Cycloaddition reactions of N-benzotriazolylketene as a heteroarylketene: A practical approach to the synthesis of novel azetidinones

Article abstract of DOI:10.1055/s-0033-1340280

A series of novel functionalized azetidinones containing the benzotriazole moiety were synthesized stereoselectively by a ?reaction of benzotriazolylacetic acid, aromatic amines, and ?Mukaiyama's reagent in the presence of triethylamine in dichloromethane at ambient temperature. This transformation generates a four-membered lactam and presumably proceeds via in situ generation of benzotriazolylketene as a heteroarylketene. In contrast to the products obtained from the reaction of pyrrolylketene with imines in which cis-azetidinones were formed as major products, the generated benzotriazolylyketene reacted with imines forming the trans-lactams as major products. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1340280

LETTER
▌229
lCettyercloaddition Reactions of N-Benzotriazolylketene as a Heteroarylketene:
A Practical Approach to the Synthesis of Novel Azetidinones
Novel Azetidinones from Benzotriazolylketene
Fatemeh Zigheimat,a Mohammad Reza Islami,*a Farahnaz Nourmohammadianb
a
Department of Chemistry, Shahid Bahonar University of Kerman, 76169, Kerman, Iran
Fax +98(341)3222033; E-mail: mrislami@uk.ac.ir
b
Department of Organic Colorants, Institute for Color Science and Technology, 654-16765, Tehran, Iran
Received: 01.10.2013; Accepted after revision: 14.10.2013
done and barbituric acid derivatives37 (Scheme 1). In this
present work we have synthesized new β-lactams includ-
ing a benzotriazole moiety in a stereoselective manner by
producing the corresponding ketene and trapping it by dif-
Abstract: A series of novel functionalized azetidinones containing
the benzotriazole moiety were synthesized stereoselectively by a
reaction of benzotriazolylacetic acid, aromatic amines, and
Mukaiyama’s reagent in the presence of triethylamine in dichloro-
methane at ambient temperature. This transformation generates a ferent Schiff bases. Herein we wish to report our results.
four-membered lactam and presumably proceeds via in situ genera-
tion of benzotriazolylketene as a heteroarylketene. In contrast to the
products obtained from the reaction of pyrrolylketene with imines
N
R1
R2
N
O
in which cis-azetidinones were formed as major products, the gen-
erated benzotriazolylyketene reacted with imines forming the trans-
lactams as major products.
O
N
anhyd CH2Cl2
CO2Me
OH
N
R1
R2
Key words: ketenes, Schiff bases, N-benzotriazolylketene,
[2π+2π] cycloaddition, azetidinones
O
OMe
H
N
N
N2
hv
N
+
+
N
CO2Me
MeOH
H
β-Lactams (azetidinones) are an important class of antibi-
otics,1–6 and in recent years their clinical use has expanded
significantly.7–13 The β-lactam ring plays an important
role in medical treatment of infection by inhibiting the
synthesis of the peptidoglycan layer of bacterial cell
walls.12 Since Staudinger prepared the first synthetic β-
lactam,13 there have been numerous reports in the litera-
ture regarding the synthesis and application of such com-
pounds.14–17 One of the most important methods for the
synthesis of β-lactams is the use of ketenes. Ketenes are
an important class of compounds in the synthesis of four-
and six-membered rings.18–22 Ketenes are remarkable for
the variety of ways in which they can be prepared23–25 and
also for the range of useful products from their reactions
with unsaturated compounds.26,27 They have long been
known for their unique reactivity in [2+2]-cycloaddition
reactions.28–30
Benzotriazoles such as 1-alkylbenzotriazoles31 and nitro
derivatives are interesting due to their biological activities
as herbicides.32–34 Furthermore, benzotriazoles connected
to acylonitriles showed interesting activity against the
mycobacterium turberculosis.35 However, benzotriazoles
directly substituted with a β-lactam ring have received lit-
tle attention36 probably due to the lack of convenient
methods for their preparation. Recently, one of the focus-
es in our research group has been to develop the synthesis
of new heterocyclic compounds by the reaction of ketenes
with imines,14 1,3-dicarbonyl compounds, such as dime-
O
O
OH
O
O
Me
O
Ph
O
Ph
Me
Me
N
anhyd Et2O
N
N
C
C O
+
Cl
N
C
O
O
Me
O
Scheme 1 Reaction of ketenes with imines, methanol, and 1,3-di-
methylbarbituric acid
Firstly, we tried to prepare benzotriazolyl acetic acid as a
precursor by known procedures. Although our literature
survey showed there are several procedures for achieving
this goal, several of these methods suffered from draw-
backs such as prolonged reaction times, esoteric starting
materials, the need for catalysts such as copper(II) bronze,
the use of an organic solvent such as xylene, cumbersome
apparatus, microwave conditions, and in some cases ben-
zotriazolylmethyl cyanide was required as a precursor.38–
40 Therefore, in order to modify and simplify the synthe-
sis, benzotriazole (1) was mixed with 2-bromoacetic acid
(2), heated until the mixture melted and heating was con-
tinued for 60 minutes. Upon cooling to room temperature
the desired product 3 was formed as a solid and, after re-
crystallization from water, was used in the following reac-
tions.
As shown in Scheme 2, treatment of imines 6 with N-ben-
zotriazolylketene 5 generated in situ from benzotriazolyl
acetic acid (3) and 2-chloro-1-methylpyridinium iodide
(4) in the presence of Et3N gave products which were
characterized as β-lactams 7 on the basis of spectroscopic
analysis. In contrast to the obtained products from the re-
action of pyrrolylketene with imines in which cis-azetidi-
SYNLETT 2014, 25, 0229–0232
Advanced online publication: 02.12.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1340280; Art ID: ST-2013-D0927-L
© Georg Thieme Verlag Stuttgart · New York

230
F. Zigheimat et al.
LETTER
nones were formed as major products,14 ketene 5 reacted were observed corresponding to the carbonyl carbon at δ
with imines 6, forming the trans-lactams 7a–e as major = 159.70 ppm and signals at δ = 71.42 and 62.88 ppm cor-
1
products (Table 1).
responding to methine carbons. The H NMR and 13C
NMR of cis-7a were similar to those of trans-7a except
for the coupling constant of the vicinal methine protons
(3JHH = 5.4 Hz). The 1H NMR and 13C NMR spectroscopic
data of trans- and cis-isomers of compounds 7b–e are pre-
sented in the experimental section.
N
N
N
heat
OH
Br
N
N
+
– HBr
N
H
O
2
OH
C
1
O
A plausible mechanistic pathway that best explains the
formation of these isomers is shown in Scheme 3. It is
generally accepted,15,41,42 that the stereochemistry in the
ketene–imine cycloaddition involves initial attack of the
imine onto the ketene with formation of intermediate 8a
which undergoes competitive ring closure to the cis-β-lac-
tam 7, with isomerization to the less crowded intermediate
8b and ring closure to trans-β-lactam 7.
3
H
O
C
N
Et3N
N
N
N
+
N
+
N
CH2Cl2
OH
Cl
I–
N
r.t., overnight
Me
O
4
5
3
Ar1
N
N
H
O
N
N
N
H
C
Ar1
H
Ar2
N
C
k1
N
R
R
+
Ar2
H
6
N
+
Ar1
N
N
C
C O
N
H
k–1
–O
Ar2
Ar2
N
Ar2
O
O
8a
k2
N
Ar1
N
Ar1
R
O
H
H
5
N
k3
trans-7
cis-7
Ar1
Ar2
cis-7
Scheme 2 β-Lactams from Benzotriazolylketene
Table 1 β-Lactams 7 from Benzotriazolylketene 5 and Imines 6
Ar1
H
H
R
O
R
Product
Ar1
Ar2
Yield
Yield
N
–O
N
(%) cisa
(%) transa
Ar2
Ar1
Ar2
8b
trans-7
7a
7b
7c
7d
7e
Ph
Ph
Ph
Ph
Ph
Ph
1
23
35
38
46
40
Scheme 3 Plausible mechanism for the stereoselective formation of
β-lactams
4-BrC6H4
4-ClC6H4
4-MeC6H4
4-MeOC6H4
1
1
The difference between stereochemistry of products from
pyrrolylketene14 and products from benzotriazolylketene
may be attributed to differences in steric effects in the
mechanistic pathways leading to the different products.15
The nitrogen of the imine attacks the ketene forming ini-
tial intermediate 8a. Since the benzotriazole ring is larger
than pyrrole ring k3 is enhanced relative to k2 so the trans-
β-lactams 7 are favored.
20
11
a Isolated yield of pure product.
1
The structures of products fully characterized by IR, H
NMR, and 13C NMR spectroscopy (see Supporting Infor-
mation) along with elemental analysis data. The IR spec-
tra of these compounds showed absorption bands due to
the carbonyl group at 1752–1774 cm–1. 1H NMR spectros-
copy is generally used for distinguishing between cis- and
trans-β-lactam isomers using H–H coupling constants, as
the J value is smaller (2.0–2.5 Hz) in a trans-β-lactam
In conclusion, the present work describes the synthesis of
a series of novel β-lactams containing the benzotriazole
moiety in a stereoselective manner via reaction of benzo-
triazolylacetic acid, aromatic amine, and 2-chloro-1-
methylpyridinium iodide in the presence of triethylamine
in dichloromethane at ambient temperature. This transfor-
mation generates a four-membered lactam and presum-
1
than in a cis-β-lactam (5.0–6.0 Hz). The H NMR spec-
trum of trans-7a exhibited signals corresponding to the
vicinal methine protons at δ = 5.87 and 5.54 ppm which
appear as two doublets (3JHH = 2.4 Hz). The aromatic pro-
tons appeared as a multiplet at δ = 7.45–7.07 ppm. The 1H-
decoupled 13C NMR spectrum of trans-7a showed 17 dis-
tinct resonances in agreement with the suggested struc-
ture; partial assignment of these resonances is given in the
experimental section. Characteristic 13C NMR signals
ably
proceeds
via
in
situ
generation
of
benzotriazolylketene and its [2+2]-cycloaddition reaction
with Schiff bases. It is worthy of note that, in contrast to
the products obtained from the reaction of pyrrolylketene
with imines, in the present work trans-β-lactams were iso-
lated as the main products.
Synlett 2014, 25, 229–232
© Georg Thieme Verlag Stuttgart · New York

LETTER
Novel Azetidinones from Benzotriazolylketene
231
Modified Procedure for the Synthesis of 2-(1H-1,2,3-Benzotri-
azol-1-yl) Acetic Acid 3
Calcd (%) for C21H15BrN4O (429.28): C, 60.16; H, 3.61; N, 13.36.
Found: C, 60.49; H, 3.47; N, 13.15.
In a 100 mL round-bottomed flask were placed 2-bromoacetic acid
(1.4 g, 10 mmol) and benzotriazole (0.6 g, 5 mmol). The mixture
was heated until it melted, and then heating was continued for 60
min. On cooling, the product formed as a white solid that was re-
crystallized from H2O (0.5 g, 58% yield).
3-(1H-1,2,3-Benzotriazol-1-yl)-1-(4-chlorophenyl)-4-phenyl-2-
azetanone (trans-7c)
Pale yellow solid; yield: 140 mg (38%); mp 189–190 °C (dec.). IR
(KBr): νmax = 1773 (C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ =
8.04 (d, 1 H, 3JH–H=8.4 Hz, Ar), 7.43–7.18 (m, 12 H, Ar), 5.84 (d, 1
H, 3JH–H = 2.4 Hz), 5.54 (d, 1 H, 3JH–H = 2.4 Hz) ppm. 13C NMR (100
MHz, CDCl3): δ = 159.65 (C=O), 146.23, 135.05, 134.50, 132.55,
130.44 (5 C), 129.79, 129.75, 129.52, 128.54, 126.12, 124.70,
120.56, 119.01, 109.18, 71.44, 63.09 (11 C–H) ppm. Anal. Calcd
(%) for C21H15ClN4O (374.83): C, 67.29; H, 4.03; N, 14.95. Found:
C, 67.29; H, 3.93; N, 14.71.
Typical Procedure for the Preparation of Compounds 7a–e
Benzotriazolylacetic acid (3, 0.18 g, 1.0 mmol) was mixed with 2-
chloro-N-methylpyridinium iodide (4, 0.30 g, 1.2 mmol) and dry
Et3N (0.50 mL, 3.6 mmol) in anhydrous CH2Cl2 (20 mL) under a ni-
trogen atmosphere at ambient temperature. The suspension was
stirred for 5 min, and then a solution of N-benzylideneaniline (0.2
g, 1.1 mmol) in dry CH2C12 (5 mL) was added, and the reaction
mixture was stirred overnight. The brown solution was washed with
8% aq HCl and then with H2O. The organic layer was dried over
Na2SO4, filtered, and the solvent was removed under reduced pres-
sure. The products were purified by column chromatography using
n-hexane–EtOAc 5:3(v/v) as eluent. The trans- and cis-3-(1H-
1,2,3-benzotriazol-1-yl)-1,4-diphenyl-2-azetanones (trans- and cis-
7a) were isolated as the major and minor products, respectively.
3-(1H-1,2,3-Benzotriazol-1-yl)-1-(4-chlorophenyl)-4-phenyl-2-
azetanone (cis-7c)
Pale yellow solid; yield: 5 mg (1%); mp 218–220 °C (dec.). IR
(KBr): νmax = 1773 (C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ =
7.77 (d, 1 H, 3JH–H = 9.2 Hz, Ar), 7.40–6.87 (m, 12 H, Ar), 6.51 (d,
1 H, 3JH–H = 5.4 Hz), 5.64 (d, 1 H, 3JH–H = 5.4 Hz) ppm. 13C NMR
(100 MHz, CDCl3): δ = 158.91 (C=O), 145.63, 135.42, 132.64,
130.49, 128.79 (5 C), 129.56, 129.00, 128.39, 127.75, 126.59,
124.05, 120.05, 118.82, 109.59, 66.92, 61.71 (11 C–H) ppm. Anal.
Calcd (%) for C21H15ClN4O (374.83): C, 67.29; H, 4.03; N, 14.95.
Found: C, 67.33; H, 4.28; N, 14.80.
Analytical Data
3-(1H-1,2,3-Benzotriazol-1-yl)-1,4-diphenyl-2-azetanone
(trans-7a)
White solid; yield: 80 mg (23%); mp 158–159 °C. IR (KBr): νmax
=
3-(1H-1,2,3-Benzotriazol-1-yl)-1-(4-methylphenyl)-4-phenyl-2-
azetanone (trans-7d)
1
1774 (C=O) cm–1. H NMR (400 MHz, CDCl3): δ = 8.06 (d, 1 H,
3JH–H = 8.3 Hz, Ar), 7.45–7.07 (m, 13 H, Ar), 5.87 (d, 1 H, 3JH–H
=
Yellow solid; yield: 160 mg (46%); mp 160–161 °C. IR (KBr): νmax
= 1752 (C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.05 (d, 1 H,
3JH–H = 8.3 Hz, Ar), 7.44–7.18 (m, 8 H, Ar), 7.23 (d, 2 H, 3JH–H = 8.3
Hz, Ar), 7.05 (d, 2 H, 3JH–H = 8.3 Hz, Ar), 5.85 (d, 1 H, 3JH–H = 2.3
Hz), 5.50 (d, 1 H, 3JH–H = 2.3 Hz), 2.24 (s, 3 H, Me) ppm. 13C NMR
(100 MHz, CDCl3): δ = 159.39 (C=O), 146.30, 135.02, 135.00,
134.10, 132.46 (5 C), 129.89, 129.60, 129.53, 128.45, 126.15,
124.62, 120.51, 117.75, 109.35, 71.45, 62.82 (11 C–H), 21.00 (Me)
ppm. Anal. Calcd (%) for C22H18N4O (354.41): C, 74.56; H, 5.12;
N, 15.81. Found: C, 74.77; H, 5.10; N, 15.75.
3
2.4 Hz), 5.54 (d, 1 H, JH–H = 2.4 Hz) ppm. 13C NMR (100 MHz,
CDCl3): δ = 159.70 (C=O), 146.28, 136.54, 134.90, 132.49 (4 C),
129.66, 129.60, 129.41, 128.49, 126.13, 125.22, 124.66, 120.55,
117.81, 109.30, 71.42, 62.88 (12 C–H) ppm. Anal. Calcd (%) for
C21H16N4O (340.39): C, 74.10; H, 4.74; N, 16.46. Found: C, 73.85;
H, 5.13; N, 16.33.
3-(1H-1,2,3-Benzotriazol-1-yl)-1,4-diphenyl-2-azetanone (cis-
7a)
Yellow solid; yield: 4 mg (1%); mp 191–193 °C. IR (KBr): νmax
=
1774 (C=O) cm–1. H NMR (400 MHz, CDCl3): δ = 7.77 (d, 1 H,
1
3-(1H-1,2,3-Benzotriazol-1-yl)-1-(4-methylphenyl)-4-phenyl-2-
azetanone (cis-7d)
3JH–H = 9.8 Hz, Ar), 7.46–6.87 (m, 13 H, Ar), 6.52 (d, 1 H, 3JH–H
=
5.4 Hz), 5.66 (d, 1 H, JH–H = 5.4 Hz) ppm. 13C NMR (100 MHz,
CDCl3): δ = 158.97 (C=O), 145.69, 136.97, 132.71, 130.96 (4 C),
129.44, 128.79, 128.29, 127.62, 126.62, 125.30, 123.93, 119.99,
117.60, 109.85, 66.85, 61.57 (12 C–H) ppm. Anal. Calcd (%) for
C21H16N4O (340.39): C, 74.10; H, 4.74; N, 16.46. Found: C, 73.97;
H, 5.10; N, 16.65.
Yellow solid; yield: 70 mg (20%); mp 176–178 °C. IR (KBr): νmax
= 1752 (C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.76 (d, 1 H,
3JH–H = 8.4 Hz, Ar), 7.41 (d, 2 H, 3JH–H = 8.3Hz, Ar), 7.35–7.00 (m,
5 H, Ar), 7.09 (d, 2 H, 3JH–H = 8.3 Hz, Ar), 6.87–6.86 (m, 3 H, Ar),
6.50 (d, 1 H, 3JH–H = 5.4 Hz), 5.63 (d, 1 H, 3JH–H = 5.4 Hz), 2.26 (s,
3 H, Me) ppm. 13C NMR (100 MHz, CDCl3): δ = 158.71 (C=O),
145.68, 135.08, 134.56, 132.73, 131.11 (5 C), 129.91, 128.71,
128.24, 127.58, 126.64, 123.90, 119.94, 117.52, 109.90, 66.84,
61.51 (11 C–H), 21.02 (Me) ppm. Anal. Calcd (%) for C22H18N4O
(354.41): C, 74.56; H, 5.12; N, 15.81. Found: C, 74.89; H, 5.17; N,
15.87.
3
3-(1H-1,2,3-Benzotriazol-1-yl)-1-(4-bromophenyl)-4-phenyl-2-
azetanone (trans-7b)
Light yellow solid; yield: 150 mg (35%); mp 188–189 °C. IR (KBr):
νmax = 1754 (C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.05 (d,
1 H, 3JH–H = 8.3 Hz, Ar), 7.47–7.19 (m, 12 H, Ar), 5.84 (d, 1 H, 3JH–
H = 2.4 Hz), 5.54 (d, 1 H, 3JH–H = 2.4 Hz) ppm. 13C NMR (100 MHz,
CDCl3): δ = 159.68 (C=O), 146.23, 135.50, 134.44, 132.53, 118.13
(5 C), 132.46, 129.81, 129.77, 128.56, 126.11, 124.72, 120.58,
119.32, 109.16, 71.46, 63.06 (11 C–H) ppm. Anal. Calcd (%) for
C21H15BrN4O (419.28): C, 60.16; H, 3.61; N, 13.36. Found: C,
60.55; H, 3.56; N, 12.99.
3-(1H-1,2,3-Benzotriazol-1-yl)-1-(4-methoxyphenyl)-4-phenyl-
2-azetanone (trans-7e)
Pale yellow solid; yield: 150 mg (40%); mp 168 °C. IR (KBr): νmax
= 1760 (C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.04 (d, 1 H,
3JH–H = 8.3 Hz, Ar), 7.44–7.32 (m, 8 H, Ar), 7.28 (d, 2 H, 3JH–H = 9.0
Hz, Ar), 6.78 (d, 2 H, 3JH–H = 9.0 Hz, Ar), 5.85 (d, 1 H, 3JH–H = 2.3
3
Hz), 5.49 (d, 1 H, JH–H = 2.3 Hz), 3.69 (s, 3 H, OMe) ppm. 13C
3-(1H-1,2,3-Benzotriazol-1-yl)-1-(4-bromophenyl)-4-phenyl-2-
azetanone (cis-7b)
NMR (100 MHz, CDCl3): δ = 159.09 (C=O), 156.95, 146.29,
134.96, 132.48, 129.96 (5 C), 129.61, 129.56, 128.44, 126.19,
124.62, 120.50, 119.20, 114.60, 109.36, 71.45, 62.96 (11 C–H),
55.49 (OMe) ppm. Anal. Calcd for C22H18N4O2 (370.41): C, 71.34;
H, 4.90; N, 15.13. Found: C, 71.39; H, 5.00; N, 15.48.
Pale yellow solid; yield: 4 mg (1%); mp 176–178 °C (dec.). IR
(KBr): νmax = 1754 (C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ =
7.77 (d, 1 H, 3JH–H = 8.4 Hz, Ar), 7.42–6.88 (m, 12 H, Ar), 6.51 (d,
1 H, 3JH–H = 5.4 Hz), 5.64 (d, 1 H, 3JH–H = 5.4 Hz) ppm. 13C NMR
(100 MHz, CDCl3): δ = 158.94 (C=O), 145.64, 135.89, 132.65,
130.46, 119.15 (5 C), 132.49, 131.72, 128.99, 128.39, 127.74,
126.59, 124.03, 120.06, 109.59, 66.95, 61.69 (11 C–H) ppm. Anal.
3-(1H-1,2,3-Benzotriazol-1-yl)-1-(4-methoxyphenyl)-4-phenyl-
2-azetanone (cis-7e)
Yellow solid; yield: 40 mg (11%); mp 158–160 °C. IR (KBr): νmax
= 1760 (C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.75 (d, 1 H,
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 229–232

232
F. Zigheimat et al.
LETTER
(15) Jiao, L.; Liang, Y.; Xu, J. J. Am. Chem. Soc. 2006, 128,
3JH–H = 8.4 Hz, Ar), 7.43–7.41 (m, 1 H, Ar), 7.38 (d, 2 H, 3JH–H = 9.0
Hz, Ar), 7.29–7.00 (m, 5 H, Ar), 6.88–6.86 (m, 2 H, Ar), 6.81 (d, 2
H, 3JH–H = 9.0 Hz, Ar), 6.50 (d, 1 H, 3JH–H = 5.3 Hz), 5.62 (d, 1 H,
3JH–H = 5.3 Hz), 3.72 (s, 3 H, OMe) ppm. 13C NMR (100 MHz,
CDCl3): δ = 158.36 (C=O), 156.97, 145.66, 132.73, 131.11, 130.46
(5 C), 128.74, 128.25, 127.59, 126.67, 123.91, 119.93, 118.92,
114.59, 109.89, 66.87, 61.62 (11 C–H), 55.52 (OMe) ppm. Anal.
Calcd (%) for C22H18N4O2 (370.41): C, 71.34; H, 4.90; N, 15.13.
Found: C, 71.50; H, 5.05; N, 15.51.
6060.
(16) Lee, S. H. Bull. Korean Chem. Soc. 2013, 34, 121.
(17) Tidwell, T. T. Angew. Chem. Int. Ed. 2008, 47, 1016.
(18) Leung-Toung, R.; Tidwell, T. T. J. Am. Chem. Soc. 1990,
112, 1042.
(19) Sharma, A. K.; Mahajan, M. P. Tetrahedron 1997, 53,
13841.
(20) Bandyopadhyay, D.; Cruz, J.; Banik, B. K. Tetrahedron
2012, 68, 10686.
(21) Liu, R.; Tidwell, T. T. Can. J. Chem. 1995, 73, 1818.
(22) Allen, A. D.; Tidwell, T. T. Eur. J. Org. Chem. 2012, 1081.
(23) Penn, J. H.; Owens, W. H. J. Am. Chem. Soc. 1993, 115, 82.
(24) Baigrie, L. M.; Seikaly, H. R.; Tidwell, T. T. J. Am. Chem.
Soc. 1985, 107, 5391.
Acknowledgment
The authors express appreciation to the Shahid Bahonar University
of Kerman Faculty Research committee funds for its support of this
investigation.
(25) Leung-Toung, R.; Wentrup, C. J. Org. Chem. 1992, 57,
4850.
(26) Alonso, E.; Lόpez-Ortiz, F.; del Pozo, C.; Peralta, E.;
Macίas, A.; González, J. J. Org. Chem. 2001, 66, 6333.
(27) Bennett, D. M.; Okamoto, I.; Danheiser, R. L. Org. Lett.
1999, 1, 641.
(28) Brady, W. T.; Saidi, K. J. Org. Chem. 1979, 44, 733.
(29) Montaigne, R.; Ghosez, L. Angew. Chem., Int. Ed. Engl.
1968, 7, 221.
(30) Brady, W. T.; Saidi, K. J. Org. Chem. 1980, 45, 727.
(31) Katritzky, A. R.; Wu, J.; Kuzmierkiewicz, W.; Rachwal, S.
Liebigs Ann. Chem. 1994, 1.
(32) Eugene, D. R.; Vernon, K. R. US 4,240,822, 1980.
(33) Eugene, D. R.; Vernon, K. R. US 4,086,242, 1978.
(34) Suma, B. V.; Natesh, N. N.; Madhavan, V. J. Chem. Pharm.
Res. 2011, 3, 375.
(35) Sanna, P.; Carta, A.; Rahbar Nikookar, M. E. Eur. J. Med.
Chem. 2000, 35, 535.
(36) Sharma, S. D.; Saluja, A.; Bhaduri, S. Indian J. Chem., Sect.
B.: Org. Chem. Incl. Med. Chem. 2000, 39, 156.
(37) Sheibani, H.; Islami, M. R.; Khabazzadeh, H.; Saidi, K.
Tetrahedron 2004, 60, 5931.
(38) Pellicciari, R.; Fringuelli, R.; Natalini, B.; Brucato, L.;
Contessa, A. R. Arch. Pharm. 1985, 318, 393.
(39) Gupton, J. T.; Hicks, F. A.; Smith, S. Q.; Main, A. D.;
Petrich, S. A.; Wilkinson, D. R.; Sikorski, J. A.; Katritzky,
A. R. Tetrahedron 1993, 49, 10205.
(40) Khalafi-Nezhad, A.; Zare, A.; Parhami, A.; Soltani Rad, M.
N.; Nejabat, G. R. J. Iran. Chem. Soc. 2007, 4, 271.
(41) Fu, N.; Tidwell, T. T. Tetrahedron 2008, 64, 10465.
(42) Cossio, F. P.; Ugalde, J. M.; Lopez, X.; Lecea, B.; Palomo,
C. J. Am. Chem. Soc. 1993, 115, 995.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
References
(1) Elander, R. P. Appl. Microbiol. Biotechnol. 2003, 61, 385.
(2) Pichichero, M. E. Pediatrics 2005, 115, 1048.
(3) Fisher, J. F.; Meroueh, S. O.; Mobashery, S. Chem. Rev.
2005, 105, 395.
(4) Kasten, B.; Reski, R. J. Plant Physiol. 1997, 150, 137.
(5) Nangia, A.; Biradha, K.; Desiraju, G. R. J. Chem. Soc.,
Perkin Trans. 2 1996, 943.
(6) Cohen, N. C. J. Med. Chem. 1983, 26, 259.
(7) O’Boyle, N. M.; Carr, M.; Greene, L. M.; Bergin, O.;
Nathwani, S. M.; McCabe, T.; Lloyd, D. G.; Zisterer, D. M.;
Meegan, M. J. J. Med. Chem. 2010, 53, 8569.
(8) O’Boyle, N. M.; Greene, L. M.; Bergin, O.; Jean-Baptiste,
F.; McCabe, T.; Lloyd, D. G.; Zisterer, D. M.; Meegan, M.
J. Bioorg. Med. Chem. 2011, 19, 2306.
(9) Hengzhuang, W.; Ciofu, O.; Yang, L.; Wu, H.; Song, Z.;
Oliver, A.; Høiby, N. Antimicrob. Agents Chemother. 2013,
57, 196.
(10) Herzberg, O.; Moult, J. Science 1987, 236, 694.
(11) Nichol, K. A.; Zhanel, G. G.; Hoban, D. J. Antimicrob.
Agents Chemother. 2002, 46, 3261.
(12) Tipper, D. J. Rev. Infect. Dis. 1979, 1, 39.
(13) Staudinger, H. Justus Liebigs Ann. Chem. 1907, 356, 51.
(14) Islami, M. R.; Allen, A. D.; Vukovic, S.; Tidwell, T. T. Org.
Lett. 2011, 13, 494.
Synlett 2014, 25, 229–232
© Georg Thieme Verlag Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.