Crystal structure of ethyl (1RS,6SR)-4-(2-methyl-1H-imidazol-4-yl)-2-oxo-6-(2,3,5-trichlorophenyl)cyclohex-3-ene-1-carboxylate

The cyclohexenone ring in the title compound adopts an envelope conformation and in the crystal, molecules are linked by N—H⋯O and C—H⋯N hydrogen bonds, forming ribbons of edge-fused rings propagating along [010].

The title compound, C 19 H 17 Cl 3 N 2 O 3 , has been prepared in a cyclocondensation reaction between 2,3,5-trichlorobenzaldehye and 4-acetyl-2-methyl-1H-imidazole. The cyclohexenone ring adopts an envelope conformation with the C atom substituted by the trichlorophenyl ring as the flap. The mutually trans ester and aryl substituents both occupy equatorial sites. In the crystal, a combination of N-HÁ Á ÁO and C-HÁ Á ÁN hydrogen bonds links the molecules into ribbons of edge-fused centrosymmetric rings, which enclose R 2 2 (14) and R 4 4 (16) alternate ring motifs, propagating along the b-axis direction.

Chemical context
We have recently reported (Salian et al., 2015) a simple and versatile synthesis of substituted 1,1 0 :3 0 1 00 -terphenyls based upon the two-electron oxidation of substituted cyclohex-2-en-1-ones, themselves readily synthesized in reactions between 1,3-diarylprop-2-en-1-ones (chalcones) and compounds containing activated methylene units. This method points to a similar routes to substituted biphenyls carrying a wide range of substituents, including heterocyclic units. To this end, we have now synthesized the title compound (I) as a key intermediate in this proposed pathway. It was prepared by reaction of ethyl 3-oxobutanoate with the chalcone intermediate (A) (Fig. 1), which was itself prepared by base-catalysed condensation between 2,3,5-trichlorobenzaldehye and 4-acetyl-2methyl-1H-imidazole. The conversion of the intermediate (A) to the final product (I) is a two-step, but one-pot, process involving both Michael addition and a condensation reaction. ISSN 2056-9890

Structural commentary
The molecule of compound (I) contains two stereogenic centres at atoms C1 and C6 (Fig. 2). The reference molecule was selected as one having the R-configuration at atom C1 and in this molecule atom C6 has the S-configuration; the centrosymmetric space group confirms that the compound has crystallized as a racemic mixture of the (1R,6S) and (1S,6R) diastereoisomers.
The ester and aryl substituents at atoms C1 and C6, respectively, are trans to one another and both occupy equatorial sites (Fig. 2). The dihedral angle between the mean plane through atoms (C1-C5) and the adjacent imidazole ring is only 2.18 (16) but, despite this, the bond lengths in the imidazolyl-cyclohexenone portion of the molecule, atoms (N41,C45,C44,C4,C3,C2,O2), provide no evidence for delocalization of the lone pair from the planar atom N41 through the vinylogous amide fragment onto atom O2. In contrast, the dihedral angle between the mean plane through atoms (C1-C5) and the carboxyl group (C11/O11/O12) is 89.0 (3) .

Database survey
The structures of a number of analogues of compound (I), usually carrying aryl substituents on atoms C4 and C6, have been reported in recent years (Fischer et al., 2008;Fun et al., 2008Fun et al., , 2012Dutkiewicz et al., 2011a,b,c;Kant et al., 2012;Salian et al., 2015). Without exception, these compounds all crystallize as racemic mixtures of the (1R,6S) and (1S,6R) forms, with mutually trans substituents at the sites corresponding to atoms C1 and C6 in compound (I), although in quite a number of these reports, the stereochemistry is not mentioned at all. The consistency of the stereochemistry indicates that the first step in the reaction between the chalcone and ester reagents is condensation between the chalcone and the acyl group of the ester component, followed by the Michael addition step, whose transition state is organized to minimize steric repulsions, leading to the mutually trans disposition of the substituents at sites C1 and C6. Of particular interest is the structure of methyl (1RS,6SR)-4-(4-chlorophenyl)-6-[4-(propan-2-yl)phenyl]-2-oxocyclohex-3-ene-1carboxylate, which exhibits enantiomeric disorder where the reference site contains both (1R,6S) and (1S,6R) forms with occupancies of 0.923 (3) and 0.077 (3), respectively (Salian et al., 2015), There appears to be no evidence for such disorder in the structure reported earlier nor, indeed, in the structure of compound (I) reported here.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. All the H atoms were located in difference-Fourier maps. For the H atom bonded to atom N41, the atomic coordinates were refined with U iso (H) = 1.2U eq (N), giving an N-H distance of 0.79 (3) Å . The C-bound H atoms were subsequently treated as riding atoms in geometrically idealized positions: C-H distances 0.93-98 Å with U iso (H) = 1.5U eq (Cmethyl) and 1.2U eq (C) for other H atoms. SHELXL2014 (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015) and PLATON (Spek, 2009).

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.