4, 135.7, 143.0, 148.9, 150.1 (aromatic carbons), 163.4
+
(CO), 164.5 (CO, β-lactam); GC-MS m/z = 397 [M ]; Anal. Calcd for
C19H15N3O7: C, 57.43; H, 3.81; N, 10.58 Found: C, 57.37; H, 3.88; N,
0.55.
1
3
-(Naphthalen-2-yloxy)-4-(4-nitrophenyl)-azetidin-2-one (2e)
◦
−1
1
Mp 172–174 C IR (KBr) cm :1769.6 (CO), 3354.4 (NH); H NMR
(
4
DMSO-d6) δ 5.38 (H-3, d, 1H, J = 4.5), 5.86 (H-4, dd, 1H, J = 2.3,
1
3
.5), 7.31–7.78 (ArH, m, 11H), 9.10 (NH, brs, 1H); C NMR (DMSO-
d6) δ 56.0 (C-4), 82.7 (C-3), 117.5, 117.7, 122.9, 123.2, 124.1, 126.5,
1
26.7, 127.4, 128.8, 129.32, 130.6, 139.6, 144.5, 153.9 (aromatic car-
+
bons), 165.7 (CO, β-lactam); GC-MS m/z = 334 [M ]; Anal. Calcd for
C19H14N2O4: C, 68.26; H, 4.22; N, 8.38. Found: C, 68.23; H, 4.26; N,
8.42.

CAN on Silica Gel
1747
4
-(4-Chlorophenyl)-3-(naphthalen-2-yloxy)-azetidin-2-one (2f)
◦
−1
Mp 122–124 C IR (KBr) cm : 1765.8 (CO, β-lactam), 3358.3 (NH);
1
H NMR (DMSO-d6) δ 5.18 (H-3, d, 1H, J = 4.2), 5.53 (H-4, dd, 1H,
1
3
J = 1.9, 4.2), 6.46–7.96 (ArH, m, 15H), 8.87 (NH, brs, 1H); C NMR
DMSO-d6) δ 58.3 (C-4), 81.5(C-3), 106.8, 118.9, 122.7, 124.0, 126.3,
27.1, 128.9, 129.5, 129.8, 130.5, 133.4, 134.2, 155.6, 158.1 (aromatic
(
1
+
37
+
carbons), 165.92 (CO, β-lactam); GC-MS m/z = 325 [M , Cl], 323 [M ,
3
5
Cl]; Anal. Calcd for C19H14ClNO2: C, 70.48; H, 4.36; N, 4.33. Found:
C, 70.40; H, 4.42; N, 4.28.
3
-(2,4-Dichlorophenoxy)-4-(4-nitrophenyl)-azetidin-2-one (2g)
◦
−1
Mp 160–162 C IR (KBr) cm :1775.5 (CO, β-lactam), 3320.5 (NH);
1
H NMR (DMSO-d6) δ 5.34 (H-3, d, 1H, J = 3.5), 5.77 (H-4, dd, 1H, J =
1
3
2
.4, 3.5), 7.32–8.22 (ArH, m, 7H), 9.20 (NH, brs, 1H); C NMR (DMSO-
d6) δ 55.5 (C-4), 83.0 (C-3), 116.3, 122.2, 122.9, 125.8, 127.8, 128.8,
29.2, 143.9, 147.1, 150.7 (aromatic carbons), 165.0 (CO, β-lactam);
1
+
37
+
35
GC-MS m/z = 356 [M , Cl], 354, 352 [M , Cl]; Anal. Calcd for
C15H10Cl2N2O4: C, 51.01; H, 2.85; N, 7.93. Found: C, 51.05; H, 2.92; N,
7.97.
4
-(4-Chlorophenyl)-3-(2,4-dichlorophenoxy)azetidin-2-one (2h)
◦
−1
Mp 143–145 C IR (KBr) cm :1770.1 (CO, β-lactam), 3324.6 (NH);
1
H NMR (DMSO-d6) δ 5.23 (H-3, d, 1H, J = 4.5), 5.63 (H-4, dd, 1H, J =
1
3
2
.3, 4.5), 6.94–8.13 (ArH, m, 7H), 9.06 (NH, brs, 1H); C NMR (DMSO-
d6) δ 59.3 (C-4), 80.6 (C-3), 114.19, 117.3, 123.6, 126.7, 128.1, 129.9,
30.6, 135.4, 151.0, 156.9 (aromatic carbons), 163.2 (CO, β-lactam);
1
+
37
+
35
GC-MS m/z = 348 [M , Cl], 346, 344, 342 [M , Cl]; Anal. Calcd for
C15H10Cl3NO2: C, 52.59; H, 2.94; N, 4.09. Found: C, 52.56; H, 3.07; N,
4.00.
3
-Methoxy-4-p-tolylazetidin-2-one (2i)
◦
−1
1
Mp 92–94 C IR (KBr) cm :1765.8 (CO, β-lactam), 3414.0 (NH); H
NMR (DMSO-d6) δ 2.11 (Me, s, 3H), 2.82 (OMe, s, 3H), 4.51 (H-4, dd,
1
8
H, J = 2.2, 4.4), 4.59 (H-3, d, 1H, J = 4.4), 6.69–7.07 (ArH, m, 4H),
.41 (NH, brs, 1H); 13C NMR (DMSO-d6) δ 20.7 (Me), 56.2 (OMe), 57.1
(
(
6
C-4), 86.3 (C-3), 127.3, 128.6, 134.1, 136.8 (aromatic carbons), 167.5
+
CO, β-lactam); GC-MS m/z = 191 [M ]; Anal. Calcd for C11H13NO2: C,
9.09; H, 6.85; N, 7.32. Found: C, 69.14; H, 6.92; N, 7.28.
3
-Methoxy-4-(4-nitrophenyl)-azetidin-2-one (2j)
◦
−1
Mp 101–103 C IR (KBr) cm :1763.9 (CO, β-lactam), 3430.3 (NH);
1
H NMR (DMSO-d6) δ 2.91 (OMe, s, 3H), 4.43 (H-4, dd, 1H, J = 1.9,

1748
A. Jarrahpour and M. Zarei
4
1
1
.7), 4.50 (H-3, d, 1H, J = 4.7), 6.56–7.71 (ArH, m, 4H), 8.53 (NH, brs,
13
H); C NMR (DMSO-d6) δ 57.1 (OMe), 59.1 (C-4), 84.4 (C-3), 124.7,
29.5, 136.3, 139.3 (aromatic carbons), 165.9 (CO, β-lactam); GC-MS
+
m/z = 222 [M ]; Anal. Calcd for C10H10N2O4: C, 54.05; H, 4.54; N,
12.61. Found: C, 54.11; H, 4.63; N, 12.58.
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