Synthesis of N-[1-(1H-Benzimidazol-2-ylsulfanyl)- 2,2,2-trichloroethyl] arenesulfonamides by reaction of N-(2,2,2-Trichloroethylidene)arenesulfonamides with 1H-Benzimidazole-2-thiol

Full text of DOI:10.1134/S1070428012040276

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 4, pp. 607–609. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © I.B. Rozentsveig, V.Yu. Serykh, G.G. Levkovskaya, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 4,
pp. 609–610.
SHORT
COMMUNICATIONS
Synthesis of N-[1-(1H-Benzimidazol-2-ylsulfanyl)-
2,2,2-trichloroethyl]arenesulfonamides by Reaction
of N-(2,2,2-Trichloroethylidene)arenesulfonamides
with 1H-Benzimidazole-2-thiol
I. B. Rozentsveig, V. Yu. Serykh, and G. G. Levkovskaya
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: i_roz@irioch.irk.ru
Received November 13, 2011
DOI: 10.1134/S1070428012040276
Electron-deficient character of the azomethine
moiety in N-sulfonyl imines derived from polyhalo-
carbonyl compounds is determined by the effect of
strong electron-withdrawing substituents, which favors
their reactions with various nucleophiles and polynu-
cleophiles [1]. Such transformations provide conven-
ient approaches to various functionalized sulfonamide
derivatives [1–14] as interesting models for stereo-
chemical studies [5–8] and reagents [1, 9–16].
activated C=N bond in N-(trichloroethylidene)arene-
sulfonamides was studied. Polyfunctional S-adducts
obtained in these reactions were then used to synthe-
size thiazolidine derivatives [12–16].
Reactions of N-(trichloroethylidene)arenesulfon-
amides (that are readily obtained in one step from
accessible N,N-dichloroarenesulfonamides and tri-
chloroethylene [1]) with aromatic or heteroaromatic
thiols were not reported previously. On the other hand,
expected products of such reactions may be promising
for the development of procedures for the preparation
of fused heterocyclic systems, as well as of N-protect-
ed hetarylsulfanyl-substituted amino acids.
Reactions of N-sulfonyl polyhaloaldehyde and
polyhaloketone imines with oxygen- and nitrogen-
centered nucleophiles have been studied in most detail.
However, only a few examples of analogous reactions
with sulfur-centered nucleophiles were reported; in
particular, addition of phenylmethanethiol, benzene-
thiols, 2-sulfanylethanol, and 2-sulfanylacetic acid to
N-[1-(dialkoxyphosphoryl)-2,2,2-trichloroethylidene]-
arenesulfonamides was described in [12]. Further-
more, addition of alkanethiols [1, 13], 2-sulfanyl-
ethanol [14], and 2-sulfanylacetic acid [15, 16] to the
In continuation of our studies on reactions of sulfur-
centered nucleophiles with N-sulfonyl imines derived
from polyhalocarbonyl compounds the present com-
munication reports on the reaction of N-(2,2,2-tri-
chloroethylidene)arensulfonamides Ia and Ib with
1H-benzimidazole-2-thiol as a possible route to func-
tionalized imidazole and sulfonamide derivatives.
Cl
95°C, 8–10 h
–Cl2
N
CCl3
+
ArSO2NCl2
Cl
ArSO2
Cl
Ia, Ib
Cl3C
NHSO2Ar
N
N
30°C, 5 h
Ia, Ib
+
SH
S
N
H
N
H
IIa, IIb
Ar = 4-ClC6H4 (a), 4-MeC6H4 (b).
607

ROZENTSVEIG et al.
608
1
3255, 3150 (NH); 1348, 1171 (SO2). H NMR spec-
Imines Ia and Ib were synthesized by radical addition
of N,N-dichloroarenesulfonamides to trichloroethyl-
ene, which was developed by us previously [17].
1H-Benzimidazole-2-thiol reacted as S-nucleophile
with compounds Ia and Ib under stirring in excess
trichloroethylene or in diethyl ether on slight heating,
and the corresponding addition products at the C=N
bond, N-[1-(1H-benzimidazol-2-ylsulfanyl)-2,2,2-tri-
chloroethyl]arenesulfonamides IIa and IIb, were
formed in good yield.
3
trum, δ, ppm: 2.36 s (CH3), 5.19 d (1H, CH, J =
9.2 Hz), 7.12 m (4H, C6H4), 7.36 d and 7.78 d (2H
3
3
each, Harom, J = 8.2 Hz), 8.82 d (1H, NHSO2, J =
9.2 Hz), 12.45 br.s (1H, NH). 13C NMR spectrum,
δC, ppm: 21.15 (CH3), 85.11 (SCH), 101.33 (CCl3),
109.81, 122.72, 132.54, 168.30, 126.50, 129.41,
137.83, 141.14. Found, %: C 42.68; H 3.18; Cl 23.43;
N 9.24; S 14.16. C16H14Cl4N3O2S2. Calculated, %:
C 42.63; H 3.13; Cl 23.59; N 9.32; S 14.22.
1
The H and 13C NMR spectra were recorded on
Compounds IIa and IIb were isolated as colorless
crystalline substances which were readily soluble in
DMSO and acetone, poorly soluble in other organic
solvents, and insoluble in water. Their structure was
confirmed by spectral (NMR, IR) and analytical data.
a Bruker DPX-400 spectrometer at 400.61 and
100.13 MHz, respectively, from solutions in DMSO-d6
using tetramethylsilane as internal reference. The IR
spectra were measured in KBr on a Bruker IFS-25
instrument.
Thus we have synthesized new halogen-containing
polyfunctional sulfonamide derivatives IIa and IIb.
A unique combination of pharmacophoric sulfonamide
group, imidazole ring, and polyhalomethyl moiety in
their molecules makes them promising as biologically
active substances and reagents for subsequent hetero-
cyclization.
REFERENCES
1. Levkovskaya, G.G., Drozdova, T.I., Rozentsveig, I.B.,
and Mirskova, A.N., Usp. Khim., 1999, vol. 68, p. 638.
2. Rozentsveig, G.N., Popov, A.V., Rozentsveig, I.B., and
Levkovskaya, G.G., Russ. J. Org. Chem., 2008, vol. 44,
p. 1486.
3. Rozentsveig, I.B., Ushakova, I.V., Kondrashov, E.V.,
Rozentsveig, G.N., Levkovskaya, G.G., and Mirsko-
va, A.N., Russ. J. Org. Chem., 2005, vol. 41, p. 1558.
4. Rozentsveig, G.N., Aizina, Yu.A., Rozentsveig, I.B.,
Levkovskaya, G.G., Sarapulova, G.I., Mirskova, A.N.,
and Drozdova, T.I., Russ. J. Org. Chem., 2003, vol. 39,
p. 554.
5. Sarapulova, G.I., Rozentsveig, G.N., Rozentsveig, I.B.,
and Levkovskaya, G.G., Russ. J. Gen. Chem., 2003,
vol. 73, p. 996.
6. Sarapulova, G.I., Rozentsveig, G.N., Aizina, Yu.A.,
Rozentsveig, I.B., and Levkovskaya, G.G., Russ. J. Gen.
Chem., 2004, vol. 74, p. 610.
7. Chernyshev, K.A., Krivdin, L.B., Rozentsveig, G.N.,
Ushakova, I.V., Rozentsveig, I.B., and Levkov-
skaya, G.G., Russ. J. Org. Chem., 2008, vol. 44, p. 76.
8. Shainyan, B.A., Chipanina, N.N., Aksamentova, T.N.,
Oznobikhina, L.P., Rosentsveig, G.N., and Rosen-
tsveig, I.B., Tetrahedron, 2010, vol. 66, p. 8551.
N-[1-(1H-Benzimidazol-2-ylsulfanyl)-2,2,2-tri-
chloroethyl]-4-chlorobenzenesulfonamide (IIa).
A solution of 2.61 g (0.010 mol) of N,N,4-trichloro-
benzenesulfonamide in 10–12 ml of trichloroethylene
was heated under reflux in an inert atmosphere (argon
or nitrogen) until chlorine no longer evolved (8–10 h,
starch–iodine test). The solution was evaporated under
reduced pressure, 50 ml of anhydrous diethyl ether was
added to the solid residue, 1.20 g (0.008 mol) of
1H-benzimidazole-2-thiol was added, and the mixture
was stirred for 4–5 h at 25–30°C. The precipitate was
filtered off, washed with chloroform (3×30 ml), and
dried. Yield 3.50 g (93%), mp 159–161°C. IR spec-
trum, ν, cm–1: 3279, 3146 (NH); 1354, 1165 (SO2).
3
1H NMR spectrum, δ, ppm: 5.17 d (1H, CH, J =
9.2 Hz), 7.11 m (4H, C6H4), 7.64 d and 7.88 d (2H
3
3
each, Harom, J = 8.5 Hz), 9.01 d (1H, NHSO2, J =
9.2 Hz), 12.48 br.s (1H, NH). 13C NMR spectrum, δC,
ppm: 86.06 (SCH), 102.52 (CCl3), 109.89, 122.70,
132.67, 168.49, 129.10, 129.45, 137.80, 140.97.
Found, %: C 38.55; H 2.48; Cl 30.56; N 8.85; S 13.43.
C15H11Cl4N3O2S2. Calculated, %: C 38.24; H 2.35;
Cl 30.10; N 8.92; S 13.61.
9. Rozentsveig, G.N., Rozentsveig, I.B., Levkov-
skaya, G.G., and Mirskova, A.N., Russ. J. Org. Chem.,
2003, vol. 39, p. 1804.
10. Rozentsveig, I.B., Evstaf’eva, I.T., Sarapulova, G.I.,
Levkovskaya, G.G., and Aizina, J.A., Arkivoc, 2003,
part (xiii), p. 45.
N-[1-(1H-Benzimidazol-2-ylsulfanyl)-2,2,2-tri-
chloroethyl]-4-methylbenzenesulfonamide (IIb) was
synthesized in a similar way from 2.40 g (0.01 mol) of
N,N-dichloro-4-methylbenzenesulfonamide. Yield
3.21 g (89%), mp 167–168°C. IR spectrum, ν, cm–1:
11. Rozentsveig, I.B., Rozentsveig, G.N., Serykh, V.Yu.,
Chernyshev, K.A., and Levkovskaya, G.G., Eur. J. Org.
Chem., 2011, p. 4415.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 4 2012

SYNTHESIS OF N-[1-(1H-BENZIMIDAZOL-2-YLSULFANYL)-2,2,2-TRICHLOROETHYL]...
609
12. Rassukana, Yu.V., Onys’ko, P.P., Davydova, K.O., and
15. Mirskova, A.N., Drozdova, T.I., Levkovskaya, G.G.,
Bannikova, O.B., Kalikhman, I.D., and Voronkov, M.G.,
Sinitsa, A.D., Eur. J. Org. Chem., 2004, p. 3643.
Zh. Org. Khim., 1982, vol. 18, p. 1407.
16. Evstaf’eva, I.T., Levkovskaya, G.G., Bannikova, O.B., and
13. Levkovskaya, G.G., Drozdova, T.I., Mirskova, A.N.,
and Voronkov, M.G., USSR Inventor’s Certificate
no. 908012, 1996; Byull. Izobret., 1997, no. 7, p. 292.
Mirskova, A.N., Zh. Org. Khim., 1993, vol. 29, p. 794.
14. Bryuzgin, A.A., Levkovskaya, G.G., Mirskova, A.N.,
and Kalikhman, I.D., Zh. Org. Khim., 1990, vol. 26,
p. 1296.
17. Mirskova, A.N., Levkovskaya, G.G., Drozdova, T.I.,
Kalikhman, I.D., and Voronkov, M.G., Zh. Org. Khim.,
1982, vol. 18, p. 452.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 4 2012