A new, fast and easy strategy for one-pot synthesis of full substituted cyclopropanes: Direct transformation of aldehydes to 3-aryl-1,1,2,2- tetracyanocyclopropanes

JOURNAL OF THE CHINESE

CHEMICAL SOCIETY

Article

A New, Fast and Easy Strategy for One-pot Synthesis of Full Substituted

Cyclopropanes: Direct Transformation of Aldehydes to 3-Aryl-1,1,2,2-

tetracyanocyclopropanes

Nader Noroozi Pesyan,^a* Mohammad Ali Kimia,^aMohammad Jalilzadeh^aand Ertan Ôahin^b

^aDepartment of Chemistry, Faculty of Science, Urmia University, 57159, Urmia, Iran

^bDepartment of Chemistry, Faculty of Science, Atatürk University, 25240, Erzurum, Turkey

(Received: Apr. 4, 2012; Accepted: Jun. 28, 2012; Published Online: Oct. 4, 2012; DOI: 10.1002/jccs.201200189)

A new, fast and easy method for one-pot reaction of aromatic aldehydes and dialdehydes with malono-

nitrile and cyanogen bromide has been developed to afford full substituted 3-arylcyclopropane-1,1,2,2-

tetracarbonitriles in excellent yields in very short time (about 5 seconds). The structures elucidations were

characterized by IR, ¹H NMR, ¹³C NMR, mass spectrometry and X-ray crystallography techniques. For

these compounds the crystallographic data showed two structures in mirror image in solid case and one

distinct structure in solution. The reaction mechanism was discussed.

Keywords: Malononitrile; One-pot reaction; Tetracyanopropanes; Cyanogen bromide.

INTRODUCTION

In multicomponent reactions (MCRs), three or more

Synthesis of 3-alkylcyclopropane-1,1,2,2-

tetracarbonitrile in the reaction with bro-

mine⁷

Scheme I

reactants come together in a single reaction vessel to form

new products that contain structural unit so fall the compo-

nents. This type of reaction becomes increasingly impor-

tant in organic and medicinal chemistry because it allows to

obtain highly sophisticated polyfunctional molecules through

simple one-pot procedures. Multicomponent reactions

have been successfully employed to generate highly di-

verse combinatorial libraries for high-throughput screen-

ing of biological and pharmacological activities. By using

of three or more building blocks in a one-pot, a high yield-

ing multicomponent reaction leads to a wide structural and

functional diversity combined with excellent combina-

torial efficiency. Over the past decade, industrial and aca-

demic research has made powerful MCRs strategies into

one of the most efficient and cost-effective tools for combi-

natorial synthesis.^1,2The development of novel MCRs is an

intellectually challenging task since one has to consider not

only the reactivity match of the starting materials but also

the reactivity of the intermediate molecules generated in

situ, their compatibility and their compartmentalization.³

The cyclopropyl group is an important structural mo-

tif in many herbal compounds, displaying antibacterial, an-

tiviral and some enzyme inhibition activities.^4-6First syn-

thesis of 3-substituted cyclopropane was described by

Mariella et al. ⁷(Scheme I). In this reaction, at first the sim-

ple condensation reaction of aldehyde and malononitrile

affordes alkylidenemalononitriles then reaction with the

second malononitrile affords Michael adduct. Then bro-

mination of this product with bromine is done, and finally

intramolecular nucleophilic attack of carbon atom to the

other carbon containing bromine atom (pushing the bro-

mide ion out) produces 3-substituted cyclopropane.⁷

The methods of cyclopropane synthesis have been di-

vided into two main groups: namely intramolecular cy-

clization and addition between alkenes and carbenes.^4,6On

the other hand, Michael Initiated Ring Closer (MIRC) is an

important synthetic method for cyclization.⁵Reaction of

halogenated acid anion with the activated alkene followed

by cyclization along with elimination of halogen has gener-

ated tetramethyl 3,3-dialkylcyclopropane-1,1,2,2-tetracar-

boxylates (full substituted cyclopropanes)⁶(Scheme II).

The use of alkylidenemalononitriles is common in or-

ganic synthesis. Direct transformation of benzylidenemal-

ononitriles and malononitrile into 3-aryl-1,1,2,2-tetracy-

* Corresponding author. Tel: (+98) 441 2972147; Fax: (+98) 441 2776707; E-mail: n.noroozi@urmia.ac.ir; nnp403@gmail.com

J. Chin. Chem. Soc. 2013, 60, 35-44

35

Article

Noroozi Pesyan et al.

Synthesis of tetramethyl 3,3-dialkylcyclo-

propane-1,1,2,2-tetracarboxylates⁶

Scheme II

Synthesis of 3-arylcyclopropane-1,1,2,2-

tetracarbonitriles (3) in the reaction of al-

dehydes (1) with malononitrile (2) in the

presence of cyanogen bromide and tri-

ethylamine

Scheme III

anocyclopropanes in basic alcohol solution has been de-

scribed by Elinson et al.⁸On the other hand, one-pot cas-

cade assembling of 3-substituted tetracyanocyclopropanes

from alkylidenemalononitriles and malononitrile by the

only bromine direct reaction has also been reported by the

same group.^9,10

Cyanogen bromide is a toxic but very useful reagent

in organic synthesis.^11,12It is a capable reagent for the syn-

thesis of cyanamides,¹¹cyanates,¹²and also used to selec-

tive cleavage of the methionyl peptide bonds in ribonu-

clease¹³and etc. Furthermore this compound is a useful

brominating and cyanating agent for the bromination and

cyanation of imidazoles,¹⁴free radical reaction with al-

kanes that results in bromination of alkanes¹⁵and a-bro-

mination of b-aminoenones.¹⁶More recently, we have re-

ported the reaction of (thio)barbituric acids (as a symmetri-

cal barbituric acids) with aldehydes¹⁷and ketones¹⁸in the

presence of cyanogen bromide and triethylamine. Based on

these concepts, we have accomplished a new and a very

fast one-pot transformation of aldehydes and malononitrile

to 3-arylcyclopropane-1,1,2,2-tetracarbonitriles in the pres-

ence of cyanogen bromide and triethylamine in excellent

yields in a few seconds.

Scheme IV Proposed mechanism for the synthesis of

7

RESULTS AND DISCUSSION

This paper describes a new route one-pot reaction of

aldehydes (1a-1l) with malononitrile (2) and cyanogen

bromide into 3-arylcyclopropane-1,1,2,2-tetracarbonitriles

(3a-3l) in the presence of triethylamine in excellent yields

in very short time (5 seconds) (Scheme III).

spectrum of 7 shows the frequency of NH⁺stretching at the

broad range of 2500-3300 cm^-1, frequency of CN and C-Br

stretching at 2167 and 565 cm^-1, respectively. The ¹H NMR

spectrum of this compound shows (integration in parenthe-

sis) a triplet at d 1.39 (9H) and a multiplet (a quartet ap-

proximately) at d 3.14 ppm (6H) are corresponding to

methyl and methylene protons in triethylammonium salt

As described in Scheme IV, in these reactions, the in

situ generated salt triethylammonium bromodicyanometh-

anide (7) plays an essential role for the synthesis of 3. Pro-

posed reaction mechanism for the formation of 7 is shown

in Scheme IV. According to our search, there is no report

about this compound in literature. The salt of 7 was isolated

and characterized by spectroscopy techniques. The IR

36

www.jccs.wiley-vch.de

J. Chin. Chem. Soc. 2013, 60, 35-44

JOURNAL OF THE CHINESE

CHEMICAL SOCIETY

One-pot Synthesis of 3-Arylcyclopropane-1,1,2,2-tetracarbonitriles

moiety, respectively. A broad singlet at d 9.78 ppm (1H) is

of NH⁺in this salt. ¹³C NMR spectrum of this salt shows

four distinct peaks that confirm the structure of 7 (Fig. 1

and see supplementary data). Unfortunately, all attempts

failed to separate or characterize intermediates 5 and 6.

Other evidence for the formation and confirmation of 7 (the

existence of bromine atom in this salt structure) was per-

formed by Beilstein test and the wet silver nitrate test (pre-

cipitate of pale yellow silver bromide). On the basis of the

well established chemistry of barbituric acids in the reac-

tion with cyanogen bromide in the presence of triethyl-

amine^17,18and also the mechanism of the bromination of

imidazoles by cyanogen bromide,¹⁴it is reasonable to as-

sume that the compound 2 reacts directly with cyanogen

bromide to form 2,2-dicyanoacetimidoyl bromide (5) inter-

mediate through path a. Intramolecular rearrangement of

this intermediate produces 2-bromomalononitrile (6) inter-

mediate. Finally, triethylamine as a base captures the acidic

proton to afford 7 (Scheme IV). Malononitrile 2 directly re-

acts with triethylamine to form the salt of triethylammo-

nium dicyanomethanide (4) in the absence of cyanogen

bromide (path b). The salt of 4 was also separated and char-

acterized in direct reaction of 2 with triethylamine through

path b (see experimental and Scheme IV). We performed

the reaction of 2 with cyanogen bromide in the presence of

triethylamine and in the absence of aldehydes, 1 so the

compound 7 was isolated in excellent yield. On the other

hand, in the presence of aldehyde, compounds 3 and 7 were

isolated as major and minor products, respectively. These

experiments confirm the major role of 7 in the synthesis of

3.

Another evidences for the confirmation of 7 is the

formation of reported salts of triethylammonium-5-bromo

(thio)barbiturates (13a¢-13c¢).^17,18Representatively, the re-

action of 2 with cyanogen bromide in the presence of

triethylamine in ethanol afforded the salt of 7 as we have

described recently the reaction mechanism in the case of

(thio)barbituric acid (11a¢-11c¢),^17-205,5-dimethylcyclo-

hexane-1,3-dione (dimedone, 12a¢) and 2,2-dimethyl-

1,3-dioxane-4,6-dione (Meldrum’s acid, 12b¢). Similarly,

the reaction of 11a¢-11c¢, 12a¢ and 12b¢ with BrCN af-

forded the corresponding salts of 13a¢-13c¢,^17,18triethyl-

ammonium 1-bromo-4,4-dimethyl-2,6-dioxocyclohexan-

1-ide (14a¢) and triethylammonium 5-bromo-2,2-dimeth-

yl-4,6-dioxo-1,3-dioxan-5-ide (14b¢) in the presence of

triethylamine at the range of 0 °C to room temperature (Fig.

2).

Representatively, the reaction mechanism for the for-

mation of 3e is shown in Scheme V. First, the reaction of al-

Fig. 2. Formula structures of (thio)barbituric acids

(11a¢-11c¢), dimedone (12a¢), Meldrum’s acid

(12b¢), triethylammonium-5-bromo (thio)bar-

biturates (13a¢-13c¢),^17,18triethylammonium

1-bromo-4,4-dimethyl-2,6-dioxocyclohexan-1

-ide (14a¢) and triethylammonium 5-bromo-

2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ide

(14b¢).

Fig. 1. Characterized ¹H (a) and ¹³C NMR (b) spectra

of 7.

J. Chin. Chem. Soc. 2013, 60, 35-44

www.jccs.wiley-vch.de

37

Article

Noroozi Pesyan et al.

pound shows eight distinct peaks. The peaks at d 108.9 and

110.4 ppm corresponds to the cyano groups with different

chemical shifts. The IR spectrum shows two peaks at the

frequency of 2264 and 2211 cm^-1that confirms the exis-

tence of cyano groups in the molecule. These data are in

good agreement together with the formula structure of 3e

as representative (see experimental section and supplemen-

tary data).

Representatively, proposed mechanism for

the synthesis of 3e (path a) and no path b

was occurred

Scheme V

The reaction of bulky aldehyde such as 9-anthracene

carbaldehyde (1m) and aldehydes containing exchange-

able protons such as 2-pyrrole carbaldehyde (1n) and con-

taining hydroxyl group (1o-1s) with 2 and BrCN in the

presence of triethylamine afforded Knoevenagel adducts

(8m-8s) and did not match cyclopropane products (3m-s).

Presumably, the hindrance effect in 1m led to formation of

8m. Instead, the existence of acidic NH group on 8n and

OH group upon 8o-8s, caused the 7 as nucleophile to be

able to capture acidic proton on NH and/or OH group (path

a) prior to Michael addition to b-carbon position of

Knoevenagel adducts 8n-8s (path b) (Scheme VI). There-

fore, the path a is favored than that of path b. It seems that

the existence of exchangeable proton having acidic nature

dehyde 1e with malononitrile 2 was afforded 2-(4-chloro-

benzylidene)malononitrile (8e) then the nucleophilic at-

tacking of 7 to the b-carbon position of 8e as an a,b-unsat-

urated compound afforded intermediate triethylammonium

3-bromo-2-(4-chlorophenyl)-1,1,3,3-tetracyanopropan-1-

ide (9e). Intramolecular C-attack of carbanion to carbon

atom containing bromine atom (path a) as an electrophile

(pushing the bromide ion out) produced 3-(4-chlorophen-

yl)cyclopropane-1,1,2,2-tetracarbonitrile (3e). All attempts

to separate and characterize the intermediates 8 and 9

failed. No 22e was observed through intermediate 21e.

This observation indicated that the C-attack of carbanion to

nitrile group did not occur (Scheme V, path b).

Proposed mechanism for the favoring of

Scheme VI

path a and unfavored path b

Representatively, the reaction of 1e and 2 exclusively

were obtained 8e in the presence of triethylamine and ab-

sence of cyanogen bromide. It has been shown that the salt

of 7 plays the major role in these reactions. First, it is a

nucleophile in the reaction with 8e then it has an electro-

philic character (carbon atom containing of bromine) in the

intermediate 9e to form 3e (Scheme V). The reaction condi-

tion, time and yields are outlined in Table 1.

1

Representatively, H NMR spectrum of 3e show a

singlet at d 5.03 ppm corresponding to cyclopropyl C-H

proton and two doublets at d 7.63 and 7.95 ppm (J = 8.4 Hz)

for 4-chlorophenyl ring. ¹³C NMR spectrum of this com-

38

www.jccs.wiley-vch.de

J. Chin. Chem. Soc. 2013, 60, 35-44

JOURNAL OF THE CHINESE

CHEMICAL SOCIETY

One-pot Synthesis of 3-Arylcyclopropane-1,1,2,2-tetracarbonitriles

on Knoevenagel adducts prevented the Michael addition of

7 and made the path a more favorable (Scheme VI). An-

other possible pathway can be path c. Triethylamine as a

base can attack to acidic proton on phenol derivative (4-

hydroxy benzaldehyde 1o as representative) to form tri-

ethylammonium 4-formylphenolate 20o (Scheme VI, path

c). Our attempt to separate and characterize 8o, 10o and

20o failed. These results demonstrated the reason of unsuc-

cessful cyclopropanation of aromatic aldehydes possessing

exchangeable proton.

The reaction of picolinaldehyde (1l) with some b-di-

carbonyl compounds such as 1,3-dialkylated (thio)barbitu-

J. Chin. Chem. Soc. 2013, 60, 35-44

www.jccs.wiley-vch.de

39

Article

Noroozi Pesyan et al.

Reaction of phthalaldehyde (17a²), iso-

phthalaldehyde (17b²) and terphthalal-

dehyde (17c²) with 2 in the presence of

cyanogen bromide and triethylamine

ric acids (For instance 11a¢-d¢) was exclusively afforded

zwitterionic salts of (thio)barbiturates (15b¢)²¹and (15a¢-

d¢)²²(Scheme VII, path c). Based on this concept, our aim

was an attempt for synthesis of the zwitterionic salt of

dicyano (2,2-dicyano-3-(pyridin-2-yl)-2,3-dihydro-1H-

indolizin-4-ium-1-yl)methanide (16l) in the reaction of 1l

with 2 under natural condition and no 16l was observed

(path a). In this current reaction, 3l was obtained in the

presence of BrCN and triethylamine in excellent yield

(Scheme VII, path b).

Scheme VIII

Reaction of picolinaldehyde (1l) with

malononitrile (2) for synthesis of 3l in the

presence of Et₃N. An attempt for synthe-

sis of zwiterionic salt of 16l under natural

condition was unsuccessful

Scheme VII

ene)bis(cyclopropane-1,1,2,2-tetracarbonitrile) (19c²), re-

spectively. The reaction condition and yields of aromatic

dialdehydes 17a²-17c² are outlined in Table 2.

Representatively, ¹H NMR spectrum of 18a² show a

singlet at d 5.08 ppm corresponding to cyclopropyl C-H

proton and three multiplets at d 7.95, 8.20 and 8.30 ppm for

phenyl ring and a singlet at d 10.27 corresponds to alde-

hyde proton. ¹³C NMR spectrum of this compound shows

We also performed the reaction of phthalaldehyde

(17a²), isophthalaldehyde (17b²) and terphthalaldehyde

(17c²) with 2 in the presence of cyanogen bromide and

triethylamine under the same condition (Scheme VIII). The

reaction of 17a² with 2 and cyanogen bromide in the pres-

ence of triethylamine was afforded 3-(2-formylphenyl)cy-

clopropane-1,1,2,2-tetracarbonitrile (18a²) due to ortho

hindrance effect. In respect to the 17b² and 17c², both alde-

hyde groups in each compound were reacted with 2 and

were obtained 3,3¢-(1,3-phenylene)bis(cyclopropane-

1,1,2,2-tetracarbonitrile) (19b²) and 3,3¢-(1,4-phenyl-

40

www.jccs.wiley-vch.de

J. Chin. Chem. Soc. 2013, 60, 35-44

JOURNAL OF THE CHINESE

CHEMICAL SOCIETY

One-pot Synthesis of 3-Arylcyclopropane-1,1,2,2-tetracarbonitriles

Table 3. Selected crystallographic data for 3b

eleven distinct peaks. The peaks at d 109.2 and 110.7 ppm

corresponds to the cyano groups with different chemical

shifts and a peak at 193.8 related to carbonyl group. The IR

spectrum shows two peaks at the frequency of 2259 and

1682 cm^-1that confirms the existence of cyano and car-

bonyl groups in the molecule. The ¹H NMR spectrum of

19b² show a singlet at d 5.24 ppm, a triplet at d 7.81 (J = 8.1

Hz), a doublet at d 8.14 (J = 7.8 Hz) and a singlet at d 8.44

ppm corresponding to cyclopropyl C-H and phenyl pro-

tons, respectively. ¹³C NMR spectrum of this compound

shows eight distinct peaks. IR spectrum show a distinct

peak at the frequency of 2262 cm^-1and no carbonyl fre-

quency absorption was observed in the IR spectrum. These

data are in good agreement together with the formula struc-

ture of the 18a² and 19b², respectively (see experimental

section and supplementary data). In the reaction of terphth-

alaldehyde 17c², the 18c² (»7%) an unknown compound

(»10%) was also obtained. Attempt for the separation of

18c² and unknown compound was unsuccessful due to

their equal polarity.

Crystal data (3b)

Emprical Formula

M

C₁₃H₅N₅O₂

263.22

T(K)

293

Space group

Crystal system

a (Å)

b (Å)

c (Å)

P2₁/c

Monoclinic

13.8529 (2)

12.2866 (5)

14.1879 (4)

90

a (°)

b (°)

g (°)

V (Å³)

90.415 (3)

90

2414.79 (12)

8

Z

F(000)

1072

1.448

0.71073 Å

0.105

D_x(mg m^{- 3})

l (Å)

m (mm^{- 1})

Data collection

R_int

0.116

q_max, q_min(°)

Refinement

R[F²> 2s(F²)]

wR(F²)

S

26.5/ 2.2

0.0752

0.236

0.976

Representatively, for further study of compound 3b,

an X-ray diffraction analysis of 3b was undertaken. The re-

sults of this study confirmed unambiguously the proposed

structure (Fig. 3). The crystal packing diagram of 3b is

shown in Fig. 4. The selected crystal data, bond lengths, an-

gles and torsion angles are summarized in Tables 3 and 4,

respectively. For the crystal structure determination, the

single-crystal of the compound 3b was used for data collec-

tion on a four-circle Rigaku R-AXIS RAPID-S diffract-

ometer (equipped with a two-dimensional area IP detector).

The graphite-monochromatized Mo K_aradiation (l =

Dr_max, Dr_min(e Å^{- 3})

0.19, -0.25

0.71073 Å) and oscillation scans technique with Dw = 5°

for one image were used for data collection. The lattice pa-

rameters were determined by the least-squares methods on

the basis of all reflections with F²> 2s(F²). Integration of

Fig. 3. ORTEP drawing of the compound 3b. The

asymmetric unit contains two isomers in mirror

image. Thermal ellipsoids are shown at 30%

probability level.

Fig. 4. Packing diagram of the compound 3b.

J. Chin. Chem. Soc. 2013, 60, 35-44

www.jccs.wiley-vch.de

41

Article

Noroozi Pesyan et al.

Table 4. Selected bond length (Å), angles (q, °) and torsion

angles (j, °) for 3b

were measured with a digital melting point apparatus (Electro-

thermal) and were uncorrected. IR spectra were determined in the

region 4000-400 cm^-1on a NEXUS 670 FT IR spectrometer by

Bond length (Å), angles (q, °) and

Atom

1

preparing KBr pellets. The H and ¹³C NMR spectra were re-

torsion angles (j, °)

C8—C9

C22—C21

N6—O4

N1—O1

C6—C7

C20—C19

C26—N9

N5—C11

1.556 (6)

1.561 (6)

1.210 (5)

1.216 (5)

1.492 (6)

1.496 (6)

1.139 (6)

1.142 (6)

0.9800

corded on Bruker 300 FT-NMR at 300 and 75 MHz, respectively

(Urmia University, Urmia, Iran). ¹H and ¹³C NMR spectra were

obtained on solution in DMSO-d₆acetone-d₆and/or CDCl₃as sol-

vent using TMS as internal standard. The data are reported as (s =

singlet, d = doublet, t = triplet, q = quartet, m = multiplet or unre-

solved, bs = broad singlet, coupling constant(s) in Hz, integra-

tion). Cyanogen bromide was synthesized based on reported ref-

erences.²⁵Aromatic aldehydes, triethylamine and solvents pur-

chased from Merck and Aldrich without further purification.

General Procedures for the Preparation of 3-aryl-

cyclopropane-1,1,2,2-tetracarbonitriles

C7—H7

C20—H20

0.9800

C13—C8—C12

C25—C21—C24

C6—C7—C9

C19—C20—C22

C1—C6—C7

C14—C19—C20

O4—N6—O3

O2—N1—O1

N7—C23—C22

N2—C10—C9

O1—N1—C1—C2

O4—N6—C14—C15

C21—C20—C19—C14

C1—C6—C7—C8

C13—C8—C9—C11

C26—C22—C21—C25

115.1 (4)

114.2 (4)

121.6 (4)

123.8 (4)

124.6 (4)

122.2 (5)

122.4 (5)

176.8 (6)

176.7 (5)

2.6 (6)

14.2 (6)

61.8 (6)

-68.6 (6)

-0.4 (6)

-1.2 (6)

In a 10 mL with Teflon-faced screw cap tube equipped by a

magnetically stirrer, dissolved 0.106 g (1 mmol) benzaldehyde,

0.132 g (2 mmol) malononitrile, 0.202 g (2 mmol) triethylamine

in 5 mL ethanol and then 0.106 g (1 mmol) cyanogen bromide was

added into solution at range of 0 °C to room temperature. Cream

color solid precipitate immediately during 5 seconds, after about

2 minutes filtered off, washed with ethanol (3 × 3 mL) and dried.

(0.218 g, 100% yield).

Triethylammonium dicyanomethanide 4

White crystalline solid; FT-IR (KBr) 3446, 2943, 2738,

2677, 2491, 2166, 1475, 1397, 1036 cm^-1; ¹H NMR (CDCl₃, 300

MHz) d 1.22 (t, 9H, J = 6 Hz), 3.00 (m, 6H), 3.77 (s, 1H), 9.03 (bs,

1H); ¹³C NMR (CDCl₃, 75 MHz) d 110.1, 46.7, 9.3, 8.7.

Triethylammonium bromodicyanomethanide 7

White crystalline solid; FT-IR (KBr) 3420, 3047, 2987,

the intensities, correction for Lorentz and polarization ef-

fects and cell refinement was performed using CrystalClear

(Rigaku/MSC Inc., 2005) software.²³The structures were

solved by direct methods using SHELXS-97²⁴and refined

by a full-matrix least-squares procedure using the program

SHELXL-97.²⁴H-atoms were positioned geometrically and

refined using a riding model. The final difference Fourier

maps showed no peaks of chemical significance. Crystallo-

graphic data were deposited in CSD under CCDC-871192

registration number. These data can be obtained free of

charge from the Cambridge Crystallographic Data Centre

(CCDC) via www.ccdc.cam.ac.uk/ data_request/cif and

are available free of charge upon request to CCDC, 12 Un-

ion Road, Cambridge, UK (fax: +44-1223-336033, e-mail:

deposit@ccdc.cam.ac.uk).

1

2947, 2804, 2738, 2678, 2491, 2167, 1475, 1035, 565 cm^-1; H

NMR (CDCl₃, 300 MHz) d 1.39 (t, 9H, J = 7.2 Hz), 3.14 (m, 6H),

9.78 (bs, 1H); ¹³C NMR (CDCl₃, 75 MHz) d 141.6, 121.6, 46.6,

8.8.

3-Phenylcyclopropane-1,1,2,2-tetracarbonitrile 3a

White crystalline solid, mp 225-227 °C (decompds.) (lit.

229-230 °C¹⁰); FT-IR (KBr) 3046, 3013, 2928, 2264, 1640, 1374,

1231, 741, 701, 662 cm^-1; ¹H NMR (DMSO-d₆, 300 MHz) d 5.29

(s, 1H), 7.47 (m, 3H), 7.78 (m, 2H); ¹³C NMR (DMSO-d₆, 75

MHz) d 130.4, 130.0, 129.4, 127.3, 111.4, 109.9, 42.2, 23.6.

3-(2-Nitrophenyl)cyclopropane-1,1,2,2-tetracarbonitrile

3b

White crystalline solid, mp 215-216 °C (decompds.); FT-IR

(KBr) 3108, 3089, 3031, 2924, 2866, 2258, 1610, 1530, 1346,

851, 794, 736, 702 cm^-1; ¹H NMR (Acetone-d₆, 300 MHz) d 5.45

(s, 1H), 7.96 (t, 1H, J = 7.5 Hz), 8.07 (t, 1H, J = 7.5 Hz), 8.37 (d,

1H, J = 7.5 Hz), 8.51 (d, 1H, J = 7.5 Hz); ¹³C NMR (Acetone-d₆,

EXPERIMENTAL

General

The drawing and nomenclature of compounds were done

by ChemBioDraw Ultra 12.0 version software. Melting points

42

www.jccs.wiley-vch.de

J. Chin. Chem. Soc. 2013, 60, 35-44

JOURNAL OF THE CHINESE

CHEMICAL SOCIETY

One-pot Synthesis of 3-Arylcyclopropane-1,1,2,2-tetracarbonitriles

75 MHz) d 147.9, 135.3, 132.7, 132.6, 126.6, 122.0, 110.2, 108.8,

41.7, 23.8.

MHz) d 133.2, 132.7, 131.3, 118.5, 113.3, 111.3, 109.8, 41.4,

23.8.

3-(3-Nitrophenyl)cyclopropane-1,1,2,2-tetracarbonitrile

3c

3-(Pyridin-2-yl)cyclopropane-1,1,2,2-tetracarbonitrile

3l

White crystalline solid, mp 214-216 °C (decompds.); FT-IR

(KBr) 3083, 3005, 2258, 2193, 1649, 1528, 1355, 738, 703 cm^-1;

¹H NMR (DMSO-d₆, 300 MHz) d 5.44 (s, 1H), 7.79 (m, 1H), 8.34

(m, 2H), 9.01 (s, 1H); ¹³C NMR (DMSO-d₆, 75 MHz) d 148.4,

136.9, 131.0, 129.7, 125.6, 125.3, 111.3, 109.9, 46.2, 24.1.

3-(4-Bromophenyl)cyclopropane-1,1,2,2-tetracarbo-

nitrile 3d

White crystalline solid, mp 173-175 °C (decompds.); FT-IR

(KBr) 3049, 2925, 2854, 2260, 2208, 1627, 1591, 1473, 1446,

999, 791, 748, 621 cm^-1; ¹H NMR (Acetone-d₆, 300 MHz) d 4.95

(s, 1H), 7.57 (m, 1H), 7.97-8.02 (m, 2H), 8.68 (m, 1H); ¹³C NMR

(Acetone-d₆, 75 MHz) d 149.0, 146.2, 137.5, 126.6, 125.2, 111.0,

108.3, 41.7, 21.9.

2-(Anthracen-9-ylmethylene)malononitrile 8m

Orange crystalline solid, mp 207-209 °C (decompds.);

FT-IR (KBr) 3056, 3018, 2925, 2857, 2228, 1651, 1621, 1573,

1558, 1321, 1257, 736 cm^-1; ¹H NMR (Acetone-d₆, 300 MHz) d

7.64 (t, 2H, J = 7.8 Hz), 7.72 (t, 2H, J = 8.1 Hz), 8.21-8.24 (m,

4H), 8.85 (s, 1H), 9.48 (s, 1H); ¹³C NMR (Acetone-d₆, 75 MHz) d

161.8, 131.5, 131.1, 129.2, 129.1, 128.9, 127.8, 126.0, 124.7,

47.0.

White crystalline solid, mp 218-219 °C (decompds.); FT-IR

(KBr) 3087, 3061, 3004, 2264, 1622, 1590, 1492, 1401, 1072,

1014, 844, 785, 732, 491 cm^-1; ¹H NMR (DMSO-d₆, 300 MHz) d

5.11 (s, 1H), 7.79 (d, 2H, J = 8.4 Hz), 7.89 (d, 2H, J = 8.4 Hz); ¹³

C

NMR (DMSO-d₆, 75 MHz) d 132.4, 132.3, 126.9, 124.2, 111.4,

109.9, 41.5, 23.7.

3-(4-Chlorophenyl)cyclopropane-1,1,2,2-tetracarbo-

nitrile 3e

3-(2-formylphenyl)cyclopropane-1,1,2,2-tetracarbo-

nitrile 18a²

White crystalline solid, mp 240-243 °C (decompds.) (lit.

250-251 °C¹⁰); FT-IR (KBr) 3091, 3066, 2264, 2211, 1624, 1596,

1497, 1404, 1091, 1018, 845, 790, 728, 501 cm^-1; ¹H NMR (Ace-

tone-d₆, 300 MHz) d 5.03 (s, 1H), 7.63 (d, 2H, J = 8.4 Hz), 7.95 (d,

2H, J = 8.4 Hz); ¹³C NMR (Acetone-d₆, 75 MHz) d 136.1, 131.4,

129.4, 125.5, 110.4, 108.9, 41.9, 22.9.

White crystalline solid, mp 287-289 °C (decompds.); FT-IR

(KBr) 3082, 3063, 3010, 2925, 2869, 2772, 2259, 1682, 1597,

1573, 1204, 760, 729, 676 cm^-1; ¹H NMR (Acetone-d₆, 300 MHz)

d 5.08 (s, 1H), 7.94-7.96 (m, 2H), 8.20 (m, 1H), 8.30 (m, 1H),

10.27 (s, 1H); ¹³C NMR (Acetone-d₆, 75 MHz) d 193.8, 143.9,

137.2, 134.6, 131.5, 131.4, 119.0, 110.7, 109.2, 41.7, 24.0.

3,3¢-(1,3-phenylene)bis(cyclopropane-1,1,2,2-tetracar-

bonitrile) 19b²

3-(3,4,5-Trimethoxyphenyl)cyclopropane-1,1,2,2-tetra-

carbonitrile 3f

White crystalline solid, mp 227-229 °C (decompds.); FT-IR

(KBr) 3047, 2997, 2943, 2842, 2260, 1592, 1512, 1468, 1421,

1251, 1127, 993 cm^-1; ¹H NMR (Acetone-d₆, 300 MHz) d 3.77 (s,

3H), 3.87 (s, 6H), 4.96 (s, 1H), 7.31 (s, 2H); ¹³C NMR (Ace-

tone-d₆, 75 MHz) d 153.9, 139.8, 121.4, 110.7, 109.1, 107.2, 59.8,

55.9, 42.9, 22.9.

White crystalline solid, mp 255-257 °C (decompds.); FT-IR

(KBr) 3009, 2925, 2262, 1613, 1493, 1436, 1360, 1142, 1046, 782

cm^-1; ¹H NMR (Acetone-d₆, 300 MHz) d 5.24 (s, 2H), 7.81 (t, 1H,

J = 8.1 Hz), 8.14 (d, 2H, J = 7.8 Hz), 8.44 (s, 1H); ¹³C NMR (Ace-

tone-d₆, 75 MHz) d 131.5, 131.2, 130.3, 128.1, 110.4, 108.8, 42.0,

22.8.

3-(4-Methoxyphenyl)cyclopropane-1,1,2,2-tetracarbo-

nitrile 3h

White crystalline solid, mp 209-211 °C (decompds.) (lit.

208-210 °C¹⁰); FT-IR (KBr) 3004, 2968, 2946, 2846, 2264, 1611,

1513, 1468, 1307, 1264, 1183, 1035, 844, 803 cm^-1; ¹H NMR (Ac-

etone-d₆, 300 MHz) d 3.87 (s, 3H), 4.88 (s, 1H), 7.11 (d, 2H, J =

8.7 Hz), 7.80 (d, 2H, J = 8.7 Hz); ¹³C NMR (Acetone-d₆, 75 MHz)

d 161.3, 131.0, 118.0, 114.6, 110.7, 109.0, 54.9, 42.5, 22.8.

3-(4-Cyanophenyl)cyclopropane-1,1,2,2-tetracarbo-

nitrile 3i

ACKNOWLEDGEMENTS

We gratefully acknowledge financial support by the

Research Council of Urmia University.

REFERENCES

1. Bienaymé, H.; Hulme, C.; Oddon, G.; Schmitt, P. Chem. Eur.

J. 2000, 6, 3321-3329.

2. Dömling, A. Comb. Chem. High Throughput Screen 1998, 1,

1-22.

White crystalline solid, mp 225-226 °C (decompds.); FT-IR

(KBr) 3102, 3056, 3006, 2365, 2239, 1612, 1513, 1412, 856, 800,

556 cm^-1; ¹H NMR (DMSO-d₆, 300 MHz) d 5.45 (s, 1H), 8.00 (d,

2H, J = 8.4 Hz), 8.11 (d, 2H, J = 8.4 Hz); ¹³C NMR (DMSO-d₆, 75

3. Ramón, D. J.; Yus, M. Angew. Chem. Int. Ed. 2005, 44,

1602-1634.

4. (a) Faust, R. Angew. Chem. Int. Ed. 2001, 40, 2251-2253; (b)

Donaldson, W. A. Tetrahedron 2001, 57, 8589-8627.

J. Chin. Chem. Soc. 2013, 60, 35-44

www.jccs.wiley-vch.de

43

Article

Noroozi Pesyan et al.

5. (a) Little, R. D.; Dawson, J. R. J. Am. Chem. Soc. 1978, 100,

4607-4609; (b) Little, R. D.; Dawson, J. R. Tetrahedron Lett.

1980, 21, 2609-2612; (c) Caine, D. Tetrahedron 2001, 57,

2643-2684.

48, 1492-1497.

16. Alberola, A.; Andres, C.; Ortega, A. G.; Pedrosa, R.; Vicente,

M. Synth. Commun. 1986, 16, 1161-1165.

17. Jalilzadeh, M.; Noroozi Pesyan, N.; Rezaee, F.; Rastgar, S.;

Hosseini, Y.; Ôahin, E. Mol. Divers. 2011, 15, 721-731.

18. Hosseini, Y.; Rastgar, S.; Heren, Z.; Büyükgüngör, O.;

Noroozi Pesyan, N. J. Chin. Chem. Soc. 2011, 58, 309-318.

19. Jalilzadeh, M.; Noroozi Pesyan, N. Bull. Korean Chem. Soc.

2011, 32, 3382-3388.

6. (a) Warner, D. T. J. Org. Chem. 1959, 24, 1536-1539; (b)

McCoy, L. L. J. Org. Chem. 1964, 29, 240-241.

7. Mariella, R.; Roth, A. J. Org. Chem. 1957, 22, 1130–1133.

8. Elinson, M. N.; Vereshchagin, A. N.; Stepanov, N. O.;

Zaimovskaya, T. A.; Merkulova, V. M.; Nikishin, G. I. Tetra-

hedron Lett. 2010, 51, 428–431.

20. Jalilzadeh, M.; Noroozi Pesyan, N. J. Korean Chem. Soc.

2011, 55, 940-951.

9. Vereshchagin, A. N.; Elinson, M. N.; Stepanov, N. O.;

Nikishin, G. I. Mendeleev Commun. 2009, 19, 324–325.

10. Elinson, M. N.; Feducovich, S. K.; Stepanov, N. O.; Anatolii,

N.; Vereshchagin, A. N.; Nikishin, G. I. Tetrahedron 2008,

64, 708-713.

21. Jursic, B. S.; Neumann, D. M.; Moore, Z.; Stevens, E. D. J.

Org. Chem. 2002, 67, 2372-2374.

22. Noroozi Pesyan, N.; Hosseini, Y.; Shokr, A.; Ôahin, E. J.

Chin. Chem. Soc. 2012, 59, DOI: 10.1002/jccs.201200082

(In press).

11. Kumar, V. Synlett 2005, 10, 1638.

12. Martin, D.; Bauer, M. Org. Synth. Coll. 1990, 7, 435.

13. Gross, E.; Witkop, B. J. Am. Chem. Soc. 1961, 83, 1510-

1511.

23. Rigaku/MSC, Inc. 9009 new Trails Drive, The Woodlands,

TX 77381.

24. Sheldrick, G. M., SHELXS97 and SHELXL97, University of

Göttingen: Germany, 1997.

14. McCallum, P. B. W.; Grimmett, M. R.; Blackman, A. G.;

Weavers, R. T. Aust. J. Chem. 1999, 52, 159-166.

15. Tanner, D. D.; Lycan, G.; Bunce, N. J. Can. J. Chem. 1970,

25. Hartman, W. W.; Dreger. E. E. Org. Synth. Coll. 1943, 2, 150.

44

www.jccs.wiley-vch.de

J. Chin. Chem. Soc. 2013, 60, 35-44

Article Doi

A new, fast and easy strategy for one-pot synthesis of full substituted cyclopropanes: Direct transformation of aldehydes to 3-aryl-1,1,2,2- tetracyanocyclopropanes

DOI: 10.1002/jccs.201200189

Source and publish data:

Authors:

Article abstract of DOI:10.1002/jccs.201200189

Full text of DOI:10.1002/jccs.201200189

Products guided by the article

R&D Labs maybe for 642000-31-5

Relevant to this article

Hot Product