Synthesis of substituted 2-methyl-4-quinolyl isothiocyanates and 4-mercaptoquinolines

Article abstract of DOI:10.1007/s11178-005-0242-7

Synthesis was performed of substituted 2-methyl-4-quinoline thiouronium salts by reaction of 2-methyl-4-chloroquinolines with thiourea. The alkaline hydrolysis of these salts afforded the corresponding 2-methyl-4-quinolyl- isothiocyanates and 2-methyl-4-mercaptoquinolines. 2005 Pleiades Publishing, Inc.

Full text of DOI:10.1007/s11178-005-0242-7

Russian Journal of Organic Chemistry, Vol. 41, No. 5, 2005, pp. 769-771. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 5, 2005,
pp. 783-785.
Original Russian Text Copyright Ó 2005 by Avetisyan, Aleksanyan, Ambartsumyan.
.
Synthesis of Substituted 2-Methyl-4-quinolyl Isothiocyanates and
4-Mercaptoquinolines
A.A.Avetisyan, I.L.Aleksanyan, and L.P.Ambartsumyan
Yerevan State University, Yerevan, 375025 Armenia
e-mail: organkim@sun.ysu.am
Received October 29, 2004
Abstract—Synthesis was performed of substituted 2-methyl-4-quinoline thiouronium salts by reaction of 2-
methyl-4-chloroquinolines with thiourea. The alkaline hydrolysis of these salts afforded the corresponding 2-
methyl-4-quinolyl- isothiocyanates and 2-methyl-4-mercaptoquinolines.
quinolyl isothiocyanates, and a bimolecular cleavage of a
S–C bond giving rise to substituted 2-methyl-4-mercapto-
quinolines. The ratio of the final products depended on
the character and the position of substituents, and from
the 6-methoxy derivative the substitution product was not
obtained at all. As expected, the electronic effects of
substituents in positions 6 and 8 of the benzene ring were
identical. The observed increase in the yield of rearrange-
ment products in the systems under study in all likelihood
is due to the existence of the molecule in a conformation
most feasible for the rearrangement. This fact apparently
governs the lack of compound IVc in the hydrolysis
We formerly reported on the new route of the alkaline
hydrolysis of 2-methyl-4-quinoline thiouronium salts
affording 2-methyl-4-quinolyl isothiocyanate [1]. In
extension of this research we studied here the reaction
with thiourea of 2-methyl-4-chloroquinolines containing
in the benzene ring different (electron-donor and electron-
acceptor) substituents. The reaction occurred at heating
the initial components in the ratio quinoline to thiourea
equal to 1:1.1 in anhydrous acetone resulting in the
quinolylthiouronium salts in a nearly quantitative yield.
The alkaline hydrolysis of the salts obtained took two
pathways: an intramolecular rearrangement analogous to
Smiles rearrangement [2–5] affording the corresponding
products
of
S-(2-methyl-6-methoxy-4-
quinolyl)thiouronium chloride.
1+
&O
&O
6
&
+ 1 & 1+
1+
6
5
5
1
&+
1
B
&+
,
,, ꢀꢀꢀ,,I
1D2+
1 &
6
6+
6
5
5
5
1
&+
1
+
&+
1
B
&+
B
,,, ꢀꢀꢀ,,,I
,9 ꢀꢀꢀ,9I
R = 6-CH3 (a), 8-CH3 (b), 6-OCH3 (c), 8-OCH3 (d), 6-Br (e), 8-Cl (f).
1070-4280/05/4105-0769Ó2005 Pleiades Publishing, Inc.

AVETISYAN et al.
770
bright-yellow precipitates of compounds IVa–IVf with a
EXPERIMENTAL
specific odor were filtered off.
1H NMR spectra were registered on a spectrometer
2,6-Dimethyl-4-quinolyl isothiocyanate (IIIa).
Yield 0.85 g (39.7%), mp 170–175°C, Rf 0.72 (from
Mercury-300 Varian NMR in DMSO, IR spectra were
recorded on a spectrophotometer UR-20 from mulls in
mineral oil. The purity of compounds obtained was
checked by TLC on Silufol UV-254 plates (development
in iodine vapor).
–1
ethanol). IR spectrum, cm : 2250–1930 (–N=C=S).
1H NMR spectrum, d, ppm: 2.40 s (3H, CH3), 2.80 s
(3H, NCCH3), 7.00 s (H3, Harom), 7.5–8.2 m (3H, Harom).
Found, %: C 67.41; H 4.59; N 12.95; S 15.11. C12H10N2S.
Calculated, %: C 67.29; H 4.67; N 13.08; S 14.95.
S-(2-Methyl-4-quinolyl)thiouronium chlorides
IIa–IIf. A mixture of 0.01 mol of an appropriate
substituted 2-methyl-4-chloroquinoline [6(8)-methyl, 6(8)-
methoxy, 6-bromo, 8-chloro] and 0.99 g (0.013 mol) of
thiourea in 50 ml of anhydrous acetone was heated on
a water bath for 8–10 h. On cooling the precipitated
yellow crystals were filtered off and washed with
anhydrous acetone.
2,6-Dimethyl-4-sulfanylquinoline (IVa). Yield
0.70 g (37%), mp 215°C, Rf 0.69 (from ethanol). IR
–1
1
spectrum, cm : 1215 (>C=S), 3220 (>NH). H NMR
spectrum, d, ppm: 2.22 s (3H, CH3), 2.70 s (3H, NCCH3),
6.45 s (H3, Harom), 7.2–7.9 m (3H, Harom) 9.02 s (H, >NH).
Found, %: C 69.97; H 5.98; N 7.29; S 17.15. C11H11NS.
Calculated, %: C 69.84; H 5.82; N 7.41; S 16.93.
S-(2,6-Dimethyl-4-quinolyl)thiouronium chloride
(IIa) Yield 2.54 g (95%), mp 210–215°C. Found, %:
Cl 13.31; N 15.63; S 12.05. C12H14ClN3S. Calculated,
%: Cl 13.27; N 15.70; S 11.96.
2,8-Dimethyl-4-quinolyl isothiocyanate (IIIb).
Yield 0.94 g (44%), mp 155–157°C, Rf 0.59 (from
acetone). IR spectrum, cm : 2250–1930 (–N=C=S).
1H NMR spectrum, d, ppm: 2.22 s (3H, CH3), 2.70 s
(3H, NCCH3), 6.80 s (H3, Harom), 7.2–7.9 m (3H, Harom).
Found, %: C 67.15; H 4.78; N 13.27; S 14.84. C12H10N2S.
Calculated, %: C 67.29; H 4.67; N 13.08; S 14.95.
–1
S-(2,8-Dimethyl-4-quinolyl)thiouronium chloride
(IIb. Yield 2.62 g (98%), mp 150–155°C. Found, %:
Cl 13.14; N 15.82; S 12.08. C12H14ClN3S. Calculated,
%: Cl 13.27; N 15.70; S 11.96.
2,8-Dimethyl-4-sulfanylquinoline (IVb). Yield
0.56 g (29.8%), mp 280–281°C, Rf 0.70 (from ethanol–
S-(2-Methyl-6-methoxy-4-quinolyl)-thiouronium
chloride (IIc). Yield 2.64 g (93%), mp 205–210°C.
Found, %: Cl 12.71; N 14.76; S 11.43. C12H14ClN3OS.
Calculated, %: Cl 12.52; N 14.81; S 11.29.
–1
hexane, 2:1). IR spectrum, cm : 1240 (>C=S), 3330
1
(>NH). H NMR spectrum, d, ppm: 2.33 s (3H, CH3),
2.80 s (3H, NCCH3), 7.10 s (H3, Harom), 7.3–8.0 m (3H,
H
arom), 10.20 s (H, >NH). Found, %: C 70.03; H 6.01;
S-(2-Methyl-8-methoxy-4-quinolyl)-thiouronium
chloride (IId). Yield 2.66 g (94%), mp 180–185°C.
Found, %: Cl 12.41; N 14.95; S 11.37. C12H14ClN3OS.
Calculated, %: Cl 12.52; N 14.81; S 11.29.
N 7.60; S 16.79. C11H11NS. Calculated, %: C 69.84;
H 5.82; N 7.41; S 16.93.
2-Methyl-6-methoxy-4-quinolyl isothiocyanate
(IIIc). Yield 1.62 g (70.6%), mp 195–200°C, Rf 0.62
S-(2-Methyl-6-bromo-4-quinolyl)thiouronium
chloride (IIe). Yield 3.19 g (96%), mp 175–180°C.
Found, %: Cl 10.90; N 12.46; S 9.50. C11H11BrClN3S.
Calculated, %: Cl 10.68; N 12.63; S 9.62.
–1
(from acetone). IR spectrum, cm : 2240–1940
1
(–N=C=S). H NMR spectrum, d, ppm: 2.65 s (3H,
NCCH3), 4.20 s (3H, OCH3), 7.0 s (H3, Harom), 7.20–
8.0 m (3H, Harom). Found, %: C 62.79; H 4.54; N 12.25;
S 13.70. C12H10N2OS. Calculated, %: C 62.61; H 4.35;
N 12.17; S 13.91.
S-(2-Methyl-8-chloro-4-quinolyl)thiouronium
chloride (IIf). Yield 2.56 g (89%), mp 215–217°C. Found,
%: Cl 24.78; N 14.77; S 10.98. C11H11Cl2N3S. Calculated,
%: Cl 24.65; N 14.58; S 11.11.
2-Methyl-6-methoxy-4-sulfanylquinoline (IVc).
Not found.
Substituted 2-methyl-4-quinolyl isothiocyanates
IIIa–IIIf and 2-methyl-4-mercaptoquinolines IVa–
IVf. Awater solution of 0.01 mol of thiouronium salt IIa–
IIf was alkalified to pH~10 and was heated on a water
bath for 1.5 h. On cooling the separated precipitate of
IIIa–IIIf was filtered off, washed with water, and
recrystallized from a mixture ethanol–water, 1:1. The
filtrate was acidified with hydrochloric acid to pH 6, and
2-Methyl-8-methoxy-4-quinolyl isothiocyanate
(IIId). Yield 0.91 g (39.7%), mp 193–195°C, Rf 0.66
–1
(from acetone). IR spectrum, cm : 2250–1930
1
(–N=C=S). H NMR spectrum, d, ppm: 2.55 s (3H,
NCCH3), 3.90 s (3H, OCH3), 6.90 s (H3, Harom), 7.1–
7.9 m (3H, Harom). Found, %: C 62.78; H 4.47; N 12.25;
S 14.08. C12H10N2OS. Calculated, %: C 62.61; H 4.35;
N 12.17; S 13.91.
RUSSIAN JOURNALOF ORGANIC CHEMISTRYVol. 41 No. 5 2005

SYNTHESIS OF SUBSTITUTED 2-METHYL-4-QUINOLYL ISOTHIOCYANATES
771
2-Methyl-8-methoxy-4-sulfanylquinoline (IVd).
Yield 0.69 g (33.5%), mp 170–174°C, Rf 0.67 (from
spectrum, d, ppm: 2.40 s (3H, NCCH3), 6.40 s (H3, Harom),
6.8–7.5 m (3H, Harom). Found, %: C 56.13; H 3.12;
N 12.10; S 13.78. C11H7ClN2S. Calculated, %: C 56.29;
H 2.99; N 11.94; S 13.65.
–1
ethanol–hexane, 2:1). IR spectrum, cm : 1220 (>C=S),
1
3200 (>NH). H NMR spectrum, d, ppm: 2.20 s (3H,
NCCH3), 3.20 s (3H, OCH3), 6.5 s (H3, Harom), 6.9–
7.7 m (3H, Harom) 11.00 s (H, >NH). Found, %: C 64.52;
H 5.58; N 6.70; S 15.77. C11H11NOS. Calculated, %:
C 64.39; H 5.37; N 6.83; S 15.61.
2-Methyl-8-chloro-4-sulfanylquinoline (IVf). Yield
1.36 g (65%), mp 220–223°C, Rf 0.57 (from ethanol–
–1
hexane, 1:1). IR spectrum, cm : 1215 (>C=S), 3250
(>NH). 1H NMR spectrum, d, ppm: 2.20 s (3H, NCCH3),
6.45 s (H3, Harom), 6.7–7.3 m (3H, Harom) 10.0 s (H, >NH).
Found, %: C 57.56; H 4.00; N 6.56; S 15.41. C10H8ClNS.
Calculated, %: C 57.28; H 3.82; N 6.68; S 15.27.
2-Methyl-6-bromo-4-quinolyl isothiocyanate
(IIIe). Yield 0.5 g (18%), mp 190–195°C. IR spectrum,
–1
cm : 2250–1930 (–N=C=S). 1H NMR spectrum, d, ppm:
2.60 s (3H, NCCH3), 6.80 s (H3, Harom), 7.0–7.6 m (3H,
REFERENCES
H
arom). Found, %: C 47.50; H 2.70; N 10.21; S 11.29.
C11H7BrN2S. Calculated, %: C 47.31; H 2.51; N 10.04;
S 11.47.
1. Avetisyan,A.A., Aleksanyan, I.L., andAmbartsumyan, L.P.,
Zh. Org. Khim., 2004, vol. 40, p. 434.
2-Methyl-6-bromo-4-sulfanylquinoline (IVe).
Yield 2.29 g (50.6%), mp 225°C, Rf 0.57 (from ethanol–
hexane, 1:1). IR spectrum, cm : 1225 (>C=S), 3300
(>NH). 1H NMR spectrum, d, ppm: 2.70 s (3H, NCCH3),
7.0 s (H3, Harom), 7.3–8.1 m (3H, Harom) 11.20 s (H, >NH).
Found, %: C 47.36; H 3.32; N 5.43; S 12.77. C10H8BrNS.
Calculated, %: C 47.24; H 3.15; N 5.51; S 12.60.
2. Warren, L.A. and Smiles, S., J. Chem. Soc., 1930, vol. 957,
p. 1327.
3. Ingold, C.K., Structure and Mechanism in Organic
Chemistry, Ithaca: Cornell Univ., 1969, 2nd ed. Translated
under the title Teoreticheskie osnovy organicheskoi khimii,
Moscow: Mir, 1973.
4. March, J., Advanced Organic Chemistry. Reactions,
Mechanisms, and Structure, New York: Wiley-Interscience,
1987, vol. 3, p. 114.
–1
2-Methyl-8-chloro-4-quinolyl isothiocyanate
(IIIf). Yield 0.07 g (3%), mp 300°C (decomp.). IR
–1
1
5. Org. Synth., 1967, vol. 4, p. 700.
spectrum, cm : 2245–1920 (–N=C=S). H NMR
RUSSIAN JOURNALOF ORGANIC CHEMISTRYVol. 41 No. 5 2005