Structure of a new bioactive agent containing combined antibacterial and antifungal pharmacophore sites: 4-{[(E)-(5-bromo-2-hydroxyphenyl)methylidene] amino}-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide

Article abstract of DOI:10.1007/s10870-010-9856-x

The title compound (3), C₁₇H₁₄BrN₃O ₄S, is a Schiff base compound of 5-bromosalicylaldehyde (1) and sulfamethoxazole (2). The structure of (3) was determined by spectral (IR, ¹H and ¹³C NMR

Full text of DOI:10.1007/s10870-010-9856-x

J Chem Crystallogr (2011) 41:159–162
DOI 10.1007/s10870-010-9856-x
ORIGINAL PAPER
Structure of a New Bioactive Agent Containing Combined
Antibacterial and Antifungal Pharmacophore Sites: 4-{[(E)-(5-
Bromo-2-hydroxyphenyl)methylidene]amino}-N-(5-methyl-1,2-
oxazol-3-yl)benzenesulfonamide
•
Zahid H. Chohan Hazoor A. Shad
•
•
Loic Toupet Taibi Ben Hadda Mehmet Akkurt
•
Received: 9 February 2010 / Accepted: 17 July 2010 / Published online: 6 August 2010
Ó Springer Science+Business Media, LLC 2010
Abstract The title compound (3), C17H14BrN3O4S, is a
Schiff base compound of 5-bromosalicylaldehyde (1) and
sulfamethoxazole (2). The structure of (3) was determined
by spectral (IR, 1H and 13C NMR), elemental analyses
and X-ray diffraction data. Compound (3) crystallizes
in the monoclinic space group C2/c, with a = 31.936(3),
Introduction
Sulfonamide derived Schiff bases are potential class of
compounds, which have been found to possess a wide
range of medicinal properties [1]. These compounds have
also been found to possess a variety of pharmacological
properties including antibacterial, antifungal, anti-neo-
plastic, antiulcer, antiviral and enzymatic inhibition [2–5].
As a result, there is an increasing interest in exploring
novel methodologies for the synthesis and biological
screening of more such compounds [6–8]. Motivated by
this idea and in continuation of our previous work [9–16],
we wish to report here, the title compound 4-{[(E)-(5-
bromo-2-hydroxyphenyl)methylidene]amino}-N-(5-methyl-
1,2-oxazol-3-yl)-benzene sulfonamide, synthesized from
the reaction of sulfamethoxazole with 5-bromosalicylal-
dehyde (Fig. 1).
˚
b = 6.2571(5), c = 16.903(1) A, b = 94.867(8), V =
3
3365.5(5) A , Z = 8. In the molecule of compound (3), the
˚
molecule is bent at the S atom with a C–SO2–NH–C tor-
sion angle of -86.3(3)°. Pairs of molecules, related by
inversion centres, form intermolecular N–HÁÁÁN hydrogen
bonds to produce a dimer. An intramolecular phenolic O–
HÁÁÁN hydrogen bond is also formed. Intermolecular
hydrogen bonding and p–p stacking hold the molecules
together. The average distance between stacked benzene
˚
ring planes is 3.625(2) A.
Keywords Sulfonamide Á Bidentate Á Antibacterial Á
Antifungal
Results and Discussion
Chemistry
Z. H. Chohan (&) Á H. A. Shad
Department of Chemistry, Bahauddin Zakariya University,
Multan, Pakistan
e-mail: dr.zahidchohan@gmail.com
4-{[(E)-(5-Bromo-2-hydroxyphenyl)methylidene]amino}-N-
(5-methyl-1,2-oxazolyl)-benzenesulfonamide was formed by
an equimolar reaction of 5-bromosalicylaldehyde and sulfa-
methoxazole (Scheme 1). It was stable to air and moisture and
soluble in Dioxane, DMF and DMSO. It sharply melts at
216 °C. The spectral and analytical data, agreed well with the
structure.
L. Toupet
Institut de Physique, IPR, UMR CNRS 6251,
´
Universite de Rennes 1, Rennes, France
T. B. Hadda (&)
Laboratoire de Chimie des Materiaux,
´
Universite Mohammed 1ER, 60000 Oujda, Morocco
´
e-mail: tbenhadda@yahoo.fr
X-Ray Structure Determination of O,N-Ligand (3)
M. Akkurt
Department of Physics, F.A.S., Erciyes University,
38039 Kayseri, Turkey
Suitable single crystal of malonate derivative (3) was
obtained by recrystallization from ethanol. A white-transparent
123

160
J Chem Crystallogr (2011) 41:159–162
H
Table 1 Crystal data and structure refinement for (3)
O
O
Empirical formula
Formula weight
C17H14BrN3O4S
436.28
H
N
S
N
Temperature
150(2) K
O
˚
0.71069 A
Wavelength
N
CH3
Br
O
Crystal system, space group
Unit cell dimensions
Monoclinic, C2/c
Fig. 1 Proposed structure of antimicrobial agent (3)
˚
a = 31.936(3) A
a = 90°
˚
b = 6.2571(5) A
b = 94.867(8)°
c = 90°
crystal of C17H14BrN3O4S having approximate dimensions
of 0.23 9 0.21 9 0.17 mm was mounted on a glass fibre.
All measurements were made in the x-scan technique on a
CCD Saphire 3 Xcalibur diffractometer (Oxford Diffrac-
tion) with graphite monochromatized MoKa radiation. The
structure was solved by direct methods using the program
SIR-97 [17]. The non-hydrogen atoms were refined
anisotropically by the full-matrix least-square techniques
using the program SHELXL97 [18]. All H atoms were
located geometrically and treated using a riding model,
˚
c = 16.903(1) A
3
˚
Volume
3365.5(5) A
Z
8
Calculated density
F(000)
1.722 Mg/m3
1760.0
2.597 mm-1
2.64–26.99°
-40 B h B 40, -7 B k B 7,
-21 B l B 21
Absorption coefficient
h range for data collection
Limiting indices
Reflections collected/unique
Completeness to h = 26.990
Absorption correction
20752/3554 (Rint = 0.098)
˚
˚
˚
with O–H = 0.84 A, N–H = 0.88 A, C–H = 0.95–0.98 A
and Uiso (H) = 1.2 Ueq (Caromatic, Namine) and Uiso (H) =
1.5 Ueq (Cmethyl, Ohydroxyl).
97%
None
Refinement method
Full-matrix least-squares
on F2
The details of the crystal and experimental data was
listed in Table 1. Selected bond distances and bond angles
are given in Table 2. The molecular structure of the title
O,N-ligand (3) is shown in Fig. 2. Packing and hydrogen
bonding interactions are illustrated in Fig. 3.
Data/restraints/parameters
Goodness-of-fit on F2
3554/0/236
0.83
Final R indices [1937 reflections
with I [ 2r(I)]
Largest diff. peak and hole
R1 = 0.0371, wR2 = 0.0407
-3
The structure of the same compound but without the
bromine atom, 4-[(2-hydroxy-benzylidene)-amino]-N-(5-
methyl-isoxazol-3-yl)-benzenesulfonamide, has been recently
reported by Subashini et al. [19]. The S1–C11 distance
˚
0.72 and -0.56 e A
˚
[1.759(3) A] has a normal single-bond value and agree
In the molecule, an intramolecular O–HÁÁÁN (O1–N1 =
˚
well with those reported for other sulfonamides [19]. The
atoms around the S1 atom exhibit a slightly distorted tet-
rahedral configuration with the largest angle O3–S1–O2 of
121.50(12) (Table 2). As shown in Fig. 2, the two benzene
rings C1–C6 and C8–C13 are tilted by 1.24(14)° relative to
each other. Therefore, they are almost coplanar. The is-
oxazole ring N3/O4/C14–C16 with the benzene rings C1–
C6 and C8–C13 is oriented at dihedral angles of 79.38(15)
and 80.16(16)°, respectively. The molecule is bent at the S
atom with a C–SO2–NH–C torsion angle of -86.3(3)°
(Table 3).
2.597(3) A) hydrogen bond forms a six-membered
ring of graph-set notation S(6) (Fig. 2; Table 4). Therefore,
the benzene ring and the azomethine group of the molecule
are almost coplanar as in the crystal structure of similar
compound 4-[(2-hydroxy-benzylidene)-amino]-N-(5-methyl-
isoxazol-3-yl)-benzenesulfonamide [19].
An C–HÁÁÁBr interaction is observed (Fig. 2; Table 4).
Pair of molecules are centrosymmetrically linked via
N–HÁÁÁN hydrogen bonds [N2–(H2)ÁÁÁN3] as shown in Fig. 3
(Table 4). Further the crystal structure of the title com-
pound is stabilized by intermolecular C–HÁÁÁBr interactions
Scheme 1 Preparation and
structure of antimicrobial
agent (3)
O
CH3
O
CH3
N
N
N
O
S
H
O
S
H
O
O
H
N
(2)
O
H
H
H
N
N
O
H
O
Br
Br
(1)
(3)
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J Chem Crystallogr (2011) 41:159–162
161
˚
Table 2 Bond lengths (A) and angles (°) for (3)
Table 3 Torsion angles (°) for (3)
Br1–C4
1.888(3)
O4–C16
1.342(3)
1.409(2)
1.272(3)
1.421(3)
1.388(3)
1.316(3)
120.6(3)
119.2(2)
122.6(3)
115.9(3)
124.8(3)
118.7(2)
121.1(2)
116.7(2)
112.2(3)
131.1(3)
110.8(3)
115.9(3)
O3–S1–N2–C14
O2–S1–N2–C14
O1–C1–C2–C3
O1–C1–C6–C5
29.7(3)
160.6(2)
O1–C1–C6–C7
C1–C6–C7–N1
O4–N3–C14–N2
S1–N2–C14–N3
0.0(4)
-1.0(4)
177.0(2)
168.6(2)
S1–O3
1.4179(18)
1.4236(18)
1.628(2)
O4–N3
S1–O2
N1–C7
178.6(2)
S1–N2
N1–C8
-179.2(2)
S1–C11
1.759(3)
N2–C14
O1–C1
1.351(3)
N3––C14
O3–S1–O2
O3–S1–N2
O2–S1–N2
O3–S1–C11
O2–S1–C11
N2–S1–C11
C16–O4–N3
C7–N1–C8
C14–N2–S1
C14–N3–O4
O1–C1–C2
O1–C1–C6
121.50(12)
107.99(12)
104.85(11)
108.51(13)
107.14(14)
105.84(12)
108.2(2)
C5–C4–Br1
C3–C4–Br1
N1–C7–C6
C9–C8–N1
C13–C8–N1
C12–C11–S1
C10–C11–S1
N3–C14–N2
N3–C14–C15
N2–C14–C15
C15–C16–O4
O4–C16–C17
˚
Table 4 Hydrogen-bond parameters (A, °) for (3)
˚
˚
˚
D–HÁÁÁA
D–H (A) HÁÁÁA (A) DÁÁÁA (A) D–HÁÁÁA (°)
O1–H1ÁÁÁN1
N2–H2ÁÁÁN3i
0.84
1.86
2.07
2.93
2.597(3)
2.876(3)
3.686(3)
147
152
135
0.88
C17–H17CÁÁÁBr1ii 0.98
121.7(3)
Symmetry codes: (i) 1/2 ? x, 3/2 ? y, z; (ii) -1/2 ? x, 1/2 - y,
-3/2 ? z
126.76(19)
104.6(2)
118.4(3)
Experimental Section
121.6(3)
All materials and solvents used were of reagent grade as
1
received from commercial sources. H NMR spectra were
recorded on AC 300 MHz NMR Bruker Spectrometer at
ambient temperature and chemical shifts were reference to
the internal tetramethylsilane. Infrared spectra were
recorded in KBr pellets using a Shimadzu FTIR-8400S
spectrophotometer. Mass spectra were determined by
JEOL MS Route spectrometer and elemental analyses were
performed by Perkin Elmer USA.
4-{[(E)-(5-Bromo-2-
hydroxyphenyl)methylidene]amino}-N-(5-methyl-1,
2-oxazol-3-yl)-benzenesulfonamide (3)
Fig. 2 View of the title compound with the atom numbering scheme.
Displacement ellipsoids for non-H atoms are drawn at the 50%
probability level
An ethanol solution (20 mL) of sulfamethoxazole (0.506 g,
2 mmol) was mixed with 5-bromosalicylaldehyde (0.402 g,
2 mmol) in ethanol (10 mL). The mixture was refluxed for
3 h. The colour of the solution gradually changed from
colorless to reddish yellow during refluxing. The comple-
tion of reaction was monitored by TLC. After which, the
solution was cooled to room temperature, filtered and vol-
ume reduced to about one-third on rotary. A solid product
thus obtained was filtered, washed with ethanol and re-
crystallized in a mixture of ethanol: methanol (1:1) by
standing at room temperature for 4 days. Crystals of (3)
have been obtained.
Fig. 3 View of the packing and the intermolecular N–HÁÁÁN hydro-
gen bonds (dashed lines) of the title compound down the b axis
Clear and shinny crystals: 78% of yield, IR (KBr, m
cm-1): 3325 (OH), 1345, 1108 (SO2N–H), 1605 (CH=N),
1
1108 (SO2NH). H-NMR (300 MHz, DMSO-d6) d ppm:
and p–p stacking interactions between stacked benzene
ring planes (C1–C6 and C8–C13) with a centroid-to-cen-
˚
troid distance of 3.625(2) A.
2.31 (s, 3H, methylisoxazole), 6.8 (s, 1H, isoxazole),
6.9–7.6 (m, 3H, Br–Ph), 7.7–8.2 (m, 4H, N–Ph), 8.9 (s, 1H,
azomethine), 8.9 (s, 1H, SO2NH), 12.42 (s, 1H, OH)
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J Chem Crystallogr (2011) 41:159–162
13C-NMR (300 MHz, DMSO-D6) d ppm: 12.9 (methylis-
oxazole), 95.1 (C4-isoxazole), 118.4 (C3, Br–Ph), 120.5
(C1, Br–Ph), 122.6 (C2, C6, N–Ph), 116.0 (C5, Br–Ph),
128.6 (C3, C5, N–Ph), 134.0 (C6, Br–Ph), 135.5 (C4,
Br–Ph), 138.2 (C4, N–Ph), 150.0 (C3, isoxazole), 156.4
(C1, N–Ph). 160.0 (C2, Br–Ph), 160.9 (C=N, azomethine),
169.6 (C5, isoxazole). MS (IE): Calcd. for [M]? C17H14
BrN3O4S: 436.28, [M ? H]? (m/z) = 436.32 (436.0%).
Elemental analysis: Calculated for C17H14BrN3O4S; C,
46.62; H, 3.49; N, 9.81 found C, 46.80; H, 3.23; N, 9.63%.
2. Chohan ZH (2009) Trans Met Chem 34:153–161
3. Puccetti L, Fosolis G, Daniela V, Chohan ZH, Andrea S, Supuran
CT (2005) Bioorg Med Chem Lett 15:3096–3101
4. Nishimori I, Vullo D, Innocenti A, Scozzafava A, Mastrolorenz
A, Supuran CT (2005) Bioorg Med Chem Lett 15:3828–3833
5. Chohan ZH, Youssoufi MH, Jarrahpour A, Ben Hadda T (2010)
Eur J Med Chem 45:1189–1199
6. Ben Hadda T, Akkurt M, Filali Baba M, Daoudi M, Bennani B,
Kerbal A, Chohan ZH (2009) J Enzym Inhib Med Chem
24:457–463
7. Chohan ZH, Shad HA (2008) J Enzym Inhib Med Chem
23:369–379
8. Chohan ZH, Shad HA, Nasim FH (2009) Appl Organomet Chem
23:319–328
9. Chohan ZH, Tahir MN, Shad HA, Khan IU (2008) Acta
Crystallogr E64:o648
10. Chohan ZH, Shad HA, Tahir MN, Khan IU (2008) Acta
Crystallogr E64:o725
Supplementary Information
Crystallographic data for the structural analysis has been
deposited with the Cambridge crystallographic Data Centre,
CCDC No. 761146 for compound (3). Copies of this infor-
mation can be obtained free of charge from The Director,
CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK
(fax: ?44-1223-336033; e-mail: deposit@ccdc.cam.ac.uk
or http://www.ccdc.cam.ac.uk).
11. Shad HA, Chohan ZH, Tahir MN, Khan IU (2008) Acta
Crystallogr E64:o635
12. Chohan ZH, Shad HA, Tahir MN, Thebo KH (2009) Acta
Crystallogr E65:o2450
13. Chohan ZH, Shad HA, Tahir MN (2009) Acta Crystallogr
E65:o57
14. Shad HA, Tahir MN, Chohan ZH (2009) Acta Crystallogr
E65:o98
15. Chohan ZH, Shad HA, Tahir MN (2009) Acta Crystallogr
E65:o2426
16. Tahir MN, Chohan ZH, Shad HA, Khan IU (2008) Acta Crys-
tallogr E64:o720
17. Altomare A, Burla MC, Camalli M, Cascarano GL, Giacovazzo
C, Guagliardi A, Moliterni AGG, Polidori G, Spagna R (1999) J
Appl Crystallogr 32:o115
18. Sheldrick GM (2008) Acta Crystallogr A64:112–122
19. Subashini A, Hemamalini M, Muthiah PT, Bocelli G, Cantoni A
(2009) J Chem Crystallogr 39:112
Acknowledgments This work was financially supported by Higher
Education Commission of Pakistan under Indegenous 5000 Fellow-
ship Program. Authors gratefully acknowledge Rennes (CNRS,
France)/Oujda (CNRST, Morocco) collaboration and the ‘‘Projet
´
Global de Recherche de l’Universite Mohammed Premier’’/PGR-
UMP-BH-2005.
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