New method for synthesis of 4-tosyl-5-chlorothiazole-2-thiol derivatives

Full text of DOI:10.1134/S1070363214110401

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 11, pp. 2273–2274. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © A.N. Kornienko, V.S. Zyabrev, V.S. Brovarets, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 11, pp. 1915–1916.
LETTERS
TO THE EDITOR
New Method For Synthesis
of 4-Tosyl-5-chlorothiazole-2-thiol Derivatives
A. N. Kornienko, V. S. Zyabrev, and V. S. Brovarets
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 1, Kyiv, 02660 Ukraine
e-mail: brovarets@bpci.kiev.ua
Received August 11, 2014
Keywords: thiazole, cyclocondensation, 1-tosyl-2,2-dichloroethenylisothiocyanate
DOI: 10.1134/S1070363214110401
Thiazole derivatives containing sulfonyl groups in
positions 2 and 4 are interesting objects to study
nucleophilic substitution in the thiazole ring [1–3].
acid to obtain new thiazole derivatives, 2-(methyl-
sulfonyl)-4-tosyl-5-chlorothiazole IV and 4-tosyl-5-
chlorothiazole-2-sulfonyl chloride V. Composition and
structure of the compounds IV and V were confirmed
by elemental analysis, IR and NMR spectroscopy. In
particular, IR spectra of compounds IV and V
contained strong absorption bands at 1155–1180 and
1325–1385 cm–1 assigned to the two SO2 groups
(Scheme 1).
A method for synthesis of 2,4-disulfo-5-chloro-
thiazol via cyclocondensation of 1-tosyl-2,2-dichloro-
ethenylisothiocyanate I with thiols in the presence of
pyridine hydrochloride is known [1]. A disadvantage
of this method is handling with volatile thiols, when
alkylsulfonyl group has to be introduced at position 2
of the thiazole ring.
2-(Methylsulfanyl)-4-tosyl-5-chlorothiazole (IIIa).
1-Tosyl-2,2-dichloroethenylisothiocyanate I [4], 56.74 g
(184 mmol), was added portionwise to a suspension of
47.32 g (197 mmol) of sodium sulfide nonahydrate in
200 mL of ethanol upon cooling to 5–10°C within 1 h.
After stirring during 2 h, a solution of 12.58 mL
(202 mmol) of methyl iodide in 20 mL of ethanol was
added dropwise to the mixture at 10–15°C within
We have found that isothiocyanate I undergos
cyclocondensation with sodium sulfide to form sodium
4-tosyl-5-chlorothiazole-2-thiolate II. The latter was
methylated or benzylated to give the corresponding
derivatives IIIa and IIIb with quantitative yields.
Oxidation of compounds IIIa and IIIb was further
carried out by hydrogen peroxide or chlorine in acetic
Scheme 1.
Ts
Ts
Ts
S
RHlg
N
N
Na2S 9H2O
Cl
Ts
C
N
Cl
SR
Cl
SNa
S
S
Cl
I
II
IIIа, IIIb
Ts
N
N
H2O2, AcOH
R = Me
Cl2, AcOH, H2O
R = Bn
IIIа, IIIb
Cl
SO2Me
Cl
SO2Cl
S
S
IV
V
R = Me (a), Bn (b).
2273

2274
KORNIENKO et al.
2.5 h. Then the reaction mixture was diluted with
300 mL of water, and the precipitated compound IIIa
was filtered off. Yield 99% (58.06 g), colorless
crystals, mp 98°C (MeOH) (mp 94–95°C [1]). IR
136.0, 138.0, 146.1, 150.6, 163.3. Found, %: C 37.73;
H 3.08; Cl 10.19; S 27.29. C11H10ClNO4S3. Calculated,
%: C 37.55; H 2.86; Cl 10.08; S 27.34.
1
spectrum (KВr), ν, cm–1: 1149 w, 1326 w (SO2). H
4-Tosyl-5-chlorothiazole-2-sulfonyl chloride (V).
Chlorine was bubbled through a suspension of 6.60 g
(16.7 mmol) of compound IIIb in 120 mL of acetic
acid and 12 mL of water upon cooling to 5–10°C and
stirring, during 1 h. The reaction mixture was in-
cubated at the same temperature during 12 h, and the
precipitate was filtered off. Yield 76% (4.71 g), color-
less crystals, mp 145°C (CCl4). IR spectrum (KВr), ν,
NMR spectrum (400 MHz, DMSO-d6), δ, ppm: 2.41 s
(3H, CH3C), 2.65 s (3H, CH3S), 7.49 d (2H, C6H2, 3JHH
8.2 Hz), 7.87 d (2H, C6H2, 3JHH 8.2 Hz).
2-(Benzylsulfanyl)-4-tosyl-5-chlorothiazole (IIIb)
was prepared similarly from 18.49 g (60 mmol) of
1-tosyl-2,2-dichloroethenylisothiocyanate I, 15.13g
(63 mmol) sodium sulfide nonahydrate, and 7.49 mL
(63 mmol) of benzyl bromide. Yield 91% (21.72 g),
colorless crystals, mp 86°C (MeOH) (mp 69–70°C
[1]). IR spectrum (KВr), ν, cm–1: 1150 w, 1332 w
1
cm–1: 1157 w, 1182 w, 1340 w, 1386 w (SO2). H
NMR spectrum (500 MHz, CDCl3), δ, ppm: 2.47 s
(3H, CH3), 7.40 d (2H, C6H2, 3JHH 8.5 Hz), 7.99 d (2H,
3
C6H2, JHH 8.5 Hz). 13C NMR spectrum (126 MHz,
1
(SO2). H NMR spectrum (400 MHz, DMSO-d6), δ,
CDCl3), δС, ppm: 21.4, 128.4, 129.9, 135.2, 139.3,
146.1, 150.5, 160.2. Found, %: C 32.31; H 1.92; Cl
18.72; N.57. C10H7Cl2NO4S3. Calculated, %: C 32.26;
H 1.90; Cl 19.05; N 3.76.
ppm: 2.42 s (3H, CH3), 4.43 s (2H, CH2), 7.19–7.35 m
3
(5H, C6H5), 7.51 d (2H, C6H2, JHH 7.6 Hz), 7.88 d
(2H, C6H2, 3JHH 7.6 Hz).
2-(Methylsulfonyl)-4-tosyl-5-chlorothiazole (IV).
12 mL of 35% aqueous hydrogen peroxide solution
was added to a suspension of 13.97 g (43.7 mmol) of
IIIa in 45 mL of acetic acid. After refluxing the
mixture during 1 h, 6 mL of 35% aqueous hydrogen
peroxide solution was added to it, and the mixture was
further refluxed during 0.5 h. After cooling, compound
IV was filtered off. Yield 89% (13.70 g), colorless
crystals, mp 179°C (EtOAc). IR spectrum (KВr), ν,
REFERENCES
1. Babii, B., Zyabrev, S., and Drach, S., Russ. J. Gen.
Chem., 2002, vol. 72, no. 11, p. 1730. DOI: 10.1023/
A:1023337112138.
2. Turov, V., Babii, B., Zyabrev, S., and Drach, S., Russ. J.
Gen. Chem., 2006, vol. 76, no. 10, p. 1685. DOI:
10.1134/S1070363206100355.
1
cm–1: 1155 w, 1326 w, 1339 w (SO2). H NMR spec-
3. Turov, V. and Drach, S., Russ. J. Gen. Chem., 2008,
vol. 78, no. 4, p. 629. DOI: 10.1134/S1070363208040208.
trum (500 MHz, CDCl3), δ, ppm: 2.44 s (3H, CH3C),
3
3.31 s (3H, CH3S), 7.37 d (2H, C6H2, JHH 8.0 Hz),
4. Kharchenko, A.V., Seferov, S.O., Zyabrev, V.S.,
Chervonyi, V.A., Vdovenko, S.I., and Drach, B.S., Ukr.
Khim. Zh., 1993, vol. 59, no. 6, p. 637.
7.95 d (2H, C6H2, JHH 8.0 Hz). 13C NMR spectrum
(126 MHz, CDCl3), δС, ppm: 21.8, 42.1, 128.6, 130.2,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 11 2014