Syntheses and structures of two benzoyl amides: 2-chloro-4-ethoxy-3,5-dimethoxy-N-(3-oxocyclohex-1-en-1-yl)benzamide and 2-chloro-N-(5,5-dimethyl-3-oxocyclohex-1-en-1-yl)-4-ethoxy-3,5-dimethoxybenzamide

The crystal structures of two benzoyl amides: 2-chloro-4-ethoxy-3,5-dimethoxy-N-(3-oxocyclohex-1-en-1-yl)benzamide and 2-chloro-N-(5,5-dimethyl-3-oxocyclohex-1-en-1-yl)-4-ethoxy-3,5-dimethoxybenzamide have been determined.

The first title benzoyl amide, C 17 H 20 ClNO 5 (3a), crystallizes in the monoclinic space group P2 1 /c with Z = 4 and the second, C 19 H 24 ClNO 5 (3b), also crystallizes in P2 1 /c with Z = 8 (Z 0 = 2), thus there are two independent molecules in the asymmetric unit. In 3a, the phenyl ring makes a dihedral angle of 50.8 (3) with the amide moiety with the C O group on the same side of the molecule as the C-Cl group. One methoxy group is almost in the plane of the benzene ring, while the ethoxy and other methoxy substituent are arranged on opposite sides of the ring with the ethoxy group occupying the same side of the ring as the C O group in the amide moiety. For one of the two molecules in 3b, both the amide and 5,5-dimethyl-3-oxocyclohex-1-en-1-yl moieties are disordered over two sets of sites with occupancies of 0.551 (2)/0.449 (2) with the major difference between the two conformers being due to the conformation adopted by the cyclohex-2-en-1-one ring. The three molecules in 3b (i.e., the undisordered molecule and the two disorder components) differ in the arrangement of the subsituents on the phenyl ring and the conformation adopted by their 5,5dimethyl-3-oxocyclohex-1-en-1-yl moieties. In the crystal of 3a, N-HÁ Á ÁO hydrogen bonds link the molecules into a zigzag chain propagating in the [001] direction. For 3b a combination of C-HÁ Á ÁO and N-HÁ Á ÁO intermolecular interactions link the molecules into a zigzag ribbon propagating in the [001] direction.

Chemical context
Enaminones are compounds in which a nitrogen atom is conjugated through a carbon-carbon double bond to an ester (vinylogous urethane) or a ketone (vinylogous amide) functional group (see Scheme). Enaminones may be viewed as amides into which a vinyl fragment has been interpolated. Designations often used, such as enamino ketone or -amino-, -unsaturated ketone, are misleading in that the compounds rarely exhibit the physical properties normally associated with ketones. Enaminones, compounds possessing the structural unit NH 2 -C C-C O, are versatile synthetic intermediates that combine the ambient nucleophilicity of enamines with the ambient electrophilicity of enones (Greenhill, 1976;Lue & Greenhill, 1996).
-Enaminones may be used in the synthesis of many bioactive molecules with a heterocyclic unit. Enaminones as intermediates are responsible for a wide range of therapeutic agents from both natural and synthetic sources including taxol, anticonvulsants, anti-inflammatories, and duocarmycin, and consequently have been the subject of numerous structural bioactivity investigations in recent times (Misra et al., 2008;Greenhill, 1977;Boger et al., 1989;Eddington et al., 2003;Stoltz et al., 2016;Jerach & Elassar, 2015;Kalita et al., 2017). In spite of the breadth of research related to the biological properties of enaminones, recent research also indicates that enaminones, particularly the cyclic 3-(phenylamino)-2-cyclohexen-1-one (PACO), contain spectroscopic signatures of intramolecular charge transfer (ICT), making cyclic enaminones ideal components for molecules that mimic natural photosynthetic energy and electron transfer (Lue & Greenhill, 1996). A later study conducted in 2009 concluded that PACO has a low lying strongly polar singlet excited state with significant intramolecular charge transfer (Misra et al., 2009).

Structural commentary
In view of the bioactivity of enaminones, the conformation adopted by a molecule is crucial to its activity. Thus an analysis of this for both molecules is appropriate. The benzoyl amide, C 17 H 20 ClNO 5 (3a), crystallizes in the monoclinic space group P2 1 /c with Z = 4. The compound is the result of the condensation of the enaminone 1a with the acid chloride 2. In the case of 3a (Fig. 1), the central phenyl ring makes a dihedral angle of 50.8 (3) with the amide moiety; with the C O group on the same side of the molecule as the C-Cl group; in the 3-oxocyclohex-1-en-1-yl group the C O moiety is on the same side with respect to the phenyl ring [the pseudo torsion angle for O4-C11Á Á ÁC14-O5 = 21.8 (1) ]. One of the methoxy groups (O3-C10) attached to the C1-C6 benzene ring is close to the plane of the ring [torsion angle between the ring and C5-O3-C10 = 17.72 (2) ], while the ethoxy and the other methoxy substituent are arranged on opposite sides of the ring with the ethoxy group occupying the same side of the ring as the C O group in the amide moiety [C8-O2Á Á ÁC11-O4 = À44.0 (1) and C7-O1Á Á ÁC11-O4 = 123.6 (1) ]. The extended conformation of the ethoxy group with respect to the ring is shown by a torsion angle of À170.8 (1) for C4-O2-C8-C9.
The benzoyl amide, C 19 H 24 ClNO 5 (3b), crystallizes in the monoclinic space group P2 1 /c with Z = 8 (Z 0 = 2), thus there are two independent molecules in the asymmetric unit. The compound is the result of the condensation of the enaminone 1b with the acid chloride 2. For one of the two molecules, both the amide and 5,5-dimethyl-3-oxocyclohex-1-en-1-yl moieties are disordered over two inequivalent conformations with occupancies of 0.551 (2)/0.449 (2). The major difference between the two conformers is due to the conformation adopted by the cyclohex-2-en-1-one ring (vide infra).
The conformations of both independent molecules will be discussed separately and then comparisons will be made between the conformation of 3a and the two molecules of 3b in which, due to disorder, one has adopted two different conformations. For simplicity, these will be called 3ba, 3bb and 3bc (where 3bb and 3bc are the major and minor components, respectively, of the disordered molecule). For 3ba (Fig. 2) the central phenyl ring makes a dihedral angle of 54.5 (3) with the amide moiety with the C O group on the opposite side of the molecule as the C-Cl group in contrast to the situation in 3a (this is illustrated by the respective C2-C1Á Á ÁC11-O4 The molecular structure of 3a with atom labeling and with atomic displacement parameters shown at the 30% probability level.

Supramolecular features
For 3a, N-HÁ Á ÁO hydrogen bonds (Table 1)  The molecular structure of the disordered molecule in 3b showing both disorder components (3bb and 3bc) with atom labeling and with atomic displacement parameters shown at the 30% probability level.

Database survey
A survey of the Cambridge Structural Database for similar compounds did not provide any hits. Even if the molecules are broken up into two components, one based on the trisubstituted phenyl ring and the other on the cyclohexene ring no hits for the former and only one hit for the latter fragment is obtained [Cambridge Structural Database refcode MOLPUA (Meng et al., 2014)]. Even in this structure the only similar chromophore is the cyclohex-2-ene-1-one fragment, but with the double bond in a different position in the ring. For similar structures to this fragment but containing a cyclohexane ring there are DOSDOE, DOSBUK (Romney et al., 2014) and KAVDAP (Alford et al., 2016).

Synthesis and crystallization
The methodology involves N-deprotonation of the commercially available enaminones 1a,b with sodium hydride followed by benzoylation of 2 to give the title benzoyl amides 3a,b in 54% and 51% yield, respectively, from a method previously reported (see Scheme 1; Anderson et al., 2004). Benzoyl chloride 2 was prepared via chlorination of commercially available 4 under previously reported conditions (Zheng et al., 2011).

2-Chloro-4-ethoxy-3,5-dimethoxy-N-(3-oxocyclohex-1-en-1-yl)benzamide (3a)
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.

2-Chloro-N-(5,5-dimethyl-3-oxocyclohex-1-en-1-yl)-4-ethoxy-3,5-dimethoxybenzamide (3b)
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.