One-Pot Synthesis of 2-Alkylsulfanyldihydrofuran Derivatives from Tetracyanocyclopropyl Ketones

Article abstract of DOI:10.1134/S1070428018050226

Successive treatment of 3-acylcyclopropane-1,1,2,2-tetracarbonitriles with sodium hydrogen carbonate and alkylmercaptan in water environment results in the formation of 2-(5-amino-2-aryl-2-alkyl-sulfanyl-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitrile

Full text of DOI:10.1134/S1070428018050226

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 5, pp. 795–798. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © A.A. Grigor’ev, S.V. Karpov, A.N. Vasil’ev, O.E. Nasakin, Yu.A. Gracheva, O.V. Kayukova, Ya.S. Kayukov, 2018, published in
Zhurnal Organicheskoi Khimii, 2018, Vol. 54, No. 5, pp. 790–792.
SHORT
COMMUNICATIONS
One-Pot Synthesis of 2-Alkylsulfanyldihydrofuran Derivatives
from Tetracyanocyclopropyl Ketones
A. A. Grigor’eva, S. V. Karpova, A. N. Vasil’eva, O. E. Nasakina, Yu. A. Grachevab,
O. V. Kayukovac, and Ya. S. Kayukova*
a I.N. Ul’yanov Chuvash State University, Moskovskii pr. 15, Cheboksary, 428015 Russia
*e-mail: kaukovyakov@mail.ru
b Lobachevsky State University of Nizhny Novgorod (NNSU), Nizhny Novgorod, 603950 Russia
c Chuvash State Agricultural Academy, Cheboksary, 428003 Russia
Received October 25, 2017
Abstract—Successive treatment of 3-acylcyclopropane-1,1,2,2-tetracarbonitriles with sodium hydrogen
carbonate and alkylmercaptan in water environment results in the formation of 2-(5-amino-2-aryl-2-alkyl-
sulfanyl-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitriles.
DOI: 10.1134/S1070428018050226
2-Acyltetracyanopropenides 2 are readily available
[1] precursors for the synthesis of diverse polyfun-
ctional heterocyclic compounds [2–4]. Formerly they
were applied to the development of a synthesis method
for 2-(5-amino-2-aryl-2-alkylsulfanyl-4-cyano-2,3-di-
hydrofuran-3-ylidene)propanedinitriles 3 using hydro-
chloric acid as catalyst [5]. The disadvantages of this
method consist in the necessity to apply a large excess
of mercaptan and a low reproducibility at scaling the
process. We established that the synthesis of
dihydrofuran derivatives 3 could be performed at the
catalysis with NaHCO3 in water environment in good
and high yields. Since propenides 2 are obtained at the
reaction of tetracyanocyclopropyl ketones 1 with salts
of weak acids in water solution we tested the
possibility to combine the synthesis in a single process.
The procedure of a multicomponent reaction did not
provide the desired result probably due to the
occurrence of competing reactions involving the cyano
groups. The desired dihydrofurans 3 were prepared by
successive treatment of cyclopropanes 1 first with
NaHCO3, and then after cooling the reaction mixture
with equimolar quantity of alkylthiol. The presumed
sequence of conversions includes the ring opening
under the action of sodium hydrogen carbonate as a
base with the formation of propenide 1. Further thiol
under catalysis with the base adds to the carbonyl
group with subsequent heterocyclization. The reaction
is completed by protonation to afford dihydrofurans 3.
The refined procedure was tested by the example of
several aryl tetracyanocyclopropyl ketones and alkyl-
mercaptans which led to the preparation of 2-(5-
amino-2-aryl-2-alkylsulfanyl-4-cyano-2,3-dihydro-
furan-3-ylidene)propanedinitriles 3а–3k. The structure
of compounds synthesized was proved by the data of
R2
O
S
OH
O
R1
S
R1
S
O
O
NH
NH2
CN
R2
R2
R1
CN
CN
R1
CN
CN
R1
CN
CN
R2SH
NaHCO3
NaHCO3
_CO2
_Na2CO3,
_H2O
_
_
_
CN
CN
NC
Na+
NC
NC
Na+
NC
H
Na+
CN
CN
CN
CN
CN
1a_1f
2a_2f
3a_3k
1, 2, R1 = C6H5 (a), 4-BrC6H4 (b), 4-CH3C6H5 (c), 4-CH3OC6H4 (d), thien-2-yl (e), CH3 (f); 3, R2 = С2Н5, R1 = C6H5 (a),
4-BrC6H4 (b), 4-CH3OC6H4 (c), thien-2-yl (d); R2 = C3H7, R1 = 4-BrC6H4 (e), 4-CH3OC6H4 (f), thien-2-yl (g), CH3 (h);
795

GRIGOR’EV et al.
796
1
IR, Н and 13С NMR, and mass spectra. Among the
%): 340 (41) [M + 2]+, 338 (21) [M]+, 322 (12), 296
(78), 268 (73), 236 (42), 134 (42), 107 (27), 88 (78),
62 (100). Found, %: C 60.55; H 4.16; N 16.48.
C17H14N4O2S. Calculated, %: C 60.34; H 4.17; N
16.56. M 338.39.
1
features of Н NMR spectra confirming the formation
of dihydrofuran derivatives signals should be
mentioned corresponding to the methylene unit of the
alkylsulfanyl substituent linked directly to sulfur.
Protons of this group are diastereotopic and appear as a
multiplet built of two doublets of quartets or doublets
of triplets.
2-[5-Amino-2-(thien-2-yl)-4-cyano-2-ethyl-
sulfanyl-2,3-dihydrofuran-3-ylidene]propanedi-
nitrile (3d). Yield 0.267 g (85%), white powder, mp
160–163°C (decomp). IR spectrum, ν, cm–1: 3263
2-(5-Amino-2-phenyl-4-cyano-2-ethylsulfanyl-2,3-
dihydrofuran-3-ylidene)propanedinitrile (3a).
1
A
(NH2), 2206 (C≡N), 1670 (C=C). Н NMR spectrum,
δ, ppm: 1.22 t (3H, CH3, 3J 7.3 Hz), 2.53–2.74 m (2Н,
mixture of 0.246 g (0.001 mol) of 2,2,3,3-tetracyano-
cyclopropyl ketone 1а and 0.168 g (0.002 mol) of
sodium hydrogen carbonate in 2 mL of water was
heated to boiling, and the boiling was continued till a
transparent solution was obtained. The solution was
cooled, 0.062 g (0.001 mol) of ethanethiol was added,
and the mixture was stirred at room temperature to the
completion of the reaction (TLC monitoring).
Afterwards the separated precipitate was filtered off,
washed with water, crystallized from acetic acid, and
dried in air. Yield 0.265 g (86%). White crystalline
powder, temp. decomp. 160–163°С (165–166°С [5]).
3
3
SCH2), 7.12 d.d (1Нarom, J 4.6, J 4.0 Hz), 7.34–7.38
m (1Нarom), 7.76–7.82 m (1Нarom), 10.29 s (2Н, NH2).
13C NMR spectrum, δ, ppm: 14.0, 24.3, 55.4, 70.5,
100.2, 110.8, 113.7, 113.8, 127.2, 128.7, 130.4, 136.3,
167.6, 170.3. Mass spectrum, m/z (Irel, %): 316 (11)
[M + 2]+, 244 (32), 110 (27), 88 (87), 58 (100). Found,
%: C 53.63; H 3.22; N 17.76. C14H10N4OS2.
Calculated, %: C 53.49; H 3.21; N 17.82. M 314.38.
2-[5-Amino-2-(4-bromophenyl)-2-propylsul-
fanyl-4-cyano-2,3-dihydrofuran-3-ylidene]propane-
dinitrile (3e). Yield 0.309 g (77%), white powder, mp
181–184°C (decomp). IR spectrum, ν, cm–1: 3360,
3255, 3155 (NH2), 2216 (C≡N), 1682 (C=C). 1Н NMR
Compounds 3b–3k were synthesized analogously.
2-[5-Amino-2-(4-bromophenyl)-4-cyano-2-ethyl-
sulfanyl-2,3-dihydrofuran-3-ylidene]propanedi-
nitrile (3b). Yield 0.306 g (79%), white powder, mp
155–158°C (decomp). IR spectrum, ν, cm–1: 3260
3
spectrum, δ, ppm: 0.96 t (3H, CH3, J 7.3 Hz), 1.49–
1.67 m (2Н, SCH2CH2), 2.51–2.67 m (2Н, SCH2), 7.52
3
3
d (2Нarom, J 8.7 Hz), 7.70 d (2Нarom, J 8.7 Hz), 10.32
s (2Н, NH2). 13C NMR spectrum, δ, ppm: 13.2, 21.7,
31.1, 54.7, 71.1, 103.3, 110.8, 113.6, 113.9, 124.5,
128.9, 132.2, 132.7, 168.0, 171.0. Mass spectrum, m/z
(Irel, %): 404/402/400 (6.2/9.2/5.3) [M + 2]+ and [M]+,
359 (12), 331 (21), 314 (31), 237 (42), 210 (72), 150
(98), 108 (100). Found, %: C 50.69; H 3.28; N 19.97.
C17H13BrN4OS. Calculated, %: C 50.88; H 3.27; N
13.96. M 401.28.
1
(NH2), 2214 (C≡N), 1683 (C=C). Н NMR spectrum,
δ, ppm: 1.23 t (3H, CH3, 3J 7.4 Hz), 2.53–2.73 m (2Н,
3
3
SCH2), 7.51 d (2Нarom, J 8.6 Hz), 7.70 d (2Нarom, J
8.6 Hz), 10.32 s (2Н, NH2). 13C NMR spectrum, δ,
ppm: 13.9, 23.5, 54.7, 71.1, 103.4, 110.8, 113.6, 113.9,
124.5, 128.9, 132.2, 132.6, 168.0, 171.0. Mass
spectrum, m/z (Irel, %): 388/386 (1/1) [M]+, 236 (9),
183/185 (6/9) [ArCO]+, 157/155 (4.7/4.8) [Ar]+, 62
(100). Found, %: C 49.44; H 2.87; N 14.42.
C16H11BrN4OS. Calculated, %: C 49.63; H 2.86; N
14.47. M 387.26.
2-[5-Amino-2-(4-methoxyphenyl)-2-propylsul-
fanyl-4-cyano-2,3-dihydrofuran-3-ylidene]propane-
dinitrile (3f). Yield 0.278 g (79%), white powder, mp
150–153°C (decomp). IR spectrum, ν, cm–1: 3150
2-[5-Amino-2-(4-methoxyphenyl)-4-cyano-2-
ethylsulfanyl-2,3-dihydrofuran-3-ylidene]propane-
dinitrile (3c). Yield 0.274 g (81%), white powder, mp
162–164°C (decomp). IR spectrum, ν, cm–1: 3165,
3250 (NH2), 2207 (C≡N), 1670 (C=C). 1Н NMR
1
(NH2), 2214 (C≡N), 1652 (C=C). Н NMR spectrum,
δ, ppm: 0.97 t (3H, CH3, 3J 7.3 Hz), 1.53–1.64 m (2Н,
SCH2CH2), 2.49–2.63 m (2Н, SCH2), 3.78 s (3Н,
ОСН3), 6.99–7.04 m (2Нarom), 7.44–7.50 m (2Нarom),
3
13
spectrum, δ, ppm: 1.22 t (3H, CH3, J 7.4 Hz), 2.50–
10.21 s (2Н, NH2). C NMR spectrum, δ, ppm: 13.2,
2.69 m (2Н, SCH2), 3.78 s (3Н, ОСН3), 7.01 d (2Нarom
,
21.7, 31.1, 54.6, 55.2, 70.8, 104.1, 111.0, 113.9, 114.0,
114.5, 125.4, 128.1, 160.8, 168.8, 171.0. Mass spec-
trum, m/z (Irel, %): 354 (31) [M + 2]+, 352 (30) [M]+,
310 (100), 268 (87), 236 (39), 134 (34), 88 (41), 76
(85). Found, %: C 61.12; H 4.59; N 15.96.
3
3J 8.9 Hz), 7.47 d (2Нarom, J 8.9 Hz), 10.21 s (2Н,
NH2). 13C NMR spectrum, δ, ppm: 13.8, 23.5, 54.6,
55.3, 70.8, 104.2, 111.0, 113.8, 113.9, 114.0, 125.3,
128.2, 160.8, 168.7, 171.0. Mass spectrum, m/z (Irel,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 5 2018

ONE-POT SYNTHESIS OF 2-ALKYLSULFANYLDIHYDROFURAN DERIVATIVES
797
C18H16N4O2S. Calculated, %: C 61.35; H 4.58; N
15.90. M 352.41.
2-[5-Amino-2-(para-tolyl)-2-butylsulfanyl-4-
cyano-2,3-dihydrofuran-3-ylidene]propanedinitrile
(3j). Yield 0.280 g (80%), white powder, mp 160–163°C
(decomp). IR spectrum, ν, cm–1: 3166, 3250 (NH2),
2-[5-Amino-2-propylsulfanyl-2-(thien-2-yl)-4-
cyano-2,3-dihydrofuran-3-ylidene]propanedinitrile
(3g). Yield 0.272 g (83%), white powder, mp 137–
140°C (decomp). IR spectrum, ν, cm–1: 3260, 3342
1
2208 (C≡N), 1656 (C=C). Н NMR spectrum, δ, ppm:
0.87 t (3H, CH3, 3J 7.3 Hz), 1.32–1.45 m (2Н,
SCH2CH2CH2), 1.49–1.61 m (2Н, SCH2CH2), 2.32 s
(3Н, СН3), 2.51–2.67 m (2Н, SCH2), 7.29 d (2Нarom, 3J
8.2 Hz), 7.42 d (2Нarom, 3J 8.3 Hz), 10.24 s (2Н, NH2).
13C NMR spectrum, δ, ppm: 13.3, 21.2, 28.6, 32.3, 54.7,
70.8, 104.2, 110.9, 113.8, 113.9, 126.5, 129.1, 130.3,
140.7, 168.6, 171.1. Mass spectrum, m/z (Irel, %): 352
(27) [M + 2]+, 350 (19) [M]+, 335 (6) [M – 15]+, 308
(40) [M – C3H6]+, 293 (11) [M – C4H9]+, 261 (26) [M –
SC4H9]+, 253 (81), 118 (43), 91 (75) [Ar]+, 56 (100).
Found, %: C 64.87; H 5.19; N 15.93. C19H18N4OS.
Calculated, %: C 65.12; H 5.18; N 15.99. M 350.44.
1
(NH2), 2209, 2212 (C≡N), 1673 (C=C). Н NMR
3
spectrum, δ, ppm: 0.96 t (3H, CH3, J 7.3Hz), 1.52–
1.63 m (2Н, SCH2CH2), 2.52–2.67 m (2Н, SCH2), 7.12
3
4
3
d.d (1Нarom, J 5.0, J 3.8 Hz), 7.36 d.d (1Нarom, J 3.7,
4J 1.0 Hz), 7.79 d.d (1Нarom, J 5.1, 4J 1.0 Hz), 10.28 s
3
(2Н, NH2). 13C NMR spectrum, δ, ppm: 13.2, 21.7,
31.8, 55.4, 70.5, 100.1, 110.8, 113.7, 113.8, 127.2,
128.7, 130.4, 136.2, 167.6, 170.3. Mass spectrum, m/z
(Irel, %): 330 (4) [M]+, 287 (3), 245 (5), 111 (19) [Ar]+,
88 (96), 58 (100). Found, %: C 55.01; H 3.69; N
17.11. C15H12N4OS2. Calculated, %: C 54.86; H 3.68;
N 17.06. M 328.41.
2-[5-Amino-2-butylsulfanyl-2-(para-tolyl)-4-
cyano-2,3-dihydrofuran-3-ylidene]propanedinitrile
(3k). Yield 0.277 g (81%), white powder, mp 144–
146°C (decomp). IR spectrum, ν, cm–1: 3116 (NH2),
2-(5-Amino-2-mеthyl-2-propylsulfanyl-4-cyano-
2,3-dihydrofuran-3-ylidene)propanedinitrile (3h).
Yield 0.164 g (63%), white powder, mp 215–218°C
(decomp). IR spectrum, ν, cm–1: 3137, 3273, 3368
1
2210 (C≡N), 1673 (C=C). Н NMR spectrum, δ, ppm:
0.87 t (3H, CH3, 3J 7.3 Hz), 1.31–1.44 m (2Н,
SCH2CH2CH2), 1.48–1.60 m (2Н, SCH2CH2), 2.55–
2.69 m (2Н, SCH2), 7.12 d.d (1Нarom, 3J 5.0, 3J 3.8 Hz),
7.39 d.d (1Нarom, 3J 3.7, 4J 1.1 Hz), 7.79 d.d (1Нarom, 3J
5.1, 4J 1.1 Hz), 10.28 s (2Н, NH2). 13C NMR spectrum,
δ, ppm: 13.3, 21.2, 29.5, 30.2, 55.4, 70.5, 100.1, 110.8,
113.7, 113.8, 127.2, 128.6, 130.3, 136.2, 167.8, 170.3.
Mass spectrum, m/z (Irel, %): 344 (7) [M]+, 302 (8), 245
(17), 185 (9), 111 (16) [Ar]+, 57 (100). Found, %: C
56.34; H 4.13; N 16.30. C16H14N4OS2. Calculated, %:
C 56.12; H 4.12; N 16.36. M 342.44.
1
(NH2), 2210, 2215 (C≡N), 1688 (C=C). Н NMR
spectrum, δ, ppm: 0.91 t (3H, CH3, 3J 7.3 Hz), 1.42–
1.54 m (2Н, SCH2CH2), 1.92 s (3Н, СН3), 2.36–2.54
13
m (SCH2 + DMSO-d6), 10.12 s (2Н, NH2). C NMR
spectrum, δ, ppm: 13.1, 21.9, 24.2, 30.9, 52.4, 70.3,
101.1, 111.1, 113.8, 114.6, 170.1, 171.2. Mass
spectrum, m/z (Irel, %): 260 (31) [M]+, 217 (12), 201
(12), 185 (100), 75 (23). Found, %: C 55.16; H 4.66; N
21.44. C12H12N4OS. Calculated, %: C 55.37; H 4.65; N
21.52. M 260.32.
2-[5-Amino-2-(4-bromophenyl)-2-butylsulfanyl-
4-cyano-2,3-dihydrofuran-3-ylidene]propanedi-
nitrile (3i). Yield 0.316 g (76%), white powder, mp
179–181°C (decomp). IR spectrum, ν, cm–1: 3113,
3255 (NH2), 2218 (C≡N), 1680 (C=C). 1Н NMR spec-
trum, δ, ppm: 0.87 t (3H, CH3, 3J 7.3 Hz), 1.32–1.47 m
(2Н, SCH2CH2CH2), 1.47–1.63 m (2Н, SCH2CH2),
IR spectra were recorded on a Fourier spectrophoto-
meter FSM-1202 from thin film (mull in mineral oil).
13
1Н and С NMR spectra were registered on a spectro-
meter Agilent DDR2 400 at operating frequencies 400
and 101 MHz respectively, internal reference TMS.
Mass spectra were taken on an instrument Shimadzu
GCMS-QP 2010 SE (EI, 70 eV). Elemental analysis
was carried out on a CHN-analyzer vario Micro cube.
The homogeneity of compounds obtained was checked
by TLC on plates Sorbfil PTCKh-AF-А-UF, develop-
ment under UV irradiation and at heating.
3
2.52–2.70 m (2Н, SCH2), 7.52 d (2Нarom, J 8.7 Hz),
3
7.69 d (2Нarom, J 8.7 Hz), 10.32 s (2Н, NH2). 13C
NMR spectrum, δ, ppm: 13.3, 21.2, 28.8, 30.3, 54.7,
71.1, 103.3, 110.8, 113.6, 113.9, 124.5, 128.7, 132.2,
132.7, 168.0, 171.0. Mass spectrum, m/z (Irel, %):
418/416 (2.2/3.6) [M + 2]+, 374 (9), 237 (7), 211 (12),
57 (100). Found, %: C 52.26; H 3.65; N 19.17.
C18H15BrN4OS. Calculated, %: C 52.06; H 3.64; N
13.49. M 415.31.
ACKNOWLEDGMENTS
The study was performed under the financial
support of the scholarship of the President of the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 5 2018

GRIGOR’EV et al.
798
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 5 2018