N-alkylation of N-(2,2,2-trichloroethyl)arenesulfonamides

Full text of DOI:10.1134/S1070428013030251

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 3, pp. 466–468. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © I.B. Rozentsveig, A.V. Popov, G.G. Levkovskaya, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 3,
pp. 478–480.
SHORT
COMMUNICATIONS
Dedicated to Full Member of the Russian Academy of Sciences
I.P. Beletskaya on her jubilee
N-Alkylation of N-(2,2,2-Trichloroethyl)arenesulfonamides
I. B. Rozentsveig, A. V. Popov, and G. G. Levkovskaya
Favorskii Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: i_roz@irioch.irk.ru
Received December 26, 2012
DOI: 10.1134/S1070428013030251
Intramolecular cyclization and intermolecular ad-
dition reactions with sulfonamide derivatives underlie
widely used syntheses of sulfonamide drugs [1, 2].
N-(Polyhaloalkyl)sulfonamides are convenient re-
agents for the preparation of various sulfonamide
derivatives such as biologically active N-sulfonyl-sub-
stituted amino acids [3, 4], amidines [5], and amino-
carbonyl [6] and heterocyclic compounds [6–12]. On
the other hand, reactions involving the NH group of
N-(polychloroethyl)sulfonamides have been poorly
studied; only their intramolecular heterocyclizations
[5, 6] and reactions with methyl vinyl ketone [13] have
been reported.
In continuation of our systematic studies on the
reactivity of N-(polychloroethyl)sulfonamides the
present communication reports on reactions of
N-(2,2,2-trichloroethyl)arenesulfonamides with propyl,
allyl, and propargyl bromides, which were carried out
with a view to develop synthetic approaches to new
haloalkylsulfonamide derivatives containing an alkyl,
allyl, or propargyl group on the nitrogen atom. Such
derivatives attract interest from the viewpoints of their
subsequent trans-formations and biological activity.
These reactions required fairly severe conditions (heat-
ing to 100°C), which may be due to low nucleophi-
licity of the sulfonamide nitrogen atom. The best
yields of compounds II–IV were obtained using di-
methylformamide as solvent and sodium carbonate as
base. When sodium hydroxide was used instead of
Na2CO3, the yields were considerably lower because of
side processes.
It is known that N-monosubstituted arenesulfon-
amides, including those containing functional groups,
usually react with hydrocarbyl halides to produce the
corresponding N,N-disubstituted sulfonamides. For ex-
ample, N-(2-hydroxycyclohexyl)-4-methylbenzenesul-
fonamide reacted with allyl bromide in boiling acetone
in the presence of potassium carbonate (15 h) to give
98% of the target product [14]. However, we failed to
obtain the desired N,N-disubstituted derivatives by
reacting propyl, allyl, and propargyl bromides with
accessible N-(2,2,2-trichloro-1-hydroxyethyl)arenesul-
fonamides, for the latter readily underwent decomposi-
tion into the corresponding arenesulfonamide and
chloral hydrate. N-(1-Aryl-2,2,2-trichloroethyl)sulfon-
amides of the general formula ArSO2NHCH(Ar′)CCl3
did not react with the above bromides despite variation
of the solvent, base, and temperature. Presumably, the
reason is not only reduced nucleophilicity of the sul-
fonamide nitrogen atom in these derivatives but also
N-(2,2,2-Trichloroethyl)arenesulfonamides Ia and
Ib were found to react with propyl, allyl, and propar-
gyl bromides in the presence of inorganic base to give
the corresponding N-substituted derivatives II–IV.
R
DMF, Na2CO3, 100°C
–NaBr, –CO2, –H2O
H
N
CCl3
+
N
CCl3
R
Br
ArSO2
ArSO2
Ia, Ib
II, IIIa, IIIb, IVa, IVb
I, Ar = 4-MeC6H4 (a), 4-ClC6H4 (b); II, R = Et, Ar = 4-MeC6H4; III, R = H2C=CH, Ar = 4-MeC6H4 (a), 4-ClC6H4 (b);
IV, R = HC≡C, Ar = 4-MeC6H4 (a), 4-ClC6H4 (b).
466

N-ALKYLATION OF N-(2,2,2-TRICHLOROETHYL)ARENESULFONAMIDES
467
steric factor. More severe conditions induced tarring,
polymerization of alkenes, and hydrolysis of the tri-
chloromethyl group.
mp 76–78°C. IR spectrum (KBr), ν, cm–1: 3087, 3021
(=CH2), 1588 (C=C), 1353, 1162 (SO2). H NMR
1
spectrum, δ, ppm: 2.44 s (3H, CH3), 4.16 d (2H,
3
CH2CH=, JHH = 8.2 Hz), 4.30 s (2H, CH2CCl3),
The formation of compounds II–IV was proved by
spectral and analytical data. The IR spectra of II–IV
contained absorption bands typical of sulfonyl group,
as well as those typical of allyl and propargyl groups in
the spectra of III and IV, whereas NH absorption
bands characteristic of initial sulfonamides Ia and Ib
5.23 m (2H, =CH2), 5.41 m (1H, CH=), 7.33 and 7.75
13
AA′BB′ (4H, C6H4). C NMR spectrum, δC, ppm: 21.2
(CH3), 51.0 (CH2CH=), 62.0 (CH2CCl3), 98.1 (CCl3),
121.1 (=CH2), 130.9 (CH=); 127.2, 129.5, 136.6, 143.7
(C6H4). Found, %: C 42.58; H 3.98; Cl 29.97; N 4.15;
S 9.07. C12H14Cl3NO2S. Calculated, %: C 42.06;
H 4.12; Cl 31.04; N 4.09; S 9.36.
1
were absent. Compounds II–IV showed in the H and
13C NMR spectra signals from protons and carbon
nuclei in para-substituted aromatic ring, propyl, allyl,
or propargyl substituent, and trichloroethyl group, in
keeping with the assumed structures.
4-Chloro-N-(prop-2-en-1-yl)-N-(2,2,2-trichloro-
ethyl)benzenesulfonamide (IIIb) was synthesized
from 0.97 g (0.003 mol) of 4-chloro-N-(2,2,2-trichloro-
ethyl)benzenesulfonamide (Ib) and 0.36 g (0.003 mol)
of allyl bromide. Yield 0.94 g (87%), mp 75–77°C.
IR spectrum (KBr), ν, cm–1: 3092, 3023 (=CH2), 1586
Compounds II–IV were isolated as colorless crys-
talline substances soluble in organic solvents and
insoluble in water. The solubility of N,N-disubstituted
sulfonamides II–IV in nonpolar solvents was consider-
ably higher than the solubility of initial N-trichloro-
ethyl derivatives Ia and Ib, obviously due to the
absence of highly polar NH groups in the former. The
presence of a trichloromethyl group and multiple bond
in compounds II–IV makes them promising interme-
diate products for fine organic synthesis and apparent
precursors of synthetic amino acids and functionalized
acyclic and heterocyclic compounds, including poly-
mers and copolymers.
1
(C=C), 1351, 1164 (SO2). H NMR spectrum, δ, ppm:
3
4.18 d (2H, CH2CH=, JHH = 6.8 Hz), 4.33 s (2H,
CH2CCl3), 5.28 m (2H, =CH2), 5.50 m (1H, CH=),
13
7.51 and 7.84 AA′BB′ (4H, C6H4). C NMR spectrum,
δC, ppm: 51.6 (CH2CH=), 62.3 (CH2CCl3), 98.2
(CCl3), 121.8 (=CH2), 131.0 (CH=); 129.0, 129.5,
138.6, 139.7 (C6H4). Found, %: C 36.82; H 2.95;
Cl 39.88; N 3.97; S 8.46. C11H11Cl4NO2S. Calculated,
%: C 36.39; H 3.05; Cl 39.06; N 3.86; S 8.83.
4-Methyl-N-(prop-2-yn-1-yl)-N-(2,2,2-trichloro-
ethyl)benzenesulfonamide (IVa) was synthesized
from 0.90 g (0.003 mol) of sulfonamide Ia and 0.34 g
(0.003 mol) of propargyl bromide. Yield 0.92 g (90%),
mp 73–76°C. IR spectrum (KBr), ν, cm–1: 3261 (≡CH),
4-Methyl-N-propyl-N-(2,2,2-trichloroethyl)ben-
zenesulfonamide (II). A mixture of 0.90 g (0.003 mol)
of 4-methyl-N-(2,2,2-trichloroethyl)benzenesulfon-
amide (Ia), 0.32 g (0.003 mol) of Na2CO3, 0.37 g
(0.003 mol) of propyl bromide, and 5 ml of DMF was
stirred for 5 h at 100°C. The mixture was diluted with
15 ml of water, and the precipitate was filtered off,
dried, and recrystallized from hexane. Yield 0.87 g
(84%), mp 71–74°C. IR spectrum (KBr), ν, cm–1:
1
2118 (C≡C), 1335, 1163 (SO2). H NMR spectrum, δ,
ppm: 2.10 s (1H, ≡CH), 2.45 s (3H, CH3), 4.36 s (2H,
CH2CCl3), 4.48 s (2H, NCH2C≡), 7.34 and 7.76
13
AA′BB′ (4H, C6H4). C NMR spectrum, δC, ppm: 21.5
(CH3), 38.5 (CH2C≡), 62.7 (CH2CCl3), 75.0 (≡CH),
75.8 (C≡), 97.7 (CCl3); 127.8, 129.8, 135.7, 144.4
(C6H4). Found, %: C 42.02; H 3.67; Cl 31.99; N 4.25;
S 9.08. C12H12Cl3NO2S. Calculated, %: C 42.31;
H 3.55; Cl 31.22; N 4.11; S 9.41.
1
1389, 1160 (SO2). H NMR spectrum, δ, ppm: 0.79 t,
1.66 m, 3.38 t (7H, CH2CH2CH3); 2.45 s (3H, CH3),
4.30 s (2H, CH2CCl3), 7.33 and 7.75 AA′BB′ (4H,
C6H4). 13C NMR spectrum, δC, ppm: 11.2, 21.7, 51.3
(CH2CH2CH3); 21.2 (CH3), 64.5 and 98.4 (CH2CCl3);
127.6, 129.9, 136.9, 144.0 (C6H4). Found, %: C 41.25;
H 4.57; Cl 29.73; N 4.18; S 9.11. C12H16Cl3NO2S. Cal-
culated, %: C 41.82; H 4.68; Cl 30.86; N 4.06; S 9.30.
4-Chloro-N-(prop-2-yn-1-yl)-N-(2,2,2-trichloro-
ethyl)benzenesulfonamide (IVb) was synthesized
from 0.97 g (0.003 mol) of sulfonamide Ib and 0.34 g
(0.003 mol) of propargyl bromide. Yield 1.00 g (92%),
mp 90–92°C. IR spectrum (KBr), ν, cm–1: 3281 (≡CH),
Compounds IIIa, IIIb, IVa, and IVb were synthe-
sized in a similar way.
1
2121 (C≡C), 1353, 1162 (SO2). H NMR spectrum, δ,
4-Methyl-N-(prop-2-en-1-yl)-N-(2,2,2-trichloro-
ethyl)benzenesulfonamide (IIIa) was synthesized
from 0.90 g (0.003 mol) of 4-methyl-N-(2,2,2-tri-
chloroethyl)benzenesulfonamide (Ia) and 0.36 g
(0.003 mol) of allyl bromide. Yield 0.88 g (86%),
ppm: 2.13 s (1H, ≡CH), 4.35 s (2H, CH2CCl3), 4.50 s
(2H, CH2), 7.53 and 7.82 AA′BB′ (4H, C6H4). 13C NMR
spectrum, δC, ppm: 38.8 (CH2C≡), 62.9 (CH2CCl3),
75.6 (≡CH), 75.7 (C≡), 97.6 (CCl3); 129.5, 129.8,
137.5, 140.4 (C6H4). Found, %: C 36.68; H 2.46;
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 3 2013

ROZENTSVEIG et al.
468
5. Rozentsveig, I.B., Levkovskaya, G.G., Rozen-
tsveig, G.N., Mirskova, A.N., Krivdin, L.B., Larina, L.I.,
and Albanov, A.I., Tetrahedron Lett., 2005, vol. 46,
p. 8889.
6. Rozentsveig, I.B., Popov, A.V., Rozentsveig, G.N., Se-
rykh, V.Yu., Chernyshev, K.A., Krivdin, L.B., and Lev-
kovskaya, G.G., Mol. Diversity, 2010, vol. 14, p. 533.
Cl 39.80; N 4.09; S 8.48. C11H9Cl4NO2S. Calculated,
%: C 36.59; H 2.51; Cl 39.28; N 3.88; S 8.88.
Initial N-(2,2,2-trichloroethyl)arenesulfonamides Ia
and Ib were synthesized according to the procedure
1
13
described in [15]. The H and C NMR spectra were
recorded from solutions in CDCl3 on a Bruker DPX-
400 instrument at 400.61 and 100.13 MHz, respec-
tively; the chemical shifts were measured relative to
tetramethylsilane as internal reference. The IR spectra
were recorded in KBr on a Bruker IFS-25 spec-
trometer.
7. Levkovskaya, G.G., Drozdova, T.I., Rozentsveig, I.B.,
and Mirskova, A.N., Usp. Khim., 1999, vol. 68, p. 638.
8. Rozentsveig, I.B., Popov, A.V., Rozentsveig, G.N.,
Chernyshev, K.A., and Levkovskaya, G.G., Khim.
Geterotsikl. Soedin., 2008, p. 1587.
9. Rozentsveig, G.N., Serykh, V.Yu., Chernyshev, K.A.,
Rozentsveig, I.B., Levkovskaya, G.G., and Kriv-
din, L.B., Russ. J. Org. Chem., 2011, vol. 47, p. 572.
10. Rozentsveig, I.B., Popov, A.V., Brikov, A.V., Cherny-
shev, K.A., Mirskova, A.N., and Levkovskaya, G.G.,
Russ. J. Org. Chem., 2007, vol. 43, p. 926.
This study was performed under financial support
by the Siberian Branch of the Russian Academy of
Sciences (project no. 21) and by the Belarusian
Republican Foundation for Fundamental Research
(project no. Kh12SO-012).
11. Mangelinckx, S., Giubellina, N., and De Kimpe, N.,
REFERENCES
Chem. Rev., 2004, vol. 104, p. 2353.
12. Singh, G.S., D’hooghe, M., and De Kimpe, N., Chem.
Rev., 2007, vol. 107, p. 2080.
1. Belov, G.M., Belov, D.S., Kurkin, A.V., and Yurov-
skaya, M.A., Khim. Geterotsikl. Soedin., 2012, p. 78.
13. Rozentsveig, I.B., Evstaf’eva, I.T., Levkovskaya, G.G.,
and Mirskova, A.N., Russ. J. Org. Chem., 2005, vol. 41,
p. 1561.
2. Ukrainets, I.V. and Bereznyakova, N.L., Khim. Getero-
tsikl. Soedin., 2012, p. 161.
3. Rozentsveig, I.B., Levkovskaya, G.G., Mirskova, A.N.,
and Kashik, T.V., Russ. J. Org. Chem., 2000, vol. 36,
p. 1760.
14. Backvall, J.-E., Oshima, K., Palermo, R.E., and
Sharpless, K.B., J. Org. Chem., 1979, vol. 44, p. 1953.
4. Mirskova, A.N., Rudyakova, E.V., Rozentsveig, I.B.,
Stupina, A.G., Levkovskaya, G.G., and Albanov, A.I.,
Khim.-Farm. Zh., 2001, vol. 35, no. 6, p. 21.
15. Rybakova, N.A., Dostovalova, V.I., Slepushkina, A.A.,
Robas, V.I., and Freidlina, R.Kh., Izv. Akad. Nauk SSSR,
Ser. Khim., 1973, no. 2, p. 359.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 3 2013