Synthesis of Activated Cyclopropanes by MHIRC Strategy: A Facile and Efficient Approach to Spirocyclopropanes Using N-Halosulfon-amides

Article abstract of DOI:10.1055/s-0035-1561653

In this study, a one-pot, three-component reaction of two molecules of indane-1,3-dione with aromatic aldehydes for the synthesis of spirocyclopropylindanediones using poly(N-bromo-N-ethylbenzene-1,3-disulfonamide) (PBBS), N,N,N',N'-tetrabromobenzene-1,3-

Full text of DOI:10.1055/s-0035-1561653

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–I
paper
A
R. Ghorbani-Vaghei, Y. Maghbooli
Paper
Synthesis
Synthesis of Activated Cyclopropanes by MHIRC Strategy: A Facile
and Efficient Approach to Spirocyclopropanes Using N-Halosulfon-
amides
Ramin Ghorbani-Vaghei*
Yaser Maghbooli
Faculty of Chemistry, Bu-Ali Sina University,
Hamedan 6517838683, Iran
rgvaghei@yahoo.com
Received: 17.02.2016
Accepted after revision: 28.04.2016
Published online: 20.06.2016
(MIRC), transition-metal-catalyzed carbine transfer, or-
ganocatalytic cyclopropanation, and from alkenes by
Simmons–Smith and related reactions or with ylides, for
example, phosphorus, sulfur, arsenic, and phenyliodonium
ylides.5–12
DOI: 10.1055/s-0035-1561653; Art ID: ss-2016-z0118-op
Abstract In this study, a one-pot, three-component reaction of two
molecules of indane-1,3-dione with aromatic aldehydes for the synthe-
sis of spirocyclopropylindanediones using poly(N-bromo-N-ethylben-
zene-1,3-disulfonamide) (PBBS), N,N,N′,N′-tetrabromobenzene-1,3-
disulfonamide (TBBDA), poly(N-chloro-N-ethylbenzene-1,3-disulfon-
amide) (PCBS), and N,N,N′,N′-tetrachlorobenzene-1,3-disulfonamide
(TCBDA) as novel reagents has been developed. In addition, an effective
and simple domino procedure for the preparation of spirodicyanocyclo-
propylindanediones from indane-1,3-dione and 2-arylidenemalononi-
triles is reported. These reactions involve Michael addition, halogena-
tion, and intramolecular ring-closing (MHIRC) reaction sequences.
One of the most common methods for the construction
of cyclopropane rings is Michael-initiated ring closure
(MIRC) from electron-poor alkenes.13 According to the na-
ture of the involved substrates/reactants, we can divide
these reactions into two classes.14 The first one includes
Michael addition of a substrate bearing a leaving group to
an activated alkene. The second type of MIRC method in-
volves nucleophilic addition to electrophilic substrates that
contain a leaving group for the formation of cyclopro-
panes.15 In the Michael addition–halogenation–intramolec-
ular ring-closing (MHIRC) strategy, the halogen atom as a
leaving group can attach to substrates or reactants during
the reaction, which then undergoes intramolecular ring clo-
sure to produce the corresponding three-membered ring
(Scheme 1).16
Key words N-halosulfonamides, spirocycles, Michael addition, cyclo-
propane, indane-1,3-dione, ring closure
The smallest cycloalkane is found as a main structural
element in a broad range of naturally occurring com-
pounds.1 Cyclopropanes are attractive and often sought
synthetic targets, because the specific reactivity of this car-
bocyclic ring system renders them useful as versatile inter-
mediates in the synthesis of complex molecules.2
R2
R1
EWG
R2
R3
The spiro ring effectively restricts the aromatic ring to
different conformations without a large increase in carbon
number or strict bulk. Restriction of aromatic rings to dif-
ferent areas relative to the spiro ring may produce com-
pounds with different pharmacological activity.3,4 There-
fore, the construction of spiro-cyclopropane skeletons has
attracted extensive attention, and a variety of efficient pro-
cedures have been developed for the synthesis of these im-
portant structures, including Michael-initiated ring closure
R1
Michael addition
R3
EWG
Hal
A
halogenation
R1
R1
intramolecular
ring closure
R2
R2
R3
EWG
R3
EWG
B
Scheme 1 Michael addition–halogenation–intramolecular ring-closing
(MHIRC) strategy
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

B
R. Ghorbani-Vaghei, Y. Maghbooli
Paper
Synthesis
The development of the MHIRC strategy in the synthesis
of cyclic compounds has attracted considerable attention as
attested by the huge expansion of this area in recent
years.17–25 Some methods have been developed for the syn-
thesis of spirocyclopropanes from indane-1,3-diones by the
MIRC strategy involving the oxidative addition of various
aldehydes with indane-1,3-dione in the presence of iodine
and DMAP under mechanical milling conditions,26 the reac-
tion of 2-arylideneindane-1,3-diones and 2-arylidenemalo-
nonitriles with different α-monohalogenated methylene
active compounds using trimethylamine, or the reaction of
2-arylideneindane-1,3-diones with dimethyl bromoma-
lonate in the presence of α,α-L-diarylprolinol and K2CO3,27
and the reaction of dialkyl dibromomalonates with 2-aryl-
methyleneindane-1,3-dione in the presence of zinc in
THF.28
Since halo-organic compounds are widely used in or-
ganic synthesis and in the chemistry of natural com-
pounds, many attempts have been made to develop new
methods and reagents for selective halogenation. The use of
some halogenating agents requires special equipment and
techniques because of their explosive, toxic, unstable, and
hygroscopic qualities. Consequentially, considerable efforts
have been made to find newer reagents that can minimize
the disadvantages of those presently in use. N-Halo re-
agents are easy to handle and all, not half, of their halogens
are consumed. Moreover, they exhibit high variability of the
N–X bond and various modes of their splitting. Based on
the conditions, a number of highly reactive intermediates
can be formed: halogen cations, halogen anions, halogen
radicals, N-cations, N-anions, N-radicals, etc. The second
specific feature of N-halo reagents, responsible for their
wide application, is high selectivity of processes with par-
ticipation of these compounds, which cannot be achieved
through the use of other reagents.29–32
The advantages of TBBDA, PBBS, TCBDA, and PCBS are as
follows: 1. N-Halo sulfonamides are easy to handle with all
of the halogen being consumed and the sulfonamide moi-
eties exhibit diverse pharmacological activities.40 2. The re-
agents have high reactivity and selectivity. 3. TBBDA, PBBS,
TCBDA, and PCBS are stable for at least two months under
normal conditions. 4. After completion of the reaction, the
sulfonamide is recovered, rehalogenated, and can be used
again several times without decreasing the yield.
We first investigated the reaction of benzaldehyde (1h)
as a model compound with indane-1,3-dione (2) under var-
ious reaction conditions (Table 1). At the outset of our stud-
ies, we attempted to find the effect of various bases on this
reaction (Table 1, entries 1–10). Only a trace amount of
3′-phenyldispiro[indene-2,1′-cyclopropane-2′,2′′-indene]-
1,1′′,3,3′′-tetraone (3h) was observed when Et3N or pyridine
were employed (Table 1, entries 1 and 2). Other organic and
inorganic bases including NaOH, K2CO3, NaHCO3, DBU,
DABCO, NaOEt, and KOt-Bu facilitated the reaction to some
extent, but none exceeded the result of NaOAc (Table 1, en-
tries 3–10).We also found that 1.0 mmol of NaOAc, and 0.25
mmol of TBBDA were sufficient and excessive amounts of
them did not increase the yields of products (Table 1, en-
tries 11 and 12). Other halogen sources such as PBBS,
Table 1 Optimization of the Cyclopropanation of Benzaldehyde (1h)
with Indane-1,3-dione (2) Using N-Halosulfonamides and Basic Addi-
tivesa
Entry Conditions
Time (min) Yield (%)b
1
2
Et3N (1 mmol), TBBDA (0.25 mmol)
10
10
10
10
10
10
10
5
trace
trace
42
pyridine (1 mmol), TBBDA (0.25 mmol)
NaOH (1 mmol), TBBDA (0.25 mmol)
K2CO3 (1 mmol), TBBDA (0.25 mmol)
NaHCO3 (1 mmol), TBBDA (0.25 mmol)
DBU (1 mmol), TBBDA (0.25 mmol)
DABCO (1 mmol), TBBDA (0.25 mmol)
NaOEt (1 mmol), TBBDA (0.25 mmol)
KOt-Bu (1 mmol), TBBDA (0.25 mmol)
NaOAc (1 mmol), TBBDA (0.25 mmol)
NaOAc (1.2 mmol), TBBDA (0.25 mmol)
NaOAc (1 mmol), TBBDA (0.5 mmol)
NaOAc (1 mmol), PBBS (0.2 g)
3
4
54
Based on the above facts and in continuation of our pre-
vious studies on the application of N-halo reagents in or-
ganic synthesis,33–39 we now report a convenient method
for the cyclopropanation of aromatic aldehydes 1 and 2-
arylidenemalononitriles 7 with indane-1,3-dione (2) using
poly(N-bromo-N-ethylbenzene-1,3-disulfonamide) (PBBS),
N,N,N′,N′-tetrabromobenzene-1,3-disulfonamide (TBBDA),
poly(N-chloro-N-ethylbenzene-1,3-disulfonamide) (PCBS),
5
58
6
62
7
71
8
85
9
5
91
10
11
12
13
14
15
16
17
2
94
5
94
and
N,N,N′,N′-tetrachlorobenzene-1,3-disulfonamide
(TCBDA) (Scheme 2).
2
94
5
90
Br
N
Br
N
Br
N
Br
N
NaOAc (1 mmol), TCBDA (0.25 mmol)
NaOAc (1 mmol), PCBS (0.15 g)
2
93
S
S
CH2CH2
Br
S
S
Br
Cl
5
89
O
O
O
O
n
O
O
O
O
PBBS
TBBDA
NaOAc (1 mmol), NBS (1 mmol)
10
10
78
Cl
N
Cl
N
NaOAc (1 mmol), NCS (1 mmol)
74
Cl
N
Cl
N
a Reaction conditions: benzaldehyde (1h, 1.0 mmol), indane-1,3-dione (2,
2.0 mmol), EtOH (1 mL), r.t.
S
S
CH2CH2
Cl
S
S
O
O
O
O
n
O
O
O
O
b Isolated yield.
PCBS
TCBDA
Scheme 2 The structure of PBBS, TBBDA, PCBS, and TCBDA
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

C
R. Ghorbani-Vaghei, Y. Maghbooli
Paper
Synthesis
TCBDA, and PCBS, were also screened. All of them gave the
final product in good to high yields (Table 1, entries 13–
15).When the reaction was carried out using N-bromosuc-
cinimide and N-chlorosuccinimide as halogenating agents,
a slight reduction in yield and extended reaction times
were observed (Table 1, entries 16 and 17).
Next, solvent effects on the cyclopropanation of benzal-
dehyde (1h) with indane-1,3-dione (2) were examined by
applying the optimized conditions (Table 1, entry 10). The
use of CH2Cl2, THF, and EtOAc gave moderate results (Table
2, entries 1–3). The reaction in CH3CN, MeOH, and EtOH af-
forded 3′-phenyldispiro[indene-2,1′-cyclopropane-2′,2′′-in-
dene]-1,1′′,3,3′′-tetraone (3h) in good to high yields (Table
2, entries 4–6), whereas the yield in H2O was lower after re-
fluxing the entire reaction mixture for 60 min at 100 °C (Ta-
ble 2, entry 7). In this context, EtOH is the preferred choice
as a solvent (Table 2, entry 6). When the reaction was car-
ried out at higher temperature (50 °C or refluxing the entire
reaction mixture for 10 min) this gave the same results as
the room temperature reaction in EtOH (Table 2, entries 9
and 10).Therefore, this reaction was most efficient when
using benzaldehyde (1h, 1.0 mmol), indane-1,3-dione (2,
2.0 mmol), TBBDA (0.14 g, 0.25 mmol), and NaOAc (1.0
mmol) in EtOH (1 mL) at room temperature (Table 2, entry
6).
Table 2 Effect of Various Solvents on the Reaction of Benzaldehyde
(1h) with Indane-1,3-dione (2) Using N-Halosulfonamidesa
Entry
Solvent
Temp (°C)
Time (min) Yield (%)b
1
2
CH2Cl2
THF
r.t.
10
10
5
40
49
61
79
87
94
71
92
94
94
r.t.
3
EtOAc
MeCN
MeOH
EtOH
r.t.
4
r.t.
5
5
r.t.
5
6
r.t.
2
7
H2O
reflux
r.t.
60
10
5
In order to study the generality of the process, various
aromatic aldehydes 1 with indane-1,3-dione (2) were sub-
mitted to these reaction conditions and provide the corre-
sponding 3′-phenyldispiro[indene-2,1′-cyclopropane-2′,2′′-
indene]-1,1′′,3,3′′-tetraone derivatives 3a–i in good to high
yields (Table 3).
8
H2O/EtOH
EtOH
9
50 °C
reflux
10
EtOH
2
a Reaction conditions: benzaldehyde (1h, 1.0 mmol), indane-1,3-dione (2)
(2.0 mmol), NaOAc (1.0 mmol), TBBDA (0.14 g, 0.25 mmol), solvent (1
mL).
b Isolated yield.
Table 3 Cascade One-Pot Transformation of Aromatic Aldehydes 1a–i and Indane-1,3-dione (2) into 3′-Phenyldispiro[indene-2,1′-cyclopropane-
2′,2′′-indene]-1,1′′,3,3′′-tetraones 3a–i Using N-Halosulfonamidesa
R
O
O
O
O
O
R
H
O
O
TBBDA or PBBS or TCBDA or PCBS
EtOH, NaOAc, r.t.
O
O
1
2
2
3
Entry Aldehyde
Product
TBBDA
Time (min) Yieldb (%)
PBBS
TCBDA
Time (min) Yieldb(%)
PCBS
Time (min) Yieldb (%)
Time (min) Yieldb (%)
1
2
3
4
5
6
7
8
9
2,4-dichlorobenzaldehyde
2-chlorobenzaldehyde
3a
3b
3c
3d
3e
3f
10
5
96
95
95
89
91
93
95
94
96
20
10
5
93
90
91
82
87
90
90
90
94
5
2
94
95
94
90
87
91
95
93
95
15
10
5
90
93
89
85
78
87
92
89
90
4-chloro-3-nitrobenzaldehyde
1-naphthaldehyde
1
1
5
10
20
15
2
5
15
20
15
5
biphenyl-4-carbaldehyde
3-bromobenzaldehyde
4-fluorobenzaldehyde
benzaldehyde
20
10
2
10
5
3g
3hc
3id
1
2
5
2
5
3-nitrobenzaldehyde
2
5
2
5
a Reaction conditions: aromatic aldehydes 1a–i (1.0 mmol), indane-1,3-dione (2, 2.0 mmol), NaOAc (1.0 mmol), TBBDA (0.14 g, 0.25 mmol) or PBBS (0.2 g) or
TCBDA (0.1 g, 0.25 mmol) or PCBS (0.15 g), EtOH (1 mL).
b Isolated yield.
c Mp 212–214 °C (Lit.26 210–212 °C).
d Mp 217–219 °C (Lit.26 198–199 °C).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

D
R. Ghorbani-Vaghei, Y. Maghbooli
Paper
Synthesis
It could be concluded that aromatic aldehydes bearing
both electron-donating and electron-withdrawing groups
1a–i can react with indane-1,3-dione (2) and gave the cor-
responding cyclopropanes 3a–i in good to high yields (Table
3).
A possible mechanism for the cyclopropanation of aro-
matic aldehyde 1 with indane-1,3-dione (2) using N-halo-
sulfonamides is shown in Scheme 3. First, Knoevenagel con-
densation of the aromatic aldehyde 1 with indane-1,3-di-
one (2) leads to the formation of 2-arylideneindane-1,3-
dione A. Michael addition of the second molecule of in-
dane-1,3-dione (2) to the β-carbon position of 2-arylidene-
indane-1,3-dione A as an α,β-unsaturated compound af-
forded intermediate B in the presence of an N-halosulfon-
4). First, we decided to investigate the multicomponent re-
action of aromatic aldehydes 1, malononitrile (5) and in-
dane-1,3-dione (2) to give the corresponding cyclopro-
panes. When the reaction was carried out under these con-
ditions, a complex mixture of compounds was found at the
end of the reaction (reaction progress was monitored by
TLC) and the major product was 3-phenylcyclopropane-
1,1,2,2-tetracarbonitrile (47%). In the next stage of our in-
vestigation, we decided to test the reaction of 2-arylidene-
indane-1,3-diones 4 with malononitrile (5) under the opti-
mal reaction conditions. These reactions produced corre-
sponding spirocyclopropanes 6 in good to high yields (84–
96%) (Scheme 4, path a) similar to the results of the reac-
tion between 2-arylidenemalononitriles 7 and indane-1,3-
dione (2) under the optimized conditions (Scheme 4, path
b).
Considering the procedure for the preparation of 2-
arylidenemalononitriles 7 has several advantages, such as
high yields, easy work-up, short reaction times, and pure
products, compared to the preparation of 2-arylidenein-
dane-1,3-diones 4, we preferred to carry out synthesis of
1,3-dioxo-3-phenyl-1′,3′-dihydrospiro(cyclopropane-1,2′-
indene)-2,2-dicarbonitriles 6 using 2-arylidenemalononi-
triles 7 and indane-1,3-dione (2) under the optimized con-
ditions (Table 4).41
amide as
a source of electrophilic halogen. Then,
deprotonation of intermediate B occurs to give the halodi-
carbonylcarbanion C in ethanol with use of sodium acetate.
The intermediate C should exist in equilibrium with inter-
mediate E by the negative charge delocalization possible
under the conditions studied. Intramolecular C-attack of
carbanion to carbon atom containing bromine atom as an
electrophile produces 3′-phenyldispiro[indene-2,1′-cyclo-
propane-2′,2′′-indene]-1,1′′,3,3′′-tetraones D (Scheme 3,
path a).Under these reaction conditions, preparation of
spirodihydrofuran F with O-attack of carbanion E to the
carbon atom containing bromine atom did not occur
(Scheme 3, path b).26
As shown in Table 4, reactions of aromatic aldehydes
bearing both electron-donating and -withdrawing groups
proceed smoothly to give the corresponding spirocyclo-
propanes 6 in good to high yields (84–96%).
In addition, we explored the formation of 1,3-dioxo-3-
phenyl-1′,3′-dihydrospiro(cyclopropane-1,2′-indene)-2,2-
dicarbonitriles 6 under the optimized conditions (Scheme
O
O
R
TBBDA
Br
TBBDA
Br
Br
N
Br
N
4
O
R
H
O
H
4
O
Br
S
S
Br
4
O
O
TBBDA
O
O
O
O
2
2
4
4
NaOAc
R
O
R
1
A
H2NO2S
SO2NH2
R
O
O
O
O
Na
4
C-attack
4
Br
O
– NaBr
R
path a
O
O
O
C
D
O
O
NaOAc
R
R
4
Br
path b
O
O
O
O
O
O
O-attack
4
4
B
Br
O
O
O
– NaBr
O
Na
E
F
Scheme 3 Suggested mechanism for the synthesis of 3′-phenyldispiro[indene-2,1′-cyclopropane-2′,2′′-indene]-1,1′′,3,3′′-tetraones
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

E
R. Ghorbani-Vaghei, Y. Maghbooli
Paper
Synthesis
R
conditions studied. Thereupon, halogenation of the inter-
mediate C with use of N-halosulfonamides as a source for
electrophilic halogen occurs to give the intermediate D. In
the presence of base, deprotonation of intermediate D takes
place leading to the formation of intermediate E. Intramo-
lecular C-attack of carbanion to the electrophilic bromo-
substituted carbon atom produces 1,3-dioxo-3-phenyl-
1′,3′-dihydrospiro(cyclopropane-1,2′-indene)-2,2-dicarbo-
nitriles 6.42
N
N
O
path a
R
TBBDA
or PBBS
or TCBDA
or PCBS
O
N
N
O
4
5
EtOH
NaOAc, r.t.
O
N
O
In conclusion, simple and highly efficient method for
the reaction of aromatic aldehydes 1 and 2-arylidenemalo-
nonitriles 7 with indane-1,3-dione (2) to selectively afford
spirocyclopropanes in good to high yields under mild con-
ditions using poly(N-bromo-N-ethylbenzene-1,3-disulfon-
amide), N,N,N′,N′-tetrabromobenzene-1,3-disulfonamide,
6
path b
84–96% yield
R
N
O
2
7
Scheme 4 Possible pathways for the formation of spirodicyanocyclo-
propylindanediones using N-halosulfonamides
poly(N-chloro-N-ethylbenzene-1,3-disulfonamide),
and
N,N,N′,N′-tetrachlorobenzene-1,3-disulfonamide were de-
veloped. These methods offer several significant advan-
tages, such as high atom economy, high yield, inexpensive
reagents, environmental friendliness (non-corrosive re-
agents), and ease of product isolation, which make them
useful and attractive processes for the rapid synthesis of
3′-phenyldispiro[indene-2,1′-cyclopropane-2′,2′′-indene]-
1,1′′,3,3′′-tetraone and 1,3-dioxo-3-phenyl-1′,3′-dihydro-
spiro(cyclopropane-1,2′-indene)-2,2-dicarbonitrile deriva-
tives.
Based on these results, a plausible reaction pathway for
the cyclopropanation of 2-arylidenemalononitriles 7 with
indane-1,3-dione (2) using N-halosulfonamides is present-
ed in Scheme 5. First, deprotonation of indane-1,3-dione (2)
using of an acetate anion in ethanol gives the indane-1,3-
dione anion A. Michael addition of the indane-1,3-dione
anion A to the β-carbon position of 2-arylidenemalononi-
trile 7 as an α,β-unsaturated compound afforded interme-
diate B. The intermediate B should exist in equilibrium with
intermediate C by the proton migration possible under the
Table 4 Cyclopropanation of 2-Arylidenemalononitriles 7a–h with Indane-1,3-dione (2) into 1,3-Dioxo-3-phenyl-1′,3′-dihydrospiro(cyclopropane-
1,2′-indene)-2,2-dicarbonitriles 6a–ha
R
O
N
N
N
O
TBBDA or PBBS or TCBDA or PCBS
EtOH, NaOAc, r.t.
R
N
O
O
2
7
6
Entry
Aldehyde
Product
TBBDA
PBBS
TCBDA
PCBS
Time
(min)
Yieldb
(%)
Time
(min)
Yieldb
(%)
Time
(min)
Yieldb
(%)
Time
(min)
Yieldb
(%)
1
2
3
4
5
6
7
8
4-chlorobenzaldehyde
3-bromobenzaldehyde
4-nitrobenzaldehyde
4-methoxybenzaldehyde
2-chlorobenzaldehyde
2,4-dichlorobenzaldehyde
4-methylbenzaldehyde
benzaldehyde
6a
6b
6c
6d
6e
6f
2
15
2
95
90
96
84
94
89
86
91
5
20
5
91
89
94
79
87
85
82
90
2
15
2
94
88
95
86
95
92
89
93
5
20
5
89
85
90
81
91
87
75
87
10
2
15
5
10
2
15
5
3
5
5
10
10
5
6g
6hc
2
5
5
2
10
2
a Reaction conditions: 2-arylidenemalononitrile 7a–h (1.0 mmol), indane-1,3-dione (2) (1.0 mmol), NaOAc (1.0 mmol), TBBDA (0.14 g, 0.25 mmol) or PBBS (0.2
g) or TCBDA (0.1 g, 0.25 mmol) or PCBS (0.15 g), EtOH (2 mL).
b Isolated yield.
c Mp 221–222 °C (Lit.27 222–224 °C).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

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R. Ghorbani-Vaghei, Y. Maghbooli
Paper
Synthesis
CN
Ar
Ar
O
O
O
O
O
4
Ar
Na
CN
Na
CN
CN
4
NaOAc
– HOAc
7
4
4
4
Na
CN
CN
O
O
O
2
A
B
C
Br
Br
N
Ar
Br
O
Ar
Br
O
N
O
Ar
O
Br
S
S
Br
CN
CN
CN
Na
CN
O
O
O
NaOAc
– HOAc
4
4
TBBDA
4
CN
CN
– NaBr
O
O
O
6
E
D
H2NO2S
SO2NH2
Scheme 5 Proposed mechanism for the formation of 1,3-dioxo-3-phenyl-1′,3′-dihydrospiro(cyclopropane-1,2′-indene)-2,2-dicarbonitriles
Melting points were measured with a digital melting point apparatus
(Electrothermal) and are uncorrected. Mass spectra were recorded on
a Shimadzu QP 1100 BX Mass Spectrometer (University of Tehran,
Iran). 1H and 13C NMR spectra were recorded on Bruker Avance 400 FT
NMR spectrometers (undertaken at University of Isfahan, Iran) at 400
MHz and 100 MHz spectrometer in DMSO-d6, respectively, relative to
the internal standard of TMS. Infrared spectroscopy was performed
on a Perkin Elmer GX FT-IR spectrophotometer in KBr pellets. All
starting materials were obtained from commercial sources and used
without purification.
IR (KBr): 3054, 2922, 1757, 1721, 1590, 1419, 1353, 1244, 1112, 757,
574 cm–1
1H NMR (400 MHz, DMSO-d6): δ = 4.43 (s, 1 H, CH), 7.42 (t, J = 7.2 Hz,
1 H, ArH), 7.52 (dd, J = 8, 14.8 Hz, 2 H, ArH), 7.65 (d, J = 8 Hz, 1 H, ArH),
7.95 (m, 2 H, ArH), 8.02 (m, 6 H, ArH).
13C NMR (100 MHz, DMSO-d6): δ = 37.7, 51.3, 122.3, 122.5, 126.2,
128.1, 128.5, 129.3, 133.2, 134.0, 135.1, 135.3, 141.0, 142.0, 188.7,
190.8.
.
MS: m/z (%) = 412 (M+, 48), 377 (100), 349 (35), 292 (18), 264 (40),
233 (14), 189 (27), 133 (23), 104 (72), 76 (70).
3′-Phenyldispiro[indene-2,1′-cyclopropane-2′,2′′-indene]-
1,1′′,3,3′′-tetraone Derivatives 3a–i; General Procedure Using
N-Halosulfonamides
3′-(4-Chloro-3-nitrophenyl)dispiro[indene-2,1′-cyclopropane-
2′,2′′-indene]-1,1′′,3,3′′-tetraone (3c)
White solid; yield: 434 mg (95%); mp 245–247 °C.
A mixture of aromatic aldehyde 1 (1 mmol), indane-1,3-dione (2, 0.29
g, 2 mmol), NaOAc (0.08 g, 1 mmol), TBBDA (0.14 g, 0.25 mmol) or
PBBS (0.2 g) or TCBDA (0.1 g, 0.25 mmol) or PCBS (0.15 g) in EtOH (1
mL) was placed in a test tube. The mixture was stirred at r.t. for the
time given in Table 3. After completion of the reaction [Table 3, moni-
tored by TLC (n-hexane/acetone 5:1)], the solid phase was filtered off,
washed with EtOH (2 × 1 mL) and dried under reduced pressure to
isolate pure product. The filtrate was evaporated and washed with
hot water, CH2Cl2 (3 mL) was added, and the precipitated sulfonamide
was removed by filtration. The sulfonamide was rehalogenated and
used several times.
IR (KBr): 3075, 2920, 1759, 1720, 1594, 1534, 1352, 1243, 1160, 1120,
748 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 4.64 (s, 1 H, CH), 7.83 (d, J = 8.4 Hz,
1 H, ArH), 7.94 (m, 3 H, ArH), 8.01 (m, 6 H, ArH), 8.55 (s, 1 H, ArH).
13C NMR (100 MHz, DMSO-d6): δ = 36.3, 51.2, 122.3, 122.5, 123.7,
128.0, 130.1, 131.7, 135.1, 136.6, 141.2, 142.2, 146.7, 189.1, 190.1.
MS: m/z (%) = 457 (M+, 16), 454 (36), 409 (28), 295 (21), 256 (83), 227
(18), 187 (27), 133 (21), 104 (100), 76 (95).
3′-(Naphthalen-1-yl)dispiro[indene-2,1′-cyclopropane-2′,2′′-in-
dene]-1,1′′,3,3′′-tetraone (3d)
3′-(2,4-Dichlorophenyl)dispiro[indene-2,1′-cyclopropane-2′,2′′-in-
dene]-1,1′′,3,3′′-tetraone (3a)
White solid; yield: 380 mg (89%); mp 189–190 °C.
White solid; yield: 428 mg (96%); mp 266–267 °C.
IR (KBr): 3052, 1755, 1719, 1592, 1466, 1351, 1245, 1157, 1095, 1045,
945, 776, 493 cm–1
.
IR (KBr): 3093, 1756, 1721, 1589, 1466, 1388, 1352, 1241, 1116, 747,
581 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 4.76 (s, 1 H, CH), 7.30 (t, J = 7.6 Hz,
1 H, ArH), 7.38 (d, J = 8.4 Hz, 1 H, ArH), 7.43 (d, J = 8.8 Hz, 1 H, ArH),
7.47 (d, J = 7.6 Hz, 1 H, ArH), 7.54 (d, J = 7.2 Hz, 1 H, ArH), 7.77 (d, J =
6.8 Hz, 2 H, ArH), 7.93 (m, 6 H, ArH), 7.97 (d, J = 7.2 Hz, 2 H, ArH).
1H NMR (400 MHz, DMSO-d6): δ = 4.27 (s, 1 H, CH), 7.38 (dd, J = 2, 8.4
Hz, 1 H, ArH), 7.56 (d, J = 2 Hz, 1 H, ArH), 7.60 (d, J = 8.4 Hz, 1 H, ArH),
7.82 (m, 2 H, ArH), 7.89 (m, 6 H, ArH).
13C NMR (100 MHz, DMSO-d6): δ = 36.8, 51.2, 122.3, 122.5, 126.3,
127.4, 128.0, 133.0, 134.6, 135.1, 135.2, 135.3, 141.0, 142.0, 188.8,
190.6.
13C NMR (100 MHz, DMSO-d6): δ = 38.0, 51.8, 122.2, 122.3, 122.6,
124.9, 125.4, 125.5, 126.4, 128.0, 128.8, 129.3, 131.9, 132.9, 135.2,
135.4, 141.0, 142.1, 188.8, 191.2.
MS: m/z (%) = 446 (M+, 23), 411 (100), 383 (24), 298 (23), 263 (36),
MS: m/z (%) = 428 (M+, 100), 383 (45), 355 (49), 326 (34), 280 (44),
223 (16), 187 (31), 133 (24), 104 (79), 76 (72).
239 (69), 163 (24), 133 (40), 104 (83), 76 (75).
3′-(2-Chlorophenyl)dispiro[indene-2,1′-cyclopropane-2′,2′′-in-
dene]-1,1′′,3,3′′-tetraone (3b)
3′-(Biphenyl-4-yl)dispiro[indene-2,1′-cyclopropane-2′,2′′-indene]-
1,1′′,3,3′′-tetraone (3e)
White solid; yield: 391 mg (95%); mp 226–229 °C.
White solid; yield: 413 mg (91%); mp 170–171 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

G
R. Ghorbani-Vaghei, Y. Maghbooli
Paper
Synthesis
IR (KBr): 3035, 2943, 1753, 1719, 1591, 1489, 1351, 1243, 1160, 966,
749, 597 cm–1
1H NMR (400 MHz, DMSO-d6): δ = 4.71 (s, 1 H, CH), 7.54 (t, J = 7.2 Hz,
1 H, ArH), 7.63 (m, 4 H, ArH), 7.72 (d, J = 8 Hz, 2 H, ArH), 7.86 (d, J = 7.2
Hz, 2 H, ArH), 7.99 (m, 2 H, ArH), 8.06 (m, 6 H, ArH).
13C NMR (100 MHz, DMSO-d6): δ = 40.1, 51.6, 122.3, 122.5, 125.6,
126.5, 127.3, 128.9, 129.5, 131.2, 135.1, 135.2, 138.8, 139.8, 141.0,
142.2, 189.1, 190.9.
and washed with hot water, CH2Cl2 (3 mL) was added, and the precip-
itated sulfonamide was removed by filtration. The sulfonamide was
rehalogenated and used several times.
.
3-(4-Chlorophenyl)-1′,3′-dioxo-1′,3′-dihydrospiro[cyclopropane-
1,2′-indene]-2,2-dicarbonitrile (6a)
White solid; yield: 315 mg (95%); mp 199–200 °C.
IR (KBr): 3075, 3017, 2250, 1746, 1711, 1590, 1499, 1356, 1222, 1093,
753, 584 cm–1
.
MS: m/z (%) = 454 (M+, 84), 409 (64), 331 (100), 309 (30), 293 (19),
1H NMR (400 MHz, DMSO-d6): δ = 4.41 (s, 1 H, CH), 7.61 (d, J = 8.4 Hz,
2 H, ArH), 7.66 (d, J = 8.4 Hz, 2 H, ArH), 8.17 (m, 3 H, ArH), 8.26 (d, J =
6.4 Hz, 1 H, ArH).
13C NMR (100 MHz, DMSO-d6): δ = 20.4, 40.8, 43.8, 110.3, 111.9,
123.0, 123.2, 127.3, 128.2, 132.0, 133.4, 136.0, 136.1, 141.5, 142.4,
188.9, 190.0.
263 (32), 189 (19), 133 (34), 104 (95), 76 (90).
3′-(3-Bromophenyl)dispiro[indene-2,1′-cyclopropane-2′,2′′-in-
dene]-1,1′′,3,3′′-tetraone (3f)
White solid; yield: 424 mg (93%); mp 172–174 °C.
IR (KBr): 3100, 1755, 1734, 1717, 1592, 1467, 1389, 1352, 1245, 1096,
752, 578 cm–1
.
MS: m/z (%) = 332 (M+, 53), 297 (100), 269 (21), 241 (36), 214 (40),
187 (14), 165 (37), 138 (19), 104 (100), 76 (97).
1H NMR (400 MHz, DMSO-d6): δ = 4.47 (s, 1 H, CH), 7.21 (t, J = 7.6 Hz,
1 H, ArH), 7.36 (d, J = 7.6 Hz, 1 H, ArH), 7.46 (d, J = 8 Hz, 1 H, ArH), 7.54
(m, 1 H, ArH), 7.79 (m, 2 H, ArH), 7.87 (m, 6 H, ArH).
13C NMR (100 MHz, DMSO-d6): δ = 38.0, 51.4, 120.6, 122.3, 122.5,
129.3, 129.8, 130.0, 132.9, 133.3, 135.1, 135.2, 141.1, 142.1, 189.0,
190.5.
3-(3-Bromophenyl)-1′,3′-dioxo-1′,3′-dihydrospiro[cyclopropane-
1,2′-indene]-2,2-dicarbonitrile (6b)
White solid; yield: 337 mg (90%); mp 168–169 °C.
IR (KBr): 3101, 3079, 2249, 1747, 1711, 1587, 1476, 1357, 1229, 1060,
751, 594 cm–1
.
MS: m/z (%) = 456 (M+, 18), 377 (59), 349 (21), 297 (25), 253 (22), 225
1H NMR (400 MHz, DMSO-d6): δ = 4.27 (s, 1 H, CH), 7.35 (t, J = 8 Hz, 1
H, ArH), 7.51 (d, J = 7.6 Hz, 1 H, ArH), 7.57 (d, J = 8 Hz, 1 H, ArH), 7.81
(s, 1 H, ArH), 8.04 (m, 3 H, ArH), 8.11 (d, J = 6.4 Hz, 1 H, ArH).
13C NMR (100 MHz, DMSO-d6): δ = 20.4, 40.4, 43.8, 110.3, 111.9,
121.1, 123.1, 123.2, 129.2, 130.2, 130.8, 131.4, 132.7, 136.0, 136.1,
141.5, 142.4, 188.9, 189.9.
(100), 176 (15), 147 (31), 104 (68), 76 (54).
3′-(4-Fluorophenyl)dispiro[indene-2,1′-cyclopropane-2′,2′′-in-
dene]-1,1′′,3,3′′-tetraone (3g)
White solid; yield: 376 mg (95%); mp 241–242 °C.
IR (KBr): 3080, 2923, 1757, 1745, 1720, 1592, 1515, 1467, 1350, 1243,
1094, 749, 565 cm–1
.
MS: m/z (%) = 376 (M+, 11), 331 (49), 297 (100), 269 (14), 241 (26),
214 (28), 165 (23), 138 (19), 104 (88), 76 (93).
1H NMR (400 MHz, DMSO-d6): δ = 4.60 (s, 1 H, CH), 7.21 (t, J = 8.8 Hz,
2 H, ArH), 7.57 (dd, J = 2, 6 Hz, 2 H, ArH), 7.94 (m, 2 H, ArH), 8.01 (m, 6
H, ArH).
13C NMR (100 MHz, DMSO-d6): δ = 38.5, 51.6, 114.0, 114.2, 122.3,
122.5, 132.6, 132.7, 135.1, 135.2, 141.0, 142.1, 189.0, 190.8.
3-(4-Nitrophenyl)-1′,3′-dioxo-1′,3′-dihydrospiro[cyclopropane-
1,2′-indene]-2,2-dicarbonitrile (6c)
White solid; yield: 329 mg (96%); mp 220–223 °C.
MS: m/z (%) = 396 (M+, 100), 367 (42), 351 (56), 323 (44), 283 (31),
248 (46), 207 (53), 133 (29), 104 (84), 76 (70).
IR (KBr): 3096, 3001, 2246, 1750, 1721, 1602, 1523, 1345, 1291, 1074,
760, 609 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 4.45 (s, 1 H, CH), 7.84 (d, J = 8 Hz, 2
H, ArH), 8.03 (m, 3 H, ArH), 8.13 (d, J = 6.8 Hz, 1 H, ArH), 8.23 (d, J = 8
Hz, 2 H, ArH).
3′-(Phenyl)dispiro[indene-2,1′-cyclopropane-2′,2′′-indene]-
1,1′′,3,3′′-tetraone (3g)26
Known compound; mp 212–214 °C (Lit.26 mp 210–212 °C).
13C NMR (100 MHz, DMSO-d6): δ = 20.4, 40.4, 43.9, 110.2, 111.8,
123.1, 123.2, 131.8, 135.9, 136.0, 136.1, 141.7, 142.4, 147.4, 189.0,
189.7.
MS: m/z (%) = 343 (M+, 43), 297 (87), 269 (13), 241 (22), 214 (29), 187
(7), 165 (11), 138 (14), 104 (100), 76 (100).
3′-(3-Nitrophenyl)dispiro[indene-2,1′-cyclopropane-2′,2′′-in-
dene]-1,1′′,3,3′′-tetraone (3g)26
Known compound; mp 217–219 °C (Lit.26 mp 198–199 °C).
3-(4-Methoxyphenyl)-1′,3′-dioxo-1′,3′-dihydrospiro[cyclopro-
pane-1,2′-indene]-2,2-dicarbonitrile (6d)
1,3-Dioxo-3-phenyl-1′,3′-dihydrospiro(cyclopropane-1,2′-indene)-
2,2-dicarbonitrile Derivatives 6a–h; General Procedure Using
N-Halosulfonamides
White solid; yield: 275 mg (84%); mp 189–190 °C.
2-Arylidenemalononitriles 7 (1 mmol), indane-1,3-dione (2, 0.146 g,
1 mmol), NaOAc (0.08 g, 1 mmol), TBBDA (0.14 g, 0.25 mmol) or PBBS
(0.2 g) or TCBDA (0.1 g, 0.25 mmol) or PCBS (0.15 g), and EtOH (2 mL)
were added to a test-tube. Then the mixture was magnetically stirred
at r.t. for the duration as shown in Table 4 and reaction progress was
monitored by TLC (n-hexane/acetone, 5:2). The mixture was filtered
and rinsed with EtOH (2 × 1 mL). The pure product was isolated by
filtration through a Büchner funnel. Then, the filtrate was evaporated
IR (KBr): 2970, 2838, 2246, 1752, 1718, 1594, 1516, 1355, 1260, 1023,
760, 608 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 3.77 (3, 3 H, OCH3), 4.16 (s, 1 H,
CH), 6.94 (d, J = 8.8 Hz, 2 H, ArH), 7.39 (d, J = 8.4 Hz, 2 H, ArH), 8.03 (m,
3 H, ArH), 8.11 (d, J = 4 Hz, 1 H, ArH).
13C NMR (100 MHz, DMSO-d6): δ = 20.5, 41.6, 44.0, 55.1, 110.5, 112.1,
113.6, 119.8, 123.0, 123.2, 131.3, 136.0, 141.3, 142.4, 159.3, 188.9,
190.2.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

H
R. Ghorbani-Vaghei, Y. Maghbooli
Paper
Synthesis
MS: m/z (%) = 328 (M+, 100), 297 (82), 257 (40), 229 (24), 201 (18),
165 (18), 126 (13), 104 (68), 76 (65), 50 (16).
tored by TLC (n-hexane/acetone, 5:1). After completion of the reac-
tion, the solid phase was filtered off, washed with cold EtOH, and
dried to isolate pure 2-arylidenemalononitriles 7 in 75–97% yields.
3-(2-Chlorophenyl)-1′,3′-dioxo-1′,3′-dihydrospiro[cyclopropane-
1,2′-indene]-2,2-dicarbonitrile (6e)
Acknowledgment
White solid; yield: 312 mg (94%); mp 236–237 °C.
IR (KBr): 3187, 2973, 2255, 1748, 1717, 1590, 1472, 1310, 1248, 1079,
We are thankful to Bu-Ali Sina University, Center of Excellence in De-
velopment of Environmentally Friendly Methods for Chemical Syn-
thesis (CEDEFMCS) for financial support.
755, 610 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 4.30 (s, 1 H, CH), 7.53 (m, 2 H, ArH),
7.61 (d, J = 6.8 Hz, 1 H, ArH), 7.71 (d, J = 7.2 Hz, 1 H, ArH), 8.14 (m, 3 H,
ArH), 8.24 (d, J = 8 Hz, 1 H, ArH).
References
13C NMR (100 MHz, DMSO-d6): δ = 20.6, 39.9, 43.8, 110.1, 111.8,
123.1, 123.3, 126.3, 127.1, 129.3, 130.7, 132.0, 134.0, 136.2, 136.4,
141.0, 142.2, 188.4, 190.0.
MS: m/z (%) = 332 (M+, 25), 297 (100), 269 (18), 241 (33), 214 (38),
187 (8), 165 (28), 138 (19), 104 (91), 76 (89).
(1) (a) Donaldson, W. A. Tetrahedron 2001, 57, 8589. (b) Schneider,
T. F.; Kaschel, J.; Werz, D. B. Angew. Chem. Int. Ed. 2014, 53, 2.
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3-(2,4-Dichlorophenyl)-1′,3′-dioxo-1′,3′-dihydrospiro[cyclopro-
pane-1,2′-indene]-2,2-dicarbonitrile (6f)
(3) Maas, G. Chem. Soc. Rev. 2004, 33, 183.
(4) (a) King, S. B.; Stratford, E. S.; Craig, C. R.; Fifer, E. K. Pharm. Res.
1995, 12, 1240. (b) Fraser, W.; Suckling, C. J.; Wood, H. C. S.
White solid; yield: 325 mg (89%); mp 215–216 °C.
J. Chem. Soc., Perkin Trans.
1 1990, 3137. (c) Kim, S.-H.;
IR (KBr): 3088, 2989, 2250, 1742, 1714, 1591, 1477, 1355, 1242, 1103,
Pudzianowski, A. T.; Leavitt, K. J.; Barbosa, J.; McDonnell, P. A.;
Metzler, W. J.; Rankin, B. M.; Liu, R.; Vaccaro, W.; Pitts, W.
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752, 605 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 4.35 (s, 1 H, CH), 7.68 (d, J = 8.4 Hz,
1 H, ArH), 7.82 (d, J = 8.4 Hz, 1 H, ArH), 7.88 (s, 1 H, ArH), 8.19 (m, 3 H,
ArH), 8.28 (d, J = 4.8 Hz, 1 H, ArH).
(5) Lebel, H.; Marcoux, J. F.; Molinaro, C.; Charette, A. B. Chem. Rev.
2003, 103, 977.
13C NMR (100 MHz, DMSO-d6): δ = 20.8, 39.1, 43.7, 110.0, 111.7,
123.1, 123.3, 125.6, 127.2, 128.9, 133.4, 134.5, 135.2, 136.3, 136.4,
141.1, 142.2, 188.5, 189.8.
MS: m/z (%) = 366 (M+, 8), 364 (28), 331 (100), 296 (23), 267 (31), 239
(18), 213 (51), 147 (25), 104 (76), 76 (69).
(6) (a) Davies, H. M. L.; Panaro, S. A. Tetrahedron Lett. 1999, 40,
5287. (b) Bauta, W.; Dodd, J.; Bullington, J.; Gauthier, D.; Leo, G.;
McDonnell, P. Tetrahedron Lett. 2000, 41, 1491. (c) Muthusamy,
S.; Gunanathan, C. Synlett 2003, 1599. (d) Rasool, N.; Rashid, M.
A.; Adeel, M.; Gorls, H.; Langer, P. Tetrahedron Lett. 2008, 49,
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(f) Revuelta, J.; Cicchi, S.; Faggi, C.; Kozhushkov, S. I.; de Meijere,
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D.; Humphrey, G. R.; Journet, M.; McKeown, A. E. J. Org. Chem.
2006, 71, 2192.
1′,3′-Dioxo-3-(p-tolyl)-1′,3′-dihydrospiro[cyclopropane-1,2′-in-
dene]-2,2-dicarbonitrile (6g)
White solid; yield: 268 mg (86%); mp 185–187 °C.
(7) (a) Krysiak, J.; Kato, T.; Gornitzka, H.; Baceiredo, A.; Mikolajczyk,
M.; Bertrand, G. J. Org. Chem. 2001, 66, 8240. (b) Singh, V. K.;
DattaGupta, A.; Sekar, G. Synthesis 1997, 137. (c) Grieco, P. A.;
Finkelhor, R. S. Tetrahedron Lett. 1972, 13, 3781. (d) Trost, B. M. J.
Am. Chem. Soc. 1967, 89, 138. (e) Yamamote, Y.; Schmibaur, H. J.
Chem. Soc., Chem. Commun. 1975, 668. (f) Muller, P.; Allenbach,
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(8) (a) Luo, J.; Wu, B.; Chen, M.-W.; Jiang, G.-F.; Zhou, Y.-G. Org. Lett.
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W. J. Org. Chem. 1960, 25, 1440. (c) Liu, X.-G.; Wei, Y.; Shi, M.
Tetrahedron 2010, 66, 304.
IR (KBr): 3095, 2987, 2251, 1750, 1716, 1593, 1518, 1333, 1224, 1074,
757, 490 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 2.31 (s, 3 H, CH3), 4.20 (s, 1 H, CH),
7.19 (d, J = 8 Hz, 2 H, ArH), 7.31 (d, J = 8 Hz, 2 H, ArH), 8.04 (m, 3 H,
ArH), 8.11 (d, J = 6.4 Hz, 1 H, ArH).
13C NMR (100 MHz, DMSO-d6): δ = 20.3, 20.7, 41.8, 44.0, 110.4, 112.1,
123.0, 123.2, 125.1, 128.8, 129.8, 136.1, 136.1, 138.0, 141.3, 142.3,
188.9, 190.2.
MS: m/z (%) = 312 (M+, 100), 297 (100), 267 (21), 241 (28), 214 (19),
189 (14), 165 (19), 127 (9), 104 (81), 76 (74).
(9) (a) Liao, W.-W.; Li, K.; Tang, Y. J. Am. Chem. Soc. 2003, 125,
13030. (b) Maghsoodlou, M. T.; Khorassani, S. M. H.; Heydari, R.;
Charati, F. R.; Hazeri, N.; Lashkari, M.; Rostamizadeh, M.;
Marandi, G.; Sobolev, A.; Makha, M. Tetrahedron Lett. 2009, 50,
4439.
1′,3′-Dioxo-3-phenyl-1′,3′-dihydrospiro[cyclopropane-1,2′-in-
dene]-2,2-dicarbonitrile (6h)27
Known compound; mp 221–222 °C (Lit.27 mp 222–224 °C).
(10) Ma, S.; Jiao, N.; Yang, Q.; Zheng, Z. J. Org. Chem. 2004, 69, 6463.
(11) Okamoto, N.; Sasaki, M.; Kawahata, M.; Yamaguchi, K.; Takeda,
K. Org. Lett. 2006, 8, 1889.
(12) Li, J.; Liao, S.-H.; Xiong, H.; Zhou, Y.-Y.; Sun, X.-L.; Zhang, Y.;
Zhou, X.-G.; Tang, Y. Angew. Chem. Int. Ed. 2012, 51, 8838.
(13) Little, R. D.; Dawson, J. R. Tetrahedron Lett. 1980, 21, 2609.
(14) Stereoselective Multiple Bond-Forming Transformations in
Organic Synthesis; Rodriguez, J.; Bonne, D., Eds.; Wiley: Hobo-
ken, 2015.
2-Arylidenemalononitriles 7;41 General Procedure Using Aromatic
Aldehyde 1 and Malononitrile
To a solution of aromatic aldehyde 1 (2 mmol) and malononitrile (5,
0.15 g, 2.2 mmol) in EtOH (5 mL) in a 25-mL round-bottomed flask,
sat. aq NaHCO3 solution (0.5 mL) was added. The mixture was mag-
netically stirred at r.t. for an appropriate time (5 min to 1 h) moni-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

I
R. Ghorbani-Vaghei, Y. Maghbooli
Paper
Synthesis
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I