4-Methyl-N-(2-phenylethyl)-2-propyl-1H-benzimidazole-6-carboxamide

There are two independent molecules in the asymmetric unit of the title compound, C20H23N3O, in which the dihedral angles between the phenyl ring of the phenylethylamino group and the benzimidazole system are 73.98 (15) and 15.93 (16)°. The crystal packing features N—H⋯O and N—H⋯N hydrogen bonds.


Jin-Liang Wang and Wei-Fa Yu Comment
Benzimidazole is an important scaffold with biological activities generally ultilized in antihypertensive drugs, proton pump inhibitors and antimicrobial agents, etc. (Mahiuddin et al., 2007.;Namrata et al., 2012). As a part of our study of 6substituted carbamoyl benzimidazoles as a nonpeptidic angiotensin II AT1 receptor antagonist (Zhang et al., 2012), herein we report the synthesis and crystal structure of the title compound of this family. In the asymmetric unit of the title compound, there are two independent molecules with different dihedral angles between the phenyl ring of the phenylethylamino and the benzimidazole ring. In the O1(carbonyl)-containing molecule, the dihedral angle between the phenyl ring of the phenylethylamino and the benzimidazole ring is -1.8 (5) °, while the O2(carbonyl)-containing one has the value of -1.0 (5) ° (Fig. 1). Intermolecular N-H···O and N-H···N hydrogen-bonding (Desiraju, 1995) interactions (Table 1 and Fig. 2,3) are found to stabilize the whole packing structure of the title compound. As shown in Fig.2, each one O2-containing molecule is surrounded by four O1-containing ones through H-bonding interactions.

Experimental
A suspension of 4-methyl-2-propyl-1H-benzimidazole-6-carboxylic acid (2.18 g, 10 mmol) in thionyl chloride (20 ml, 276 mmol) was refluxed for 2 h, and then the excess thionyl chloride was removed under reduced pressure to provide the crude acid chloride as an off-white solid. The crude product was used in the next step without further purification. To a stirred suspension of above acid chloride in 100 ml of dichloromethane at 293 K was added triethylamine (1.52 g, 15 mmol) dropwise, followed by a solution of phenylethylamine (10 mmol) in 10 ml of dichloromethane. The resulted mixture was stirred overnight and then was filtered, the filtrate was washed with brine and dried over anhydrous sodium sulphate, then was filtered and concentrated. The residue was purified by column chromatography (ethyl acetatemethanol, 4:1 v/v) to afford the title compound as a white solid, yield 72%, m.p. 425 ~ 427 K; Single crystals suitable for X-ray diffraction were prepared by slow evaporation of a solution of the title compound in ethanol at room temperature.

Refinement
The completeness of the final refinement is less than 97 percent due to the deficient diffraction on high degree.All H atoms were discernible in the difference electron density maps.Nevertheless, the hydrogen atoms were placed into idealized positions and allowed to ride on their respective carrier atoms, with C-H = 0.93 for aryl, 0.96 Å and 0.97 Å for methyl and methylene H atoms, respectively. The N-H bonds were defined with constraint refinement at 0.88 Å. U iso (H) = 1.2U eq (C) aryl / methylene / methyl .

Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are presented as small spheres of the arbitrary radius.  The special show of the intermolecular H-bonding in the crystal structure.

Figure 3
The packing structure of the title compound, all hydrogen-bonding interactions are omitted for clarity.  (17) 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. 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 > 2sigma(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 H1 0.7674 (