Synthesis, molecular and crystal structure of 2-[2-(2-amino-3-cyano-4H- chromen-4-yl)-cyclohexylidene]malononitrile

Article abstract of DOI:10.1134/S1070363213050162

Condensation of salicylaldehyde with cyclohexylidenemalononitrile and hydrazine hydrate results in 2-[2-(2-amino-3-cyano-4H-chromen-4-yl) cyclohexylidene]malononitrile, the structure of which was studied by XRD.

Full text of DOI:10.1134/S1070363213050162

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 5, pp. 979–982. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © V.D. Dyachenko, Yu.Yu. Pugach, 2013, published in Zhurnal Obshchei Khimii, 2013, Vol. 83, No. 5, pp. 845–848.
Synthesis, Molecular and Crystal Structure
of 2-[2-(2-Amino-3-cyano-4H-chromen-4-yl)-
cyclohexylidene]malononitrile
V. D. Dyachenko and Yu. Yu. Pugach
Shevchenko Lugansk National University, ul. Oboronnaya 2, Lugansk, 91011 Ukraine
e-mail: chem@luguniv.edu.ua
Received April 9, 2012
Abstract―Condensation of salicylaldehyde with cyclohexylidenemalononitrile and hydrazine hydrate results
in 2-[2-(2-amino-3-cyano-4H-chromen-4-yl)cyclohexylidene]malononitrile, the structure of which was studied
by XRD.
DOI: 10.1134/S1070363213050162
Previously, we have studied the condensation of
salicylaldehyde with cyclohexylidenecyanothioacetamide
affording (E)-2-(2-hydroxybenzylideneamino)-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carbonitrile [1] and the
reaction of salicylaldehyde with cyclohexylidenemalo-
nonitrile and morpholine leading to 2-(morpholine-5H-
chromeno[2,3-d]pyrimidin-2-yl)phenol [2].
reaction conditions and transforms into the substituted
2-amino-4H-benzo[b]pyran IV in 32% yield. The latter
can be easily obtained in 69% yield by a three-
component condensation of salicylaldehyde I with cyclo-
hexylidenemalononitrile II and malononitrile V in
DMF at 20°C in the presence of triethylamine (method
b). Hypothetical intermediates in the method b may be
both compounds B–D and alkene E that can interact
with malononitrile V to form the Michael adduct F
followed by intramolecular heterocyclization into the
above 2-iminopyran D.
In the present study we investigated the
condensation of salicylaldehyde I with cyclohexylidene-
malononitrile II and hydrazine hydrate III in an-
hydrous ethanol at 20°C. This reaction results in a pre-
viously unknown 2-[2-(2-amino-3-cyano-4H-chromen-
4-yl)cyclohexylidene]malononitrile IV (method a),
which is a promising precursor to create antidotes [3,
4], antibacterial [5], anticancer [6], and antidiabetic
drugs. [7]
A feature of the spectral characteristics of
compound IV is a doubling with equal intensity of the
signal of С4Н-proton in the 1H NMR spectrum and the
doubling of all the signals in the 13C NMR spectrum,
which can be attributed to possible conformational
isomerism of the cyclohexane substituent.
Apparently, the reaction includes the formation of
the aza-Michael adduct A, which eliminates the malo-
nonitrile V and is stabilized as a hydrazone VI. The
presence of amines in the reaction mixture initiates
further Knoevenagel reaction to form the corres-
ponding alkene B. Under the reaction conditions the
latter undergoes the intramolecular cyclization into 2-
amino-3-cyano-4H-benzo[b]pyran V, which can easily
be formed from salicylaldehyde I and malononitrile V
in a basic medium [8, 9].
To establish the definite structure of the product of
the above reaction compound IV was investigated by
X-ray analysis. General view of the molecule is shown
in the figure. The independent part of the unit cell
contains four molecules of compound IV (A, B, C, and
D), which have similar geometrical parameters. The
presence of cyclohexane substituent leads to non-
planarity of the pyran ring. Its conformation is
asymmetrical boat. The atoms O1 and C9 are out of the
plane of other atoms in the ring by 0.24–0.28 and
0.38–0.46 Å, respectively. The С9–С10 bond is axially
oriented relative to the pyran and cyclohexane rings
[torsion angles С6С1С9С10 86.4(3)°–93.6(3)° and
Further, an interaction of intermediate C with the
CH-acid II by Michael takes place to give the
corresponding adduct D, which is unstable under the
979

980
DYACHENKO, PUGACH
H2O
NH2NH2
III
Method a
CHO
OH
+
CN
V, Et3N
CN
−H2O
II
I
Method b
CN
CN
NH
CN
CN
CN
I
−Η2O
C
N
OH
O
CN
−
NHNH2
NNH2
B
A
VI
C
V
II
CN
CN
CN
CN
CN
CN
V
CN
CN
CN
CN
CN
C
N
O
NH2
OH
O
NH
OH
IV
E
D
F
С14С15С10С9 72.4(3)°–73.8(3)°]. The hydrogen atoms
at С9 and С10 carbons are anti-oriented (torsion angles
Н9С9С10Н10 are 166°–175°). This substituent orienta-
tion leads to the location of the dicyanomethylene
moiety in the cyclohexane ring above the cyano group
of the pyran ring. The shortened intramolecular
contacts С16···С17 (3.22–3.40 Å, the sum of the van der
Waals radii [10] is 3.42 Å) indicates an attractive non-
valence interaction. Asymmetrical conformation of the
pyran ring causes a noticeable twist of the endocyclic
double bond [torsion angle N1C7C8C16 is in the range
of 6.7(3)°–10.0(3)°].
In the crystal the molecules form centrosymmetric
dimers С···С and D···D and pseudocentrosymmetric
dimers А···В due to the intermolecular hydrogen bonds
N1–H1a···N2 (H···N 2.16–2.23 Å, N–H···N 159°–166°).
Also, each of the symmetrically independent mole-
cules forms a weak intermolecular hydrogen bonds
N1–H1b···N1 (H···N 2.34–2.51 Å, N–H···N 151°–169°).
EXPERIMENTAL
Crystals of compound IV are triclinic, C19H16N4О,
at 298 K: a 11.384(2), b 11.640(2), c 25.945(4) Å; α
97.153(16), β 94.358(14), γ 91.374(15); V 3399.3 Å3,
М 316.36, Z 8, space group P1, dcalc 1.236 g cm–3,
λ(МоKα) 0.08 mm–1, F(000) 1328. The unit cell
General view of the molecules of compound IV.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 5 2013

SYNTHESIS, MOLECULAR AND CRYSTAL STRUCTURE
Table 1. Bond lengths (Å) in the structure IV Table 2. Bond angles (deg) in the structure IV
981
Bond
Angle
A
B
C
D
A
B
C
D
O1A–C7A
N1A–C7A
N2A–C16A
N3A–C18A
N4A–C19A
C1A–C2A
C1A–C6A
C1A–C9A
C2A–C3A
C3A–C4A
C4A–C5A
C5A–C6A
C7A–C8A
C8A–C9A
C8A–C16A
C9A–C10A
C10A–C11A 1.496(3)
C10A–C15A 1.527(3)
C11A–C12A 1.481(3)
C11A–C17A 1.339(4)
C12A–C13A 1.526(3)
C13A–C14A 1.512(4)
C14A–C15A 1.507(4)
C17A–C18A 1.433(4)
C17A–C19A 1.427(4)
1.364(3)
1.334(3)
1.145(3)
1.140(4)
1.135(4)
1.380(4)
1.368(4)
1.497(3)
1.371(4)
1.370(4)
1.377(4)
1.377(4)
1.348(3)
1.511(3)
1.404(4)
1.575(4)
1.366(3)
1.334(3)
1.144(3)
1.139(4)
1.135(3)
1.385(4)
1.379(4)
1.502(3)
1.377(4)
1.371(4)
1.369(4)
1.371(4)
1.338(3)
1.514(3)
1.414(4)
1.571(4)
1.507(3)
1.537(3)
1.489(4)
1.336(4)
1.528(4)
1.520(4)
1.513(4)
1.430(4)
1.433(4)
1.357(3)
1.333(3)
1.150(4)
1.132(4)
1.138(4)
1.390(4)
1.371(4)
1.504(4)
1.377(4)
1.377(4)
1.373(4)
1.381(4)
1.351(4)
1.513(4)
1.413(4)
1.573(3)
1.507(4)
1.535(4)
1.490(3)
1.340(3)
1.531(4)
1.509(4)
1.523(4)
1.430(4)
1.436(4)
1.363(3)
1.334(4)
1.145(3)
1.136(4)
1.132(3)
1.386(4)
1.369(4)
1.513(3)
1.388(4)
1.368(4)
1.380(4)
1.372(4)
1.356(4)
1.501(4)
1.414(4)
1.573(3)
1.503(3)
1.531(4)
1.495(4)
1.340(4)
1.532(5)
1.506(4)
1.513(5)
1.431(5)
1.443(4)
C7AO1AC6A
C2AC1AC9A
C6AC1AC2A
C6AC1AC9A
C3AC2AC1A
C4AC3AC2A
C3AC4AC5A
C4AC5AC6A
C1AC6AO1A
C1AC6AC5A
C5AC6AO1A
N1AC7AO1A
N1AC7AC8A
C8AC7AO1A
C7AC8AC9A
C7AC8AC16A
C16AC8AC9A
C1AC9AC8A
C1AC9AC10A
C8AC9AC10A
C11AC10AC9A
116.7(2)
123.7(3)
117.6(3)
118.7(3)
121.1(3)
119.4(3)
121.5(3)
117.3(3)
120.4(3)
123.1(3)
116.5(3)
110.9(2)
128.3(3)
120.9(2)
119.3(2)
121.1(2)
119.6(2)
107.6(2)
110.7(2)
110.1(2)
108.9(2)
117.2(2)
123.8(3)
116.5(3)
119.8(3)
121.3(3)
120.4(3)
119.6(3)
119.2(3)
120.9(2)
123.0(3)
116.2(3)
110.1(2)
128.4(2)
121.5(2)
121.0(2)
118.9(2)
120.2(2)
107.9(2)
112.8(2)
109.7(2)
109.0(2)
109.6(2)
115.3(2)
115.9(3)
122.5(3)
121.6(3)
110.8(3)
110.3(3)
110.1(3)
114.0(2)
178.8(3)
122.8(3)
122.0(3)
115.2(3)
178.2(4)
179.9(4)
117.4(2)
123.7(3)
116.9(3)
119.4(2)
120.7(3)
120.6(3)
120.0(3)
118.3(3)
120.8(3)
123.5(3)
115.8(3)
110.7(3)
127.8(3)
121.5(3)
120.0(3)
120.7(3)
119.3(3)
108.3(2)
111.6(2)
110.1(2)
108.7(2)
109.7(2)
114.9(2)
116.0(2)
122.3(3)
121.7(3)
110.3(3)
111.5(3)
111.5(2)
112.9(3)
177.0(3)
122.9(3)
121.8(3)
115.3(2)
177.2(4)
178.7(4)
117.1(2)
123.1(3)
118.0(3)
118.9(3)
120.3(3)
119.9(3)
120.6(3)
118.4(3)
121.0(3)
122.7(3)
116.3(3)
110.8(3)
128.6(3)
120.6(3)
120.6(3)
117.6(3)
121.7(3)
107.8(2)
111.7(2)
110.4(2)
108.3(2)
110.1(3)
115.7(2)
115.7(3)
122.5(3)
121.8(3)
111.8(3)
110.0(3)
110.9(3)
114.0(3)
179.3(4)
123.9(3)
121.9(3)
114.2(3)
178.1(4)
179.6(4)
C11AC10AC15A 109.4(2)
C15AC10AC9A
115.6(2)
C12AC11AC10A 116.4(2)
C17AC11AC10A 122.4(3)
C17AC11AC12A 121.1(3)
C11AC12AC13A 110.1(2)
C14AC13AC12A 110.8(2)
C15AC14AC13A 110.5(3)
C14AC15AC10A 113.8(2)
parameters and intensities of 20725 reflections (12029 in-
dependent, Rint 0.046) were measured on a Xcalibur
3 automatic four-circle diffractometer (МоKα, graphite
monochromator, CCD-detector, ω-scanning, 2θmax
50.0°).
N2AC16AC8A
176.0(3)
The structure was solved by the direct method
using SHELX-97 software [11]. Positions of the
hydrogen atoms were geometrically calculated and
refined in a rider model with Uiso = 1.2Ueq of the
carrier atom. The structure was refined by F2 full-
matrix least-square method in the anisotropic
approximation for the nonhydrogen atoms to wR2 =
0.129 for 12029 reflections (R1 0.058 for 5819 reflec-
tions with F > 4σ(F), S 1.00). The bond lengths and
angles are given in Tables 1 and 2, respectively.
C11AC17AC18A 122.2(3)
C11AC17AC19A 122.3(3)
C19AC17AC18A 115.5(3)
N3AC18AC17A
N4AC19AC17A
178.4(4)
177.4(4)
NMR spectrum was registered on a Bruker DR-500
spectrometer (500.13 MHz) from DMSO-d6 solutions
relative to internal TMS. The 13C NMR spectrum was
taken on a Varian VXR-300 spectrometer (125.74 MHz)
from DMSO-d6 solutions. The mass spectrum was
The IR spectrum was recorded on a Spectrum One
(Perkin Elmer) instrument from KBr pellets. The H
1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 5 2013

982
DYACHENKO, PUGACH
recorded on a Chrommass GC/MC (Hewlett Packard)
5890/5972 instrument (column HP-5 MS, 70 eV,
CH2Cl2 solutions). The melting point was determined
on a Koeffler heating block. The reaction progress and
individuality of the compounds obtained were
monitored by TLC on Silufol UV-254 plates eluting
with an acetone–hexane mixture (3:5) and detecting
with iodine vapor or UV irradiation.
b. To a mixture of 1.07 ml (10 mmol) of salicylal-
dehyde I and 1.5 g (10 mmol) of cyclohexylidene-
malononitrile II in 15 ml of DMF was added 3 drops
of triethylamine at 20°C. The mixture was stirred for
2 h and left standing for 24 h. Then to the reaction
mixture was added 0.66 g (10 mmol) of malononitrile
V with stirring for 20 min. The formed precipitate was
filtered off, washed with ethanol and hexane. Yield
2.2 g (69%). Melting point and spectral data are
identical to the substance synthesized by method a.
2-[2-(2-Amino-3-cyano-4H-chromen-4-yl)cyclo-
hexylidene]malononitrile (IV). a. A mixture of 1.07 ml
(10 mmol) of salicylaldehyde I, 1.5 g (10 mmol) of cyclo-
hexylidenemalononitrile II, and 0.5 ml (10 mmol) of
hydrazine hydrate III in 20 ml of ethanol was stirred at
20°C for 2 h and then left standing for 48 h. The
formed precipitate was filtered off, washed with
ethanol and hexane. Yield 1.0 g (32%), white crystals,
which fluoresce under the UV irradiation and exhibits
a lacrimator properties when heated, mp 165–167°C (i-
PrOH). IR spectrum, ν, cm–1: 3423, 3328, 3207 (NН2),
2231, 2184 (C≡N), 1651 (δNН). 1Н NMR spectrum, δН,
ppm: 1.44–1.71 m (4Н, 2CH2), 1.99–2.18 m (2Н,
CH2), 2.85 m (2Н, CH2), 3.01–3.12 m (1Н, С1'Н), 4.06
d (0.5Н, С4Н, J 12.0 Hz), 4.08 d (0.5Н, С4Н, J 8.0 Hz),
6.97 d (1Н, Нarom, J 8.0 Hz), 7.15 d (1Н, Нarom, J 8.0 Hz),
7.22–7.38 m (4Н, 2Нarom, NH2). 13С NMR spectrum,
δС, ppm: 36.60, 37.07, 39.52, 39.69, 39.86, 40.02,
40.11, 40.19, 40.28, 51.33, 52.02, 52.42, 52.66, 83.60,
85.12, 11.15, 112.06, 112.23, 112.59, 116.80, 116.95,
120.68, 121.50, 123.91, 124.06, 124.26, 124.76,
127.93, 128.97, 129.04, 129.60, 129.99, 150.65,
151.17, 164.03, 164.12, 186.19, 186.22. MS, m/z (Irel,
%): 317 (100) [M + 1]+. Found, %: C 72.01; H 4.95; N
17.62. C19H16N4О. Calculated, %: C 72.14; H 5.10; N
17.71. М 316.366.
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