Reactions of N-(2,2-dichloro-2-phenylethylidene)arenesulfonamicles with aromatic and heterocyclic compounds

Article abstract of DOI:10.1023/A:1013135722293

Benzene, toluene, and 2-chlorothiophene regioselectively react with N-(2,2-dichloro-2-phenylethylidene)arenesulfonamides in the presence of oleum to give N-[1-aryl(or hetaryl)-2,2-dichloro-2-phenylethyl]arenesulfonamides. Analogous C-amidoalkylation products are formed by the action of N-(2,2-dichloro-1-hydroxy-2-phenylethyl)- and N-(1-arylsulfonylamino-2,2-dichloro-2-phenylethyl)arenesulfonamides on toluene and 2-chlorothiophene in concentrated sulfuric acid.

Full text of DOI:10.1023/A:1013135722293

Russian Journal of Organic Chemistry, Vol. 37, No. 9, 2001, pp. 1297 1301. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 9, 2001,
pp. 1364 1368.
Original Russian Text Copyright
2001 by G. Rozentsveig, I. Rozentsveig, Levkovskaya, Evstaf’eva, Mirskova.
Reactions of N-(2,2-Dichloro-2-phenylethylidene)arene-
sulfonamides with Aromatic and Heterocyclic Compounds
G. N. Rozentsveig, I. B. Rozentsveig, G. G. Levkovskaya,
I. T. Evstaf’eva, and A. N. Mirskova
Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
fax: (3952)396046
Received February 28, 2001
Abstract Benzene, toluene, and 2-chlorothiophene regioselectively react with N-(2,2-dichloro-2-phenyl-
ethylidene)arenesulfonamides in the presence of oleum to give N-[1-aryl(or hetaryl)-2,2-dichloro-2-phenyl-
ethyl]arenesulfonamides. Analogous C-amidoalkylation products are formed by the action of N-(2,2-dichloro-
1-hydroxy-2-phenylethyl)- and N-(1-arylsulfonylamino-2,2-dichloro-2-phenylethyl)arenesulfonamides on
toluene and 2-chlorothiophene in concentrated sulfuric acid.
As shown previously [1 3], reactions of N,N-di-
chloroarenesulfonamides with phenylacetylene follow
a radical mechanism and result in formation of
N-(2,2-dichloro-2-phenylethylidene)arenesulfonamides
I. In continuation of our systematic studies on the
reactivity of the CH N group attached to strong
electron-acceptor fragments [4, 5], we examined the
behavior of N-(2,2-dichloro-2-phenylethylidene)arene-
sulfonamides I in C-amidoalkylation of aromatic and
heteroaromatic compounds with the goal of obtaining
N-polychloroethylsulfonamides having an aromatic
substituent in the -position with respect to the nitro-
gen atom. The synthesis of N-(1-arylpolychloroethyl)-
sulfonamides seemed to be important, for the hy-
drolysis of N-(1-aryl-2,2,2-trichloroethyl)amides is
known to involve the halogen atoms while the con-
current hydrolytic cleavage of the C N bond occurs
to a lesser extent [6, 7]. This opens the possibility
for synthesis of N-substituted 1-aminocarbonyl
compounds and their derivatives on the basis of N-di-
chloroethylamides.
The reaction of amide Ia with anisole was shown
[8] to occur in the presence of boron trifluoride di-
ethyl ether complex. However, we failed to effect
an analogous reaction with benzene and its alkyl and
halogen derivatives in the presence of Lewis acids.
We found that toluene, as well as 2-chlorothiophene,
readily reacts with N-(2,2-dichloro-2-phenylethyli-
dene)arenesulfonamides I in the presence of oleum.
The reactions were carried out with excess aromatic
substrate under vigorous stirring without heating;
the process was complete in 2 3 h, and the products
Scheme 1.
I, II, Ar = Ph (a), 4-ClC6H4 (b).
1070-4280/01/3709-1297$25.00 2001 MAIK Nauka/Interperiodica

1298
ROZENTSVEIG et al.
Scheme 2.
were N-(1-aryl-2,2-dichloro-2-phenylethyl)arenesul-
fonamides II and III which were formed in good
yields (Scheme 1, Table 1). It should be emphasized
that the reaction is regioselective: only 4-substituted
benzene derivatives IIa and IIb and 2,5-disubstituted
thiophene derivative III are formed (Table 2).
chloroethylidene)arenesulfonamides with furan. The
yield of VII can be increased by heating the mixture
for 24 h at 40 50 C.
C-Amidoalkylation products II and III were also
synthesized by the action of N-(2,2-dichloro-1-hy-
droxy-2-phenylethyl)arenesulfonamides V and VIII
and 1,1-dichloro-2,2-bis(4-chlorophenylsulfonyl-
amino)-1-phenylethane (VI) on toluene and 2-chloro-
thiophene in the presence of concentrated sulfuric acid
(Scheme 4). The highest yields of compounds IIa and
IIb were obtained when the aromatic substrate was
used as solvent. With equimolar amounts of the
reactants in carbon tetrachloride or chloroform amide
V is converted into bis-amide VI.
Amides I reacted with benzene in the presence of
1
oleum in a more complicated manner. H NMR study
of the reaction mixture obtained from compound Ib
showed the formation of C-amidoalkylation product
IV. In addition, N-(2,2-dichloro-1-hydroxy-2-phenyl-
ethyl)-4-chlorobenzenesulfonamide (V) and 1,1-di-
chloro-2,2-bis(4-chlorophenylsulfonylamino)-1-phe-
nylethane (VI) were formed, the latter being the major
product (Scheme 2). Unlike N-(2,2,2-trichloroethyli-
dene)arenesulfonamides which readily react with both
benzene and chlorobenzene [9], amides I failed to
react with chlorobenzene. Under more severe condi-
tions (heating for 10 h at 50 C in the presence of
excess oleum) the mixture underwent tarring.
Scheme 4.
We previously found [10] that N-(2,2,2-trichloro-
ethylidene)arenesulfonamides are capable of reacting
with 1,8-bis(dimethylamino)naphthalene without
a catalyst to give C-amidoalkylation products. We did
not succeed in obtaining the corresponding products
by reactions of 1,8-bis(dimethylamino)naphthalene
with amides I despite prolonged keeping (20 days)
of the reaction mixture.
Amide Ib was brought into reaction with furan
in the presence of boron trifluoride ether complex.
The reaction was carried out in carbon tetrachloride
using a small excess of furan. As a result, N-[2,2-di-
chloro-1-(2-furyl)-2-(4-chlorophenyl)ethyl]-4-chloro-
benzenesulfonamide (VII) was obtained (Scheme 3).
No reaction occurred in the absence of a catalyst, in
contrast to the known [11] reaction of N-(2,2,2-tri-
VIII, R = OH, Ar = Ph.
Reactions of V with benzene and chlorobenzene in
the presence of concentrated sulfuric acid gave no
corresponding C-amidoalkylation products, but amide
V was converted into 1,1-dichloro-2,2-bis(4-chloro-
phenylsulfonylamino)-1-phenylethane (VI). By special
experiments we showed that compound VI itself
reacts neither with benzene nor with chlorobenzene.
Presumably, bis-amide VI is formed as a result of
condensation of V with 4-chlorobenzenesulfonamide
which is formed from V in acid medium. The forma-
tion of structures like VI was also noted in [12] where
we studied the amidoalkylating activity of N-(2,2,2-
trichloroethyl)arenesulfonamides having a readily
departing group in the -position with respect to the
nitrogen atom [12].
Scheme 3.
The structure of products II IV and VII was
1
confirmed by elemental analysis and IR and H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 9 2001

REACTIONS OF N-(2,2-DICHLORO-2-PHENYLETHYLIDENE)ARENESULFONAMIDES
Table 1. Yields, melting points, and elemental analyses of compounds II, III, and V VIII
1299
Found, %
Cl
Calculated, %
Cl
Comp. Yield, %
mp,
C
Formula
no.
IIa
IIb
(method)
C
N
S
C
N
S
91 (a),
93 (b)
206 208
225 227
59.83 16.67 3.10
55.19 23.06 2.59
7.43
C21H19Cl2NO2S
C21H18Cl3NO2S
60.00 16.87 3.33
55.46 23.39 3.08
7.63
95 (a),
87 (b),
63 (c)
6.79
7.05
III
73 (a),
68 (b),
58 (c)
179 180
44.62 30.99 2.80 12.99
C18H13Cl4NO2S2
C14H12Cl3NO3S
44.93 29.47 2.91 13.32
V
100
123 125
218 220
44.01 27.50 3.43
8.83
44.17 27.94 3.68
8.42
VI
21 (a),
76 (b)
43.21 25.05 4.88 11.71
C20H16Cl4N2O4S2 43.48 25.34 5.07 11.59
VII
58
99
151 153
127 129a 48.32 20.41 3.92
50.53 23.50 3.39
7.23
9.37
C18H14Cl3NO3S
C14H13Cl2NO3S
50.19 24.69 3.25
48.57 20.48 4.05
7.44
9.26
VIII
a
Published data [2]: mp 126 127 C.
Table 2. IR and 1H NMR spectra of compounds II, III, and V VIII
1
IR spectrum, , cm
SO2
1H NMR spectrum (DMSO-d6), , ppm
Comp.
no.
JNHCH,
Hz
NH
other bands
CH
NH
Harom
IIaa
IIba
3270 1320,
1180
2950 2850 (C Haliph),
5.36 d 9.03 d
5.20 d 8.85 d
6.77; 7.03 (AA BB , 4-MeC6H4);
10.8
10.4
1450 (C Carom
)
7.27 7.70 m
3270 1330,
1160
2950 2850 (C Haliph),
1480 (C Carom
6.72; 6.91 (AA BB , 4-MeC6H4);
7.16; 7.52 (AA BB , 4-ClC6H4);
)
7.31 7.62 m (Harom
)
IIc
III
V
3280 1320,
1170
1480 (C Carom
1440 (C Carom
)
)
5.35 d 9.01 d
5.47 d 9.04 d
6.96 7.57 m
10.0
10.2
9.7
3250 1330,
1170
3190b 1330,
3260 1160
6.64 d, 6.68 d (2-thienyl);
7.38 7.70 m
3520, 3430 (OH)b; 1450 5.44 d 8.56 d
(C Carom
7.52 7.82 m
)
VI
3280 1340,
1160
1480 (C Carom
)
5.73 t
9.01 d
7.25 7.60 m
9.2
VII
VIII
3230 1360,
1180
1440 (C Carom
)
5.23 d 8.93 d
5.42 d 8.52 d
6.10 6.18 m (2-furyl);
7.23 7.62 m
10.3
9.0
3280 1340,
1170
3490 (OH), 1450
(C Carom
7.55 7.73 m
)
a
(CH3), ppm: 2.11 s (IIa), 2.10 s (IIb).
Doublet bands are likely to result from the existence of two stable conformers.
b
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 9 2001

1300
ROZENTSVEIG et al.
spectroscopy (Tables 1, 2). Their IR spectra contained
absorption bands typical of NH and SO2 groups,
aromatic C C bonds, and alkyl C H bonds. In the
1H NMR spectra of II IV and VII we observed
signals from protons of aromatic and heteroaromatic
rings and characteristic doublet signals from the
NHCH fragment. The aromatic proton signals of
toluene derivatives IIa and IIb form an AA BB spin
system, which indicates that the substitution occurred
at the para-position. The signals from the thienyl ring
protons in III correspond to the 2,5-substitution
IIa (method a) from 3.62 g (0.01 mol) of amide Ib
[1] and toluene in the presence of oleum.
b. The procedure was similar to that described
above for compound IIa (method b); 3.81 g
(0.01 mol) of amide V and 5 ml of toluene were taken.
c. A mixture of 2.27 g (0.005 mol) of compound
VI, 5 ml of toluene, and 1 1.5 ml of concentrated
sulfuric acid was vigorously stirred for 5 h. Excess
toluene was distilled off under reduced pressure, and
the residue was washed first with 30% aqueous
ammonia and then with water until neutral reaction.
The undissolved material was recrystallized from
benzene.
N-[2,2-Dichloro-1-(5-chloro-2-thienyl)-2-phenyl-
ethyl]-4-chlorobenzenesulfonamide (III). a. Amide
III was synthesized as described above for IIa
(method a) from 3.62 g (0.01 mol) of amide Ib [1]
and 5 ml of 2-chlorothiophene in the presence of
oleum.
b. Amide III was synthesized as described above
for IIa (method b) from 3.81 g (0.01 mol) of amide V
and 5 ml of 2-chlorothiophene in the presence of con-
centrated sulfuric acid.
c. Amide III was synthesized as described above
for compound IIb (method c) from 2.27 g (0.005 mol)
of amide VI and 5 ml of 2-chlorothiophene in the
presence of 1 1.5 ml of concentrated sulfuric acid.
1
pattern. Likewise, the H NMR spectrum of VII is
consistent with the presence of 2-furyl substituent
(Table 2). The NHCH group in amide V gives rise
1
to two doublets in the H NMR spectrum, but the
CH signal is located in a weaker field than those of
compounds II and IV (Table 2); this may be due
to effect of the hydroxy group oxygen atom in the
-position. The NHCHNH fragment of VI appears
in the spectrum as a doublet (NH) and a triplet at
5.73 ppm (CH); the doublet being twice as intense
as the triplet. Thus the 1H NMR spectrum of a mixture
of products IV, V, and VI can readily be interpreted.
Compounds II IV and VII are colorless or slightly
colored crystalline substances with a specific odor.
They are soluble in DMSO, acetone, and aromatic
hydrocarbons and insoluble in water.
Our results indicate a weaker C-amidoalkylating
activity of N-(2,2-dichloro-2-phenylethylidene)arene-
sulfonamides and their derivatives, as compared to
N-(2,2,2-trichloroethylidene) analogs.
N-(2,2-Dichloro-1,2-diphenylethyl)-4-chloro-
benzenesulfonamide (IV). A mixture of 3.62 g
(0.01 mol) of amide Ib, 5 ml of benzene, and 0.5 ml
of oleum was stirred for 5 h and was then treated as
described for compound IIa (method a). According
EXPERIMENTAL
1
to the H NMR data, the mixture contained 22% of
1
amide IV, 10% of hydroxyethylamide V, and 68% of
The H NMR spectra were recorded on a Bruker
1
diamide VI. H NMR spectrum, , ppm: amide IV:
DPX-400 instrument at 400 MHz from 5 10 wt %
solutions in DMSO-d6 containing HMDS as internal
reference. The IR spectra were obtained on a Specord
75IR spectrometer in KBr.
N-[2,2-Dichloro-1-(4-methylphenyl)-2-phenyl-
ethyl]benzenesulfonamide (IIa). a. A mixture of
3.28 g (0.01 mol) of amide Ia [2], 5 ml of toluene,
and 0.5 ml of oleum ( 20% of SO3) was vigorously
stirred for 3 h. Water, 5 ml, was added, and the
undissolved material was filtered off, dried, and re-
crystallized from acetone carbon tetrachloride (1:1).
b. A mixture of 3.46 g (0.01 mol) of amide VIII
[2], 5 ml of toluene, and 2 ml of concentrated sulfuric
acid was vigorously stirred for 3 h. The mixture was
then treated as described above in a.
N-[2,2-Dichloro-1-(4-methylphenyl)-2-phenyl-
ethyl]-4-chlorobenzenesulfonamide (IIb). a. Com-
pound IIb was synthesized as described above for
5.34 d (CH, JNHCH = 9.31 Hz), 9.01 d (NH); V: 5.42 d
(CH, JNHCH = 9.36 Hz), 8.57 d (NH); VI: 5.73 t (CH,
JNHCH = 9.43 Hz), 9.01 d (NH). Signals from aromatic
protons were difficult to assign.
N-(2,2-Dichloro-1-hydroxy-2-phenylethyl)-4-
chlorobenzenesulfonamide (V). A mixture of 3.62 g
(0.01 mol) of amide Ib [1] and 5 ml of water was
vigorously stirred and was then left to stand for 20 h.
The undissolved material was filtered off and dried.
1,1-Dichloro-2,2-bis(4-chlorophenylsulfonyl-
amino)-1-phenylethane (VI). a. Compound VI was
obtained by the procedure reported in [2] as a by-
product of the reaction of 7.82 g (0.03 mol) of N,N,4-
trichlorobenzenesulfonamide and 4 ml ( 0.04 mol) of
phenylacetylene.
b. A mixture of 3.81 g (0.01 mol) of amide V,
1 ml of concentrated sulfuric acid, and 5 ml of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 9 2001

REACTIONS OF N-(2,2-DICHLORO-2-PHENYLETHYLIDENE)ARENESULFONAMIDES
1301
benzene, chlorobenzene, or chloroform was vigorously
stirred for 5 h. Water, 5 ml, was added, and the pre-
cipitate was filtered off, dried under reduced pressure,
and recrystallized from benzene.
N-[2,2-Dichloro-1-(2-furyl)-2-phenylethyl]-4-
chlorobenzenesulfonamide (VII). A mixture of
3.62 g (0.01 mol) of amide Ib, 1.2 ml ( 0.02 mol)
of furan, 5 ml of carbon tetrachloride, and 1 drop of
freshly distilled boron trifluoride ether complex was
thoroughly stirred and was kept for 5 h at 40 50 C
and for 20 h at 5 C. The precipitate of amide VII
was filtered off and recrystallized from benzene.
4. Mirskova, A.N., Drozdova, T.I., Levkovskaya, G.G.,
and Voronkov, M.G., Usp. Khim., 1989, vol. 58,
no. 3, p. 417.
5. Levkovskaya, G.G., Drozdova, T.I., Rozen-
tsveig, I.B., and Mirskova, A.N., Usp. Khim., 1999,
vol. 68, no. 7, pp. 638 652.
6. Rozentsveig, I.B., Levkovskaya, G.G., and Mirsko-
va, A.N., Russ. J. Org. Chem., 1999, vol. 35, no. 9,
pp. 1398 1399.
7. Rozentsveig, I.B., Levkovskaya, G.G., Mirsko-
va, A.N., and Kashik, T.V., Russ. J. Org. Chem.,
2000, vol. 36, no. 12, pp. 1760 1764.
8. Drozdova, T.I. and Mirskova, A.N., Russ. J. Org.
Chem., 1998, vol. 34, no. 6, p. 898.
N-(2,2-Dichloro-1-hydroxy-2-phenylethyl)ben-
zenesulfonamide (VIII) was synthesized by treatment
with water of 3.28 g (0.01 mol) of amide Ia, follow-
ing the procedure reported in [2].
9. Rozentsveig, I.B., Levkovskaya, G.G., and Mirsko-
va, A.N., Russ. J. Org. Chem., 1999, vol. 35, no. 6,
pp. 895 898.
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