N-Hexyl-3-(4-hydroxy-3,5-dimethoxyphenyl)propanamide

In the title compound, C17H27NO4, which is an hydrosinapic acid derivative with increased lipophilicity conferred by an additional alkyl chain, the central and the hexyl linear chains contain slightly shorter bond lengths [C—N = 1.316 (2) Å; average linear chain C—C = 1.487 (6) Å] than reported average values [Csp 2—N = 1.334, C—C for CH2—CH2 = 1.524 and 1.513 Å for CH2—CH3]. The 4-hydroxy-3,5-dimethoxyphenyl plane [r.m.s. deviation 0.055 (12) Å] makes an angle of 59.89 (5)° with the central plane of the molecule (composed of the N atom, the carbonyl group and the two methylene C atoms linking the carbonyl group and the ring, [r.m.s. deviation 0.0026 (10) Å], which, in turn, makes an angle of 64.24 (13)° with the essentially planar hexyl chain [r.m.s. deviation 0.035 (18) Å]. The N—H group of the amide group is involved in a bifurcated hydrogen bond towards the hydroxy and one of the methoxy O atoms of the 4-hydroxy-3,5-dimethoxyphenyl substituent of a neighbouring molecule, forming a two-dimensional network in the (100) plane. In addition, the same hydroxy group acts as a donor towards the carbonyl O atom of another neighbouring molecule, forming chains running along the b axis.

In the title compound, C 17 H 27 NO 4 , which is an hydrosinapic acid derivative with increased lipophilicity conferred by an additional alkyl chain, the central and the hexyl linear chains contain slightly shorter bond lengths [C-N = 1.316 (2) Å ; average linear chain C-C = 1.487 (6) Å ] than reported average values [Csp 2 -N = 1.334, C-C for CH 2 -CH 2 = 1.524 and 1.513 Å for CH 2 -CH 3 ]. The 4-hydroxy-3,5-dimethoxyphenyl plane [r.m.s. deviation 0.055 (12) Å ] makes an angle of 59.89 (5) with the central plane of the molecule (composed of the N atom, the carbonyl group and the two methylene C atoms linking the carbonyl group and the ring, [r.m.s. deviation 0.0026 (10) Å ], which, in turn, makes an angle of 64.24 (13) with the essentially planar hexyl chain [r.m.s. deviation 0.035 (18) Å ]. The N-H group of the amide group is involved in a bifurcated hydrogen bond towards the hydroxy and one of the methoxy O atoms of the 4-hydroxy-3,5dimethoxyphenyl substituent of a neighbouring molecule, forming a two-dimensional network in the (100) plane. In addition, the same hydroxy group acts as a donor towards the carbonyl O atom of another neighbouring molecule, forming chains running along the b axis.

Related literature
For the dependence on their structural characteristics of the anticancer activity of phenolic acids and their derivatives, see: Gomes et al. (2003). For restrictions on protection of lipophilic systems due to the hydrophilic nature of molecules in aqueous media, see: Gao & Hu (2010). For the synthesis, see: Roleira et al. (2010). For reference bond lengths, see: Allen et al. (1987).  Table 1 Hydrogen-bond geometry (Å , ). Symmetry codes: (i) x; Ày þ 1 2 ; z þ 1 2 ; (ii) x; y þ 1; z.

Experimental
Data collection: SMART (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97. and more effective phenolic agents suitable for chemopreventive and/or chemotherapeutic purposes, hydrosinapic acid derivatives with increased lipophilicity conferred by an additional alkyl chain, were developed. For this, N-hexyl-3-(4-hydroxy-3,5-dimethoxyphenyl)propanamide was synthesized by reaction of the corresponding acid with hexylamine, in the presence of the coupling agent (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) (Roleira et al., 2010). Single crystal X-ray measurements evidence normal bond length values for the phenyl ring and its substituents. However the C sp 2 -N bond length in the molecule's central chain [1.316 (2) Å] is shorter than the reported average value of 1.334 Å (Allen et al., 1987). Furthermore the average value of the five measured C sp 3 -C sp 3 bond lengths of the hexyl chain [1.487 (6) Å] is also significantly shorter then the average reported values (1.524 for CH 2 -CH 2 and 1.513 for CH 2 -CH 3 , Allen et al., 1987). The molecule is characterized by an intramolecular C11-H11A···O9 pseudohydrogen bond within the central chain plane (deviation 0.0026 Å). The dihedral angle between this plane and the phenyl one (deviation 0.0545 Å) is 59.89 (5)°, being 64.24 (13)° the corresponding value between the central plane and the one of the hexyl chain (deviation 0.0349 Å). Cohesion of the structure is obtained through an extended newtork of H-bonds.
The H atom of the amide group is involved in a bifurcated H-bond towards the hydroxy and one of the methoxy O atoms of the 4-hydroxy-3,5-dimethoxyphenyl substituent of a neignhbour molecule, forming a two dimensional network in the (100) plane. In addition, the same hydroxy group acts as a donnor towards the carbonyl O atom of another neighbour molecule forming chains running along the b axis.

Experimental
The title amide was prepared from the 3-(4-hydroxy-3,5-dimethoxyphenyl)propanoic acid by dissolution of 5 mmol of the acid in 10 ml of DMF followed by the addition of triethylamine (0.7 ml, 5 mmol). The solution was cooled in an icewater bath and 0.657 ml (5 mmol) of N-hexylamine were added followed by a solution of 2.21 g (5 mmol) of BOP in 10 ml of methylene chloride. The mixture was stirred at 273 K for 30 min and then at room temperature for 30 min. Methylene chloride was removed under reduced pressure and the solution was diluted with 150 ml of water and extracted with ethyl acetate (150 ml). The organic phase was washed successively with 1 N hydrochloride acid (3x100 ml), water (150 ml), 1M NaHCO 3 (3x100 ml), and water (2x100 ml), dried over anhydrous magnesium sulfate, filtered and evaporated, affording a crude material which was purified by crystallization yielding the desired amide. Suitable crystals for X-ray

Refinement
All hydrogen atoms were placed at idealized positions and refined as riding on their parent atoms using SHELXL97 defaults; the hydroxyl H atom was initialy positioned at the maximum of the difference electronic density around the parent O atom and refined using the HFIX 147 instruction.
Only 4255 out of 4259 independent reflections were used in the refinement because 4 low angle reflections were omitted due to overshadowing from the beam-stop.

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq N 0.75497 (7