Synthesis and crystal structures of o-[(Phenyl/p-methoxyphenyl)carbamoyl] benzene sulfonamides

Article abstract of DOI:10.1007/s10870-009-9611-3

o-[(Phenyl/p-methoxyphenyl)carbamoyl]benzene sulfonamides were synthesized in a straightforward manner utilizing directly saccharin and aniline/p-anisidine as starting material and their crystal structures have been determined. (C ₁₃H₁₂N₂O₃S): Mr = 276.31, monoclinic, P2₁/c, a = 10.277(6), b = 7.501(2), c = 16.261(10) A, β = 96.37(2)°, V = 1,245.8(11) A³, Z = 4. (C₁₄ H₁₄ N₂ O₄ S): Mr = 306.33, monoclinic, P2₁/c, a = 10.381(5), b = 7.861(2), c = 16.837(9) A, β = 93.43(2)°, V = 1,371.5(10) A³, Z = 4. In both structures the phenyl rings are inclined at 47.09(7) and 39.88(5)° with respect to each other and the structures are characterized by extensive inter and intramolecular hydrogen bonds.

Full text of DOI:10.1007/s10870-009-9611-3

J Chem Crystallogr (2010) 40:116–121
DOI 10.1007/s10870-009-9611-3
ORIGINAL PAPER
Synthesis and Crystal Structures of o-[(Phenyl/p-
methoxyphenyl)carbamoyl]benzene Sulfonamides
Waseeq Ahmad Siddiqui Æ Saeed Ahmad Æ
Hamid Latif Siddiqui Æ Tanvir Hussain Æ
Masood Parvez
Received: 21 January 2009 / Accepted: 8 August 2009 / Published online: 22 August 2009
Ó Springer Science+Business Media, LLC 2009
Abstract o-[(Phenyl/p-methoxyphenyl)carbamoyl]benzene
sulfonamides were synthesized in a straightforward manner
utilizing directly saccharin and aniline/p-anisidine as
starting material and their crystal structures have been
determined. (C13H12N2O3S): Mr = 276.31, monoclinic,
Introduction
Saccharin derivatives have been of interest due to their
widespread applications [1, 2], particularly their open ring
benzene sulfonamide derivatives have shown cyclooxy-
genase-2 (COX-2) inhibitory action to act as analgesic and
anti-inflammatory agents [3]. The crystal structure and
convenient straightforward synthesis of the very first
derivative of this important molecule has recently been
reported by our research group [4]. Earlier, synthesis of
only two unsubstituted o-cyclohexyl and o-phenylcarba-
moyl benzene sulfonamide derivatives was reported uti-
lizing indirectly N-vinylsulfobenzimide as starting material
[5]. While continuing our research on the synthesis of o-
carbamoyl benzene sulfonamide derivatives [6, 7], we have
devised a simple and straightforward synthesis of the title
compounds o-[(phenyl/p-methoxyphenyl)carbamoyl]-ben-
zene sulfonamides (IIa) and (IIB), utilizing directly sac-
charin as starting material. Herein, we report the synthesis
and crystal structures of these derivatives.
˚
P21/c, a = 10.277(6), b = 7.501(2), c = 16.261(10) A, b =
3
˚
96.37(2)°, V = 1,245.8(11) A , Z = 4. (C14 H14 N2 O4 S):
Mr = 306.33, monoclinic, P21/c, a = 10.381(5), b =
˚
7.861(2), c = 16.837(9) A, b = 93.43(2)°, V = 1,371.5(10)
3
A , Z = 4. In both structures the phenyl rings are inclined at
˚
47.09(7) and 39.88(5)° with respect to each other and the
structures are characterized by extensive inter and intramo-
lecular hydrogen bonds.
Keywords Sulfonamides Á
o-[(Aryl)carbamoyl]benzene sulfonamides Á
Biological activities Á Crystal structure
W. A. Siddiqui
Department of Chemistry, University of Sargodha,
Sargodha, Pakistan
Experimental
Synthesis of o-[(Phenyl/p-methoxyphenyl)
carbamoyl]benzene Sulfonamides
S. Ahmad
Department of Chemistry, University of Science
and Technology, Bannu, Pakistan
A suspension of saccharin I (1.0 g, 5.46 mmol) and an
excess of freshly distilled aniline (5 mL), whereas an
exactly mole-equivalent quantity in case of p-anisidine
(0.44 g, 5.46 mmol) in xylene (25 mL) was first stirred at
room temperature (15 min.) and then under reflux (2 h).
The reaction mixture was cooled to room temperature
followed by ice-bath cooling (1 h), filtered and dried to
obtain dark violet solid products (IIa) and (IIb). The
H. L. Siddiqui Á T. Hussain
Institute of Chemistry, University of the Punjab,
Lahore, Pakistan
M. Parvez (&)
Department of Chemistry, University of Calgary,
2500 University Drive, N.W. Calgary,
AB T2N 1N4, Canada
e-mail: parvez@ucalgary.ca
123

J Chem Crystallogr (2010) 40:116–121
117
Scheme 1
O
S
O
S
N
H
NH
O
X
reflux, 2 hrs
+
X
H2N
NH2
O
O
O
I
II
X = IIa = H
IIb = 4-OMe
products were crystallized from MeOH by slow evapora-
tion at 313 K to obtain light violet crystals (yields =
78–83%).
DMSO-d6) d: 3.76 (s, 3H, CH3), 6.95–6.96 (m, 2H, aro-
matic), 7.15 (s, 2H, NH2), 7.62–7.64 (m, 2H, aromatic),
7.70–7.75 (m, 3H, aromatic), 7.97–7.99 (m, 1H, aromatic),
10.56 (s, 1H, NH); 13C-NMR (100 MHz, DMSO-d6) d:
166.7, 155.8, 140.7, 135.1, 132.2, 131.9, 130.2, 128.9,
127.1, 121.7, 113.8, 55.2. LRMS (ES?): m/z: 306.4 [M]?
(53.5%); m.p. 451–452 K (Scheme 1).
IIa: IR (Neat, mmax, cm-1): NH and NH2 3304 (br) and
1
3234, CO 1626, SO21331 and 1160; H-NMR (400 MHz,
DMSO-d6) d: 7.00–7.25 (m, 3H, aromatic), 7.30–7.50 (m,
2H, aromatic), 7.60–7.85 (m, 3H ? 2H, aromatic and
NH2), 7.90–8.05 (m, 1H, aromatic), 10.65 (s, 1H, NH);
13C-NMR (100 MHz, DMSO-d6) d: 167.0, 140.7, 138.8,
135.1, 132.2, 130.2, 128.9, 128.7, 127.2, 124.0, 120.1.
LRMS (ES?): m/z: 276 [M]? (39.5%); m.p. 453–454 K.
IIb: IR (Neat, mmax, cm-1): NH and NH2 3357 (br) and
X-ray Structure Determination
A colorless needle crystal of (IIa) and a colorless prismatic
crystal of (IIb) were coated with Paratone 8277 oil (Exxon)
and mounted on glass fibers for data collection. All
1
3274, CO 1632, SO21337 and 1162; H-NMR (400 MHz,
Table 1 Crystal data and
Compound
(IIa)
(IIb)
structure refinement for (IIa)
and (IIb)
CCDC deposit No.
711413
711414
Empirical formula
Formula weight
Temperature
C13H12N2O3S
276.31
C14H14N2O4S
306.33
173(2) K
173(2) K
˚
0.71073 A
˚
0.71073 A
Wavelength
Crystal system & space group
Unit cell dimensions
a
Monoclinic, P21/c
Monoclinic, P21/c
˚
10.277(6) A
˚
10.381(5) A
˚
7.501(2) A
˚
7.861(2) A
b
˚
16.261(10) A
˚
16.837(9) A
c
b
96.37(2)°
1,245.8(11) A
93.43(2)°
1,371.5(10) A
3
3
˚
˚
Volume
Z
4
4
Density (calculated)
Absorption coefficient
F(000)
1.473 Mg/m3
0.265 mm-1
576
1.484 Mg/m3
0.254 mm-1
640
Crystal size
0.26 9 0.10 9 0.07 mm3
0.20 9 0.12 9 0.12 mm3
h range for data collection
Reflections collected
Independent reflections
Completeness to h = 27.5°
Absorption correction
Max. and min. transmission
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2.0 r(I)]
R indices (all data)
Largest diff. peak and hole
3.0–27.5°
4,680
3.5–27.5°
5,556
2,827 [R(int) = 0.035]
98.7%
3,104 [R(int) = 0.034]
98.9%
Multi-scan method
0.982 and 0.934
2,827/0/181
Multi-scan method
0.970 and 0.951
3,104/0/200
1.10
1.03
R1 = 0.049, wR2 = 0.115
R1 = 0.069, wR2 = 0.124
R1 = 0.042, wR2 = 0.097
R1 = 0.058, wR2 = 0.108
-3
-3
˚
0.24 and -0.41 e.A
˚
0.48 and -0.40 e.A
123

118
J Chem Crystallogr (2010) 40:116–121
Table 2 Atomic coordinates (9104) and equivalent isotropic dis-
measurements were made on a Nonius Kappa CCD dif-
fractometer with graphite monochromated Mo-Ka radia-
tion. Details of crystal data and structure refinement for
both structures have been provided in Table 1. The data
were corrected for Lorentz and polarization effects and for
absorption using multi-scan method [8, 9]. The structures
were solved by direct methods [10] and expanded using
2
placement parameters (A 9 10 ) for (IIa)
3
˚
Atom
x
y
z
U(eq)
S(1)
3,160(1)
941(2)
3,417(1)
408(2)
7,182(1)
6,784(1)
7,412(1)
6,648(1)
7,113(1)
6,727(1)
8,101(1)
8,855(2)
9,580(2)
9,555(2)
8,804(2)
8,067(1)
7,255(1)
6,370(2)
5,611(2)
4,903(2)
4,946(2)
5,707(2)
6,422(2)
24(1)
26(1)
38(1)
31(1)
22(1)
27(1)
23(1)
29(1)
33(1)
31(1)
27(1)
21(1)
21(1)
22(1)
26(1)
33(1)
36(1)
35(1)
28(1)
O(1)
O(2)
O(3)
N(1)
N(2)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
4,341(2)
2,123(2)
-691(2)
3,597(2)
2,504(2)
3,234(3)
2,749(3)
1,537(3)
782(3)
4,403(3)
4,219(2)
2,262(3)
1,629(3)
2,772(3)
3,095(3)
2,577(4)
1,778(4)
1,507(3)
1,973(3)
1,489(3)
2,242(3)
1,745(3)
1,959(4)
2,634(4)
3,081(4)
2,883(3)
˚
Table 4 Selected bond lengths [A] and angles [°] for (IIa) and (IIb)
(IIa)
(IIb)
S(1)–O(3)
1.430(2)
1.436(1)
S(1)–O(2)
1.435(2)
1.620(2)
1.773(3)
1.239(3)
1.345(3)
1.425(3)
–
1.433(1)
1.609(2)
1.777(2)
1.244(2)
1.337(2)
1.425(2)
1.391(2)
1.398(2)
119.67(8)
106.26(9)
106.78(9)
107.40(9)
106.83(9)
109.69(9)
127.3(2)
113.6(2)
1,265(2)
493(2)
S(1)–N(2)
S(1)–C(1)
-1,567(2)
-1,181(2)
-2,051(3)
-3,297(3)
-3,686(3)
-2,832(2)
O(1)–C(7)
N(1)–C(7)
N(1)–C(8)
O(4)–C(11)
O(4)–C(14)
–
O(2)–S(1)–O(3)
O(3)–S(1)–N(2)
O(2)–S(1)–N(2)
O(3)–S(1)–C(1)
O(2)–S(1)–C(1)
N(2)–S(1)–C(1)
C(7)–N(1)–C(8)
C(11)–O(4)–C(14)
119.55(13)
107.25(12)
106.06(12)
107.39(12)
108.09(12)
108.05(12)
128.0(2)
–
U(eq) is defined as one-third of the trace of the orthogonalized Uij
tensor
Table 3 Atomic coordinates (9104) and equivalent isotropic dis-
2
placement parameters (A 9 10 ) for (IIb)
3
˚
Atom
x
y
z
U(eq)
S(1)
-3,164(1)
-991(1)
-2,152(1)
-4,288(1)
3,797(1)
574(1)
2,787(1)
-164(2)
3,504(2)
3,786(2)
1,952(2)
1,735(2)
1,126(2)
2,177(2)
2,571(2)
2,130(2)
1,324(2)
964(2)
7,741(1)
8,108(1)
8,252(1)
7,521(1)
21(1)
23(1)
27(1)
30(1)
41(1)
21(1)
26(1)
20(1)
25(1)
28(1)
29(1)
24(1)
19(1)
19(1)
21(1)
26(1)
29(1)
29(1)
33(1)
28(1)
45(1)
O(1)
O(2)
O(3)
O(4)
N(1)
N(2)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
˚
Table 5 Hydrogen bonding geometry [A and °]
10,582(1)
7,808(1)
8,185(1)
6,848(1)
6,124(1)
5,422(1)
5,449(1)
6,173(1)
6,882(1)
7,661(1)
8,523(1)
9,258(1)
9,945(1)
9,897(1)
9,168(1)
8,479(1)
11,087(1)
D–HÁÁÁA
d(D–H) d(HÁÁÁA) d(DÁÁÁA) \(DHA)
N(1)–H(1N)ÁÁÁO(1)#1
0.89(3)
N(2)–H(21N)ÁÁÁO(2)#2 0.85(3)
2.14(3)
2.11(3)
2.13(3)
2.49
2.992(3) 160(2)
2.929(3) 162(3)
2.890(3) 146(3)
-3,671(2)
-2,458(2)
-3,092(2)
-2,538(2)
-1,356(2)
-702(2)
-1,246(2)
-546(2)
1,381(2)
888(2)
N(2)–H(22N)ÁÁÁO(1)
C(2)–H(2)ÁÁÁO(2)
0.87(3)
0.95
2.891(4)
2.911(3)
3.451(4)
105
119
162
C(9)–H(9)ÁÁÁO(1)
0.95
2.32
C(5)–H(5)ÁÁÁO(3)#3
N(1)–H(1N)ÁÁÁO(1)#1
N(2)–H(21N)ÁÁÁO(1)
0.95
2.54
0.85(2)
0.87(2)
2.13(2)
2.24(2)
2.16(2)
2.49
2.930(2) 158(2)
2.971(3) 142(2)
2.997(2) 164(2)
1,383(2)
920(2)
N(2)–H(22N)ÁÁÁO(3)#2 0.86(2)
1,693(2)
1,391(2)
1,488(3)
1,883(2)
2,176(3)
2,079(3)
3,302(3)
C(2)–H(2)ÁÁÁO(3)
C(9)–H(9)ÁÁÁO(1)
C(2)–H(2)ÁÁÁO(4)#3
0.95
0.95
0.95
2.887(3)
2.933(3)
3.324(3)
105
114
145
2.41
1,693(2)
2,982(2)
3,478(2)
2,680(2)
3,528(2)
2.50
(IIa): Symmetry transformations used to generate equivalent atoms:
#1 -x, y ? ‘, -z ? 3/2 #2 –x ? 1, y - ‘, -z ? 3/2 #3 -x, y
- ‘, -z ? 3/2
(IIb): Symmetry transformations used to generate equivalent atoms:
#1 -x, y ? ‘, -z ? 3/2 #2 –x - 1, y - ‘, -z ? 3/2 #3 x - 1,
-y ? ‘, z - ‘
U(eq) is defined as one-third of the trace of the orthogonalized Uij
tensor
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J Chem Crystallogr (2010) 40:116–121
119
C4
C4
C3
C5
C5
C3
C13
C13
N1
C12
C11
N1
C6
C12
C8
C8
C7
C7
C6
C2
C11
C2
C1
C1
O4
O3
O2
S1
O1
S1
C9
C10
C9
O1
C10
C14
O2
O3
N2
N2
Fig. 3 ORTEP-3 [13] drawing of (IIb) with displacement ellipsoids
plotted at 50% probability level; intramolecular hydrogen bonds are
represented by dashed lines
Fig. 1 ORTEP-3 [13] drawing of (IIa) with displacement ellipsoids
plotted at 50% probability level; intramolecular hydrogen bonds are
represented by dashed lines
Results and Discussion
Fourier techniques [11]. The non-hydrogen atoms were
refined anisotropically. Hydrogen atoms bonded to
C-atoms were included at geometrically idealized positions
and were refined in riding model while H-atoms bonded to
N-atoms were allowed to refine; isotropic temperature
factors Uiso were allowed for all H-atoms times 1.2(Ueq) of
the parent atoms. The structures were refined by full-matrix
least-squares calculations using F2 with the aid of SHEL-
XL-97 [12]. The weighting schemes were based on
counting statistics and the final difference Fourier maps
were essentially featureless. The Figures were plotted with
the aid of ORTEP-3 for Windows [13]. Atomic coordinates
and equivalent isotropic displacement parameters have
been provided in Tables 2 and 3 for (IIa) and (IIb),
respectively, selected bond distances and angles in Table 4
and hydrogen bonding geometry in Table 5.
The molecular structure of (IIa) is presented in Fig. 1. The
mean-planes formed by the phenyl rings C(1)–C(6) and
C(8)–C(13) are inclined at 47.09(7)° with respect to each
other and are oriented at 62.92(11)° and 24.10(18)°,
respectively, with respect to the carbamoyl group, C(7)/
N(1)/O(1). The structure is characterized by classical
intermolecular hydrogen bonds of the type N–HÁÁÁO
resulting in a three dimensional frame-work (Fig. 2). In
addition, non-classical hydrogen bonding interactions,
C(5)–H(5)ÁÁÁO3#3, link the molecules into sheets. The
structure also exhibits intramolecular interactions, N(2)–
H(22 N)ÁÁÁO(1), C(9)–H(9)ÁÁÁO1 and C(2)–H(2)ÁÁÁO(2)
resulting in seven, six and five membered rings with S(7),
S(6) and S(5) motifs, respectively [14]; details of hydro-
gen-bonding geometry have been provided in Table 5.
Fig. 2 Unit cell packing of
(IIa) viewed down the c-axis
showing N–HÁÁÁO type
hydrogen bonds
c
o
a
b
123

120
J Chem Crystallogr (2010) 40:116–121
Fig. 4 Unit cell packing of
(IIb) viewed down the c-axis
showing N–HÁÁÁO type H-bonds
a
o
c
b
In the structure of (IIb) (Fig. 3), the mean-planes
formed by the phenyl rings C(1)–C(6) and C(8)–C(13) are
inclined at 39.88(5)° with respect to each other and are
oriented at 65.85(8)° and 31.95(11)°, respectively, with
respect to the carbamoyl group, C(7)/N(1)/O(1). The
methoxy group, C(11)/O(4)/C(14), forms an angle
67.31(16)° with the plane of the phenyl ring with which it
is bonded. Like the structure of (IIa), the structure of (IIb)
also shows classical intermolecular hydrogen bonds of the
type N–HÁÁÁO (Fig. 4). In addition, non-classical hydrogen
bonding interactions, C(2)–H(2)ÁÁÁO2#3, link the molecules
into sheets. The structure also exhibits intramolecular
interactions, N(2)–H(22 N)ÁÁÁO(1), C(9)–H(9)ÁÁÁO1 and
C(2)–H(2)ÁÁÁO(3) resulting in seven, six and five membered
rings with S(7), S(6) and S(5) motifs, respectively [14];
details of hydrogen-bonding geometry have been provided
in Table 5.
Supplementary Material
CCDC-711413 and CCDC-711414 contain the crystallo-
graphic data for compounds (IIa) and (IIb), respectively,
reported in this article. These data can be obtained free of
charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or
from the Cambridge Crystallographic Data Center
(CCDC), 12 Union Road, Cambridge CB2 1EZ, UK: fax:
?44(0)1223-336033; email: deposit@ccdc.cam.ac.uk].
Acknowledgments The authors acknowledge the Higher Education
Commission (HEC), Pakistan, for funding this research.
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˚
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