The discrete role of chlorine substitutions in the conformation and supra-molecular architecture of aryl-sulfonamides

Article abstract of DOI:10.1107/S0108270111019196

Two aryl-sulfonamide derivatives, N-(4-acetyl-phen-yl)benzene-sulfonamide, C₁₄H₁₃NO₃S, and N-(4-acetyl-phen-yl)-2,5-di- chloro-benzene-sulfonamide, C₁₄H₁₁Cl₂NO ₃S, differing by t

Full text of DOI:10.1107/S0108270111019196

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
In this study, two arylsulfonamide derivatives, N-(4-acetyl-
phenyl)benzenesulfonamide, (I), and N-(4-acetylphenyl)-2,5-
dichlorobenzenesulfonamide, (II), differing in by the presence
or absence of two chloro substituents on one of the phenyl
rings, were synthesized and characterized by X-ray diffraction
in order to establish structural relationships and the affect of
chloro substitution on the molecular conformation and crystal
assembly. Based on such knowledge, pharmacological profiles
of these compounds could be further rationalized.
ISSN 0108-2701
The discrete role of chlorine
substitutions in the conformation
and supramolecular architecture
of arylsulfonamides
William B. Fernandes,a Angelo Q. Arag˜ao,a Felipe T.
Martins,b Caridad Noda-Perez,b Carlito Lariuccic and
Hamilton B. Napolitanoa*
a
´
´
Science and Technology Center, State University of Goias, Anapolis, GO 75132-
903, Brazil, bInstitute of Chemistry, Federal University of Goias, Goiania, GO 74001-
´
ˆ
c
´
ˆ
970, Brazil, and Institute of Physics, Federal University of Goias, Goiania, GO
Despite the significant differences in the substitution
patterns of the two compounds determined here, sulfonamides
(I) and (II) exhibit similar intramolecular geometry (Fig. 1). A
superposition of their molecular backbones shows the
conformational similarity between the two compounds (Fig. 2),
except for a slight rotation about the sulfamyl bridge bond axis
(see below). As a practice in analyzing the intramolecular
features of small molecules determined by X-ray diffraction,
the geometric parameters of sulfonamides (I) and (II) were
submitted to a Mogul check (Bruno et al., 2004). All geometric
values agree with those of other reported sulfonamide struc-
tures (e.g. Perlovich et al., 2011; Martins et al., 2009;
74001-970, Brazil
Correspondence e-mail: hamilton@ueg.br
Received 15 March 2011
Accepted 20 May 2011
Online 4 June 2011
Two arylsulfonamide derivatives, N-(4-acetylphenyl)benzene-
sulfonamide, C14H13NO3S, and N-(4-acetylphenyl)-2,5-dichloro-
benzenesulfonamide, C14H11Cl2NO3S, differing by the
absence or presence of two chloro substituents on one of
the phenyl rings, were synthesized and characterized in order
to establish structural relationships and the role of chloro
substitution on the molecular conformation and crystal
assembly. Both arylsulfonamides form inversion-related dimers
through C—Hꢀ ꢀ ꢀꢀ and ꢀ–ꢀ interactions. These dimers pack in
a similar way in the two structures. The substitution of two H
atoms at the 2- and 5-positions of one phenyl ring by Cl atoms
did not substantially alter the molecular conformation or the
intermolecular architecture displayed by the unsubstituted
sulfonamide. The structural information controlling the
assembly of such compounds in their crystal phases is in the
(phenyl)benzenesulfonamide molecular framework.
Comment
Compounds containing a sulfonamide group, –SO2NH, are
known to be powerful inhibitors of carbonic anhydrases. They
are among the most widely used antibacterial agents, mainly
due to their low cost, low toxicity and excellent activity against
common bacterial diseases (Ozbek et al., 2007). The sulfon-
amide group occurs in many biologically active compounds,
including antimicrobial, antithyroid, antitumor and anti-
malarial drugs (Ozdemir et al., 2009; Seo et al., 2010; Domin-
guez et al., 2005; Connor, 1998; Hanson et al., 1999). In
addition, several substituted aromatic and heterocyclic sul-
fonamides have been synthesized and evaluated for their
potential therapeutic use as antiglaucoma agents (Remko et
al., 2010).
Figure 1
Aview of the molecular structures of (I) (top) and (II) (bottom), showing
the atom- and ring-labeling schemes. Displacement ellipsoids are drawn
at the 30% probability level and H atoms are shown as spheres of
arbitrary radii.
o226 # 2011 International Union of Crystallography
doi:10.1107/S0108270111019196
Acta Cryst. (2011). C67, o226–o229

organic compounds
Figure 2
A superposition of sulfonamides (I) (grey) and (II) (black). H atoms have
been omitted for clarity.
Drebushchak et al., 2006, 2007). A near-90ꢁ angle between the
planes of the two aromatic rings is a remarkable intra-
molecular feature observed in other related bioactive sulfo-
namides and was found in both (I) and (II). The planes
through the benzene rings form a dihedral angle of 88.27 (8)ꢁ
in (I) and 75.72 (8)ꢁ in (II) suggesting that their relationship is
related to hindrance effects involving the two rings. However,
the assignment of structural features as a result of only
intermolecular forces is a very difficult exercise.
Not only are the molecular structures of sulfonamides (I)
and (II) similar but so also are the supramolecular assemblies.
In both structures, infinite one-dimensional chains are formed
along the [010] direction by translation-related molecules
(Fig. 3). Each chain is therefore composed of only one
enantiomorph. In (I), these chains are created by a classical
N1—H1ꢀ ꢀ ꢀO3i [symmetry code: (i) x, y + 1, z] hydrogen bond
and a nonclassical C9—H9ꢀ ꢀ ꢀO1ii [symmetry code: (ii) x, y ꢂ 1,
z] hydrogen bond, while the bifurcated acceptor N1—
H1ꢀ ꢀ ꢀO3i and C12—H12ꢀ ꢀ ꢀO3i hydrogen-bond interactions
connect such ribbons in (II). The geometric parameters of the
hydrogen-bond interactions are shown in Tables 1 and 2.
Enantiopure chains are stacked parallel to the direction [100]
to create layers where the neighboring ribbon is composed of
the same enantiomorph [in the case of the structure of
sulfonamide (II)] or the other enantiomorph [in the case of
the structure of sulfonamide (I)].
Figure 3
Infinite one-dimensional chains of (a) (I) and (b) (II), growing along
the [010] direction. Classical N—Hꢀ ꢀ ꢀO and nonclassical C—Hꢀ ꢀ ꢀO
hydrogen-bonding interactions are shown as dashed lines, as is the Oꢀ ꢀ ꢀC
dipole interaction in (b). [Symmetry codes: (i) x, y + 1, z; (ii) x, y ꢂ 1, z;
1
2
1
2
(vi) ꢂx + 2, y ꢂ , ꢂz + .]
The hydrogen-bond patterns that assemble the chains differ
between (I) and (II), as mentioned above. This can be viewed
as a result of displacing molecules of (II) onto the (100) plane
when compared to (I) (Fig. 4). Such a displacement is related
to the formation of a halogen–ꢀ interaction between the 21-
screw axis symmetry-related molecules of (II). The occurrence
of this intermolecular contact is supported by the short
distance between Cl2 and the centroid of ring A (CgA; atoms
iii
˚
C1–C6) [3.528 (7) A]. This halogen–ꢀ interaction Cl2ꢀ ꢀ ꢀCgA
Figure 4
The halogen–ꢀ interaction occurring only in the structure of (II).
1
2
1
2
[symmetry code: (iii) ꢂx + 1, y ꢂ , ꢂz ꢂ ], along with the
1
1
iv
[Symmetry code: (iii) ꢂx + 1, y ꢂ , ꢂz ꢂ .]
˚
2
2
halogen–halogen contacts Cl1ꢀ ꢀ ꢀCl2 [3.453 (2) A; symmetry
v
3
1
˚
code: (iv) x, ꢂy + , z + ] and Cl1ꢀ ꢀ ꢀCl1 [3.581 (1) A;
symmetry code: (v) ꢂ2x + 1, ꢂy + 2, ꢂz], occurring in (II), are
the main differences between the crystal structures of the two
sulfonamides.
2
halogen–halogen interactions, together with the dipole–dipole
O2ꢀ ꢀ ꢀC13vi [3.223 (3) A; symmetry code: (vi) ꢂx + 2, y ꢂ ,
1
2
˚
ꢂz + 12] contact occurring between the sulfonyl and carbonyl
groups of 21-screw axis symmetry-related molecules of (II)
stacked parallel to the [100] direction, are responsible for the
Besides the three-dimensional connection of the [100]-
stacked [010] chains along the c axis, these halogen–ꢀ and
ꢃ
Acta Cryst. (2011). C67, o226–o229
Fernandes et al.
C14H13NO3S and C14H11Cl2NO3S o227

organic compounds
Cl1ꢀ ꢀ ꢀCl2ix [3.852 (1) A] contacts between inversion-related
˚
molecules kept in contact by the face-to-face and face-to-edge
stacking interactions.
In conclusion, it was possible to characterize the existence
of several classical and nonclassical hydrogen bonds and ꢀ–ꢀ
stacking interactions contributing to the stabilization of the
crystal packing of both compounds. Although the substitution
of two H atoms at positions 2 and 5 of ring A by Cl atoms did
not alter greatly the conformation and intermolecular archi-
tecture of the two sulfonamide analogs, despite halogen–ꢀ,
halogen–halogen and dipole–dipole interactions present only
in (II), it plays a discrete role in the conformation, which
differs slightly from that of (I). This reveals that the structural
information controlling the assembly of such compounds in
their crystal phases is in the (phenyl)benzenesulfonamide
molecular framework.
Experimental
Compounds (I) and (II) were obtained by equimolar coupling
between phenylsulfonyl chloride or 2,5-dichlorophenylsulfonyl
chloride and 4-aminoacetophenone in dichloromethane or acetone as
solvent. The reactions were performed at 343 K for about 6 h. The
precipitate was recrystallized from suitable solvents to obtain the
single crystals used for analysis. The reaction yields were 54 and 55%
for compounds (I) and (II), respectively.
Figure 5
The C—Hꢀ ꢀ ꢀꢀ and ꢀ–ꢀ interactions in the structures of (a) (I) and (b)
Compound (I)
(II). [Symmetry codes: (viii) ꢂx + 1, ꢂy, ꢂz + 1; (ix) ꢂx + 1, ꢂy + 1, ꢂz.]
Crystal data
3
˚
C14H13NO3S
Mr = 275.31
V = 1347.13 (10) A
Z = 4
most significant conformational difference between the two
compounds reported in this study: there is a conformational
flexibility on the bridge connecting the benzene rings, which
features a slight rotation about the N1—S1 bond axis of (II) if
the sulfamyl group conformation of (I) is used as a reference.
The values of the X—N1—S1—Y torsion angles (Table 3)
deviate by approximately 15ꢁ between the two sulfonamides,
which is in agreement with the rotation mentioned above.
No dipole–dipole O2ꢀ ꢀ ꢀC13vi interaction occurs in (I). In
this structure, along the direction [010], the C5—H5ꢀ ꢀ ꢀO1vii
Monoclinic, P21=c
Mo Kꢂ radiation
ꢃ = 0.24 mmꢂ1
T = 293 K
0.4 ꢄ 0.4 ꢄ 0.35 mm
˚
a = 13.0007 (5) A
˚
b = 8.3615 (4) A
˚
c = 12.5179 (6) A
ꢁ = 98.118 (3)ꢁ
Data collection
Nonius KappaCCD diffractometer
9368 measured reflections
3006 independent reflections
2214 reflections with I > 2ꢄ(I)
Rint = 0.046
1
2
3
2
˚
[3.332 (3) A; symmetry code: (vii) ꢂx + 1, y ꢂ , ꢂz + ;
Table 1
Hydrogen-bond geometry (A, ) for (I).
Table 1] hydrogen bond also connects 21-screw axis symmetry-
related molecules of (I) from different one-dimensional chains
made up of the same enantiomorph.
ꢁ
˚
D—Hꢀ ꢀ ꢀA
D—H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
Additionally, both structures are stabilized by C—Hꢀ ꢀ ꢀꢀ
N1—H1ꢀ ꢀ ꢀO3i
C9—H9ꢀ ꢀ ꢀO1ii
C5—H5ꢀ ꢀ ꢀO1vii
0.85 (2)
0.93
0.93
2.03 (3)
2.56
2.42
2.879 (2)
3.486 (2)
3.332 (3)
173 (2)
172
165
and ꢀ–ꢀ interactions, which generate inversion-related dimers.
The contacts C4—H4ꢀ ꢀ ꢀCgBviii [2.87 A; CgB is the centroid of
˚
Symmetry codes: (i) x; y þ 1; z; (ii) x; y ꢂ 1; z; (vii) ꢂx þ 12 ; y ꢂ 21 ; ꢂz þ .
the C7–C12 ring; symmetry code: (viii) ꢂx + 1, ꢂy, ꢂz + 1] and
3
2
CgAꢀ ꢀ ꢀCgAviii [4.207 (7) A] assemble these pairs of molecules
˚
in (I). Likewise, the contacts C4—H4ꢀ ꢀ ꢀCgBix [2.64 A;
˚
Table 2
Hydrogen-bond geometry (A, ) for (II).
symmetry code: (ix) ꢂx + 1, ꢂy + 1, ꢂz] and CgAꢀ ꢀ ꢀCgAix
ꢁ
˚
˚
[4.010 (8) A] play such a role in (II) (Fig. 5). These dimers can
D—Hꢀ ꢀ ꢀA
D—H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
be considered as the building units of both crystal archi-
tectures, while their interaction patterns differ between the
structures of (I) and (II). Contributing to the stabilization of
the dimers of (II), there are two other halogen–halogen
N1—H1ꢀ ꢀ ꢀO3i
0.81 (3)
0.93
2.11 (3)
2.64
2.903 (2)
3.388 (2)
166 (2)
137
C12—H12ꢀ ꢀ ꢀO3i
Symmetry code: (i) x; y þ 1; z.
ꢃ
o228 Fernandes et al. C14H13NO3S and C14H11Cl2NO3S
Acta Cryst. (2011). C67, o226–o229

organic compounds
Table 3
program(s) used to solve structure: SIR92 (Altomare et al., 1993);
program(s) used to refine structure: SHELXL97 (Sheldrick, 2008);
molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and
Mercury (Macrae et al., 2006); software used to prepare material for
publication: WinGX (Farrugia, 1999).
Selected torsion angles (ꢁ) of (I) and (II).
(I)
(II)
C7—N1—S1—O1
C7—N1—S1—O2
C7—N1—S1—C1
ꢂ177.62 (17)
ꢂ48.6 (2)
166.97 (17)
ꢂ63.21 (19)
50.4 (2)
67.46 (19)
The authors thank Professor Dr Carlos A. Simone for data
collection and the Brazilian Federal Agency CAPES for
financial support.
Refinement
R[F2 > 2ꢄ(F2)] = 0.048
wR(F2) = 0.147
S = 1.03
3006 reflections
177 parameters
H atoms treated by a mixture of
independent and constrained
refinement
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SF3150). Services for accessing these data are
described at the back of the journal.
ꢂ3
˚
Áꢅmax = 0.25 e A
ꢂ3
˚
Áꢅmin = ꢂ0.40 e A
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3
˚
V = 1477.24 (5) A
Z = 4
Mo Kꢂ radiation
ꢃ = 0.59 mmꢂ1
T = 293 K
C14H11Cl2NO3S
Mr = 344.2
Monoclinic, P21=c
˚
a = 13.3622 (2) A
˚
b = 8.1542 (2) A
˚
c = 15.6845 (3) A
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´
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˚
Áꢅmax = 0.39 e A
ꢂ3
˚
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˚
˚
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ꢃ
Acta Cryst. (2011). C67, o226–o229
Fernandes et al.
C14H13NO3S and C14H11Cl2NO3S o229