A new type of cascade reaction: direct conversion of carbonyl compounds and malononitrile into substituted tetracyanocyclopropanes

Article abstract of DOI:10.1016/j.tet.2009.05.062

A new type of chemical cascade reaction was found: the direct formation of cyclopropanes from carbonyl compounds and C-H acid. The action of free halogen or active halogen containing compounds on a mixture of 1 equiv of carbonyl compound and 2 equiv of malononitrile in a basic alcohol solution results in the formation of substituted 1,1,2,2-tetracyanocyclopropanes in 15-80% yield. The latter are well-known precursors for the different bicyclic heterosystems, among them compounds containing a cyclopropane ring and possessing different types of pharmacological activity. Thus, the new, simple and efficient 'one-pot' way to substituted tetracyanocyclopropanes in 50-80% yield was found directly from such simple and reasonable starting compounds as aldehydes, or some cyclic ketones, or substituted cyclohexanones and malononitrile.

Full text of DOI:10.1016/j.tet.2009.05.062

Tetrahedron 65 (2009) 6057–6062
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A new type of cascade reaction: direct conversion of carbonyl compounds
and malononitrile into substituted tetracyanocyclopropanes
*
*
Michail N. Elinson , Anatolii N. Vereshchagin , Nikita O. Stepanov, Alexey I. Ilovaisky,
Alexander Ya. Vorontsov, Gennady I. Nikishin
N.D. Zelinsky Institute of Organic Chemistry, Leninsky prospect 47, 119991 Moscow, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
A new type of chemical cascade reaction was found: the direct formation of cyclopropanes from carbonyl
compounds and C–H acid. The action of free halogen or active halogen containing compounds on
a mixture of 1 equiv of carbonyl compound and 2 equiv of malononitrile in a basic alcohol solution
results in the formation of substituted 1,1,2,2-tetracyanocyclopropanes in 15–80% yield. The latter are
well-known precursors for the different bicyclic heterosystems, among them compounds containing
a cyclopropane ring and possessing different types of pharmacological activity. Thus, the new, simple and
efficient ‘one-pot’ way to substituted tetracyanocyclopropanes in 50–80% yield was found directly from
such simple and reasonable starting compounds as aldehydes, or some cyclic ketones, or substituted
cyclohexanones and malononitrile.
Received 5 March 2009
Received in revised form 5 May 2009
Accepted 21 May 2009
Available online 28 May 2009
Keywords:
Cyclopropanes
Cascade reactions
Carbonyl compounds
Malononitrile
Ó 2009 Elsevier Ltd. All rights reserved.
Tetracyanocyclopropanes
1. Introduction
Wideqvist reaction, namely the interaction of two molecules of
bromomalononitrile with carbonyl compounds 1 in the presence
The discovery of new synthetic methodologies to facilitate the
preparation of organic compounds is a pivotal focal point of re-
search activity in the field of modern organic, bioorganic and me-
dicinal chemistry.1
of a stoichiometric quantity of potassium iodide with the forma-
tion of the corresponding substituted tetracyanocyclopropanes 2
(Scheme 1).5
The cyclopropyl group is a vital structural unit in many synthetic
and naturally occurring compounds, exhibiting a wide spectrum of
biologic properties ranging from enzyme inhibition to herbicidal,
antibiotic, antitumour and antiviral activities.2–4 Thus, the preva-
lence of cyclopropane containing compounds with biological ac-
tivity, whether isolated from natural sources or rationally designed
pharmaceutical agents, has inspired chemists to find novel and
diverse approaches to their synthesis.
Though methods of cyclopropane synthesis have long been
documented, so far, all of them consist of two main groups: (1)
intramolecular cyclization or (2) interaction of two different
molecules (addition of carbenes to olefins or Michael initiated
ring closure (MIRC) are the most known examples of this
type).2,4
R1
R2
R1
R2
Br
Br
CN
CN
KI
NC
NC
CN
CN
+
C O
2
EtOH-H2O
1
2
Scheme 1.
Later, in the electrochemical variant of Wideqvist reaction,
bromomalononitrile was replaced by malononitrile and a catalytic
amount of sodium bromide.6,7 In the electrochemical variant for
the reaction of aldehydes a low temperature (0 ꢀC) is necessary;7
whereas for ketones a three- to four-fold excess of ketone is
needed to obtain tetracyanocyclopropanes 2 in good yields.6,7
Additionally, in the case of cyclohexanone, the electrochemical
process cannot be stopped on the formation of the corresponding
tetracyanocyclopropane; co-electrolysis of cyclohexanone and
malononitrile in ethanol in the presence of sodium bromide under
these conditions furnishes 2-amino-1,5-dicyano-4,4-diethoxy-6,6-
pentamethylene-3-azabicyclo[3.1.0]-hex-2-ene in 62% yield
(Scheme 2).6
Nevertheless there are some special famous methods of cy-
clopropane ring construction. One of them is well-known
* Corresponding authors. Tel.: þ7 499 137 38 42; fax: þ7 499 135 53 28.
E-mail address: elinson@ioc.ac.ru (M.N. Elinson).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.05.062

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M.N. Elinson et al. / Tetrahedron 65 (2009) 6057–6062
Excellent conversions of starting compounds were obtained
under all conditions studied. The best yield of cyclopropane 2a
(75%) was achieved when the reaction was carried out in ethanol by
the action of bromine in the presence of 1 equiv of EtONa (entry 10,
Table 1). The second step was devoted to the careful evaluation of
EtONa quantity needed for the reaction (Table 2).
electrolysis
NaBr, EtOH
CN
NH2
NC
EtO
EtO
2 CH2(CN)2
+
NC
NC
CN
CN
O
N
Scheme 2.
The best yield of cyclopropane 2a (83%) was obtained when
1.2 equiv of EtONa was used (entry 3, Table 2). The increase of
EtONa quantity beyond 1.2 equiv (entries 4 and 5, Table 2) resulted
in a sufficient decrease of the reaction yield, that may be connected
with the activation of undesired base induced oligomerization
processes of malononitrile.10
Under the optimal conditions thus found, i.e., bromine as active
halogen compound, 1.2 equiv of EtONa as base, and ethanol as
solvent, the substituted carbonyl compounds 1a–o and malononi-
trile 4 were transformed into corresponding substituted 1,1,2,2-
tetracyanocyclopropanes 2a–o in 61–83% yields (Table 3).
In the case of aldehydes 1d and 1i (entries 4 and 9, Table 3) the
quantity of EtOH was increased up to 40 mL because of the lower
Recently we suggested a new strategy of chemical route to the
cyclopropane structure: the direct transformation of benzylidene-
malononitriles 3 and malononitrile 4 into 1,1,2,2-tetracyanocyclo-
propanes 2 (Scheme 3).8
R2
R1
CN
R1
R2
XHal
R3OH,
CN
CN
CN
CN
_
NC
NC
+
C
C
B
CN
4
2
3
Hal = I, Br
X=I, Br,
O
N
O
Table 1
Scheme 3.
Cascade transformation of benzaldehyde 1a and malononitrile 4 into 3-phenyl-
1,1,2,2-tetracyanocyclopropane 2aa
Yield of 2ab (%)
Cascade reactions have been utilized as powerful method to
Entry
Alcohol
XHal
Base
construct molecular complexity from readily available starting
materials by combining two or more reactions into a single trans-
formation.9 As such, cascade reactions are of increasing importance
in modern organic chemistry. This is not only due to the need for the
more efficient and less labour-intense methodologies for the
synthesis of organic compounds, but also a consequence of the in-
creasing importance of the environmental considerations in
chemistry. Thus, cascade reactions have significant economical and
ecological benefits when one performs several synthetic steps in
one operationwithout isolating the reaction intermediates. From this
point of view the best route to the substituted 1,1,2,2-tetracyano-
cyclopropanes 2 could be the ‘one-pot’ chemical cascade process
starting directly from carbonyl compounds and malononitrile.
1
2
3
4
5
6
7
8
9
10
MeOH
MeOH
EtOH
EtOH
MeOH
EtOH
EtOH
MeOH
EtOH
EtOH
I2
I2
I2
I2
NBS
NBS
NBS
Br2
Br2
Br2
NaOH
KOH
KOH
NaOEt
KOH
KOH
NaOEt
KOH
KOH
25
31
38
45
32
43
56
39
62
75
EtONa
a
Benzaldehyde 1a (10 mmol), 20 mmol of malononitrile 4, 10 mmol of halogen or
NBS, 10 mmol of base, 20 mL of alcohol, time of the reactiond3 h.
b
Isolated yield (isolated by filtration of the reaction mixture).
Table 2
Influence of EtONa quantity on the 3-phenyl-1,1,2,2-tetracyanocyclopropane 2a
yielda
2. Results and discussion
Entry
Quantity of EtONa (equiv)
Yield of 2ab (%)
1
2
3
4
5
0.5
1.0
1.2
1.5
2.0
55
75
83
57
32
In the present study we report our results on the direct ‘one-pot’
cascade transformation of carbonyl compounds and malononitrile
into the substituted 1,1,2,2-tetracyanocyclopropanes 2 (Scheme 4).
First, to evaluate the synthetic potential of the proposed pro-
cedure and to optimize the general conditions, the cascade trans-
formation of benzaldehyde 1a, and malononitrile 4 into the
corresponding 3-phenyl-1,1,2,2-tetracyanocyclopropanes 2a was
studied (Table 1).
a
Benzaldehyde 1a (10 mmol), 20 mmol of malononitrile 4, 10 mmol of bromine,
20 mL of alcohol, time of the reactiond3 h.
b
Isolated yield (isolated by filtration of the reaction mixture).
R1
2a-r
R2
CN
CN
R1
R2
XHal
R3OH,
NC
NC
CN
CN
_
+
+
O
C
B
CN
CN
1a-r
4
4
Hal = I, Br
X=I, Br,
O
N
O
a R1 = H, R2 = Ph; b R1 = H, R2 = 4-MeC6H4; c R1 = H, R2 = 4-MeOC6H4; d R1 = H, R2 = 2-MeOC6H4;
e R1 = H, R2 = 4-FC6H4; f R1 = H, R2 = 2-ClC6H4; g R1 = H, R2 = 3-ClC6H4; h R1 = H, R2 = 4-ClC6H4;
i R1 = H, R2 = 2,4-Cl2C6H3; j R1 = H, R2 = 3-BrC6H4; k R1 = H, R2 = 3-NO2C6H4; l R1 = H, R2 = 4-NO2C6H4;
m R1 = H, R2 = naphth-1-yl; n R1 = H, R2 = Et; o R1 = H, R2 = n-Pr; p R1 = Me, R2 = Me; q R1 = Me, R2 = Et;
r R1 = Et, R2 = Et
Scheme 4.

M.N. Elinson et al. / Tetrahedron 65 (2009) 6057–6062
6059
Table 3
This new cascade process is also useful for substituted cyclo-
hexanones (Scheme 6, Table 5).
Hence this cascade method is useful for the direct ‘one-pot’
synthesis of tetracyanocyclopropanes from aldehydes, acetone, some
cyclic ketones, substituted cyclohexanones and malononitrile.
Cascade transformation of carbonyl compounds 1a–r and malononitrile 4 into 3-
substituted-1,1,2,2-tetracyanocyclopropanes 2a–ra
Entry
Carbonyl compound
R1
R2
Cyclopropane,
yieldb (%)
1
2
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
C6H5
2a, 83
2b, 72
2c, 77
2d, 63
2e, 75
2f, 71
2g, 65
2h, 82
2i, 63
2j, 61
2k, 78
2l, 62
2m, 76
2n, 65
2o, 73
2p, 43
2q, 33
2r, 15
4-MeC6H4
4-MeOC6H4
2-MeOC6H4
4-FC6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
2,4-Cl2C6H4
3-BrC6H4
3-NO2C6H4
4-NO2C6H4
Naphth-1-yl
Et
R1
3
R2
4c
5
R2
R1
CN
CN
4
CN
CN
4
Br2
+
+
O
6
7
8
NC
NC
CN
CN
EtONa/EtOH
7a-d
8a-d
9c
10
11
12
13
14
15
16
17
18
a R1 = Me, R2 = H;b R1 = t-Bu, R2 = H; c R1 = Ph, R2 = H; d R1 = H, R2 = Me;
Scheme 6.
n-Pr
Me
Et
Et
Table 5
Me
Me
Et
Cascade transformation of substituted cyclohexanones 7a–d and malononitrile 4
into spirobicyclic tetracyanocyclopropanes 8a–da
Entry
Cyclic ketone
R1
R2
Cyclopropane, yieldb (%)
a
Carbonyl compounds 1a–r (10 mmol), 20 mmol of malononitrile 4, 10 mmol of
bromine, 12 mmol of EtONa, 20 mL of EtOH, time of the reactiond3 h.
1
2
3
4
7a
7b
7c
7d
Me
t-Bu
Ph
H
H
H
Me
8a, 63
8b, 76
8c, 70
8d, 61
b
Isolated yield (isolated by filtration of the reaction mixture).
EtOH (40 mL).
c
H
a
Cyclic ketones 7a–d (10 mmol), 20 mmol of malononitrile 4, 10 mmol of bro-
mine, 12 mmol of EtONa, 20 mL of EtOH, time of the reactiond3 h.
solubility of the corresponding intermediate benzylidenemalono-
nitriles in EtOH. When 20 mL of ethanol was used in the cases of
aldehydes 1d and 1i the corresponding 4-methoxybenzylide-
nemalononitrile and 2,4-dichlorobenzylidenemalononitrile were
obtained in 42% and 47% yields, accompanied by cyclopropanes 2d
and 2i, 28% and 25% yields according to the data of NMR spec-
troscopy. Thus, under conditions used from the aliphatic and
aromatic aldehydes 1a–o the substituted 1,1,2,2-tetracyano-
cyclopropanes 2a–o were obtained in 61–83% yields. This cascade
process is not very good in the case of linear ketones; the yields of
3,3-disubstituted 1,1,2,2-tetracyanocyclopropanes 2p–r were only
in the range 15–43%. The next part of the investigation was con-
cerned with cyclic ketones (Scheme 5, Table 4).
Among the cyclic ketones the best result was found in the case of
cyclohexanone; spirobicyclic tetracyanocyclopropane 6b was
obtained in 75% yield. Sufficiently good results were achieved also
in the cases of cyclopentanone and cycloheptanone, the yields of
corresponding spirobicyclic tetracyanocyclopropanes 6a and 6c
were 52% and 63% correspondingly (Table 4).
b
Isolated yield (isolated by filtration of the reaction mixture).
Taking into consideration the data obtained, the following re-
action scheme was proposed for the direct cascade transformation
of carbonyl compounds and malononitrile into substituted tetra-
cyanocyclopropanes (Scheme 7).
First, by the action of base, the anions of malononitrile arise in
the solution, then by the usual way Knoevenagel condensation of
carbonyl compound with anion of malonitrile takes place with the
formation of alkylidenemalononitrile 3.11 Addition of the second
anion of malononitrile to alkylidenemalononitrile 3 leads to anion
A, which exist in alcohol solution in the equilibrium with alkyli-
denemalononitrile
3
and the anion of malononitrile.12 Then
halogenation of anion A results in 1-halogeno-1,1,3,3-tetracyano-
propane 9 formation, which is cyclized into tetracyanocyclopro-
pane 2 (pathway A). Alternative malononitrile anion halogenation,
and addition of halogenomalononitrile anion to alkylidenemalo-
nonitrile 3 leads also to tetracyanocyclopropane 2 (pathway B).
Concerted realization of two last reaction pathways A and B ensures
for the most part of carbonyl compounds studied 50–80% yield of
the substituted tetracyanocyclopropanes 2.
The pathway A correlates with the earlier known method of the
synthesis of tetracyanosubstituted cyclopropanes suggested by
Mariella and Roth.13 This method includes bromination of 2-
alkylsubstituted 1,1,3,3-tetracyanopropanes in aqueous ethanol
with instant formation of 3-alkyl substituted 1,1,2,2-tetracyano-
substituted cyclopropanes.
(CH2)n
(CH2)n
CN
CN
Br2
NC
NC
CN
CN
+
+
EtONa/EtOH
CN
4
CN
4
6a-d
O
5a-d
a n = 1, b n= 2, c n = 3, d n = 8
Scheme 5.
The pathway B is similar to the earlier known method for the syn-
thesis of tetracyanosubstituted cyclopropanes as the reaction of alky-
lidene- or benzylidenemalononitriles and bromomalononitrile14–18 in
aqueous ethanol without use of base as bromomalononitrile is a rea-
sonably strong acid, which can furnish a sufficient concentration of
bromodicyanocarbanion for the reaction.19
Table 4
Cascade transformation of cyclic ketones 5a–d and malononitrile 4 into spirobicyclic
tetracyanocyclopropanes 6a–da
Entry
Cyclic ketone
n
Cyclopropane, yieldb (%)
1
2
3
4
5a
5b
5c
5d
1
2
3
8
6a, 52
6b, 75
6c, 63
6d, 25
3. Conclusion
a
Cyclic ketones 5a–d (10 mmol), 20 mmol of malononitrile 4, 10 mmol of bro-
mine, 12 mmol of EtONa, 20 mL of EtOH, time of the reactiond3 h.
In conclusion, a new cascade ‘one-pot’ reaction was found,
namely the direct formation of cyclopropane structures from
b
Isolated yield (isolated by filtration of the reaction mixture).

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M.N. Elinson et al. / Tetrahedron 65 (2009) 6057–6062
CN
CN
CN
R1
R2
R1
R2
R3ONa
-R3OH
CN
CN
_
_
C
+
O
C
+
C
OH
CN
3
CN
CN
CN
B, -BH
_
CN
R2
R1
CN
CN
R1
R2
NC
CN
_
_
C
+
C
CN
CN
3
CN
CN
A
-
XHal
Hal
-X
XHal
Pathway A
-
-X
CN
CN
Pathway B
R3OH
R1
R2
CN
Hal
NC
CN
CN
R1
R2
R3OH
9
NC
NC
CN
CN
2
Hal = I, Br
O
N
X=I, Br,
O
Scheme 7.
carbonyl compounds and malononitrile. The action of free halogen
or active halogen containing compounds on the 1 equiv of carbonyl
compound and 2 equiv of malononitrile in basic alcohol solution
results in the formation of substituted-1,1,2,2-tetracyanocyclopro-
panes in 15–80% yields. The latter are well-known precursors for
different bicyclic heterosystems, among them compounds con-
taining a cyclopropane ring7,20 and possessing different types of
pharmacological activity.2,21 Thus, a new simple and efficient way
to 3-substituted tetracyanocyclopropanes in 60–80% yields was
found starting from such simple and reasonable compounds as
aldehydes, some cyclic ketones or substituted cyclohexanones and
malononitrile. The procedure utilizes inexpensive reagents, it is
easily carried out and the work up is not complicated.
3-Substituted-1,1,2,2-tetracyanocyclopropanes are crystallized di-
rectly from the reaction mixture, consequently, the isolation in-
cludes only filtration and washing with warm water.
DMSO-d6 and CDCl3 solutions. IR spectra were registered with
a SPECORD M82 spectrometer in KBr pellets. Mass spectra (EI,
70 eV) were obtained directly using Finningan MAT INCOS 50
spectrometer.
4.2. Typical procedure
To a 10 mL ethanolic solution of carbonyl compound (10 mmol)
and malononitrile 4 (1.32 g, 20 mmol) in a 50 mL beaker, 0.82 g
(12 mmol) of sodium ethoxide in 10 mL of ethanol was added
during 1 min. Then 10 mmol (0.51 mL) of bromine was added for
1 min without external cooling. The mixture was magnetically
stirred at room temperature for 3 h. Then solid phase was filtered
off, washed with warm water and dried in a desiccator over P2O5 to
isolate pure product.
All compounds gave expected NMR spectra. For new com-
pounds, satisfactory elemental analyses, mass and IR spectroscopy
data were obtained.
4. Experimental section
4.1. General remarks
4.2.1. 3-Phenyl-1,1,2,2-tetracyanocyclopropane (2a)
White solid. Yield 1.81 g (83%); mp 229–230 ꢀC (lit. mp15 227–
230 ꢀC); 1H NMR dH (250 MHz, DMSO-d6) 5.27 (s, 1H, CH), 7.44–7.52
(m, 3H, Ar), 7.74–7.82 (m, 2H, Ar).
Chemicals were purchased from AldrichÒ and AcrosÒ. All
melting points were measured with a Gallenkamp melting point
apparatus and are uncorrected. 1H and 13C NMR spectra were
recorded with a Bruker WM-250, Bruker AM-300 and Bruker
Avance II 300 spectrometers at ambient temperature. Chemical
4.2.2. 3-(4-Methylphenyl)-1,1,2,2-tetracyanocyclopropane (2b)
White solid. Yield 1.67 g (72%); mp 226–229 ꢀC (lit. mp15
227–230 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 2.33 (s, 3H,
shifts (d) are given in parts per million relative to Me4Si for

M.N. Elinson et al. / Tetrahedron 65 (2009) 6057–6062
6061
CH3), 5.23 (s, 1H, CH), 7.30 (d, J 7.8 Hz, 2H, Ar), 7.68 (d, J 7.8 Hz,
2H, Ar).
4.2.15. 3-n-Propyl-1,1,2,2-tetracyanocyclopropane (2o)
White solid. Yield 1.34 g (73%); mp 136–138 ꢀC (lit. mp7 136–
138 ꢀC); 1H NMR dH (250 MHz, DMSO-d6) 0.96 (t, J 7.3 Hz, 3H, CH3),
1.51–1.65 (m, 2H, CH2), 1.69–1.77 (m, 2H, CH2) 3.87 (t, J 7.3 Hz, 1H, CH).
4.2.3. 3-(4-Methoxyphenyl)-1,1,2,2-tetracyanocyclopropane (2c)
Yellow solid. Yield 1.91 g (77%); mp 208–210 ꢀC (lit. mp15
209–210 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 3.79 (s, 3H,
OCH3), 5.15 (s, 1H, CH), 7.04 (d, J 8.4 Hz, 2H, Ar), 7.73 (d, 8.4 Hz,
2H, Ar).
4.2.16. 3,3-Dimethyl-1,1,2,2-tetracyanocyclopropane (2p)
White solid. Yield 0.73 g (43%); mp 208–210 ꢀC (lit. mp14 209.5–
210 ꢀC); 1H NMR dH (300 MHz, DMSO-d6): 1.58 (s, 6H, CH3).
4.2.4. 3-(2-Methoxyphenyl)-1,1,2,2-tetracyanocyclopropane (2d)
Yellow solid. Yield 1.56 g (63%); mp 240–241 ꢀC (lit. mp8 240–
241 ꢀC); 1H NMR dH (250 MHz, DMSO-d6) 3.89 (s, 3H, OCH3), 5.04 (s,
1H, CH), 7.05 (t, J 7.6 Hz, 1H, Ar), 7.19 (d, J 8.6 Hz, 1H, Ar), 7.48 (t, J
7.6 Hz, 1H, Ar), 7.76 (d, J 7.3 Hz, 1H, Ar).
4.2.17. 3-Ethyl-3-methyl-1,1,2,2-tetracyanocyclopropane (2q)
White solid. Yield 0.61 g (33%); mp 207–208 ꢀC (lit. mp7 208–
209 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 1.33 (t, J 7.4 Hz, 3H, CH3),
1.75 (s, 3H, CH3), 2.16 (q, J 7.4 Hz, 2H, CH2).
4.2.18. 3,3-Diethyl-1,1,2,2-tetracyanocyclopropane (2r)
White solid. Yield 0.30 g (15%); mp 165–166 ꢀC (lit. mp22 167–
168 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 1.29 (t, J 7.4 Hz, 6H, CH3),
2.05 (q, J 7.4 Hz, 4H, CH2).
4.2.5. 3-(4-Fluorophenyl)-1,1,2,2-tetracyanocyclopropane (2e)
White solid. Yield 1.77 g (75%); mp 216–217 ꢀC (lit. mp8 216–
217 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 5.25 (s, 1H, CH), 7.34 (t, J
8.5 Hz, 2H, Ar), 7.86–8.00 (m, 2H, Ar).
4.2.19. 1,1,2,2-Tetracyanospiro[2.4]heptane (6a)
White solid. Yield 1.02 g (52%); mp 250–251 ꢀC (lit. mp7 250–
251 ꢀC); 1H NMR (300 MHz, DMSO-d6) 1.86–1.49 (m, 4H, CH2),
2.01–2.07 (m, 4H, CH2).
4.2.6. 3-(2-Chlorophenyl)-1,1,2,2-tetracyanocyclopropane (2f)
White solid. Yield 1.79 g (71%); mp 245–247 ꢀC (lit. mp15 246–
248 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 5.48 (s, 1H, CH), 7.48–7.62
(m, 2H, Ar), 7.68–7.74 (m, 1H, Ar), 8.03–8.09 (m, 1H, Ar).
4.2.20. 1,1,2,2-Tetracyanospiro[2.5]octane (6b)
4.2.7. 3-(3-Chlorophenyl)-1,1,2,2-tetracyanocyclopropane (2g)
White solid. Yield 1.65 g (65%); mp 187–189 ꢀC (lit. mp15 183–
185 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 5.35 (s, 1H, CH), 7.51–7.59
(m, 2H, Ar), 7.77–7.85 (m, 1H, Ar), 8.08 (s, 1H, Ar).
White solid. Yield 1.57 g (75%); mp 178–180 ꢀC (lit. mp14 177–
179 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 1.46–1.56 (m, 2H, CH2),
1.61–1.73 (m, 4H, CH2), 1.80–1.90 (m, 4H, CH2).
4.2.21. 1,1,2,2-Tetracyanospiro[2.6]nonane (6c)
4.2.8. 3-(4-Chlorophenyl)-1,1,2,2-tetracyanocyclopropane (2h)
White solid. Yield 2.07 g (82%); mp 250–251 ꢀC (lit. mp15 248–
250 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 5.28 (s, 1H, CH), 7.59 (d, J
8.5 Hz, 2H, Ar), 7.88 (d, J 8.5 Hz, 2H, Ar).
White solid. Yield 1.41 g (63%); mp 169–170 ꢀC (lit. mp8 170–
171 ꢀC); 1H NMR dH (300 MHz, CDCl3) 1.70–1.79 (m, 4H, CH2), 1.80–
1.92 (m, 4H, CH2), 2.08–2.16 (m, 4H, CH2).
4.2.22. 1,1,2,2-Tetracyanospiro[2.10]tetradecane (6d)
4.2.9. 3-(2,4-Dichlorophenyl)-1,1,2,2-tetracyanocyclopropane (2i)
White solid. Yield 1.81 g (63%); mp 226–228 ꢀC (lit. mp15 225–
228 ꢀC); 1H NMR dH (250 MHz, DMSO-d6) 5.48 (s, 1H, CH), 7.66 (dd,
J1 8.5 Hz, J2 1.9 Hz, 1H, Ar), 7.93 (d, J 1.9 Hz, 1H, Ar), 8.10 (d, J 8.5 Hz,
1H, Ar).
White solid. Yield 0.73 g (25%); mp 198–200 ꢀC (lit. mp14 197–
200 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 1.26–1.46 (m, 14H, CH2),
1.55–1.69 (m, 4H, CH2), 1.80–1.92 (m, 4H, CH2).
4.2.23. 1,1,2,2-Tetracyano-6-methylspiro[2.5]octane (8a)
White solid. Yield 1.41 g (63%); mp 165–166 ꢀC (lit. mp23 166–
167 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 0.97 (d, J 6.5 Hz, 3H, CH3),
1.12–1.32 (m, 2H, CH2),1.45–1.67 (m, 3H, CH, CH2),1.78–1.90 (m, 2H,
CH2), 2.12–2.28 (m, 2H, CH2).
4.2.10. 3-(3-Bromophenyl)-1,1,2,2-tetracyanocyclopropane (2j)
White solid. Yield 1.81 g (61%); mp 186–187 ꢀC (lit. mp8 186–
187 ꢀC); 1H NMR dH (250 MHz, DMSO-d6) 5.32 (s, 1H, CH), 7.45 (t, J
8.5 Hz,1H, Ar), 7.69 (d, J 8.5 Hz,1H, Ar), 7.88 (d, J 8.5 Hz,1H, Ar), 8.23
(s, 1H, Ar).
4.2.24. 6-tert-Butyl 1,1,2,2-tetracyanospiro[2.5]octane (8b)
White solid. Yield 2.02 g (76%); mp 176–178 ꢀC (lit. mp23 177–
179 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 0.88 (s, 9H, CH3), 1.08–
1.30 (m, 3H, CH, CH2), 1.56–1.66 (m, 2H, CH2), 1.90–2.00 (m, 2H,
CH2), 2.15–2.30 (m, 2H, CH2).
4.2.11. 3-(3-Nitrophenyl)-1,1,2,2-tetracyanocyclopropane (2k)
White solid. Yield 2.05 g (78%); mp 244–245 ꢀC (lit. mp15 246–
247 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 5.46 (s, 1H, CH), 7.82 (t, J
8.0 Hz, 1H, Ar), 8.28–8.41 (m, 2H, Ar), 9.01 (s, 1H, Ar).
4.2.25. 1,1,2,2-Tetracyano-6-phenylspiro[2.5]octane (8c)
White solid. Yield 2.00 g (70%); mp 170–171 ꢀC (lit. mp23 171–
173 ꢀC); 1H NMR dH (300 MHz, CDCl3) 1.75–1.85 (m, 2H, CH2), 2.07–
2.19 (m, 2H, CH2), 2.35–2.47 (m, 4H, CH2), 2.76–2.94 (m, 1H, CH),
7.25–7.52 (m, 5H, Ph).
4.2.12. 3-(4-Nitrophenyl)-1,1,2,2-tetracyanocyclopropane (3l)
White solid. Yield 1.63 g (62%); mp 232–234 ꢀC (lit. mp15 232–
235 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 5.50 (s, 1H, CH), 8.20 (d, J
8.8 Hz, 2H, Ar), 8.36 (d, J 8.8 Hz, 2H, Ar).
4.2.13. 3-(1-Naphthyl)-1,1,2,2-tetracyanocyclopropane (2m)
White solid. Yield 2.04 g (76%); mp 257–259 ꢀC (lit. mp15 249–
252 ꢀC); 1H NMR dH (300 MHz, DMSO-d6) 5.85 (s, 1H, CH), 7.59–7.72
(m, 2H, Ar), 7.77–7.92 (m, 2H, Ar), 8.06–8.16 (m, 3H, Ar).
4.2.26. 1,1,2,2-Tetracyano-5-methylspiro[2.5]octane (8d)
White solid. Yield 1.37 g (61%); mp 165–166 ꢀC; 1H NMR dH
(300 MHz, DMSO-d6) 1.10 (d, J 5.6 Hz, 3H, CH3), 1.48–1.62 (m, 1H,
CH), 1.70–1.86 (m, 4H, CH2), 1.78–1.90 (m, 2H, CH2), 2.12–2.28 (m,
2H, CH2); 13C NMR dc (75 MHz, DMSO-d6) 21.6, 23.6, 24.5, 25.9,
29.6, 31.4, 32.6, 37.4, 46.1, 107.5, 107.9; MS (70 eV) m/z (relative
intensity %): 224 (2) [M]þ, 209 (3), 196 (4), 96 (52), 95 (54), 81
4.2.14. 3-Ethyl-1,1,2,2-tetracyanocyclopropane (2n)
White solid. Yield 1.11 g (65%); mp 194–196 ꢀC (lit. mp22 197 ꢀC);
1H NMR dH (300 MHz, DMSO-d6) 1.14 (t, J 7.4 Hz, 3H, CH3), 1.70–1.82
(m, 2H, CH2), 3.81 (t, J 7.4 Hz, 3H, CH).
(93), 67 (79), 55 (77), 41 (95), 39 (100); IR (KBr):
n
¼2956, 2932,
2904, 2856, 2264, 2256, 1452, 1376, 1284, 1132 cmꢁ1. Anal. Calcd

6062
M.N. Elinson et al. / Tetrahedron 65 (2009) 6057–6062
7. Elinson, M. N.; Feducovich, S. K.; Lizunova, T. L.; Nikishin, G. I. Tetrahedron 2000,
56, 3063–3069.
8. Elinson, M. N.; Feducovich, S. K.; Stepanov, N. O.; Vereshchagin, A. N.; Nikishin,
G. I. Tetrahedron 2008, 64, 708–713.
(%) for C13H12N4: C 69.62, H 5.39, N 24.98. Found (%): C 69.41, H
5.53, N 24.87.
9. For reviews see: (a) Tietze, L. F. Chem. Rev. 1996, 96, 115–136; (b) Padwa, A. Pure
Appl. Chem. 2003, 75, 47–62; (c) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G.
Angew. Chem. 2006, 45, 7134–7186.
Acknowledgements
10. Fatiadi, A. J. Synthesis 1978, 165–204.
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The authors gratefully acknowledge the financial support of the
Russian Foundation for Basic Research (Project No. 09-03-00003).
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