Convenient synthesis of 2-imino-3-(2-thienyl)-2(5H)-furans and their certain transformations

Article abstract of DOI:10.1134/S1070428011020175

A convenient and effi cient method was described of the preparation of 2-imino-3-(2-thienyl)-2,5-dihydrofurans by the condensation of α-ketol with the thiophene-2-acetonitrile and some their chemical transformations were performed.

Full text of DOI:10.1134/S1070428011020175

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 2, pp. 265268. 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. 2, pp. 273276.
Convenient Synthesis of 2-Imino-3-(2-thienyl)-2(5H)-furans
and Their Certain Transformations
A. A. Avetisyan, A. G. Alvandzhyan, and K. S. Avetisyan
Yerevan State University, Yerevan, 375025 Armenia
e-mail: avetisyan_ks@yahoo.com
Received May 4, 2010
Abstract—A convenient and efficient method was described of the preparation of 2-imino-3-(2-thienyl)-
2,5-dihydrofurans by the condensation of α-ketol with the thiophene-2-acetonitrile and some their chemical
transformations were performed.
DOI: 10.1134/S1070428011020175
3-Functionalized 2(5H)-furanones are relatively wide
spread in the nature, they are contained in the composi-
tion of many plants and animal bodies and they exhibit
a wide range of biologic action [1–5].
The hydrolysis of 2-imino derivatives Iа–Id provided
previously unknown 3-(2-thienyl)-2,5-dihydrofuran-2-
ones IIа–IId. The reaction occurred in the presence of
acids (pH 4–5) at heating on a water bath for 3 h.
The theoretical and practical interest is attracted by
functionally substituted 2-furanones containing various
substituents in the position 3. No compounds were de-
scribed containing in this position heterocyclic substitu-
ents, therefore the development of their synthesis was
especially interesting.
Compounds Iа–Id readily formed hydrochlorides at
passing the gaseous hydrogen chloride through their ben-
zene solutions. The obtained salts IIIа–IIId were easily
transformed into the initial 2-imino derivatives Iа–Id by
treating with a solution of potassium carbonate.
In extension of the investigation of the synthesis and
chemical reactions of new derivatives of iminolactones
we carried out in this research the reaction of α-ketols with
the thiophene-2-acetonitrile in the presence of sodium
ethylate. The reaction proceeds at the equimolar reagents
ratio in the presence of the catalytical quantity of the so-
dium ethylate in anhydrous ethanolover 10 h and results
in substituted 2-imino-3-(2-thienyl)-2,5-dihydrofurans
Iа–Id in high yields (up to 96%).
Me
Me
S
S
H+
HCl
R1
R2
R1
R2
Ia_Id
.
K2CO3
O
NH HCl
IIIa_IIId
O
O
IIa_IId
R1 = R2 = Me (a); R1,R2 = (CH2)5 (b); R1 = Me, R2 = Et
(c); R1 = Me, R2 = Ph (d).
It is known that 2-dicyanomethylene derivatives of
furans are chromophores, they possess electrooptical and
photorefractive properties [6], and are fluorophores with
the fluorescent characteristics [7].
S
Me
H2C
Me
R1
R2
O
S
CN
EtONa
R1
R2
Aiming at the preparation of new dicyanomethylene
furan derivatives we studied the reaction of synthesized
2-imino derivatives Iа–Id with malononitrile. The reac-
tion proceeded readily at mixing the initial components
in the 1:1 ratio at the room temperature with ammo-
nia evolution and the formation of the corresponding
NH
O
Ia_Id
OH
R1 = R2 = Me (a); R1,R2 = (CH2)5 (b); R1 = Me, R2 = Et
(c); Ph (d).
265

AVETISYAN et al.
266
2-dicyanomethylene derivatives IVа–IVd in the nearly
quantitative yield.
(20 mmol) of thiophene-2-acetonitrile. The reaction mix-
ture was left standing for 10 h at room temperature (TLC
monitoring). The separated precipitate was filtered off,
washed with water, dried, and recrystallized from heptane.
Me
S
b. To a water solution of 5 mmol of compound IIIa–
IIId (pH 2–3) was added the concentrated solution of
K2CO3 till pH 7–8. The workup of the precipitate was as
in the procedure а.
CH2(CN)2
R1
Ia_Id
CN
_NH3
R2
C
O
_
CN
IVa IVd
2-Imino-3-(2-thienyl)-4,5,5-trimethyl-2,5-dihydro-
furan (Iа). Yield 3.9 g (95%) (а), 0.92 g (89%) (b),
mp 78–79°C. IR spectrum, ν, cm–1: 3290, 1650, 1625,
1040. 1Н NMR spectrum, δ, ppm: 1.43 s (6H, 2CH3),
2.10 s (3H, CH3), 6.85–7.15 m (2H, NH, Hthiophene),
7.40–7.75 m (2H, Hthiophene). Found, %: C 63.57; H 6.63;
N 6.51; S 15.74. C11H13NOS. Calculated, %: C 63.77;
H 6.28; N 6.76; S 15.46.
R1 = R2 = Me (a); R1,R2 = (CH2)5 (b); R1 = Me, R2 = Et
(c); R1 = Me, R2 = Ph (d).
Taking into account the lability of the hydrogen atoms
of the methyl groupattached to the multiple carbon-carbon
bond we also studied the reactions of iminolactones Ia,
Ib, lactones IIIa, IIIb, and dicyanomethylenefurans IVa,
IVb with aromatic aldehydes in the alcoholic solution of
NaOH that occurred with the retention of the lactone ring
affording derivatives Vа–Vl with the styryl and furylvi-
nyl substituents in the position 4. 2-Dicyano-methylene
derivatives Ve, Vf, Vk, Vl were also obtained by the inde-
pendent synthesis from the corresponding iminolactones
Vа, Vb, Vg, Vh and malononitrile analogously to the
preparation of compounds IVа–IVd.
2-Imino-4-methyl-5,5-pentamethylene-3-(2-
thienyl)-2,5-dihydrofuran (Ib). Yield 4.77 g (97%)
(а), 1 g (87%) (b), mp 92–93°C. IR spectrum, ν, cm–1:
1
3270, 1640, 1620, 1040. Н NMR spectrum, δ, ppm:
1.20–1.25 m (2H, CH2), 1.50–1.75 m (8H, 4CH2), 1.90 s
(3H, CH3), 6.90–7.20 m (2H, NH, Hthiophene), 7.52–7.85 m
(2H, Hthiophene). Found, %: C 68.21; H 6.72; N 5.83;
S 13.01. C14H17NOS. Calculated, %: C 68.02; H 6.89;
N 5.67; S 12.96.
R3HC
HC
2-Imino-4,5-dimethyl-3-(2-thienyl)-5-ethyl-2,5-
S
R3CHO
R1
R2
dihydrofurans (Ic). Yield 3.6 g (82%) (а), 0.92 g (84%)
Ia, Ib, IIIa, IIIb, IVa, IVb
X
1
(b). Oily substance. Н NMR spectrum, δ, ppm: 0.85
O
Va_Vl
t (3H, CH2CH3, J 16.5 Hz), 1.48 s (6H, 2CH3), 1.75–
1.80 m (2H, CH2CH3), 6.78–7.10 m (2H, NH, Hthiophene),
7.35–7.68 m (2H, Hthiophene). Found, %: C 65.27; H 6.48;
N 6.47; S 14.62. C12H15NOS. Calculated, %: C 65.27;
H 6.48; N 6.47; S 14.48.
R1 = R2 = Me (а, c, e, g, i, k); R1,R2 = (CH2)5 (b, d, f, h,
j, l); R3 = Ph (а–f), 2-furyl (g–l); X = NH (а, b, g, h), O
(c, d, i, j), C(CN)2 (e, f, k, l).
2-Imino-4,5-dimethyl-3-(2-thienyl)-5-phenyl-
EXPERIMENTAL
2,5-dihydrofurans (Id). Yield: 4.3 g (80%) (а), 1 g
1
(82%) (b). Oily substance. Н NMR spectrum, δ, ppm:
IR spectra were recorded on a spectrophotometer
UR-20 from mulls in mineral oil. 1Н NMR spectra were
taken on a spectrometer Varian Mercury-300 (300 MHz)
from solutions in DMSO-d6, internal reference HMDS.
The reaction progress was monitored and the purity of
compounds obtained was checked by TLC on Silufol
UV-254 plates, eluent acetone–benzene, 1:2, development
under the iodine vapor or UV irradiation.
1.45 s (3H, CH3), 1.51 s (3H, CH3), 6.75 m (2H, NH,
H
H
thiophene), 7.25 d (2H, Harom, J 16.5 Hz), 7.37 d (2H,
arom, J 16.5 Hz), 7.40–7.45 m (2H, Harom, Hthiophene).
Found, %: C 71.51; H 5.63; N 5.36; S 11.49. C16H15NOS.
Calculated, %: C 71.38; H 5.58; N 5.20; S 11.89.
3-(2-Thienyl)-2,5-dihydrofuran-2-ones IIa–IId.
To a mixture of 10 mmol of compound Iа–Id and 5 ml
of water was added HCl to pH 4–5, and the mixture was
heated on a water bath for 3 h. The separated precipitate
was filtered off, washed with water, and dried .
5,5-Substituted 2-imino-4-methyl-3-(2-thienyl)-
2,5-dihydrofurans Iа–Id. а. To a solution of 0.046 g (2
mmol) of Na in 20 ml of anhydrous ethanol was added 20
mmol of an appropriate tertiary α-ketoalcohol and 2.43 g
3-(2-Thienyl)-4,5,5-trimethyl-2,5-dihydrofuran-2-
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CONVENIENT SYNTHESIS OF 2-IMINO-3-(2-THIENYL)-2(5H)-FURANS
267
one (IIa). Yield 2 g (95%), mp 82–83°C. IR spectrum,
room temperature for 15–20 h. After partial removal of
the solvent the precipitate was filtered off, washed with
water, dried, and recrystallized from a mixture ethanol–
water, 2:1.
1
ν, cm–1: 1730, 1630, 1620, 1040. Н NMR spectrum,
δ, ppm: 1.45 s (6H, 2CH3), 2.15 and 2.20 s (3H, CH3),
7.05 m (1H, Hthiophene), 7.45 m (2H, Hthiophene). Found,
%: C 63.64; H 5.67; S 15.83. C11H12O2S. Calculated, %:
C 63.46; H 5.77; S 15.39.
2-Dicyanomethylene-4,5,5-trimethyl-3-(2-thienyl)-
2,5-dihydrofuran (IVa). Yield 2.5 g (98%), mp 208–
209°C. IR spectrum, ν, cm–1: 2230, 1630, 1620, 1040.
1Н NMR spectrum, δ, ppm: 1.50 s (6H, 2CH3), 2.15 s (3H,
CH3), 6.95–7.15 m (3H, Hthiophene). Found, %: C 65.26;
H 4.86; N 10.39; S 12.41. C14H12N2OS. Calculated, %:
C 65.63; H 4.69; N 10.94; S 12.50.
4-Methyl-5,5-pentamethylene-3-(2-thienyl)-2,5-
dihydrofuran-2-one (IIb). Yield 2.5 g (98%), mp 116–
117°C. Found, %: C 67.47; H 6.54; S 12.49. C14H16O2S.
Calculated, %: C 67.74; H 6.45; S 12.90.
4,5-Dimethyl-3-(2-thienyl)-5-ethyl-2,5-dihydro-
furan-2-one (IIc). Yield 2.1 g (94%), mp 69–70°C.
Found, %: C 64.68; H 6.63; S 14.14. C12H14O2S.
Calculated, %: C 64.87; H 6.31; S 14.41.
2-Dicyanomethylene-4-methyl-5,5-penta-
methylene-3-(2-thienyl)-2,5-dihydrofuran (IVb).
Yield 2.9 g (96%), mp 168–169°C. 1Н NMR spectrum, δ,
ppm: 1.28–1.31 m (2H, CH2), 1.38–1.65 m (8H, 4CH2),
1.90 s (3H, CH3), 6.92–7.12 m (3H, Hthiophene). Found,
%: C 68.29; H 5.50; N 9.54; S 10.18. C17H16N2OS.
Calculated, %: C 68.92; H 5.41; N 9.46; S 10.81.
4,5-Dimethyl-3-(2-thienyl)-5-phenyl-2,5-dihydro-
furan-2-one (IId). Yield 2.6 g (97%), mp 74–75°C.
Found, %: C 71.31; H 5.51; S 11.58. C16H14O2S.
Calculated, %: C 71.11; H 5.19; S 11.85.
2-Dicyanomethylene-4,5-dimethyl-3-(2-thienyl)-
5-ethyl-2,5-dihydrofuran (IVc). Yield 2.5 g (93%),
mp 177–178°C. Found, %: C 66.77; H 5.58; N 10.73;
2-Imino-3-(2-thienyl)-2,5-dihydrofurans hydro-
chlorides IIIа–IIId. Through a benzene solution of
4 mmol of compound Iа–Id was passed gaseous HCl.
The separated precipitate was filtered off, washed with
anhydrous benzene, and dried.
S 11.28. C
15H17N2OS. Calculated, %: C 66.67; H 5.19;
N 10.37; S 11.85.
2-Imino-4,5,5-trimethyl-3-(2-thienyl)-2,5-dihydro-
furan hydrochloride (IIIa). Yield 0.96 г (99%),
mp 215–217°C. Found, %: C 54.34; H 5.82; Cl 14.69;
N 5.61; S 13.41. C11H14ClNOS. Calculated, %: C 54.21;
H 5.74; Cl 14.58; N 5.75; S 13.14.
2-Dicyanomethylene-4,5-dimethyl-3-(2-thienyl)-
5-phenyl-2,5-dihydrofuran (IVd). Yield 3 g (92%),
mp 145–146°C. Found, %: C 71.96; H 4.45; N 8.58;
S 10.18. C19H14N2OS. Calculated, %: C 71.70; H 4.40;
N 8.81; S 10.06.
2-Imino-4-methyl-5,5-pentamethylene-3-(2-
thienyl)-2,5-dihydrofuran hydrochloride (IIIb). Yield
1.12 g (99%), mp 205–207°C. Found, %: C 59.14; H 6.42;
Cl 12.45; N 5.01; S 11.38. C14H18ClNOS. Calculated, %:
C 59.26; H 6.35; Cl 12.52; N 4.94; S 11.29.
2-Functionally substituted 4-arylvinyl-3-(2-
thienyl)-2,5-dihydrofurans Vа–Vl. General procedure.
A mixture of 10 mmol of compound Ia, Ib, IIIa, IIIb,
IVa, IVb, 0.01 g of sodium hydroxide, and 12 mmol of
an appropriate aldehyde in 10 ml of anhydrous ethanol
was heated on a water bath for 4 h. After partial removal
of the solvent the precipitate was filtered off, washed
with water, dried, and recrystallized from a mixture
ethanol–water, 2:1.
2-Imino-4,5-dimethyl-3-(2-thienyl)-5-ethyl-2,5-
dihydrofuran hydrochloride (IIIc). Yield 1 g (96%),
mp 202–204°C. Found, %: C 56.04; H 6.33; Cl 13.87;
N 5.63; S 12.54. C12H16ClNOS. Calculated, %: C 55.92;
H 6.21; Cl 13.79; N 5.44; S 12.43.
2-Imino-5,5-dimethyl-4-styryl-3-(2-thienyl)-2,5-
dihydrofuran (Vа). Yield 2.3 g (80%) mp 153–154°C. IR
spectrum, ν, cm–1: 3260, 1650, 1630, 1620, 1495, 1040.
Found, %: C 73.38; H 5.43; N 4.39; S 10.42. C18H17NOS.
Calculated, %: C 73.22; H 5.75; N 4.75; S 10.85.
2-Imino-4,5-dimethyl-3-(2-thienyl)-5-phenyl-2,5-
dihydrofuran hydrochloride (IIId).Yield 1.14 d (93%),
mp 218–220°C. Found, %: C 62.48; H 5.32; Cl 11.26;
N 4.85; S 10.74. C16H16ClNOS. Calculated, %: C 62.85;
H 5.24; Cl 11.62; N 4.58; S 10.48.
2-Imino-5,5-pentamethylene-4-styryl-3-(2-thienyl)-
2,5-dihydrofuran (Vb). Yield 2.5 g (81%), mp 141–
142°C. Found, %: C 74.12; H 6.97; N 4.22; S 9.78.
C21H21NOS. Calculated, %: C 75.22; H 6.27; N 4.18;
S 9.55.
2-Dicyanomethylene-3-(2-thienyl)-4-methyl-
2,5-dihydrofurans (IVa–IVd). General procedure.
A mixture of 10 mmol of iminolactone Ia–Id and 0.66 g
(10 mmol) of malononitrile in 10 ml was left standing at
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AVETISYAN et al.
268
5,5-Dimethyl-4-styryl-3-(2-thienyl)-2,5-dihydro-
Calculated, %: C 75.00; H 5.95; S 9.52.
furan-2-one (Vc). Yield 2.45 g (84%), mp 137–138°C.
Found, %: C 72.83; H 5.62; S 10.49. C18H16O2S.
Calculated, %: C 72.97; H 5.41; S 10.81.
5,5-Pentamethylene-3-(2-thienyl)-4-(2-furylvinyl)-
2,5-dihydrofuran-2-one (Vj). Yield 2.7 g (83%),
mp 174°C. Found, %: C 69.49; H 5.67; S 9.79. C19H18O3S.
Calculated, %: C 69.94; H 5.52; S 9.82.
5,5-Pentamethylene-4-styryl-3-(2-thienyl)-2,5-
dihydrofuran-2-one (Vd). Yield 2.8 g (84%), mp
144°C. Found, %: C 75.14; H 5.89; S 9.65. C21H20O2S.
Calculated, %: C 75.00; H 5.95; S 9.52.
2-Dicyanomethylene-5,5-dimethyl-3-(2-thienyl)-
4-(2-furylvinyl)-2,5-dihydrofuran (Vk). Yield 2.9 g
(87%), mp 201–202°C.1Н NMR spectrum, δ, ppm: 1.60 s
(6H, 2CH3), 6.35 m (1H, CH=CH, J 16.5 Hz), 6.55 m
2-Dicyanomethylene-5,5-dimethyl-4-styryl-3-(2-
thienyl)-2,5-dihydrofuran (Ve). Yield 2.63 g (79%),
mp 180–181°C. IR spectrum, ν, cm–1: 2230, 1630, 1620,
1500, 1040. Found, %: C 73.17; H 5.23; N 8.44; S 9.17.
C21H16N2OS. Calculated, %: C 72.07; H 5.11; N 8.41;
S 9.61.
(1H, CH=CH, J 16.5 Hz), 6.95–7.10 m (2H, Hthiophene
,
Hfuran), 7.30–7.45 m (1H, Hthiophene), 7.60–7.75 m (3H,
Hthiophene, Hfuran). Found, %: C 68.49; H 4.67; N 8.51;
S 9.29. C19H14N2O2S. Calculated, %: C 68.26; H 4.19;
N 8.38; S 9.58.
2-Dicyanomethylene-5,5-pentamethylene-4-
styryl-3-(2- thienyl)-2,5-dihydrofuran (Vf). Yield 3.1 g
(83%), mp 215–216°C. Found, %: C 75.45; H 5.37;
N 7.75; S 8.97. C24H20N2OS. Calculated, %: C 75.00;
H 5.21; N 7.29; S 8.33.
2-Dicyanomethylene-5,5-pentamethylene-3-(2-
thienyl)-4-(2-furylvinyl)-2,5-dihydrofuran (Vl). Yield
3.3 g (89%), mp 209–210°C. Found, %: C 70.65; H 4.25;
N 7.18; S 8.42. C22H18N2OS. Calculated, %: C 70.59;
H 4.81; N 7.49; S 8.56.
2-Imino-5,5-dimethyl-3-(2-thienyl)-4-(2-furyl-
vinyl)-2,5-dihydrofuran (Vg). Yield 2.1 g (80%),
mp 149–150°C. 1Н NMR spectrum, δ, ppm: 1.60 s (6H,
2CH3), 6.50 d (1H, CH=CH, J 16.5 Hz), 6.72 d (1H,
CH=CH, J 16.5 Hz), 7.0–7.2 m (2H, Hthiophene, Hfuran),
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011