Syntheses and crystal structures of two piperine derivatives

The title compounds, 5-(2H-1,3-benzodioxol-5-yl)-N-cyclohexylpenta-2,4-dienamide, (I), and 5-(2H-1,3-benzodioxol-5-yl)-1-(pyrrolidin-1-yl)penta-2,4-dien-1-one (II), are derivatives of piperine, which is known as a pungent component of pepper. Their geometrical parameters are similar to those of the three polymorphs of piperine, which indicate conjugation of electrons over the length of the molecules. The extended structure of (I) features N—H⋯O amide hydrogen bonds, which generate C(4) [010] chains. The crystal of (II) features aromatic π–π stacking, as for two of three known piperine polymorphs.


Structural commentary
Compound (I) (Fig. 2) crystallizes in the monoclinic space group P2 1 /c with four molecules per unit cell. The C1-C6 cyclohexyl ring adopts a chair conformation with the exocyclic C5-N1 bond in an equatorial orientation. The C7-C12/O2/ O3 fused-ring system is almost planar (r.m.s. deviation = 0.020 Å ) and subtends a dihedral angle of 21.57 (4) with the cyclohexyl ring. The bond distances and angles (amide, pentadiene and methylenedioxyphenyl moieties) of (I) are not significantly different from the equivalent data for the three polymorphs of piperine (Pfund et al., 2015) (Table 1).

Figure 3
Displacement ellipsoid drawing at a 50% probability level of the asymmetric unit of (II).   (Table 1) (Pfund et al., 2015). The packing for forms II and III features aromaticstacking interactions, while that of form I does not.

Supramolecular features
The crystal structure of (I) does not featurestacking interactions, which is similar to piperine form I. Compound (I) possesses an N-H grouping, which forms a classical N1-HÁ Á ÁO1 hydrogen bond (Table 2) between the amide-bond sites, generating [010] C(4) chains ( Fig. 4) with adjacent molecules related by simple translation. The unit-cell packing for (I) is illustrated in Fig. 5.

Synthesis and crystallization
Piperine was purchased from Fujifilm Wako Pure Chemical Co., Ltd. The synthesis of piperine derivatives was performed using a previously reported procedure (Takao et al., 2015). After dissolving piperine in ethanol, hydrolysis was performed by stirring for 20 h in the presence of KOH. After evaporating the solvent under vacuum, the resulting reaction mixture was suspended in water and acidified with 4 M HCl to pH < 1. The resultant pale-brown precipitate was collected by filtration, washed with cold water and recrystallized from methanol A view along the c-axis direction of the crystal packing of (I). The N-HÁ Á ÁO hydrogen bonds are drawn as dashed lines.

Figure 6
Fragment of the crystal of (II) showing close CÁ Á ÁC contacts due tostacking.
solution to give piperic acid. The piperic acid (1.0 mmol) was dissolved in CH 2 Cl 2 (5 ml) and oxalyl chloride (10 mmol) was added and the mixture was stirred at room temperature for 3 h. The solvent and excess oxalyl chloride were then evaporated under reduced pressure.
To prepare (I), the crude acid chloride generated was dissolved in CH 2 Cl 2 (2 ml) and cyclohexylamine (1.2 mmol) and Et 3 N (8 mmol) were added, and the mixture was stirred at 273 K for 5 h. Ice-cold water was added to the mixture, followed by extraction with chloroform (5 ml). The organic layer was dried over Na 2 SO 4 and the solvent was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography (eluent hexane:etyl acetate 1:1 v/v) to give (I) in the form of a yellow powder. Light-yellow needles of (I) were recrystallized from ethyl acetate solution.
Compound (II) was prepared by the same procedure with pyrrolidine (1.2 mmol) replacing the cyclohexylamine to give (II) in the form of a white powder. Colourless needles of (II) were recrystallized from ethyl acetate solution.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. Hydrogen atoms for carbon atom were included in their calculated positions and refined as riding atoms with U iso (H) = 1.2U eq (C). The hydrogen atom attached to N1 in (I) was located in a difference-Fourier map and its position freely refined with U iso (H) = 1.2U eq (N).

5-(2H-1,3-Benzodioxol-5-yl)-N-cyclohexylpenta-2,4-dienamide (I)
Crystal data Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.