6-(4-Bromophenyl)-2-ethoxy-4-(4-ethoxyphenyl)nicotinonitrile

The molecule of the title nicotinonitrile derivative, C22H19BrN2O2, is non-planar, the central pyridine ring making dihedral angles of 7.34 (14) and 43.56 (15)° with the 4-bromophenyl and 4-ethoxyphenyl rings, respectively. The ethoxy group of the 4-ethoxyphenyl is slightly twisted from the attached benzene ring [C—O—C—C = 174.2 (3)°], whereas the ethoxy group attached to the pyridine ring is in a (+)syn-clinal conformation [C—O—C—C = 83.0 (3)°]. A weak intramolecular C—H⋯N interaction generates an S(5) ring motif. In the crystal structure, the molecules are linked by weak intermolecular C—H⋯N interactions into screw chains along the b axis. These chains stacked along the a axis. π–π interactions with centroid–centroid distances of 3.8724 (16) and 3.8727 (16) Å are also observed.

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009). 6-(4-Bromophenyl)-2-ethoxy-4-(4-ethoxyphenyl)nicotinonitrile S. Chantrapromma, H.-K. Fun, T. Suwunwong, M. Padaki and A. M. Isloor Comment A large number of substituted pyridines have been claimed to exhibit biological activities in a number of areas (Borgna et al., 1993;Goda et al., 2004;Kamal et al., 2007;Malinka et al., 1998). The pyridine ring is among the most common heterocyclic compounds found in the naturally occurring heterocycles and in various therapeutic agents. Our research is aimed at the synthesis and preliminary pharmacological screening (in vivo) of the nicotinonitrile derivatives. Therefore the title nicotinonitrile derivative, which is a substituted pyridine compound, was synthesized by cyclization of a chalcone derivative (Fun et al., 2008) and malononitrile in order to investigate its analgesic and anti-inflammatory activities. Our results of these pharmacological studies showed that the title compound is a promising candidate for analgesic and anti-inflammatory activities. The analgesic and anti-inflammatory profiles of the title compound together with some other related nicotinonitrile derivatives will be reported elsewhere.
The title compound (I), C 22 H 19 BrN 2 O 2 is a non-planar molecule (Fig. 1) interaction generates an S(5) ring motif (Bernstein et al., 1995). The bond distances agree with the literature values (Allen et al., 1987) and are comparable with those for a related structure (Chantrapromma et al., 2009).
Experimental (E-1-(4-Bromophenyl)-3-(4-ethoxyphenyl)prop-2-en-1-one (0.50 g, 0.0015 mole) were added with continuous stirring to a freshly prepared sodium alkoxide (0.0014 mole of sodium in 100 ml of ethanol). Malononitrile (1.30 g, 0.02 mol) was then added with continuous stirring at room temperature until the precipitate separated out. The resulting solid was filtered (yield 65%). Colorless needle-shaped single crystals of the title compound suitable for x-ray structure determination were recrystalized from acetone/ethanol (1:1 v/v) by the slow evaporation of the solvent at room temperature over several days, Mp. 418-419 K.
supplementary materials sup-2 Refinement All H atoms were positioned geometrically and allowed to ride on their parent atoms, with d(C-H) = 0.93 Å for aromatic, 0.97 for CH 2 and 0.96 Å for CH 3 atoms. The U iso values were constrained to be 1.5U eq of the carrier atom for methyl H atoms and 1.2U eq for the remaining H atoms. A rotating group model was used for the methyl groups. The highest residual electron density peak is located at 1.07 Å from Br1 and the deepest hole is located at 0.96 Å from Br1. Fig. 1. The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme.

Special details
Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K. 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 Rfactors(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 Br1