Synthesis of some novel indeno[1,2-b]quinoxalin spiro-β-lactam conjugates

Article abstract of DOI:10.1016/j.tet.2017.01.009

This article reports the synthesis of some new spiro-β-lactams bearing an indeno[1,2-b]quinoxaline ring system, prepared by a [2?+?2] cycloaddition of ketenes with imines derived from 11-H-indeno[1,2-b]quinoxalin-11-one. The structures of newly synthesized spiro-β-lactams 2a–i and 3a-i were characterized by FT-IR,¹H NMR,¹³C NMR, mass spectrometry and elemental analyses. The relative stereochemistry of spiro-β-lactams 2a and 3a was determined unequivocally by X-ray crystallographic studies.

Full text of DOI:10.1016/j.tet.2017.01.009

Accepted Manuscript
Synthesis of some novel indeno[1,2-b]quinoxalin spiro-β-lactam conjugates
Javad Ameri Rad, Aliasghar Jarrahpour, Cem Cüneyt Ersanlı, Zeliha Atioğlu, Mehmet
Akkurt, Edward Turos
PII:
S0040-4020(17)30009-1
10.1016/j.tet.2017.01.009
TET 28379
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 10 July 2016
Revised Date: 24 December 2016
Accepted Date: 5 January 2017
Please cite this article as: Rad JA, Jarrahpour A, Ersanlı CC, Atioğlu Z, Akkurt M, Turos E, Synthesis
of some novel indeno[1,2-b]quinoxalin spiro-β-lactam conjugates, Tetrahedron (2017), doi: 10.1016/
j.tet.2017.01.009.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Synthesis of some novel indeno[1,2-b]quinoxalin
Leave this area blank for abstract info.
spiro-β-lactam conjugates
Javad Ameri Rada, Aliasghar Jarrahpoura*, Cem Cüneyt Ersanlıb, Zeliha Atioğluc, Mehmet Akkurtd, Edward Turose
a Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71946-84795 Iran.
b Department of Physics, Faculty of Arts and Sciences, Sinop University, 57010 Sinop, Turkey,
C Ilke Education and Health Foundation, Cappadocia Vocational College, The Medical Imaging Techniques Program,
50420 Mustafapaşa, Ürgüp, Nevşehir, Turkey
d Department of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Turkey
e Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, CHE 205, Tampa, FL, USA

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Synthesis of some novel indeno[1,2-b]quinoxalin spiro-β-lactam conjugates
Javad Ameri Rada, Aliasghar Jarrahpoura*, Cem Cüneyt Ersanlıb, Zeliha Atioğluc, Mehmet Akkurtd,
Edward Turose
a Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71946-84795 Iran
b Department of Physics, Faculty of Arts and Sciences, Sinop University, 57010 Sinop, Turkey
c Ilke Education and Health Foundation, Cappadocia Vocational College, The Medical Imaging Techniques Program, 50420 Mustafapaşa, Ürgüp, Nevşehir,
Turkey
d
Department of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Turkey
e Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, CHE 205, Tampa, FL, USA
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
This article reports the synthesis of some new spiro-β-lactams bearing an indeno[1,2-
b]quinoxaline ring system, prepared by a [2+2] cycloaddition of ketenes with imines derived
from 11-H-indeno[1,2-b]quinoxalin-11-one. The structures of newly synthesized spiro-β-lactams
2a–i and 3a-i were characterized by FT-IR, 1H NMR, 13C NMR, mass spectrometry and
elemental analyses. The relative stereochemistry of spiro-β-lactams 2a and 3a was determined
unequivocally by X-ray crystallographic studies.
Available online
Keywords:
indeno[1,2-b]quinoxalin
Staudinger reaction
β-lactams
2009 Elsevier Ltd. All rights reserved
.
spiro
1. Introduction
intermediates to access α,α-disubstituted β-amino acids and
peptide derivatives.21
The four-membered 2-azetidinone ring, commonly known as
the β-lactam, is a privileged structural unit encountered in the
most widely used antibiotics that include penicillins,
cephalosporins, and carbapenems.1 To counter deadly pathogenic
microorganisms that have built up resistance against traditional
antibiotic drugs, researchers continue to explore new β-lactam
compounds with the objective of identifying variants having
improved antibacterial capabilities.2 In this respect, a variety of
different methods have been reported for the synthesis of 2-
azetidinones, including cyclization reactions, carbene insertion
Quinoxalines comprise another important class of heterocyclic
compounds also having a diverse range of biological activities
22
such as anti-hypertensive, anti-tubercular,23 convulsant,24 anti-
malarial,25 anti-anti-HIV,26 anti-depressant,27 anti-diabetic,28 anti-
inflammatory,29 antibacterial,30 antimicrobial,31 and anticancer.32
The quinoxaline derivatives brimonidine and varenicline have
been approved by the U.S. Food and Drug Administration for the
treatment of glaucoma.33 Tetracyclic indenoquinoxalines are also
important types of heterocycles containing quinoxaline.
Indenoquinoxalines are not only used as intermediates in the
synthesis of several types of spiro compounds such as spiro-
indenoquinoxaline pyrrolizidines, 34 and spiro-lactones,35 but also
as potent α-glucosidase inhibitor and antibacterial agents. 36
reactions,
rearrangement
of
heterocyclic
compounds,
Reformatsky reaction, Ugi-4CR/ cyclization and [2+2] ketene-
imine cycloaddition (Staudinger reaction).3-9 The classical
Staudinger reaction remains one of the most popular procedures
for the synthesis of β-lactam ring systems,10-12 including spiro-β-
lactams,13-14 which have shown a great variety of important
biological properties such as antimalarial activity,15 cholesterol
absorption inhibition,16 TRPV1 antagonism,17 T-type calcium
channel blocking,18 and as β-turn mimics.19 Jarrahpour et al have
recently synthesized spiro-β-lactams having potent antimalarial
capabilities.20 Spiro-β-lactams also serve as synthetic
To further capitalize on the unique properties of both β-
lactams and quinoxalines, we have expanded upon our work on
conjugated β-lactams37 towards the syntheses of some interesting
indenoquinoxaline-bearing spiro-β-lactams 2 and 3, depicted in
Scheme 1.

2
Tetrahedron
ACCEPTED MANUSCRIPT
Scheme 1. Synthesis of indeno[1,2-b]quinoxaline spiro-β-lactams 2a-i and 3a-i
2. Results and Discussion
2.1. Synthesis of novel spiro-β-lactams bearing the 2,11'-
indeno[1,2-b]quinoxalin moiety:
Spirocyclic indeno[1,2-b]quinoxaline β-lactams 2a-i and 3a-i
were synthesized by a modified Staudinger reaction between N-
phenyl-11H-indeno[1,2-b]quinoxalin-11-imine derivatives 1 and
various phenoxyacetic acid derivatives. The reactions were
carried out in the presence of triethylamine and tosyl chloride in
anhydrous CH2Cl2 at room temperature, in molar ratios of
1:1.5:5:1.5, respectively. Purification of the reaction mixture by
thick-layer silica gel chromatography confirmed the formation of
diastereomers, 2a-i and 3a-i, in equal amounts and in isolated
yields varying from 46-83%. The ratio of diastereomers 2 and 3
was determined by the integration of the proton H-3 of the β-
lactam rings in the 1H NMR spectrum.
X-ray crystallographic studies were done on diastereomers 2a
and 3a (Figures 1 and 2). All bond lengths and bond angles
appear to be normal and comparable with those reported for
related compounds.33-42 Intramolecular C-H…O hydrogen bonds
stabilize the molecular conformations of 2a and 3a. In the
crystals of both 2a and 3a exist evidence of C-H…π interactions,
and in 3a, additional O-H…N hydrogen bonds, forming a three-
dimensional structure. The IR spectra of 2a and 3a showed the
characteristic absorption of the β-lactam carbonyl at 1759 cm-1
and 1766 cm-1, respectively. The 1H NMR spectrum of 2a
exhibited the aryl methoxy protons as a singlet at 3.53 ppm, and
at 3.84 ppm for 3a. The β-lactam H-3 proton appeared to be
highly deshielded for 2a and 3a, appearing downfield at 6.13 and
6.24, respectively. The 13C NMR spectrum exhibited signals at
55.05 ppm and 55.07 ppm for the methyl carbon for 2a and 3a,
respectively, 68.87 ppm for the C-3 and 84.85 ppm for the C-4 in
2a, 86.89 ppm for the C-3 and 95.42 ppm for the C-4 in 3a, the
aromatic carbons at appropriate shifts, and the β-lactam carbonyl
carbon at 161.0 ppm and 161.3 for 2a and 3a, respectively. The
GC-MS analysis showed the expected parent ion at m/z 471 for
both diastereomers.
Figure 1. ORTEP diagram of diastereomer 2a.
The cycloaddition reaction between N-(4-methoxyphenyl)-
11H-indeno [1,2-b]quinoxalin-11-imine (1a) and phenoxyacetyl
chloride was then attempted in the presence of triethylamine in
anhydrous CH2Cl2 and toluene at different temperatures (Scheme
2). To investigate the diastereoselectivity of the cycloaddition
reaction under different reaction conditions, the same mixture
with the same ratios of reagents was treated at room temperature,
-10 °C or -83 °C in anhydrous CH2Cl2 or refluxed in toluene
Figure 2. ORTEP diagram of diastereomer 3a. A molecule of EtOH as a
crystallizing solvent was trapped in the crystal structure (top left quadrant).

3
ACCEPTED MANUSCRIPT
Ar1
N
N
O
H
O
N
N
H
O
Et3N
Cl
O
+
N
Ar1
N
N
Ar1
N
solvent
N
O
O
1a
Ar1: 4ꢀMeOC6H4
2a
3a
Scheme 2. Staudinger reaction of imine 1a with phenoxyacetyl chloride
(Table 1). The isolated yields of the two products were drastically
Then it was decided to evaluate the order of addition of the
diminished at lower temperature, or when toluene was used as
the solvent. It is noteworthy that the Staudinger reaction did not
reactants on the diastereoselectivity and overall yield of the
reaction of imine 1a with phenoxyacetic acid. Two conditions
were compared: the first was the dropwise addition of the acyl
chloride to the mixture of imine and triethylamine at -83 °C, and
the second was the same reaction at room temperature after
addition of reactants at -83 °C. Next the order of addition was
reversed and triethylamine was added dropwise to the mixture of
phenoxyacetyl chloride and imine under both sets of reaction
conditions. Although the diastereoselectivity of the cycloaddition
reaction using the carboxylic acid and tosyl chloride was similar
to that using the acid chloride, the former method proved to be
more efficient.
afford
any
cyclization
product
when
using
4-
methoxyphenylacetic acid, 4-hydroxyphenylacetic acid, 4-
biphenylacetic acid, phthaloyl glycine, or methoxyacetic acid as
the coupling partner with the imine.
Table 1. Different conditions for the reaction of imine 1 and
phenoxyacetic acid
Entry Solvent
Temperature °C
Yield
1
2
3
4
5
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
Toluene
rt
61%
Trace
Trace
15%
-10
-83
Reflux
rt
Using these preferred reaction conditions, we synthesized 18
spiro-β-lactam derivatives 2a-i and 3a-i (Table 2).
No reaction
Table 2. Structures of different diastereomeric spiro-β-lactam derivatives 2a–i and 3a-i.
Yielda
(2+3)
β-lactam
Structure
β-lactam
Structure
(%)
2a
61
3a
2b
64
3b

4
Tetrahedron
ACCEPTED MANUSCRIPT
2c
2d
2e
55
83
65
3c
3d
3e
2f
46
80
3f
2g
3g
2h
73
3h

5
ACCEPTED MANUSCRIPT
2i
50
3i
a Isolated yields.
The appropriate aromatic imine (N-phenyl-11H-indeno[1,2-
b]quinoxalin-11-imine) (1 mmol), triethylamine (5 mmol),
phenoxyacetic acid (1.5 mmol) and tosyl chloride (1.5 mmol)
were added to anhydrous CH2Cl2 (5 mL) and the mixture was
stirred at room temperature for 24 h (TLC control in a solvent
system n-hexane: ethyl acetate = 10:3). The mixture was washed
twice with 1N aqueous HCl solution (20 mL), and once with
saturated aqueous NaHCO3 solution (50 mL). The organic layer
was dried over anhydrous Na2SO4 and the solvent was removed
to yield the product as a crystal that was then purified by
recrystallization from ethanol. Diastereomers were purified by
silica gel chromatography.
3. Conclusion
In this study, a library of novel indeno[1,2-b]quinoxaline
spiro-β-lactams has been synthesized. These β-lactams were
prepared in good yields from N-phenyl-11H-indeno[1,2-
b]quinoxalin-11-imines and different phenoxyacetic acids in the
presence of triethylamine and p-toluenesulfonyl chloride. The
structures of cycloadducts 2a-i and 3a-i were established by IR,
1H NMR, 13C NMR, mass spectra and elemental analyses. The
three-dimensional structures of β-lactams 2a and 3a were
unambiguously determined by X-ray single crystal diffraction
analysis, as a means to assign relative stereochemistry. Efforts to
evaluate the potential biological properties of these new β-
lactams-quinoxaline hybrids are underway.
4. 2. 1: 1-(4-Methoxyphenyl)-3-phenoxyspiro[azetidine-2,11'-
indeno[1,2-b]quinoxalin]-4-one (2a):
4. Experimental Section
Yellow crystals; Mp. 220-222 ºC; IR (KBr, cm-1): 1759 (CO
1
4.1. General:
β-lactam),; H NMR (250 MHz, DMSO-d6): 3.53 (3H, s, CH3),
6.12 (1H, s, H-3), 6.42 (2H, d, J 7.75 Hz, ArH), 6.64-6.86 (5H,
m, ArH), 6.98 (2H, t, J 7.87 Hz, ArH), 7.50-7.67 (2H, m, ArH),
7.76-8.00 (3H, m, ArH), 8.12 (1H, dd, J 5.50, 1.75 Hz, ArH),
8.21 (2H, td, J 9.25, 1.50 Hz, ArH); 13C NMR (63 MHz, DMSO-
d6) δ 161.0 (CO β-lactam), 142.6, 141.0, 139.8, 139.0, 138.7,
137.1, 131.9, 131.3, 131.0, 130.0, 129.5, 129.3, 129.2, 126.7,
122.4, 122.1, 118.4, 118.2, 114.7, 114.4, 114.4, 109.6 (aromatic
carbons), 84.8 (C spiro β-lactam), 68.8 (C β-lactam), 55.0 (O-
CH3); GC-MS m/z = 471 [M+]; Analysis calculated for
C30H21N3O3: C, 76.42; H, 4.49; N, 8.91%. Found: C, 75.12; H,
5.04; N, 8.22%.
All needed chemicals were purchased from Merck, Fluka and
Acros chemical companies. and were used without further
purification, All reagents and solvents were dried prior to use
according to standard methods.43 IR spectra were run on a
Shimadzu FT-IR 8300 spectrophotometer using potassium
1
bromide pellets (ʋ in cm-1). H NMR and 13C NMR spectra were
recorded in dimethylsulfoxide-d6 (DMSO-d6) or chloroform-d
(CDCl3) using a Bruker Avance DPX instrument (1H NMR 250
MHz, 13C NMR 62.9 MHz). Chemical shifts were reported in
parts per million (δ) downfield from tetramethylsilane (TMS).
1
The coupling constants (J) are reported in Hertz (Hz). H NMR
splitting patterns are indicated as s: singlet, d: doublet, t: triplet,
q: quartet, m: multiplet, dd: doublet of doublet. 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 obtained on a Buchi 510
melting point apparatus. X-ray data were collected on a Bruker
APEX-II CCD diffractomer.
4. 2. 2: 1-(4-Methoxyphenyl)-3-phenoxyspiro[azetidine-2,11'-
indeno[1,2-b]quinoxalin]-4-one (3a):
White crystals; Mp. 180-181ºC; IR (KBr, cm-1): 1766 (CO β-
lactam); 1H NMR (250 MHz, DMSO-d6): 3.84 (3H, s, CH3), 6.52
(1H, s, H-3), 6.57 (2H, dd, J 7.75, 1.00 Hz, ArH), 6.88-7.05 (3H,
m, ArH), 7.08–7.22 (4H, m, ArH), 7.95–8.17 (4H, m, ArH),
8.28-8.57 (4H, m, ArH); 13C NMR (63 MHz, DMSO-d6) δ 161.3
(CO β-lactam), 155.5, 142.0, 141.7, 140.6, 138.9, 136.2, 132.8,
131.4, 130.9, 129.9, 129.4, 129.3, 128.8, 128.8, 124.9, 122.7,
122.0, 121.5, 118.5, 118.4, 114.7, 114.1 (aromatic carbons), 95.4
(C spiro β-lactam), 86.8 (C β-lactam), 55.0 (O-CH3); GC-MS m/z
= 471[M+]; Analysis calculated for C30H21N3O3: C, 76.42; H,
4.49; N, 8.91%. Found: C, 77.08; H, 4.58; N, 9.15%.
4.2. General procedure for preparation of Schiff bases 1a-d:
A
mixture of ninhydrin (5.00 mmol) and 1,2-
phenylenediamine (5.0 mmol) were combined in absolute ethanol
(20 mL) and then heated at reflux for 20 min to produce the
corresponding aromatic ketone (not isolated), and after cooling
the mixture to room temperature, the desired aniline derivative
(5.5 mmol) and 3 drops of glacial AcOH were added. The
reaction mixture was returned to reflux for several hours to
produce the imine derivatives 1a-d in high yield. The progress of
the reaction was monitored by thin-layer silica gel
chromatography (TLC). Evaporation of the solvent afforded the
crude imine as a solid, which was used for the next step without
further purification.
4. 2. 3: 3-(4-Chlorophenoxy)-1-(4-methoxyphenyl)spiro-
[azetidine-2,11'-indeno[1,2-b]quinoxalin]-4-one: (2b):
Yellow crystals; Mp. 200-201 ºC; IR (KBr, cm-1): 1759 (CO
1
β-lactam); H NMR (250 MHz, DMSO-d6): 3.52 (3H, s, CH3),
6.14 (1H, s, H-3), 6.48 (2H, d, J 7.50 Hz, ArH), 6.70 (2H, d, J
7.75 Hz, ArH), 6.79 (2H, d, J 8.75 Hz, ArH), 7.03 (2H, d, J 8.75
Hz, ArH), 7.52-7.65 (2H, m, ArH), 7.75-7.96 (3H, m, ArH),
8.07-8.27 (3H, m, ArH); 13C NMR (63 MHz, DMSO-d6) δ 160.7
(CO β-lactam), 156.3, 154.4, 141.0, 138.6, 137.1, 131.9, 131.3,
131.0, 131.0, 130.0, 129.4, 129.2, 129.2, 129.1, 129.1, 126.7,
4.3. General procedure for the preparation of spiro-β-lactams 2
and 3 by a modified Staudinger reaction:

6
Tetrahedron
122.5, 118.4, 116.4, 116.3, 114.7, 112.8 (aromatic carbons),
4. 2. 8: 3-Phenoxy-1-(p-tolyl)spiro[azetidine-2,11'-indeno[1,2-
ACCEPTED MANUSCRIPT
98.0 (C spiro β-lactam), 84.7 (C β-lactam), 55.0 (O-CH3); GC-
MS m/z = 507 [M+, 37Cl], 505 [M+, 35Cl]; Analysis calculated for
C30H20ClN3O3: C, 71.22; H, 3.98; N, 8.31%. Found: C, 72.05; H,
4.36; N, 8.57%.
b]quinoxalin]-4-one (3d):
Yellow crystals; Mp. 169-171ºC; IR (KBr, cm-1): 1766 (CO β-
lactam); H NMR (250 MHz, CDCl3): 2.06 (3H, s, CH3), 5.64
1
(1H, s, H-3), 5.84 (1H, s, ArH), 6.21-6.56 (2H, m, ArH), 6.61-
7.03 (6H, m, ArH), 7.34-7.85 (5H, m, ArH), 7.97-8.26 (3H, m,
ArH), 6.30 (2H, dd, J 7.50, 1.25 Hz, ArH), 6.63 (1H, d, J 7.50
Hz, ArH), 6.77-6.93 (6H, m, ArH), 7.54-7.72 (5H, m, ArH), 7.99
(1H, d, J 7.50 Hz, ArH), 8.06 (1H, d, J 7.50 Hz, ArH); 13C NMR
(63 MHz, CDCl3) δ 161.7 (CO β-lactam), 142.5, 137.1, 134.7,
132.4, 131.2, 130.5, 130.4, 130.3, 130.2, 129.8, 129.6, 129.5,
129.4, 129.2, 129.1, 129.0, 123.6, 123.2, 122.2, 117.5, 114.9,
114.7 (aromatic carbons), 88.3 (C spiro β-lactam), 77.1 (C β-
lactam), 20.8 (-CH3); GC-MS m/z = 455 [M+], Analysis
calculated for C30H21N3O2: C, 79.10; H, 4.65; N, 9.22%. Found:
C, 81.91; H, 5.02; N, 10.32%.
4.
2.
4:
3-(4-Chlorophenoxy)-1-(4-methoxyphenyl)-
spiro[azetidine-2,11'-indeno[1,2-b]quinoxalin]-4-one (3b):
White crystals; Mp. 210-212ºC; IR (KBr, cm-1): 1766 (CO β-
lactam); 1H NMR (250 MHz, DMSO-d6): 3.54 (3H, s, CH3), 6.16
(1H, s, H-3), 6.34 (2H, dd, J 7.00, 2.25 Hz, ArH), 6.50 (2H, dd, J
6.75, 2.25 Hz, ArH), 6.69-6.75 (5H, m, ArH), 6.78–6.85 (5H, m,
ArH), 6.95 (2H, dd, J 6.75, 2.25 Hz, ArH), 7.05 (2H, dd, J 7.00,
2.25 Hz, ArH); 13C NMR (63 MHz, DMSO-d6) δ 161.0 (CO β-
lactam),156.3, 156.2, 154.3, 132.8, 131.4, 131.4, 131.0, 129.4,
129.2, 129.1, 128.9, 128.7, 125.8, 124.9, 122.8, 118.5, 118.4,
116.3, 116.0, 114.7, 114.7 (aromatic carbons), 86.7 (C spiro β-
lactam), 68.7 (C β-lactam), 55.0 (O-CH3); GC-MS m/z = 507
[M+, 37Cl], 505 [M+, 35Cl]; Analysis calculated for C30H20ClN3O3:
C, 71.22; H, 3.98; N, 8.31%. Found: C, 70.65; H, 4.59; N, 8.61%.
4. 2. 9: 1-(3,4-Dimethoxyphenyl)-3-phenoxyspiro[azetidine-
2,11'-indeno[1,2-b]quinoxalin]-4-one (2e):
Yellow crystals; Mp. 170-171ºC; IR (KBr, cm-1): 1766 (CO β-
1
4. 2. 5: 3-(2,4-dichlorophenoxy)-1-(4-methoxyphenyl)spiro-
lactam); H NMR (250 MHz, CDCl3): 3.66 (6H, s, 2CH3), 5.93
[azetidine- 2,11'-indeno[1,2-b]quinoxalin]-4-one (2c):
(1H, s, H-3), 5.95-6.07 (1H, m, ArH), 6.34-6.55 (4H, m, ArH),
6.80 (1H, t, J 7.00 Hz, ArH), 6.99 (1H, t, J 7.75 Hz, ArH), 7.12
(1H, s, ArH), 7.55 (3H, t, J 6.50 Hz, ArH), 7.71-7.96 (4H, m,
ArH); 13C NMR (63 MHz, CDCl3) δ 166.8 (CO β-lactam), 134.2,
132.6, 131.8, 131.0, 130.8, 130.7, 129.9, 129.8, 129.7, 129.4,
128.2, 127.1, 125.3, 123.9, 122.6, 122.3, 119.9, 116.9, 115.0,
111.0, 108.6, 103.9, 102.8, 102.8 (aromatic carbons), 98.6 (C
spiro β-lactam), 85.5 (C β-lactam), 55.8 (O-CH3), 55.7 (O-CH3);
GC-MS m/z = 501 [M+], Analysis calculated for C31H23N3O4: C,
74.24; H, 4.62; N, 8.38%. Found: C, 73.61; H, 5.42; N, 9.83%.
White crystals; Decompose 250 ºC; IR (KBr, cm-1): 1766 (CO
1
β-lactam); H NMR (250 MHz, DMSO-d6): 3.51 (CH3, s, 3H),
6.27 (H-3, s, 1H), 6.47 (ArH, d, 1H, J =8.75), 6.65-6.76 (ArH, m,
2H), 6.79 (ArH, d, 2H, J=9.00), 6.98 (1H, dd, J 9.00, 2.50 Hz,
ArH), 7.39-7.69 (3H, m, ArH), 7.79-7.94 (3H, m, ArH), 8.07-
8.26 (3H, m, ArH); 13C NMR (63 MHz, DMSO-d6) δ 165.6 (CO
β-lactam), 156.3, 152.5, 142.7, 138.5, 137.1, 132.7, 131.9, 131.5,
131.4, 131.0, 130.0, 128.4, 129.4, 129.3, 129.2, 129.2, 128.6,
127.7, 126.6, 124.1, 122.4, 122.4, 118.5, 114.7 (aromatic
carbons), 84.8 (C spiro β-lactam), 55.0 (C β-lactam), 54.6 (O-
CH3); GC-MS m/z = 541 [M+, 37Cl], 539 [M+, 35Cl]; Analysis
calculated for C30H19Cl2N3O3: C, 66.68; H, 3.54; N, 7.78%.
Found: C, 67.54; H, 4.27; N, 8.54%.
4. 2. 10: 1-(3,4-Dimethoxyphenyl)-3-phenoxyspiro[azetidine-
2,11'-indeno[1,2-b]quinoxalin]-4-one (3e):
Yellow crystals; Mp. 175-177ºC; IR (KBr, cm-1): 1751 (CO β-
1
lactam); H NMR (250 MHz, CDCl3): 3.66 (3H, s, CH3), 3.67
4. 2. 6: 3-(2,4-Dichlorophenoxy)-1-(4-methoxyphenyl)spiro
[azetidine-2,11'-indeno[1,2-b]quinoxalin]-4-one (3c):
(3H, s, CH3), 5.07 (1H, s, H-3), 6.00 (1H, dd, J 8.5, 2.5 Hz, ArH),
6.40 (2H, t, J 8.25 Hz, ArH), 6.70 (1H, t, J 8.25 Hz, ArH), 6.89
(2H, t, J 8.00 Hz, ArH), 7.10-7.32 (2H, m, ArH), 7.61-7.83 (5H,
m, ArH), 7.99-8.21 (2H, m, ArH), 8.31 (1H, d, J 7.00 Hz, ArH);
13C NMR (63 MHz, CDCl3) δ 164.6 (CO β-lactam), 149.2, 146.3,
146.2, 142.7, 142.6, 141.6, 139.3, 132.4, 131.2, 130.8, 130.5,
130.2, 129.7, 129.4, 129.2, 129.0, 128.7, 123.7, 123.2, 122.2,
114.7, 111.0, 108.6, 102.9 (aromatic carbons), 88.2 (C spiro β-
lactam), 77.2 (C β-lactam), 55.8 (O-CH3), 55.7 (O-CH3); GC-MS
m/z = 501 [M+], Analysis calculated for C31H23N3O4: C, 74.24;
H, 4.62; N, 8.38%. Found: C, 75.83; H, 4.42; N, 8.91%.
Gray crystals; Mp. 178-180ºC; IR (KBr, cm-1): 1766 (CO β-
lactam); 1H NMR (250 MHz, DMSO-d6): 3.53 (3H, s, CH3), 6.30
(1H, s, H-3), 6.50 (1H, d, J 7.00 Hz, ArH), 6.72 (2H, dd, J 9.00,
1.75 Hz, ArH), 6.82 (2H, dd, J 9.00, 2.25 Hz, ArH), 6.98- 7.05
(1H, m, ArH), 7.53-7.68 (2H, m, ArH), 7.71-7.94 (4H, m, ArH),
8.11-8.24 (3H, m, ArH); 13C NMR (63 MHz, DMSO-d6) δ 161.4
(CO β-lactam), 158.4, 156.0, 153.4, 148.3, 148.3, 142.4, 141.0,
139.6, 136.6, 133.1, 131.8, 131.2, 130.3, 129.8, 129.7, 129.3,
129.3, 125.4, 132.1, 122.4, 119.1, 116.8, 114.5, 113.0, (aromatic
carbons), 87.1 (C spiro β-lactam), 69.3 (C β-lactam), 40.3 (O-
CH3); GC-MS m/z = 541 [M+, 37Cl], 539 [M+, 35Cl]; Analysis
calculated for C30H19Cl2N3O3: C, 66.68; H, 3.54; N, 7.78%.
Found: C, 67.59; H, 4.86; N, 8.73%.
4. 2. 11: 3-(4-Chlorophenoxy)-1-(p-tolyl)spiro[azetidine-2,11'-
indeno[1,2-b]quinoxalin]-4-one (2f):
Gray crystals; Mp. 290 decompose ºC; IR (KBr, cm-1): 1766
1
(CO β-lactam); H NMR (250 MHz, DMSO-d6): 2.05 (3H, s,
4. 2. 7: 3-Phenoxy-1-(p-tolyl)spiro[azetidine-2,11'-indeno
[1,2-b]quinoxalin]-4-one (2d):
CH3), 5.77 (1H, s, H-3), 6.32 (2H, d, J 9.00 Hz, ArH), 6.78 (2H,
d, J 6.25 Hz, ArH), 6.86 (2H, d, J 9.00 Hz, ArH), 7.38-7.56 (3H,
m, ArH), 7.62-7.80 (4H, m, ArH), 8.04 (1H, d, J 8.00 Hz, ArH),
8.14 (2H, d, J 7.75 Hz, ArH); 13C NMR (63 MHz, DMSO-d6) δ
162.9 (CO β-lactam), 155.9, 147.3, 142.6, 138.9, 137.6, 135.3,
131.8, 131.3, 131.2, 131.1, 130.9, 130.1, 129.3, 129.1, 127.5,
123.0, 123.0, 117.7, 114.7, 111.2, 104.3, 102.7, (aromatic
carbons), 91.0 (C spiro β-lactam), 73.6 (C β-lactam), 23.5 (-
CH3); GC-MS m/z = 491 [M+, 37Cl], 489 [M+, 35Cl], Analysis
calculated for C30H20ClN3O2: C, 73.54; H, 4.11; N, 8.58%.
Found: C, 74.93; H, 5.25; N, 9.12%.
White crystals; Mp. 258-260ºC; IR (KBr, cm-1): 1766 (CO β-
1
lactam); H NMR (250 MHz, CDCl3): 2.06 (3H, s, CH3), 4.15
(1H, s, H-3), 5.84 (1H, s, ArH), 6.21-6.56 (2H, m, ArH), 6.61-
7.03 (6H, m, ArH), 7.34-7.85 (5H, m, ArH), 7.97-8.26 (3H, m,
ArH); 13C-NMR (62 MHz, CDCl3) δ 163.0 (CO β-lactam), 153.2,
144.3, 131.8, 131.8, 131.0, 130.9, 130.8, 130.6, 130.0, 129.9,
129.7, 129.6, 129.5, 129.4, 129.3, 128.7, 127.0, 122.6, 122.3,
122.3, 117.4, 115.0 (aromatic carbons), 85.6 (C spiro β-lactam),
68.1 (C β-lactam), 29.6 (-CH3); GC-MS m/z = 455 [M+],
Analysis calculated for C30H21N3O2: C, 79.10; H, 4.65; N, 9.22%.
Found: C, 81.68; H, 4.92; N, 10.14%.
4. 2. 12: 3-(4-Chlorophenoxy)-1-(p-tolyl)spiro[azetidine-2,11'-
indeno[1,2-b]quinoxalin]-4-one (3f):

7
White crystals; 250 decompose ºC; IR (KBr, cm-1): 1766 (CO
β-lactam); H NMR (250 MHz, CDCl3): 1.54 (3H, s, CH3), 5.64
dd, J 7.50, 1.00 Hz, ArH), 6.67 (2H, d, J 7.00 Hz, ArH), 6.82-
ACCEPTED MANUSCRIPT
1
7.06 (6H, m, ArH), 7.59-7.86 (5H, m, ArH), 8.04-8.14 (2H, m,
ArH) 8.31 (1H, d, J 7.00 Hz, ArH); 13C NMR (63 MHz, CDCl3) δ
161.8 (CO β-lactam), 156.3, 154.4, 153.2, 145.6, 143.7, 142.6,
141.6, 137.1, 133.8, 132.4, 131.1, 130.4, 130.2, 129.4, 129.2,
129.0, 127.0, 123.7, 123.2, 122.2, 117.5, 114.8 (aromatic
carbons), 88.3 (C spiro β-lactam), 69.3 (C β-lactam), 33.4 (CH),
23.7 (CH3); GC-MS m/z = 483 [M+]; Analysis calculated for
C32H25N3O2: C, 79.48; H, 5.21; N, 8.69%. Found: C, 80.93; H,
5.27; N, 8.98%.
(1H, s, H-3), 6.32 (2H, d, J 7.25 Hz, ArH,), 7.19-7.30 (5H, m,
ArH), 7.57-7.92 (6H, m, ArH), 8.10 (2H, t, J 8.00 Hz, ArH), 8.31
(1H, t, J 7.00 Hz, ArH); 13C NMR (63 MHz, CDCl3) δ 162.0 (CO
β-lactam), 158.6, 157.1, 149.2, 146.8, 145.9, 140.5, 138.4, 137.0,
132.4, 131.3, 130.6, 129.6, 129.5, 129.2, 129.1, 123.3, 120.7,
120.1, 118.0, 117.5, 116.0, 101.8 (aromatic carbons), 88.2 (C
spiro β-lactam), 77.3 (C β-lactam), 20.8 (-CH3); GC-MS m/z =
491 [M+, 37Cl], 489 [M+, 35Cl], Analysis calculated for
C30H20ClN3O2: C, 73.54; H, 4.11; N, 8.58%. Found: C, 72.98; H,
4.35; N, 9.17%.
4. 2. 17: 3-(2,4-Dichlorophenoxy)-1-(4-isopropylphenyl)spiro
[azetidine-2,11'-indeno[1,2-b]quinoxalin]-4-one (2i):
4. 2. 13: 3-(4-Chlorophenoxy)-1-(4-isopropylphenyl)spiro
[azetidine-2,11'-indeno[1,2-b]quinoxalin]-4-one (2g):
White crystals; Mp. 158-160ºC; IR (KBr, cm-1): 1759 (CO β-
lactam); H NMR (250 MHz, CDCl3): 2.14 (6H, s, 2CH3), 2.60-
1
White crystals; Mp. 169-171ºC; IR (KBr, cm-1): 1766 (CO β-
2.77 (1H, m, CH), 5.85 (1H, s, H-3), 6.48 (1H, d, J 8.75 Hz,
ArH), 6.87-6.97 (5H, m, ArH), 7.24 (1H, s, ArH), 7.51-7.64 (2H,
m, ArH), 7.69-7.83 (2H, m, ArH), 7.92 (1H, dd, J 7.50, 1.25 Hz,
ArH), 8.21 (1H, dd, J 8.25, 1.75 Hz, ArH), 8.21 (2H, t, J 7.00 Hz,
ArH,); 13C NMR (63 MHz, CDCl3) δ 161.3 (CO β-lactam),151.1,
145.7, 142.2, 141.7, 139.3, 137.6, 133.7, 132.8, 131.8, 131.2,
130.7, 130.1, 129.8, 129.7, 129.4, 127.4, 127.1, 124.7, 124.0,
122.6, 117.5, 116.7, 115.5, 106.9 (aromatic carbons), 85.8 (C
spiro β-lactam), 77.21 (C β-lactam), 30.9 (CH), 23.7 (CH3); GC-
MS m/z = 553 [M+,37Cl], 551 [M+,35Cl];, Analysis calculated for
C32H23Cl2N3O2: C, 69.57; H, 4.20; N, 7.61%. Found: C, 70.83; H,
5.67; N, 8.91%.
1
lactam); H NMR (250 MHz, CDCl3): 1.07 (6H, d, J 7.00 Hz,
2CH3), 2.61-2.78 (1H, m, CH), 5.86 (1H, s, H-3), 6.41 (2H, dd, J
7.00, 2.25 Hz, ArH), 6.87-6.98 (6H, m, ArH), 7.45-7.62 (2H, m,
ArH), 7.72-7.81 (1H, m, ArH), 7.85 (2H, d, J 7.00 Hz, ArH,),
8.13 (1H, dd, J 8.25, 1.5 Hz, ArH), 8.22 (2H, d, J 7.75 Hz, ArH) ;
13C NMR (63 MHz, CDCl3) δ 161.6 (CO β-lactam), 155.0, 153.1,
145.7, 143.3, 141.7, 139.5, 137.6, 133.8, 131.8, 131.1, 130.7,
129.9, 129.7, 129.4, 129.3, 127.4, 127.1, 127.0, 127.0, 122.7,
117.5, 116.4 (aromatic carbons), 85.6 (C spiro β-lactam), 69.0 (C
β-lactam), 33.4 (CH), 23.7 (CH3); GC-MS m/z = 519 [M+,37Cl],
517 [M+,35Cl]; Analysis calculated for C32H24ClN3O2: C, 74.20;
H, 4.67; N, 8.11%. Found: C, 73.13; H, 4.73; N, 7.91%.
4. 2. 18: 3-(2,4-Dichlorophenoxy)-1-(4-isopropylphenyl) spiro
4. 2. 14. 3-(4-Chlorophenoxy)-1-(4-isopropylphenyl)spiro
[azetidine-2,11'-indeno[1,2-b]quinoxalin]-4-one (3i):
[azetidine-2,11'-indeno[1,2-b]quinoxalin]-4-one (3g):
Yellow crystals; Mp. 170-172ºC; IR (KBr, cm-1): 1766 (CO β-
lactam); H NMR (250 MHz, CDCl3): 2.14 (6H, s, 2CH3), 2.60-
Yellow crystals; Mp. 224-226ºC; IR (KBr, cm-1): 1751 (CO β-
1
1
lactam); H-NMR (250 MHz, CDCl3): 1.02 (3H, , s, CH3), 1.05
2.77 (1H, m, CH), 5.85 (1H, s, H-3), 6.48 (1H, d, J 8.75 Hz,
ArH), 6.87-6.97 (5H, m, ArH), 7.24 (1H, s, ArH), 7.51-7.64 (2H,
m, ArH), 7.69-7.83 (2H, m, ArH), 7.92 (1H, dd, J 7.50, 1.25 Hz,
ArH), 8.21 (1H, dd, J 8.25, 1.75 Hz, ArH), 8.21 (2H, t, J 7.00 Hz,
ArH); 13C NMR (63 MHz, CDCl3) δ 163.0 (CO β-lactam),157.3,
152.6, 144.9, 143.7, 140.1, 136.4, 136.1, 132.8, 129.8, 129.7,
129.3, 127.0, 126.7, 126.0, 123.2, 122.7, 120.9, 120.5, 120.4,
119.9, 119.8, 115.6, 108.1, 102.6 (aromatic carbons), 98.6 (C
spiro β-lactam), 80.33 (C β-lactam), 45.16 (CH), 27.31 (CH3);
GC-MS m/z = 553 [M+,37Cl], 551 [M+,35Cl];, Analysis calculated
for C32H23Cl2N3O2: C, 69.57; H, 4.20; N, 7.61%. Found: C,
69.51; H, 4.37; N, 8.50%.
(3H, s, CH3), 2.60-2.81(1H, m, CH), 5.62 (1H, s, H-3), 6.30 (2H,
d, J 6.75 Hz, ArH), 6.79-7.09 (6H, m, ArH), 7.22 (1H, s, ArH),
7.59-7.88 (5H, m, ArH), 8.09 (1H, t, J 8.25 Hz, ArH), 8.30 (1H,
d, J 7.00 Hz, ArH) ; 13C NMR (63 MHz, CDCl3) δ 161.3 (CO β-
lactam), 153.1, 145.7, 142.7, 137.1, 135.1, 133.7, 132.5, 131.3,
130.6, 130.2, 129.5, 129.2, 129.1, 129.0, 127.3, 127.1, 123.7,
123.6, 123.3, 117.5, 116.1, 105.4 (aromatic carbons), 88.2 (C
spiro β-lactam), 86.4 (C β-lactam), 33.5 (CH), 23.75 (CH3); GC-
MS m/z = 519 [M+,37Cl], 517 [M+,35Cl];, Analysis calculated for
C32H24ClN3O2: C, 74.20; H, 4.67; N, 8.11%. Found: C, 75.53; H,
5.78; N, 8.78%.
4. 2. 15: 1-(4-Isopropylphenyl)-3-phenoxyspiro[azetidine-
2,11'-indeno[1,2-b]quinoxalin]-4-one (2h):
Acknowledgements
Yellow crystals; Mp. 180-181 ºC; IR (KBr, cm-1): 1759 (CO
β-lactam); 1H NMR (250 MHz, CDCl3): 1.05-1.09 (6H, m,
2CH3), 2.64-2.76 (1H, m, CH), 5.92 (1H, s, H-3), 6.46 (2H, d, J
8.75 Hz, ArH); 6.79 (1H, d, J 7.75 Hz, ArH), 6.91-6.93 (4H, m,
ArH), 6.98 (2H, d, J 7.75 Hz, ArH), 7.46-7.61 (2H, m, ArH),
7.70-7.90 (3H, m, ArH), 8.11-8.25 (3H, m, ArH); 13C NMR (63
MHz, CDCl3) δ 160.0 (CO β-lactam), 156.7, 156.4, 153.2, 145.5,
144.5, 143.3, 141.7, 139.8, 139.8, 137.6, 133.9, 131.8, 130.9,
130.6, 129.9, 129.6, 129.3, 127.1, 122.6, 122.3, 117.5, 115.0
(aromatic carbons), 85.6 (C spiro β-lactam), 69.2 (C β-lactam),
33.4 (CH), 23.7 (CH3); GC-MS m/z = 483 [M+];, Analysis
calculated for C32H25N3O2: C, 79.48; H, 5.21; N, 8.69%. Found:
C, 77.93; H, 6.27; N, 9.18%.
The authors would like to thank the Shiraz University
Research Council for financial support (Grant No. 94-GR-SC-
23).
Conflict of interest
The authors declare that they have no conflict of interest.
References
1. Coulton, S.; Hunt, E. Recent Progress in the Chemical Synthesis
of Antibiotics and Related Microbial Products; Lukacs, G., Ed.;
Springer: Berlin, 1993; Vol. 2, p 621;
2. Page, M. I. The Chemistry of β-Lactams; Chapman and Hall:
London, 1992.
3. Singh, G. S.; D’hooghe, M.; De Kimpe, N. In Azetidines, Azetines
and Azetes: Monocyclic; Stevens, C. V., Ed.; Comprehensive
Heterocyclic Chemistry III; Elsevier: Oxford, UK, 2008; Vol. 2,
Chapter 2.01, p 1.
4. Walton, J. C. Top. Curr. Chem. 2006, 264, 163.
5. Magriotis, P. A. Angew. Chem, Int. Ed. 2001, 40, 4377.
4. 2. 16: 1-(4-Isopropylphenyl)-3-phenoxyspiro[azetidine-
2,11'-indeno[1,2-b]quinoxalin]-4-one (3h):
Yellow crystals; Mp. 190-191ºC; IR (KBr, cm-1): 1751 (CO β-
1
lactam); H NMR (250 MHz, CDCl3): 1.04 (3H, s, CH3), 1.07
(3H, s, CH3), 2.59-2.85 (1H, m, CH), 5.71 (1H, s, H-3), 6.37 (2H,

8
Tetrahedron
ACCEPTED MANUSCRIPT
6. Gomez-Gallego, M.; Mancheno, M. J.; Sierra, A. M. Tetrahedron
2000, 56, 5743.
7. Soengas, R. G.; Segade, Y.; Jimenez, C.; Rodríguez, J.
Tetrahedron 2011, 67, 2617.
8. Ghabraie, E.; Balalaie, S.; Mehrparvar, S.; Rominger, F. J. Org.
Chem. 2014, 17, 7926.
9. Ocampo, R.; Dolbier, J. W. R. Tetrahedron 2004, 60, 9325.
10. Zarei, M. Tetrahedron 2013, 12, 6620.
11. Jarrahpour, A. A.; Zarei, M. Tetrahedron Lett. 2007, 48, 8712.
12. Jarrahpour, A. A.; Zarei, M. Tetrahedron 2009, 65, 2927.
13. Jarrahpour, A.; Khalili, D. Tetrahedron Lett. 2007, 48, 7140.
14. Alcaide, B.; Almendros, P.; Del Campo, T. M.; Rodríguez-
Acebes, R. Adv. Synth. Catal. 2007, 349, 749.
15. Jarrahpour, A.; Ebrahimi, E.; Clercq, E. D.; Sinou, V.; Latour, C.;
Bouktab, L. D.; Brunel, J. M. Tetrahedron 2011, 67, 8699.
16. Wu, G.; Tormos, W. J. Org. Chem. 1997, 62, 6412.
17. Xiao, D.; Palani, A.; Aslanian, R.; McKittrick, B. A.; McPhail, A.
T.; Correll, C.; Phelps, P. T.; Anthens, J. C. Bioorg. Med. Chem.
2009, 19, 783.
18. Smith, E. M.; Sorota, S.; Kim, H. M.; McKittrick, B. A.; Nechuta,
T. L.; Bennett, C.; Knutson, C.; Burnett, D. A.; Kieselgof, J.; Tan,
Z.; Rindgen, D.; Bridal, T.; Zhou, X.; Jia, Y-P.; Dong, Z.; Mullins,
D.; Zhang, X.; Priestley, T.; Correll, C. C.; Tulshian, D.;
Czarniecki, M.; Greenlee, W. J. Bioorg. Med. Chem. Lett. 2010,
20, 4602.
19. Alonso, E.; López-Ortiz, F.; del Pozo, C.; Peralta, E.; Macías, A.;
González, J. J. Org. Chem. 2001, 66, 6333.
20. Jarrahpour, A.; Ebrahimi, E. Molecules 2010, 15, 515.
21. Alonso, E.; delPozo, C.; Gonzalez, J. Synlett. 2002, 1, 69.
22. Monge, A.; Palop, J. A.; Urbasos, I.; Fernández-Alvarez, E. J.
Heterocycl. Chem. 1989, 26, 1623.
23. Vicente, E.; Pérez-Silanes, S.; Lima, L. M.; Ancizu, S.; Burguete,
A.; Solano, B.; Villar, R.; Aldana, I.; Monge, A. Bioorg. Med.
Chem. Lett. 2009, 17, 385.
24. Wagle, S.; Adhikari, A. V.; Kumari, N. S. Eur. J. Med. Chem.
2009, 44, 1135.
25. Guillon, J.; Moreau, S.; Mouray, E.; Sinou, V.; Forfar, I.; Fabre, S.
B.; Desplat, V.; Millet, P.; Parzy, D.; Jarry, C.; Grellier, P. Bioorg.
Med. Chem. 2008, 16, 9133.
26. Kleim, J. P.; Bender, R.; Billhardt, U. M.; Meichsner, C.; Riess,
G.; Rösner, M.; Winkler, I.; Paessens, A. Antimicrob. Agents
Chemother. 1993, 37, 1659.
27. Becker, I. J. Heterocycl. Chem. 2008, 45, 1005.
28. Kulkarni, N. V.; Revankar, V. K.; Kirasur, B. N.; Hugar, M. H.
Med. Chem. Res. 2012, 21, 663.
29. Abouzid, K. A. M.; N. Khalil, A.; Ahmed, E. M.; AbdEl-Latif, H.
A.; El-Araby, M. E. Med. Chem. Res. 2010, 19, 629.
30. Nasir, W.; Munawar, M. A.; Ahmed, E.; Sharif, A.; Ahmed, S.;
Ayub, A.; Khan, M. A.; Nasim, F. H. Arch. Pharm. Res, 2011, 34,
1605.
31. Kurasawa, Y.; Kim, H. O. J. Heterocycl. Chem. 2002, 39, 551.
32. Amin, K. M.; Ismail, M. M. F.; Noaman, E.; Soliman, D. H.;
Ammar, Y. A. Bioorg. Med. Chem. 2006, 14, 6917.
33. Danylkova, N.; Alcala, S. R.; Pomeranz, H. D.; McLoon. L. K.;
Exp. Eye Res. 2007, 84, 293.
34. Shahrestani, N.; Salahi, F.; Tavakoli, N.; Jadidi, K.;
Hamzehloueian, M.; Notash, B. Tetrahedron: Asymmetry 2015,
26, 1117.
35. Maghsoodlou, M. T.; Habibi-Khorassani, S-M.; Moradi, A.;
Hazeri, N.; Davodi, A.; Sajadikhah, S-S. Tetrahedron 2011, 67,
8492.
36. Sahar Khan, M.; Munawar, M. A.; Ashraf, M.; Alam, U.; Ata, A.;
Asiri, A. M.; Kousar, S.; Khan, M. A. Bioorg. Med. Chem. 2014,
22, 1195.
37. Jarrahpour, A.; Nazari, M. Iran. J. Sci. Tech. Transaction A 2015,
39, 259.
38. Çelik, İ.; Akkurt, M.; Jarrahpour, A.; Ameri Rad, J.; Çelik, Ö.
Acta Cryst. 2015, E71, o184.
39. Çelik, İ.; Akkurt, M.; Jarrahpour, A.; Ameri Rad, J.; Çelik, Ö.
Acta Cryst. 2015, E71, o129.
40. Butcher, R. J.; Akkurt, M.; Jarrahpour, A.; Badrabady, S. A. T.
Acta Cryst. 2011, E67, o1101.
41. Atioğlu, Z.; Akkurt, M.; Jarrahpour, A.; Heiran, R.; Özdemir, N.;
Acta Cryst. 2014, E70, o835.
42. Jarrahpour, A.; Ebrahimi, E.; Khalifeh, R.; Sharghi, H.; Sahraei,
M.; Sinou, V.; Latour, C.; Brunel, J. M. Tetrahedron 2012, 68,
4740.
43. Amarego, W. L.; Chai, C. L. L. Purification of Laboratory
Chemicals, 5th Ed., Elsevier, New York, NY, USA, 2003.

ACCEPTED MANUSCRIPT