Synthesis of new unsaturated derivatives of functionally substituted 2-imino-2,5-dihydrofurans

Article abstract of DOI:10.1134/S1070428011030183

5,5-Substituted 2-imino-4-methyl-2,5-dihydrofuran-3-carbonitriles reacted with aromatic aldehydes to give the corresponding 5,5-substituted 2-imino-4-(2-R-vinyl)-2,5-dihydrofuran-3-carbonitriles. The latter were converted into hydrochlorides which were hy

Full text of DOI:10.1134/S1070428011030183

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 3, pp. 433–436. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © A.A. Avetisyan, A.G. Alvandzhyan, K.S. Avetisyan, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 3,
pp. 439–441.
Synthesis of New Unsaturated Derivatives of Functionally
Substituted 2-Imino-2,5-dihydrofurans
A. A. Avetisyan†, A. G. Alvandzhyan, and K. S. Avetisyan
Erevan State University, ul. A. Manukyana 1, Erevan, 375025 Armenia
e-mail: organkim@sun.ysu.am
Received April 1, 2010
Abstract—5,5-Substituted 2-imino-4-methyl-2,5-dihydrofuran-3-carbonitriles reacted with aromatic aldehydes
to give the corresponding 5,5-substituted 2-imino-4-(2-R-vinyl)-2,5-dihydrofuran-3-carbonitriles. The latter
were converted into hydrochlorides which were hydrolyzed to 3-cyano-4-(2-R-vinyl)-2,5-dihydrofuran-2-ones
whose condensation with malononitrile afforded dicyanomethylidene derivatives.
DOI: 10.1134/S1070428011030183
It is known that compounds containing an unsatu-
rated lactone ring exhibit a broad spectrum of biologi-
cal activity [1–3]. On the other hand, biological activ-
ity of γ-lactones also depends on the nature of substit-
uents in the lactone ring. We previously reported on
the lability of hydrogen atoms in the methyl group
at the endocyclic double bond of Δ3-butenolides in
cyanoethylation [4] and condensation with various
aromatic aldehydes [5, 6].
(2-furylvinyl)-2-imino-2,5-dihydrofuran-3-carboni-
triles Ia–Id and IIa–IId (Scheme 1).
2-Imino derivatives Ia–Id and IIa–IId are reactive
compounds. They readily form salts with acids. By
passing gaseous hydrogen chloride through solutions
of compounds Ia, Ib, and IIa in benzene we obtained
the corresponding hydrochlorides IIIa–IIIc in quanti-
tative yield (Scheme 2). Hydrochlorides IIIa–IIIc
readily underwent hydrolysis in water at 70–80°C (re-
action time 3 h) to give lactones IVa–IVc.
In continuation of our studies in the field of syn-
thesis of new functionally substituted 2,5-dihydro-
furans, the present article reports on the reaction of
2-imino-4-methyl-2,5-dihydrofuran-3-carbonitriles
with aromatic aldehydes. The condensation involved
labile hydrogen atoms in the methyl group in position
4 of the ring. Optimal conditions for this reaction were
found. The best results were obtained at a reactant ratio
of 1:1 in an alcoholic solution of sodium hydroxide.
The products were the corresponding 4-styryl- and 4-
Scheme 2.
R3
R3
CN
CN
HCl
R1
R2
Ia, Ib, IIa
R1
R2
NH
NH·HCl
O
O
IIIa–IIIc
R3
CN
Scheme 1.
R1
R2
IVa–IVc
R3
O
O
Me
CN
CN
R3CHO
R1
R2
R1
R2
Ia–Id, IIa–IId
R1R2 = (CH2)5, R3 = Ph (a), 2-furyl (b); R1 = R2 = Me,
R3 = Ph (d).
NH
NH
O
O
4-Substituted 2-imino-2,5-dihydrofuran-3-carbo-
nitriles Ia, Ib, IIa, and IIb were brought into reaction
with malononitrile. Under the optimal conditions
(equimolar amounts of the reactants, room tempera-
R1R2 = (CH2)5 (a); R1 = R2 = Me (b); R1 = Me, R2 = Et (c),
Ph (d); I, R3 = Ph; II, R = 2-furyl.
†
Deceased.
433

AVETISYAN et al.
434
ture), the corresponding 2-dicyanomethylidene deriva-
tives Va–Vd were obtained in good yields (Scheme 3).
10.50 s (1H, ΝH). Found, %: C 75.53; H 5.68;
N 11.46. C15H14N2O. Calculated, %: C 75.63; H 5.88;
N 11.76.
Scheme 3.
5-Ethyl-2-imino-5-methyl-4-(2-phenylvinyl)-2,5-
dihydrofuran-3-carbonitrile (Ic). Yield 84%,
mp 117–119°C. 1H NMR spectrum, δ, ppm: 0.85 t (3H,
CH2CH3, J = 7.5 Hz), 1.45 s (3H, CH3), 1.78–1.83 m
(2H, CH2CH3), 6.15 d and 6.48 d (1H each, CH=CH,
J = 16.3 Hz), 7.18–7.24 m (5H, Harom), 10.55 s (1H,
ΝH). Found, %: C 76.09; H 6.45; N 11.14. C16H16N2O.
Calculated, %: C 76.19; H 6.35; N 11.11.
R3
CN
CH2(CN)2
Ia, Ib, IIa, IIb
CN
R1
R2
–NH3
O
CN
Va–Vd
R1R2 = (CH2)5, R3 = Ph (a), 2-furyl (b); R1 = R2 = Me,
R3 = Ph (c), 2-furyl (d).
2-Imino-5-methyl-5-phenyl-4-(2-phenylvinyl)-
2,5-dihydrofuran-3-carbonitrile (Id). Yield 80%,
mp 120–122°C. IR spectrum, ν, cm–1: 3280, 3052,
2910, 2848, 2230, 1660, 1615, 1492, 1450, 1385,
1342, 1250, 1135, 1090, 986, 907, 835, 595. H NMR
spectrum, δ, ppm: 1.63 s (3H, CH3), 6.08 d and 6.35 d
(1H each, CH=CH, J = 16.2 Hz), 7.12–7.35 m (5H,
EXPERIMENTAL
The IR spectra were recorded on a UR-20 spec-
trometer from samples dispersed in mineral oil. The
1H NMR spectra were measured on a Varian Mercury-
300 spectrometer at 300 MHz using CDCl3 as solvent
and hexamethyldisiloxane as internal reference.
1
H
arom), 7.42–7.55 m (5H, Harom), 10.35 s (1H, ΝH).
Found, %: C 79.80; H 5.45; N 9.13. C20H16N2O. Cal-
culated, %: C 80; H 5.33; N 9.33.
5,5-Substituted 2-imino-4-(2-R-vinyl)-2,5-dihy-
drofuran-3-carbonitriles Ia–Id and IIa–IId (general
procedure). The corresponding 5,5-substituted
2-imino-4-methyl-2,5-dihydrofuran-3-carbonitrile,
5 mmol, and aldehyde, 5 mmol, were added to a solu-
tion of 0.01 g of sodium hydroxide in 20 ml of anhy-
drous ethanol. The mixture was heated for 4 h under
reflux. The solvent was distilled off, the residue was
treated with ice water, and the precipitate was filtered
off, washed with water, dried, and recrystallized from
diethyl ether–petroleum ether (1:4).
4-[2-(2-Furyl)vinyl]-2-imino-5,5-pentamethylene-
2,5-dihydrofuran-3-carbonitrile (IIa). Yield 88%,
1
mp 162–163°C. H NMR spectrum, δ, ppm: 1.20–
1.25 m (2H, CH2), 1.48–1.55 m (2H, CH2), 1.63–
1.90 m (6H, CH2), 6.17 d and 6.33 d (1H each,
CH=CH, J = 16.1 Hz), 7.60–7.75 m (3H, furan),
10.70 s (1H, ΝH). Found, %: C 70.62; H 6.07; N 9.72.
C16H16N2O2. Calculated, %: C 71.64; H 5.97; N 10.45.
4-[2-(2-Furyl)vinyl]-2-imino-5,5-dimethyl-2,5-di-
hydrofuran-3-carbonitrile (IIb). Yield 77%, mp 123–
124°C. IR spectrum, ν, cm–1: 3284, 3050, 2972, 2234,
1649, 1612, 1494, 1452, 1380, 1345, 1256, 1136,
1090, 985, 835, 598. 1H NMR spectrum, δ, ppm: 1.65 s
(6H, CH3), 6.25 d and 6.52 d (1H each, CH=CH, J =
16.5 Hz), 7.48–7.67 m (3H, furan), 10.50 s (1H, ΝH).
Found, %: C 67.98; H 5.02; N 12.32. C13H12N2O2.
Calculated, %: C 68.42; H 5.26; N 12.28.
2-Imino-5,5-pentamethylene-4-(2-phenylvinyl)-
2,5-dihydrofuran-3-carbonitrile (Ia). Yield 87%,
mp 164–166°C. IR spectrum, ν, cm–1: 3280, 3050,
2965, 2230, 1665, 1600, 1490, 1445, 1380, 1365,
1290, 1245, 1136, 1098, 985, 905, 865, 850, 765, 695.
1H NMR spectrum, δ, ppm: 1.22–1.28 m (2H, CH2),
1.50–1.63 m (2H, CH2), 1.67–1.90 m (6H, CH2),
6.15 d and 6.32 d (1H each, CH=CH, J = 16 Hz),
7.10–7.28 m (5H, Harom), 10.8 s (1H, ΝH), Found, %:
C 77.82; H 6.15; N 10.12. C18H18N2O. Calculated, %:
C 77.69; H 6.47; N 10.07.
5-Ethyl-4-[2-(2-furyl)vinyl]-2-imino-5-methyl-
2,5-dihydrofuran-3-carbonitrile (IIc). Yield 86%,
mp 112–114°C. 1H NMR spectrum, δ, ppm: 0.86 t (3H,
CH2CH3, J = 7.4 Hz), 1.50 s (3H, CH3), 1.75–1.84 m
(2H, CH2CH3), 6.21 d and 6.52 d (1H each, CH=CH,
J = 16.3 Hz), 7.52–7.69 m (3H, furan), 10.82 s (1H,
ΝH). Found, %: C 69.03; H 5.21; N 11.26.
C14H14N2O2. Calculated, %: C 69.42; H 5.79; N 11.57.
2-Imino-5,5-dimethyl-4-(2-phenylvinyl)-2,5-di-
hydrofuran-3-carbonitrile (Ib). Yield 72%, mp 107–
108°C. IR spectrum, ν, cm–1: 3282, 3053, 2913, 2850,
2229, 1660, 1610, 1494, 1450, 1380, 1345, 1255,
1
1136, 1092, 985, 904, 832, 596. H NMR spectrum, δ,
ppm: 1.62 s (6H, CH3), 6.18 d and 6.52 d (1H each,
4-[2-(2-Furyl)vinyl]-2-imino-5-methyl-5-phenyl-
CH=CH, J = 16.1 Hz), 7.25–7.35 m (5H, Harom),
2,5-dihydrofuran-3-carbonitrile (IId). Yield 83%,
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SYNTHESIS OF NEW UNSATURATED DERIVATIVES
435
1
mp 105–107°C. H NMR spectrum, δ, ppm: 1.62 s
6.18 d and 6.4 d (1H each, CH=CH, J = 16.4 Hz),
7.58–7.65 m (3H, furan). Found, %: C 71.22; H 5.14;
N 5.31. C16H15NO3. Calculated, %: C 71.38; H 5.58;
N 5.20.
(3H, CH3), 6.10 d and 6.38 d (1H each, CH=CH, J =
16.1 Hz), 6.95–7.15 m (5H, Harom), 7.45–7.58 m (3H,
furan), 10.75 s (1H, ΝH). Found, %: C 74.65; H 4.72;
N 9.69. C16H19N2O2. Calculated, %: C 74.48; H 4.83;
N 9.66.
3-Cyano-5,5-dimethyl-4-(2-phenylvinyl)-2,5-di-
hydrofuran-2-one (IVc). Yield 68%, mp 175–177°C;
published data [6]: mp 176–178°C. 1H NMR spectrum,
δ, ppm: 1.60 s (6H, CH3), 6.15 d and 6.30 d (1H each,
CH=CH, J = 16.1 Hz), 7.32–7.40 m (5H, Harom).
Found, %: C 75.71; H 5.88; N 5.71. C15H13NO2. Cal-
culated, %: C 75.31; H 5.44; N 5.86.
5,5-Substituted 2-imino-4-(2-R-vinyl)-2,5-dihy-
drofuran-3-carbonitrile hydrochlorides IIIa–IIIc
(general procedure). Gaseous hydrogen chloride was
passed through a solution of 2.5 mmol of compound
Ia, Ib, or IIa in benzene. The precipitate was filtered
off, washed with anhydrous benzene, and dried.
2-[3-Cyano-4-(2-R-vinyl)-2,5-dihydrofuran-2-
ylidene]malononitriles Va–Vd (general procedure).
A mixture of 0.01 mol of compound Ia, Ib, IIa, or IIb
and 0.66 g (0.01 mol) of malononitrile in 10 ml of an-
hydrous ethanol was kept for 20 h at room tempera-
ture. The solvent was partially distilled off under
reduced pressure, and the precipitate was filtered off
and recrystallized from ethanol–water (2:1).
2-Imino-5,5-pentamethylene-4-(2-phenylvinyl)-
2,5-dihydrofuran-3-carbonitrile hydrochloride
(IIIa). Yield 92%, mp 170–172°C. Found, %: C 68.32;
H 6.15; Cl 11.36; N 8.63. C18H19ClN2O. Calculated,
%: C 68.68; H 6.04; Cl 11.28; N 8.90.
4-[2-(2-Furyl)vinyl]-2-imino-5,5-pentamethyl-
ene-2,5-dihydrofuran-3-carbonitrile hydrochloride
(IIIb). Yield 94%, mp 208–210°C. Found, %: C 63.21;
H 5.35; Cl 11.59; N 9.16. C16H17ClN2O2. Calculated,
%: C 63.05; H 5.58; Cl 11.66; N 9.19.
2-[3-Cyano-5,5-pentamethylene-4-(2-phenyl-
vinyl)-2,5-dihydrofuran-2-ylidene]malononitrile
1
(Va). Yield 74%, mp 224–226°C. H NMR spectrum,
δ, ppm: 1.22–1.28 m (2H, CH2), 1.45–1.54 m (2H,
CH2), 1.62–1.80 m (6H, CH2), 6.20 d and 6.45 d (1H
each, CH=CH, J = 16.3 Hz), 7.15–7.40 m (5H, Harom).
Found, %: C 77.16; H 5.29; N 12.64. C21H17N3O. Cal-
culated, %: C 77.86; H 5.19; N 12.84.
2-Imino-5,5-dimethyl-4-(2-phenylvinyl)-2,5-di-
hydrofuran-3-carbonitrile hydrochloride (IIIc).
Yield 91%, mp 145–147°C. Found, %: C 65.42;
H 5.37; Cl 12.89; N 10.12. C15H15ClN2O. Calculated,
%: C 65.57; H 5.46; Cl 12.93; N 10.2.
2-{3-Cyano-4-[2-(2-furyl)vinyl]-5,5-pentameth-
ylene-2,5-dihydrofuran-2-ylidene}malononitrile
5,5-Substituted 3-cyano-4-(2-R-vinyl)-2,5-dihy-
drofuran-2-ones IVa–IVc (general procedure).
A mixture of 0.01 mol of compound IIIa–IIIc and
8 ml of water was heated for 3 h on a water bath. The
precipitate was filtered off and recrystallized from
aqueous ethanol (1:1).
1
(Vb). Yield 72%, mp 315–317°C. H NMR spectrum,
δ, ppm: 1.25–1.30 m (2H, CH2), 1.40–1.52 m (2H,
CH2), 1.60–1.76 m (6H, CH2), 6.20 d and 6.45 d (1H
each, CH=CH, J = 16.2 Hz), 7.50–7.70 m (3H, furan).
Found, %: C 71.12; H 4.21; N 13.08. C19H15N3O2. Cal-
culated, %: C 71.92; H 4.73; N 13.25.
3-Cyano-5,5-pentamethylene-4-(2-phenylvinyl)-
2,5-dihydrofuran-2-one (IVa). Yield 72%, mp 220–
222°C. IR spectrum, ν, cm–1: 2935, 2860, 1735, 1662,
1490, 1445, 1380, 1204, 1120, 985, 945, 860, 795.
1H NMR spectrum, δ, ppm: 1.18–1.23 m (2H, CH2),
1.48–1.60 m (2H, CH2), 1.65–1.85 m (6H, CH2),
6.10 d and 6.28 d (1H each, CH=CH, J = 16.1 Hz),
7.18–7.32 m (5H, Harom). Found, %: C 77.31; H 6.18;
N 5.21. C18H17NO2. Calculated, %: C 77.42; H 6.09;
N 5.02.
2-[3-Cyano-5,5-dimethyl-4-(2-phenylvinyl)-2,5-
dihydrofuran-2-ylidene]malononitrile (Vc). Yield
70%, mp 238–240°C. IR spectrum, ν, cm–1: 3285,
3056, 2975, 2237, 1650, 1615, 1495, 1453, 1382,
1350, 1255, 1135, 1092, 985, 832, 596. 1H NMR spec-
trum, δ, ppm: 1.67 s (6H, CH3), 6.30 d and 6.48 d (1H
each, CH=CH, J = 16.5 Hz), 7.30–7.50 m (5H, Harom).
Found, %: C 75.01; H 4.32; N 14.74. C18H13N3O. Cal-
culated, %: C 75.26; H 4.53; N 14.63.
3-Cyano-4-[2-(2-furyl)vinyl]-5,5-pentamethylene-
2-{3-Cyano-4-[2-(2-furyl)vinyl]-5,5-dimethyl-2,5-
dihydrofuran-2-ylidene}malononitrile (Vd). Yield
76%, mp 247–248°C; published data [7]: mp 245–
2,5-dihydrofuran-2-one (IVb). Yield 75%, mp 126–
1
128°C. H NMR spectrum, δ, ppm: 1.20–1.26 m (2H,
1
CH2), 1.52–1.63 m (2H, CH2), 1.65–1.87 m (6H, CH2),
246°C. H NMR spectrum, δ, ppm: 1.62 s (6H, CH3),
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AVETISYAN et al.
436
3. Avetisyan, A.A. and Tokmadzhyan, G.G., Khim. Getero-
tsikl. Soedin., 1987, p. 723.
4. Avetisyan, A.A., Kagramanyan, A.A., and Meli-
kyan, G.S., Khim. Geterotsikl. Soedin., 1986, p. 563.
5. Avetisyan, A.A., Akhnazaryan, A.A., and Melikyan, G.S.,
6.18 d and 6.48 d (1H each, CH=CH, J = 16.3 Hz),
7.62–7.75 m (3H, furan). Found, %: C 69.39; H 3.38;
N 15.25. C16H11N3O2. Calculated, %: C 69.31; H 3.97;
N 15.16.
Arm. Khim. Zh., 1988, vol. 41, p. 756.
REFERENCES
6. Perjessy, A., Avetisyan, A.A., Aknazaryan, A.A., and
Melikyan, A.A., Collect. Czech. Chem. Commun., 1989,
vol. 54, p. 1666.
7. Melikian, G., Rouessac, F.P., and Alexandre, Ch., Synth.
Commun., 1995, vol. 25, p. 3045.
1. Avetisyan, A.A. and Dangyan, M.T., Usp. Khim., 1977,
vol. 46, p. 1250.
2. Rao, J.S., Chem. Rev., 1976, vol. 76, p. 625.
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