Solvent-free synthesis of 4-oxoalkane-1,1,2,2-tetracarbonitriles

Full text of DOI:10.1134/S1070428016090189

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 9, pp. 1353–1355. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © O.V. Ershov, M.Yu. Ievlev, M.Yu. Belikov, O. E. Nasakin, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 9,
pp. 1364–1366.
SHORT
COMMUNICATIONS
Solvent-Free Synthesis of 4-Oxoalkane-1,1,2,2-tetracarbonitriles
O. V. Ershov,* M. Yu. Ievlev, M. Yu. Belikov, and O. E. Nasakin
I.N. Ul’yanov Chuvash State University, Moskovskii pr. 15, Cheboksary, 428015 Russia
*e-mail: oleg.ershov@mail.ru
Received March 22, 2016
DOI: 10.1134/S1070428016090189
Problems related to directed synthesis of complex
functionalized heterocyclic compounds constitute
an important field of modern organic chemistry. Target
structures may be constructed in several steps via
successive introduction of particular substituents.
However, this approach is often associated with low
conversion of initial reactants, high expenditures of
time, energy, and labor, the necessity of isolation and
purification of intermediate products in every step, and
other difficulties. These difficulties can be avoided
by using special substrates capable of reacting in
a domino (cascade) mode which implies that several
consecutive chemical transformations can be accom-
plished as a single synthetic operation. Examples of
such compounds are 4-oxoalkane-1,1,2,2-tetracarbo-
nitriles 1 which were successfully used as starting
compounds in the synthesis of difficultly accessible
heterocyclic systems [1–6]. Up to now, more than
20 types of heterocycles have been obtained on the
basis of 4-oxoalkane-1,1,2,2-tetracarbonitriles 1, and
some compounds have been found to possess prac-
tically useful properties (e.g., fluorescence), which
determines the importance of studies in this line [1].
cyanoethylene and carbonyl compounds in the pres-
ence of a catalytic amount of water, propan-1-ol, or
ethanol [8], sulfur dioxide [9], and acetic or trichloro-
acetic acid [10] have been reported. However, these
procedures are not general, and their results were
demonstrated only with a few particular aliphatic
ketones. The most widely used method is the reaction
of tetracyanoethylene with ketones in 1,4-dioxane con-
taining a catalytic amount of HCl [6, 11–13]. It is the
most general among the above listed ones, and it
provides the possibility of obtaining 4-oxoalkane-
1,1,2,2-tetracarbonitriles 1 with two aromatic substit-
uents R1 and R2. A drawback of this method is long
reaction time (up to several days for some ketones).
We have developed a new experimentally con-
venient procedure for the synthesis of 4-oxoalkane-
1,1,2,2-tetracarbonitriles 1 in 84–98% yield under
solvent-free conditions; this procedure conforms to the
green chemistry principles since it requires no toxic
solvents and ensures high conversion of the initial
compounds.
Tetracyanoethylene and the corresponding ketone
were mixed at a molar ratio of 1:1, and addition of
p-toluenesulfonic acid as catalyst considerably short-
ened the reaction time. For example, the synthesis of
4-oxo-4-phenylbutane-1,1,2,2-tetracarbonitrile (1a) in
the presence of a catalytic amount of hydrochloric acid
required 2–3 days, whereas the solvent-free reaction
was complete in 5 min.
Several known procedures for the synthesis of
4-oxoalkane-1,1,2,2-tetracarbonitriles are not free from
a number of disadvantages. The historically first proce-
dure based on the use of “molecular” silver requires
expensive catalyst [7]. Methods for the preparation of
4-oxoalkane-1,1,2,2-tetracarbonitriles 1 from tetra-
CN
O
NC
CN
R1
TsOH, ∆
R2
NC
CN
+
CN
R1
O
CN
R2
CN
1a–1g
R1 = Ph, R2 = H (a), Me (b); R1 = 3,4-(MeO)2C6H3, R2 = H (c); R1 = 4-MeC6H4, R2 = Me (d); R1 = 3-O2NC6H4, R2 = H (e);
R1 = 4-ClC6H4, R2 = Me (f); R1 = 2,5-dimethylthiophen-3-yl, R2 = Ph (g).
1353

ERSHOV et al.
1354
CHCN), 6.96 d (1H, Harom, J = 8.4 Hz), 7.49 d (1H,
Compound 1a was reported previously [7], while
Harom, J = 2.1 Hz), 7.55 d.d (1H, Harom, J = 2.1,
8.4 Hz). Mass spectrum: m/z 308 (Irel, 3%) [M]+.
Found, %: C 62.27; H 3.90; N 18.19. C16H12N4O3.
Calculated, %: 62.33; H 3.92; N 18.17. M 308.09.
compounds 1b–1g were synthesized for the first time.
Their structure was confirmed by IR, H NMR, and
1
mass spectra and elemental analyses. The IR spectra of
1a–1g contained absorption bands 1672‒1699 and
2250‒2256 cm–1 due to stretching vibrations of car-
bonyl group and unconjugated cyano groups, respec-
3-Methyl-4-(methylphenyl)-4-oxobutane-1,1,2,2-
tetracarbonitrile (1d). Yield 2.48 g (90%), mp 166‒
167°C (decomp.). IR spectrum, ν, cm–1: 2250 (C≡N),
1
tively. In the H NMR spectra of these compounds the
1
acidic CH(CN)2 proton resonated at δ 5.74–6.15 ppm,
and signals from protons in the α-position with respect
to the carbonyl group were observed in the region
δ 4.56–4.84 ppm (1a–1f) or at δ 5.57 ppm (1g). Their
downfield position is determined by strong deshielding
by the electron-withdrawing CO and CN groups.
Signals from protons in the corresponding alkyl and
aryl groups were also present.
1699 (C=O). H NMR spectrum (acetone-d6), δ, ppm:
1.52 d (3H, CH3CH, J = 7.3 Hz), 2.39 s (3H, CH3),
4.71 q (1H, CH3CH), 5.83 s (1H, CHCN), 7.16 d (2H,
Harom, J = 8.8 Hz), 8.15 d (2H, Harom, J = 8.8 Hz). Mass
spectrum: m/z 276 (Irel 5%) [M]+. Found, %: C 69.46;
H 4.41; N 20.35. C16H12N4O. Calculated, %: 69.55;
H 4.38; N 20.28. M 276.10.
4-(3-Nitrophenyl)-4-oxobutane-1,1,2,2-tetra-
carbonitrile (1e). Yield 2.87 g (98%), mp 137‒138°C
(decomp.). IR spectrum, ν, cm–1: 2255 (C≡N), 1693
(C=O). 1H NMR spectrum (acetone-d6), δ, ppm: 4.82 s
4-Oxo-4-phenylbutane-1,1,2,2-tetracarbonitrile
(1a). A mixture of 1.28 g (0.01 mol) of tetracyano-
ethylene, 0.011 mol of acetophenone, and 2–3 crystals
of p-toluenesulfonic acid was thoroughly stirred and
heated to 50‒60°C with stirring until a homogeneous
solution was formed. When the reaction was complete
(the absence of tetracyanoethylene was checked by
a hydroquinone test), the mixture was cooled and
treated with 100 mL of water. The precipitate was
filtered off and washed with water and propan-2-ol.
Yield 2.31 g (93%).
(2H, CH2CO), 6.15 s (1H, CHCN), 7.95 t (1H, Harom
,
J = 8.0 Hz), 8.59 m (2H, Harom) 8.93 t (1H, Harom, J =
1.8 Hz). Mass spectrum: m/z 293 (Irel 6%) [M]+. Found,
%: C 57.27; H 2.40; N 23.94. C14H7N5O3. Calculated,
%: 57.34; H 2.41; N 23.88. M 293.05.
4-(4-Chlorophenyl)-3-methyl-4-oxobutane-
1,1,2,2-tetracarbonitrile (1f). Yield 2.49 g (84%),
mp 160‒161°C (decomp.). IR spectrum, ν, cm–1: 2255
1
Compounds 1b–1g were synthesized in a similar
way.
(C≡N), 1693 (C=O). H NMR spectrum (acetone-d6),
δ, ppm: 1.84 d (3H, CH3, J = 7.3 Hz), 4.79 m (1H,
CH3CH), 5.98 s (1H, CHCN), 7.12 d (2H, Harom, J =
8.7 Hz), 8.14 d (2H, Harom, J = 8.7 Hz). Mass spec-
trum: m/z 296 (Irel 2%) [M]+. Found, %: C 60.61;
H 3.04; N 18.92. C15H9ClN4O. Calculated, %: 60.72;
H 3.06; N 18.88. M 296.04.
3-Methyl-4-oxo-4-phenylbutane-1,1,2,2-tetra-
carbonitrile (1b). Yield 2.54 g (97%), mp 130‒131°C
(decomp.). IR spectrum, ν, cm–1: 2256 (C≡N), 1672
(C=O). 1H NMR spectrum (acetone-d6), δ, ppm: 1.81 d
(3H, CHCH3, J = 7.2 Hz), 4.84 q (1H, CH3CH,
J = 7.2 Hz), 5.99 (1H, CHCN), 7.65 t (2H, Ph, J =
7.7 Hz), 7.65 t (1H, Ph, J = 7.7 Hz), 8.19 d (2H,
Ph, J = 7.7 Hz). Mass spectrum: m/z 262 (Irel 2%)
[M]+. Found, %: C 68.78; H 3.82; N 21.40.
C15H10N4O. Calculated, %: C 68.69; H 3.84; N 21.36.
M 262.08.
4-(2,5-Dimethylthiophen-3-yl)-4-oxo-3-phenyl-
butane-1,1,2,2-tetracarbonitrile (1g). Yield 3.29 g
(92%), mp 125‒126°C (decomp.). IR spectrum, ν,
1
cm–1: 2254 (C≡N), 1678 (C=O). H NMR spectrum
(acetone-d6), δ, ppm: 2.27 s (3H, CH3), 2.73 s (3H,
CH3), 5.57 s (1H, CHCO), 5.74 s (1H, CHCN), 7.11 d
(1H, 4′-H), 7.54–7.58 m (3H, Ph), 7.66‒7.69 m (2H,
Ph). Mass spectrum: m/z 358 (Irel 1%) [M]+. Found, %:
C 66.93; H 3.92; N 15.66. C20H14N4OS. Calculated, %:
67.02; H 3.94; N 15.63. M 358.09.
4-(3,4-Dimethoxyphenyl)-4-oxobutane-1,1,2,2-
tetracarbonitrile (1c). Yield 2.71 g (88%), mp 156‒
157°C (decomp.). IR spectrum, ν, cm–1: 2250 (C≡N),
1694 (C=O). 1H NMR spectrum, δ, ppm: in acetone-d6:
3.91 s (3H, CH3O), 3.94 s (3H, CH3O), 4.56 s (2H,
CH2CO), 6.14 s (1H, CHCN), 7.13 d (1H, Harom, J =
8.5 Hz), 7.64 d (1H, Harom, J = 2.1 Hz), 7.55 d.d (1H,
Harom, J = 2.1, 8.5 Hz); in CDCl3: 3.96 s (3H, CH3O),
4.01 s (3H, CH3O), 4.03 s (2H, CH2CO), 5.50 s (1H,
The purity of the isolated compounds was checked
by TLC on Sorbfil PTSKh-AF-A-UF plates; spots
were visualized under UV light, by treatment with
iodine vapor, or by calcination. The decomposition
points were determined on an Optimelt MPA100
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 9 2016

SOLVENT-FREE SYNTHESIS OF 4-OXOALKANE-1,1,2,2-TETRACARBONITRILES
1355
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melting point apparatus. The IR spectra were recorded
on an FSM-1202 spectrometer with Fourier transform
from samples dispersed in mineral oil. The H NMR
spectra were recorded on a Bruker DRX-500 spec-
trometer at 500.13 MHz relative to tetramethylsilane as
internal standard. The mass spectra (electron impact,
70 eV) were obtained on a Finnigan MAT INCOS-50
instrument. The elemental compositions were deter-
mined using a Vario Micro cube CHN analyzer.
1
This study was performed in the framework of the
base part of state assignment no. 872 of the Ministry of
Education and Science of the Russian Federation.
9. Masilamani, D., Reuman, M.E., and Rogic, M.M.,
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