6-Methyl-2-oxo-N-(quinolin-6-yl)-2H-chromene-3-carboxamide: crystal structure and Hirshfeld surface analysis

The 6-methyl-2-oxo-N-(quinolin-6-yl)-2H-chromene-3-carboxamide coumarin derivative displays intramolecular N—H⋯O and weak C—H⋯O hydrogen bonds, which probably contribute to the approximate planarity of the molecule [dihedral angle between the coumarin and quinoline ring systems = 6.08 (6)°]. The supramolecular structures feature C—H⋯O hydrogen bonds and π–π interactions, as confirmed by Hirshfeld surface analyses.


Chemical context
Coumarin and its derivatives are widely recognized by their unique biological properties (Matos et al., 2014;Vazquez-Rodriguez et al., 2013;Chimenti et al., 2010). Our work in this area has shown that coumarin is a valid scaffold for the development of new drugs for aging related diseases, specifically within the class of monoamino oxidase B inhibitors (Matos et al., 2009). On the other hand, quinoline is a nitrogen heterocycle also often used in drug-discovery programs due to its remarkable biological properties, some of them related to neurodegenerative diseases (Sridharan et al., 2011), for instance, as -secretase and acetylcholinesterase inhibitors (Camps et al., 2009). As part of our ongoing studies in this area (Gomes et al., 2016), we describe the synthesis and crystal structure of the title coumarin-quinoline hybrid, 6-methyl-2oxo-N-(quinolin-6-yl)-2H-chromene-3-carboxamide, (1) (see Scheme). Fig. 1 shows an ellipsoid plot of the molecular structure of (1). An inspection of the bond lengths shows that there is a slight ISSN 2056-9890 asymmetry of the electronic distribution around the coumarin ring: the C3-C4 [1.3609 (15) Å ] and C3-C2 [1.4600 (18) Å )] bond lengths are shorter and longer, respectively, than those expected for a C ar -C ar bond, suggesting that the electronic density is rather located near the C3-C4 bond at the pyrone ring, as occurs in other coumarin-3-carboxamide derivatives (Gomes et al., 2016). Also, the C3-C31 bond length [1.5075 (18) Å ] is similar to the mean value displayed by other coumarin-3-carboxamide derivatives previously characterized (Gomes et al., 2016) and is of the same order as a Csp 3 -Csp 3 bond.

Structural commentary
The C-N rotamer of the amide group governs the conformation of the molecule: the Àanti orientation where the N atom is Àcis positioned with respect to the oxo O atom of the coumarin system allows the establishment of an intramolecular N32-H32Á Á ÁO2 hydrogen bond between the amino group of the carboxamide and the oxo group of the coumarin system, and of a weak intramolecular C317-H317Á Á ÁO31 hydrogen bond that connects the quinoline ring with the O atom of the carboxamide group (Table 1). Both these interactions form S(6) rings and connect the spacer carboxamide group with the heteroaromatic rings, probably constraining the rotation/bending of those rings with respect to the plane formed by the amide atoms. In fact, the molecule is roughly planar, as may be evaluated by the set of values for the dihedral angles which are less than 7 (Table 2).

Supramolecular features
In the crystal of (1), molecules are linked by a weak C314-H314Á Á ÁO31 i hydrogen bond to form a C(8) chain, which runs parallel to the a axis ( Fig. 2 and Table 1). There are several contacts that will be described below.

Hirshfeld surface analyses
The Hirshfeld surfaces and two-dimensional fingerprint (FP) plots (Rohl et al., 2008) were generated using Crystal Explorer (Wolff et al., 2012). Compound (1) has three O atoms and an N atom that can potentially act as acceptors for hydrogen bonds, but one of the lone pairs of the oxo O atoms of the coumarin nucleus and of the amide moiety are involved in the establishment of intramolecular hydrogen bonds, as discussed above. As such, they contribute to the electronic density of the pro-molecule in the calculation of the Hirshfeld surface, leaving only the remaining pairs available for participation in the supramolecular structure formation. The surface mapped over d norm displays several red spots that correspond to areas of close contacts between the surface and the neighbouring environment, and the FP plot is presented in Fig. 3.
Compound 1 ( ) 2 ( ) 3 ( ) (1) 6.08 (6) 5.0 (12) 1.73 (11) Notes: 1 is the dihedral angle between the mean planes of the coumarin and quinoline rings; 2 is the dihedral angle between the mean plane of the coumarin ring and the plane defined by atoms O31/C31/N32; 3 is the dihedral angle between the mean plane of the quinoline ring and the plane defined by atoms O31/C31/N32.

Figure 2
The simple C4 chain in compound (1) withstacking (17.9%): (iii) HÁ Á ÁC/CÁ Á ÁH contacts (14.3%). The HÁ Á ÁN/O contacts appear as three highlighted red spots on the top and bottom edges of the surface which form pairs of spots of comlementary size, indicating the contact points of the labelled atoms participating in the C-HÁ Á ÁN/O interactions (Fig. 3). The strongest spots correspond to oxo atom O31 of the carboxamide acceptor and donor atom H314, which forms the C314-H314Á Á ÁO31 i hydrogen bond (Table 1), and the other spots correspond to very weak hydrogen-bond contacts, one involving pyrone atom O1 and a H atom of the methyl group (C61-H61BÁ Á ÁO1 ii ; Table 1), and the other appearing perpendicular to the quinoline N atom indicating a very weak C8-H8Á Á ÁN311 ii contact (Table 1). In spite of the weakness of these contacts, their relative strength is reflected in the FP plots where the pair of sharp spikes pointing to south-west is highlighted in light blue.
In this structure, C/NÁ Á ÁC contacts prevail over the C-HÁ Á ÁC ones. In fact, the packing in (1) is built up by severalinteractions (Table 4). The red spots in the frontal zone of the surface correspond to these close contacts. Furthermore, the FP plot also reveals an intense cluster at d e /d i at 1.8 Å characteristic of CÁ Á ÁC contacts. Also, when the surface is mapped with shape index, several complementary triangular red hollows and blue bumps appear that are characteristic of the six-ring stacking (Fig. 4). The molecules stack in a column in a head-to-tail fashion along the b axis (Fig. 5). The molecules in these stacks lie across centres of symmetry at ( 1 2 , 1, 1 2 ), Views of the Hirshfeld surface mapped over d norm (left) and fingerprint plot (right, FP) for (1). The highlighted red spots on the top face of the surfaces indicate contact points with the atoms participating in the intermolecular C-HÁ Á ÁO interactions, whereas those on the middle of the surface corresponds to CÁ Á ÁC contacts consequent of thestacking. The CÁ Á ÁC contacts contribute to the higher frequency of the pixels at d e /d i at 1.8 on the FP plot (yellow spot). The FP plot displays two light-blue spikes (external ends corresponding to CÁ Á Á H contacts).

Figure 4
Shape index plots showing the interactions arising fromstacking. The upper corresponds to the stacking across ( 1 2 , 1, 1 2 ), while the lower corresponds to the stacking across ( 1 2 , 1 2 , 1 2 ). a centrosymetrically related contact between the pyran and pyridine rings, and across the centre at ( 1 2 , 1 2 , 1 2 ), which involves three short centrosymmetrically related contacts: (i) between the pyran and pyridine rings, (ii) between the pyran ring and the quinoline phenyl ring and (iii) between the coumarin phenyl ring and the pyridine ring. The present compound also contains these bonds, as described above.

Refinement
H atoms were treated as riding atoms, with aromatic C-H = 0.95 Å , with U iso (H) = 1.2U eq (C), and methyl C-H = 0.98 Å , with U iso (H) = 1.5U eq (C). The amino H atoms were freely refined. Crystal data, data collection and structure refinement details are summarized in Table 5.  Table 4 Selectedcontacts.

Data collection
Three-circle diffractometer Radiation source: synchrotron, DLS beamline I19, undulator Si 111, double crystal monochromator Detector resolution: 5.81 pixels mm -1 profile data from ω-scans Absorption correction: empirical (using intensity measurements) aimless ccp4 (Evans, 2006) 18408 measured reflections 4587 independent reflections 3717 reflections with I > 2σ(I) R int = 0.060 θ max = 29.5°, θ min = 2.9°h 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.