Iminofurans chemistry. Decyclization of ethyl 2-[2-oxo-5-phenylfuran-3(2H)- ylideneamino]-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate under the action of aliphatic amines

Full text of DOI:10.1134/S1070428014020286

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 2, pp. 298−300. © Pleiades Publishing, Ltd., 2014.
Original English Text © S.A. Shipilovskikh, A.E. Rubtsov, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 2, pp. 305−307.
SHORT
COMMUNICATIONS
Iminofurans Chemistry. Decyclization
of Ethyl 2-[2-Oxo-5-phenylfuran-3(2H)-ylideneamino]-
4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
under the Action of Aliphatic Amines
S. A. Shipilovskikh and A. E. Rubtsov
Perm State University, Perm, 614990 Russia
e-mail: rubtsov@psu.ru
Received September 11, 2013
DOI: 10.1134/S1070428014020286
Publications on compounds containing in the structure
3-imino-3H-furan-2-one are scarce [1]. We formerly
developed a simple preparation method for a series of
ethyl 2-[5-aryl-2-oxofuran-3(2H)-ylideneamino]-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carboxylates through
an intramolecular cyclization of (Z)-4-aryl-4-oxo-2-[3-
(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-
2-ylamino]but-2-enoic acids under the action of acetic
anhydride [2]. At the same time this rare type of furan-2-
one derivatives is promising in view of the high reactivity
and possible biologic action. The introduction into the
structure of a thiophene substituent [3–5] at the imine
nitrogen atom even more increases the promising quali-
ties of these compounds. Moreover, it has been shown
that the proper (Z)-4-aryl-4-oxo-2-[3-(ethoxycarbonyl)-
4,5,6,7-tetrahydrobenzo[b]-thiophen-2-ylamino]but-2-
enoic acids exhibit the biological activity exceeding the
activity of drugs used in medicine [6, 7].
It was shown by an example of 5-aryl-3-arylimino-
3H-furan-3-one that in reaction with anilines the furan
ring suffered opening giving amides of 4-aryl-4-oxo-2-
arylaminobut-2-enoic acids [8]. In the molecule of ethyl
2-[2-oxo-5-phenylfuran-3(2H)-ylideneamino]-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carboxylate (I) at least
two obvious sites are present for nucleophilic attack with
aliphatic amines.
The reaction of ethyl 2-[2-oxo-5-phenylfuran-3(2H)-
ylideneamino]-4,5,6,7-tetrahydrobenzo[b]thiophene-3-
carboxylate (I) with amines IIа–IIc in an inert aprotic
solvent afforded the corresponding ethyl 2-[(Z)-3-oxo-
3-phenyl-1-(carbamoyl)-prop-1-enylamino]-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carboxylates IIIа–IIIc.
OEt
O
O
O
Ph
R
N
H
S
H
S
.
.
S
OEt
N
.
TolH
O
N
+
H
NH2R
O
R
N
O
NH
Ph
Ph
O
O
O
OEt
IIIa_IIIc
IIa_IIc
A
B
I
R = Et (а), Bn (b), Cy (c).
298

IMINOFURANS CHEMISTRY.
299
As a result of the study of the reaction it was estab-
lished that the attack of the amino group was directed at
the carbon atom of the lactone carbonyl group of com-
pound I and resulted in the products of the decyclization
of the furan ring. The ester group under the reaction
conditions is not involved into the reaction with amines.
Compounds IIIа–IIIc are crystalline substances.
We registered 1Н NMR spectra of compounds IIIа–
IIIc in DMSO-d6 and СDCl3. It was established that
compounds IIIа–IIIc when dissolved in DMSO-d6 ex-
isted in form А characterized by the presence of a singlet
at 13.19–13.25 ppm corresponding to the proton of NH
group involved in a strong intramolecular hydrogen bond,
of proton signal of group NHCO at 8.99–9.62 ppm , and
of proton of СН group at 6.25–6.35 ppm.
atom and involvement of the hydrogen atom of the amide
group into the hydrogen bond with the carbonyl С4=О.
Ethyl 2-[(Z)-3-oxo-3-phenyl-1-(ethylcarbamoyl)-
prop-1-enylamino]-4,5,6,7-tetrahydro-benzo[b]thio-
phene-3-carboxylate (IIIa). To a solution of 0.079 g of
ethylamine hydrochloride (IIa) and 0.04 g (1 mmol) of
sodium hydroxide in 0.5 mLof Н2O was added a solution
of 0.381 g (1 mmol) of compound I in 3 mLof anhydrous
toluene, and the mixture was stirred at room temperature
for 24 h. The separated precipitate was filtered off and re-
crystallized from 2-propanol. Yield 0.339 g (75%), orange
crystals, t.decomp. 155–156°С (i-PrOH). IR spectrum, ν,
cm–1: 3332 (NH), 1664 (CONH, COOEt), 1603, 1579,
1513. 1Н NMR spectrum (DMSO-d6), δ, ppm: 1.19 t (3Н,
СН3, J 6.9 Hz), 1.39 t (3Н, СН3, J 7.2 Hz), 1.74 m (4H,
CH2), 2.61 m (2H, CH2), 2.74 m (2H, CH2), 3.30 q.d (2H,
CH2N, J 6.9, 5.7 Hz), 4.39 q (2Н, СН2О, J 7.2 Hz), 6.30 s
(1Н, СН), 7.62 m (3Harom), 8.06 d (2Harom, J 7.1 Hz),
9.09 t (1H, NH, J 5.7 Hz), 13.24 s (1Н, NH). 1Н NMR
spectrum (CDCl3), δ, ppm, form А (47%): 1.29 m
(3Н, СН3), 1.38 m (3Н, СН3), 1.74–2.84 m (8H, CH2),
3.15 m (2H, CH2N), 4.39 m (2Н, СН2О), 6.81 br.t (1Н,
In СDCl3 solutions compounds IIIа–IIIc are present
in two forms А and B. The existence of two forms in
this case evidently is due to the higher thermodynamic
stability of form B originating from the formation of
several intramolecular hydrogen bonds which are de-
stroyed under the action of more polar DMSO-d6, and the
energy gain becomes prevailing for the solvated form А.
It was formerly shown by an example of 4-aryl-4-oxo-
2-arylaminobut-2-enoic acids derivatives [8–12] that in
DMSO-d6 solution two forms Z- and Е- were present
and predominantly Z-form existed in chloroform due to
stronger stabilization by six-membered intramolecular
hydrogen bond between the hydrogen of the amino
group in the position 2 and the carbonyl group С4=О. In
compounds IIIа–IIIc the presence of a bulky substituent
at the nitrogen atom and of an additional carbonyl group
leads to an opposite effect.
NН), 7.09 s (1Н, СН), 7.52 m (3Harom), 7.87 d (2Harom
,
J 7.1 Hz), 13.38 s (1Н, NH); form B (53%): 1.29 m (3Н,
СН3), 1.38 m (3Н, СН3), 1.74–2.84 m (8H, CH2), 3.15 m
(2H, CH2N), 4.39 m (2Н, СН2О), 6.11 s (1Н, СН), 7.52 m
(3Harom), 7.98 d (2Harom, J 7.1 Hz), 12.29 s (1Н, NH),
12.46 br.t (1H, NH). Found, %: С 64.74; Н 6.10; N 6.57.
C23H26N2O4S. Calculated, %: С 64.77; Н 6.14; N 6.57.
Ethyl 2-[(Z)-1-(benzylcarbamoyl)-3-oxo-3-phen-
ylprop-1-enylamino]-4,5,6,7-tetrahydrobenzo[b]-
thiophene-3-carboxylate (IIIb). A solution of 0.381
g (1 mmol) of compound I and 0.107 g (1 mmol) of
benzylamine (IIb) in 3 mL of anhydrous toluene was
stirred at 70°С for 2 h. On cooling the reaction mixture
to –5°С the separated precipitate was filtered off and re-
crystallized from 2-propanol. Yield 0.31 g (64%), orange
crystals, t.decomp. 176–176°С (i-PrOH). IR spectrum,
ν, cm–1: 3341(NH), 1662 (CONH, COOEt), 1600, 1578,
1511. 1Н NMR spectrum (DMSO-d6), δ, ppm: 1.39 t (3Н,
СН3, J 6.9 Hz), 1.75 m (4H, CH2), 2.51 m (2H, CH2),
2.73 m (2H, CH2), 4.39 q (2Н, СН2О, J 6.9 Hz), 4.46 d
(2H, CH2N, J 6 Hz), 6.35 s (1Н, СН), 7.37 m (5Harom),
7.59 m (3Harom), 8.05 d (2Harom, J 6.9 Hz),9.62 t (1H, NH,
J 6 Hz), 13.19 s (1Н, NH). 1Н NMR spectrum (CDCl3), δ,
ppm, form А (54%): 1.34 t (3Н, СН3, J 7.5 Hz), 1.72 m
(4H, CH2), 2.48 m (2H, CH2), 2.65 m (2H, CH2), 4.32 q
(2Н, СН2О, J 7.5 Hz), 4.61 d (2H, CH2N, J 5.4 Hz), 7.11 s
1
In the Н NMR spectrum taken in CDCl3 form А
is characterized by the presence of a singlet at 13.19–
13.25 ppm corresponding to the proton of NH group
involved in a strong intramolecular hydrogen bond, by
a proton signal of group NHCO at 6.26–7.17 ppm, and
by a singlet of proton of СН group at 7.07–7.11 ppm.
Form B gives rise to a singlet of the proton of NH group
at 12.28–12.32 ppm, a singlet of proton of СН group at
6.11–6.18 ppm, and a signal of the amide group proton at
12.43–12.97 ppm. This downfield location of the amide
group signal is apparently due to the weakening of the
N–H bond because of the increase in its acidic charac-
ter originating from two effects of the same direction:
withdrawing the electron density from the oxygen atom
of the amide carbonyl at the formation of the hydrogen
bond with the hydrogen atom of the amino group at the С2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 2 2014

SHIPILOVSKIKH, RUBTSOV
300
(decomposition) points were measured on devices PTP-2
and SMP40.
(1Н, СН), 7.17 br.t (1Н, NН), 7.35 m (3Harom), 7.77 d
(2Harom, J 7.1 Hz), 13.25 s (1Н, NH); form B (46%):
1.39 t (3Н, СН3, J 7.5 Hz), 1.82 m (4H, CH2), 2.71 m (2H,
CH2), 2.82 m (2H, CH2), 4.42 q (2Н, СН2О, J 7.5 Hz),
4.71 d (2H, CH2N, J 5.4 Hz), 6.15 s (1Н, СН), 7.52 m
(3Harom), 7.95 d (2Harom, J 7.1 Hz), 12.32 s (1Н, NH),
12.97 br.t (1H, NH). Found, %: С 68.84; Н 5.80; N 5.77.
C28H28N2O4S. Calculated, %: С 68.83; Н 5.78; N 5.73.
In the study we used commercially available eth-
ylamine hydrochloride, cyclohexylamine, and benzyl-
amine Fluka®; solvents toluene and 2-propanol were of
“chemically pure” grade. Compound I was synthesized
as described in [2].
ACKNOWLEDGMENTS
Ethyl 2-[(Z)-3-oxo-3-phenyl-1-(cyclohexylcarb-
amoyl)prop-1-enylamino]-4,5,6,7-tetrahydrobenzo[b]-
thiophene-3-carboxylate (IIIc) was similarly obtained
from compound I and amine IIc. Yield 0.236 g (49%),
orange crystals, t.decomp. 193–194°С (i-PrOH). IR spec-
trum, ν, cm–1: 3258 (NH), 1708 (COOEt), 1667 (CONH),
The study was carried out under a financial support
of the Russian Foundation for Basic Research (grants
nos. 12-03-31739 and 14-03-96016).
REFERENCES
1
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ppm: 1.37 m (4Н, СН2), 1.39 t (3Н, СН3, J 7.4 Hz),
1.51–1.94 m (8H, CH2), 2.63 m (2H, CH2), 2.75 m (2H,
CH2), 3.72 m (1H, CHN), 4.41 q (2Н, СН2О, J 7.4 Hz),
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,
J 7.1 Hz), 8.99 d (1H, NH, J 7.5 Hz), 13.25 s (1Н, NH).
1Н NMR spectrum (CDCl3), δ, ppm, form А (49%):
1.17–2.84 m (21H, CH2), 3.94 m (2H, CHN), 4.18 m
(2Н, СН2О), 6.26 br.d (1Н, NН), 7.07 s (1Н, СН), 7.52 m
(3Harom), 7.99 d (2Harom, J 6.9 Hz), 13.15 s (1Н, NH);
form B (51%): 1.17–2.84 m (21H, CH2, CH3), 3.94 m
(2H, CH2N), 4.18 m (2Н, СН2О), 6.18 s (1Н, СН),
7.52 m (3Harom), 7.93 d (2Harom, J 6.9 Hz), 12.29 s (1Н,
NH), 12.43 d (1H, NH, J 6.6 Hz). Found, %: С 67.44;
Н 6.70; N 5.87. C27H32N2O4S. Calculated, %: С 67.47;
Н 6.71; N 5.83.
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IR spectra were recorded on a spectrophotometer
FSM-1202 from pellets with KBr. 1Н NMR spectra were
registered on a spectrometer Varian-Mercury Plus-300
(operating frequency 300 МHz), internal reference TMS.
Elemental analysis was carried out on an instrument Leco
CHNS-932. The chemical purity of compounds and the
reaction progress was monitored by TLC on Sorbfil plates,
eluent ethyl ether–benzene–acetone, 10 : 9 : 1, spots visu-
alized under UV irradiation and in iodine vapor. Melting
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 2 2014