Synthesis of new furopyrans and angularly fused furopyranochromenes from 3-arylmethylidenefuran-2-ones

Article abstract of DOI:10.1134/S1070428013100187

Reactions of 5-aryl-3-arylmethylidenefuran-2-ones with malononitrile gave 6-amino-2,4-diaryl-4Hfuro[2,3-b]pyran-5-carbonitriles and 2-aryl-5-imino-5H, 11bH-furo[3′,2′: 5,6]pyrano[3,4-c]chromen-6-amines as potentially biologically active substances.

Full text of DOI:10.1134/S1070428013100187

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 10, pp. 1514–1516. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © T.V. Anis’kova, A.Yu. Egorova, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 10, pp. 1534–1536.
Synthesis of New Furopyrans and Angularly Fused
Furopyranochromenes from 3-Arylmethylidenefuran-2-ones
T. V. Anis’kova and A. Yu. Egorova
Institute of Chemistry, Chernyshevsky Saratov State University,
ul. Astrakhanskaya 83-1, Saratov, 410012 Russia
e-mail: aniskovatv@mail.ru
Received March 11, 2013
Abstract—Reactions of 5-aryl-3-arylmethylidenefuran-2-ones with malononitrile gave 6-amino-2,4-diaryl-4H-
furo[2,3-b]pyran-5-carbonitriles and 2-aryl-5-imino-5H,11bH-furo[3′,2′:5,6]pyrano[3,4-c]chromen-6-amines
as potentially biologically active substances.
DOI: 10.1134/S1070428013100187
Arylmethylidene-substituted 3H-furan-2-ones are
structural fragments of natural compounds and con-
venient building blocks for the synthesis of complex
angularly and linearly fused heterocyclic compounds.
3-Arylmethylidene-3H-furan-2-ones react with various
carbon-centered nucleophiles (ethyl acetoacetate [1],
acetylacetone [2], cyclohexanone [3]) at the carbon
atom of the exocyclic double bond, while their reac-
tions with mono- and binucleophiles involve the
carbonyl carbon atom [4, 5].
In continuation of our studies on the reactivity of
3-arylmethylidene-3H-furan-2-ones, in the present
work we examined their behavior in reactions with
malononitrile. The presence of highly reactive methy-
lene and cyano groups in malononitrile molecule
makes it useful as reagent for cyclization reactions
leading to carbo- and heterocyclic compounds.
were isolated in up to 70% yield; their structure was
1 1
proved by H NMR spectroscopy. The H NMR
spectra of IIa and IIb contained a singlet at δ 6.00–
6.45 ppm (1H) from proton in the furan ring, a down-
field broadened two-proton singlet at δ 6.98–7.20 ppm
from the amino group, and a singlet at δ 4.74–
4.97 ppm (1H) from 4-H. Protons in the aromatic sub-
stituents resonated in the region δ 6.90–7.50 ppm.
The reaction of 5-aryl-3-arylmethylidene-3H-furan-
2-ones with malononitrile in the presence of triethyl-
amine follows a cascade heterocyclization pattern.
Carbanion derived from malononitrile initially adds to
the activated exocyclic C=C bond of compound I to
form the corresponding Michael adduct, and the subse-
quent nucleophilic attack by the oxygen atom on the
carbon atom of the cyano group yields O-hetero-
cyclization product which is stabilized as enamino
tautomer, 6-amino-2,4-diaryl-4H-furo[2,3-b]pyran-5-
carbonitrile II (Scheme 2).
The reactions of 5-aryl-3-arylmethylidene-3H-
furan-2-ones Ia–Ic with malononitrile were carried out
at a molar ratio of 1:1 on heating in dimethyl sulfoxide
in the presence of a catalytic amount of triethylamine
(Scheme 1). The products were 6-amino-2,4-diaryl-
4H-furo[2,3-b]pyran-5-carbonitriles IIa–IIc which
Scheme 2.
Ia–Ic +
NC
CN
CN
CN
Ar
Ar
CN
CN
Et3N
Scheme 1.
Ar
Ar'
O
Ar'
OH
Ar
O
O
NCCH2CN
NC
Et3N, DMSO
Ar
Ar'
CN
Ar'
O
O
O
H2N
O
IIa–IIc
Ar'
Ia–Ic
IIa–IIc
O
NH
Ar = 2-ClC6H4, Ar′ = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4 (c).
1514

SYNTHESIS OF NEW FUROPYRANS
1515
Scheme 3.
OH
O
O
Et3N, DMSO
+
NC
CN
NH2
NH
NH2
Ar
Ar
Ar
O
O
O
O
O
NH
O
Id–If
IIIa–IIIc
IVa–IVc
Id, IIIa, IVa, Ar = Ph; Ie, IIIb, IVb, Ar = 4-MeC6H4; If, IIIc, IVc, R = 4-MeOC6H4.
Scheme 4.
O
a
NH2
Ar
CN
OH
CN
O
O
A
Id–If
+
IIIa–IIIc
IVa–IVc
NC
CN
CN
Ar
O
O
OH
CN
b
Ar
O
O
NH2
B
CN
O
Ar
A
O
N
H
C
diate A. Intramolecular interaction between the cyano
group and carbonyl oxygen atom in A leads to hetero-
cyclization to final product III (or IV). Following path
b, heterocyclization of the Michael adduct with partic-
ipation of one cyano group and carbonyl oxygen atom
in the furan ring gives furopyran intermediate B whose
subsequent heterocyclization via intramolecular nu-
cleophilic attack by the phenolic hydroxy group on the
cyano carbon atom yields the same product (III or IV)
as in a. No bridged tetracyclic compounds C which
could be formed from intermediates A were detected.
5-Aryl-3-(2-hydroxyphenylmethylidene)-3H-furan-
2-ones Id–If reacted with malononitrile under analo-
gous conditions to afford 2-aryl-5-imino-5H,11bH-furo-
[3′,2′:5,6]pyrano[3,4-c]chromen-6-amines III (or tau-
tomeric structures IV; Scheme 3). The product struc-
ture was consistent with their 1H and 13C NMR spectra.
However, we failed to unambiguously identify the
products as tautomers III or IV on the basis of their
spectral data and quantum-chemical calculations.
Presumably, the condensation involves initial
Michael addition of malononitrile carbanion to the
activated exocyclic double C=C bond of substituted
furanone Id–If (Scheme 4). The resulting Michael
adduct may be stabilized according to several paths.
Path a implies participation of the aromatic hydroxy
group with formation of substituted chromene interme-
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded at
20–25°C on a Varian-400 spectrometer at 400 and
100 MHz, respectively, from solutions in CDCl3 using
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 10 2013

ANIS’KOVA, EGOROVA
1516
TMS as internal reference. Analytical TLC was per-
formed on Silufol UV-254 plates using hexane–ethyl
acetate–chloroform (2:2:1) as eluent; spots were visu-
alized by treatment with iodine vapor.
6-Amino-2-aryl-4-(2-chlorophenyl)-4H-furo-
[2,3-b]pyran-5-carbonitriles II (general procedure).
A few drops of triethylamine were added to a mixture
of 0.01 mol of 5-aryl-3-arylmethylidene-3H-furan-2-
one Ia–Ic and 0.01 mol of malononitrile in 10 ml of
DMSO. The mixture was heated for 4–5 h at 110°C,
poured into cold water, and neutralized with dilute
hydrochloric acid. The precipitate was filtered off
through a Schott filter and recrystallized from hexane.
5-Imino-2-phenyl-5H,11bH-furo[3′,2′:5,6]-
pyrano[3,4-c]chromen-6-amine (IIIa or IVa). Yield
1
87%, mp 191–193°C. H NMR spectrum, δ, ppm:
4.31 s (1H, CH), 6.52 s (1H, =CH), 7.35–7.69 m (9H,
H
arom), 7.91 s (1H, NH), 8.92 s (2H, NH2). 13C NMR
spectrum, δC, ppm: 25.9, 97.6, 116.5, 118.3, 119.1,
120.4, 121.5, 125.3, 126.6, 127.6, 128.5, 128.7, 129.3,
131.7, 132.4, 132.2, 157.9, 168.5. Found, %: C 73.00;
H 4.54; N 8.69. C20H14N2O3. Calculated, %: C 72.72;
H 4.27; N 8.48.
5-Imino-2-(4-methylphenyl)-5H,11bH-furo-
[3′,2′:5,6]pyrano[3,4-c]chromen-6-amine (IIIb or
1
IVb). Yield 89%, mp197–199°C. H NMR spectrum,
δ, ppm: 2.34 s (3H, CH3), 4.36 s (1H, CH), 6.52 s (1H,
=CH), 7.35–7.69 m (8H, Harom), 7.92 s (1H, NH),
8.87 s (2H, NH2). 13C NMR spectrum, δC, ppm: 21.5,
26.6, 99.4, 114.5, 116.3, 118.3, 119.2, 122.7, 124.9,
128.5, 129.2, 129.5, 130.5, 131.6, 132.54, 134.4, 137.3,
159.6, 170.5. Found, %: C 73.57; H 4.94; N 7.68.
C21H16N2O3. Calculated, %: C 73.24; H 4.68; N 8.13.
6-Amino-4-(2-chlorophenyl)-2-phenyl-4H-furo-
[2,3-b]pyran-5-carbonitrile (IIa). Yield 75%,
1
mp 122–124°C. H NMR spectrum, δ, ppm: 4.97 s
(1H, 4-H), 6.41 s (1H), 7.04 s (2H, NH2), 7.26–7.65 m
(9H, Harom). Found, %: C 68.48; H 3.39; N 8.51.
C20H13ClN2O2. Calculated, %: C 68.87; H 3.76; N 8.03.
6-Amino-4-(2-chlorophenyl)-2-(4-methylphenyl)-
5-Imino-2-(4-methoxyphenyl)-5H,11bH-furo-
[3′,2′:5,6]pyrano[3,4-c]chromen-6-amine (IIIc or
4H-furo[2,3-b]pyran-5-carbonitrile (IIb). Yield
1
83%, mp 145–147°C. H NMR spectrum, δ, ppm:
1
IVc). Yield 93%, mp 206–208°C. H NMR spectrum,
2.35 s (3H, CH3), 4.80 s (1H, 4-H), 6.45 s (1H), 7.20 s
(2H, NH2), 7.30–7.53 m (8H, Harom). Found, %:
C 69.46; H 4.43; N 7.26. C21H15ClN2O2. Calculated,
%: C 69.52; H 4.17; N 7.72.
δ, ppm: 3.48 s (3H, OCH3), 4.47 s (1H, CH), 6.68 s
(1H, =CH), 7.35–7.69 m (8H, Harom), 8.06 s (1H, NH),
9.10 s (2H, NH2). 13C NMR spectrum, δC, ppm: 26.56,
53.8, 98.3, 109.5, 112.6, 115.3, 116.2, 120.8, 122.3,
124.5, 127.3, 128.1, 131.5, 131.9, 133.8, 136.3, 139.8,
158.1, 171.2. Found, %: C 70.31; H 4.65; N 8.03.
C21H16N2O4. Calculated, %: C 69.99; H 4.48; N 7.77.
6-Amino-4-(2-chlorophenyl)-2-(4-methoxy-
phenyl)-4H-furo[2,3-b]pyran-5-carbonitrile (IIc).
1
Yield 68%, mp 153–155°C. H NMR spectrum, δ,
ppm: 3.73 s (3H, OCH3), 4.88 s (1H, 4-H), 6.40 s (1H),
7.15 s (2H, NH2), 6.90–7.56 m (8H, Harom). Found, %:
C 66.23; H 4.32; N 7.54. C21H15ClN2O3. Calculated,
%: C 66.58; H 3.99; N 7.40.
REFERENCES
1. Aniskova, T.V., Yegorova, A.Yu., and Chadina, V.V.,
2-Aryl-5-imino-5H,11bH-furo[3′,2′:5,6]pyrano-
[3,4-c]chromen-6-amines III or IV (general proce-
dure). A few drops of triethylamine were added to
a mixture of 0.01 mol of 3-salicylidene-3H-furan-2-
one Id–If and 0.01 mol of malononitrile in 10 ml of
DMSO. The mixture was heated for 4–5 h at 110°C,
poured into cold water, and neutralized with dilute
hydrochloric acid. The precipitate was filtered off
through a Schott filter and recrystallized from hexane.
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