Synthesis and alkylation of 1-substituted 3-thioxo-2,3,5,6,7,8- hexahydroisoquinoline-4-carbonitriles

Article abstract of DOI:10.1134/S1070428012120081

The condensation of cyclohexylidene(cyano)thioacetamides with aldehydes or of 2-acyl-1-(morpholin-4-yl)cycloalkenes with dithiomalonamide gave 1-alkyl(aryl)-3-thioxo-2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitriles. Reactions of the latter with various a

Full text of DOI:10.1134/S1070428012120081

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 12, pp. 1544–1549. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © I.V. Dyachenko, M.V. Vovk, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 12, pp. 1573–1578.
Synthesis and Alkylation of 1-Substituted
3-Thioxo-2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitriles
I. V. Dyachenkoa and M. V. Vovkb
a Taras Shevchenko Lugansk National University. ul. Oboronnaya 2, Lugansk, 91011 Ukraine
e-mail: ivladya87@e-mail.ua
b Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 5, Kiev, 02660 Ukraine
Received May 30, 2012
Abstract—The condensation of cyclohexylidene(cyano)thioacetamides with aldehydes or of 2-acyl-1-(mor-
pholin-4-yl)cycloalkenes with dithiomalonamide gave 1-alkyl(aryl)-3-thioxo-2,3,5,6,7,8-hexahydroisoquino-
line-4-carbonitriles. Reactions of the latter with various alkylating agents selectively produced the correspond-
ing isoquinolin-3-yl sulfides or products of their subsequent Thorpe cyclization, thieno[2,3-c]isoquinolines.
DOI: 10.1134/S1070428012120081
Some 3-thioxo-2,3,5,6,7,8-hexahydroisoquinoline-
4-carbonitriles were found to exhibit cardiotonic [1],
anticonvulsant [2], antimicrobial [3], antitumor [4],
fungicidal [5], and bactericidal [6] properties, as well
as to inhibit HIV-1 reverse transcriptase [7]. These
compounds are generally synthesized by Michael addi-
tion of cyanothioacetamide to 1-acylcycloalkenes [8],
recyclization of carbo[c]-annulated 2-aminothiopyran-
3-carbonitriles [9], reaction of cycloalkylidenemalono-
nitriles with aryl(hetaryl)methylidene(cyano)thioacet-
amides [10], or condensation of 1-acylcycloalkanones
with cyanothioacetamide [11].
The present study was aimed at developing new
methods for the synthesis of 1-substituted 3-thioxo-
2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitriles. The
first of these (Scheme 1, path a) implies condensation
of cyclohexylidene(cyano)thioacetamides Ia and Ib
with aldehydes IIa–IId in boiling anhydrous ethanol in
Scheme 1.
CN
CN
CN
R'CHO (IIa–IId)
R
S
R
S
R
S
a
–2[H]
NH2
NH2
NH
R'
R'
Ia, Ib
A
Va–Vf
–H2S
S
S
R
R
S
NH2
H2N
NH2
NH2
R
S
IV
b
–H2O
N
S
NH
O
R'
O
R'
O
H2N
S
R'
IIIa–IIIf
B
C
I, R = H (a), Me (b); II, R′ = Me (a), i-Pr (b), Ph (c), 4-BrC6H4 (d); III, V, R = H, R′ = Me (a), i-Pr (b), Ph (c), 4-BrC6H4 (d);
R = Me, R′ = Me (e), Ph (f).
1544

SYNTHESIS AND ALKYLATION OF 1-SUBSTITUTED 3-THIOXO-2,3,5,6,7,8-...
1545
Scheme 2.
CN
CN
Ph
Br
CN
(X)
S
CN
Ph
N
CN
CN
Ph
Me
S
XI
CH2=CHCN (VI)
CN
N
CN
R
S
X
XCH2Hlg (XIIb, XIId, XIIe)
KOH
VII
Va–Vc
Ve, Vf
N
O
CN
O
R'
(VIII)
Br
Me
S
XIIIa–XIIId
N
R
H2N
X
Ph
XIIa, XIIc, KOH
IX
S
N
R'
XIVa–XIVc
XII, Hlg = Cl, X = CN (a), PhCH2OC(O) (b); Hlg = Br, X = PhC(O) (c), 3,4-(HO)2C6H3C(O) (d), 2-oxo-2H-chromen-3-ylcarbonyl
(e); XIII, R = H, R′ = i-Pr, X = 3,4-(HO)2C6H3C(O) (a), 2-oxo-2H-chromen-3-ylcarbonyl (b); R′ = Ph, X = PhCH2OC(O) (c),
3,4-(HO)2C6H3C(O) (d); XIV, R = H, R′ = i-Pr, X = CN (a); R′ = Ph, X = PhC(O) (b); R = R′ = Me, X = CN (c).
the presence of sodium ethoxide, and the second
procedure (path b) is based on nucleophilic vinylic
substitution in 2-acyl-1-(morpholin-4-yl)cycloalkenes
IIIa–IIIh by dithiomalonamide (IV) at room tempera-
ture in anhydrous ethanol in the presence of sodium
ethoxide. According to path a, initially formed Knoe-
venagel condensation products A undergo intramolec-
ular cyclization (aza-Michael reaction) with elimina-
tion of hydrogen to form 1-substituted 3-thioxo-
2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitriles Va–
Vf. The closest analogs of compounds V, substituted
2-thioxo(selenoxo)-1,2,3,4,5,6,7,8-octahydroquino-
lines, are also known to readily undergo dehydration
under mild conditions [12]. Path b is most likely to
involve initial formation of nucleophilic vinylic substi-
tution products B whose intramolecular dehydration
leads to isoquinolines C. The latter lose hydrogen
sulfide from the thiocarbamoyl group, yielding nitriles
Va–Vf.
group at δC 112–114 ppm and pyridine ring, δC, ppm:
151–156 (C1), 173–175 (C3), and 119–121 (C4).
The presence in molecules V of a nucleophilic
thiolactam fragment makes them liable to further mod-
ifications with various alkylating agents. The reaction
of isoquinolinethione Vc with acrylonitrile (VІ) in
boiling ethanol in the presence of triethylamine afford-
ed 3-cyanoethylsulfanyl derivative VII (Scheme 2). By
alkylation of Vf with 2-bromocyclohexanone (VIIІ)
and of Va with 2-(2-bromo-1-phenylethylidene)-
malononitrile (X) in DMF at 20°C in alkaline medium
we obtained the corresponding sulfides ІX and XI.
Compounds Vb and Ve reacted under analogous con-
ditions with chloroacetonitrile (XIIa), benzyl chloro-
acetate (XIIb), and bromomethyl ketones XIIc–XIIe.
However, the corresponding sulfides XIIIa–XIIId
were isolated only in the reactions with XIIb, XIId,
and XIIe. Sulfides XIII formed in reactions with
chloroacetonitrile (XIIa) and bromoacetophenone
(XIIc) readily underwent intramolecular Thorpe cy-
clization to give substituted 1-amino-6,7,8,9-tetrahy-
drothieno[2,3-c]isoquinolines XIVa–XIVc.
The structure of isoquinolinecarbonitriles Va–Vf
was confirmed by their spectral parameters. The most
characteristic absorption band in their IR spectra was
that belonging to C≡N stretching vibrations in the
The IR spectra of S-alkylation products VII, IX,
XI, and XIIIa–XIIId contained an absorption band at
2214–2228 cm–1 due to stretching vibrations of the
13
region 2213–2222 cm–1. The C NMR spectra of Vb–
Ve contained signals from carbon atoms in the cyano
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012

DYACHENKO, VOVK
1546
1
conjugated cyano group. In the H NMR spectra of
these compounds we observed singlets from protons in
the SCH2 group at δ 4.35–5.04 ppm, which is typical
of 2-alkylsulfanyltetrahydroquinolines [13]. Tetrahy-
drothieno[2,3-c]isoquinolines XIVa–XIVc displayed
in the IR spectra absorption bands belonging to stretch-
ing (3195–3412 cm–1) and bending vibrations (1642–
1648 cm–1) of the primary amino group. The latter
stand for 48 h. The precipitate was filtered off, washed
with water and ethanol, dried, and recrystallized from
glacial acetic acid.
1-Methyl-3-thioxo-2,3,5,6,7,8-hexahydroiso-
quinoline-4-carbonitrile (Va). Yield 1.53 g (75%) (a),
1.14 g (56%) (b); yellow powder, mp 290–292°C;
13
published data [15]: mp 292–294°C. C NMR spec-
trum, δC, ppm: 16.64, 20.62, 21.03, 23.55, 28.70,
112.69, 113.90, 115.98, 151.73, 155.76, 173.85. Mass
spectrum: m/z 205 (Irel 100%) [M + 1]+. Calculated:
M 204.296.
1
gave rise to a broadened singlet in the H NMR spec-
trum at δ 6.14–8.20 ppm.
EXPERIMENTAL
1-Isopropyl-3-thioxo-2,3,5,6,7,8-hexahydroiso-
quinoline-4-carbonitrile (Vb). Yield 1.58 g (68%)
(a), 1.49 g (64%) (b); yellow powder, mp 260–262°C.
IR spectrum, ν, cm–1: 3382 (NH), 2219 (C≡N), 1212
(C=S). 1H NMR spectrum, δ, ppm: 1.31 d (6H, Me, J =
6.8 Hz), 1.32–1.42 m (4H, CH2), 2.56 m (2H, CH2),
2.79 m (2H, CH2), 3.27 m (1H, CH), 12.71 br.s (1H,
NH). 13C NMR spectrum, δC, ppm: 19.11, 20.43,
20.63, 21.36, 23.52, 28.07, 29.19, 113.76, 115.92,
119.76, 156.74, 158.84, 174.94. Mass spectrum:
m/z 233 (Irel 100%) [M + 1]+. Found, %: C 67.04;
H 6.82; N 11.98. C13H16N2S. Calculated, %: C 67.20;
H 6.94; N 12.06. M 232.350.
The IR spectra were recorded in KBr on a Perkin
Elmer Spectrum One FTIR spectrometer. The 1H NMR
spectra were measured on a Bruker DR-500 instrument
at 500.13 MHz from solutions in DMSO-d6 containing
tetramethylsilane as internal reference. The 13C NMR
spectra were obtained on a Varian VXR-300 spectrom-
eter at 125.74 MHz using DMSO-d6 as solvent and
tetramethylsilane as internal reference. The mass spec-
tra were recorded on an HP 5890/5972 GC–MS system
(HP-5 MS column; electron impact, 70 eV). The melt-
ing points were determined on a Kofler hot stage. The
progress of reactions and the purity of products were
monitored by TLC on Silufol UV-254 plates using
acetone–hexane (3:5) as eluent; spots were visualized
by treatment with iodine vapor or under UV light.
1-Phenyl-3-thioxo-2,3,5,6,7,8-hexahydroiso-
quinoline-4-carbonitrile (Vc). Yield 1.84 g (69%) (a),
1.81 g (68%) (b); yellow powder, mp 248–250°C
(sublimes at 195°C to form cubic crystals); published
data [16]: mp 259–262°C. IR spectrum, ν, cm–1: 3348
(NH), 2222 (C≡N), 1195 (C=S). 1H NMR spectrum, δ,
ppm: 1.58–1.65 m (2H, CH2), 1.75–1.84 m (2H, CH2),
2.32 t (2H, CH2, J = 4.5 Hz), 2.87 t (2H, CH2, J =
6.0 Hz), 7.42 d (2H, Ph, J = 7.0 Hz), 7.51–7.56 m (3H,
Ph), 13.94 br.s (1H, NH). 13C NMR spectrum, δC, ppm:
20.65, 20.90, 25.19, 28.86, 114.85, 115.84, 121.10,
128.22, 128.83, 129.95, 131.45, 151.24, 156.69,
174.74. Mass spectrum: m/z 267 (Irel 100%) [M + 1]+.
Found, %: C 71.98; H 5.22; N 10.39. C16H14N2S. Cal-
culated, %: C 72.15; H 5.30; N 10.52. M 266.365.
Cyclohexylidene(cyano)thioacetamides Іa and Ib
were synthesized according to the procedure described
in [14].
1-Substituted 3-thioxo-2,3,5,6,7,8-hexahydroiso-
quinoline-4-carbonitriles Va–Vf (general procedure).
a. A solution of 0.23 g (10 mmol) of metallic sodium
in 10 ml of anhydrous ethanol was added to a mixture
of 10 mmol of cycloalkylidene(cyano)thioacetamide Іa
or Ib and 10 mmol of aldehyde ІІa–IId in 15 ml of
anhydrous ethanol. The mixture was heated for 2 h
under reflux and was left to stand for 24 h. It was then
treated with 10% hydrochloric acid to pH 5 and was
left to stand for 48 h. The precipitate was filtered off,
washed with water and ethanol, dried, and recrystal-
lized from glacial acetic acid.
1-(4-Bromophenyl)-3-thioxo-2,3,5,6,7,8-hexahy-
droisoquinoline-4-carbonitrile (Vd). Yield 2.52 g
(73%) (a), 2.24 g (65%) (b); yellow powder, mp 285–
288°C. IR spectrum, ν, cm–1: 3334 (NH), 2220 (C≡N).
1H NMR spectrum, δ, ppm: 1.53–1.59 m (2H, CH2),
1.61–1.72 m (2H, CH2), 2.08 t (2H, CH2, J = 6.5 Hz),
2.79 t (2H, CH2, J = 6.4 Hz), 7.33 d and 7.75 d (2H
each, BrC6H4, J = 7.52 Hz), 14.02 br.s (1H, NH).
13C NMR spectrum, δC, ppm: 20.82, 21.78, 25.72,
27.71, 114.29, 116.71, 120.74, 123.29, 130.26, 132.27,
134.79, 153.07, 157.03, 175.90. Mass spectrum:
b. A solution of 0.23 g (10 mmol) of metallic so-
dium in 10 ml of anhydrous ethanol was added under
stirring at 20°C to a mixture of 10 mmol of enamino
ketone ІІІa–IIIf and 1.34 g (10 mmol) of propanebis-
(thioamide) (ІV) in 15 ml of anhydrous ethanol. The
mixture was stirred for 4 h, left to stand for 24 h,
treated with 10% hydrochloric acid to pH 5, and left to
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SYNTHESIS AND ALKYLATION OF 1-SUBSTITUTED 3-THIOXO-2,3,5,6,7,8-...
1547
m/z 345 (Irel 100%) [M + 1]+. Found, %: C 55.49;
H 3.71; N 8.02. C16H13BrN2S. Calculated, %: C 55.66;
H 3.79; N 8.11. M 345.261.
in 15 ml of DMF, 5.6 ml (10 mmol) of 10% aqueous
KOH and 1.8 g (10 mmol) of 2-bromocyclohexanone
(VІІІ) were added in succession under stirring at 20°C,
and the mixture was stirred for 2 h and left to stand for
24 h. The mixture was then diluted with an equal
volume of water and left to stand for 48 h, and the
precipitate was filtered off, washed with water and
ethanol, dried, and recrystallized from glacial acetic
acid. Yield 2.6 g (69%), white powder, mp 150–152°C
(from AcOH). IR spectrum, ν, cm–1: 2222 (C≡N), 1695
1,6-Dimethyl-3-thioxo-2,3,5,6,7,8-hexahydroiso-
quinoline-4-carbonitrile (Ve). Yield 1.56 g (71%) (a),
1.53 g (70%) (b); yellow powder, mp 230–232°C. IR
1
spectrum, ν, cm–1: 3318 (NH), 2214 (C≡N). H NMR
spectrum, δ, ppm: 1.01 d (3H, Me, J = 6.6 Hz), 1.14–
1.26 m (1H, 6-H), 1.53–1.82 m (2H, CH2), 2.68 s (3H,
Me), 2.72–2.93 m (4H, CH2), 13.70 br.s (1H, NH).
13C NMR spectrum, δC, ppm: 16.78, 20.98, 23.51,
26.74, 29.09, 36.72, 112.61, 116.04, 120.91, 151.74,
155.52, 173.99. Mass spectrum: m/z 219 (Irel 100%)
[M + 1]+. Found, %: C 65.95; H 6.33; N 12.71.
C12H14N2S. Calculated, %: C 66.02; H 6.46; N 12.83.
M 218.323.
1
(C=O). H NMR spectrum, δ, ppm: 1.07 d (3H, Me,
J = 6.7 Hz), 1.19–1.28 m (1H, 6-H), 1.47–2.01 m (8H,
CH2), 2.28–2.46 m (2H, CH2), 2.58–2.79 m (2H, CH2),
2.84–3.07 m (2H, CH2), 4.69 m (1H, SCH), 7.26–
13
7.64 m (5H, Ph). C NMR spectrum, δC, ppm: 21.71,
25.09, 27.27, 27.71, 36.75, 39.56, 39.72, 40.39, 41.75,
54.08, 105.49, 115.26, 127.23, 128.77, 129.34, 129.44,
139.11, 152.52, 157.07, 160.11, 205.43. Mass spec-
trum: m/z 377 (Irel 100%) [M + 1]+. Found, %: C 73.28;
H 6.30; N 7.35. C23H24N2OS. Calculated, %: C 73.37;
H 6.42; N 7.44. M 376.523.
6-Methyl-1-phenyl-3-thioxo-2,3,5,6,7,8-hexahy-
droisoquinoline-4-carbonitrile (Vf). Yield 1.9 g
(68%) (a), 2.16 g (77%) (b); yellow powder, mp 223–
225°C. IR spectrum, ν, cm–1: 2922 (NH), 2219 (C≡N),
1
1225 (C=S). H NMR spectrum, δ, ppm: 0.72–1.19 m
Compounds XI, XIIIa–XIIId, and XIVa–XIVc
were synthesized in a similar way.
(4H, Me, 6-H), 1.26–1.99 m (4H, CH2), 2.33–3.11 m
(2H, CH2), 7.14–7.85 m (5H, Ph), 13.99 br.s (1H, NH).
Mass spectrum: m/z 281 (Irel 100%) [M + 1]+. Found,
%: C 72.70; H 5.69; N 9.80. C17H16N2S. Calculated,
%: C 72.82; H 5.75; N 9.99. M 280.395.
2-[2-(4-Cyano-1-methyl-5,6,7,8-tetrahydroiso-
quinolin-3-ylsulfanyl)-1-phenylethylidene]malono-
nitrile (XI) was synthesized from 2.04 g (10 mmol) of
compound Va and 2.5 g (10 mmol) of 2-(2-bromo-
methyl-1-phenylethylidene)malononitrile (X). Yield
2.52 g (68%), green powder fluorescing under UV
irradiation, mp 141–143°C (from AcOH). IR spectrum,
3-(2-Cyanoethylsulfanyl)-1-phenyl-5,6,7,8-tetra-
hydroisoquinoline-4-carbonitrile (VІІ). Three drops
of triethylamine were added to a mixture of 2.7 g
(10 mmol) of isoquinoline Vc and 0.7 ml (10 mmol) of
acrylonitrile (VІ) in 20 ml of anhydrous ethanol, and
the mixture was heated for 3 h under reflux and left to
stand for 24 h. The precipitate was filtered off and
recrystallized from ethanol. Yield 2.42 g (76%), color-
less crystals fluorescing under UV irradiation,
mp 122–123°C. IR spectrum, ν, cm–1: 2253, 2215
1
ν, cm–1: 2213, 2207 (C≡N). H NMR spectrum, δ,
ppm: 1.56–1.72 m (4H, CH2), 2.11 s (3H, Me), 2.54–
2.66 m (2H, CH2), 2.71–2.82 m (2H, CH2), 4.78 s (2H,
SCH2), 7.56 t (2H, Ph, J = 7.6 Hz), 7.66 t (1H, Ph, J =
7.6 Hz), 8.06 d (2H, Ph, J = 7.2 Hz). Mass spectrum:
m/z 371 (Irel 100%) [M + 1]+. Found, %: C 71.19;
H 4.82; N 15.01. C22H18N4S. Calculated, %: C 71.32;
H 4.90; N 15.12. M 370.479.
1
(C≡N). H NMR spectrum, δ, ppm: 1.55–1.72 m (2H,
CH2), 1.74–1.86 m (2H, CH2), 2.65 t (2H, CH2, J =
5.41 Hz), 2.93 t (2H, CH2, J = 6.0 Hz), 2.98 t (2H,
CH2CN, J = 6.4 Hz), 3.49 t (2H, SCH2, J = 6.4 Hz),
Compounds XIIIa–XIIId were synthesized from
isoquinolinethiones Vb and Vc and alkyl halides XIIb,
XIId, and XIIe.
13
7.44–7.63 m (5H, Ph). C NMR spectrum, δC, ppm:
17.82, 20.80, 21.78, 24.99, 26.80, 28.00, 105.38,
114.60, 119.09, 127.67, 128.12, 128.84, 128.91,
138.54, 152.43, 155.95, 160.25. Mass spectrum:
m/z 320 (Irel, 100%) [M + 1]+. Found, %: C 71.38;
H 5.21; N 13.02. C19H17N3S. Calculated, %: C 71.44;
H 5.36; N 13.16. M 319.431.
3-[2-(3,4-Dihydroxyphenyl)-2-oxoethylsulfanyl]-
1-isopropyl-5,6,7,8-tetrahydroisoquinoline-4-carbo-
nitrile (XIIІa). Yield 3.4 g (89%), dark crystals,
mp 187–189°C (from BuOH). IR spectrum, ν, cm–1:
1
3440 (OH), 2225 (C≡N), 1688 (C=O). H NMR spec-
trum, δ, ppm: 0.94 d (6H, Me, J = 4.1 Hz), 1.54–
1.78 m (4H, CH2), 2.55 m (2H, CH2), 2.80 m (2H,
CH2), 3.02–3.19 m (1H, CH), 4.77 s (2H, SCH2),
6.86 d (1H, Harom, J = 8.0 Hz), 7.42 s (1H, Harom),
6-Methyl-3-(2-oxocyclohexylsulfanyl)-1-phenyl-
5,6,7,8-tetrahydroisoquinoline-4-carbonitrile (ІX).
Isoquinolinethione Vf, 2.8 g (10 mmol), was dissolved
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012

DYACHENKO, VOVK
1548
7.50 d (1H, Harom, J = 8.0 Hz), 9.57 br.s (2H, OH).
13C NMR spectrum, δC, ppm: 21.23, 21.36, 22.24,
24.35, 28.59, 30.91, 37.23, 104.05, 115.50, 115.59,
115.63, 122.09, 126.31, 128.26, 145.75, 151.28,
151.44, 156.86, 168.11, 191.23. Mass spectrum: m/z
383 (Irel 100%) [M + 1]+. Found, %: C 65.84; H 5.74;
N 7.19. C21H22N2O3S. Calculated, %: C 65.95; H 5.80;
N 7.32. M 382.484.
8.0 Hz), 7.35 t (2H, Harom, J = 7.2 Hz), 7.36 m (4H,
arom), 7.43 d (1H, Harom, J = 8.4 Hz), 9.48 br.s (2H,
H
OH). 13C NMR spectrum, δC, ppm: 20.87, 21.87,
26.89, 28.00, 36.65, 104.70, 114.91, 115.04, 115.09,
121.81, 127.19, 127.76, 127.81, 128.80, 129.01,
138.17, 145.24, 151.00, 152.17, 156.73, 159.66,
191.27. Mass spectrum: m/z 417 (Irel 100%) [M + 1]+.
Found, %: C 69.04; H 4.70; N 6.68. C24H20N2O3S.
Calculated, %: C 69.21; H 4.84; N 6.73. M 416.502.
1-Isopropyl-3-[2-oxo-2-(2-oxo-2H-chromen-
3-yl)ethylsulfanyl]-5,6,7,8-tetrahydroisoquinoline-
4-carbonitrile (XIIІb). Yield 2.97 g (71%), white
powder, mp 161–162°C (from BuOH). IR spectrum, ν,
Compounds XIVa–XIVc were synthesized from
isoquinolinethiones Vb, Vc, and Ve and alkylating
agents XIIa and XIIc.
1
cm–1: 2216 (C≡N), 1711, 1690 (C=O). H NMR spec-
1-Amino-5-isopropyl-6,7,8,9-tetrahydrothieno-
[2,3-c]isoquinoline-2-carbonitrile (XIVa). Yield 2.1 g
(77%), white powder fluorescing under UV irradiation,
mp 198–201°C (from BuOH). IR spectrum, ν, cm–1:
3214, 3335, 3411 (NH2), 2211 (C≡N), 1648 (δNH2).
1H NMR spectrum, δ, ppm: 1.17 d (6H, Me, J =
7.9 Hz), 1.67–1.82 m (4H, CH2), 2.68–2.81 m (2H,
CH2), 3.21–3.32 m (2H, CH2), 3.36 m (1H, CHMe2),
6.39 br.s (2H, NH2). 13C NMR spectrum, δC, ppm:
21.55, 21.99, 22.06, 25.45, 27.10, 30.83, 73.39,
116.42, 121.21, 126.57, 144.75, 152.60, 157.89,
167.17. Mass spectrum: m/z 272 (Irel 100%) [M + 1]+.
Found, %: C 66.31; H 6.28; N 15.33. C15H17N3S.
Calculated, %: C 66.39; H 6.31; N 15.48. M 271.386.
trum, δ, ppm: 1.02 d (6H, Me, J = 7.87 Hz), 1.58–
1.82 m (4H, CH2), 2.63 m (2H, CH2), 2.78 m (2H,
CH2), 3.08–3.22 m (1H, CHMe2), 4.88 s (2H, SCH2),
7.44 t (1H, Harom, J = 8.1 Hz), 7.40 d (1H, Harom, J =
8.1 Hz), 7.78 t (1H, Harom, J = 8.0 Hz), 7.98 d (1H,
13
Harom, J = 8.04 Hz), 8.75 s (1H, 4′-H). C NMR spec-
trum, δC, ppm: 21.19, 21.42, 22.20, 24.35, 28.58,
30.99, 104.22, 115.41, 116.67, 118.51, 123.79, 125.62,
126.59, 131.40, 135.43, 148.86, 151.42, 155.13,
156.51, 158.98, 168.16, 190.97. Mass spectrum:
m/z 419 (Irel 100%) [M + 1]+. Found, %: C 68.72;
H 5.18; N 6.45. C24H22N2O3S. Calculated, %: C 68.88;
H 5.30; N 6.69. M 418.518.
Benzyl 2-(4-cyano-1-phenyl-5,6,7,8-tetrahydro-
isoquinolin-3-ylsulfanyl)acetate (XIIІc). Yield 3.52 g
(85%), colorless crystals fluorescing under UV irradia-
tion, mp 99–101°C (from BuOH). IR spectrum, ν,
cm–1: 2220 (C≡N), 1714 (C=O). 1H NMR spectrum, δ,
ppm: 1.63 m (2H, CH2), 1.79 m (2H, CH2), 2.63 t (2H,
CH2, J = 6.0 Hz), 2.91 t (2H, CH2, J = 6.4 Hz), 4.16 s
(2H, OCH2), 5.04 s (2H, SCH2), 7.14–7.21 m (2H, Ph),
7.24–7.31 m (3H, Ph), 7.36–7.59 m (5H, Ph).
13C NMR spectrum, δC, ppm: 20.80, 21.79, 26.80,
27.96, 31.89, 66.41, 104.85, 114.63, 114.64, 127.52,
127.79, 127.95, 128.00, 128.25, 128.83, 128.87,
135.54, 138.33, 152.22, 156.12, 159.96, 168.43. Mass
spectrum: m/z 415 (Irel 100%) [M + 1]+. Found, %:
C 72.30; H 5.22; N 6.69. C25H22N2O2S. Calculated, %:
C 72.44; H 5.35; N 6.76. M 414.530.
(1-Amino-5-phenyl-6,7,8,9-tetrahydrothieno-
[2,3-c]isoquinolin-2-yl)(phenyl)methanone (XIVb).
Yield 3.23 g (84%), yellow lustrous crystals, mp 186–
188°C (from AcOH). IR spectrum, ν, cm–1: 3211,
3345, 3412 (NH2), 1698 (C=O), 1642 (δNH2). 1H NMR
spectrum, δ, ppm: 1.61–1.72 m (2H, CH2), 2.82–
2.93 m (2H, CH2), 2.64 t (2H, CH2, J = 7.92 Hz),
3.41 t (2H, CH2, J = 7.88 Hz), 7.43–7.58 m (8H,
H
arom), 7.74 d (2H, Harom, J = 8.1 Hz), 8.20 br.s (2H,
NH2). Mass spectrum, m/z 385 (Irel 100%) [M + 1]+.
Found, %: C 74.88; H 5.13; N 7.15. C24H20N2OS.
Calculated, %: C 74.97; H 5.24; N 7.29. M 384.503.
1-Amino-5,8-dimethyl-6,7,8,9-tetrahydrothieno-
[2,3-c]isoquinoline-2-carbonitrile (XIVc). Yield 2.0 g
(80%), colorless crystals fluorescing under UV irradia-
tion, mp 253–255°C (from AcOH); sublimes at 180°C.
IR spectrum, ν, cm–1: 3195, 3211, 3344 (NH2), 2210
3-[2-(3,4-Dihydroxyphenyl)-2-oxoethylsulfanyl]-
1-phenyl-5,6,7,8-tetrahydroisoquinoline-4-carbo-
nitrile (XIIІd). Yield 2.9 g (70%), brown crystals,
mp 155–158°C (from BuOH). IR spectrum, ν, cm–1:
1
(C≡N), 1647 (δNH2). H NMR spectrum, δ, ppm:
1.09 d (3H, Me, J = 6.4 Hz), 1.21–1.42 m (1H, 8-H),
1.63–1.92 m (2H, CH2), 2.42 s (3H, Me), 2.57–2.72 m
(2H, CH2), 3.18–3.36 m (2H, CH2), 6.14 br.s (2H,
NH2). 13C NMR spectrum, δC, ppm: 28.96, 30.06,
32.95, 34.48, 36.47, 40.86, 76.51, 116.63, 120.92,
126.82, 141.86, 150.11, 154.65, 156.60. Mass spec-
1
3410 (OH), 2226 (C≡N), 1675 (C=O). H NMR spec-
trum, δ, ppm: 1.62 m (2H, CH2), 1.79 m (2H, CH2),
2.63 t (2H, CH2, J = 5.6 Hz), 2.92 t (2H, CH2, J =
6.0 Hz), 4.73 s (2H, SCH2), 6.78 d (1H, Harom, J =
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012

SYNTHESIS AND ALKYLATION OF 1-SUBSTITUTED 3-THIOXO-2,3,5,6,7,8-...
1549
trum: m/z 258 (Irel 100%) [M + 1]+. Found, %: C 65.25;
H 5.77; N 16.22. C14H15N3S. Calculated, %: C 65.34;
H 5.87; N 16.33. M 257.360.
9. Gewald, K., Buchwelder, M., and Peukert, M., J. Prakt.
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p. 477; Elgemeie, G.H., Alnaimi, I.S., and Gawad, M.A.,
J. Chem. Res., Synop., 1995, p. 48; Elgemeie, G.H. and
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