Synthesis of (2-methylquinolin-4-ylsulfanyl)-substituted acetic and propionic acids and propionitriles

Article abstract of DOI:10.1134/S1070428010040226

A procedure has been developed for the synthesis of (2-methylquinolin-4- ylsulfanyl)-substituted acetic and propionic acids and propionitriles having methyl, methoxy, or carboxy groups or halogen atom in position 6 or 8 of the quinoline ring via reactions of the corresponding substituted 2-methylquinoline-4-thiols with chloroacetic or acrylic acid and acrylonitrile.

Full text of DOI:10.1134/S1070428010040226

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 4, pp. 571–576. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © A.A. Avetisyan, I.L. Aleksanyan, V.G. Durgaryan, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 4,
pp. 579–583.
Synthesis of (2-Methylquinolin-4-ylsulfanyl)-Substituted
Acetic and Propionic Acids and Propionitriles
A. A. Avetisyan†, I. L. Aleksanyan, and V. G. Durgaryan
Erevan State University, ul. Aleka Manukyana 1, Erevan, 375025 Armenia
e-mail: organkim@sun.ysu.am
Received March 17, 2009
Abstract—A procedure has been developed for the synthesis of (2-methylquinolin-4-ylsulfanyl)-substituted
acetic and propionic acids and propionitriles having methyl, methoxy, or carboxy groups or halogen atom in
position 6 or 8 of the quinoline ring via reactions of the corresponding substituted 2-methylquinoline-4-thiols
with chloroacetic or acrylic acid and acrylonitrile.
DOI: 10.1134/S1070428010040226
Quinoline-4-thiol derivatives occupy a particular
place among nitrogen-and-sulfur-containing hetero-
cycles. They are used as starting compounds in the
synthesis of various fused heterocyclic systems [1–3]
exhibiting antitumor, analgesic, antimicrobial, and
other kinds of biological activity [4, 5].
In continuation of out studies on the synthesis and
properties of 2-methylquinoline-4-thiols [6], in the
present work we synthesized (2-methylquinolin-4-yl-
sulfanyl)-substituted acetic and propionic acids and
propionitriles with various groups at position 6 or 8 in
the quinoline ring. 2-Methylquinoline-4-thiols Ia–Ii,
Scheme 1.
S
N
COOH
R'
ClCH2COOH, NaOH
CH2=CHCOOH, H+
CH2=CHCN
R
Me
IVa–IVi, Va–Vi, VIa–VIi
COOH
SH
N
S
N
R'
R'
R
R
Me
Me
Ia–Ii, IIa–IIi, IIIa–IIIi
VIIa–VIIf, VIIIa–VIIIf, IXa–IXf
CN
S
R'
R
N
Me
Xc, Xd, Xf, XIa, XIg, XIh, XIIa
R = H (a), 6-Me (b), 8-Me (c), 6-MeO (d), 8-MeO (e), 6-Br (f), 8-Br (g), 8-Cl (h), 6-HOCO (i);
I, IV, VII, X, R′ = Et; II, V, VIII, XI, R′ = Pr; III, V, VI, IX, XII, R′ = Bu.
†
Deceased.
571

AVETISYAN et al.
572
IIa–IIi, and IIIa–IIIi [6] reacted with chloroacetic
acid to give (2-methylquinolin-4-ylsulfanyl)acetic
acids IVa–IVi, Va–Vi, and VIa–VIi (Scheme 1). We
examined the effects of different factors on the reac-
tion course and the yield of the products and found
optimal conditions which included initial reactant ratio
1:1.25, alkaline medium, and room temperature. These
conditions ensured high yields of substituted (quinolyl-
sulfanyl)acetic acids IV–VI.
(3-Ethyl-2,8-Dimethylquinolin-4-ylsulfanyl]-
acetic acid (IVc). Yield 1.31 g (95%), mp 175°C. IR
spectrum, ν, cm–1: 2700–3000 (OH), 1730 (C=O).
Found, %: C 65.24; N 6.38; N 4.96; S 11.79.
C15H17NO2S. Calculated, %: C 65.45; N 6.18; N 5.09;
S 11.64.
(3-Ethyl-6-methoxy-2-methylquinolin-4-ylsulfa-
nyl)acetic acid (IVd). Yield 1.40 g (96%), mp 205°C.
1H NMR spectrum, δ, ppm: 1.38 t (3H, CH2CH3),
2.60 s (3H, CH3), 3.40 q (2H, 3-CH2), 3.95 s (3H,
OCH3), 5.15 s (2H, SCH2), 7.30–8.30 m (3H, Harom),
11.60 s (1H, OH). Found, %: C 61.97; H 5.59; N 4.95;
S 10.86. C15H17NO3S. Calculated, %: C 61.85; H 5.84;
N 4.81; S 11.00.
3-(2-Methylquinolin-4-ylsulfanyl)propionic acids
VIIa–VIIf, VIIIa–VIIIf, and IXa–IXf and propio-
nitriles Xc, Xd, Xf, XIa, XIg, XIh, and XIIa were
synthesized in high yield by Michael addition of quin-
oline-4-thiols I–III to acrylic acid and acrylonitrile.
(3-Ethyl-8-methoxy-2-methylquinolin-4-ylsulfa-
nyl)acetic acid (IVe). Yield 1.37 g (94%), mp 210°C.
Found, %: C 61.67; H 5.98; N 4.69; S 11.17.
C15H17NO3S. Calculated, %: C 61.85; H 5.84; N 4.81;
S 11.00.
EXPERIMENTAL
The IR spectra were recorded on a UR-20 spec-
trometer from samples dispersed in mineral oil. The
1H NMR spectra were measured from solutions in
DMSO-d6 on a Varian Mercury-300 instrument. The
purity of the isolated compounds was checked by TLC
on Silufol UV-254 plates; spots were visualized by
treatment with iodine vapor.
(6-Bromo-3-ethyl-2-methylquinolin-4-ylsulfanyl)-
acetic acid (IVf). Yield 1.53 g (90%), mp 245°C.
IR spectrum, ν, cm–1: 3250–3420 (OH), 1700 (C=O).
1H NMR spectrum, δ, ppm: 1.10 t (3H, CH2CH3), 2.60 s
(3H, CH3), 4.00 q (2H, 3-CH2), 4.50 s (2H, SCH2),
8.10–8.75 m (3H, Harom), 10.20 s (1H, OH). Found, %:
C 49.24; H 4.33; N 4.07; S 9.52. C14H14BrNO2S. Cal-
culated, %: C 49.41; H 4.12; N 4.12; S 9.41.
Substituted (3-alkyl-2-methylquinolin-4-ylsul-
fanyl)acetic acids IVa–IVi, Va–Vi, and VIa–VIi
(general procedure). Chloroacetic acid, 0.59 g
(625 mmol), was added under stirring to a solution of
5 mmol of substituted 3-alkyl-2-methylquinoline-4-
thiol Ia–Ii, IIa–IIi, or IIIa–IIIi and 0.80 g (0.02 mol)
of sodium hydroxide in 4 ml of water, and the mixture
was left to stand overnight at room temperature. The
mixture was then diluted with 10 ml of water and
filtered, the filtrate was acidified to pH 4–5, and the
precipitate was filtered off and washed with water.
(8-Bromo-3-ethyl-2-methylquinolin-4-ylsulfanyl)-
acetic acid (IVg). Yield 1.60 g (94%), mp 160°C.
1H NMR spectrum, δ, ppm: 1.22 t (3H, CH2CH3), 2.70 s
(3H, CH3), 3.02 q (2H, 3-CH2), 3.86 s (2H, SCH2),
7.10–7.90 m (3H, Harom), 10.20 s (1H, OH). Found, %:
C 49.57; H 4.01; N 4.28; S 9.55. C14H14BrNO2S. Cal-
culated, %: C 49.41; H 4.12; N 4.12; S 9.41.
(8-Chloro-3-ethyl-2-methylquinolin-4-ylsulfa-
nyl)acetic acid (IVh). Yield 1.37 g (93%), mp 195°C.
1H NMR spectrum, δ, ppm: 1.05 t (3H, CH2CH3), 2.50 s
(3H, CH3), 3.40 q (2H, 3-CH2), 4.50 s (2H, SCH2),
7.00–7.90 m (3H, Harom), 10.10 s (1H, OH). Found, %:
C 56.63; H 4.81; N 4.91; S 10.62. C14H14ClNO2S. Cal-
culated, %: C 56.85; H 4.74; N 4.74; S 10.83.
(3-Ethyl-2-methylquinolin-4-ylsulfanyl)acetic
acid (IVa). Yield 1.27 g (97%), mp 230°C. IR spec-
trum, ν, cm–1: 2700–3300 (OH), 1730 (C=O). 1H NMR
spectrum, δ, ppm: 1.26 t (3H, CH2CH3), 2.55 s (3H,
CH3), 3.10 q (2H, 3-CH2), 5.00 s (2H, SCH2), 7.40–
8.10 m (4H, Harom), 10.05 s (1H, OH). Found, %:
C 64.25; H 5.94; N 5.24; S 12.34. C14H15NO2S. Calcu-
lated, %: C 64.37; H 5.75; N 5.36; S 12.26.
4-(Carboxymethylsulfanyl)-3-ethyl-2-methyl-
quinoline-6-carboxylic acid (IVi). Yield 1.40 g
(92%), mp 256°C (decomp.). IR spectrum, ν, cm–1:
(3-Ethyl-2,6-dimethylquinolin-4-ylsulfanylacetic
1
acid (IVb). Yield 1.25 g (91%), mp 325°C. H NMR
1
spectrum, δ, ppm: 1.14 t (3H, CH2CH3), 2.50 s (3H,
CH3), 2.70 s (3H, CH3), 3.25 q (2H, 3-CH2), 5.10 s
(2H, SCH2), 7.40–8.20 m (3H, Harom), 10.10 s (1H,
OH). Found, %: C 65.70; H 6.42; N 5.20; S 11.87.
C15H17NO2S. Calculated, %: C 65.45; H 6.18; N 5.09;
S 11.64.
2700–3300 (OH), 1730 (C=O). H NMR spectrum, δ,
ppm: 1.38 t (3H, CH2CH3), 2.70 s (3H, CH3), 3.65 q
(2H, 3-CH2), 4.50 s (2H, SCH2), 7.10–7.80 m (3H,
Harom), 10.00 s (1H, OH), 10.50 s (1H, OH). Found, %:
C 59.25; H 4.75; N 4.68; S 10.31. C15H15NO4S. Calcu-
lated, %: C 59.02; H 4.92; N 4.59; S 10.49.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

SYNTHESIS OF (2-METHYLQUINOLIN-4-YLSULFANYL)-SUBSTITUTED ACETIC
573
(2-Methyl-3-propylquinolin-4-ylsulfanyl)acetic
acid (Va). Yield 1.32 g (96%), mp 200°C. H NMR
1H NMR spectrum, δ, ppm: 1.22 t (3H, CH2CH3),
1.65 m (2H, 3-CH2), 2.55 s (3H, CH3), 3.10 t (2H,
CH3CH2), 4.00 s (2H, SCH2), 7.50–7.80 m (3H, Harom),
10.20 s (1H, OH). Found, %: C 58.00; H 5.31; N 4.67;
S 10.28. C15H16ClNO2S. Calculated, %: C 58.16;
H 5.17; N 4.52; S 10.34.
1
spectrum, δ, ppm: 1.22 t (3H, CH2CH3), 1.65 m (2H,
3-CH2), 2.40 s (3H, CH3), 3.10 t (2H, CH3CH2), 4.80 s
(2H, SCH2), 7.30–8.00 m (4H, Harom), 10.10 s (1H,
OH). Found, %: C 66.25; H 6.02; N 5.27; S 11.75.
C15H17NO2S. Calculated, %: C 65.45; H 6.18; N 5.09;
S 11.64.
4-(Carboxymethylsulfanyl)-2-methyl-3-propyl-
quinoline-6-carboxylic acid (Vi). Yield 1.37 g (86%),
mp 210°C (decomp.). Found, %: C 60.04; H 5.51;
N 4.23; S 10.19. C16H17NO4S. Calculated, %: C 60.19;
H 5.33; N 4.39; S 10.03.
(2,6-Dimethyl-3-propylquinolin-4-ylsulfanyl)ace-
tic acid (Vb). Yield 1.34 g (93%), mp 215°C. IR spec-
trum, ν, cm–1: 2700–3200 (OH), 1720 (C=O). Found,
%: C 66.25; H 6.74; N 4.67; S 11.26. C16H19NO2S.
Calculated, %: C 66.44; H 6.57; N 4.84; S 11.07.
(3-Butyl-2-methylquinolin-4-ylsulfanyl)acetic
1
acid (VIa). Yield 1.30 g (91%), mp 153°C. H NMR
(2,8-Dimethyl-3-propylquinolin-4-ylsulfanyl)ace-
tic acid (Vc). Yield 1.30 g (90%), mp 110°C. 1H NMR
spectrum, δ, ppm: 1.38 t (3H, CH2CH3), 1.70 m (2H,
3-CH2), 2.40 s (3H, CH3), 2.60 s (3H, CH3), 3.25 t
(2H, CH3CH2), 5.00 s (2H, SCH2), 7.10–8.20 m (3H,
Harom), 9.90 s (1H, OH). Found, %: C 66.52; H 6.39;
N 4.98; S 10.89. C16H19NO2S. Calculated, %: C 66.44;
H 6.57; N 4.84; S 11.07.
spectrum, δ, ppm: 1.25 t (3H, CH2CH3), 1.65 m (4H,
CH2CH2), 2.75 s (3H, CH3), 3.25 t (2H, 3-CH2), 3.95 s
(2H, SCH2), 7.50–8.20 m (4H, Harom), 10.20 s (1H,
OH). Found, %: C 66.62; H 6.44; N 4.73; S 11.22.
C16H19NO2S. Calculated, %: C 66.44; H 6.57; N 4.84;
S 11.07.
(3-Butyl-2,6-dimethylquinolin-4-ylsulfanyl)acetic
1
acid (VIb). Yield 1.44 g (95%), mp 156°C. H NMR
(6-Methoxy-2-methyl-3-propylquinolin-4-ylsul-
fanylacetic acid (Vd). Yield 1.46 g (96%), mp 167°C.
1H NMR spectrum, δ, ppm: 1.25 t (3H, CH2CH3),
1.60 m (2H, 3-CH2), 2.50 s (3H, CH3), 3.10 t (2H,
CH3CH2), 4.60 s (3H, OCH3), 4.60 s (2H, SCH2),
7.40–8.00 m (3H, Harom), 10.15 s (1H, OH). Found, %:
C 62.78; H 6.41; N 4.48; S 10.61. C16H19NO3S. Calcu-
lated, %: C 62.95; H 6.23; N 4.59; S 10.49.
spectrum, δ, ppm: 1.35 t (3H, CH2CH3), 1.75 m (4H,
CH2CH2), 2.45 s (3H, CH3), 2.70 s (3H, CH3), 3.20 t
(2H, 3-CH2), 3.80 s (2H, SCH2), 7.60–8.10 m (3H,
Harom), 11.00 s (1H, OH). Found, %: C 67.18; H 6.98;
N 4.47; S 10.29. C17H21NO2S. Calculated, %: C 67.33;
H 6.93; N 4.62; S 10.56.
(3-Butyl-2,8-dimethylquinolin-4-ylsulfanyl)acetic
acid (VIc). Yield 1.42 g (94%), mp 90°C. Found, %:
C 67.49; H 6.76; N 4.75; S 10.74. C17H21NO2S. Calcu-
lated, %: C 67.33; H 6.93; N 4.62; S 10.56.
(8-Methoxy-2-methyl-3-propylquinolin-4-ylsul-
fanyl)acetic acid (Ve). Yield 1.45 g (95%), mp 161°C.
IR spectrum, ν, cm–1: 2800–3300 (OH), 1735 (C=O).
Found, %: C 63.14; H 6.09; N 4.75; S 10.32.
C16H19NO3S. Calculated, %: C 62.95; H 6.23; N 4.59;
S 10.49.
(3-Butyl-6-methoxy-2-methylquinolin-4-ylsulfa-
nyl)acetic acid (VId). Yield 1.48 g (93%), mp 175°C.
1H NMR spectrum, δ, ppm: 1.22 t (3H, CH2CH3),
1.60 m (4H, CH2CH2), 2.50 s (3H, CH3), 3.10 s (2H,
3-CH2), 4.00 s (3H, OCH3), 4.65 s (2H, SCH2), 7.30–
8.00 m (3H, Harom), 10.00 s (1H, OH). Found, %:
C 63.78; H 6.71; N 4.23; S 10.21. C17H21NO3S. Calcu-
lated, %: C 63.95; H 6.58; N 4.39; S 10.03.
(6-Bromo-2-methyl-3-propylquinolin-4-ylsulfa-
nyl)acetic acid (Vf). Yield 1.66 g (94%), mp 171°C.
1H NMR spectrum, δ, ppm: 1.22 t (3H, CH2CH3),
1.60 m (2H, 3-CH2), 2.55 s (3H, CH3), 3.20 t (2H,
CH3CH2), 4.10 s (2H, SCH2), 7.60–7.90 m (3H, Harom),
10.10 s (1H, OH). Found, %: C 50.67; H 4.70; N 3.76;
S 9.21. C15H16BrNO2S. Calculated, %: C 50.85;
H 4.52; N 3.95; S 9.04.
(3-Butyl-8-methoxy-2-methylquinolin-4-ylsulfa-
nyl)acetic acid (VIe). Yield 1.44 g (90%), mp 140°C.
Found, %: C 63.76; H 6.74; N 4.28; S 10.19.
C17H21NO3S. Calculated, %: C 63.95; H 6.58; N 4.39;
S 10.03.
(8-Bromo-2-methyl-3-propylquinolin-4-ylsulfa-
nyl)acetic acid (Vg). Yield 1.68 g (95%), mp 157°C.
Found, %: C 51.04; H 4.70; N 4.11; S 9.20.
C15H16BrNO2S. Calculated, %: C 50.85; H 4.52;
N 3.95; S 9.04.
(6-Bromo-3-butyl-2-methylquinolin-4-ylsulfa-
nyl)acetic acid (VIf). Yield 1.67 g (91%), mp 152°C.
1H NMR spectrum, δ, ppm: 1.22 t (3H, CH2CH3),
1.70 m (4H, CH2CH2), 2.70 s (3H, CH3), 3.00 t (2H,
3-CH2), 3.85 s (2H, SCH2), 7.30–8.10 m (3H, Harom),
(8-Chloro-2-methyl-3-propylquinolin-4-ylsulfa-
nyl)acetic acid (Vh). Yield 1.42 g (92%), mp 145°C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

AVETISYAN et al.
574
10.50 s (1H, OH). Found, %: C 52.02; H 4.98; N 3.71;
S 8.52. C16H18BrNO2S. Calculated, %: C 52.17;
H 4.89; N 3.80; S 8.70.
3-(3-Ethyl-2,8-dimethylquinolin-4-ylsulfanyl)-
propionic acid (VIIc). Yield 1.16 g (80%), mp 140°C.
1H NMR spectrum, δ, ppm: 1.14 t (3H, CH2CH3),
2.50 s (3H, CH3), 2.70 s (3H, CH3), 3.20 q (2H,
CH2CH3), 3.45 t (2H, CH2), 4.10 t (2H, SCH2), 7.30–
7.90 m (3H, Harom), 10.00 s (1H, OH). Found, %:
C 66.62; H 6.42; N 4.96; S 10.92. C16H19NO2S. Cal-
culated, %: C 66.44; H 6.57; N 4.84; S 11.07.
(8-Bromo-3-butyl-2-methylquinolin-4-ylsulfa-
nyl)acetic acid (VIg). Yield 1.71 g (93%), mp 145°C.
IR spectrum, ν, cm–1: 2800–3100 (OH), 1720 (C=O).
Found, %: C 52.28; H 4.71; N 3.94; S 8.89.
C16H18BrNO2S. Calculated, %: C 52.17; H 4.89;
N 3.80; S 8.70.
3-(3-Ethyl-6-methoxy-2-methylquinolin-4-ylsul-
fanyl)propionic acid (VIId). Yield 1.24 g (81%),
mp 170°C. Found, %: C 62.77; H 6.39; N 4.42;
S 10.65. C16H19NO3S. Calculated, %: C 62.95; H 6.23;
N 4.59; S 10.49.
(3-Butyl-8-chloro-2-methylquinolin-4-ylsulfanyl)-
acetic acid (VIh). Yield 1.49 g (92%), mp 110°C.
1H NMR spectrum, δ, ppm: 1.25 t (3H, CH2CH3),
1.75 m (4H, CH2CH2), 2.75 s (3H, CH3), 3.10 t (2H,
3-CH2), 4.00 s (2H, SCH2), 7.20–8.00 m (3H, Harom),
10.50 s (1H, OH). Found, %: C 59.17; H 5.69; N 4.18;
S 9.76. C16H18ClNO2S. Calculated, %: C 59.35;
H 5.56; N 4.33; S 9.89.
3-(3-Ethyl-8-methoxy-2-methylquinolin-4-ylsul-
fanyl)propionic acid (VIIe). Yield 1.19 g (78%),
1
mp 210°C. H NMR spectrum, δ, ppm: 1.25 t (3H,
CH2CH3), 2.60 s (3H, CH3), 3.10 q (2H, CH2CH3),
3.95 s (3H, OCH3), 4.50 t (2H, SCH2), 7.10–7.80 m
(3H, Harom), 9.90 s (1H, OH). Found, %: C 63.11;
H 6.09; N 4.71; S 10.33. C16H19NO3S. Calculated, %:
C 62.95; H 6.23; N 4.59; S 10.49.
3-Butyl-4-(carboxymethylsulfanyl)-2-methyl-
quinoline-6-carboxylic acid (VIi). Yield 1.48 g
(89%), mp 200°C (decomp.). IR spectrum, ν, cm–1:
2700–3300 (OH), 1720 (C=O). Found, %: C 61.14;
H 5.83; N 4.37; S 9.48. C17H19NO4S. Calculated, %:
C 61.26; H 5.70; N 4.20; S 9.61.
3-(6-Bromo-3-ethyl-2-methylquinolin-4-ylsul-
fanyl)propionic acid (VIIf). Yield 1.40 g (79%),
mp 216°C. IR spectrum, ν, cm–1: 2800–3300 (OH),
1720 (C=O). Found, %: C 50.71; H 4.68; N 4.07;
S 9.13. C15H16BrNO3S. Calculated, %: C 50.85;
H 4.62; N 3.95; S 9.04.
Substituted 3-(3-alkyl-2-methylquinolin-4-ylsul-
fonyl)propionic acids VIIa–VIIf, VIIIa–VIIIf, and
IXa–IXf (general procedure). A mixture of 5 mmol of
substituted 3-alkyl-2-methylquinoline-4-thiol Ia–If,
IIa–IIf, or IIIa–IIIf, 0.432 g (6 mmol) of acrylic acid,
and two drops of hydrochloric acid was stirred for 3 h
and was left overnight at room temperature. The mix-
ture was treated with 10 ml of water, the precipitate
was dissolved in dilute alkali, the alkaline solution was
filtered, and the filtrate was acidified with hydrochloric
acid. The precipitate was filtered off and washed with
water.
3-(2-Methyl-3-propylquinolin-4-ylsulfanyl)pro-
pionic acid (VIIIa). Yield 1.16 g (80%), mp 159°C.
1H NMR spectrum, δ, ppm: 1.25 t (3H, CH2CH3),
1.70 m (2H, CH2), 2.40 s (3H, CH3), 3.20 t (2H, CH2),
3.40 t (2H, CH2), 3.85 t (2H, SCH2), 7.20–8.00 m (4H,
Harom), 10.11 s (1H, OH). Found, %: C 66.28; H 6.72;
N 4.73; S 11.21. C16H19NO2S. Calculated, %: C 66.44;
H 6.57; N 4.84; S 11.07.
3-(2,6-Dimethyl-3-propylquinolin-4-ylsulfanyl)-
propionic acid (VIIIb). Yield 1.24 g (82%),
mp 195°C. IR spectrum, ν, cm–1: 1725 (C=O), 2800–
3200 (OH). Found, %: C 67.49; H 6.78; N 4.76;
S 10.44. C17H21NO2S. Calculated, %: C 67.33; H 6.93;
N 4.62; S 10.56.
3-(3-Ethyl-2-methylquinolin-4-ylsulfanyl)propi-
onic acid (VIIa). Yield 1.11 g (81%), mp 185°C.
1H NMR spectrum, δ, ppm: 1.25 t (3H, CH2CH3),
2.60 s (3H, CH3), 3.10 q (2H, CH2CH3), 3.40 t (2H,
CH2), 4.00 t (2H, SCH2), 7.40–8.10 m (4H, Harom),
10.10 s (1H, OH). Found, %: C 65.61; H 6.05; N 5.24;
S 11.78. C15H17NO2S. Calculated, %: C 65.45; H 6.18;
N 5.09; S 11.64.
3-(2,8-Dimethyl-3-propylquinolin-4-ylsulfanyl)-
propionic acid (VIIIc). Yield 1.20 g (79%),
mp 113°C. Found, %: C 67.18; H 7.04; N 4.49;
S 10.68. C17H21NO2S. Calculated, %: C 67.33; H 6.93;
N 4.62; S 10.56.
3-(3-Ethyl-2,6-dimethylquinolin-4-ylsulfanyl)-
propionic acid (VIIb). Yield 1.18 g (82%), mp 145°C.
IR spectrum, ν, cm–1: 2700–3300 (OH), 1730 (C=O).
Found, %: C 66.27; H 6.71; N 4.67; S 11.25.
C16H19NO2S. Calculated, %: C 66.44; H 6.57; N 4.84;
S 11.07.
3-(6-Methoxy-2-methyl-3-propylquinolin-4-yl-
sulfanyl)propionic acid (VIIId). Yield 1.29 g (81%),
1
mp 176°C. H NMR spectrum, δ, ppm: 1.30 t (3H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

SYNTHESIS OF (2-METHYLQUINOLIN-4-YLSULFANYL)-SUBSTITUTED ACETIC
575
CH2CH3), 1.75 m (2H, CH2), 2.80 s (3H, CH3), 3.20 t
(2H, CH2), 3.45 t (2H, CH2), 3.87 s (3H, OCH3), 4.20 t
(2H, SCH2), 7.20–8.00 m (3H, Harom), 11.00 s (1H,
OH). Found, %: C 64.08; H 6.47; N 4.81; S 11.15.
C17H21NO3S. Calculated, %: C 63.95; H 6.58; N 4.93;
S 10.03.
C18H23NO3S. Calculated, %: C 64.86; H 6.91; N 4.20;
S 9.61.
3-(3-Butyl-8-methoxy-2-methylquinolin-4-ylsul-
fanyl)propionic acid (IXe). Yield 1.35 g (81%),
1
mp 182°C. H NMR spectrum, δ, ppm: 1.25 t (3H,
CH2CH3), 1.65 m (4H, CH2CH2), 2.55 s (3H, CH3),
2.90 t (2H, CH2), 3.20 t (2H, CH2), 3.90 s (3H, OCH3),
4.40 s (2H, SCH2), 7.10–7.90 m (3H, Harom), 10.20 s
(1H, OH). Found, %: C 64.72; H 7.03; N 4.09; S 9.74.
C18H23NO3S. Calculated, %: C 64.86; H 6.91; N 4.20;
S 9.61.
3-(8-Methoxy-2-methyl-3-propylquinolin-4-yl-
sulfanyl)propionic acid (VIIIe). Yield 1.26 g (79%),
mp 207°C. Found, %: C 63.79; H 6.72; N 5.07;
S 10.19. C17H21NO3S. Calculated, %: C 63.95; H 6.58;
N 4.93; S 10.03.
3-(6-Bromo-3-butyl-2-methylquinolin-4-ylsul-
3-(6-Bromo-2-methyl-3-propylquinolin-4-ylsul-
fanyl)propionic acid (IXf). Yield 1.53 g (80%),
fanyl)propionic acid (VIIIf). Yield 1.47 g (80%),
1
1
mp 149°C. H NMR spectrum, δ, ppm: 1.25 t (3H,
mp 181°C. H NMR spectrum, δ, ppm: 1.38 t (3H,
CH2CH3), 1.60 m (4H, CH2CH2), 2.60 s (3H, CH3),
3.00 t (2H, CH2), 3.30 t (2H, CH2), 3.95 s (2H, SCH2),
7.20–8.00 m (3H, Harom), 10.10 s (1H, OH). Found, %:
C 53.29; H 5.36; N 3.56; S 8.52. C17H20BrNO2S. Cal-
culated, %: C 53.40; H 5.24; N 3.66; S 8.38.
CH2CH3), 1.70 m (2H, CH2), 2.75 s (3H, CH3), 3.15 t
(2H, CH2), 3.40 t (2H, CH2), 4.10 s (2H, SCH2), 7.40–
7.80 m (3H, Harom), 10.00 s (1H, OH). Found, %:
C 52.08; H 4.97; N 3.71; S 8.86. C16H18BrNO2S. Cal-
culated, %: C 52.17; H 4.89; N 3.80; S 8.70.
Substituted (3-alkyl-2-methylquinolin-4-ylsulfa-
nyl)propionitriles Xc, Xd, Xf, XIa, XIg, XIh, and
XIIa (general procedure). A mixture of 5 mmol of
3-alkyl-2-methylquinoline-4-thiol Ic, Id, If, IIa, IIg,
IIh, or IIIa, 0.318 g (6 mmol) of acrylonitrile, 20 ml
of dioxane, and 4–5 drops of a 10% solution of sodium
hydroxide was stirred at room temperature and left
overnight. The mixture was then heated for 2 h on
a water bath, the solvent was distilled off, the residue
was treated with water, and the precipitate was filtered
off, washed with water, and recrystallized from
50% ethanol.
3-(3-Butyl-2-methylquinolin-4-ylsulfanyl)propi-
onic acid (IXa). Yield 1.26 g (83%), mp 122°C. IR
spectrum, ν, cm–1: 2900–3250 (OH), 1690 (C=O).
1H NMR spectrum, δ, ppm: 1.25 t (3H, CH2CH3),
1.65 m (4H, CH2CH2), 2.70 s (3H, CH3), 3.25 t (2H,
CH2), 3.45 t (2H, CH2), 3.90 s (2H, SCH2), 7.50–
8.20 m (4H, Harom), 10.20 s (1H, OH). Found, %:
C 67.46; H 6.79; N 4.73; S 10.74. C17H21NO2S. Calcu-
lated, %: C 67.33; H 6.93; N 4.62; S 10.56.
3-(3-Butyl-2,6-dimethylquinolin-4-ylsulfanyl)-
propionic acid (IXb). Yield 1.27 g (80%), mp 143°C.
1H NMR spectrum, δ, ppm: 1.35 t (3H, CH2CH3),
1.75 m (4H, CH2CH2), 2.45 s (3H, CH3), 2.70 s (3H,
CH3), 3.20 t (2H, CH2), 3.40 t (2H, CH2), 4.10 s (2H,
SCH2), 7.60–8.10 m (3H, Harom), 10.10 s (1H, OH).
Found, %: C 68.31; H 7.14; N 4.57; S 10.25.
C18H23NO2S. Calculated, %: C 68.14; H 7.26; N 4.42;
S 10.09.
3-(3-Ethyl-2,8-dimethylquinolin-4-ylsulfanyl)-
propionitrile (Xc). Yield 1.22 g (90%), mp 84–85°C.
IR spectrum: ν 2210–2250 cm–1 (C≡N). 1H NMR spec-
trum, δ, ppm: 1.26 t (3H, CH2CH3), 2.40 s (3H, CH3),
2.70 s (3H, CH3), 2.90 t (2H, CH2), 3.20 q (2H, CH2),
4.10 t (2H, SCH2), 7.50–8.10 m (3H, Harom). Found, %:
C 71.26; H 6.53; N 10.29; S 11.98. C16H18N2S. Calcu-
lated, %: C 71.11; H 6.67; N 10.37; S 11.85.
3-(3-Butyl-2,8-dimethylquinolin-4-ylsulfanyl)-
propionic acid (IXc). Yield 1.25 g (79%), mp 135°C.
Found, %: C 68.03; H 7.38; N 4.55; S 9.97.
C18H23NO2S. Calculated, %: C 68.14; H 7.26; N 4.42;
S 10.09.
3-(-3-Ethyl-6-methoxy-2-methylquinolin-4-yl-
sulfanyl)propionitrile (Xd). Yield 1.30 g (91%),
1
mp 115°C. H NMR spectrum, δ, ppm: 1.35 t (3H,
CH2CH3), 2.60 s (3H, CH3), 2.95 t (2H, CH2), 3.10 q
(2H, CH2), 3.85 s (3H, OCH3), 4.20 t (2H, SCH2),
7.10–7.90 m (3H, Harom). Found, %: C 67.28; H 6.17;
N 9.92; S 11.08. C16H18N2OS. Calculated, %: C 67.13;
H 6.29; N 9.79; S 11.19.
3-(3-Butyl-6-methoxy-2-methylquinolin-4-ylsul-
fanyl)propionic acid (IXd). Yield 1.40 g (84%),
1
mp 151°C. H NMR spectrum, δ, ppm: 1.30 t (3H,
CH2CH3), 1.70 m (4H, CH2CH2), 2.70 s (3H, CH3),
3.00 t (2H, CH2), 3.30 t (2H, CH2), 4.00 s (3H, OCH3),
4.75 s (2H, SCH2), 7.30–8.10 m (3H, Harom), 11.00 s
(1H, OH). Found, %: C 64.95; H 6.78; N 4.31; S 9.48.
3-(6-Bromo-3-ethyl-2-methylquinolin-4-ylsulfa-
nyl)propionitrile (Xf). Yield 1.47 g (88%), mp 105°C.
1H NMR spectrum, δ, ppm: 1.30 t (3H, CH2CH3),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

AVETISYAN et al.
576
2.65 s (3H, CH3), 3.00 t (2H, CH2), 3.20 q (2H, CH2),
4.00 t (2H, SCH2), 7.40–7.90 m (3H, Harom). Found, %:
C 53.65; H 4.37; N 8.54; S 9.76. C15H15BrN2S. Calcu-
lated, %: C 53.73; H 4.48; N 8.36; S 9.55.
C16H17ClN2S. Calculated, %: C 63.05; H 5.58; N 9.20;
S 10.51.
3-(3-Butyl-2-methylquinolin-4-ylsulfanyl]propio-
nitrile (XIIa). Yield 1.29 g (91%), mp 74–75°C.
1H NMR spectrum, δ, ppm: 1.30 t (3H, CH2CH3),
1.70 m (4H, CH2CH2), 2.60 s (3H, CH3), 3.20 t (2H,
CH2), 3.40 t (2H, CH2), 4.00 t (2H, SCH2), 7.60–
8.10 m (4H, Harom). Found, %: C 71.68; H 7.17;
N 9.73; S 11.42. C17H20N2S. Calculated, %: C 71.83;
H 7.04; N 9.86; S 11.27.
3-(2-Methyl-3-propylquinolin-4-ylsulfanyl)pro-
pionitrile (XIa). Yield 1.23 g (91%), mp 95–96°C.
1H NMR spectrum, δ, ppm: 1.25 t (3H, CH2CH3),
1.72 m (2H, CH2), 2.70 s (3H, CH3), 3.25 t (2H, CH2),
3.40 t (2H, CH2), 4.10 t (2H, SCH2), 7.20–7.90 m (4H,
Harom). Found, %: C 71.28; H 6.53; N 10.48; S 11.67.
C16H17N2S. Calculated, %: C 71.11; H 6.67; N 10.37;
S 11.85.
REFERENCES
3-(8-Bromo-2-methyl-3-propylquinolin-4-ylsul-
1. Avetisyan, A.A. and Aleksanyan, I.L., Khim. Geterotsikl.
Soedin., 2005, p. 403.
2. Kim, D.G., Arslambekov, R.M., Subbotina, Yu.O., and
Belik, A.B., Khim. Geterotsikl. Soedin., 1999, p. 1519.
3. Moiseev, D.V., Aksenov, A.V., and Smushkevich, Yu.S.,
Khim. Geterotsikl. Soedin., 2000, p. 512.
4. Okada, E. and Tsukushi, N., Heterocycles, 2000, vol. 53,
fanyl)propionitrile (XIg). Yield 1.55 g (89%), mp 86–
1
87°C. H NMR spectrum, δ, ppm: 1.38 t (3H,
CH2CH3), 1.70 m (2H, CH2), 2.65 s (3H, CH3), 3.20 t
(2H, CH2), 3.45 t (2H, CH2), 4.00 t (2H, SCH2), 7.50–
7.90 m (3H, Harom). Found, %: C 55.18; H 4.73;
N 8.18; S 9.32. C16H17BrN2S. Calculated, %: C 55.01;
H 4.87; N 8.02; S 9.17.
p. 709.
3-(8-Chloro-2-methyl-3-propylquinolin-4-ylsul-
fanyl)propionitrile (XIh). Yield 1.34 g (88%),
mp 90–91°C. IR spectrum: ν 2255–2215 cm–1 (C≡N).
Found, %: C 63.21; H 5.39; N 9.31; S 10.37.
5. Skrzypek, Z. and Suwinska, K., Heterocycles, 2002,
vol. 57, p. 2035.
6. Avetisyan A.A., Aleksanyan I.L., Durgaryan V.G. Uch.
Zap. Erevan. Gos. Univ., 2008, p. 89.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010