Cerium(IV) tetrabutylammonium nitrate (CTAN): A mild and efficient N-dearylation agent for synthesis of N-unsubstituted 2-azetidinones

Article abstract of DOI:10.3184/174751917X14902201357392

A simple and efficient protocol for the conversion of N-p-methoxyphenyl, N-p-ethoxyphenyl, N-p-methoxynaphthyl, N-3,4-dimethoxybenzyl and N-p-methoxybenzyl-2-azetidinones to N-unsubstituted 2-azetidinones using cerium(IV) tetrabutylammonium nitrate (CTAN) in dichloromethane is described. The method is compatible with a number of functional groups, and N-unsubstituted 2-azetidinones can be prepared under mild conditions at room temperature. The reaction is rapid, and pure products are obtained in good yields.

Full text of DOI:10.3184/174751917X14902201357392

246 RESEARCH PAPER
VOL. 41 APRIL, 246–249
JOURNAL OF CHEMICAL RESEARCH 2017
Cerium(IV) tetrabutylammonium nitrate (CTAN): A mild and efficient
N-dearylation agent for synthesis of N-unsubstituted 2-azetidinones
Maaroof Zarei*
Department of Chemistry, Faculty of Sciences, University of Hormozgan, Bandar Abbas 71961, Iran
A simple and efficient protocol for the conversion of N-p-methoxyphenyl, N-p-ethoxyphenyl, N-p-methoxynaphthyl, N-3,4-dimethoxybenzyl
and N-p-methoxybenzyl-2-azetidinones to N-unsubstituted 2-azetidinones using cerium(IV) tetrabutylammonium nitrate (CTAN) in
dichloromethane is described. The method is compatible with a number of functional groups, and N-unsubstituted 2-azetidinones can be
prepared under mild conditions at room temperature. The reaction is rapid, and pure products are obtained in good yields.
Keywords: N-unsubstituted 2-azetidinones, β-lactams, N-dearylation, CTAN
Results and discussion
2-Azetidinones (β-lactams) represent a unique heterocyclic
ring, with interesting chemistry and potentially significant
biological activities.1–2 N-Unsubstituted 2-azetidinones have
been used as intermediates in the synthesis of several β-lactam
antibiotics, tabtoxin (the glutamine synthetase inhibitor)3 and in
the semi-synthesis of the anticancer agents Taxol and Taxotere.4
N-Deprotection of N-alkoxyphenyl-β-lactams is the best
method for the preparation of NH-2-azetidinones in β-lactam
chemistry.5 Some oxidation reagents for this purpose are
cerium(IV) ammonium nitrate (CAN),6–7 cobalt(III) fluoride,8
argentic oxide,9 silver(II) persulfate10 and persulfate in the
presence of catalytic AgNO3.11 Also, anodic N-dearylation of
2-azetidinones has been reported.12 N-Alkoxyphenyl-β-lactams
have been prepared by several methods.13–15
CAN has proved to be a very useful oxidant in synthetic
organic chemistry over four decades.16–18 The solubility of
CAN in non-polar organic solvents is very low, and hence
CAN-mediated reactions must be performed in polar organic
solvents or mixable water–organic solvents such as acetonitrile
and require cold conditions and a tedious workup using ethyl
acetate. Also, the solubility of some organic compounds in
mixed acetonitrile–water is low. The poor solubility of CAN
in less polar solvents can be circumvented by the preparation
of ceric(IV) tetra-n-butylammonium nitrate (CTAN), also
known as tetrabutylammoniumcerium(IV) nitrate (TBACN).19
CTAN’s greater lipophilic activity makes it soluble in common
organic solvents like dichloromethane.
CTAN was readily prepared in high yield from an
aqueous solution of cerium(IV) ammonium nitrate and
tetrabutylammonium hydrogen sulphate.21
To determine suitable conditions for N-dearylation of
2-azetidinones the reaction of 4-(4-chlorophenyl)-1-(4-
methoxyphenyl)-3-phenoxyazetidin-2-one 1a (1 mmol) and
CTAN as test reaction for the synthesis of N-unsubstituted
2-azetidinone 2a was examined. The conditions were
optimised for various parameters, such as the effect of solvent,
temperature, the quantity of reagent and the influence of
reaction time. The results of these experiments are summarised
in Table 1. Acetonitrile–water and dichloromethane–water
gave better yields of product than other solvents, but use of
acetonitrile requires an extraction with ethyl acetate. When
2-azetidinone 1a was mixed with CTAN in dry CH2Cl2 (entry
5) at room temperature, no reaction was observed after 90
minutes, showing that water is necessary for this reaction to
occur. Water alone as solvent was not suitable because of the
poor solubility of the substrates in water. CH2Cl2–H2O (19 : 1)
was therefore chosen as the most suitable solvent.
Table 1 Optimisation of the N-dearylation of 2-azetidinone 1a with CTAN
Cl
Cl
O
PhO
PhO
CTAN
+
N
NH
O
O
O
CTAN has been used for the synthesis of pyrroles
from β-aminocinnamates.20 Muathen used this reagent
for oxidation of benzyl alcohols, dehydrogenation of
hydroquinones, oxidative coupling of thiols and iodination of
polymethylbenzenes and methoxybenzenes.21 Flowers and co-
workers reported solvent-dependent chemoselectivity in the
reaction of allyltrimethylsilane with 1,3-dicarbonyl compounds
in the presence of CTAN in the preparation of dihydrofuran
derivatives and α-tetralones in methanol and dichloromethane,
respectively.22
While each of the methods used for the preparation of
N-unsubstituted 2-azetidinones has its advantages there are
also some limitations, such as expensive reagents and tedious
isolation procedures. Taking these points into account a mild,
neutral, efficient and functional group-compatible procedure
for the synthesis of N-unsubstituted 2-azetidinones via
N-dearylation of N-(p-alkoxyaryl)- and N-(p-alkoxybenzyl)-2-
azetidinones with CTAN is reported.
OMe
1a
2a
3
Temp
(°C)
rt
rt
rt
rt
rt
rt
rt
−10
rt
CTAN
(mmol)
3
3
3
3
3
3
3
3
4
2.5
2.0
2.5
2.5
Time
(min)
Yield
(%)
Entry Solvent
1
2
3
4
5
6
7
8
1,4-Dioxane–H2O (3 : 1) a
CH3CN–H2O (3 : 1) a
THF–H2O (3 : 1) a
DMF–H2O (3 : 1) a
CH2Cl2–H2O (19 : 1)
CHCl3–H2O (19 : 1)
dry CH2Cl2
CH2Cl2–H2O (19 : 1)
CH2Cl2–H2O (19 : 1)
CH2Cl2–H2O (19 : 1)
CH2Cl2–H2O (19 : 1)
CH2Cl2–H2O (19 : 1)
CH2Cl2–H2O (19 : 1)
30
30
30
30
30
30
90
30
30
30
30
20
10
80
85
79
51
87
82
–
48
84
86
63
88
65
9
10
11
12
13
rt
rt
rt
rt
aExtraction with ethyl acetate was required.
* Correspondent. E-mail: maaroof1357@yahoo.com

JOURNAL OF CHEMICAL RESEARCH 2017 247
When N-dearylation of 2-azetidinone 1a was performed at
−10 °C the yield of 2a increased significantly to 48% (entry 8).
It was found that 2.5 equiv. of CTAN and at least 20 minutes
of reaction time were needed for the complete consumption of
1a, giving a high yield of product 2a. Finally, for deprotection
of N-p-methoxyphenyl-2-azetidinone 1a the best result was
obtained in CH2Cl2–H2O (19 : 1) with 2.5 equiv. of CTAN at
room temperature for 20 minutes (entry 12).
was easily eliminated by forming the corresponding bisulfite
adduct, which could be washed out with water after workup
with aqueous NaHSO3 solution.
Having determined the best reaction conditions the scope of
the reaction was extended to a diverse range of 2-azetidinones
(Scheme 1 and Table 2). N-Dearylation of monocyclic and
spirocyclic 2-azetidinones containing aromatic and aliphatic
substituents was investigated (Table 2).
Benzoquinone
3
was one of the by-products, and
N-p-Alkoxyphenyl-,
N-p-alkoxynaphthyl-
and
N-p-
identification was achieved by direct comparison with an
alkoxybenzyl-2-azetidinones can be converted into the
authentic sample using thin-layer chromatography (TLC). It
corresponding N-unsubstituted 2-azetidinones in good to
Scheme 1 N-Dearylation of 2-azetidinones with CTAN
Table 2 N-dearylation of 2-azetidinones 1a–y
Yield (%)
Cis/
Entry
R1
R2
R3
Product
trans
CTAN
87
CANa
1
2
3
4
5
6
7
8
4-MeOC6H4
4-EtOC6H4
4-EtOC6H4
4-MeOC6H4
4-MeOC6H4
4-EtOC6H4
3,4-(MeO)2C6H3CH2
4-EtOC6H4
4-(MeO)C6H4CH2
4-(MeO)C6H4CH2
4-MeOC6H4
4-ClC6H4
4-MeC6H4
4-ClC6H4
C6H5
4-MeOC6H4
PhCH=CH
4-NO2C6H4
4-ClC6H4
4-NO2C6H4
4-(NMe2)C6H4
C6H5
PhO
PhO
4-ClC6H4O
2,4-Cl2C6H3O
MeSO2
PhthN
PhO
CH3CO
2,4-Cl2C6H3O
2,4-Cl2C6H3O
Cl
Cis
Cis
Cis
Cis
Cis
Cis
Cis
Trans
Cis
Cis
2a
2b
2c
2d
2e
2f
2g
2h
2i
81 (19)b
84
85
86
86
80
74
80
81
85
83
83
88
83
77
73
82
84
81
86
9
10
11
2j
2k
Cis
85
O
12
4-MeOC6H4
PhO
Cis
2l
89
88
O
13
14
15
16
17
18
4-MeOC6H4
4-EtOC6H4
4-MeOC6H4
4-(MeO)naphthyl
4-EtOC6H4
4-MeC6H4
CH2=CH–CH=CH
2-NaphthO
PhthN
MeO
CH2=CH
PhthN
Trans
Cis
Cis
Cis
Trans
Trans
2m
2n
2o
2p
2q
2r
75
85
80
91
71
78
78
84
77
87
73
75
4-(Me2CH)C6H4
4-(Me2CH)C6H4
4-ClC6H4
4-NO2C6H4
4-ClC6H4
4-(MeO)naphthyl
O
19
4-MeOC6H4
2,4-Cl2C6H3
–
2s
88
88
20
4-MeOC6H4
2,3,4-(MeO)3C6H2
–
2t
84
87
21
22
23
4-EtOC6H4
4-EtOC6H4
C6H5CH2
4-MeOC6H4
4-ClC6H4
4-NO2C6H4
N3
Cis
Cis
Cis
2u
2v
–
83
85
–
80
83
–
2-naphthO
2-naphthO
24
4-NO2C6H4
PhO
Cis
–
–
–
N
Cl
a3 equiv. of CAN in CH3CN/H2O (3 : 1), 45 min, 0 °C.
b3 equiv. of CAN in CH2Cl2/H2O (19 : 1), 30 min, rt.

248 JOURNAL OF CHEMICAL RESEARCH 2017
20 mmol ) in water (25 mL). The resulting solid was filtered and
purified by recrystallisation from light petroleum.
excellent yields and with high purity. Note that the substitutions
on C-2 and C-3 of 2-azetidinones (even the 4-methoxyphenyl-
and 3,4,5-trimethoxyphenyl- groups) remain intact during this
oxidative N-dearylation reaction. Benzyl and pyridyl groups
at the N-1 position of 2-azetidinones 1x and 1y were not
deprotected.
Synthesis of 2-azetidonones (1y)
2-Azetidonone 1y was synthesised by the same reported procedure24 using
N-(2-chloropyridin-3-yl)-1-(4-nitrophenyl)methanimine,25 phenoxyacetic
acid, phosphonitrilic chloride and triethylamine in dry CH2Cl2 at room
temperature.
All NH-2-azetidinones 2a–v were characterised from spectral
data and by elemental analysis. The stereochemistry of the
starting 2-azetidinones was retained in the products. This new
procedure was also compared with N-dearylation using CAN
(Table 2). The isolated yields of N-unsubstituted 2-azetidinones
2a–v were comparable with those obtained using CAN. 3-Chloro
N-unsubstituted 2-azetidinone 2k (entry 11) was successfully
obtained from 2-azetidinone 1k, whereas N-dearylation of this
compound with silver reagents such as AgO gave a lower yield.9
The N-dearylation of β-lactams 1a–v was faster using CTAN
(20 min) than with CAN (45 min). Reaction with CTAN can
be performed in CH2Cl2, and extraction is not needed after
completion of the reaction, but reaction with CAN requires
extraction with ethyl acetate. N-p-Methoxyphenyl, N-p-
ethoxyphenyl, N-p-methoxynaphthyl, N-p-methoxybenzyl and
N-3,4-dimethoxybenzyl-2-azetidinones 1a–v readily undergo
oxidative N-dearylation to afford NH-2-azetidinones 2a–v
using CTAN at room temperature. In contrast, the use of CAN
requires cold reaction conditions. Also, it was found that 2.5
equiv. of CTAN were sufficient for the complete transformation
to N-unsubstituted 2-azetidinones 2a–v. This method is clean
and simple, yielding pure products after workup with aqueous
solution followed by recrystallisation from Et2O without the need
for extraction and column chromatography.
1-(2-Chloropyridin-3-yl)-4-(4-nitrophenyl)-3-phenoxyazetidin-
2-one (1y): White solid; m.p. 185–187 °C; FTIR (KBr) (νmax cm−1):
1337, 1519 (NO2), 1621 (C=N, pyridine ring), 1742 (CO); 1H NMR: δ
5.39 (H-4, d, 1H, J = 5.1), 5.52 (H-3, d, 1H, J = 5.1), 7.09–8.25 (ArH,
m, 12H); 13C NMR: δ 63.8 (C-4), 82.4 (C-3), 117.2, 118.4, 121.2, 123.5,
125.7, 126.4, 128.0, 132.3, 135.9, 140.8, 144.6, 153.5, 156.2 (aromatic
carbons), 164.4 (CO). Anal. calcd for C20H14ClN3O4: C, 60.69; H, 3.57;
N, 10.62; found: C, 60.82; H, 3.73; N, 10.71%.
N-Dearylation reaction; general procedure
CTAN (2.5 mmol) was added at room temperature to a solution of
2-azetidinones 1a–y (1.0 mmol) in CH2Cl2–H2O (20 mL) (19 : 1).
The mixture was stirred for 20 min, then H2O (20 mL) was added.
The organic layer was separated and washed with 20% aqueous
NaHSO3 (20 mL) and brine (20 mL) and then dried over Na2SO4.
After filtration and evaporation of the solvent the crude residue was
purified by recrystallisation from Et2O to give pure N-unsubstituted
2-azetidinones 2a–v.
4-(4-Chlorophenyl)-3-phenoxyazetidin-2-one (2a): M.p. 184–186 °C
(lit.6 188–190 °C).
3-Phenoxy-4-(p-tolyl)azetidin-2-one (2b): M.p. 181–183 °C (lit.6
180–182 °C).
3-(4-Chlorophenoxy)-4-(4-chlorophenyl)azetidin-2-one (2c): White
solid; m.p. 163–165 °C; FTIR (KBr) (νmax cm−1): 1769 (CO), 3308 (NH);
1H NMR: δ 5.27 (H-3, d, 1H, J = 4.7), 5.41 (H-4, dd, 1H, J = 4.7, 2.6),
6.96–7.42 (ArH, m, 8H), 9.04 (NH, br s, 1H); 13C NMR: δ 60.4 (C-4),
81.7 (C-3), 118.8, 122.4, 124.6, 126.0, 127.2, 131.9, 143.1, 154.0 (aromatic
carbons), 162.5 (CO). Anal. calcd for C15H11Cl2NO2: C, 58.47; H, 3.60;
N, 4.55; found: C, 58.59; H, 3.74; N, 4.48%.
3-(2,4-Dichlorophenoxy)-4-phenylazetidin-2-one (2d): White solid.
m.p. 157–159 °C; FTIR (KBr) (νmax cm−1): 1772 (CO), 3301 (NH);
1H NMR: δ 5.09 (H-3, d, 1H, J = 5.0), 5.25 (H-4, dd, 1H, J = 5.0, 2.2),
6.88–7.54 (ArH, m, 8H), 8.96 (NH, br s, 1H); 13C NMR: δ 62.1 (C-4),
82.6 (C-3), 116.5, 120.2, 122.9, 123.4, 125.0, 127.6, 129.4, 133.4, 145.8,
155.8 (aromatic carbons), 161.7 (CO). Anal. calcd for C15H11Cl2NO2: C,
58.47; H, 3.60; N, 4.55; found: C, 58.55; H, 3.71; N, 4.59%.
4-(4-Methoxyphenyl)-3-(methylsulfonyl)azetidin-2-one (2e): M.p.
106–108 °C (lit.23 103–105 °C).
The by-product of N-p-methoxyphenyl and N-p-
ethoxyphenyl is benzoquinone 3, and for N-p-methoxynaphthyl
it is naphthoquinone 4. p-Methoxybenzaldehyde
5 and
3,4-dimethoxybenzaldehyde 6 are the by-products of N-p-
methoxybenzyl and N-3,4-dimethoxybenzyl groups, respectively.
Waste Ce(III) and methanol or ethanol are produced during these
reactions, but these by-products were removed with an aqueous
solution of NaHSO3. The mechanisms of these reactions are the
same as those with CAN and have been previously reported.6,23
Conclusions
In conclusion, CTAN readily prepared from cerium(IV)
ammonium nitrate and a tetrabutylammonium salt brings
about efficient N-dearylation of N-p-methoxyphenyl, N-p-
ethoxyphenyl, N-p-methoxynaphthyl, N-3,4-dimethoxybenzyl
and N-p-methoxybenzyl 2-azetidinones. This oxidative
N-deprotection reaction provides a novel method for the
synthesis of highly substituted N-unsubstituted 2-azetidinones.
The reaction is general, working for a variety of 2-azetidinones,
and generates the desired products in good to excellent yields.
The reaction conditions are straightforward, with short reaction
times at room temperature.
2-(2-Oxo-4-styrylazetidin-3-yl)isoindoline-1,3-dione (2f): M.p.
168–170 °C (lit.6 167–169 °C).
4-(4-Nitrophenyl)-3-phenoxyazetidin-2-one (2g): M.p. 164–166 °C
(lit.6 160–162 °C).
3-Acetyl-4-(4-chlorophenyl)azetidin-2-one (2h): Light-yellow solid;
m.p. 64–66 °C; FTIR (KBr) (νmax cm−1): 1717 (CO, ketone), 1760 (CO,
1
β-lactam), 3296 (NH); H NMR: δ 2.35 (MeCO, s, 3H), 3.94 (H-3, d,
1H, J = 2.6), 4.81 (H-4, dd, 1H, J = 2.6, 2.3), 6.92–7.37 (ArH, m, 4H),
8.90 (NH, br s, 1H); 13C NMR: δ 25.3 (Me), 64.8 (C-3), 67.2 (C-4),
117.5, 123.9, 129.7, 150.0 (aromatic carbons), 163.6 (CO, β-lactam),
195.2 (CO, ketone). Anal. calcd for C11H10ClNO2: C, 59.07; H, 4.51; N,
6.26; found: C, 59.01; H, 4.42; N, 6.20%.
Experimental
All required chemicals were purchased from Merck, Aldrich or Acros
chemical companies. The melting points were determined on a Buchi
535 apparatus. IR spectra were measured on a Galaxy Series FTIR
5000 spectrometer. NMR spectra were recorded in CDCl3 or DMSO-d6
using a Bruker instrument (1H NMR 300 MHz, 13C NMR 75 MHz),
and coupling constants are given in cycles per second (Hz). Elemental
analyses were run on a Vario EL III Elemental Analyzer. TLC was
carried out on silica gel 254 analytical sheets obtained from Fluka.
3-(2,4-Dichlorophenoxy)-4-(4-nitrophenyl)azetidin-2-one (2i): M.p.
158–160 °C (lit.6 160–162 °C).
3-(2,4-Dichlorophenoxy)-4-(4-(dimethylamino)phenyl)azetidin-2-
one (2j): White solid; m.p. 119–121 °C; FTIR (KBr) (νmax cm−1): 1779
1
(CO), 3311 (NH); H NMR: δ 2.87 (2Me, s, 6H), 5.28 (H-3, d, 1H,
J = 4.7), 5.35 (H-4, dd, 1H, J = 4.7, 2.5), 6.81–7.44 (ArH, m, 7H), 9.19
(NH, br s, 1H); 13C NMR: δ 42.4 (NMe2), 60.7 (C-4), 83.3 (C-3), 119.1,
120.9, 122.0, 122.8, 126.8, 129.2, 130.6, 136.4, 143.9, 156.1 (aromatic
carbons), 162.3 (CO). Anal. calcd for C17H16Cl2N2O2: C, 58.14; H, 4.59;
N, 7.98; found: C, 58.27; H, 4.77; N, 8.07%.
Preparation of cerium(IV) tetrabutylammonium nitrate (CTAN)21
Cerium(IV) ammonium nitrate (5.5 g, 10 mmol) in water (15 mL) was
added to a solution of tetrabutylammonium hydrogen sulphate (6.8 g,

JOURNAL OF CHEMICAL RESEARCH 2017 249
3-Chloro-4-phenylazetidin-2-one (2k): M.p. 75–77 °C (lit.8
71–73 °C).
(CO), 3318 (NH); 1H NMR: δ 3.66, 3.80 (2 s, 9H, 3 OMe), 5.63 (H-4, d,
1H, J = 2.9), 6.59–7.84 (ArH, m, 10H), 8.93 (NH, br s, 1H); 13C NMR:
δ 56.6, 58.7 (OMe), 63.9 (C-4), 73.5 (C-3), 104.8, 110.1, 118.7, 123.9,
125.1, 125.9, 135.2, 144.8, 154.8, 155.6 (aromatic carbons), 163.6 (CO).
Anal. calcd for C24H21NO4: C, 74.40; H, 5.46; N, 3.62; found: C, 74.49;
H, 5.58; N, 3.57%.
4-(Benzo[d][1,3]dioxol-5-yl)-3-phenoxyazetidin-2-one
(2l):
White solid; m.p. 173–175 °C; FTIR (KBr) (νmax cm−1): 1769 (CO),
3307 (NH); 1H NMR: δ 5.19 (H-3, d, 1H, J = 4.6), 5.27 (H-4, dd, 1H,
J = 4.6, 2.1), 5.73 (OCH2O, s, 2H), 6.86–7.73 (ArH, m, 8H), 8.94 (NH,
br s, 1H); 13C NMR: δ 61.3 (C-4), 81.9 (C-3), 103.8 (OCH2O), 118.4,
120.9, 123.5, 123.7, 125.2, 128.6, 132.4, 147.3, 151.9, 154.6 (aromatic
carbons), 160.8 (CO). Anal. calcd for C16H13NO4: C, 67.84; H, 4.63; N,
4.94; found: C, 67.94; H, 4.76; N, 5.01%.
3-Azido-4-(4-methoxyphenyl)azetidin-2-one (2u): m.p. 121–123 °C
(lit.23 127–128 °C).
4-(4-Chlorophenyl)-3-(naphthalen-2-yloxy)azetidin-2-one
m.p. 119–121 °C (lit.6 122–124 °C).
(2v):
3-(Buta-1,3-dien-1-yl)-4-(p-tolyl)azetidin-2-one
(2m):
White
solid; m.p. 75–77 °C; FTIR (KBr) (νmax cm−1): 1763 (CO), 3288 (NH);
1H NMR: δ 2.25 (Me, s, 3H), 3.75 (H-3, dd, 1H, J = 2.5, 8.0 Hz), 4.74
(H-4, dd, 1H, J = 2.5, 2.7), 5.26–5.34 (vinylic H, m, 2H), 5.79 (vinylic
H, dd, 1H, J = 8.0, 15.5 Hz), 6.06 (vinylic H, dd, 1H, J = 9.6, 15.5 Hz),
6.28 (vinylic H, m, 1H), 6.96–7.46 (ArH, m, 4H), 9.02 (NH, br s, 1H),
13C NMR: δ 22.7 (Me), 61.3 (C-4), 64.0 (C-3), 111.7, 119.5, 123.8,
125.5, 126.1, 131.4, 139.2, 148.6 (C=C and aromatic carbons), 160.7
(CO). Anal. calcd for C14H15NO: C, 78.84; H, 7.09; N, 6.57; found: C,
78.97; H, 7.21; N, 6.66%.
Acknowledgement
Support for this work by the University of Hormozgan Research
Council is gratefully acknowledged.
Received 16 January 2017; accepted 13 March 2017
Paper 1704540
https://doi.org/10.3184/174751917X14902201357392
Published online: 3 April 2017
4-(4-Isopropylphenyl)-3-(naphthalen-2-yloxy)azetidin-2-one (2n):
Cream-coloured solid; m.p. 180–182 °C; FTIR (KBr) (νmax cm−1): 1770
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J.R. Hwu, S.K. Ethiraj and G.H. Hakimelahi, Mini-Rev. Med. Chem., 2003,
3, 305.
(CO), 3314 (NH); H NMR: δ 1.18 (2Me, d, 6H, J = 7.6), 2.72 (CH,
septet, 1H), 5.41 (H-3, d, 1H, J = 4.5), 5.50 (H-4, dd, 1H, J = 4.5, 2.2),
6.73–7.79 (ArH, m, 11H), 9.06 (NH, br s, 1H); 13C NMR: δ 23.9 (Me),
33.6 (CH), 63.3 (C-4), 82.7 (C-3), 115.2, 116.7, 120.8, 121.4, 123.0,
126.3, 126.8, 127.5, 127.9, 130.5, 136.9, 140.1, 147.6, 158.5 (aromatic
carbons), 164.1 (CO). Anal. calcd for C22H21NO2: C, 79.73; H, 6.39; N,
4.23; found: C, 79.81; H, 6.44; N, 4.18%.
2
3
4
D.S. Salunkhe and P.B. Piste, Int. J. Pharm. Sci. Rev. Res., 2014, 5, 666.
M. Suffness, Taxol science and applications; CRC Press, Boca Raton, FL,
1995.
5
T.W. Green and P.G.M. Wuts, Green’s protective groups in organic
synthesis, 4th edn, John Wiley & Sons, NJ, 2007.
A. Jarrahpour and M. Zarei, Molecules, 2007, 12, 2364.
A. Jarrahpour and M. Zarei, Phosphorus Sulfur and Silicon, 2009, 184,
1738.
2-(2-(4-Isopropylphenyl)-4-oxoazetidin-3-yl)isoindoline-1,3-dione
(2o): Pale-yellow solid; m.p. 219–221°C; FTIR (KBr) (νmax cm−1): 1732,
6
7
1
1774 (CO, phth), 1780 (CO, β-lactam), 3326 (NH); H NMR: δ 1.23
(2Me, d, 6H, J = 7.3), 2.68 (CH, septet, 1H), 5.18 (H-3, d, 1H, J = 4.8),
5.31 (H-4, dd, 1H, J = 4.8, 2.6), 6.91–7.75 (ArH, m, 8H), 8.94 (NH, br
s, 1H); 13C NMR: δ 22.6 (Me), 33.4 (CH), 61.5 (C-4), 64.8 (C-3), 118.4,
121.9, 125.8, 126.4, 128.1, 133.8, 146.4 (aromatic carbons), 163.0 (CO,
phth), 165.3 (CO, β-lactam); Anal. calcd for C20H18N2O3: C, 71.84; H,
5.43; N, 8.38; found: C, 71.98; H, 5.55; N, 8.46%.
8
9
M. Zarei and A. Jarrahpour, Tetrahedron Lett., 2010, 51, 5791.
M. Zarei and A. Jarrahpour, Tetrahedron Lett., 2011, 52, 1192.
10 M. Zarei, Tetrahedron Lett., 2013, 54, 4174.
11 K. Bhattarai, G. Cainelli and M. Panunzio, Synlett, 1990, 4, 229.
12 E.G. Corley, S. Karady, N.L. Abramson, D. Ellison and L.M. Weinstock,
Tetrahedron Lett., 1988, 29, 1497.
13 M. Zarei, Z. Karimi-Jaberi and A. Movahedi, Synth. Commun., 2013, 43,
728.
14 M. Zarei, Tetrahedron, 2013, 69, 6620.
4-(4-Chlorophenyl)-3-methoxyazetidin-2-one (2p): M.p. 71–73 °C
(lit.8 74–76 °C).
4-(4-Nitrophenyl)-3-vinylazetidin-2-one (2q): M.p. 58–60 °C (lit.8
56–58 °C).
2-(2-(4-Chlorophenyl)-4-oxoazetidin-3-yl)isoindoline-1,3-dione
(2r): M.p. 201–203 °C (lit.8 196–198 °C).
2-(2,4-Dichlorophenyl)spiro[azetidine-3,9’-xanthen]-4-one (2s):
White solid; m.p. 228–230 °C; FTIR (KBr) (νmax cm−1): 1766 (CO),
3324 (NH); 1H NMR: δ 5.49 (H-4, d, 1H, J = 3.3), 6.74–7.80 (ArH, m,
11H), 9.19 (NH, br s, 1H); 13C NMR: δ 64.8 (C-4), 76.2 (C-3), 114.8,
115.3, 118.5, 122.9, 123.4, 127.7, 128.0, 129.9, 134.7, 142.4, 151.6, 154.2
(aromatic carbons), 164.7 (CO). Anal. calcd for C21H13Cl2NO2: C,
65.99; H, 3.43; N, 3.66; found: C, 66.11; H, 3.56; N, 3.73%.
4-(3,4,5-Trimethoxyphenyl)spiro[azetidine-3,9’-fluoren]-2-one
(2t): White solid; m.p. 194–196 °C; FTIR (KBr) (νmax cm−1): 1769
15 M. Zarei, J. Chem. Res., 2012, 36, 118.
16 V. Nair and A. Deepthi, Chem. Rev., 2007, 107, 1862.
17 A. Jarrahpour and M. Zarei, Synth. Commun., 2008, 38, 1837.
18 A. Jarrahpour and M. Zarei, Synlett, 2008, 19, 381.
19 Z. Zhang, A.J. Raines and R.A. Flowers, Org. Lett., 2003, 5, 2363.
20 A.-I. Tsai and C.-P. Chuang, Tetrahedron, 2006, 62, 2235.
21 H.A. Muathen, Indian J. Chem., 1991, 30B, 522.
22 B.M. Casey, C.A. Eakin, J. Jiao, D.V. Sadasivam and R.A. Flowers,
Tetrahedron, 2009, 65, 10762.
23 M. Zarei, A. Jarrahpour, E. Ebrahimi, M. Aye and S.A. Torabi Badrabady,
Tetrahedron, 2012, 68, 5505.
24 M. Zarei, Tetrahedron, 2013, 69, 6620.
25 M. Akkurt, S. Karaca, A. Jarrahpour, M. Zarei and O. Buyukgungor, Acta
Crystallogr. Sect. E, 2005, 61, 776.