2-acyl(aroyl)-1,1,3,3-tetracyanopropenides: II*. Synthesis of 2-[2-(alkylsulfanyl)-5-amino-2-aryl-4-cyano-2,3-dihydrofuran-3- ylidenepropanedinitriles by reaction with thiols

Article abstract of DOI:10.1134/S1070428011080070

Reactions of 2-aroyl-1,1,3,3-tetracyanopropenides with thiols in acid medium led to the formation of the corresponding 2-alkylsulfanyl-substituted 2-(5-amino-2-aryl-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitriles.

Full text of DOI:10.1134/S1070428011080070

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 8, pp. 1161−1164. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © S.V. Karpov, Ya.S. Kayukov, I.N. Bardasov, O.V. Ershov, O.E. Nasakin, O.V. Kayukova, 2011, published in Zhurnal Organicheskoi
Khimii, 2011, Vol. 47, No. 8, pp. 1144−1146.
2-Acyl(aroyl)-1,1,3,3-tetracyanopropenides: II*.
Synthesis of 2-[2-(Alkylsulfanyl)-5-amino-2-aryl-4-cyano-2,3-
dihydrofuran-3-ylidenepropanedinitriles
by Reaction with Thiols
S. V. Karpova, Ya. S. Kayukova, I. N. Bardasova, O. V. Ershova,
O. E. Nasakina, and O. V. Kayukovab
aI.N. Ul’yanov Chuvash State University, Cheboksary, 428015 Russia
e-mail: kaukovyakov@mail.ru
bChuvash Agricultural Academy, Cheboksary, Russia
Received November 13, 2010
Abstract—Reactions of 2-aroyl-1,1,3,3-tetracyanopropenides with thiols in acid medium led to the formation of the
corresponding 2-alkylsulfanyl-substituted 2-(5-amino-2-aryl-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitriles.
DOI: 10.1134/S1070428011080070
5-amino-2-aryl-4-cyano-2,3-dihydrofuran-3-ylidene]
propanedinitriles IIa–IIf, and the reaction with ethyl
mercaptoacetate provided ethyl 2-{[5-amino-2-aryl-3-
(dicyanomethylidene)-4-cyano-2,3-dihydrofuran-2-yl]-
sulfanyl}acetates IIg–IIi in up to 71–87% yields.
2-Aroyl-1,1,3,3-tetracyanopropenides I obtained from
the corresponding tetracyanocyclopropyl ketones [2] are
promising precursors for the synthesis of functionally
substituted five-memebered heterocycles. In the previous
paper on the reaction of propenides I with the hydrochlo-
ric acid we demonstrated that the chloride ion added to the
protonated carbonyl group to give 2-chlorodihydrofurans
[1]. Besides it was previously assumed that propenides I
were intermediates in the process of tetracyanocyclopro-
pyl ketones conversion into 2-alkoxydihydrofurans at the
use as nucleophiles alcohols and ketoximes in the pres-
ence of the corresponding alcoholates and oximates [2, 3].
O
CN
H2N
O
Ar
Ar
CN
NH4
+ RSH
S R
CN
NC
+
NC
CN
NC
IIа_IIi
Iа_Ic
I, Ar = C6H5 (a), 4-ClC6H4 (b), 4-CH3C6H4 (c); II, R = C2H5,
Ar = C6H5 (a), 4-ClC6H4 (b), 4-CH3C6H4 (c);R = C3H7, Ar =
C6H5 (d), 4-ClC6H4 (e), 4-CH3C6H4, (f); R = CH2CO2C2H5,
Thiols are close analogs of alcohols, and their in-
volvement into the reaction with the 2-aroyl-1,1,3,3-
tetra-cyanopropenides opens the way to the synthesis
of previously unknown 2-alkylsulfanyl-substituted
dihydrofurans. Therefore we studied the reactions of
propenides I with mercaptans in various conditions. It was
established that the expected 2-alkylsulfanyl derivatives
of dihydrofurans formed at the use of an acid catalyst and
water as a solvent. In these conditions the reaction of pro-
penides I with alkylthiols afforded 2-[2-(alkylsulfanyl)-
–––––––––––––––––––
Ar = C6H5 (g), 4-ClC6H4 (h), 4-CH3C6H4 (i).
The structure of compounds IIa–IIi was established
with the use of the data of 1H NMR, IR, and mass spec-
tra. In the 1H NMR spectra the signls of amino group are
present at 10.28–10.31 ppm, and also the proton signal
appeared of the aromatic ring and of the hydrocarbon
substituents at the sulfur atom. The protons of the methy-
lene group at the sulfur atom are diastereotopic, and their
1
signal in the H NMR spectrum is characteristic of the
* For Communication I, see [1].
1161

KARPOV et al.
1162
spin system AB. Therefore the signal of the CH2 group
linked to sulfur in the spectra of compounds IIg–IIi gives
rise to two doublets, and in the spectra of compounds
IIa–IIf, a multiplet combined from two doublets of quar-
tets (IIa–IIc) or from two doublets of triplets (IId–IIf).
Asimilar pattern is observed also for the methylene group
of the ester moiety of compounds IIg–IIi. The IR spectra
contain the absorption bands of the conjugated cyano
groups in the region 2200–2225 cm–1, of the C=C bond
of the dicyanomethylene moiety at 1669–1695 cm–1, and
of amino group at 3075–3280 cm–1.
ethyleneamine [5]. The method of the synthesis of
2-alkylsulfanyldihydrofurans II we developed is dis-
tinguished by the simplicity, high yield of the reaction
products, and by the relative availability of the reagents.
EXPERIMENTAL
The monitoring of the reaction progress and checking
the purity of compounds synthesized was carried out by
TLC on Silufol UV-254 plates (spots visualized by UV
irradiation, in iodine vapor, and by calcining). IR spectra
were recorded on a spectrophotometer FSM 1201 from
thin films or mulls in mineral oil. 1H NMR spectra were
registered on a spectrometer BrukerAM-500 at operating
frequency 500.13 MHz, solvent DMSO-d6, internal refer-
ence TMS. Mass spectra were measured on an instrument
Finnigan MAT INCOS-50 (electron impact, 70 eV).
The catalyst role apparently consists in the activation
of the carbonyl group by its protonation with the forma-
tion of an intermediate zwitter-ion A. The presumable
scheme of transformations includes further the nucleo-
philic addition of the thiol giving a hemimercaptal B and
the heterocyclization into dihydrofuran derivative IIa–IIi
(see the scheme).
Ammonium 2-benzoyl-1,1,3,3-tetracyanopropenide
(Ia) was obtained by method [5]. Yield 87%, mp 182–
183°C (decomp.). IR spectrum, ν, cm–1: 2225 (C≡N),
1675 (C=O).
Water is not an optimal solvent due to the poor solu-
bility of thiols, but the use of organic solvents or their
additives in water completely inhibits the reaction, and
we regard this fact as a confirmation of the zwitter-ionic
character of intermediate A. We attained a sufficient
success of the reaction at the use of the 5-fold excess
of the thiol. Under these conditions the reaction appar-
ently occurs at the interphase boundary, and the reaction
product crystallizes in the thiol phase. We failed to obtain
the desired result under the other conditions. The use of
basic catalyst does not lead to the formation 2-alkylsul-
fanylfurans.Applying thiolates as catalysts in anhydrous
solvents is accompanied with strong tarring impeding
the isolation of individual products, and in the aqueous
solvents the concurrent reaction with the hydroxide ion
occurs resulting in the formation of pyrrolo[3,4-C]pyri-
dine derivatives [4].
Compounds Ib, Ic were similarly prepared.
Ammonium 1,1,3,3-tetracyano-2-(4-chlorobenzoyl)
propenide (Ib). Yield 91%, mp 165–167°C (decomp.).
IR spectrum, ν, cm–1: 2210 (C≡N), 1685 (C=O).
Ammonium 2-(4-methylbenzoyl)-1,1,3,3-tetra-
cyanopropenide (Ic). Yield 85%, mp 176–178°C (de-
comp.). IR spectrum, ν, cm–1: 2200 (C≡N), 1665 (C=O).
2-[5-Amino-2-phenyl-4-cyano-2-(ethylsulfanyl)-
2,3-dihydrofuran-3-ylidene]propanedinitrile (IIa). To
a solution of 2.63 g (10 mmol) of compound Ia in 20 ml
of water was added dropwise at stirring 3.1 g (50 mmol)
of ethanethiol. The emulsion obtained was acidified with
two drops of concn. hydrochloric acid, and the mixture
was stirred for 20 min. The separated precipitate was
filtered off, washed with water, and recrystallized from
methanol. Yield 2.25 g (73%), mp 165–166°C (decomp.).
IR spectrum, ν, cm–1: 3125 (NH2), 2240 (C≡N), 1660
(C=C). 1H NMR spectrum, δ, ppm: 1.26 t (3H, CH3,
Today the 2-alkylsulfanyl-substituted 5-aminodihy-
drofurans are insufficiently described. The known method
of preparation of 5-(methylsulfanyl)-3,4-diphenylfuran-2-
(N,N-dimethyl)amine consisted in the reaction of diphen-
ylcyclopropenone with N,N-dimethyl-1-(methylsulfanyl)
2
3J 7.4 Hz), 2.64 m (ABX2 system) (2H, CH2, J 12.2,
Scheme.
OH CN
CN
CN
OH CN
H+
H+
R
SH
Ar
Ar
CN
CN
Iа_Ic
IIа_IIi
SR
NC
_H+
NC
B
А
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

2-ACYL(AROYL)-1,1,3,3-TETRACYANOPROPENIDES: II
1163
3J 7.5 Hz), 7.52–7.57 m (5H, Ph), 10.29 s (2H, NH2).
Mass spectrum, m/z (Irel, %): 308 (30). Found, %: C 62.37;
H 3.91; N 18.51. C16H12N4OS. Calculated, %: C 62.32;
H 3.92; N 18.17. M 308.36.
propanedinitrile (IIf). Yield 79%, mp 144–145°C (de-
comp.). IR spectrum, ν, cm–1: 3180 (NH2), 2220 (C≡N),
1665 (C=C). H NMR spectrum, δ, ppm: 0.99 t (3H, CH3,
3J 7.3 Hz), 1.55–1.68 m (2H, SCH2CH2CH3), 2.34 s (3H,
PhCH3), 2.53–2.65 m (2H, SCH2CH2CH3), 7.31 d (2H,
Ph, 3J 8.3 Hz), 7.44 d (2H, Ph, 3J 8.3 Hz), 10.28 s (2H,
NH2). Mass spectrum, m/z (Irel, %): 336 (18). Found, %:
C 65.2; H 4.83; N 15.65. C18H16N4OS. Calculated, %:
C 64.26; H 4.79; N 16.65. M 336.41.
1
Compounds IIb–IIi were synthesized analogously.
2-[5-Amino-2-(4-chlorophenyl)-4-cyano-2-
(ethylsulfanyl)-2,3-dihydrofuran-3-ylidene]propane-
dinitrile (IIb). Yield 81%, mp 196–198°C (decomp.).
IR spectrum, ν, cm–1: 3100 (NH2), 2210 (C≡N), 1665
(C=C). 1H NMR spectrum, δ, ppm: 1.25 t (3H, CH3,
Ethyl 2-{[5-amino-3-(dicyanomethylidene)-2-
phenyl-4-cyano-2,3-dihydrofuran-2-yl]sulfanyl}
acetate (IIg). Yield 87%, mp 153–155°C (decomp.). IR
spectrum, ν, cm–1: 3210 (NH2), 2200 (C≡N), 1650 (C=C).
1H NMR spectrum, δ, ppm: 1.26 t (3H, CH3, 3J 7.1 Hz),
2
3J 7.4 Hz), 2.65 m (ABX2 system, 2H, CH2, J 12.2,
3J 7.5 Hz), 7.57–7.62 m (4H, Ph), 10.32 s (2H, NH2).
Mass spectrum, m/z (Irel, %): 342 (3), 344 (1). Found, %:
C 57.1; H 3.31; N 16.84. C16H11ClN4OS. Calculated, %:
C 56.06; H 3.23; N 16.34. M 342.80.
2
3.57 d (1H, SCH2, J 16.0 Hz), 3.62 d (1H, SCH2,
2J 16.0 Hz), 4.09–4.20 m (OCH2CH3), 7.53–7.58 m (5H,
Ph), 10.30 s (2H, NH2). Mass spectrum, m/z (Irel, %):
246 (33), 120 (30). Found, %: C 60.32; H 4.12; N 14.45.
C18H14N4O3S. Calculated, %: C 59.01; H 3.85; N 15.29.
M 366.39.
2-[5-Amino-2-(4-methylphenyl)-4-cyano-2-
(ethylsulfanyl)-2,3-dihydrofuran-3-ylidene]propane-
dinitrile (IIc). Yield 76%, mp 173–175°C (decomp.).
IR spectrum, ν, cm–1: 3200 (NH2), 2215 (C≡N), 1655
1
(C=C). H NMR spectrum, δ, ppm: 1.25 t (3H, CH2CH3,
Ethyl 2-{[5-amino-3-(dicyanomethylidene)-2-
(4-chlorophenyl)-4-cyano-2,3-dihydrofuran-2-yl]-
sulfanyl}acetate (IIh). Yield 79%, mp 146–148°C
(decomp.). IR spectrum, ν, cm–1: 3190 (NH2), 2210
3J 7.5 Hz), 2.28 s (3H, PhCH3), 2.63–2.71 m (2H, CH2),
7.21 d (2H, C6H4, 3J 8.3 Hz), 7.55 d (2H, C6H4, 3J8.3 Hz),
10.29 s (2H, NH2). Mass spectrum, m/z (Irel, %): 322 (5),
307 (40). Found, %: C 64.81; H 4.65; N 16.9. C17H14N4OS.
Calculated, %: C 63.33; H 4.38; N 17.38. M 322.38.
1
(C≡N), 1660 (C=C). H NMR spectrum, δ, ppm: 1.25 t
2
(3H, CH3, 3J 7.1 Hz), 3.59 d (1H, SCH2, J 16.0 Hz),
2-[5-Amino-2-(propylsulfanyl)-2-phenyl-4-cyano-
2,3-dihydrofuran-3-ylidene]propanedinitrile (IId).
Yield 71%, mp 165–166°C (decomp.). IR spectrum, ν,
cm–1: 3120 (NH2), 2230 (C≡N), 1660 (C=C). 1H NMR
spectrum, δ, ppm: 1.00 t (3H, CH3, 3J 7.3 Hz), 1.57–
1.67 m (2H, SCH2CH2CH3), 2.61 m (ABX2 system, 2H,
2
3.64 d (1H, SCH2, J 16.0 Hz), 4.08–4.19 m (2H,
OCH2CH3), 7.58–7.62 m (4H, Ph), 10.33 s (2H, NH2).
Mass spectrum, m/z (Irel, %): 400 (2), 402 (1), 280 (30),
282 (10), 245 (28). Found, %: C 54.21; H 4.12; N 12.77.
C18H13ClN4O3S. Calculated, %: C 53.94; H 3.27;
N 13.98. M 400.84.
2
3
SCH2CH2CH3, J 12.2, J 7.2 Hz), 7.52–7.58 m (5H,
Ph), 10.30 s (2H, NH2). Mass spectrum, m/z (Irel, %): 322
(23). Found, %: C 64.21; H 5.07; N 16.27. C17H14N4OS.
Calculated, %: C 63.33; H 4.38; N 17.38. M 322.38.
Ethyl 2-{[5-amino-3-(dicyanomethylidene)-2-
(4-methylphenyl)-4-cyano-2,3-dihydrofuran-2-yl]-
sulfanyl}acetate (IIi). Yield 74%, mp 154–156°C
(decomp.). IR spectrum, ν, cm–1: 3210 (NH2), 2250
2-[5-Amino-2-(propylsulfanyl)-2-(4-chloro-
phenyl)-4-cyano-2,3-dihydrofuran-3-ylidene]pro-
panedinitrile (IIe). Yield 72%, mp 212–215°C (de-
comp.). IR spectrum, ν, cm–1: 3180 (NH2), 2220 (C≡N),
1650 (C=C). 1H NMR spectrum, δ, ppm: 0.99 t (3H, CH3,
3J 7.3 Hz), 1.56–1.67 m (2H, SCH2CH2CH3), 2.62 m
1
(C≡N), 1665 (C=C). H NMR spectrum, δ, ppm: 0.99 t
(3H, CH3, 3J 7.1 Hz), 2.36 s (3H, PhCH3), 3.60 d (1H,
2
2
SCH2, J 16.0 Hz), 3.63 d (1H, SCH2, J 16.0 Hz),
3
4.07–4.20 m (OCH2CH3), 7.36 d (2H, Ph, J 8.2 Hz),
7.38 d (2H, Ph, J 8.2 Hz), 10.18 s (2H, NH2). Mass
3
spectrum, m/z (Irel, %): 380 (13). Found, %: C 61.35;
H 4.87; N 14.09. C19H16N4O3S. Calculated, %: C 59.99;
H 4.24; N 14.73. M 380.42.
2
3
(ABX2 system, 2H, SCH2CH2CH3, J 12.2, J 7.2 Hz),
7.57–7.63 m (4H, Ph), 10.32 s (2H, NH2). Mass spectrum,
m/z (Irel, %): 356 (20), 358 (9). Found, %: C 57.3; H 3.71;
N 14.70. C17H13ClN4OS. Calculated, %: C 57.22; H 3.67;
N 15.70. M 356.83.
ACKNOWLEDGMENTS
2-[5-Amino-2-(4-methylphenyl)-2-(propyl-
sulfanyl)-4-cyano-2,3-dihydrofuran-3-ylidene]
The study was carried out in the framework of the
State contract no. 16.740.11.0335 Federal targeted
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KARPOV et al.
1164
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program «Scientific and scientific-pedagogical staff of
the innovation Russia.”
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011