Selective synthesis of 3-[1-(Organylsulfanyl)ethyl]-and 3-[2-(Organylsulfanyl)ethyl]-5-chloro-1H-pyrazoles

Full text of DOI:10.1134/S1070428012100259

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 10, pp. 1388–1389. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © D.O. Samultsev, E.V. Rudyakova, G.G. Levkovskaya, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 10,
pp. 1391–1392.
SHORT
COMMUNICATIONS
Selective Synthesis of 3-[1-(Organylsulfanyl)ethyl]-
and 3-[2-(Organylsulfanyl)ethyl]-5-chloro-1H-pyrazoles
D. O. Samultsev, E. V. Rudyakova, and G. G. Levkovskaya
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: ggl@irioch.irk.ru
Received May 13, 2012
DOI: 10.1134/S1070428012100259
Pyrazole ring constitutes a structural fragment of
many up-do-date pharmacologically active compounds
possessing analgesic, anti-inflammatory, antibacterial,
and other properties. Pyrazole derivatives have found
application as insectoacaricides, dyes, luminophores,
ligands, etc. [1–4]. At present, search for new synthons
for the preparation of pyrazole derivatives is an ex-
tensively developing field of study [1–3].
molar amounts of the reactants in benzene at 60°C in
the presence of azobis(isobutyronitrile) (AIBN) or
under UV irradiation over a period of 6 h (Scheme 1).
3-{1-[Butyl(benzyl)sulfanyl]ethyl}-5-chloro-1H-
pyrazoles IVa and IVb were synthesized in 80–82%
yield by reaction of 5-chloro-3-(1-chloroethyl)-1H-
pyrazoles IIIa and IIIb with an equimolar amount of
the corresponding thiol in DMSO in the presence of
KOH at room temperature (Scheme 2). It should be
noted that the use of 3-(1-bromoethyl)pyrazole deriva-
tives [5] was not efficient; in this case, mixtures of
compounds IV and vinylpyrazoles I at a ratio of ~1:10
were obtained.
We recently synthesized 3-haloalkyl-5-chloropyra-
zoles which were used as starting compounds for the
preparation of previously unknown 3-alkenyl-5-chloro-
pyrazoles [5] as versatile building blocks for purpose-
ful synthesis of materials for advanced technologies.
The present communication describes a chemo-
selective synthesis of new regioisomeric 3-{1-[butyl-
(benzyl)sulfanyl]ethyl}- and 3-{2-[butyl(benzyl)sul-
fanyl]ethyl}-5-chloropyrazoles by reaction of
3-(1-chloroethyl)- and 3-vinyl-5-chloropyrazoles with
butane-1-thiol and phenylmethanethiol, respectively.
Scheme 2.
Me
N
Me
SR2
Cl
KOH, DMSO
5 h
R2SH
N
+
Cl
Cl
N
N
Radical addition of thiols to 5-chloro-3-vinyl-1H-
pyrazoles Ia and Ib gave the corresponding anti-
Markovnikov adducts, 3-{2-[butyl(benzyl)sulfanyl]-
ethyl}-5-chloro-1H-pyrazoles IIa and IIb in 77–80%
yield. The reactions were carried out by heating equi-
R1
R1
IVa, IVb
IIIa, IIIb
R1 = Me, R2 = PhCH2 (a); R1 = PhCH2, R2 = Bu (b).
Compounds IIa, IIb, IVa, and IVb were isolated as
oily liquids which were readily soluble in organic
solvents.
Scheme 1.
H2C
SR2
PhH, AIBN
or PhH, hν
6 h
3-[2-(Benzylsulfanyl)ethyl]-5-chloro-1-methyl-
1H-pyrazole (IIa). A mixture of 0.14 g (0.001 mol) of
vinylpyrazole Ia and 0.12 g (0.001 mol) of phenyl-
methanethiol in 5 ml of benzene was irradiated with
UV light over a period of 6 h at 60°C. The solvent was
removed under reduced pressure, and the oily product
was washed with cold hexane and dried under reduced
R2SH
N
+
N
Cl
Cl
N
N
R1
R1
Ia, Ib
IIa, IIb
R1 = Me, R2 = PhCH2 (a); R1 = PhCH2, R2 = Bu (b).
1388

SELECTIVE SYNTHESIS OF 3-[1-(ORGANYLSULFANYL)ETHYL]- ...
1389
pressure. Yield 0.21 g (80%). IR spectrum, ν, cm–1:
3130 (=C–HPyr), 3084, 3061, 3027, 3003 (=C–HPh),
2941, 2919, 2850 (CHAlk), 1601, 1513 (C=C, C=N).
1H NMR spectrum (CDCl3), δ, ppm: 2.64 t (2H,
(C4), 127.00 (C5), 127.01 (Cp), 128.55 (Cm), 129.13
(Co), 138.62 (Ci), 154.94 (C3). Found, %: C 58.51;
H 5.65; Cl 13.33; N 10.51; S 11.99. C13H15ClN2S.
Calculated, %: C 58.53; H 5.67; Cl 13.29; N 10.50;
S 12.02.
3
3
CH2CH2S, J = 6.9 Hz), 2.76 t (2H, 3-CH2, J =
6.9 Hz), 3.57 s (2H, SCH2C6H5), 3.76 s (3H, NCH3),
1-Benzyl-3-[1-(butylsulfanyl)ethyl]-5-chloro-1H-
pyrazole (IVb) was synthesized in a similar way from
0.25 g (0.001 mol) of 1-benzyl-5-chloro-3-(1-chloro-
ethyl)-1H-pyrazole and 0.09 g (0.001 mol) of butane-
1-thiol. Yield 0.24 g (80%). IR spectrum, ν, cm–1: 3130
(=C–HPyr), 3083, 3063, 3010 (=C–HPh), 2952, 2940,
2930, 2919, 2850 (C–HAlk), 1601, 1513 (C=C, C=N).
1H NMR spectrum (CDCl3), δ, ppm: 0.83 t (3H, CH3,
J = 7.3 Hz), 1.30 m (2H, CH2, J = 7.3 Hz), 1.46 m (2H,
CH2, J = 7.3 Hz), 1.54 d (3H, CH3, J = 7.2 Hz), 2.39 m
(2H, CH2, J = 7.3 Hz), 3.99 q (1H, CHS, J = 7.2 Hz),
5.25 s (2H, CH2), 6.21 s (1H, 4-H), 7.26 m (5H, C6H5).
13C NMR spectrum, δC, ppm: 13.76 (CH3), 21.12
(CH3), 22.18 (CH2), 30.96 (CH2), 31.58 (CH2), 37.64
(SCH), 52.69 (NCH2), 102.51 (C4), 127.29 (C5),
127.30 (Cp), 127.91 (Cm), 128.74 (Co), 136.29 (Ci),
155.80 (C3). Found, %: C 62.31; H 6.83; Cl 11.44;
N 9.06; S 10.40. C16H21ClN2S. Calculated, %: C 62.22;
H 6.85; Cl 11.48; N 9.07; S 10.38.
13
5.96 s (1H, 4-H), 7.20 m (5H, C6H5). C NMR spec-
trum, δC, ppm: 28.43 (CH2CH2S), 30.38 (3-CH2),
35.43 (SCH2C6H5), 35.94 (NCH3), 103.05 (C4), 126.44
(C5), 126.58 (Cp), 128.08 (Cm), 128.56 (Co), 138.02
(Ci), 150.27 (C3). Found, %: C 58.50; H 5.62;
Cl 13.21; N 10.54; S 12.08. C13H15ClN2S. Calculated,
%: C 58.53; H 5.67; Cl 13.29; N 10.50; S 12.01.
1-Benzyl-3-[2-(butylsulfanyl)ethyl]-5-chloro-1H-
pyrazole (IIb) was synthesized in a similar way from
0.22 g (0.001 mol) of 1-benzyl-5-chloro-3-vinyl-1H-
pyrazole (Ib) and 0.09 g (0.001 mol) of butane-1-thiol
[yield 0.24 g (80%)], as well as by heating the same
amounts of the reactants and 0.0001 mol of AIBN in
benzene for 6 h at 60°C [yield 0.23 g (77%)]. IR spec-
trum, ν, cm–1: 3131 (=C–HPyr), 3082, 3060, 3027, 3004
(=C–HPh), 2940, 2933, 2920, 2850 (C–HAlk), 1600,
1
1515 (C=C, C=N). H NMR spectrum (CDCl3), δ,
ppm: 0.91 t (3H, CH3, J = 7.3 Hz), 1.43 m (2H, CH2,
J = 7.3 Hz), 1.57 m (2H, CH2, J = 7.3 Hz), 2.54 t (2H,
CH2, J = 7.3 Hz), 2.79 t (2H, CH2CH2S, J = 6.9 Hz),
2.81 t (2H, 3-CH2, J = 6.9 Hz), 5.28 s (2H, NCH2),
The IR spectra were recorded on a Varian-3100
1
spectrometer with Fourier transform. The H and 13C
NMR spectra were measured on a Bruker DPX-400
spectrometer at 400.13 and 101.61 MHz, respectively,
using hexamethyldisiloxane as internal reference. UV
irradiation was generated by a DRT-240 lamp (λ 240–
320 nm; 240 W). Compounds Ia, Ib, IIIa, and IIIb
were synthesized according to the procedures de-
scribed in [5].
13
6.12 s (1H, 4-H), 7.25 m (5H, C6H5). C NMR spec-
trum, δC, ppm: 13.82 (CH3), 22.09 (CH2), 22.17 (CH2),
29.57 (CH2CH2S), 31.80 (SCH2C3H7), 32.08 (3-CH2),
52.76 (NCH2), 104.18 (C4), 127.39 (C5), 127.97 (Cp),
128.07 (Ci), 128.84 (Co), 136.42 (Ci), 151.79 (C3).
Found, %: C 62.38; H 6.84; Cl 11.45; N 9.11; S 10.40.
C16H21ClN2S. Calculated, %: C 62.22; H 6.85;
Cl 11.48; N 9.07; S 10.38.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 11-03-00461_a).
3-[1-(Benzylsulfanyl)ethyl]-5-chloro-1-methyl-
1H-pyrazole (IVa). Potassium hydroxide, 0.17 g
(0.003 mol), was added to a solution of 0.18 g
(0.001 mol) of 5-chloro-3-(1-chloroethyl)-1-methyl-
1H-pyrazole (IIIa) in 3 ml of DMSO, the mixture was
stirred for 20 min, 0.12 g (0.001 mol) of phenylmeth-
anethiol was added, and the mixture was stirred for 5 h
at 20°C. Yield 0.21 g (82%). IR spectrum, ν, cm–1:
3131 (=C–HPyr), 3085, 3063, 3027, 3008 (=C–HPh),
2950, 2919, 2855 (C–HAlk), 1601, 1515 (C=C, C=N).
1H NMR spectrum (CDCl3), δ, ppm: 1.50 d (3H, CH3,
J = 7.1 Hz), 3.63 s (2H, SCH2), 3.77 s (3H, NCH3),
3.87 q (1H, CHS, J = 7.1 Hz), 6.14 s (1H, 4-H), 7.26 m
(5H, C6H5). 13C NMR spectrum, δC, ppm: 21.07 (CH3),
35.93 (SCH2), 36.21 (SCH), 37.53 (NCH3), 102.36
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012