N-(2,2,2-trichloroethylidene)- and N-(1-hydroxy-2,2,2-trichloroethyl) amides in C-amidoalkylation reaction of functionally-substituted aromatic compounds

Article abstract of DOI:10.1023/A:1015569801556

A reaction with phenol and pyrocatechol of N-(2,2,2-trichloroethylidene)arenesulfonyl-, ethoxycarbonylamides and 1-hydroxy-substituted N-(2,2,2-trichloroethyl)amides of arenesulfonic, carbamic, and acetic acids in the presence of oleum or in sulfuric acid provided the corresponding (1-amido-2,2,2-trichloroethyl)-substituted phenols. N-(2,2,2-Trichloroethylidene)-4-chlorobenzenesulfonamide reacted with salicylamide in the presence of oleum to afford 3-aminocarbonyl-4-[2,2,2-trichloro-1-(4-chlorobenzene-sulfonamido)ethyl]benzene whereas the 1-hydroxy-2,2,2-trichloroethylamides of the acetic, carbamic, and arenesulfonic acids did not enter into such reactions.

Full text of DOI:10.1023/A:1015569801556

Russian Journal of Organic Chemistry, Vol. 38, No. 2, 2002, pp. 235 238. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 2, 2002,
pp. 256 259.
Original Russian Text Copyright
2002 by Aizina, I. Rozentsweig, Levkovskaya, G. Rozentsweig, Mirskova.
N-(2,2,2-Trichloroethylidene)- and N-(1-Hydroxy-2,2,2-tri-
chloroethyl)amides in C-Amidoalkylation Reaction
of Functionally-substituted Aromatic Compounds
Yu. A. Aizina, I. B. Rozentsweig, G. G. Levkovskaya, G. N. Rozentsweig, and A. N. Mirskova
Faworsky Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, Irkutsk, 664033 Russia
Received April 3, 2001
Abstract A reaction with phenol and pyrocatechol of N-(2,2,2-trichloroethylidene)arenesulfonyl-,
ethoxycarbonylamides and 1-hydroxy-substituted N-(2,2,2-trichloroethyl)amides of arenesulfonic, carbamic,
and acetic acids in the presence of oleum or in sulfuric acid provided the corresponding (1-amido-2,2,2-
trichloroethyl)-substituted phenols. N-(2,2,2-Trichloroethylidene)-4-chlorobenzenesulfonamide reacted with
salicylamide in the presence of oleum to afford 3-aminocarbonyl-4-[2,2,2-trichloro-1-(4-chlorobenzene-
sulfonamido)ethyl]benzene whereas the 1-hydroxy-2,2,2-trichloroethylamides of the acetic, carbamic, and
arenesulfonic acids did not enter into such reactions.
The reactivity of N-sulfonyl-, acyl-, and alkoxy-
carbonylimines of chloral originates from the
presence in their structure of strong electron-with-
drawing substituents at the azomethine group [1].
Reactions of these imines with compounds containing
hydroxy, amide, or amino groups as a rule results in
products of the nucleophilic addition of OH [1, 2] or
NH [1, 3] groups across the azomethine bond. We
showed lately [4] that arenesulfonylimines of chloral
in the presence of oleum take another reaction route
with phenol, 2-halo- and 2-alkyl-substituted phenols.
Instead of products of the nucleophilic addition we
obtained compounds resulting from C-sulfonamido-
trichloroethylation of the aromatic ring [4]. The same
compounds were prepared by reaction of phenols with
N-(1-hydroxy-2,2,2-trichloroethyl)amides of sulfonic
acids in the presence of concn. sulfuric acid [4].
reacted regioselectively with pyrocatechol and salicyl-
amide affording the corresponding C-aminotrichloro-
ethylated products IVa, b in up to 90% yield
(Table 1).
R= EtOC(O) (I, III), 4-ClC6H4SO2 (II, IV); III, Ar =
4-HOC6H4 (a), 3,4-(HO)2C6H3 (b), Ph (c), 4-MeC6H4
(d), IV, Ar
=
3,4-(HO)2C6H3 (a), 4-HO-3-
NH2C(O)C6H3 (b).
The reaction is carried out in the presence of
oleum at room temperature and vigorous stirring of
the reaction mixture in a medium of the aromatic
hydrocarbon used as a substrate or in halogenated
hydrocarbon. The optimal duration of the process
3 5 h. At the use of concn. sulfuric acid instead of
oleum the reaction fails to proceed.
We continued systematic investigation on the
C-amidoalkylating ability of polyhaloaldehyde imines
and derivatives thereof [5 7] with respect to func-
tionally-substituted arenes containing hydroxy groups
or amide functions.
The heating and the use of large oleum amount
reduces the yield of C-amidoalkylation products III,
IV apparently due to side reaction of arene sulfonyl-
ation and to low stability of carbonyl and alkoxycarb-
onyl derivatives against strong mineral acids.
We were first to establish that N-(2,2,2-trichloro-
ethylidene)ethoxyformamide (I) in the presence of
oleum reacted as arenesulfonylimines with arenes and
hetarenes [4, 7], in particular, with phenol and pyro-
catechol, giving rise to ethoxycarbonylamino(tri-
chloroethyl)-substituted arenes IIIa d in 42 97%
yield (Table 1).
It is significant that in the presence of oleum the
reaction of chloral ethoxycarbonylimine with arenes
affords compounds IIIa d without noticeable damage
to the ethoxycarbonyl moiety.
4-Chlorobenzenesulfonic acid N-(2,2,2-trichloro-
ethylidene)amide (II) in the presence of oleum also
In extension of systematic investigation on
C-amidoalkylating properties of 1-functionally-sub-
1070-4280/01/3802-235$27.00 2002 MAIK Nauka/Interperiodica

236
AIZINA et al.
stituted polyhaloethylamides we studied the reaction
between N-(1-hydroxy-2,2,2-trichloroethyl)ethoxy-
formamide and N-(1-hydroxy-2,2,2-trichloroethyl)-
amides of arenesulfonic and acetic acids Va c with
phenol, pyrocatechol, and salicylamide in the
presence of sulfuric acid. It was established that
amides Va c in the presence of concn. sulfuric acid
also reacted regioselectively with phenol, pyro-
catechol, benzene, and toluene to afford the products
of C-amidotrichloroethylation of the latter, amides
IIIa d, IVa, VIa d.
discussed before. The yield is increased in the
presence of excess aromatic compound and at cooling
at the beginning of the reaction.
We failed to C-amidoalkylate the salicylamide with
hydroxytrichlroethylamides Va c under any condi-
tions.
The C-amidoalkylating activity of amides Va c
was formerly investigated with respect to benzene,
its alkyl and halo derivatives [8 10]. It was reported
that arene C-amidoalkylation with alkoxycarbonyl-
and acylamides required long time (up to 100 h) and
great excess ( 10 to 100-fold) of sulfuric acid [9, 10].
Yield of reaction products did not exceed 49% for
ethoxy derivatives [9] and 86% for acetyl derivatives
[10]. The structure of compounds formed was con-
firmed by chemical reactions [9, 10].
R = EtOC(O) (IIIa d, Va), 4-ClC6H4SO2 (Vb,
IVa), MeC(O) (Vc, VIa d); VI, Ar = 4-HOC6H4 (a),
3,4-(HO)2C6H3 (b), Ph (c), 4-MeC6H4 (d).
The composition of synthesized amidotrichloroethyl-
substituted arenes III, IV, VI is confirmed by
elemental analyses (Table 1), and the structure was
proved by spectral methods (Table 2).
The reaction was carried out in the same way as
above for 3 8 h in the presence of 6 10-fold excess
of sulfuric acid. The heating and the use of larger
amounts of sulfuric acid did not increase the yield of
compounds III, IV, VI, apparently due to the reasons
In the IR spectra of amides III, IV, VI are present
absorption bands from vibrations of the NH,
C=C arom C H bonds of alkyl groups. The IR
Table 2. IR and 1H NMR spectra of compounds RNHCHArCCl3 III, IV, VI
1
IR spectrum, , cm
1H NMR spectrum, , ppm ( JNHCH, Hz)a
CH NH Ar
NH
CO
other
solvent
R
absorption bands
IIIa 3290 1670 2950 2970 (C H aliph) (CH3)2CO-d6 5.58
6.78
6.86, 7.54 (AA BB ) 1.17 t, 4.07 q
IIIb 3240 1680 2900 2970 (C H aliph), DMSO-d6
3420 (OH)
5.49 d 7.40 d 6.82 d, 7.04 d, 7.20 s 1.16 t, 4.07 q
(10.0)
IIIc 3280 1680 2930 2960 (C H aliph), CDCl3
3050 (C H arom)
5.61 d 5.96 d 7.34, 7.47 m
(9.2)
6.01 d 5.58 d 7.14, 7.36 (AA BB ) 1.19 t, 4.12 q
1.22 t, 4.12 q
IIId 3380 1680 2930 2980 (C H aliph) CDCl3
(10.4)
3420, 3470 (OH), 1160, (CH3)2CO-d6 5.06
1320 (SO2)
IVb 3200, 1670 3480 (OH), 1170, 1350 DMSO-d6
3250 (SO2)
2.32 (Me)
6.64 d, 6.82 d, 6.97 s 7.32, 7.62
IVa 3250
8.71
(AA BB )
5.02 d 8.23 d 6.64 d, 7.28 d, 7.86 s 7.18, 7.55
(10.6)
(AA BB )
VIa 3280 1650 3400 (OH), 2870 2890 DMSO-d6
5.95 d 7.58 d 6.86, 7.25
2.11
(C H aliph)
VIb 3280 1660 3390 (OH)
(9.7)
5.89 d 7.62 d 6.82 d, 6.93 d, 7.20 s 2.03
(9.7) [3,4-(OH)2C6H3)]
(AA BB )
DMSO-d6
VIc 3260 1680 2930 2950 (C H aliph), CDCl3
3050 (C H arom)
5.87 d 6.54 d 7.23, 7.35 m
(9.7)
1.98
VId 3240 1650 2920, 2950 (C H aliph), DMSO-d6
3020 (C H arom)
5.91 d 6.56 d 7.16, 7.38 (AA BB ) 2.07
(9.8) 2.34 (Me)
a
No splitting of NHCH signal was observed in the 1H NMR spectrum recorded in acetone.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 2 2002

N-(2,2,2-TRICHLOROETHYLIDENE)-...
spectra of ethoxycarbonylamides III and acetamides In reactions was used 3 20% oleum.
237
VI contain besides the absorption bands of C=O
groups, the IR spectra of sulfonamide derivatives IV
contain the absorption band of SO2 group. In the IR
spectra of the derivatives of substituted phenols
appear strong absorption bands of the hydroxy groups
(Table 2). In the IR spectrum of compound IVb the
absorption bands of C=O, NH, and OH groups are
unlike those of the initial salicylamide by frequency
and form.
N-[1-(4-Hydroxyphenyl)-2,2,2-trichloroethyl]-
ethoxycarbonylamine (IIIa). (a) A solution of
0.01 mol of amide I in 10 ml of chloroform, 1 ml
of oleum, and 0.01 mol of phenol were vigorously
stirred at room temperature for 5 h. The reaction
mixture was diluted with 15 20 ml of cold water
and with water solution of sodium carbonate. The
insoluble reaction product was filtered off, dried
in a vacuum desiccator over P2O5, and recrystallized
from acetone chloroform mixture, 1: 1. (b) A solu-
tion of 0.01 mol of amide Va in 10 15 ml of chloro-
form, 2 ml of concn. sulfuric acid, and 0.01 mol of
phenol were vigorously stirred at room temperature
for 5 h. The workup of the reaction mixture was
carried out as in procedure a.
1
In the H NMR spectra of compounds III, IV, VI
appear a characteristic doublet of the NHCH fragment
(J 9 10 Hz), signals of aromatic protons, and of
protons from acetyl or ethoxycarbonyl group. The
relative integral intensities in the spectra correspond
to the assumed structures of compounds III, IV, VI.
The comparison of the published data [8 10] and
those obtained in the present study on the optimal
duration of reactions and on the yields of C-amido-
alkylation products permits a conclusion that the most
active in the C-amidoalkylation among the N-(1-hydr-
oxy-2,2,2-trichloroethyl)amides are the sulfonamide
derivatives. Less active are the alkoxycarbonyl-
amides, and the amides of carboxylic acids are the
least active. It is apparently caused by different ability
of the lone electron pair of the amide nitrogen to
stabilize the amido-substituted carbocations that are
generated under the action of proton-donor reagents
from trichloroethylamides containing a nucleofugal
group in the -position to the nitrogen.
Amides IIIb d, IVa were prepared similarly along
procedures a, b. Compounds VIa d were obtained
by method b.
N-[1-(3-Aminocarbonyl-4-hydroxyphenyl)-1,1,2-
trichloroethyl]-4-chlorobenzenesulfonamide (IVb).
A solution of 0.01 mol of amide II in 10 ml of
anhydrous chloroform and 0.01 mol salicylamide
were stirred in the presence of 0.5 ml of oleum for
5 h at room temperature. The solvent was distilled
off in a vacuum. The residue was washed with water
(10 ml), then with 5 7% aqueous ammonia (20 ml),
and again with water till neutral washings. Then the
insoluble product was dried in a vacuum desiccator
over P2O5, and recrystallized from acetone chloro-
form mixture, 1: 1.
In the alkoxycarbonyl- and acylamides the lone
electron pair of the amide nitrogen is capable to con-
jugation with a carbonyl group and therefore it less
stabilizes the carbocation that results in increased
duration of the reaction and decreased yield of
C-amidoalkylated products.
REFERENCES
1. Levkovskaya, G.G., Drozdova, T.I., Rozen-
tsveig, I.B., and Mirskova, A.N., Usp. khimii, 1999,
vol. 68, no. 7, pp. 638 652.
2. Mirskova, A.N., Drozdova, T.I., Levkovskaya, G.G.,
Bannikova, O.B., Kalikhman, I.D., and Voron-
kov, M.G., Zh. Org Khim., 1982, vol. 18, no. 7,
pp. 1407 1413.
3. Mirskova, A.N., Drozdova, T.I., Levkovskaya, G.G.,
Bannikova, O.B., Kalikhman, I.D., and Voron-
kov, M.G., Zh. Org. Khim., 1981, vol. 17, no. 5,
pp. 1108 1109.
4. Rudyakova, E.V., Levkovskaya, G.G., Rozen-
tsveig, I.B., Mirskova, A.N., and Albanov, A.I., Zh.
Org. Khim., 2001, vol. 37, no. 1, pp. 106 110.
5. Gogoberidze, I.T., Levkovskaya, G.G., Mirsko-
The synthesized amidotrichloroethyl-substituted
arenes III, IV, VI are colorless or lightly colored
crystalline substances with slight specific odor; they
are well soluble in organic solvents and insoluble in
water.
EXPERIMENTAL
1H NMR spectra were recorded on spectrometer
Bruker DPX-400 (400 MHz), internal reference
HMDS. IR spectra were registered on spectrophotom-
eter Specord 75IR from samples pelleted with KBr.
Trichloroethylideneamides I, II were obtained by
procedures [11] and [4] respectively.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 2 2002

238
AIZINA et al.
va, A.N., Kalikhman, I.D., Bannikova, O.B., and
va, A.H., Zh. Org. Khim., 1999, vol. 35, no. 6,
pp. 920 923.
Voronkov, M.G., Zh. Org. Khim., 1985, vol. 21,
no. 3, pp. 633 636.
9. Bal,on, Ya.G. and Smirnov, V.A., Zh. Org. Khim.,
1979, vol. 15, no. 1, pp. 68 73.
6. Rozentsveig, I.B., Levkovskaya, G.G., Mirsko-
va, A.N., Zh. Org. Khim., 1998, vol. 34, no. 6,
p. 947.
7. Rozentsveig, I.B., Levkovskaya, G.G., Albanov, A.I.,
and Mirskova A.H., Zh. Org. Khim., 2000, vol. 36,
no. 5, pp. 698 701.
10. Bal,on, Ya.G. and Smirnov, V.A., Zh. Org. Khim.,
1990, vol. 26, no. 11, pp. 2377 2381.
11. Mirskova, A.N., Levkovskaya, G.G., Bryuzgin, A.A.,
Drozdova, T.I., Kalikhman, I.D., and Voron-
kov, M.G., Zh. Org. Khim., 1990, vol. 26, no. 8,
pp. 1747 1750.
8. Rozentsveig, I.B., Levkovskaya, G.G., and Mirsko-
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