Synthesis of methyl 3-acyl-6-amino-5-cyano-4-phenyl-4H-pyran-2-carboxylates and their rearrangement into 2-hydroxy-4-[hydroxy(R)methylidene]-3-oxo-5- phenylcyclopent-1-ene-1-carbonitriles

Full text of DOI:10.1134/S1070428011070244

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 7, pp. 1117–1118. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.P. Sheverdov, O.E. Nasakin, A.Yu. Andreev, V.L. Gein, V.A. Tafeenko, 2011, published in Zhurnal Organicheskoi Khimii, 2011,
Vol. 47, No. 7, pp. 1097–1098.
SHORT
COMMUNICATIONS
Synthesis of Methyl 3-Acyl-6-amino-5-cyano-4-phenyl-
4H-pyran-2-carboxylates and Their Rearrangement
into 2-Hydroxy-4-[hydroxy(R)methylidene]-3-oxo-
5-phenylcyclopent-1-ene-1-carbonitriles
V. P. Sheverdova, O. E. Nasakina, A. Yu. Andreeva, V. L. Geinb, and V. A. Tafeenkoc
a I.N. Ul’yanov Chuvash State University, Moskovskii pr. 15, Cheboksary, 428015 Russia
e-mail: SheverdovVP@yandex.ru
b Perm State Pharmaceutical Academy, Perm, Russia
c Faculty of Chemistry, Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
Received December 13, 2010
DOI: 10.1134/S1070428011070244
Synthesis of new 4H-pyrans is an important prob-
lem of organic chemistry. 4H-Pyran derivatives can
readily be converted into organic compounds belong-
ing to different classes. 4H-Pyrans, in particular
2-amino-3-cyano-4H-pyrans, are used as drugs, pesti-
cides, analogs of natural compounds, dyes, and other
important substances. They exhibit antimicrobial
[1, 2], antiviral [3], analgesic [4], antitumor [5, 6],
herbicidal [7, 8], and fungicidal [9] activity.
heating compounds IIIa and IIIb in aqueous sulfuric
acid over a period of 4–6 h we obtained cyclopenten-
ones IVa and IVb. The structure of compounds IIIa,
IIIb, IVa, and IVb was determined by IR spectros-
copy, mass spectrometry, and X-ray analysis.
Development of new methods for the synthesis of
cyclopentenone derivatives is important, for cyclo-
pentenone fragment is a structural unit of many natural
compounds and their analogs [12–14]. Known meth-
ods for building up 3-oxo-2-hydroxycyclopent-1-ene-
1-carbonitrile fragment include three laborious steps
and are characterized by poor yields (16–22%) [14].
The synthesis described in [14] required the use of
organometallic compounds, chromium(III) carbonyl,
titanium(IV) chloride, and iodine, as well as low tem-
perature (–78 to –20°C). The overal reaction time in
the synthesis of substituted 3-oxo-2-hydroxycyclopent-
1-ene-1-carbonitrile was more than 24 h. The proce-
dure proposed in the present work is simple and con-
venient, and complex multistep transformations are
performed in one synthetic operation.
Methyl 2,4-dioxobutanoates are used in the syn-
thesis of biologically active compounds [10, 11].
However, their reaction with benzylidenemalononitrile
was not studied. We found that this reaction gives
methyl 6-amino-3-acyl-5-cyano-4-phenyl-4H-pyran-
2-carboxylates which can be used as intermediate
products in the synthesis of carbo- and heterocycles.
2-Benzylidenemalononitrile (I) reacted with methyl
2,4-dioxopentanoate (IIa) and methyl 4-(4-methoxy-
phenyl)-2,4-dioxobutanoate in propan-2-ol in the pres-
ence of a catalytic amount of morpholine to produce
substituted pyrans IIIa and IIIb, respectively. By
R
Ph
R
Ph
O
CN
CN
HO
O
H2O, H2SO4
R
+
CN
Ph
OMe
O
CN
O
NH2
O
O
O
OH
OMe
I
IIa, IIb
IIIa, IIIb
IVa, IVb
R = Me (a), 4-MeOC6H4 (b).
1117

SHEVERDOV et al.
1118
Methyl 3-acetyl-6-amino-5-cyano-4-phenyl-4H-
approximation. The positions and thermal vibration
tensors of non-hydrogen atoms were refined in full-
matrix anisotropic approximation. All non-zero reflec-
tions were involved in the refinement procedure. The
unreliability coefficient was calculated from reflec-
tions with |F2| > 2σ; number of reflections 2140 (IIIa)
and 2850 (IVb). No correction for absorption was
introduced taking into account insignificant linear
absorption coefficient. The final R factor was 0.045
(IIIa) and 0.044 (IVb). The coordinates of atoms,
bond lengths, angles, and thermal vibration parameters
for structures IIIa and IVb were deposited to the Cam-
bridge Crystallographic Data Centre [entry nos. CCDC
764770 (IIIa), CCDC 764769 (IVb)].
pyran-2-carboxylate (IIIa). Yield 82%, mp 185–
186°C. IR spectrum, ν, cm–1: 3399, 3317, 2198, 1734,
1691, 1647, 1602. Mass spectrum: m/z 298 [M]+.
Found, %: C 64.42; H 4.73; N 9.39. C16H14N2O4. Cal-
culated, %: C 65.14; H 4.88; N 9.44. M 298.30.
Methyl 6-amino-5-cyano-3-(4-methoxybenzoyl)-
4-phenyl-4H-pyran-2-carboxylate (IIIb). Yield 85%,
mp 170–171°C. IR spectrum, ν, cm–1: 3440, 3325, 2194,
1736, 1674, 1642, 1600. Mass spectrum: m/z 390 [M]+.
Found, %: C 67.75; H 4.84; N 7.02. C22H18N2O5. Cal-
culated, %: C 67.69; H 4.65; N 7.18. M 390.39.
(Z)-2-Hydroxy-4-(1-hydroxyethylidene)-3-oxo-5-
phenylcyclopent-1-ene-1-carbonitrile (IVa). Yield
28%, mp 179–180°C. IR spectrum, ν, cm–1: 3435, 3205,
2222, 1650, 1638, 1603. Mass spectrum: m/z 241 [M]+.
Found, %: C 69.42; H 4.67; N 5.96. C14H11NO3. Cal-
culated, %: C 69.70; H 4.60; N 5.81. M 241.24.
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1
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9.5147(12), b = 10.0778(13), c = 9.5877(12) Å;
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011