N-[(1,3-Benzodioxol-5-yl)meth­yl]benzene­sulfonamide: an analogue of capsaicin

Stella H Maganhi; Maurício T Tavares; Mariana C F C B Damião; Roberto Parise Filho

doi:10.1107/S1600536813028481

. 2013 Oct 23;69(Pt 11):o1700. doi: 10.1107/S1600536813028481

N-[(1,3-Benzodioxol-5-yl)methyl]benzenesulfonamide: an analogue of capsaicin

Stella H Maganhi ^a,^*, Maurício T Tavares ^b, Mariana C F C B Damião ^b, Roberto Parise Filho ^b

PMCID: PMC3884350 PMID: 24454126

Abstract

The title compound, C₁₄H₁₃NO₄S, an analogue of capsaicin, differs from the latter by having a 1,3-benzodioxole ring rather than a 2-methoxyphenol moiety, and having a benzenesulfonamide group instead of an aliphatic amide chain. The five-membered ring is in an envelope conformation with the methylene C atom lying 0.221 (6) Å out of the plane formed by the other four atoms. The dihedral angle between the phenyl ring and the mean plane of the 1,3-benzodioxole fused-ring system is 84.65 (4)°. In the crystal, molecules aggregate into supramolecular layers in the ac plane through C—H⋯O, N—H⋯O and C—H⋯π interactions.

Related literature

For background and the biological activity of capsaicin, see: Lee et al. (2011 ▶); Malagarie-Cazenave et al. (2011 ▶). For the synthesis and cytoxicity of the title compound, see: De Sá-Junior et al. (2013 ▶). For ring conformational analysis, see: Cremer & Pople (1975 ▶). graphic file with name e-69-o1700-scheme1.jpg

Experimental

Crystal data

C₁₄H₁₃NO₄S
M _r = 291.32
Orthorhombic,
a = 18.0158 (4) Å
b = 5.9346 (1) Å
c = 25.5480 (8) Å
V = 2731.51 (11) Å³
Z = 8
Mo Kα radiation
μ = 0.25 mm⁻¹
T = 290 K
0.25 × 0.22 × 0.20 mm

Data collection

Nonius KappaCCD diffractometer with Bruker APEXII CCD areadetector
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.930, T _max = 0.948
2652 measured reflections
2652 independent reflections
1860 reflections with I > 2σ(I)

Refinement

R[F ² > 2σ(F ²)] = 0.051
wR(F ²) = 0.149
S = 1.04
2652 reflections
181 parameters
H-atom parameters constrained
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.29 e Å⁻³

Data collection: COLLECT (Nonius, 1999 ▶); cell refinement: SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO (Otwinowski & Minor, 1997 ▶) and SCALEPACK; 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, 2012 ▶); software used to prepare material for publication: MarvinSketch (ChemAxon, 2010 ▶) and publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813028481/tk5268sup1.cif

e-69-o1700-sup1.cif^{(18.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813028481/tk5268Isup2.hkl

e-69-o1700-Isup2.hkl^{(127.7KB, hkl)}

Click here for additional data file.^{(5.3KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813028481/tk5268Isup3.cml

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

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

Cg1 and Cg2 are the centroids of the C2–C7 and C9–C14 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯O2ⁱ	0.99	2.00	2.945 (3)	157
C14—H14⋯O1ⁱⁱ	0.93	2.59	3.486 (3)	161
C10—H10⋯Cg1ⁱⁱⁱ	0.93	2.74	3.563 (3)	147
C8—H8B⋯Cg2^iv	0.97	2.82	3.511 (3)	129

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

Acknowledgments

We thank FAPESP (grant no. 2012/22524–9), the São Paulo Research Foundation (SMH), CNPq and CAPES for financial support.

supplementary crystallographic information

1. Comment

Capsaicin is the common name of trans-8-methyl-N-vanillyl-6-nonenamide, the main pungent component produced by hot red and chili peppers (Lee et al., 2011). It is a product of secondary metabolism from several species of the genus Capsicum (Malagarie-Cazenave et al. 2011) The beneficial effects of capsaicinoids are well known, such as their antitumoral activity. Thus, by rational approaches, the capsaicinoid structure could be used as an important prototype for the design of novel analogues. With this in mind, we intended to design a capsaicin-like analogue with potential activity against cancer cells. The title molecule, (I), N-(benzo[d][1,3]dioxol-5-ylmethyl)benzenesulfonamide was designed by converting the vanillyl system on the capsaicinoid structure to a benzodioxol group, and modifying the alkyl-lipophilic chain by an aromatic ring. The amide bond was replaced by a sulfonamide bond using bioisosteric concepts. Molecule (I) showed relevant cytotoxicity against MCF7 breast cancer cell line presenting an IC₅₀ = 32 µM (De Sá-Junior et al., 2013). The compound, Fig. 1, shows an envelope configuration in the 1,3-dioxole five membered ring, with the C7 atom lying 0,221 (6) Å out of the plane formed by the other four atoms. The ring puckering parameters are q2 = 0.140 (3) Å and φ2 = 145.7 (1)^o (Cremer & Pople, 1975). The crystal packing of (I), Table 1, is sustained by N—H···O and C—H···π interactions, leading to supramolecular layers in the ac plane.

2. Experimental

The synthesis has been already described (De Sá-Junior et al., 2013). Crystals were obtained by slow evaporation from a hexane/chloroform (4:1) solution.