Chemistry of iminofurans: X. Synthesis and hydrolysis of 5-aryl(hetaryl)-2-[(4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]furan-3(2H)-ones

Article abstract of DOI:10.1134/S107042801603009X

5-Aryl(hetaryl)furan-2,3-diones reacted with N-(triphenyl-λ⁵-phosphanylidene)-4,5,6,7-tetrahydro-1-benzothiophen-2-amines to give 5-aryl(hetaryl)-2-[(4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]furan-3(2H)-ones whose acid hydrolysis afforded 4-aryl(hetaryl)-2-hydroxy-4-oxo-N-(4,5,6,7-tetrahydro-1-benzothiophen- 2-yl)but-2-enamides.

Full text of DOI:10.1134/S107042801603009X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 3, pp. 343–348. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © A.O. Panchenko, S.A. Shipilovskikh, A.E. Rubtsov, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 3,
pp. 364–369.
Chemistry of Iminofurans: X.* Synthesis and Hydrolysis
of 5-Aryl(hetaryl)-2-[(4,5,6,7-tetrahydro-1-benzothiophen-
2
-yl)imino]furan-3(2H)-ones
A. O. Panchenko, S. A. Shipilovskikh, and A. E. Rubtsov
Perm State National Research University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: rubtsov@psu.ru
Received November 24, 2015
5
Abstract—5-Aryl(hetaryl)furan-2,3-diones reacted with N-(triphenyl-λ -phosphanylidene)-4,5,6,7-tetrahydro-
1
3
-benzothiophen-2-amines to give 5-aryl(hetaryl)-2-[(4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]furan-
(2H)-ones whose acid hydrolysis afforded 4-aryl(hetaryl)-2-hydroxy-4-oxo-N-(4,5,6,7-tetrahydro-1-benzo-
thiophen-2-yl)but-2-enamides.
DOI: 10.1134/S107042801603009X
Two methods are presently known to obtain
-iminofuran-3(2H)-ones in high yields. The first
method is based on [4+1]-cycloaddition of aroyl-
ketenes (generated by thermal decomposition of furan-
,3-diones [2, 3] or 2-diazo-1,3-diketones [3]) to iso-
It is known that furan-2,3-diones react with
2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carbo-
nitrile to give not 2(3)-iminofuran-3(2)-ones but
N-(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)-
4-aryl-2,4-dioxobutanamides as a result of furan ring
opening [10]. The most general and widely studied
procedure allowing introduction of various substituents
to the imino nitrogen atom and avoidance of undesir-
able reaction pathway is Staudinger imination (aza-
Wittig reaction of carbonyl compounds with triphenyl-
phosphine imines [11–13]).
2
2
nitriles. The second method implies the reaction of
5
substituted furan-2,3-diones with N-(triphenyl-λ -phos-
phanylidene)anilines, which has been represented by
only two examples [4, 5]. 2-Iminofuran-3(2H)-one
derivatives constitute a poorly explored class of com-
pounds; however, even scarce published data on their
reactivity demonstrate their high synthetic potential as
starting materials for the preparation of biologically
active compounds [6]. In order to extend the synthetic
potential of 2-iminofuran-3(2H)-ones and obtain new
biologically active compounds in the present work we
made an attempt to introduce a pharmacophoric
Gewald thiophene fragment [7–9] to the imino
nitrogen atom.
We examined the potential of this procedure with
the goal of extending the series of substituted 2-imino-
furan-3(2H)-ones. For this purpose, we have synthe-
5
sized N-(triphenyl-λ -phosphanylidene)thiophen-2-
amines 1a and 1b from the corresponding thiophen-
2-amines according to the procedures reported in
[14–17] for the preparation of phosphine imines from
5
primary amines and dibromo(triphenyl)-λ -phosphane.
Scheme 1.
Ar
R
O
R
O
PPh3
+
N
–Ph P=O
3
Ar
O
N
O
S
S
O
1
a, 1b
2a–2d
3a–3h
1
, R = CN (a), COOEt (b); 2, Ar = Ph (a), 4-ClC
H
6 4
(b), 4-MeC H
6 4
(c), thiophen-2-yl (d); 3, R = CN, Ar = Ph (a), 4-ClC
6 4
H (b),
4
-MeC (c), thiophen-2-yl (d); R = COOEt, Ar = Ph (e), 4-ClC
6
H
4
H
6 4
(f), 4-MeC (g), thiophen-2-yl (h).
6 4
H
*
For communication IX, see [1].
3
43

3
44
PANCHENKO et al.
Scheme 2.
Ar
Ar
O
Ar
R
R
R
H+
O
O
H
2
O
O
N
N
H
N
S
S
S
O
H OH
2
O
3
a–3h
I1
I2
Ar
R
R
R
HO
N
O
O
H+
Ar
OH
Ar
–
N
N
H
S
O
S
S
H OH
H
O
O
OH
I3
I4
4a–4h
R = CN, Ar = Ph (a), 4-ClC
6
H
4
(b), 4-MeC (c), thiophen-2-yl (d); R = COOEt, Ar = Ph (e), 4-ClC
6
H
4
6 4
H (f),
4
-MeC H (g), thiophen-2-yl (h).
6 4
Compounds 1a and 1b reacted with 5-substituted
furan-2,3-diones 2a–2d to afford a series of 5-aryl-
bands due to stretching vibrations of the NH group
(both H-bonded and not, 3119–3196 and 3350–
–
1
(
hetaryl)-2-[(4,5,6,7-tetrahydro-1-benzothiophen-2-yl)-
imino]furan-3(2H)-ones 3a–3h (Scheme 1).
-Iminofuranones 3a–3h were isolated as orange
3365 cm , respectively), cyano group (2204–
–
1
–1
2213 cm ) or ester carbonyl (1682–1693 cm ), and
–
1
1
2
amide carbonyl (1665–1691 cm ). In the H NMR
spectra of these compounds we observed a singlet from
the NH proton (δ 12.50–12.57 ppm, H-bonded, 4e–4h;
9.75–9.88 ppm, free, 4a–4d), signals from aromatic
protons (δ 7.19–8.03 ppm), a singlet from the vinylic
proton (δ 7.08–7.28 ppm), signals from protons in the
cyclohexene fragment (δ 2.63–2.81 and 1.80–
1.85 ppm), and signals from the ester ethyl group in
crystalline substances which displayed in the IR spec-
tra absorption bands due to substituent in position 3 of
the tetrahydrobenzothiophene fragment (CN group in
–
1
3
3
(
a–3d, 2215–2220 cm , or ester carbonyl group in
–
1
3
e–3h, 1686–1693 cm ) and C =O carbonyl group
–
1
1
1693–1717 cm ). Their H NMR spectra showed
signals from aromatic protons at δ 7.17–8.01 ppm,
a singlet from the vinylic proton in the furan ring at
δ 6.20–6.35 ppm, signals from protons in the cyclo-
hexene ring at δ 2.71–2.83 and 1.84–1.90 ppm, and
signals from the ester ethyl group (in 3e–3h) at δ 4.38–
4
e–4h (δ 4.38–4.39, 1.40–1.85 ppm).
Presumably, the hydrolysis of 3a–3h begins with
protonation of the imino nitrogen atom to form inter-
2
mediate I which takes up water molecule at C of the
1
4
.40 and 1.39–1.41 ppm.
furan ring to give intermedate I . Proton migration in
2
The reaction was regioselective, and compounds
I2 to the endocyclic oxygen atom yields intermediate I3
3
a–3h were formed in almost quantitative yield.
which undergoes opening of the furan ring at the
Furthermore, it may be regarded as a rare case of
reactions of triphenylphosphine imines at the lactone
carbonyl, presumably due to increased electron density
1
2
O –C bond with subsequent elimination of proton,
and [1,5]-prototropic shift in intermediate I thus
4
2
formed leads to amides 4a–4h (Scheme 2)
on C of the furan ring.
Furan-2,3-diones [18–20], as well as their 3-imino
analogs [21–27], readily undergo hydrolysis even by
the action of atmospheric moisture. However, 2-imino-
furanones 3a–3h remained unchanged on prolonged
storage in air and on heating in aqueous solvents.
Compounds 3a–3h were hydrolyzed by heating for
The spectral parameters of 4a–4c coincided with
those of the products obtained by reactions of the
corresponding 5-arylfuran-2,3-diones with 2-amino-
4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile
[10], but the melting points were different. The struc-
ture of the hydrolysis products was additionally con-
firmed by independent synthesis of amide 4a from
benzoylpyruvic acid (5) and nitrile 6 by heating for
a short time in ethanol (Scheme 3). The physical con-
stants and spectral data of samples of 4a prepared by
the two methods were identical.
1
5 min in boiling dioxane–water (6:1) containing
a catalytic amount of HCl; as a result, amides 4a–4h
were obtained (Scheme 2).
Amides 4a–4h are yellow or orange crystalline
substances. They showed in the IR spectra absorption
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

CHEMISTRY OF IMINOFURANS: X.
345
5
Scheme 3.
2-[(Triphenyl-λ -phosphanylidene)amino]-
O
OH
CN
4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile
(
1a). Yield 16.4 g (75%), yellow crystals, mp 196.4–
OH
+
4a
Ph
NH2 –H O
2
196.6°C (from EtOH); published data [14]: mp 198°C.
IR spectrum: ν 2209 cm (CN). H NMR spectrum
–
1
1
O
S
5
6
(CDCl ), δ, ppm: 1.71 m (4H, CH ), 2.32 m (2H, CH ),
3 2 2
2
.49 m (2H, CH ), 7.44–7.80 m (15H, Harom).
2
EXPERIMENTAL
5
Ethyl 2-[(triphenyl-λ -phosphanylidene)amino]-
4
,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate
The IR spectra were recorded on an FSM-1201
spectrometer from samples dispersed in mineral oil.
The H NMR spectra were measured on Varian
(
1b). Yield 18.7 g (77%), yellow crystals, mp 181–
1
182°C (from EtOH); published data [14]: mp 181°C.
IR spectrum: ν 1699 cm (C=O). H NMR spectrum
–
1
1
Mercury Plus-300 (300 MHz) and Bruker Avance III
spectrometers (400 MHz) using hexamethyldisiloxane
as internal standard. The mass spectra were obtained
on a Kratos MS-30 instrument (electron impact, 70 eV;
ion source temperature 200°C). The elemental compo-
sitions were determned on a Leco CHNS-932 analyzer.
The progress of reactions and the purity of the isolated
compounds were monitored by TLC on Sorbfil PTSKh
P-A-UF-254 plates (diethyl ether–benzene–acetone,
(
(
(
CDCl ), δ, ppm: 1.33 t (3H, Me, J = 7.1 Hz), 1.68 m
4H, CH ), 2.34 m (2H, CH ), 2.71 m (2H, CH ), 4.28 q
2H, OCH , J = 7.1 Hz), 7.42–7.85 m (15H, Harom).
3
2
2
2
2
5
-Aryl(hetaryl)-2-[(3-R-4,5,6,7-tetrahydro-
1
3
-benzothiophen-2-yl)imino]furan-3(2H)-ones
a–3h (general procedure). A mixture of 0.01 mol of
phosphine imine 1a or 1b and 0.01 mol of furan-2,3-
dione 2a–2d in 20 mL of anhydrous toluene was
stirred for 3–5 h at 50–60°C. The mixture was cooled,
and the precipitate was filtered off and recrystallized
from acetonitrile.
1
0:9:1; detection under UV light or by treatment with
iodine vapor). The melting points were measured on
an SMP40 melting point apparatus.
2
-{[3-Oxo-5-phenylfuran-2(3H)-ylidene]amino}-
,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile
3a). Yield 2.61 g (78%), orange crystals, mp 254°C.
Commercially available reagents and solvents were
used; acetonitrile of chemically pure grade was sub-
jected to additional purification [28]; rectified ethanol
was of deluxe grade. Compounds 2a–2d were synthe-
sized according to [29] from the corresponding aroyl-
4
(
–
1
3
IR spectrum, ν, cm : 2196 (CN), 1691 (C =O).
H NMR spectrum (CDCl ), δ, ppm: 1.90 m (4H,
1
3
CH ), 2.74 m (2H, CH ), 2.83 m (2H, CH ), 6.40 s
(
4
hetaroyl)pyruvic acids [30, 31]; ethyl 2-amino-
,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate
2
2
2
(
1H, CH), 7.55–7.71 m (3H, Harom), 7.94 m (2H,
Harom). Mass spectrum, m/z (I , %): 334 (91) [M] , 160
100), 176 (98), 77 (71) [Ph] , 102 (53) [PhC=CH] ,
69 (48), 188 (46). Found, %: C 68.26; H 4.21; N 8.36;
S 9.60. C H N O S. Calculated, %: C 68.24; H 4.22;
+
and 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-
carbonitrile (6) were prepared as reported in [32].
rel
+
+
(
5
3
-Substituted N-(triphenyl-λ -phosphanylidene)-
1
9
14
2
2
4
,5,6,7-tetrahydro-1-benzothiophen-2-amines 1a
N 8.38; S 9.59. M 334.39
and 1b (general procedure). A solution of 0.05 mol of
triphenylphosphine in 100 mL of anhydrous benzene
was cooled to 5°C, a solution of 0.05 mol of bromine
in 30 mL of anhydrous benzene was added dropwise
under stirring, and the mixture was stirred for 3 h at
room temperature. A solution of 0.1 mol of triethyl-
amine in 30 mL of anhydrous benzene was added to
2
-{[5-(4-Chlorophenyl)-3-oxofuran-2(3H)-
ylidene]amino}-4,5,6,7-tetrahydro-1-benzothio-
phene-3-carbonitrile (3b). Yield 3.24 g (88%), orange
crystals, mp 235–236°C. IR spectrum, ν, cm : 2215
CN), 1697 (C =O). H NMR spectrum (CDCl ), δ,
ppm: 1.90 m (4H, CH ), 2.71 m (2H, CH ), 2.83 m
2H, CH ), 6.32 s (1H, CH), 7.38 and 7.81 (2H each,
Harom, AA′BB′, J = 7.6 Hz). Mass spectrum, m/z
–
1
3
1
(
3
2
2
5
(
2
the resulting suspension of dibromo(triphenyl)-λ -
phosphane, a solution of 0.05 mol of nitrile 6 or ethyl
+
(
I , %): 368 (100) [M] , 188 (100), 204 (77), 139 (75),
rel
2
-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-car-
+
4
5 (56), 111 (33) [ClC H ] . Found, %: C 61.90;
6 4
H 3.56; N 7.63; S 8.70. C H ClN O S. Calculated,
: C 61.87; H 3.55; N 7.60; S 8.69. M 368.83.
boxylate in 50 mL of anhydrous benzene was added,
and the mixture was stirred for 20 min at 50°C. After
cooling, the precipitate of triethylamine hydrobromide
was filtered off, the filtrate was evaporated under
reduced pressure, and the residue was purified by
recrystallization.
19 13
2
2
%
2-{[5-(4-Methylphenyl)-3-oxofuran-2(3H)-
ylidene]amino}-4,5,6,7-tetrahydro-1-benzothio-
phene-3-carbonitrile (3c). Yield 3.45 g (99%), orange
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

3
46
PANCHENKO et al.
–
1
crystals, mp 184–185°C. IR spectrum, ν, cm : 2215
Calculated, %: C 60.65; H 4.36; N 3.37; S 7.71.
M 415.89.
3
1
(
CN), 1697 (C =O). H NMR spectrum (CDCl ), δ,
3
ppm: 1.89 m (4H, CH ), 2.39 s (3H, Me), 2.71 m (2H,
2
Ethyl 2-{[-5-(4-methylphenyl)-3-oxofuran-2(3H)-
ylidene]amino}-4,5,6,7-tetrahydro-1-benzothio-
phene-3-carboxylate (3g). Yield 3.08 g (78%), orange
CH ), 2.83 m (2H, CH ), 6.33 s (1H, CH), 7.33 and
2
2
7
.81 (2H each, Harom, AA′BB′, J = 8.1 Hz). Mass spec-
+
–
1
trum, m/z (I , %): 348 (100) [M] , 176 (100)
rel
crystals, mp 197–198°C. IR spectrum, ν, cm : 1714
+
+
3
1
[
(
[
C H N S] , 119 (83) [MeC H CO] , 161 (47), 204
69.5) [C H N OS] , 91 (35) [MeC H ] , 322 (7)
M – CN] . Found, %: C 68.97; H 4.60; N 8.07;
9 8 2 6 4
(
(
C =O), 1682 (C=O, ester). H NMR spectrum
+
+
1
0
8
2
6
4
DMSO-d ), δ, ppm: 1.32 t (3H, Me, J = 7.1 Hz),
6
+
1
2
6
.81 m (4H, CH ), 2.47 s (3H, Me), 2.63 m (2H, CH ),
2
2
S 9.21. C H N O S. Calculated, %: C 68.94; H 4.63;
2
0
16
2
2
.85 m (2H, CH ), 4.28 q (2H, OCH , J = 7.1 Hz),
2
2
N 8.04; S 9.20. M 348.42.
.85 s (1H, CH), 7.48 and 7.70 (2H each, Harom
,
2
-{[3-Oxo-5-(thiophen-2-yl)furan-2(3H)-ylidene]-
AA′BB′, J = 8.1 Hz). Mass spectrum, m/z (Irel, %): 395
+
+
amino}-4,5,6,7-tetrahydro-1-benzothiophene-3-car-
bonitrile (3d). Yield 3.34 g (98%), orange crystals,
mp 201–202°C. IR spectrum, ν, cm : 2220 (CN),
693 (C =O). H NMR spectrum (CDCl ), δ, ppm:
(20) [M] , 322 (100) [M – COOEt] , 116 (80)
+
[MeC
(43), 91 (42) [MeC ] . Found, %: C 66.83; H 5.33;
N 3.55; S 8.12. C22H21NO S. Calculated, %: C 66.82;
4
H C=CH] , 206 (75), 121 (73), 43 (53), 349
6 4
–
1
+
H
4
6
3
1
1
1
3
.90 m (4H, CH ), 2.72 m (2H, CH ), 2.81 m (2H,
H 5.35; N 3.54; S 8.11. M 395.47.
2
2
CH ), 6.20 s (1H, CH), 7.30 t (1H, Harom, J = 4.2 Hz),
2
Ethyl 2-{[3-oxo-5-(thiophen-2-yl)furan-2(3H)-
ylidene]amino}-4,5,6,7-tetrahydro-1-benzothio-
phene-3-carboxylate (3h). Yield 3.02 g (78%), orange
7
3
2
.83 d (1H, Harom, J = 4.8 Hz), 7.88 d (1H, Harom, J =
+
.0 Hz). Mass spectrum, m/z (I , %): 340 (72) [M] ,
rel
+
–1
77 (100), 111 (100), 204 (67), 312 (53) [M – CO] .
crystals, mp 201–202°C. IR spectrum, ν, cm : 1717
3
1
Found, %: C 60.00; H 3.53; N 8.20; S 18.85.
C H N O S . Calculated, %: C 59.98; H 3.55;
(C =O), 1690 (C=O, ester). H NMR spectrum
1
7
12
2
2
2
(CDCl ), δ, ppm: 1.39 t (3H, Me, J = 6.9 Hz), 1.84 m
3
N 8.23; S 18.84. M 340.42.
(4H, CH ), 2.75 m (2H, CH ), 2.81 m (2H, CH ),
2
2
2
4
.38 q (2H, OCH , J = 6.9 Hz), 6.17 s (1H, CH), 7.28 t
2
Ethyl 2-{[3-oxo-5-phenylfuran-2(3H)-ylidene]-
amino}-4,5,6,7-tetrahydro-1-benzothiophene-3-car-
boxylate (3e). Yield 2.48 g (65%), orange crystals,
(
1H, Harom, J = 3.9 Hz), 7.86 m (2H, Harom). Found, %:
C 58.93; H 4.42; N 3.61; S 16.52. C H NO S . Cal-
culated, %: C 58.90; H 4.42; N 3.61; S 16.55.
1
9
17
4 2
–
1
3
mp 146–148°C. IR spectrum, ν, cm : 1698 (C =O),
1
1
686 (C=O, ester). H NMR spectrum (CDCl ), δ,
N-(4,5,6,7-Tetrahydro-1-benzothiophen-2-yl)-
4-aryl(hetaryl)-2-hydroxy-4-oxobut-2-enamides 4a–
4h (general procedure). a. A solution of 0.01 mol of
furan-3-one 3a–3h in 20 mL of water–dioxane (1:6)
containing a catalytic amount of aqueous HCl was
heated for 15–20 min under reflux. After cooling to
room temperature, the precipitate was filtered off and
recrystallized from chloroform–ethanol (1:1).
3
ppm: 1.41 t (3H, Me, J = 7.2 Hz), 1.82 m (4H, CH2),
.73 m (2H, CH ), 2.81 m (2H, CH ), 4.38 q (2H,
2
2
2
OCH , J = 7.2 Hz), 6.35 s (1H, CH), 7.47–7.63 m (3H,
2
Harom), 7.93 d (2H, Harom, J = 8.4 Hz). Mass spectrum,
+
+
m/z (I , %): 381 (80) [M] , 308 (65) [M – COOEt] ,
rel
1
79 (57). Found, %: C 66.10; H 5.00; N 3.65; S 8.42.
C H NO S. Calculated, %: C 66.12; H 5.02; N 3.67;
2
1
19
4
S 8.41. M 381.45.
b. A solution of 0.48 g (2.5 mmol) of benzoyl-
pyruvic acid (5) in 3 mL of ethanol was heated to the
boiling point, and a solution of 0.445 g (2.5 mmol) of
aminothiophene 6 in 3 mL of ethanol, heated to the
boiling point, was added. After cooling to room tem-
perature, the precipitate was filtered off and recrystal-
lized from ethanol. Yield of 4a 0.546 g (62%).
Ethyl 2-{[5-(4-chlorophenyl)-3-oxofuran-2(3H)-
ylidene]amino}-4,5,6,7-tetrahydro-1-benzothio-
phene-3-carboxylate (3f). Yield 3.20 g (77%), orange
–
1
crystals, mp 169–170°C. IR spectrum, ν, cm : 1715
3
1
(
C =O), 1693 (C=O, ester). H NMR spectrum
(
CDCl ), δ, ppm: 1.39 t (3H, Me, J = 7.2 Hz), 1.85 m
3
(
4
4H, CH ), 2.73 m (2H, CH ), 2.83 m (2H, CH ),
N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothiophen-
2-yl)-2-hydroxy-4-oxo-4-phenylbut-2-enamide (4a).
Yield 2.85 g (81%, a), orange crystals, mp 214–215°C;
published data [10]: mp 204–205°C. IR spectrum, ν,
2
2
2
.40 q (2H, CH , J = 7.2 Hz), 6.34 s (1H, CH), 7.55
2
and 7.87 (2H each, Harom, AA′BB′, J = 8.4 Hz). Mass
spectrum, m/z (I , %): 415 (100) [M] , 369 (100), 206
(
+
rel
+
–1
90), 278 (88), 342 (76) [M – COOEt] , 136 (73)
cm : 3405 (NH), 2218 (CN), 1701 (C=O, amide).
+
1
[ClC H C=CH] , 225 (73), 51 (62), 179 (55). Found,
H NMR spectrum (CDCl ), δ, ppm: 1.85 m (4H,
6
4
3
%
: C 60.66; H 4.36; N 3.40; S 7.70. C H ClNO S.
CH ), 2.58–2.73 m (4H, CH ), 7.25 s (1H, CH), 7.51 m
2
1
18
4
2
2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

CHEMISTRY OF IMINOFURANS: X.
347
(
9
2H, Harom), 7.61 m (1H, Harom), 8.01 m (2H, Harom),
.88 s (1H, NH), 15.02 br.s (1H, OH). Mass spectrum,
carboxylate (4e). Yield 2.80 g (70%), orange crystals,
–
1
mp 168–169°C. IR spectrum, ν, cm : 3204 (NH),
+
1
m/z (I , %): 352 (30) [M] , 69 (100), 178 (75), 147
(
1
1684 (C=O, ester), 1665 (C=O, amide). H NMR spec-
rel
+
+
+
53) [BzCH=COH] , 77 (51) [Ph] , 43 (32) [NHCO] ,
05 (27) [Bz] . Found, %: C 64.77; H 4.59; N 7.93;
trum (CDCl
1.81 m (4H, CH
CH ), 4.39 q (2H, OCH
7.47–7.63 m (3H, Harom), 8.00–8.03 m (2H, Harom),
2.57 s (1H, NH), 15.69 br.s (1H, OH). Mass spec-
3
), δ, ppm: 1.42 t (3H, Me, J = 7.5 Hz),
), 2.70 m (2H, CH ), 2.81 m (2H,
, J = 7.5 Hz), 7.28 s (1H, CH),
+
2
2
S 9.09. C H N O S. Calculated, %: C 64.76; H 4.58;
2
2
1
9
16
2
3
N 7.95; S 9.10. M 352.41.
-(4-Chlorophenyl)-N-(3-cyano-4,5,6,7-tetra-
hydro-1-benzothiophen-2-yl)-2-hydroxy-4-oxobut-
-enamide (4b). Yield 2.71 g (70%), yellow crystals,
mp 225–226°C; published data [10]: mp 209–211°C.
1
4
+
trum, m/z (I , %): 399 (71) [M] , 179 (100), 105 (89)
rel
+
[Bz] , 151 (71), 69 (61), 225 (51). Found, %: C 63.15;
2
H 5.30; N 3.50; S 8.03. C H NO S. Calculated, %:
2
1
21
5
–
1
C 63.14; H 5.30; N 3.51; S 8.03. M 399.46.
IR spectrum, ν, cm : 3356 (NH), 2211 (CN), 1688
(
1
CH ), 7.20 s (1H, CH), 7.48 and 7.95 (2H each, Harom,
AA′BB′, J = 8.7 Hz), 9.85 s (1H, NH), 15.48 br.s (1H,
OH). Mass spectrum, m/z (I , %): 386 (58) [M] , 181
(
(
1
C=O, amide). H NMR spectrum (CDCl ), δ, ppm:
Ethyl 2-{[4-(4-chlorophenyl)-2-hydroxy-1,4-di-
oxobut-2-en-1-yl]amino}-4,5,6,7-tetrahydro-1-ben-
zothiophene-3-carboxylate (4f). Yield 3.69 g (85%),
3
.85 m (4H, CH ), 2.63 m (2H, CH ), 2.68 m (2H,
2 2
2
–
1
orange crystals, mp 203–204°C. IR spectrum, ν, cm :
+
3211 (NH), 1680 (C=O, ester), 1660 (C=O, amide).
rel
+
1
100), 69 (91), 139 (54) [ClC H CO] , 150 (41), 43
25) [NHCO] , 209 (75). Found, %: C 58.97; H 3.90;
H NMR spectrum (CDCl
3
), δ, ppm: 1.41 t (3H, Me,
), 2.69 m (2H, CH ),
), 4.39 q (2H, OCH , J = 6.9 Hz),
7.25 s (1H, CH), 7.47 and 7.93 (2H each, Harom
AA′BB′, J = 8.4 Hz), 12.54 s (1H, NH), 15.43 br.s (1H,
6
4
+
J = 6.9 Hz), 1.80 m (4H, CH
2.81 m (2H, CH
2
2
N 7.24; S 8.32. C H ClN O S. Calculated, %:
C 58.99; H 3.91; N 7.24; S 8.29. M 386.85.
2
2
1
9
15
2
3
,
N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothiophen-
-yl)-2-hydroxy-4-(4-methylphenyl)-4-oxobut-2-en-
+
OH). Mass spectrum, m/z (I , %): 433 (29) [M] , 179
(
(
2
rel
+
+
100), 139 (76) [ClC H CO] , 69 (75) [C H NO] , 225
amide (4c). Yield 3.55 g (97%), yellow crystals,
mp 191–192°C; published data [10]: mp 182–184°C.
IR spectrum, ν, cm : 3350 (NH), 2213 (CN), 1691
(
6 4 3 3
+
51), 43 (33) [NHCO] . Found, %: C 58.10; H 4.66;
–
1
N 3.23; S 7.42. C H ClNO S. Calculated, %:
21 20
5
1
C 58.13; H 4.65; N 3.23; S 7.39. M 433.90.
C=O, amide). H NMR spectrum (CDCl ), δ, ppm:
3
1
2
.84 m (4H, CH ), 2.44 s (3H, Me), 2.63 m (2H, CH ),
Ethyl 2-{[2-hydroxy-4-(4-methylphenyl)-1,4-di-
oxobut-2-en-1-yl]amino}-4,5,6,7-tetrahydro-1-ben-
zothiophene-3-carboxylate (4g). Yield 2.99 g (72%),
2
2
.67 m (2H, CH ), 7.21 s (1H, CH), 7.30 and 7.91 (2H
2
each, Harom, AA′BB′, J = 8.1 Hz), 9.88 s (1H, NH),
5.41 br.s (1H, OH). Mass spectrum, m/z (I , %): 366
–
1
1
orange crystals, mp 204°C. IR spectrum, ν, cm : 3392
rel
+
+
(
50) [M] , 178 (100), 119 (51) [MeC H CO] , 69 (38),
(NH), 1698 (C=O, ester), 1637 (C=O, amide).
6
4
+
1
1
61 (28), 44 (23), 91 (16) [MeC H ] . Found, %:
H NMR spectrum (CDCl ), δ, ppm: 1.41 t (3H, Me,
6
4
3
C 65.53; H 4.97; N 7.62; S 8.75. C H N O S. Calcu-
J = 7.1 Hz), 1.80 m (4H, CH ), 2.38 s (3H, Me),
20
18
2
3
2
lated, %: C 65.55; H 4.95; N 7.64; S 8.75. M 366.44.
2.64 m (2H, CH ), 2.80 m (2H, CH ), 4.39 m (2H,
2
2
OCH , J = 7.1 Hz), 7.27 and 7.88 (2H each, Harom,
N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothiophen-
-yl)-2-hydroxy-4-oxo-4-(thiophen-2-yl)but-2-en-
2
AA′BB′, J = 8.1 Hz), 12.53 s (1H, NH), 15.43 br.s (1H,
2
+
OH). Mass spectrum, m/z (I , %): 413 (63) [M] , 179
amide (4d). Yield 3.48 g (97%), yellow crystals,
rel
+
–
1
(
[
100), 225 (54), 69 (46) [C H NO] , 151 (35), 43 (24)
NHCO] . Found, %: C 69.89; H 5.62; N 3.41; S 7.73.
mp 182–183°C. IR spectrum, ν, cm : 3365 (NH),
3 3
+
1
2
(
2
208 (CN), 1682 (C=O, amide). H NMR spectrum
C H NO S. Calculated, %: C 63.90; H 5.61; N 3.39;
CDCl ), δ, ppm: 1.84 m (4H, CH ), 2.63 m (2H, CH ),
22 23
5
3
2
2
S 7.75. M 413.49.
.68 m (2H, CH ), 7.08 s (1H, CH), 7.21 t (1H, Harom,
2
J = 4.2 Hz), 7.76 d (1H, Harom, J = 4.4 Hz), 7.89 d (1H,
Ethyl 2-{[2-hydroxy-1,4-dioxo-4-(thiophen-2-yl)-
but-2-en-1-yl]amino}-4,5,6,7-tetrahydro-1-benzo-
thiophene-3-carboxylate (4h). Yield 3.37 g (83%),
Harom, J = 3.3 Hz), 9.75 s (1H, NH), 15.02 br.s (1H,
+
OH). Mass spectrum, m/z (I , %): 358 (47) [M] , 153
rel
–
1
(
[
100), 179 (77) , 69 (63), 111 (51), 181 (44), 43 (28)
NHCO] . Found, %: C 56.95; H 3.96; N 7.82;
orange crystals, mp 191–192°C. IR spectrum, ν, cm :
119 (NH), 1684 (C=O, ester), 1668 (C=O, amide).
+
3
1
S 17.90. C H N O S . Calculated, %: C 56.96;
1
7
14
2
3
2
H NMR spectrum (CDCl ), δ, ppm: 1.40 t (3H, Me,
3
H 3.94; N 7.82; S 17.89. M 358.43.
J = 6.9 Hz), 1.80 m (4H, CH ), 2.69 m (2H, CH ),
2
2
Ethyl 2-[(2-hydroxy-1,4-dioxo-4-phenylbut-2-en-
2.80 m (2H, CH ), 4.38 q (2H, OCH , J = 6.9 Hz),
2
2
1
-yl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-
7.10 s (1H, CH), 7.19 t (1H, Harom, J = 4.2 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

3
7
48
PANCHENKO et al.
.73 d.d (1H, Harom, J = 1.1 Hz, 4.9 Hz), 7.87 d.d (1H,
17. Wang, H., Guo, S., Hu, Y., Zeng, X., and Yang, G., Chin.
J. Org. Chem., 2015, vol. 35, p. 1075.
Harom, J = 1.1, 3.9 Hz), 12.50 s (1H, NH), 15.01 br.s
+
(
1
(
1H, OH). Mass spectrum, m/z (I , %): 405 (71) [M] ,
18. Kollenz, G., Kappe, C.O., and Abd el Nabey, H.,
rel
+
Heterocycles, 1991, vol. 32, p. 669.
79 (100), 225 (82), 69 (77) [C H NO] , 153 (60), 111
3 3
+
43), 206 (42), 43 (19) [NHCO] . Found, %: C 56.30;
H 4.72; N 3.44; S 15.80. C H NO S . Calculated, %:
19. Ziegler, E., Eder, M., Belegratis, C., and Prewedoura-
kis, E., Monatsh. Chem., 1967, vol. 98, p. 2249.
1
9
19
5 2
C 56.28; H 4.72; N 3.45; S 15.82. M 405.48.
20. Andreichikov, Yu.S., Gein, V.L., Zalesov, V.V., Koz-
lov, A.P., Kollenz, G., Maslivets, A.N., Pimenova, E.V.,
and Shurov, S.N., Khimiya pyatichlennykh 2,3-diokso-
geterotsiklov (Chemistry of Five-Membered 2,3-Dioxo
Heterocycles), Perm: Perm. Gos. Univ., 1994, p. 5.
REFERENCES
1
2
. Pulina, N.A., Kuznetsov, A.S., and Rubtsov, A.E., Russ.
J. Org. Chem., 2015, vol. 51, p. 967.
. Andreichikov, Yu.S., Shurov, S.N., Zalesov, V.V., and
Shapet’ko, N.N., Russ. J. Org. Chem., 1986, vol. 22,
p. 857.
2
1. Rubtsov, A.E. and Zalesov, V.V., Russ. J. Org. Chem.,
2003, vol. 39, p. 869.
2
2. Rubtsov, A.E., Makhmudov, R.R., Kovylyaeva, N.V.,
Prosyanik, N.I., Bobrov, A.V., and Zalesov, V.V.,
Pharm. Chem. J., 2002, vol. 36, no. 11, p. 608.
3
. Lisovenko, N.Yu., Merkushev, A.A., Nasibullina, E.R.,
Slepukhin, P.A., and Rubtsov, A.E., Russ. J. Org.
Chem., 2014, vol. 50, p. 759.
2
2
2
3. Komarova, O.A., Igidov, N.M., Rubtsov, A.E., Zale-
sov, V.V., Makarov, A.S., and Toksarova, Yu.S., Russ. J.
Org. Chem., 2010, vol. 46, p. 236.
4
. Nasibullina, E.R., Shurov, S.N., Dmitriev, M.V., and
Rubtsov, A.E., Russ. J. Org. Chem., 2015, vol. 51,
p. 284.
4. Komarova, O.A., Igidov, N.M., Koryagina, N.N.,
Makarov, A.S., Toksarova, Yu.S., and Rubtsov, A.E.,
Russ. J. Org. Chem., 2011, vol. 47, p. 109.
5
6
7
8
9
. Capuano, L. and Tammer, T., Chem. Ber., 1981,
vol. 114, p. 456.
. Zalesov, V.V. and Rubtsov, A.E., Chem. Heterocycl.
Compd., 2004, vol. 40, p. 133.
. Puterová, Z., Krutošíková, A., and Végh, D., Nova
Biotechnol., 2009, vol. 9, no. 2, p. 167.
5. Tyuneva, A.V., Igidov, N.M., Koryagina, N.N., Boro-
din, A.Yu., Zakhmatov, A.V., Makarov, A.S., Toksaro-
va, Yu.S., and Rubtsov, A.E., Russ. J. Org. Chem., 2011,
vol. 47, p. 258.
2
2
2
6. Rubtsov, A.E. and Zalesov, V.V., Chem. Heterocycl.
Compd., 2001, vol. 37, p. 1038.
. Puterová, Z., Krutošíková, A., and Végh, D., Arkivoc,
2
010, part (i), p. 209.
7. Shipilovskikh, S.A., Rubtsov, A.E., and Zalesov, V.V.,
. El-Mekabaty, A., Synth. Commun., 2014, vol. 44, p. 1.
Chem. Heterocycl. Compd., 2009, vol. 45, p. 658.
1
0. Nekrasov, D.D., Kol’tsova, S.V., and Andreichi-
kov, Yu.S., Chem. Heterocycl. Compd., 1994, vol. 30,
p. 154.
8. Becker, H.G.O., et al., Organikum. Organisch-
chemisches Grundpraktikum, Weinheim: Wiley, 2004,
2
2nd edn. Translated under the title Organikum,
11. Palacios, F., Alonso, C., Aparicio, D., Rubiales, G., and
Moscow: Mir, 2008, vol. 2, p. 488.
Santos, J.M., Tetrahedron, 2007, vol. 63, p. 523.
2. Molina, P. and Vilaplana, M.J., Synthesis., 1994,
2
9. Andreichikov, Yu.S., Nalimova, Yu.A., Plakhina, G.D.,
Saraeva, R.F., and Tendryakova, S.P., Chem. Heterocycl.
Compd., 1975, vol. 11, p. 1252.
1
1
1
1
1
p. 1197.
3. Wamhoff, H., Richardt, G., and Stölben, S., Adv.
Heterocycl. Chem., 1995, vol. 64, p. 159.
4. Wamhoff, H. and Haffmanns, G., Chem. Ber., 1984,
vol. 117, p. 585.
5. Ding, M.-W., Huang, N.-Y., and He, H.-W., Synthesis,
30. Yanoborisov, T.N., Zhikina, I.A., Andreichikov, Yu.S.,
Milyutin, A.V., and Plaksina, A.N., Pharm. Chem. J.,
1998, vol. 32, no. 9, p. 480.
31. Verbic, T.Z., Drakulic, B.J., Zloh, M.F., Pecelj, J.R.,
Popovic, G.V., and Juranic, I.O., J. Serb. Chem. Soc.,
2007, vol. 72, p. 1201.
2
005, p. 1601.
6. Wamhoff, H., Herrmann, S., Stölben, S., and Nieger, M.,
32. Gewald, K., Schinke, E., and Böttcher, H., Chem. Ber.,
Tetrahedron, 1993, vol. 49, p. 581.
1966, vol. 99, p. 94.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016