One-step transformation of tetracyanocyclopropyl ketones into pyrrolo[3,4-c]pyridine derivatives

Full text of DOI:10.1134/S1070428010080282

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 8, pp. 1266–1267. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © Ya.S. Kayukov, I.N. Bardasov, O.V. Kayukova, O.V. Ershov, O.E. Nasakin, 2010, published in Zhurnal Organicheskoi Khimii,
2010, Vol. 46, No. 8, pp. 1263–1264.
SHORT
COMMUNICATIONS
One-Step Transformation of Tetracyanocyclopropyl Ketones
into Pyrrolo[3,4-c]pyridine Derivatives
Ya. S. Kayukova, I. N. Bardasova, O. V. Kayukovab, O. V. Ershova, and O. E. Nasakina
a I.N. Ul’yanov Chuvash State University, Moskovskii pr. 15, Cheboksary, 428015 Russia
e-mail: kaukovyakov@mail.ru
b Chuvash Agricultural Academy, Cheboksary, Russia
Received January 9, 2010
DOI: 10.1134/S1070428010080282
Tetracyanocyclopropyl ketones obtainable via mod-
ified Wideqvist reaction are accessible and convenient
precursors of a number of heterocyclic systems [1–3].
Reactions of cyclopropyl ketones Ia–Ic with alkoxides
give rise to 2-[2-alkoxy-5-amino-4-cyano-2-phenyl-
furan-3(2H)-ylidene]malononitriles [3]. We anticipated
that replacement of the ketone acetal fragment in the
latter by more labile semiacetal moiety should facili-
tate recyclization of the furan ring into pyrrole. Such
transformation could be promoted using hydroxide ion
instead of alkoxide in reactions with cyclopropyl
ketones Ia–Ic.
The above assumption was verified by studying the
reaction of cyclopropyl ketones Ia–Ic with aqueous
sodium hydroxide. We found that this reaction in-
volves not only expected recyclization of furan ring
into pyrrole but also annelation of pyridine ring. The
structure of compounds IIa–IIc isolated by neutraliza-
tion of the reaction mixture with a solution of sulfuric
acid was confirmed by the 1H NMR and mass spectra.
1
The H NMR spectra contained singlets at δ 7.12–
7.69 and 8.78–9.02 ppm, which were assigned to the
hydroxy and NH protons, respectively, in the pyrrole
ring. The NH proton in the pyridine ring resonated as
NC
NC
CN
CN
NC
NC
NC
CN
OH
CN
OH
O
R
NC
NC
OH–
NH
O
R
HN
O
O
O
N
N
H
CN
R
R
H
Ia–Ic
NH2
NC
NC
O
NH
OH
NH
NC
NC
H2O (OH–)
N
NH
OH
OH
R
O
R
O
O
N
N
OH
R
H
CN
O
NH2
O
O
HN
HN
H2SO4
NH
OH
NH
OH
–Na2SO4
O
H2N
R
R
CN
IIa–IIc
CN
A
R = Ph (a), 4-MeC6H4 (b), 3-O2NC6H4 (c).
1266

ONE-STEP TRANSFORMATION OF TETRACYANOCYCLOPROPYL KETONES
1267
a broadened singlet at δ 11.4 ppm. Protons in the
amino group also gave rise to a broadened singlet
which was overlapped (except for compound IIc) by
signals from aromatic protons in the region δ 7.3–
8.8 ppm. The molecular ion peak in the mass spectra of
IIa–IIc had low intensity (5–10%), but its m/z value
indicated addition of two water molecules during the
process. The above data led us to assign the products
the structure of 4-amino-1-hydroxy-3,6-dioxo-1-phen-
yl-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-c]pyridine-7-car-
bonitriles IIa–IIc. The IR spectra and elemental anal-
yses did not contradict the assumed structure. On the
other hand, the spectral parameters of the products are
also consistent with regioisomeric structure A which
differs from II by the position of amino and oxo
groups in the pyridine ring. Nevertheless, structure II
seems to be more probable, taking into account that the
formation of pyridine ring is preceded by hydrolysis of
one cyano group under assistance with the acyl frag-
ment, as shown in scheme.
7.38 d (2H, C6H4, J = 8.9 Hz), 7.5–7.2 br.s (2H, NH2),
8.78 s (1H, NH), 11.3–11.5 br.s (1H, NH). Mass spec-
trum: m/z 312 (Irel 6%). Found, %: C 57.61; H 3.82;
N 17.86. C15H12N4O4. Calculated, %: C 57.69; H 3.87;
N 17.94.
4-Amino-1-hydroxy-1-(3-nitrophenyl)-3,6-dioxo-
2,3,4,6-tetrahydro-1H-pyrrolo[3,4-c]pyridine-7-car-
bonitrile (IIc). Yield 2.29 g (70%), mp 183–184°C
(decomp.). IR spectrum, ν, cm–1: 3288, 3211 (NH2);
2221 (C≡N); 1721, 1691 (C=O); 1533, 1377 (NO2).
1H NMR spectrum, δ, ppm: 7.4–7.6 br.s (2H, NH2);
7.64 s (1H, OH), 7.69 t (1H, C6H4, J = 8.0 Hz), 7.85 d
(1H, C6H4, J = 8.0 Hz), 8.24 d.d (1H, C6H4, J = 7.7,
2.3 Hz), 8.33 t (1H, C6H4, J = 2.0 Hz), 9.02 s (1H,
NH), 11.2–11.6 br.s (1H, NH). Mass spectrum: m/z 327
(Irel 5%). Found, %: C 51.29; H 2.82; N 21.32.
C14H9N5O5. Calculated, %: C 51.38; H 2.77; N 21.40.
The progress of reactions and the purity of products
were monitored by TLC on Silufol UV-254 plates;
spots were detected under UV light, by treatment with
iodine vapor, or by thermal treatment. The IR spectra
were recorded from samples dispersed in mineral oil
on an FSM-1202 spectrometer with Fourier transform.
4-Amino-1-hydroxy-3,6-dioxo-1-phenyl-2,3,4,6-
tetrahydro-1H-pyrrolo[3,4-c]pyridine-7-carboni-
trile (IIa). 3-Benzoylcyclopropane-1,1,2,2-tetracarbo-
nitrile (Ia), 2.46 g (0.01 mol), was dissolved under
stirring in 15 ml of a 7% solution of sodium hydroxide,
and the solution was left to stand for 24 h. The mixture
was then acidified with a 10% solution of sulfuric acid,
and the precipitate was filtered off and washed with
water. Yield 1.89 g (67%), mp 145–147°C (decomp.).
IR spectrum, ν, cm–1: 3280, 3222 (NH2); 2228 (C≡N);
1
The H NMR spectra were measured on a Bruker
DRX-500 instrument at 500.13 MHz using DMSO-d6
as solvent and tetramethylsilane as internal reference.
The mass spectra (electron impact, 70 eV) were ob-
tained on a Finnigan MAT INCOS 50 instrument.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 10-03-97013r-povolzh’e-a).
1
1719, 1697 (C=O). H NMR spectrum, δ, ppm: 7.22 s
(1H, OH), 7.33–7.49 m (5H, C6H5), 7.3–7.6 br.s (2H,
NH2), 8.86 s (1H, NH), 11.39 s (1H, NH). Mass spec-
trum: m/z 282 (Irel 10%). Found, %: C 59.49; H 3.59;
N 19.78. C14H10N4O3. Calculated, %: C 59.57; H 3.57;
N 19.85.
4-Amino-1-hydroxy-1-(4-methoxyphenyl)-3,6-di-
oxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-c]pyridine-7-
carbonitrile (IIb). Yield 2.28 g (73%), mp 142–144°C
(decomp.). IR spectrum, ν, cm–1: 3280, 3230 (NH2);
2220 (C≡N); 1717, 1695 (C=O). 1H NMR spectrum, δ,
ppm: 6.91 d (2H, C6H4, J = 8.9 Hz), 7.12 s (1H, OH),
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010