An IR study of the structure of new thiocarboxylic acid N-(1-arenesulfonamido-2-phenyl-2,2-dichloroethyl- and -2,2,2-trichloroethyl) amides

Article abstract of DOI:10.1023/B:RUGC.0000031866.70337.cc

An IR study of thiocarboxylic acid N-(1-arenesulfonamido-2-phenyl-2,2- dichloroethyl- and -2,2,2-trichloroethyl)amides revealed intramolecular hydrogen bonds whose formation is accompanied by electron density delocalization and stabilization of conformati

Full text of DOI:10.1023/B:RUGC.0000031866.70337.cc

Russian Journal of General Chemistry, Vol. 74, No. 4, 2004, pp. 610 614. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 4, 2004,
pp. 669 673.
Original Russian Text Copyright
2004 by Sarapulova, G. Rozentsveig, Aizina, I. Rozentsveig, Levkovskaya.
An IR Study of the Structure of New Thiocarboxylic Acid
N-(1-Arenesulfonamido-2-phenyl-2,2-dichloroethyl- and
-2,2,2-trichloroethyl)amides
G. I. Sarapulova, G. N. Rozentsveig, Yu. A. Aizina,
I. B. Rozentsveig, and G. G. Levkovskaya
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, Irkutsk, Russia
Received May 28, 2002
Abstract An IR study of thiocarboxylic acid N-(1-arenesulfonamido-2-phenyl-2,2-dichloroethyl- and
-2,2,2-trichloroethyl)amides revealed intramolecular hydrogen bonds whose formation is accompanied by
electron density delocalization and stabilization of conformations with quasiaromatic rings. Formation of
chelate species was confirmed by AM1 calculations.
Among sulfamides exhibiting biological activity,
polyfunctional haloalkylamides of sulfonic acids, syn-
thesized by reactions of various nucleophiles with
sulfonylimines derived from polyhalo aldehydes [1],
have a peculiar steric structure. A combination of
functional fragments differing in the steric configura-
tion and of several electron-donor and proton-donor
centers in polyfunctional molecules may favor forma-
tion of an intramolecular hydrogen bond and stabiliza-
tion of the resulting chelate quasicyclic structure due
to electron density delocalization [2]. A similar effect
was observed previously with acetylacetone, thioace-
tylacetone, vinyl ketones, malonaldehyde, and enol
forms of -diketones, containing O=C C=C O H and
related fragments [3 6]. Neutron and X-ray diffraction
studies showed that, in structures with intramolecular
hydrogen bonds involving double bonds, quasiaroma-
ticity of the chelate structures should be expected
(the concept of resonance-assisted hydrogen bonding,
RAHB) [2].
compounds and their peculiar behavior in chemical
reactions; in particular, involvement of an amino
group in hydrogen bonding can decrease its reactivity
as a nucleophile by a factor of 100 [10].
The reactions were performed in benzene or tri-
chloroethylene. We have found that thioamides react
in the amide form to give the products of addition of
the NH2 group across the C=N bond of ethyliden-
amides I and II, N-(1-arenesulfonamidopolychloro-
ethyl)thioamides III VI. The reaction is complete in
5 h. The yield of amides III VI is increased by heat-
ing of the reaction mixture.
ArSO2N=CHCCl2X + NH2C(S)R
ArSO2NHCHCCl2X,
NHC(S)R
Ia, Ib, IIa, IIb
III VI
X = Cl, Ar = Ph (Ia), 4-ClC6H4 (Ib©); X = Ph, Ar = Ph
(IIa), 4-ClC6H4 (IIb); R = Me, X = Cl, Ar = Ph (III); R =
Me, X = Ph, Ar = 4-ClC6H4 (IV); R = NHC(O)Me,
X = Cl, Ar = 4-ClC6H4 (V); R = NHC(O)Me, X = Ph,
Ar = Ph (VI).
Proceeding with studies of the synthetic potential
of the electron-deficient azomethine group in sulfonyl-
imines derived from polyhalo aldehydes [1, 7 9], we
studied reactions of N-(2,2,2-trichloroethylidene)-
arenesulfonamides I and N-(2-phenyl-2,2-dichloroeth-
ylidene)arenesulfonamides II with thioacetamide and
N-acetylthiourea. We prepared compounds in which
formation of an intramolecular hydrogen bond is
stereochemically possible. This allows us to study the
mutual influence of conjugation and hydrogen bond-
ing in polyfunctional molecules and to take into ac-
count this influence when evaluating the reactivity of
sulfonamide derivatives. The hydrogen bonding is
responsible for specific physicochemical properties of
The products of addition of the isothiuronium form
of the thioamides to I and II are not formed under
these conditions. The products of simultaneous addi-
tion of the NH2 and SH groups of thioureas to 2 equiv
of ethylidenamides I and II were not obtained either.
Formation of III VI was proved by 1H NMR spec-
troscopy, and their composition was confirmed by
1
elemental analysis (Table 1). In the H NMR spectra
of III VI (in DMSO-d6), the protons of the SO2NH
1070-3632/04/7404-0610 2004 MAIK Nauka/Interperiodica

AN IR STUDY OF THE STRUCTURE OF NEW THIOCARBOXYLIC ACID
Table 1. Yields, melting points, 1H NMR spectra, and elemental analyses of amides III VI
1H NMR spectrum (DMSO-d6), , ppm
611
Comp. Yield,
mp, C
no.
%
J(SO2NH, CH), J[C(S)NH, CH],
CH
NH
CH3
Ar
Hz
Hz
III
IV
78
88
106 108 6.91 d.d
153 154 6.95 d.d
9.16 d, 10.34 d
8.79 d, 10.14 d
2.14 s 7.51 7.82 m
10.0
10.0
9.0
9.1
2.07 s
2.02 s
7.53, 7.72
(AA BB )
7.39 7.66 m
7.59, 7.89
(AA BB )
V
67
64
155 156 6.69 d.d
143 144 6.84 d.d
9.65 d, 11.36 d,
11.49 s
9.00 d, 11.26 d,
11.14 s
10.1
10.0
9.7
9.6
VI
1.96 s 7.42 7.79 m
Found, %
Calculated, %
Comp. no.
Formula
C
Cl
N
S
C
Cl
N
S
III
IV
V
31.97
43.12
29.54
45.60
28.85
24.11
31.92
15.18
7.51
17.88
14.90
14.83
14.61
C10H11Cl3N2O2S2
C16H15Cl3N2O2S2
C11H11Cl4N3O3S2
C17H17Cl2N3O3S2
33.21
43.90
30.09
45.74
29.41
24.29
32.29
15.89
7.75
6.40
9.57
9.41
17.73
14.65
14.60
14.36
6.15
9.31
9.22
VI
1
CHNHC=S fragment give a characteristic group of
signals: a doublet of doublets in the range 6.69
6.95 ppm (CH) and two doublets (SO2NH and
NHC=S) of equal intensity in lower field (Table 1).
[ (NH) 3409 cm ], suggesting that these groups are
involved in hydrogen bonding [14 17]. The lack of
the concentration dependence of the frequencies and
intensities of these bands indicates that the hydrogen
bonds in III VI are intramolecular.
1
Also, the H NMR spectra of III VI contain proton
signals of aromatic rings and methyl groups with the
relative integral intensities consistent with the
suggested structures.
In the IR spectra of III VI, the intensity ratio of
the (C=O) [ (C=S)], amide II, and amide III bands
differs from that characteristic of amides. In particu-
lar, the amide II and amide III bands are very weak
relative to the carbonyl and thiocarbonyl bands,
whereas in the IR spectra of usual amides and thio-
amides these bands have comparable intensity [14
17]. There are also some other differences in the spec-
tra of III VI and related model compounds. Further-
more, appreciable differences are observed within the
series III VI: In the spectra of more complex com-
pounds V and VI, there are additional bands of vari-
In IR study of structural features of III VI, we pro-
ceeded from the fact that these compounds combine
amide, thioamide, and sulfonamide fragments. Where-
as amide and thioamide fragments are characterized
by so-called amide conjugation between the lone
electron pair of the nitrogen atom and the system of
the carbonyl and thiocarbonyl groups, the conjugation
in the SO2N group, according to the IR spectra and
dipole moments, is insignificant or absent at all [11].
However, the extent of participation of pharmacophor-
ic sulfonamide group in intramolecular interactions
in biologically active compounds is very important
[1, 12, 13].
1
able intensity at 1500 and 1640 cm .
As the solutions of III VI are heated to 100 C,
new stretching vibration bands of free NH, C=O, and
C=S groups appear (Table 2), suggesting cleavage of
hydrogen bonds. Interaction of arenesulfonamides
with DMSO and THF is also accompanied by cleav-
age of H bonds and simultaneous formation of new
intermolecular complexes with the (NH) bands at
Comparative analysis of the IR spectra of III VI
and of amides and thioamides modeling their molecu-
lar fragments shows that the (NH), (C=O), and
[ (C=S)] frequencies in III VI (Table 2) are appreci-
ably lower than those in usual N-substituted amides
1
3050 3200 cm . Under these conditions, the inten-
1
[ (NH) 3440 3470, (C=O) 1680 1700 cm ], thio-
sity ratio of the (C=O) [ (C=S)], amide II, and
amide III bands becomes typical of amides and thio-
1
amides [ (NH) 3440 3400 cm ], and sulfonamides
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 4 2004

612
SARAPULOVA et al.
1
Table 2. Absorption frequencies ( , cm ) of the main functional groups in the IR spectra (C2H2Cl4) of arenesulfon-
amides I IV at 20 C (data for 100 C in parentheses)
Comp. no.
(NH)
Amide II
Amide III
(C=S) or (C=O)
I
II
III
IV
3382, 3350 (3400, 3420)
3375, 3340 (3405, 3420)
3390, 3340, 3310 (3402, 3420, 3450) 1530 1550 (1510)
3390, 3350, 3310 (3400, 3420 3440) 1530 1560 (1510)
1550 (1505)
1530 (1500)
1280 (1300)
1290 (1310)
1260 (1300)
1270 (1310)
1210 (1240)
1200 (1235)
1660 (1700)
1660 (1700)
1
amides, and the absorption at 1500 and 1640 cm in
the IR spectra of V and VI fully disappears.
Comparison of the torsion angles shows that
H-bonded chelate ring B is virtually planar, whereas
in pseudorings A the NH group of the sulfonamide
moiety deviates from the plane of the other atoms
(Table 3). The internal bond angles in the H-bonded
rings in III VI are smaller than those in the corre-
sponding open conformations and in common amides
and thioamides. For example, the mean (S)OCN bond
angles in amides and thioamides are 124.7 and
122.9 , respectively, whereas the related angles in III
VI are 122.0 and 120.7 , respectively. The increased
N5 H6 and N3 H bond lengths in III VI (1.04 ) and
C8=O7 bond lengths in V and VI (1.245 ) also indi-
cate that these atoms participate in a hydrogen bond
(Table 3), whereas the bond length in a free NH group
To explain the unusual spectroscopic behavior,
determine the molecular and electronic structure, and
reveal major conformations of III VI, we performed
AM1 calculations with full geometry optimization,
based on data from the Cambridge Structural Database
[18, 19]. The calculations showed that the thermo-
dynamically preferable forms of III VI are arenesul-
fonamide forms with an intramolecular hydrogen bond
and Z conformation of the thioamide and amide
fragments [with respect to the relative arrangement
of the oxygen (sulfur) atom of the carbonyl (thiocar-
bonyl) group and NH hydrogen atom].
According to the calculations, the distance between
the H-bonded atoms is considerably shorter than the
sum of the van der Waals radii, which is characteristic
of chelate forms [20]. The hydrogen bond energy in
is 0.988
1.009
according to our calculations and 0.99
according to [19].
Comparative analysis of the bond orders (P ) for
the conformations of III VI with the hydrogen bond
and without it revealed their appreciable alternation.
This may be due to formation of quasiaromatic struc-
tures as a result of electron density delocalization in
the heteroconjugated system. Variation of P is espe-
cially significant in pseudorings B of bicyclic systems
of V and VI, which is quite understandable, since a
planar H-bonded cross-conjugated system is formed.
The order of the C2 N3 bond changes most signifi-
cantly upon H bonding, suggesting transformation of
the amide conjugation. This apparently accounts for
an unusual intensity ratio of the bands in the IR spec-
tra of III VI and for appearance of additional absorp-
tion in the spectra of V and VI, characterizing the
whole cross-conjugated system with delocalized
bonds. The unexpected results are somewhat increased
P of the S1 N2 bond and decreased order of the S=O
bond (Table 4). This indicates that the sulfonamide
fragment is sensitive to the electronic pressure [21]
from the chelate group, causing strengthening of the
S N bond.
1
III and IV is 3.7 and 4.0 kcal mol , respectively.
For V and VI, the energy of each of the two types of
intramolecular hydrogen bonds, which are not com-
plementary, was estimated from successive structure
calculations as the energy boundary between the con-
formers with the hydrogen bond and without it; we
obtained for V and VI the values of 3.6 and 4.05
1
(ring A), and 4.6 and 4.8 kcal mol (ring B), respec-
tively.
CCl2X
4CH
ArSO2
2.38
5
H
N
N3
A
6H
C2
1
CH3
S
I, II
CCl2X
2.08
4
3
N
C2 9
ArSO2
O7
C8
H
5
CH
N
A
B
6H
1
CH3
N
S
2.38
Thus, the revealed intramolecular hydrogen bonds
stabilize the forms of III VI in which the S=C N H
and O=C N H fragments have the Z conformation.
The spectroscopic and quantum-chemical parameters
H
III, IV
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 4 2004

AN IR STUDY OF THE STRUCTURE OF NEW THIOCARBOXYLIC ACID
613
1
1
Table 3. Geometric parameters of conformations of III VI
with intramolecular hydrogen bonds, according to AM1
calculations
1 cm . In the (NH) range, the resolution was 2 cm .
The 1H NMR spectra were recorded on a Bruker
DPX-400 spectrometer (400.13 MHz) in DMSO-d6.
The quantum-chemical calculations were performed
in the RHF approximation by the AM1 method with
full geometry optimization [17].
Parameter
III
IV
V
VI
Angle, deg
2.3
N-(1-Benzenesulfonamido-2,2,2-trichloroethyl)-
thioacetamide III. A 2.87-g portion of Ia [8] was
stirred with 2.25 g of thioacetamide in 10 15 ml of
dry benzene for 5 h at 50 C under argon. The precipi-
tate was filtered off, washed with 50 ml of water, and
dried. Yield of amide III 2.82 g (78%).
S1C2N3C4
C2N3C4N5
N3C4N5H6
O7C8N9C2
C8N9C2N3
C9C2N3C4
3.7
35.3
60.7
5.5
38.5
62.1
0.1
1.9
4.1
6.0
39.9
61.7
0.2
2.3
4.9
36.3
60.1
Bond length,
N-[1-(4-Chlorobenzene)sulfonamido-2-phenyl-
2,2-dichloroethyl]thioacetamide IV was prepared
similarly from 1.81 g of IIb [9] and 0.75 g of thio-
acetamide in 1.93 g yield (88%).
S1=C2
C8=O7
N5 H6
1.590
1.590
1.627
1.245
1.020
1.040
1.371
1.163
1.245
1.020
1.040
1.372
1.010
0.988
1.366
1.010
0.988
1.366
N3
H
N-[1-(4-Chlorobenzene)sulfonamido-2,2,2-tri-
chloroethyl]-N -acetylthiourea V. A 0.59-g portion
of acetylthiourea was added to a solution of 1.61 g of
Ib [8] in trichloroethylene. The mixture was stirred
with heating to 70 80 C for 1 h and then allowed to
stand at room temperature for a day. The precipitate
was filtered off and washed with CCl4. Yield of V
1.47 g (67%).
C2 N3
of III VI adequately reflect formation of quasiaromat-
ic forms with fairly strong hydrogen bonds and strong
delocalization of the electron density, demonstrating
synergism in the effects of conjugation and hydrogen
bonding.
N-(1-Benzenesulfonamido-2-phenyl-2,2-dichlo-
roethyl)-N -acetylthiourea VI. A mixture of 1.64 g
of IIa [9] and 0.59 g of acetylthiourea in 10 ml of ben-
zene was refluxed with stirring for 4 h, after which
the solvent was distilled off. The residue was recrys-
tallized from ethanol. Yield of VI 1.43 g (64%).
EXPERIMENTAL
The IR spectra were recorded on a Specord IR-75
spectrometer. Samples of III VI were prepared as KBr
pellets and as 0.04 0.005 M solutions in CHCl3 and
C2H2Cl4; such concentrations exclude association of
the molecules. Measurements at variable temperature
were performed with a Carl Zeiss cell equipped with a
calibrated thermocouple. The measurement scale in the
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