4-Chloro-N-(4-chloro­phenyl­sulfon­yl)-N-(3-oxo-2,3-dihydro-1,2-benzisothia­zol-2-yl)benzene­sulfonamide

Corrado Rizzoli; Paola Vicini; Matteo Incerti

doi:10.1107/S1600536809003195

. 2009 Jan 31;65(Pt 2):o416–o417. doi: 10.1107/S1600536809003195

4-Chloro-N-(4-chlorophenylsulfonyl)-N-(3-oxo-2,3-dihydro-1,2-benzisothiazol-2-yl)benzenesulfonamide

Corrado Rizzoli ^a,^*, Paola Vicini ^b, Matteo Incerti ^b

PMCID: PMC2968287 PMID: 21582006

Abstract

In the title compound, C₁₉H₁₂Cl₂N₂O₅S₃, the benzene rings of the chlorophenylsulfonyl groups form a dihedral angle of 35.85 (8)° and are inclined at angles of 23.51 (6) and 59.22 (6)° with respect to the essentially planar benzisothiazole ring system [maximum deviation = 0.030 (2) Å]. The molecular conformation is stabilized by an intramolecular C—H⋯O hydrogen bond. In the crystal packing, molecules are linked into chains parallel to the a axis by intermolecular C—H⋯O hydrogen bonds and π–π stacking interactions, with centroid–centroid distances of 3.592 (5) Å.

Related literature

For the synthesis and biological activity of 1,2-benzisothiazol-3(2H)-ones and 2-amino-1,2-benzisothiazol-3(2H)-one derivatives, see: Clerici et al. (2007 ▶); Siegemund et al. (2002 ▶); Vicini et al. (1997 ▶). For the synthesis of the title compound, see: Vicini et al. (2009 ▶). For the crystal structures of related benzisothiazole compounds, see: Cavalca et al. (1970 ▶); Ranganathan et al. (2002 ▶); Steinfeld & Kersting (2006 ▶); Kim et al. (1996 ▶); Xu et al. (2006 ▶); Sarma & Mugesh (2007 ▶); Kolberg et al. (1999 ▶).

Experimental

Crystal data

C₁₉H₁₂Cl₂N₂O₅S₃
M _r = 515.39
Triclinic,
a = 9.5358 (12) Å
b = 10.7757 (14) Å
c = 11.0393 (14) Å
α = 102.719 (2)°
β = 94.385 (3)°
γ = 105.598 (2)°
V = 1054.6 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.64 mm⁻¹
T = 295 (2) K
0.22 × 0.14 × 0.12 mm

Data collection

Bruker SMART 1000 CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1997 ▶) T _min = 0.872, T _max = 0.927
10953 measured reflections
3930 independent reflections
2267 reflections with I > 2σ(I)
R _int = 0.037

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.060
S = 0.94
3930 reflections
280 parameters
H-atom parameters constrained
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: SMART (Bruker, 1997 ▶); cell refinement: SAINT (Bruker, 1997 ▶); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶) and SCHAKAL (Keller, 1997 ▶); software used to prepare material for publication: SHELXL97 and PARST95 (Nardelli, 1995 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809003195/lh2763sup1.cif

e-65-0o416-sup1.cif^{(18.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809003195/lh2763Isup2.hkl

e-65-0o416-Isup2.hkl^{(192.6KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C13—H13⋯O1	0.93	2.42	3.275 (4)	153
C5—H5⋯O2ⁱ	0.93	2.58	3.353 (4)	140
C6—H6⋯O3ⁱⁱ	0.93	2.58	3.289 (3)	133

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

Financial support from the Italian MIUR (Ministero dell’Istruzione, dell’Universitá e della Ricerca) is gratefully acknowledged.

supplementary crystallographic information

Comment

Among 1,2-benzisothiazol-3(2H)-ones, a class of compounds with a wide spectrum of biological activities (Clerici et al., 2007; Siegemund et al., 2002), 2-amino-1,2-benzisothiazol-3(2H)-one derivatives have a rather recent history and 2-amino-1,2-benzisothiazol-3(2H)-one was first synthesized by our group in 1997 (Vicini et al., 1997). Due to their peculiar reactivity, 2-amino-1,2-benzisothiazol-3(2H)-one derivatives have recently emerged as effective antiplatelet, spasmolytic and antimicrobial agents (Clerici et al., 2007; Siegemund et al., 2002). The therapeutic significance of the 2-amino-1,2-benzisothiazol-3(2H)-one ring system with suitably functionalized substituents has encorauged us to develop novel compounds. The title compound was obtained unintentionally as a by-product during the synthesis of 2-(benzenesulfonyl)amino-1,2-benzisothiazol-3(2H)-ones that have been demonstrated to possess anti-HIV-1 activity against wild type virus and against viral strains carrying clinically relevant mutations (Vicini et al., 2008). The unexpected 2-(bisphenylsulfonyl)amino-1,2-benzisothiazol-3(2H)-ones, subjected to biological evaluation as well, resulted fairly active and, interestingly, endowed with lower cytotoxicity with respect to their monophenylsulfonyl substituted counterparts. In view of the structure-activity relationship study of the novel 1,2-benzisothiazol-3(2H)-one benzenesulfonamides aimed at optimizing their antiretroviral potency, the representative title compound was synthesized and its crystal structure is reported here.

The molecular structure of the title compound is shown in Fig. 1. The bond lengths and angles are unexceptional. The S1—N1 and S1—C7 bond distances within the benzoisothiazole ring system are 1.7347 (19) and 1.744 (2) Å respectively, in good agreement with those reported is related compounds (Cavalca et al., 1970; Ranganathan et al., 2002; Steinfeld & Kersting, 2006; Kim et al., 1996; Xu et al., 2006; Sarma & Mugesh, 2007). The N1—N2 bond distance (1.381 (2) Å) is not significantly different from the corresponding distance in 4,5-dimethyl-2-(3-nitrobenzenesulfonylamino)isothiazol-3(2H)-one 1,1-dioxide (1.387 (4) Å; Kolberg et al., 1999). The C8–C13 and C14–C19 benzene rings form a dihedral angle of 35.85 (8)° and are tilted by 23.51 (6) and 59.22 (6)° with respect to the essentially planar benzoisothiazole rings system (maximum deviation 0.030 (2) Å for atom N1). The molecular structure is stabilized by an intramolecular C—H···O hydrogen bond (Table 1). In the crystal packing (Fig. 2), molecules are linked into chains running parallel to the a axis by intermolecular C—H···O hydrogen interactions (Table 1) and π-π stacking interactions occurring between the benzene rings of centrosymmetrically related benzisothiazole rings, with a centroid-to-centroid separation of 3.592 (5) Å, a perpendicular interplanar distance of 3.514 (5) Å and a centroid-centroid offset of 0.746 (4) Å (symmetry code linking the adjacent rings: 1 - x, -y, 1 - z).

Experimental

The title compound was synthesized by reaction of 2-amino-1,2-benzisothiazol-3(2H)-one (10 mmol) with 4-chlorobenzenesulfonyl chloride (11 mmol) in pyridine (8 ml) for 2 h at 273K, resulting in a mixture of 4-chloro-N-(3-oxo-1,2-benzisothiazol-2(3H)-yl)benzenesulfonamide and 4-chloro-N-[(4-chlorophenyl)sulfonyl]-N-(3-oxo-1,2-benzisothiazol-2(3H)-yl)benzenesulfonamide (% yield ratio 33/66). Indeed, once the monophenylsulfonyl product is formed, a subsequent sulfonylation yielding the bisphenylsulfonyl derivative readily occurs, by the action of the electrophilic benzenesulfonyl chloride. The two products were simply separated because of the acidic character of the former. The crude product was poured into water (30 ml) and treated with a 10% aqueous sodium carbonate under stirring for 1 h, affording the title compound as insoluble solid that was collected by filtration. Pale yellow crystals suitable for X-ray analysis were obtained on slow evaporation of an ethanol solution at room temperature.