Ultrasound-Promoted Synthesis of Spirocyclopropanes from Switchable Starting Materials via Azomethine Ylide [3+2]-Cycloaddition

Article abstract of DOI:10.1055/a-1370-1884

An ultrasound-promoted green protocol to access a new series of spirocyclopropanes from indeno[1,2- b ]quinoxaline derivatives and azomethine ylides, generated in situ from the iodine-catalyzed reaction of acetophenones as well as of 2-methylquinoline with pyridine in the presence of a base, is described. These transformations proceed via a spirocyclopropanation reaction followed by elimination of pyridine. Clear evidence for the structure of a spirocyclopropane-linked indenoquinoxaline derivative was obtained from single-crystal X-ray analysis. The most important feature of this reaction is the fact it forms three stereogenic centers, one of which is quaternary, with excellent selectivity.

Full text of DOI:10.1055/a-1370-1884

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–J
paper
A
en
I. Yavari et al.
Paper
Synthesis
Ultrasound-Promoted Synthesis of Spirocyclopropanes from
Switchable Starting Materials via Azomethine Ylide [3+2]-Cyclo-
addition
Issa Yavari*a
Sara Sheikhia
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7
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2
O
Jamil Sheykhahmadia
Zohreh Taheria
Mohammad Reza Halvagarb
N
R2
O
R2
O
pyridine, I2, DIPEA
USI, 15–30 min
MeCN, r.t.
pyridine, I2, DIPEA
USI, 20–30 min
MeCN, r.t.
N
R1
N
R1
R1
O
O
75–92% yield
10 examples
N
62–88% yield
10 examples
N
N
N
N
a Department of Chemistry, Tarbiat Modares University,
PO Box 14115-175, Tehran, Iran
R3
R3
ds ≥19:1
R1 = OEt, Ph, 4-Br-C6H4, 4-Cl-C6H4, 4-Me-C6H4, 4-MeO-C6H4, 4-NO2-C6H4
R2 = H, Br, Cl; R3 = H, Me, Cl
R3
ds ≥19:1
yavarisa@modares.ac.ir
b Department of Inorganic Chemistry, Chemistry and Chemical
Engineering Research Center of Iran, PO Box 14335-186,
Tehran, Iran
• Efficient and Short Reactions • Easily Accessible Substrates • Remarkable Stereocontrol
• Operationally Simple
Corresponding Author
Received: 30.07.2020
Accepted after revision: 22.01.2021
Published online: 22.01.2021
development of efficient methods toward these privileged
skeletons.6 The construction of carbocyclic and heterocyclic
spiranes, besides the creation of chemical libraries of struc-
turally diverse compounds, plays a key role in combinatori-
al synthesis.7 Spirocyclic scaffolds have received much at-
tention due to their special conformational features and
their presence in bioactive natural products.8
Cyclopropanes are versatile building blocks in organic
synthesis that can be found in natural products, bioactive
agents, and functional materials.9 This saturated ring is a vi-
tal structural unit in some plants, fungi, and microorgan-
isms, mainly as a structural motif in terpenoids, fatty acid
metabolites, pheromones, and unusual amino acids.10 For
example, bioactive compounds such as milnacipran,11 spi-
rocyclopropane-1,3-oxindole A,12 and bis(spiropyrazolone)-
cyclopropane B13 contain a cyclopropane ring (Figure 1).
The construction of spirocyclopropanes has attracted inter-
est and synthetic protocols including Simmons–Smith-type
reactions, Michael-initiated ring closures, and metal-
catalyzed decomposition of diazoalkanes have been de-
scribed.9e,14
DOI: 10.1055/a-1370-1884; Art ID: ss-2020-n0215-op
Abstract An ultrasound-promoted green protocol to access a new
series of spirocyclopropanes from indeno[1,2-b]quinoxaline derivatives
and azomethine ylides, generated in situ from the iodine-catalyzed re-
action of acetophenones as well as of 2-methylquinoline with pyridine
in the presence of a base, is described. These transformations proceed
via a spirocyclopropanation reaction followed by elimination of pyri-
dine. Clear evidence for the structure of a spirocyclopropane-linked in-
denoquinoxaline derivative was obtained from single-crystal X-ray anal-
ysis. The most important feature of this reaction is the fact it forms
three stereogenic centers, one of which is quaternary, with excellent se-
lectivity.
Key words sonochemical synthesis, [3+2]-cycloaddition, spirocyclo-
propanes, azomethine ylides, iodine
Ultrasound-assisted synthesis is a clean, green, and ef-
fective technique in organic chemistry.1 The ultrasonic
waves cause chemical reactions in either homogeneous or
heterogeneous systems.2 The ultrasound irradiation leads
to the creation and implosive collapse of bubbles in a liquid
medium. The implosion of the bubble induces intense local
heating and high pressures, which promotes a range of
chemical reactions to occur.3 In comparison with tradition-
al methods, the ultrasound approach has important bene-
fits such as improved yields, enhancement of reaction rates,
increased selectivity, and lower costs through saving energy
and raw materials.4
EtO2C
O
Ph
H2N
Br
N
N
N
O
N
N
O
N
O
H
A
B
Milnacipran
antidepressant agent
NNRTIs HIV-1 inhibitor
AGE formation inhibitor
Figure 1 Cyclopropane- and spirocyclopropane-containing drugs and
bioactive compounds
The molecular hybridization of two or more bioactive
subunits in one molecular framework has been widely
studied as a preferred approach for the design of new
drugs.5 In this respect, much effort has been devoted to the
In continuation of our studies on cyclopropane synthe-
sis,15 we wish to report the reaction of acetophenones 3, as
well as of 2-methylquinoline (11), with indeno[1,2-b]-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–J
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
I. Yavari et al.
Paper
Synthesis
The cyclopropanation reactions of nitrogen ylides 5 and
12, prepared by iodine-mediated reaction of 4 with 3 and
11, respectively, were investigated (see Schemes 2 and 4).
Initially, to assess the feasibility of the reaction shown in
Table 1, we started our studies by testing the model reac-
tion between 3a, 4, and indenoquinoxaline 2a by evaluating
the effect of various catalysts, bases, and solvents. Thus, 3a
and 4 were allowed to react in MeCN at ambient tempera-
ture; then, 2a and N,N-diisopropylethylamine (DIPEA) were
added. In the presence of copper salts such as CuBr, CuI,
Cu(OAc)2, and CuSO4, the reactions were fruitless (Table 1,
entries 1–4). Also, Lewis acids, such as AlCl3 and BF3·OEt2,
did not catalyze the reaction (entries 5 and 6). When mo-
lecular iodine (100 mol%) was used as an oxidant (entry 7),
product 6a was obtained in 40% yield. Subsequently, vari-
ous bases, such as NaHCO3, K2CO3, Cs2CO3, Et3N, and DBU,
were examined (entries 8–12). All of these bases were prac-
tically fruitless, except Et3N, which afforded 6a in 28% yield.
Product 6a was obtained in 24% and 35% yield in CH2Cl2 and
DMF, respectively (entries 13 and 14).
O
O
O
R1
N
O
O
PPh3
R1
N
1
O
+
EtOH
5 min
USI, 25 min
R3
NH2
N
N
R3
2
R3
NH2
R1 = OEt, Ph, 4-Br-C6H4, 4-Cl-C6H4, 4-Me-C6H4, 4-MeO-C6H4
R3 = H, Me, Cl
Scheme 1 Synthesis of indeno[1,2-b]quinoxalines 2
quinoxaline derivatives 2. These iodine-mediated reactions
lead to the formation of spirocyclopropane-linked indeno-
quinoxalines 6 and 13, respectively. These transformations
were performed under ultrasonic irradiation (USI)4 to
achieve better yields in shorter reaction times.
To begin, we prepared indeno[1,2-b]quinoxalines 2 via
Wittig reaction of 11H-indeno[1,2-b]quinoxalin-11-one,
generated from ninhydrin and 1,2-diaminobenzenes, with
phosphorus ylides 1 (Scheme 1).
These results led us to search for a different and more
efficient procedure to improve the yield of product 6a.
Thus, we turned to USI as an alternate energy source. Con-
O
R1
O
O
N
R1
Ar
N
N
O
I2, DIPEA
O
R3
2
+
N
Ar
N
Ar
USI, r.t.
15–30 min
MeCN, r.t.
USI, 15 min
N
R3
3
4
5
6
EtO
EtO
O
O
O
O
O
O
N
O
N
O
O
O
N
N
N
N
N
N
N
N
Br
Br
Cl
6a, 83%
ds ≥19:1
6b, 88%
ds ≥19:1
6c, 69%
ds ≥19:1
6d, 78%
ds ≥19:1
6e, 73%
ds ≥19:1
MeO
Cl
Cl
O
O
O
O
O
O
N
O
N
O
N
O
N
O
N
N
N
N
N
N
Br
Cl
Br
Cl
6f, 81%
ds ≥19:1
6g, 76%
ds ≥19:1
6h, 71%
ds ≥19:1
6i, 67%
ds ≥19:1
6j, 62%
ds ≥19:1
Scheme 2 Iodine-mediated diastereoselective synthesis of spirocyclopropane-linked indenoquinoxaline derivatives 6 under USI. Reagents and condi-
tions: (i) 3 (1.1 mmol), 4 (2.2 mmol), I2 (1 mmol), MeCN (5 mL), 15 min; (ii) DIPEA (2 equiv), 2 (1.0 equiv), r.t., 15–30 min, under USI (40% amplitude).
Isolated yields; the diastereoselectivity (ds) was estimated by 1H NMR spectroscopic analysis of the reaction mixtures.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–J

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I. Yavari et al.
Paper
Synthesis
Table 1 Optimization of the Reaction Conditions for the Diastereoselective Formation of Spirocyclopropane Derivative 6aa
O
O
O
O
O
N
Ph
H
OEt
N
Ph
H
O
O
Ph
O
Ph
H
H
OEt
OEt
H
H
H
OEt
H
OEt
O
O
N
N
2a
O
N
N
cat., base
N
N
3a
N
N
N
N
4
not observed
5a
6a
8a
9a
10a
Entry
Catalyst
Base
Solvent
Ultrasonic (amplitude)
Time
Yield (%)b
Selectivityc
1
2
CuI
DIPEA
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
CH2Cl2
DMF
–
12 h
ND
ND
ND
ND
ND
ND
40
–
CuBr
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
Et3N
–
12 h
–
3
Cu(OAc)2
–
12 h
–
4
CuSO4
–
12 h
–
5
AlCl3
–
12 h
–
6
BF3·OEt2
–
12 h
–
7
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
–
12 h
–
8
–
12 h
28
–
9
NaHCO3
K2CO3
Cs2CO3
DBU
–
12 h
trace
trace
trace
trace
24
–
10
11
12
13
14
15
16
17
18
19
20
21
22
–
12 h
–
–
12 h
–
–
12 h
–
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
–
12 h
–
–
12 h
35
–
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
ultrasound (10%)
ultrasound (20%)
ultrasound (30%)
ultrasound (35%)
ultrasound (40%)
ultrasound (40%)
ultrasound (40%)
ultrasound (40%)
10 min
10 min
10 min
15 min
20 min
25 min
30 min
35 min
27
–
51
–
56
ds ≥19:1
ds ≥19:1
ds ≥19:1
ds ≥19:1
ds ≥19:1
ds ≥19:1
64
72
75
83
83
a Reaction conditions: (i) 3a (1 mmol), 4 (2 mmol), catalyst (1 mmol), solvent (5 mL); (ii) base (2 equiv), 2a (1.2 mmol).
b Yield of isolated product 6a; ND = not detected.
c The diastereoselectivity (ds) was estimated by 1H NMR spectroscopic analysis of the reaction mixtures.
sequently, the model reaction between 3a, 4, and 2a in
MeCN was repeated under USI with different amplitudes
and reaction times (Table 1). As shown in entry 21, product
6a was obtained in 83% yield using USI with an amplitude
of 40% in 30 minutes. Thus, the optimized reaction condi-
tions under USI are 40% amplitude, 100 mol% iodine, 2
equivalents of DIPEA in MeCN at room temperature for 30
minutes.
With the optimized conditions in hand, the scope of this
approach was investigated by using a number of precursors
2 and 3. As shown in Scheme 2, the reactivities of these pre-
cursors were almost the same and the reactions proceeded
smoothly, giving the spirocyclopropane derivatives 6 in
satisfactory yields. Using acetophenones having electron-
donating groups, such as methoxy or amino groups, failed
to give the corresponding spiranes 6.
The structures of products 6a–j were elucidated by IR,
1H NMR, and 13C NMR spectroscopic analysis. The mass
spectrum of 6a displayed the molecular ion peak at m/z =
420. The IR spectrum of 6a showed two strong absorption
bands at 1734 and 1632 cm–1 for the ester and ketone
groups, respectively. In the 1H NMR spectrum of spirane 6a,
the two vicinal protons of the cyclopropyl moiety displayed
two doublets at 3.94 and 4.71 ppm with coupling constant
3J = 7.9 Hz. The ethyl and aromatic protons showed charac-
teristic multiplets in appropriate regions of the spectrum.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–J

D
I. Yavari et al.
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Synthesis
The diastereoselective formation of spirocyclopropane
6a can be explained by a plausible mechanism depicted in
Scheme 3. The initial event is nucleophilic addition of nitro-
gen ylide 5a to the exocyclic C=C double bond of inde-
no[1,2-b]quinoxaline derivative 2a affording enolate 7a, fol-
lowed by cyclopropanation to generate 6a by anti-elimina-
tion of pyridine. The enolate moiety in 7a is prochiral (and
sp2) with a specific geometry that undergoes a facially se-
lective displacement. Hence, the high diastereocontrol in
the first step is partially responsible for the selective clo-
sure. As shown in Scheme 3, the nucleophilic attack of ylide
5a upon 2a may result in 7a as diastereoisomers I–IV.
Spirocyclopropane 6a can be formed from diastereoisomer
I. The diastereoisomeric products 8a, 9a, and 10a, which are
expected to form from diastereoisomers II, III, and IV, re-
spectively, could not be detected in the reaction mixture.
The transition states for cyclopropanation of diastereoiso-
mers II–IV may suffer from unfavorable steric interactions
(see Scheme 3).
Figure 2 X-ray crystal structure of compound 6a. Nitrogen atoms are
shown in blue and oxygen atoms in red.16
Recently, C–H functionalization reactions of 2-meth-
ylquinoline (11) and its reaction with various nucleophiles
have emerged as a useful tool in organic synthesis.17 In or-
der to extend the scope of the above spirocyclopropanation
reaction, we investigated the iodine-promoted reaction of
11 with 4 in the presence of 2, under USI conditions. As
shown in Scheme 4, spirocyclopropane-linked indenoqui-
noxalines 13a–j were prepared in the presence of iodine as
Lewis acid and DIPEA as Lewis base under USI. The struc-
The observation of 25 distinct resonances in the 1H-decou-
pled 13C NMR spectrum of 6a was in agreement with the
proposed structure. The NMR spectra of compounds 6b–j
were similar to those of 6a, except for the substituents,
which showed characteristic signals in the appropriate re-
gions of the spectra.
The stereochemical outcome of this spirocyclopropana-
tion reaction was also established by the X-ray crystal
structure of ethyl 2-benzoylspiro[cyclopropane-1,11′-inde-
no[1,2-b]quinoxaline]-3-carboxylate (6a), whose ORTEP
presentation is shown in Figure 2.16 The same structures
were assumed for the other derivatives on the basis of their
NMR spectroscopic similarities.
1
tures of compounds 13a–j were deduced from their IR, H
NMR, and 13C NMR spectroscopic data. The mass spectrum
of 13a displayed the molecular ion peak at m/z = 443. The
1H NMR spectrum of 13a exhibited two doublets at 4.72
and 3.95 ppm with the vicinal coupling constant 3J = 7.9 Hz
for protons attached to the cyclopropane ring. The alkyl and
aromatic protons appear as typical multiplets in the proper
O
Ph
COPh
H
N
CO2Et
H
N
H
OEt
H
CO2Et
O
N
- Py
O
+
N
N
N
Ph
N
N
5a
2a
6a
7a (Diastereoisomer I)
O
O
O
H
H
H
Ph
COPh
H
H
N
N
N
COPh
COPh
H
Ph
OEt
Ph
H
CO2Et
H
CO2Et
H
CO2Et
H
H
CO2Et
CO2Et
H
O
N
N
N
N
N
N
N
N
N
N
N
N
7a (Diastereoisomer II)
8a
7a (Diastereoisomer III)
9a
7a (Diastereoisomer IV)
10a
Scheme 3 Plausible mechanism for the diastereoselective formation of product 6a
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–J

E
I. Yavari et al.
Paper
Synthesis
O
R1
N
O
R1
N
N
N
R3
I2, DIPEA
2
+
N
N
MeCN, r.t.
USI, 15 min
USI, r.t.
15–30 min
R3
N
N
N
11
4
12
13
O
O
O
O
O
N
N
N
N
OEt
N
OEt
N
N
N
N
N
N
N
N
N
N
Cl
Cl
13a, 87%
ds ≥19:1
13b, 79%
ds ≥19:1
13c, 89%
ds ≥19:1
13d, 81%
ds ≥19:1
13e, 76%
ds ≥19:1
O
O
O
O
O
N
N
N
N
N
Br
NO2
Cl
N
N
OMe
N
N
N
N
N
N
N
N
13f, 91%
ds ≥19:1
13g, 92%
ds ≥19:1
13h, 89%
ds ≥19:1
13i, 92%
ds ≥19:1
13j, 75%
ds ≥19:1
Scheme 4 Iodine-mediated diastereoselective synthesis of spirocyclopropane-linked indenoquinoxaline derivatives 13 under USI. Reagents and condi-
tions: (i) 11 (1.1 mmol), 4 (2.2 mmol), I2 (1 mmol), MeCN (5 mL), 15 min; (ii) DIPEA (2 equiv), 2 (1.0 equiv), r.t., 15–30 min, under USI (40% amplitude).
Isolated yields; the diastereoselectivity (ds) was estimated by 1H NMR spectroscopic analysis of the reaction mixtures.
1
regions of the spectrum. The H-decoupled 13C NMR spec-
All reagents and solvents were commercially available and used as re-
ceived. Compounds 2 were prepared according to the literature.18 IR
trum of 13a showed 27 distinct signals, in agreement with
the proposed structure.
spectra were taken on an IR-460 Shimadzu spectrometer using KBr
pellets and are reported in cm–1 1H NMR (13C NMR) spectra were
.
In summary, in continuation of our studies on cyclopro-
pane synthesis and as an extension of earlier studies, we
developed a synthesis of novel cyclopropane derivatives
from azomethine ylides, prepared from iodine, pyridine,
and acetophenones as well as 2-methylquinoline. We used
USI as an alternate energy source, which led to the forma-
tion of products in higher yields in short reaction times
compared to the conventional method. This result illus-
trates the utility of ultrasound-promoted synthesis in or-
ganic chemistry. Structures of the new spirocyclopropanes
were determined by NMR analysis and the X-ray crystal
structure of compound 6a. The importance of spirocyclo-
propanes may render this protocol attractive for synthetic
and medicinal chemists. The carbocyclic spiranes reported
in this work may deserve further attention not only from a
synthetic but also from a pharmacological point of view.
The most important feature of this strategy is the fact it
forms three stereogenic centers, one of which is quaternary,
with remarkable selectivity.
measured in CDCl3 on a Bruker DRX 500 MHz spectrometer with
chemical shifts () given in ppm [s = singlet, d = doublet, t = triplet, m
= multiplet; coupling constants (Hz)]. Mass measurements were per-
formed using an Agilent instrument with the EI-MS technique. Ele-
mental analyses for C, H, and N were performed using a Heraeus
CHN-O-Rapid analyzer. Melting points: Electrothermal 9100 appara-
tus. The ultrasound-promoted reactions were performed using a Mis-
onix ultrasonic processor Model S-4000-010 with a maximum power
of 600 W, operating at an amplitude of 40% and a frequency of 20 kHz.
X-ray crystal structure data were collected on an STOE IPDS 2T dif-
fractometer using Mo K radiation (0.71073 Å) at 295 K. The struc-
ture was solved by direct methods using SHELXS-97 and the obtained
model refined with SHELXL-97. All non-hydrogen atoms were refined
anisotropically. Hydrogen atoms were added at ideal positions and
refined using a riding model.
Compounds 2; General Procedure
A mixture of ninhydrin (1 mmol) and o-phenylenediamine (1 mmol)
in EtOH (4 mL) was stirred at r.t. for 5 min. To this mixture was added
1-aryl-2-(triphenylphosphoranylidene)ethanone 1 (1.2 mmol) and
the contents were reacted under ultrasound irradiation (frequency =
20 kHz, amplitude = 40% of the maximum power output). The prog-
ress of the reaction was monitored by TLC. The reaction typically took
15–30 min. Upon completion, as monitored by TLC, the product 2 was
collected by filtration and washed with EtOH.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–J

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I. Yavari et al.
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Synthesis
Compounds 6a–j; General Procedure
(2 H, m, Ar), 7.68–7.74 (5 H, m, Ar), 7.83 (2 H, d, 3J = 7.8 Hz, Ar), 8.09 (1
3
H, d, J = 8.1 Hz, Ar), 8.14 (1 H, d, 3J = 8.1 Hz, Ar), 8.28–8.30 (1 H, m,
A mixture of acetophenone 3 (1.1 mmol), pyridine (0.174 g, 2.2
mmol), and I2 (0.253 g, 1 mmol) in MeCN (4 mL) was irradiated by an
ultrasonic probe sonicator (frequency = 20 kHz, amplitude = 40% of
the maximum power output) for 15 min. Then, DIPEA (0.258 g, 2
mmol) and a solution of 2 (1 mmol) in MeCN (1 mL) were added and
the reaction mixture was again sonicated for the required time frame
(15–30 min). Upon reaction completion (the progress of the reaction
was monitored by TLC), the solvent was removed under reduced pres-
sure. The crude residue was purified by column chromatography [sili-
ca gel (230–400 mesh, Merck); n-hexane/EtOAc, 5:1] to give product
6a–j.
Ar).
13C NMR (125.7 MHz, CDCl3):  = 38.8 (CH), 40.3 (CH), 42.8 (C), 122.5
(CH), 123.0 (CH), 128.1 (2 CH), 128.5 (2 CH), 128.6 (2 CH), 128.7 (2
CH), 128.8 (CH), 128.9 (CH), 129.0 (CH), 129.5 (CH), 129.7 (CH), 131.7
(CH), 133.3 (CH), 133.7 (CH), 136.6 (C), 136.8 (C), 137.4 (C), 141.2 (C),
142.1 (C), 142.2 (C), 152.9 (C=N), 156.4 (C=N), 191.0 (C=O), 192.8
(C=O).
MS: m/z (%) = 452 (M+, 35), 347 (100), 331 (50), 231 (17), 105 (99), 77
(69).
Anal. Calcd for C31H20N2O2 (452.51): C, 82.28; H, 4.46; N, 6.19. Found:
C, 82.39; H, 4.48; N, 6.21.
Ethyl 2-Benzoylspiro[cyclopropane-1,11′-indeno[1,2-b]quinoxal-
ine]-3-carboxylate (6a)
(2-Benzoylspiro[cyclopropane-1,11′-indeno[1,2-b]quinoxalin]-3-
yl)(4-bromophenyl)methanone (6d)
Yield: 348 mg (83%); colorless powder; mp 162–164 °C.
IR (KBr): 3065, 2924, 1734, 1632, 1265 cm–1
.
Yield: 414 mg (78%); colorless powder; mp 156–158 °C.
1H NMR (500 MHz, CDCl3):  = 1.21 (3 H, t, 3J = 7.1 Hz, Me), 3.94 (1 H,
IR (KBr): 3066, 2925, 1689, 1586, 1268 cm–1
.
3
3
d, J = 7.9 Hz, CH), 4.21 (2 H, q, J = 7.1 Hz, CH2), 4.71 (1 H, d, 3J = 7.9
Hz, CH), 7.30 (2 H, t, 3J = 7.9 Hz, Ar), 7.44–7.51 (4 H, m, Ar), 7.75–7.81
(4 H, m, Ar), 8.15 (1 H, d, 3J = 7.5 Hz, Ar), 8.22–8.25 (2 H, m, Ar).
1H NMR (500 MHz, CDCl3):  = 4.45 (1 H, d, 3J = 7.9 Hz, CH), 4.88 (1 H,
d, 3J = 7.9 Hz, CH), 7.32 (2 H, t, 3J = 7.7 Hz, Ar), 7.38 (2 H, d, 3J = 7.8 Hz,
Ar), 7.48 (1 H, t, 3J = 7.7 Hz, Ar), 7.56–7.59 (3 H, m, Ar), 7.68–7.75 (4 H,
m, Ar), 7.76 (2 H, d, 3J = 7.8 Hz, Ar), 8.07 (1 H, d, 3J = 8.0 Hz, Ar), 8.15 (1
H, d, 3J = 8.0 Hz, Ar), 8.28–8.29 (1 H, m, Ar).
13C NMR (125.7 MHz, CDCl3):  = 38.8 (CH), 40.0 (CH), 41.8 (C), 122.6
(CH), 125.3 (CH), 127.2 (CH), 127.4 (CH), 127.6 (C), 128.3 (CH), 128.4
(2 CH), 128.6 (3 CH), 128.8 (CH), 129.1 (CH), 129.5 (2 CH), 131.3 (C),
131.9 (2 CH), 132.4 (CH), 133.7 (C), 135.4 (C), 137.5 (C), 141.6 (C),
141.8 (C), 152.8 (C=N), 156.2 (C=N), 190.1 (C=O), 192.6 (C=O).
13C NMR (125.7 MHz, CDCl3):  = 14.1 (Me), 35.6 (CH), 39.2 (CH), 40.7
(C), 61.4 (CH2), 122.4 (CH), 123.0 (CH), 128.0 (C), 128.3 (2 CH), 128.5
(CH), 128.6 (2 CH), 129.0 (CH), 129.3 (CH), 129.4 (CH), 129.5 (CH),
131.4 (CH), 133.6 (CH), 136.7 (C), 137.2 (C), 141.2 (C), 142.3 (C), 153.3
(C=N), 157.1 (C=N), 166.6 (C=O), 192.2 (C=O).
MS: m/z (%) = 420 (M+, 35), 374 (9), 347 (50), 304 (16), 242 (43), 231
(47), 105 (100), 77 (66).
Anal. Calcd for C27H20N2O3 (420.47): C, 77.13; H, 4.79; N, 6.66. Found:
C, 77.38; H, 4.80; N, 6.68.
MS: m/z (%) = 531 (M+, 20), 533 (M+ + 2, 20), 450 (11), 427 (39), 347
(64), 319 (41), 242 (18), 182 (47), 155 (26), 105 (100), 77 (68).
Anal. Calcd for C31H19BrN2O2 (531.41): C, 70.07; H, 3.60; N, 5.27.
Found: C, 70.22; H, 3.61; N, 5.29.
Ethyl 2-(4-Bromobenzoyl)spiro[cyclopropane-1,11′-indeno[1,2-b]-
quinoxaline]-3-carboxylate (6b)
Yield: 439 mg (88%); colorless powder; mp 196–198 °C.
(2-Benzoylspiro[cyclopropane-1,11′-indeno[1,2-b]quinoxalin]-3-
yl)(4-chlorophenyl)methanone (6e)
IR (KBr): 3062, 2927, 1745, 1786, 1672, 1266, 1111 cm–1
1H NMR (500 MHz, CDCl3):  = 1.19 (3 H, t, 3J = 7.1 Hz, Me), 3.92 (1 H,
.
Yield: 355 mg (73%); colorless powder; mp 176–178 °C.
3
3
d, J = 7.8 Hz, CH), 4.21 (2 H, q, J = 7.1 Hz, CH2), 4.63 (1 H, d, 3J = 7.8
Hz, CH), 7.43–7.47 (4 H, m, Ar), 7.51 (1 H, t, 3J = 7.5 Hz, Ar), 7.62 (2 H,
d, 3J = 8.3 Hz, Ar), 7.78–7.82 (2 H, m, Ar), 8.14 (1 H, d, 3J = 8.0 Hz, Ar),
8.23–8.26 (2 H, m, Ar).
IR (KBr): 3058, 2923, 1686, 1672, 1585, 1223, 1011 cm–1
.
1H NMR (500 MHz, CDCl3):  = 4.51 (1 H, d, 3J = 8.2 Hz, CH), 4.91 (1 H,
d, 3J = 8.2, CH), 7.23 (2 H, t, 3J = 7.8 Hz, Ar), 7.28–7.32 (3 H, m, Ar), 7.38
(1 H, t, 3J = 7.5 Hz, Ar), 7.56–7.59 (2 H, m, Ar), 7.68 (1 H, d, 3J = 7.2 Hz,
Ar), 7.70–7.73 (3 H, m, Ar), 7.77 (2 H, d, 3J = 7.9 Hz, Ar), 8.09 (1 H, d, 3J
= 8.2 Hz, Ar), 8.14 (1 H, d, 3J = 8.1 Hz, Ar), 8.29 (1 H, d, 3J = 8.6 Hz, Ar).
13C NMR (125.7 MHz, CDCl3):  = 38.8 (CH), 40.4 (CH), 42.1 (C), 122.7
(CH), 123.0 (CH), 128.2 (2 CH), 128.6 (CH), 128.7 (2 CH), 129.0 (CH),
129.1 (3 CH), 129.2 (CH), 129.7 (CH), 129.8 (CH), 130.0 (2 CH), 131.8
(CH), 133.4 (C), 135.6 (C), 137.6 (C), 140.4 (C), 141.3 (C), 142.0 (C),
142.3 (C), 153.0 (C=N), 156.3 (C=N), 191.1 (C=O), 192.3 (C=O).
13C NMR (125.7 MHz, CDCl3):  = 14.3 (Me), 35.7 (CH), 39.2 (CH), 40.5
(C), 61.7 (CH2), 122.6 (CH), 123.0 (CH), 128.8 (CH), 129.2 (CH), 129.5
(CH), 129.6 (CH), 129.7 (CH), 129.9 (2 CH), 131.6 (CH), 132.1 (C),
132.2 (2 CH), 135.6 (C), 137.4 (C), 141.3 (C), 142.2 (C), 142.6 (C), 153.4
(C=N), 157.0 (C=N), 166.6 (C=O), 191.5 (C=O).
MS: m/z (%) = 499 (M+, 28), 501 (M+ + 2, 28), 454 (16), 427 (39), 315
(43), 242 (47), 183 (100), 155 (31).
Anal. Calcd for C27H19BrN2O3 (499.36): C, 64.94; H, 3.84; N, 5.61.
Found: C, 65.29; H, 3.86; N, 5.63.
MS: m/z (%) = 487 (M+, 15), 489 (M+ + 2, 5), 381 (39), 365 (27), 347
(64), 319 (41), 242 (38), 139 (76), 105 (100), 77 (48).
Anal. Calcd for C31H19ClN2O2 (486.96): C, 76.46; H, 3.93; N, 5.75.
Found: C, 76.72; H, 3.95; N, 5.77.
(Spiro[cyclopropane-1,11′-indeno[1,2-b]quinoxaline]-2,3-diyl)-
bis(phenylmethanone) (6c)
Yield: 312 mg (69%); colorless powder; mp 145–147 °C.
(2-(4-Bromobenzoyl)spiro[cyclopropane-1,11′-indeno[1,2-b]-
quinoxalin]-3-yl)(4-chlorophenyl)methanone (6f)
IR (KBr): 3060, 2923, 1675, 1595, 1224 cm–1
.
1H NMR (500 MHz, CDCl3):  = 4.53 (1 H, d, 3J = 8.0 Hz, CH), 4.98 (1 H,
d, 3J = 8.0 Hz, CH), 7.24 (2 H, t, 3J = 7.8 Hz, Ar), 7.32 (2 H, t, 3J = 7.8 Hz,
Ar), 7.38 (1 H, t, 3J = 7.8 Hz, Ar), 7.48 (1 H, t, 3J = 7.5 Hz, Ar), 7.56–7.58
Yield: 458 mg (81%); colorless powder; mp 189–191 °C.
IR (KBr): 3065, 2926, 1694, 1586, 1268 cm–1
.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–J

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I. Yavari et al.
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Synthesis
1H NMR (500 MHz, CDCl3):  = 4.45 (1 H, d, 3J = 7.8 Hz, CH), 4.88 (1 H,
d, 3J = 7.8 Hz, CH), 7.20 (1 H, d, 3J = 8.1 Hz, Ar), 7.45 (1 H, d, 3J = 8.2 Hz,
Ar), 7.55–7.58 (3 H, m, Ar), 7.63–7.69 (5 H, m, Ar), 7.73–7.75 (2 H, m,
(2-(4-Chlorobenzoyl)spiro[cyclopropane-1,11′-indeno[1,2-b]-
quinoxalin]-3-yl)(p-tolyl)methanone (6i)
Yield: 335 mg (67%); colorless powder; mp 151–153 °C.
3
Ar), 8.06 (1 H, d, J = 8.1 Hz, Ar), 8.14–8.16 (2 H, m, Ar), 8.32 (1 H, d,
IR (KBr): 2925, 1703, 1587, 1265 cm–1
.
3J = 8.3 Hz, Ar).
3
1H NMR (500 MHz, CDCl3):  = 2.21 (3 H, s, Me), 4.49 (1 H, d, J = 8.1
Hz, CH), 4.92 (1 H, d, 3J = 8.1 Hz, CH), 7.00 (2 H, d, 3J = 7.8 Hz, Ar), 7.27
(2 H, d, 3J = 8.1 Hz, Ar), 7.55–7.57 (2 H, m, Ar), 7.62 (2 H, d, 3J = 7.8 Hz,
13C NMR (125.7 MHz, CDCl3):  = 38.4 (CH), 39.8 (CH), 41.6 (C), 122.9
(CH), 123.0 (CH), 128.8 (2 CH), 129.0 (2 CH), 129.1 (CH), 129.4 (2 CH),
129.6 (CH), 129.7 (CH), 129.8 (CH), 130.2 (CH), 131.7 (CH), 131.8 (C),
132.0 (2 CH), 134.7 (C), 135.3 (C), 137.2 (C), 139.7 (C), 140.9 (C), 141.6
(C), 142.0 (C), 152.5 (C=N), 155.8 (C=N), 189.5 (C=O), 191.7 (C=O).
MS: m/z (%) = 566 (M+, 20), 568 (M+ + 2, 25), 570 (M+ + 4, 6), 427 (43),
409 (30), 381 (74), 318 (41), 242 (38), 185 (79), 139 (100), 111 (38),
76 (10).
3
Ar), 7.66–7.72 (3 H, m, Ar), 7.77 (2 H, d, J = 8.1 Hz, Ar), 8.09 (1 H, d,
3J = 7.6 Hz, Ar), 8.13 (1 H, d, 3J = 7.6 Hz, Ar), 8.28 (1 H, d, 3J = 8.1 Hz, Ar).
13C NMR (125.7 MHz, CDCl3):  = 21.6 (Me), 38.8 (CH), 40.5 (CH), 42.1
(C), 122.7 (CH), 123.1 (CH), 128.3 (2 CH), 128.7 (CH), 128.9 (CH),
129.1 (2 CH), 129.2 (CH), 129.4 (2 CH), 129.5 (CH), 129.6 (CH), 129.9
(CH), 130.0 (2 CH), 134.3 (C), 135.3 (C), 137.6 (C), 140.3 (C), 141.3 (C),
142.1 (C), 142.3 (C), 144.0 (C), 153.0 (C=N), 156.5 (C=N), 190.4 (C=O),
191.9 (C=O).
Anal. Calcd for C31H18BrClN2O2 (565.85): C, 65.80; H, 3.21; N, 4.95.
Found: C, 66.09; H, 3.22; N, 4.96.
MS: m/z (%) = 501 (M+, 8), 503 (M+ + 2, 3), 381 (46), 361 (74), 319 (58),
242 (21), 139 (78), 119 (100), 91 (67).
(Spiro[cyclopropane-1,11′-indeno[1,2-b]quinoxaline]-2,3-diyl)-
bis((4-chlorophenyl)methanone) (6g)
Anal. Calcd for C32H21ClN2O2 (500.98): C, 76.72; H, 4.23; N, 5.59.
Found: C, 76.98; H, 4.24; N, 5.61.
Yield: 396 mg (76%); colorless powder; mp 181–183 °C.
IR (KBr): 3056, 2924, 1655, 1582, 1268, 1089 cm–1
.
1H NMR (500 MHz, CDCl3):  = 4.45 (1 H, d, 3J = 9.2 Hz, CH), 4.87 (1 H,
(2-Benzoylspiro[cyclopropane-1,11′-indeno[1,2-b]quinoxalin]-3-
yl)(4-methoxyphenyl)methanone (6j)
d, 3J = 9.2 Hz, CH), 7.21 (2 H, d, 3J = 8.2 Hz, Ar), 7.31 (2 H, d, 3J = 8.2 Hz,
3
Ar), 7.44 (1 H, d, J = 8.3 Hz, Ar), 7.57–7.59 (2 H, m, Ar), 7.65 (2 H, d,
Yield: 299 mg (62%); colorless powder; mp 143–145 °C.
3J = 8.2 Hz, Ar), 7.69–7.70 (1 H, m, Ar), 7.76 (2 H, d, 3J = 8.2 Hz, Ar),
8.07 (2 H, m, Ar), 8.15 (1 H, d, 3J = 8.2 Hz, Ar), 8.28–8.30 (1 H, m, Ar).
IR (KBr): 3059, 2924, 1669, 1590, 1575, 1262, 1168 cm–1
.
1H NMR (500 MHz, CDCl3):  = 3.71 (3 H, s, MeO), 4.48 (1 H, d, 3J = 8.4
Hz, CH), 4.94 (1 H, d, 3J = 8.4 Hz, CH), 6.70 (2 H, d, 3J = 8.3 Hz, Ar), 6.78
(1 H, d, 3J = 8.4 Hz, Ar), 7.33 (2 H, t, 3J = 7.9 Hz, Ar), 7.47 (1 H, t, 3J = 7.7
13C NMR (125.7 MHz, CDCl3):  = 38.1 (CH), 40.7 (CH), 42.7 (C), 121.7
(CH), 122.6 (CH), 123.7 (CH), 125.5 (CH), 127.2 (CH), 128.2 (CH), 129.3
(2 CH), 129.5 (2 CH), 130.0 (2 CH), 130.4 (2 CH), 132.0 (CH), 132.3
(CH), 133.5 (C), 134.4 (C), 136.7 (C), 137.2 (C), 137.9 (C), 138.4 (C),
140.4 (C), 143.2 (C), 153.3 (C=N), 155.7 (C=N), 190.8 (C=O), 192.3
(C=O).
3
Hz, Ar), 7.57 (2 H, m, Ar), 7.68–7.73 (4 H, m, Ar), 7.83 (2 H, d, J = 7.6
Hz, Ar), 8.10 (1 H, d, 3J = 8.0 Hz, Ar), 8.15 (1 H, d, 3J = 8.1 Hz, Ar), 8.27–
8.30 (1 H, m, Ar).
13C NMR (125.7 MHz, CDCl3):  = 39.0 (CH), 40.5 (CH), 43.0 (C), 55.4
(MeO), 113.9 (2 CH), 122.7 (CH), 123.2 (CH), 128.3 (CH), 128.6 (2 CH),
128.8 (2 CH), 129.0 (CH), 129.6 (CH), 129.9 (CH), 130.5 (2 CH), 131.0
(CH), 131.9 (CH), 132.7 (C), 133.7 (CH), 136.5 (C), 137.5 (C), 140.1 (C),
141.0 (C), 142.1 (C), 163.6 (C=N), 164.8 (C=N), 167.5 (C), 191.2 (C=O),
192.8 (C=O).
MS: m/z (%) = 520 (M+, 40), 522 (M+ + 2, 25), 524 (M+ + 4, 4), 381 (43),
318 (21), 242 (38), 185 (79), 139 (100), 111 (49), 77 (5).
Anal. Calcd for C31H18Cl2N2O2 (521.40): C, 71.41; H, 3.48; N, 5.37.
Found: C, 71.80; H, 3.49; N, 5.39.
(2-(4-Bromobenzoyl)spiro[cyclopropane-1,11′-indeno[1,2-b]-
quinoxalin]-3-yl)(p-tolyl)methanone (6h)
MS: m/z (%) = 482 (M+, 8), 377 (88), 361 (35), 347 (76), 331 (49), 242
(18), 135 (100), 105 (91), 77 (39).
Yield: 387 mg (71%); colorless powder; mp 159–161 °C.
IR (KBr): 3038, 2922, 1671, 1606, 1583, 1224, 1008 cm–1
Anal. Calcd for C32H22N2O3 (482.54): C, 79.65; H, 4.60; N, 5.81. Found:
C, 79.86; H, 4.62; N, 5.83.
.
1H NMR (500 MHz, CDCl3):  = 2.19 (3 H, s, Me), 4.49 (1 H, d, J = 8.2
Hz, CH), 4.92 (1 H, d, 3J = 8.2 Hz, CH), 7.00 (2 H, d, 3J = 7.7 Hz, Ar), 7.09
(1 H, d, 3J = 7.8 Hz, Ar), 7.35 (1 H, d, 3J = 7.9 Hz, Ar), 7.42 (2 H, d, 3J = 7.7
Hz, Ar), 7.56–7.58 (2 H, m, Ar), 7.62 (2 H, d, 3J = 8.1 Hz, Ar), 7.68–7.71
3
Compounds 13a–j; General Procedure
A mixture of 2-methylquinoline (11; 0.157 g, 1.1 mmol), pyridine
(0.174 g, 2.2 mmol), and I2 (0.253 g, 1 mmol) in MeCN (4 mL) was son-
icated (frequency = 20 kHz, amplitude = 40% of the maximum power
output) for 15 min. Then, DIPEA (0.258 g, 2 mmol) and a solution of 2
(1 mmol) in MeCN (1 mL) were added and the reaction mixture was
subjected to ultrasound irradiation for the stipulated time frame (15–
30 min). Upon reaction completion (the progress of the reaction was
monitored by TLC), the solvent was removed under reduced pressure.
The crude residue was purified by column chromatography [silica gel
(230–400 mesh, Merck); n-hexane/EtOAc, 4:1] to give product 13a–j.
3
(3 H, m, Ar), 8.09 (1 H, d, 3J = 7.7 Hz, Ar), 8.12 (1 H, t, J = 7.7 Hz, Ar),
8.29 (1 H, d, 3J = 8.0 Hz, Ar).
13C NMR (125.7 MHz, CDCl3):  = 21.7 (Me), 38.8 (CH), 40.5 (CH), 42.1
(C), 122.7 (CH), 123.1 (CH), 128.4 (2 CH), 129.0 (CH), 129.1 (CH),
129.2 (CH), 129.4 (2 CH), 129.7 (CH), 129.9 (CH), 130.0 (2 CH), 131.9
(CH), 132.1 (C), 132.2 (2 CH), 134.3 (C), 135.7 (C), 137.6 (C), 141.3 (C),
142.1 (C), 142.3 (C), 144.4 (C), 153.0 (C=N), 156.5 (C=N), 190.5 (C=O),
192.1 (C=O).
MS: m/z (%) = 545 (M+, 14), 547 (M+ + 2, 14), 441 (23), 349 (30), 293
(28), 230 (23), 119 (48), 91 (100), 77 (44).
Ethyl 3-(Quinolin-2-yl)spiro[cyclopropane-1,11′-indeno[1,2-b]-
quinoxaline]-2-carboxylate (13a)
Anal. Calcd for C32H21BrN2O2 (545.44): C, 70.47; H, 3.88; N, 5.14.
Found: C, 70.69; H, 3.90; N, 5.16.
Yield: 385 mg (87%); colorless powder; mp 174–176 °C.
IR (KBr): 3025, 2925, 1729, 1681, 1585, 1570 cm–1
.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–J

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I. Yavari et al.
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Synthesis
1H NMR (500 MHz, CDCl3):  = 1.22 (3 H, t, 3J = 7.1 Hz, Me), 3.95 (1 H,
(7′-Chloro-2-(quinolin-2-yl)spiro[cyclopropane-1,11′-indeno-
[1,2-b]quinoxalin]-3-yl)(phenyl)methanone (13d)
d, J = 7.9 Hz, CH), 4.22 (2 H, q, J = 7.1 Hz, CH2), 4.72 (1 H, d, 3J = 7.9
Hz, CH), 7.28–7.33 (2 H, m, Ar), 7.45–7.52 (4 H, m, Ar), 7.66–7.69 (1 H,
m, Ar), 7.77–7.80 (3 H, m, Ar), 7.83 (1 H, t, 3J = 7.6 Hz, Ar), 8.16 (1 H, d,
3J = 8.0 Hz, Ar), 8.26–8.30 (2 H, m, Ar).
3
3
Yield: 413 mg (81%); colorless powder; mp 198–200 °C.
IR (KBr): 3051, 2935, 1683, 1586, 1570 cm–1
.
1H NMR (500 MHz, CDCl3):  = 4.76 (1 H, d, 3J = 8.2 Hz, CH), 5.19 (1 H,
d, 3J = 8.2 Hz, CH), 7.03 (1 H, d, 3J = 8.4 Hz, Ar), 7.08 (1 H, d, 3J = 8.4 Hz,
Ar), 7.26 (1 H, t, 3J = 7.7 Hz, Ar), 7.32 (2 H, t, 3J = 7.7 Hz, Ar), 7.45 (2 H,
d, 3J = 7.7 Hz, Ar), 7.48–7.53 (3 H, m, Ar), 7.71 (1 H, d, 3J = 8.2 Hz, Ar),
7.74–7.78 (2 H, m, Ar), 7.85 (1 H, s, Ar), 7.87 (1 H, d, 3J = 8.2 Hz, Ar),
8.01 (1 H, t, 3J = 8.4 Hz, Ar), 8.09 (1 H, d, 3J = 8.1 Hz, Ar), 8.23 (1 H, d,
3J = 8.1 Hz, Ar).
13C NMR (125.7 MHz, CDCl3):  = 40.9 (CH), 41.8 (CH), 42.9 (C), 122.7
(CH), 123.4 (CH), 127.3 (CH), 127.6 (CH), 127.7 (2 CH), 127.7 (CH),
127.8 (CH), 127.9 (CH), 128.1 (CH), 128.3 (C), 128.6 (2 CH), 128.8 (2
CH), 129.5 (CH), 130.4 (CH), 132.0 (CH), 133.6 (CH), 134.9 (C), 135.4
(C), 136.8 (C), 139.5 (C), 142.5 (C), 144.1 (C), 154.4 (C), 161.0 (C=N),
161.4 (C=N), 164.0 (C=N), 193.4 (C=O).
13C NMR (125.7 MHz, CDCl3):  = 14.1 (Me), 35.6 (CH), 39.2 (CH), 40.7
(C), 61.5 (CH2), 122.6 (CH), 123.1 (CH), 123.5 (CH), 128.0 (CH), 128.4
(2 CH), 128.6 (C), 128.6 (CH), 128.7 (2 CH), 129.1 (CH), 129.5 (CH),
129.6 (CH), 131.6 (CH), 133.7 (CH), 136.7 (C), 137.0 (C), 141.2 (C),
142.4 (C), 147.8 (C), 151.7 (C=N), 153.1 (C=N), 157.2 (C=N), 166.6
(C=O).
MS: m/z (%) = 443 (M+, 15), 398 (19), 315 (100), 242 (43), 128 (17), 73
(24).
Anal. Calcd for C29H21N3O2 (443.51): C, 78.54; H, 4.77; N, 9.47. Found:
C, 78.89; H, 4.76; N, 9.50.
Ethyl 7′-Chloro-3-(quinolin-2-yl)spiro[cyclopropane-1,11′-
indeno[1,2-b]quinoxaline]-2-carboxylate (13b)
MS: m/z (%) = 510 (M+, 21), 512 (M+ + 2, 7), 404 (89), 368 (41), 339
Yield: 377 mg (79%); colorless powder; mp 183–185 °C.
(62), 252 (37), 230 (19), 128 (24), 105 (100), 77 (68).
IR (KBr): 3028, 2925, 1732, 1683, 1589, 1571 cm–1
.
Anal. Calcd for C33H20ClN3O (509.99): C, 77.72; H, 3.95; N, 8.24.
Found: C, 77.98; H, 3.96; N, 8.27.
1H NMR (500 MHz, CDCl3):  = 1.24 (3 H, t, 3J = 7.1 Hz, Me), 4.27 (2 H,
3
3
q, J = 7.1 Hz, CH2), 4.37 (1 H, d, 3J = 8.1 Hz, CH), 4.54 (1 H, d, J = 8.1
Hz, CH), 7.32 (1 H, t, 3J = 7.8 Hz, Ar), 7.41 (1 H, t, 3J = 7.7 Hz, Ar), 7.58
(1 H, d, 3J = 7.7 Hz, Ar), 7.62 (1 H, d, 3J = 7.7 Hz, Ar), 7.67–7.69 (1 H, m,
(7′-Methyl-2-(quinolin-2-yl)spiro[cyclopropane-1,11′-indeno-
[1,2-b]quinoxalin]-3-yl)(phenyl)methanone (13e)
3
Ar), 7.74–7.78 (2 H, m, Ar), 7.86 (1 H, d, J = 7.5 Hz, Ar), 7.99 (1 H, d,
Yield: 372 mg (76%); colorless powder; mp 195–197 °C.
3J = 7.8 Hz, Ar), 8.05 (1 H, s, Ar), 8.07–8.09 (1 H, m, Ar), 8.10–8.12 (1 H,
m, Ar), 8.27 (1 H, d, 3J = 7.7 Hz, Ar).
IR (KBr): 3048, 2931, 1680, 1584, 1567 cm–1
.
3
1H NMR (500 MHz, CDCl3):  = 2.59 (3 H, s, Me), 4.76 (1 H, d, J = 8.2
Hz, CH), 4.95 (1 H, d, 3J = 8.2 Hz, CH), 7.21 (1 H, t, 3J = 7.7 Hz, Ar), 7.32
(2 H, t, 3J = 7.7 Hz, Ar), 7.49 (2 H, d, 3J = 7.7 Hz, Ar), 7.54–7.58 (2 H, m,
13C NMR (125.7 MHz, CDCl3):  = 14.3 (Me), 36.9 (CH), 40.7 (C), 40.9
(CH), 61.7 (CH2), 122.3 (CH), 122.7 (CH), 123.5 (CH), 123.9 (CH), 127.3
(CH), 127.6 (CH), 128.1 (C), 128.4 (CH), 128.6 (CH), 128.8 (CH), 129.4
(CH), 130.3 (CH), 131.9 (CH), 134.7 (C), 139.3 (CH), 142.4 (C), 143.9
(C), 146.3 (C), 149.3 (C), 154.2 (C), 157.7 (C=N), 158.8 (C=N), 160.3
(C=N), 170.9 (C=O).
3
Ar), 7.68 (1 H, d, J = 7.9 Hz, Ar), 7.72–7.78 (3 H, m, Ar), 7.85 (1 H, s,
3
Ar), 7.89–7.93 (2 H, m, Ar), 8.00 (1 H, d, J = 7.9 Hz, Ar), 8.04 (1 H, d,
3J = 8.0 Hz, Ar), 8.08 (1 H, d, 3J = 8.0 Hz, Ar), 8.21 (1 H, d, 3J = 8.0 Hz, Ar).
13C NMR (125.7 MHz, CDCl3):  = 22.1 (Me), 40.2 (CH), 41.1 (CH), 41.7
(C), 122.5 (CH), 123.4 (CH), 123.7 (CH), 124.7 (CH), 126.6 (CH), 127.5
(CH), 127.8 (C), 128.4 (CH), 128.6 (CH), 128.7 (CH), 129.0 (CH), 129.3
(2 CH), 131.0 (2 CH), 131.2 (CH), 132.4 (CH), 132.5 (CH), 136.7 (CH),
137.5 (C), 139.5 (C), 141.2 (C), 141.7 (C), 143.3 (C), 143.7 (C), 148.5
(C), 156.9 (C=N), 158.4 (C=N), 161.4 (C=N), 190.2 (C=O).
MS: m/z (%) = 478 (M+, 19), 480 (M+ + 2, 6), 431 (20), 404 (100), 369
(21), 315 (100), 266 (33), 128 (19), 105 (72), 77 (34), 29 (16).
Anal. Calcd for C29H20ClN3O2 (477.95): C, 72.88; H, 4.22; N, 8.79.
Found: C, 73.11; H, 4.21; N, 8.82.
Phenyl(2-(quinolin-2-yl)spiro[cyclopropane-1,11′-indeno[1,2-b]-
quinoxalin]-3-yl)methanone (13c)
MS: m/z (%) = 489 (M+, 7), 384 (100), 368 (41), 246 (79), 218 (49), 128
(12), 105 (98), 77 (45).
Yield: 423 mg (89%); colorless powder; mp 191–193 °C.
Anal. Calcd for C34H23N3O (489.58): C, 83.41; H, 4.74; N, 8.58. Found:
C, 83.63; H, 4.75; N, 8.62.
IR (KBr): 3049, 2937, 1681, 1589, 1569 cm–1
.
1H NMR (500 MHz, CDCl3):  = 4.68 (1 H, d, 3J = 8.2 Hz, CH), 4.74 (1 H,
d, 3J = 8.2 Hz, CH), 7.54–7.60 (6 H, m, Ar), 7.69 (2 H, d, 3J = 8.5 Hz, Ar),
7.77 (1 H, t, 3J = 8.4 Hz, Ar), 7.85 (1 H, d, 3J = 8.2 Hz, Ar), 7.94–7.98 (2 H,
m, Ar), 8.11–8.18 (5 H, m, Ar), 8.19–8.24 (2 H, m, Ar).
(4-Chlorophenyl)(2-(quinolin-2-yl)spiro[cyclopropane-1,11′-
indeno[1,2-b]quinoxalin]-3-yl)methanone (13f)
Yield: 464 mg (91%); colorless powder; mp 203–205 °C.
13C NMR (125.7 MHz, CDCl3):  = 39.5 (CH), 40.1 (CH), 41.4 (C), 122.8
(CH), 123.6 (CH), 127.2 (CH), 128.3 (CH), 128.7 (CH), 129.1 (CH), 129.2
(CH), 129.5 (2 CH), 129.6 (2 CH), 129.7 (CH), 130.1 (CH), 130.2 (CH),
130.4 (CH), 130.9 (CH), 132.4 (CH), 134.0 (CH), 134.5 (CH), 136.9 (C),
137.2 (C), 140.9 (C), 141.7 (C), 142.0 (C), 142.4 (C), 149.8 (C), 153.0
(C=N), 153.7 (C=N), 157.1 (C=N), 191.8 (C=O).
IR (KBr): 3058, 2924, 1682, 1588, 1571 cm–1
.
1H NMR (500 MHz, CDCl3):  = 4.77 (1 H, d, 3J = 8.2 Hz, CH), 4.95 (1 H,
d, 3J = 8.2 Hz, CH), 7.23 (2 H, d, 3J = 8.3 Hz, Ar), 7.32 (1 H, t, 3J = 8.2 Hz,
Ar), 7.45 (1 H, t, 3J = 7.6 Hz, Ar), 7.52–7.54 (1 H, m, Ar), 7.59 (1 H, t, 3J =
7.6 Hz, Ar), 7.67–7.70 (3 H, m, Ar), 7.78 (2 H, d, 3J = 8.3 Hz, Ar), 7.80–
7.82 (2 H, m, Ar), 8.03–8.07 (2 H, m, Ar), 8.13 (1 H, d, J = 8.1 Hz, Ar),
8.25–8.27 (2 H, m, Ar).
13C NMR (125.7 MHz, CDCl3):  = 40.5 (CH), 41.0 (CH), 42.3 (C), 122.5
(CH), 123.4 (CH), 123.6 (CH), 126.7 (CH), 127.5 (C), 127.8 (CH), 128.1
(CH), 128.9 (CH), 129.0 (2 CH), 129.1 (CH), 129.2 (CH), 129.7 (CH),
3
MS: m/z (%) = 475 (M+, 12), 381 (45), 370 (100), 293 (7), 216 (10), 139
(73), 128 (12), 111 (20), 77 (18).
Anal. Calcd for C33H21N3O (475.55): C, 83.35; H, 4.45; N, 8.84. Found:
C, 83.51; H, 4.47; N, 8.86.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–J

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129.8 (2 CH), 130.0 (CH), 131.2 (CH), 132.3 (CH), 135.6 (C), 136.7
(CH), 139.1 (C), 139.6 (C), 140.3 (C), 141.3 (C), 142.1 (C), 147.4 (C),
154.4 (C=N), 156.7 (C=N), 157.4 (C=N), 191.3 (C=O).
MS: m/z (%) = 510 (M+, 19), 512 (M+ + 2, 6), 445 (16), 370 (100), 291
1H NMR (500 MHz, CDCl3):  = 3.71 (3 H, s, MeO), 4.79 (1 H, d, 3J = 7.8
Hz, CH), 4.95 (1 H, d, 3J = 8.2 Hz, CH), 6.76 (2 H, d, 3J = 8.1 Hz, Ar), 7.25
(1 H, t, 3J = 8.1 Hz, Ar), 7.41 (1 H, t, 3J = 7.9 Hz, Ar), 7.48–7.52 (3 H, m,
Ar), 7.59–7.62 (1 H, m, Ar), 7.65 (1 H, d, 3J = 7.9 Hz, Ar), 7.69 (1 H, t, 3J =
7.9 Hz, Ar), 7.77 (1 H, d, J = 7.9 Hz, Ar), 7.80 (1 H, d, J = 7.9 Hz, Ar),
7.85 (2 H, d, 3J = 7.8 Hz, Ar), 8.00 (1 H, d, 3J = 8.1 Hz, Ar), 8.07–8.11 (2
H, m, Ar), 8.24 (1 H, d, 3J = 8.1 Hz, Ar).
13C NMR (125.7 MHz, CDCl3):  = 40.8 (CH), 41.3 (CH), 41.7 (C), 55.5
(MeO), 114.0 (2 CH), 122.4 (CH), 123.3 (CH), 126.6 (CH), 127.6 (CH),
127.8 (CH), 128.1 (C), 128.7 (CH), 129.1 (2 CH), 129.2 (CH), 129.3
(CH), 129.4 (CH), 129.8 (CH), 130.6 (CH), 131.0 (2 CH), 131.2 (C),
131.7 (CH), 136.6 (C), 141.1 (C), 142.0 (C), 144.1 (C), 147.6 (C), 153.7
(C=N), 154.9 (C=N), 158.0 (C=N), 163.9 (C), 193.0 (C=O).
3
3
(7), 241 (10), 185 (10), 139 (71), 128 (9), 111 (19), 77 (14).
Anal. Calcd for C33H20ClN3O (509.99): C, 77.72; H, 3.95; N, 8.24.
Found: C, 77.56; H, 3.97; N, 8.23.
(4-Bromophenyl)(2-(quinolin-2-yl)spiro[cyclopropane-1,11′-
indeno[1,2-b]quinoxalin]-3-yl)methanone (13g)
Yield: 510 mg (92%); colorless powder; mp 221–223 °C.
IR (KBr): 3060, 2927, 1685, 1589, 1574 cm–1
.
1H NMR (500 MHz, CDCl3):  = 4.77 (1 H, d, 3J = 8.2 Hz, CH), 4.95 (1 H,
d, 3J = 8.2 Hz, CH), 7.26 (1 H, d, 3J = 7.7 Hz, Ar), 7.32 (1 H, d, 3J = 8.4 Hz,
Ar), 7.41 (2 H, d, 3J = 8.3 Hz, Ar), 7.45 (1 H, t, 3J = 7.5 Hz, Ar), 7.51 (1 H,
d, J = 7.8 Hz, Ar), 7.59 (1 H, t, J = 7.5 Hz, Ar), 7.68–7.72 (4 H, m, Ar),
7.81–7.84 (2 H, m, Ar), 8.04–8.07 (2 H, m, Ar), 8.15 (1 H, d, 3J = 7.7 Hz,
Ar), 8.26–8.28 (2 H, m, Ar).
13C NMR (125.7 MHz, CDCl3):  = 40.3 (CH), 40.7 (CH), 42.5 (C), 122.3
(CH), 123.2 (CH), 123.5 (CH), 126.6 (CH), 127.7 (CH), 128.0 (CH), 128.4
(C), 128.8 (CH), 129.0 (CH), 129.1 (2 CH), 129.5 (CH), 129.7 (2 CH),
129.8 (CH), 131.1 (CH), 131.8 (2 CH), 132.2 (C), 135.9 (CH), 136.6 (C),
137.5 (C), 141.1 (C), 142.0 (C), 143.3 (C), 150.6 (C), 153.1 (C=N), 154.0
(C=N), 157.8 (C=N), 191.4 (C=O).
MS: m/z (%) = 505 (M+, 7), 370 (46), 242 (5), 218 (9), 135 (100), 128
(17), 91 (35), 77 (82).
Anal. Calcd for C34H23N3O2 (505.58): C, 80.77; H, 4.59; N, 8.31. Found:
C, 80.53; H, 4.60; N, 8.34.
3
3
(4-Nitrophenyl)(2-(quinolin-2-yl)spiro[cyclopropane-1,11′-
indeno[1,2-b]quinoxalin]-3-yl)methanone (13j)
Yield: 390 mg (75%); colorless powder; mp 229–231 °C.
IR (KBr): 3058, 2923, 1681, 1584, 1572 cm–1
.
1H NMR (500 MHz, CDCl3):  = 4.75 (1 H, d, 3J = 8.1 Hz, CH), 4.98 (1 H,
d, 3J = 8.1 Hz, CH), 7.26 (1 H, t, 3J = 8.0 Hz, Ar), 7.31 (1 H, d, 3J = 8.2 Hz,
Ar), 7.43–7.47 (2 H, m, Ar), 7.50 (1 H, t, 3J = 8.0 Hz, Ar), 7.58 (1 H, t, 3J =
MS: m/z (%) = 554 (M+, 21), 556 (M+ + 2, 21), 474 (28), 425 (32), 370
(100), 242 (16), 182 (34), 77 (54).
3
7.2 Hz, Ar), 7.65–7.70 (2 H, m, Ar), 7.82 (1 H, d, J = 7.2 Hz, Ar), 7.99–
3
8.01 (2 H, m, Ar), 8.05 (1 H, d, J = 8.2 Hz, Ar), 8.09–8.12 (3 H, m, Ar),
Anal. Calcd for C33H20BrN3O (554.45): C, 71.49; H, 3.64; N, 7.58.
Found: C, 71.61; H, 3.65; N, 7.59.
8.24–8.29 (3 H, m, Ar).
13C NMR (125.7 MHz, CDCl3):  = 40.6 (CH), 40.9 (CH), 42.8 (C), 122.6
(CH), 123.4 (CH), 123.5 (CH), 123.8 (CH), 123.9 (2 CH), 126.9 (CH),
127.6 (C), 127.9 (CH), 128.4 (CH), 129.1 (CH), 129.3 (2 CH), 129.5
(CH), 129.8 (CH), 130.0 (CH), 130.1 (CH), 131.3 (CH), 136.9 (CH), 137.7
(C), 138.1 (C), 141.1 (C), 141.7 (C), 142.2 (C), 143.2 (C), 150.3 (C),
153.2 (C=N), 154.0 (C=N), 157.7 (C=N), 191.5 (C=O).
(2-(Quinolin-2-yl)spiro[cyclopropane-1,11′-indeno[1,2-b]quinox-
alin]-3-yl)(p-tolyl)methanone (13h)
Yield: 435 mg (89%); colorless powder; mp 199–201 °C.
IR (KBr): 3060, 2927, 1680, 1588, 1572 cm–1
.
1H NMR (500 MHz, CDCl3):  = 2.26 (3 H, s, Me), 4.80 (1 H, d, 3J = 8.2
Hz, CH), 4.97 (1 H, d, 3J = 8.2 Hz, CH), 7.01 (1 H, d, 3J = 8.0 Hz, Ar), 7.09
(1 H, d, 3J = 8.0 Hz, Ar), 7.30 (1 H, d, 3J = 7.9 Hz, Ar), 7.41 (1 H, t, 3J = 7.9
Hz, Ar), 7.43–7.47 (2 H, m, Ar), 7.51 (1 H, t, 3J = 7.9 Hz, Ar), 7.52–7.56
(2 H, m, Ar), 7.59 (1 H, d, 3J = 7.9 Hz, Ar), 7.61–7.65 (2 H, m, Ar), 7.72 (2
H, d, 3J = 7.6 Hz, Ar), 7.75 (2 H, d, 3J = 7.6 Hz, Ar), 8.09 (1 H, d, 3J = 8.0
Hz, Ar), 8.24 (1 H, d, 3J = 8.0 Hz, Ar).
13C NMR (125.7 MHz, CDCl3):  = 21.7 (Me), 40.6 (CH), 41.4 (CH), 42.8
(C), 122.4 (CH), 123.3 (CH), 124.8 (CH), 126.6 (CH), 127.6 (CH), 127.8
(C), 128.1 (CH), 128.5 (CH), 128.7 (2 CH), 129.1 (CH), 129.2 (CH),
129.3 (2 CH), 129.4 (CH), 129.5 (CH), 129.8 (2 CH), 131.2 (C), 131.7
(CH), 132.6 (C), 136.6 (C), 141.1 (C), 142.1 (C), 143.9 (C), 147.5 (C),
153.7 (C=N), 154.8 (C=N), 158.0 (C=N), 193.0 (C=O).
MS: m/z (%) = 520 (M+, 8), 370 (100), 242 (5), 218 (69), 182 (21), 150
(44), 128 (37), 105 (39), 91 (23), 77 (32).
Anal. Calcd for C33H20N4O3 (520.55): C, 76.14; H, 3.87; N, 10.76.
Found: C, 76.41; H, 3.85; N, 10.79.
Funding Information
We are grateful to the Research Council of Tarbiat Modares University
for support of this work.
T
arbiat
M
o
dares
U
n
iversiyt()
Supporting Information
MS: m/z (%) = 489 (M+, 17), 398 (6), 370 (86), 272 (7), 242 (5), 218 (9),
128 (7), 119 (100), 91 (45).
Supporting information for this article is available online at
https://doi.org/10.1055/a-1370-1884. Su
p
p
ortingInformationS
u
p
p
ortingI
n
formati
o
n
Anal. Calcd for C34H23N3O (489.58): C, 83.41; H, 4.74; N, 8.58. Found:
C, 83.17; H, 4.76; N, 8.60.
References
(4-Methoxyphenyl)(2-(quinolin-2-yl)spiro[cyclopropane-1,11′-
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© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–J

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© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–J