New approach to the preparation of p-(1-cyanoethyl)arenesulfonamides by reaction of arylsulfonyl imines of polychloroacetaldehydes with acetone cyanohydrin

Article abstract of DOI:10.1134/S1070428017080061

Reaction of N-(2,2,2-trichloroethylidene)- or N-(1-phenyl-2,2-dichloroethylidene)arenesulfonamides with acetone cyanohydrin in acetone in the presence of potassium carbonate led to the formation of N- (2,2,2-trichloro-1-cyanoethyl)- or N-(2-phenyl-2,2-dic

Full text of DOI:10.1134/S1070428017080061

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 8, pp. 1191–1194. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © A.R. Kaliev, V.Yu. Serykh, I.B. Rosentsveig, 2017, published in Zhurnal Organicheskoi Khimii, 2017, Vol. 53, No. 8, pp. 1177–1180.
New Approach to the Preparation
of p-(1-Cyanoethyl)arenesulfonamides by Reaction
of Arylsulfonyl Imines of Polychloroacetaldehydes
with Acetone Cyanohydrin
A. R. Kaliev, V. Yu. Serykh, and I. B. Rosentsveig*
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 April 7, 2017
Abstract—Reaction of N-(2,2,2-trichloroethylidene)- or N-(1-phenyl-2,2-dichloroethylidene)arenesulfon-
amides with acetone cyanohydrin in acetone in the presence of potassium carbonate led to the formation of N-
(2,2,2-trichloro-1-cyanoethyl)- or N-(2-phenyl-2,2-dichloro-1-cyanoethyl)arenesulfonamides.
DOI: 10.1134/S1070428017080061
Arylsulfonyl imines of polyhaloaldehydes are
valuable reagents for preparation of a wide range of
amides derivatives and sulfonamides [1, 2]. The high
electrophilicity of the azomethine group in this type
imines originating from the effect of strong electron-
acceptor sulfonyl and polyhalomethyl groups makes it
possible to carry out the addition to the imines of O-,
N-, S-, P-, C-nucleophiles [1, 2] affording func-
tionalized sulfonamides which in their turn may be
utilized in the synthesis of heterocyclic derivatives
[1–7], aminocarbonyl compounds [8], biologically
active amino acids [9].
Similar transformations of chloral N-acyl imines were
described in more detail; obtained N-(2,2,2-trichloro-1-
cyanoethyl)amides are valuable reagents for the
synthesis of functionalized amide derivatives, in
particular, of the heterocyclic structure [11–13].
Aminonitriles are well known key intermediates in the
process of Strecker amino acid synthesis [14].
The accessible specimens of activated highly
electrophilic sulfonyl imines, N-(2,2,2-trichloro-
ethylidene)- and N-(2-phenyl-2,2-dichloroethylidene)-
arenesulfonamides 1 and 2, were prepared by radical
reactions of N,N-dichloroarenesulfonamides with
trichloroethylene or phenylacetylene [15, 16]. We
carried out the cyanation of imines 1а–1с and 2а–2с
using acetone cyanohydrin as a precursor of the
cyanide anion in contrast to the above mentioned
procedures that applied sodium cyanide [11] or
hydrogen cyanide [10]. In the laboratory practice
acetone cyanohydrin due to lower toxicity and higher
Sulfonyl imines of polyhaloaldehydes were not
practically investigated in reactions resulting in the
corresponding sulfonylamino-substituted nitriles. In
[10] a reaction was described between hydrogen
cyanide and arylsulfonyl imines of chloral in the
presence of trimethylamine leading to the formation of
N-(2,2-dichloro-1-cyanovinyl)arenesulfonamides.
Scheme 1.
Cl
Cl
Cl
X
10 mol % K2CO3
H
HO
CN
Cl
X
N
+
N
acetone, 65_70°C, 6 h
ArSO2
ArSO2
CN
3a_3c, 4a_4c
1a_1c, 2a_2c
X = Cl (1, 3), Ph (2, 4); Ar = Ph (a), 4-MeC6H4 (b), 4-ClC6H4 (c).
1191

KALIEV et al.
1192
Scheme 2.
_
O
_
K2CO3
KHCO3
CN
O
CN
_
CN
HO
+
HO
CN
Cl
Cl
_
Cl
Cl
X
H
Cl
_
Cl
X
CN
O
CN
N
N
+
N
ArSO2
ArSO2
X
ArSO2
CN
CN
1a_1c, 2a_2c
A
3a_3c, 4a_4c
_
O
CN
HO
CN
K2CO3
_H2O, _CO2
or
or
Cl
Cl
Cl
X
H
_
Cl
N
N
ArSO2
ArSO2
X
CN
CN
A
3a_3c, 4a_4c
Cl
Cl
Cl
H
Cl
H2O
N
N
ArSO2
X
ArSO2
X
OH
5a_5c, 6a_6c
1a_1c, 2a_2c
X = Cl (1, 3, 5), Ph (2, 4, 6); Ar = Ph (a), 4-MeC6H4 (b), 4-ClC6H4 (c).
accessibility is more feasible than sodium or hydrogen
cyanide.
compounds 3 and 4 and favoring further generation of
cyanide anions (Scheme 2). At a large amount of
potassium carbonate it reacts with sufficiently acidic
hydroxy and sulfonamide groups of acetone cyano-
hydrin and sulfonamides 3 and 4 providing carbonic
acid that decomposes in carbon dioxide and water, and
the latter in its turn extremely easily reacts with the
activated azomethine group of initial imines 1 and 2
giving hemiaminals 5 and 6 as side products (Scheme 2).
The reaction of sulfonyl imines 1а–1с and 2а–2с
with acetone cyanohydrin led to the formation of N-
(2,2,2-trichloro-1-cyanoethyl)- and N-(2-phenyl-2,2-
dichloro-1-cyanoethyl)arenesulfonamides 3а–3с and
4а–4с in the presence of potassium carbonate in
acetone as the optimum solvent (Scheme 1).
In the absence of potassium carbonate the reaction
proceeds insufficiently effectively, yet this reagent
used in amount exceeding 10–15 mol % caused the
decrease in the yield of cyano derivatives 3 and 4 due
to an intensive formation of the corresponding hemi-
aminals, N-(1-hydroxyethyl)sulfonamides 5 and 6.
The formation of cyano-substituted sulfonamides
3а–3с and 4а–4с was proved by NMR spectra and
confirmed by IR spectra and elemental analysis. IR
spectra of compounds 3 and 4 contain absorption
1
bands of C≡N, SO2, NH groups. In the H NMR
spectra of sulfonamides 3 and 4 along with the signals
of the protons of aromatic rings doublets are observed
corresponding to the fragment NHCH, J 9‒10 Hz. The
13C NMR spectra contain the signals of carbon atoms
of the aromatic rings, of C≡N group, of trichloro-
methyl or phenyldichloromethyl groups, and also of
methine group.
Apparently some potassium carbonate is necessary
to generate cyanide ions from acetone cyanohydrin. As
a result of cyanide ions addition to the azomethine
group of highly electrophilic imines 1 and 2 the corres-
ponding N-(polychlorocyanoethyl)amidyl ions А are
formed which react with acetone cyanohydrin giving
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 8 2017

NEW APPROACH TO THE PREPARATION OF p-(1-CYANOETHYL)ARENESULFONAMIDES
1193
Hemiaminals 5 and 6 are thoroughly studied
compounds [17–19]. The side process affording these
compounds was unambiguously proved by the
comparison of their NMR and IR spectra with the
spectra of authentic samples.
8.25; S 9.18. C10H9Cl3N2O2S. Calculated, %: C 36.66;
H 2.77; N 8.55; S 9.79.
N-(2,2,2-Trichloro-1-cyanoethyl)-4-chlorobenze-
nesulfonamide (3c) was prepared similarly from 2 g
(6.2 mmol) of N-(2,2,2-trichloroethylidene)-4-chloro-
benzenesulfonamide 1с, 0.060 g (7 mol %) of K2CO3
and 8 mL of 50% acetone solution of acetone cyano-
hydrin. Yield 1.78 g (83%), white crystalline powder,
mp 127‒130°С. IR spectrum (KBr), ν, cm–1: 3230 (N‒
N-(2,2,2-Trichloro-1-cyanoethyl)- and N-(2-phenyl-
2,2-dichloro-1-cyanoethyl)arenesulfonamides are
promising reagents for further transformations
involving the polychloroethyl and cyano groups.
1
H), 2263 (С≡N), 1348, 1159 (SO2). H NMR spec-
3
trum, δ, ppm: 6.03 d (1H, CH, J 9.22 Hz), 7.69–7.81
EXPERIMENTAL
m (2H, 4-ClC6H4), 7.96–8.04 m (2H, 4-ClC6H4), 10.11
3
d (1H, NH, J 9.22 Hz). 13C NMR spectrum, δ, ppm:
IR spectra were recorded on a spectrophotometer
60.62 (CH), 96.22 (CCl3), 113.87 (CN), 128.79,
129.02, 129.46, 138.56 (4-ClC6H4). Found, %: С
29.98; H 2.28; N 8.36; S 9.68. C9H6Cl4N2O2S.
Calculated, %: C 31.06; H 1.74; N 8.05; S 9.21.
1
Bruker IFS-25, Н, 13С NMR spectra were registered
on
a spectrometer Bruker DPX-400 (operating
frequencies 400.13 and 100.62 МHz respectively) in
DMSO-d6. Imines 1 and 2 were prepared by
procedures [15, 16].
N-(2-Phenyl-2,2-dichloro-1-cyanoethyl)benzene-
sulfonamide (4а) was prepared similarly from 0.551 g
(1.6 mmol) of N-(2-phenyl-2,2-dichloroethylidene)-
benzenesulfonamide 2а, 0.016 g (7 mol %) of K2CO3
and 3 mL of 50% acetone solution of acetone
cyanohydrin. Yield 0.369 g (63%), white crystalline
powder, mp 137‒139°С. IR spectrum (KBr), ν, cm–1:
3218 (N‒H), 2262 (С≡N), 1355, 1171 (SO2). 1H NMR
spectrum, δ, ppm: 5.78 d (1H, CH, 3J 10.04 Hz), 7.43‒
7.49 m (2Harom), 7.52‒7.63 m (3Harom), 7.63‒7.73 m
N-(2,2,2-Trichloro-1-cyanoethyl)benzenesulfon-
amide (3а). A mixture of 0.49 g (1.7 mmol) of N-
(2,2,2-trichloroethylidene)benzenesulfonamide 1а,
0.015 g (7 mol %) of K2CO3, 3 mL of 50% acetone
solution of acetone cyanohydrin, and 5 mL of acetone
was stirred under an argon atmosphere at 65–70°С for
6 h. The reaction mixture was diluted with 20 mL of
water, the precipitate was filtered off, dried, and
recrystallized from benzene. Yield 0.52 g (97%),
colorless crystals, mp 107‒109°С. IR spectrum (KBr),
ν, cm–1: 3247 (N‒H), 2221 (С≡N), 1340, 1169 (SO2).
3
(2Harom), 7.73‒7.91 m (3Harom), 9.47 d (1H, NH, J
10.04 Hz). 13C NMR spectrum, δ, ppm: 58.60 (CH),
90.22 (CCl2), 115.05 (CN), 126.91, 127.42, 128.40,
129.16, 130.26, 133.20, 136.90, 139.69 (Ar). Found,
%: С 51.12; H 3.66; N 8.12; S 9.55. C15H12Cl2N2O2S.
Calculated, %: C 50.72; H 3.41; N 7.89; S 9.03.
3
1H NMR spectrum, δ, ppm: 5.74 d (1H, CH, J
9.78 Hz), 7.30, 7.46, 7.75 m (5Harom), 9.37 d (1H, NH,
3J 9.78 Hz). 13C NMR spectrum, δ, ppm: 60.69 (CH),
96.38 (CCl3), 113.91 (CN), 126.94, 129.31, 133.44,
139.79 (C6H5). Found, %: С 34.69; H 2.34; N 8.82; S
10.08. C9H7Cl3N2O2S. Calculated, %: C 34.47; H 2.25;
N 8.93; S 10.22.
4-Methyl-N-(2-phenyl-2,2-dichloro-1-cyano-
ethyl)benzenesulfonamide (4b) was prepared similar-
ly from 0.5 g (1.4 mmol) of 4-methyl-N-(2-phenyl-2,2-
dichloroethylidene)benzenesulfonamide 2b, 0.015 g
(7 mol %) of K2CO3, and 3 mL of 50% acetone
solution of acetone cyanohydrin. Yield 0.46 g (83%),
white crystalline powder, mp 73‒75°С. IR spectrum
(KBr), ν, cm–1: 3227 (N‒H), 2226 (С≡N), 1352, 1173
4-Methyl-N-(2,2,2-trichloro-1-cyanoethyl)ben-
zenesulfonamide (3b) was prepared similarly from 0.5 g
(1.66 mmol) of 4-methyl-N-(2,2,2-trichloroethylide-
ne)-benzenesulfonamide 1b. Yield 0.38 g (70%), white
powder, mp 112‒115°С. IR spectrum (KBr), ν, cm–1:
3227 (N‒H), 2229 (С≡N), 1339, 1166 (SO2). 1H NMR
spectrum, δ, ppm: 2.37 s (3H, CH3), 5.95 d (1H, CH, 3J
9.29 Hz), 7.35–7.45 m (2H, 4-MeC6H4), 7.74–7.82 m
1
(SO2). H NMR spectrum, δ, ppm: 2.37 s (3H, Me),
3
5.74 d (1H, CH, J 9.78 Hz), 7.31‒7.51 m (6Harom),
7.63‒7.90 m (3Harom), 9.39 d (1H, NH, 3J 9.78 Hz). 13C
NMR spectrum, δ, ppm: 21.01 (Me), 58.56 (CH),
90.23 (CCl2), 115.11 (CN), 126.94, 127.38, 128.29,
128.35, 129.52, 130.16, 136.90, 143.50 (Ar). Found,
%: С 53.28; H 3.55; N 8.22; S 8.61. C16H14Cl2N2O2S.
Calculated, %: C 52.04; H 3.82; N 7.59; S 8.68.
3
(2H, 4-MeC6H4), 9.90 d (1H, NH, J 9.29 Hz). 13C
NMR spectrum, δ, ppm: 20.95 (Me), 60.31 (CH),
95.63 (CCl3), 112.89 (CN), 126.68, 129.24, 132.54,
138.78 (4-MeC6H4). Found, %: С 34.08; H 3.19; N
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 8 2017

KALIEV et al.
1194
6. Serykh, V.Y., Chernysheva, G.N., Kondrashov, E.V.,
N-(2-Phenyl-2,2-dichloro-1-cyanoethyl)-4-chlo-
Vashchenko, A.V., Smirnov, V.I., and Rozentsveig, I.B.,
Arkivoc, 2015, vol. VII, p. 377.
robenzene-sulfonamide (4c) was prepared similarly
from 0.5 g (1.3 mmol) of N-(2-phenyl-2,2-dichloro-
ethyl)-4-chlorobenzenesulfonamide 2c, 0.015 g (7 mol %)
of K2CO3, and 4 mL of 50% acetone solution of
acetone cyanohydrin. Yield 0.52 g (97%), white
crystalline powder, mp 163‒165°С. IR spectrum
(KBr), ν, cm–1: 3232 (N‒H), 2232 (С≡N), 1354, 1173
7. Rozentsveig, I.B., Popov, A.V., Rozentsveig, G.N.,
Serykh, V.Yu., Chernyshev, K.A., Krivdin, L.B., and
Levkovskaya, G.G., Mol. Div., 2010, vol. 14, p. 533.
8. Rozentsweig, I.B., Popov, A.V., Brikov, A.V.,
Mirskova, A.N., and Levkovskaya, G.G., Russ. J. Org.
Chem., 2007, vol. 43, p. 780. doi 10.1134/
S1070428007050260
9. Mirskova, A.N., Rudyakova, E.V., Rozentsveig, I.B.,
Stupina, A.G., Levkovkskaya, G.G., and Albanov, A.I.,
Pharm. Chem. J., 2001, vol. 35, p. 312. doi 10.1023/
A:1012341604254
1
3
(SO2). H NMR spectrum, δ, ppm: 5.83 d (1H, CH, J
9.98 Hz), 7.41‒7.49 m (3Harom), 7.64‒7.68 m (2Harom),
7.73‒7.80 m (2Harom), 7.83‒7.86 m (2Harom), 9.58 d
(1H, NH, J 9.98 Hz). 13C NMR spectrum, δ, ppm:
3
58.50 (CH), 90.05 (CCl2), 115.05 (CN), 127.35,
128.35, 128.91, 129.25, 130.19, 136.79, 138.09,
138.43 (Ar). Found, %: С 47.03; H 3.03; N 6.89; S
8.01. C15H11Cl3N2O2S. Calculated, %: C 46.23; H
2.85; N 7.19; S 8.23.
10. Drach, B.S. and Mis’kevich, G.N., Zh. Org. Chem.,
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osnove amidoalkiliruyushchikh agentov (Synthesis of
Nitrogen-containing Heterocyclic Compounds Based on
Amidoalkylating Agents), Kiev: Naukova Dumka,
1992.
ACKNOWLEDGMENTS
The main results were obtained using the
equipment of the Baikal Analytic Center of Joint
Usage of the Siberian Branch, Russian Academy of
Sciences.
12. Drach, B.S., Sviridov, E.P., Kisilenko, A.A., and
Kirsanov, A.V., Zh. Org. Khim., 1973, vol. 9, p. 1818.
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Translated under the title Organicheskaya khimiya.
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