Synthesis of 5-Amino-3H-pyrrole-3,4-dicarbonitriles from 4-Aryl-4-oxobutane-1,1,2,2-tetracarbonitriles

Full text of DOI:10.1134/S1070428011090272

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 9, pp. 1426–1427. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © M.Yu. Belikov, O.V. Ershov, I.V. Lipovskaya, A.V. Eremkin, O.E. Nasakin, 2011, published in Zhurnal Organicheskoi Khimii, 2011,
Vol. 47, No. 9, pp. 1401–1402.
SHORT
COMMUNICATIONS
Synthesis of 5-Amino-3H-pyrrole-3,4-dicarbonitriles
from 4-Aryl-4-oxobutane-1,1,2,2-tetracarbonitriles
M. Yu. Belikov, O. V. Ershov, I. V. Lipovskaya, A. V. Eremkin, and O. E. Nasakin
I.N. Ul’yanov Chuvash State University, Moskovskii pr. 15, Cheboksary, 428015 Russia
e-mail: belikovmil@mail.ru
Received April 1, 2011
DOI: 10.1134/S1070428011090272
It is known that 4-oxoalkane-1,1,2,2-tetracarbo-
nitriles react with nitrogen-centered nucleophiles, such
as ammonia and amines, to give 3-amino-7-oxo-4,6-di-
azabicyclo[3.2.1]oct-2-ene-1,2-dicarbonitriles [1],
3-amidinio-2-aminopyridine-4-carboxylates [2], di-
ethylammonium 3,4-dicyano-5,6,7,8-tetrahydroquino-
lin-2-olates [3], and ammonium 4-aryl-4-oxo-1,1,2-tri-
cyanobut-2-en-1-ides [4]. However, these results do
not allow us to draw a definite conclusion on the direc-
tion of attack by N-nucleophiles on the reaction centers
in polyelectrophilic 4-oxoalkane-1,1,2,2-tetracarbo-
nitriles.
ring in IIa–IIc. Attack on the β-cyano group is deter-
mined by reduced electrophilicity of the terminal cy-
ano groups due to delocalization of the negative charge
in the anion of salt A. 3H-Pyrrole IIc possesses two
asymmetric carbon atoms (C2, C11), but this compound
was isolated as a single diastereoisomer.
The structure of pyrroles IIa–IIc was confirmed by
1
their IR, H and 13C NMR, and mass spectra and ele-
mental analyses. The structure of compound IIa was
unambiguously proved by the X-ray diffraction data.
General procedure for the synthesis of com-
pounds IIa–IIc. A solution of 0.5 mmol of 4-aryl-4-
oxobutane-1,1,2,2-tetracarbonitrile Ia–Ic in 3 ml of
anhydrous ethyl acetate was cooled to –10 to –15°C,
0.087 g (1 mmol) of morpholine was added under
vigorous stirring, and the resulting yellow–orange
solution was left to stand at –10 to –15°C in a closed
vessel. After 2–3 days, the yellowish precipitate was
filtered off, washed on a filter with cold ethyl acetate
and diethyl ether, and dried in air.
While continuing studies on reactions of tetracy-
anoethylated ketones with N-nucleophiles, we found
that 4-aryl-4-oxobutane-1,1,2,2-tetracarbonitriles Ia–Ic
react with morpholine to produce 80–93% of previ-
ously unknown 5-amino-3-(2-aryl-2-oxoethyl)-2-mor-
pholino-3H-pyrrole-3,4-dicarbonitriles IIa–IIc.
Presumably, the initial step in this reaction is
formation of morpholinium salt A with CH acid Ia–Ic.
Analogous salts containing metal and ammonium ions
as cationic species have been reported [4–6]. Salts A
undergo further transformations by the action of excess
morpholine. These transformations involve primarily
the β-cyano group, as follows from the presence of
morpholine fragment in position 2 of the 3H-pyrrole
5-Amino-2-morpholino-3-(2-oxo-2-phenylethyl)-
3H-pyrrole-3,4-dicarbonitrile (IIa). Yield 0.156 g
(93%), mp 208–209°C (decomp.). IR spectrum, ν,
cm–1: 3184–3311 (NH2); 2232, 2182 (C≡N); 1691
1
(C=O). H NMR spectrum, δ, ppm (J, Hz): 3.62–
3.80 m (8H, NCH2CH2O), 3.92 d (1H, CH2, J = 17.8),
Ar
O
5CN
NH
NH
12
11
6
CN
O
CN
O
CN
O
O
R
NH2
3
CN
CNH2
2
Ar
Ar
1
7
O
NC
R
NC
8
NH
4
N
NH2
N
–
CN
R
CN
O
10
O
9
Ia–Ic
A
IIa–IIc
Ar = Ph, R = H (a); Ar = 4-ClC6H4, R = H (b); Ar = 4-MeOC6H4, R = Me (c).
1426

SYNTHESIS OF 5-AMINO-3H-PYRROLE-3,4-DICARBONITRILES
1427
4.06 d (1H, CH2, J = 17.8), 7.27 s (2H, NH2), 7.53–
7.57 m (2H, Harom), 7.60–7.70 m (1H, Harom), 7.98–
8.01 m (2H, Harom). 13C NMR spectrum, δC, ppm:
42.73 (C11), 47.45 (C2, C7, C10), 57.54 (C3), 65.98 (C8,
C9), 117.56, 118.54 (C5, C6), 128.66, 129.17, 134.24,
136.17 (C6H5); 170.66, 170.94 (C1, C4); 194.10 (C12).
Mass spectrum, m/z (Irel, %): 335 (43) [M]+, 216 (100).
Found, %: C 64.57; H 5.02; N 20.97. C18H17N5O2. Cal-
culated, %: C 64.47; H 5.11; N 20.88. M 335.36.
(spots were visualized by UV irradiation, treatment
with iodine vapor, or thermal decomposition). The IR
spectra were recorded on an FSM-1202 spectrometer
with Fourier transform from samples dispersed in min-
1
eral oil. The H and 13C NMR spectra were measured
on a Bruker DRX-500 spectrometer at 500.13 and
125.76 MHz, respectively, using DMSO-d6 as solvent
and tetramethylsilane as internal reference. The ele-
mental compositions were determined on a Laboratorni
Přistroje instrument. The mass spectra (electron
impact, 70 eV) were obtained on a Finnigan MAT
INCOS-50 spectrometer.
5-Amino-3-[2-(4-chlorophenyl)-2-oxoethyl]-2-
morpholino-3H-pyrrole-3,4-dicarbonitrile (IIb).
Yield 0.157 g (85%), mp 220–221°C (decomp.). IR
spectrum, ν, cm–1: 3157–3403 (NH2); 2233, 2172
This study was performed under financial support
by the Federal Special-Purpose Program “Scientific
and Scientific–Pedagogical Staff of Innovation Russia
2009–2013” (state contract no. 14.740.11.0715).
1
(C≡N); 1667 (C=O). H NMR spectrum, δ, ppm
(J, Hz): 3.66–3.78 m (8H, NCH2CH2O), 3.90 d and
4.06 d (1H each, CH2CO, J = 17.7), 7.26 s (2H, NH2),
7.61–7.64 m (2H, Harom), 7.99–8.03 m (2H, Harom).
Mass spectrum, m/z (Irel, %): 369 (3) [M]+, 216 (100).
Found, %: C 58.53; H 4.31; N 19.02. C18H16ClN5O2.
Calculated, %: C 58.46; H 4.36; N 18.94. M 369.80.
REFERENCES
1. Nasakin, O.E., Sheverdov, V.P., Moiseeva, I.V., Lyshchi-
kov, A.N., Ershov, O.V., and Nesterov, V.N., Tetrahedron
Lett., 1997, vol. 38, p. 4455.
5-Amino-3-[2-(4-methoxyphenyl)-1-methyl-2-
oxoethyl]-2-morpholino-3H-pyrrole-3,4-dicarbo-
nitrile (IIc). Yield 0.152 g (80%), mp 211–212°C
(decomp.). IR spectrum, ν, cm–1: 3149–3347 (NH2);
2233, 2169 (C≡N); 1672 (C=O). 1H NMR spectrum, δ,
ppm (J, Hz): 0.98 d (3H, CH3, J = 6.9), 3.68–3.76 m
(8H, NCH2CH2O), 3.86 s (3H, OCH3), 4.26 q (1H,
CHCH3, J = 6.9), 7.08 d (2H, Harom, J = 8.9), 7.28 s
(2H, NH2), 8.00 d (2H, Harom, J = 8.9). Mass spectrum,
m/z (Irel, %): 379 (3) [M]+, 216 (100). Found, %:
C 63.33; H 5.51; N 18.52. C20H21N5O3. Calculated, %:
C 63.31; H 5.58; N 18.46. M 379.41.
2. Nasakin, O.E., Sheverdov, V.P., Ershov, O.V., Moisee-
va, I.V., Lyshchikov, A.N., Khrustalev, V.N., and Anti-
pin, M.Yu., Mendeleev Commun., 1997, vol. 7, p. 112.
3. Belikov, M.Yu., Ershov, O.V., Eremkin, A.V., Kayu-
kov, Ya.S., and Nasakin, O.E., Russ. J. Org. Chem., 2010,
vol. 46, p. 615.
4. Belikov, M.Yu., Ershov, O.V., Eremkin, A.V., Kayu-
kov, Ya.S., and Nasakin, O.E., Russ. J. Org. Chem., 2010,
vol. 46, p. 597.
5. Nasakin, O.E., Lukin, P.M., and Nikolaev, E.G., Zh. Org.
Khim., 1987, vol. 23, p. 659.
The progress of reactions and the purity of products
were monitored by TLC on Silufol UV-254 plates
6. Carlucci, L., Ciani, G., Proserpio, D.M., and Sironi, A.,
Angew. Chem., Int. Ed. Engl., 1996, vol. 35, p. 1088.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011