N-[(1,3-Benzodioxol-5-yl)methyl]-4-methylbenzamide: an analogue of capsaicin

In the title compound, C16H15NO3, the five-membered 1,3-dioxole ring is in an envelope conformation with the methylene C atom as the flap atom [lying 0.202 (3) Å out of the plane formed by the other four atoms]. The benzene ring makes a dihedral angle of 84.65 (4)° with the best least-squares plane through the 1,3-benzodioxole fused-ring system, which substitutes the 2-methoxyphenol moiety in capsaicin. In the crystal, molecules are connected into a zigzag supramolecular chain along the c-axis direction by N—H⋯O hydrogen bonds. These chains are connected into a layer in the ac plane by C—H⋯π interactions.

In the title compound, C 16 H 15 NO 3 , the five-membered 1,3dioxole ring is in an envelope conformation with the methylene C atom as the flap atom [lying 0.202 (3) Å out of the plane formed by the other four atoms]. The benzene ring makes a dihedral angle of 84.65 (4) with the best leastsquares plane through the 1,3-benzodioxole fused-ring system, which substitutes the 2-methoxyphenol moiety in capsaicin. In the crystal, molecules are connected into a zigzag supramolecular chain along the c-axis direction by N-HÁ Á ÁO hydrogen bonds. These chains are connected into a layer in the ac plane by C-HÁ Á Á interactions.
Cg1 and Cg2 are the centroids of the C1-C6 and C10-C15 rings, respectively.  Capsaicin is the main pungent compound found in chilli peppers of the genus Capsicum and is found to exert multiple pharmacological and physiological effects, including analgesic, anti-cancer, anti-inflammatory, anti-oxidant and antiobesity (Okamoto et al. 2011). This makes capsaicin an excellent scaffold for the rational design of analogues with better biological activity. The title compound (I) is a capsaicin-like derivative where the 2-methoxyphenol ring was substituted with a benzodioxol ring and the amide aliphatic chain was replaced with a 4-methylbenzoyl group. As suitable crystals were obtained from its hexane solution, a crystal structure determination of (I) was undertaken.
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.

Refinement
The H atoms were geometrically placed (C-H = 0.93-0.97 Å) and refined as riding with U iso (H) = 1.2-1.5U eq (C). The N -H H atom was located in a difference map, fixed in this position with U iso (H) = 1.2U eq (N).

Figure 1
The molecular structure of (I) showing atom labelling scheme and displacement ellipsoids at the 50% probability level (arbitrary spheres for the H atoms).

N-[(1,3-Benzodioxol-5-yl)methyl]-4-methylbenzamide
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.21 e Å −3 Δρ min = −0.20 e Å −3 Special details Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.