Crystal structure of the triethylammonium salt of 3-[(4-hydroxy-3-methoxyphenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-2-oxo-2H-chromen-4-olate

3,3′-[(3-Methoxy-4-hydroxyphenyl)methanediyl]bis(4-hydroxy-2H-chromen-2-one), the 4-hydroxy-3-methoxyphenyl-substituted derivative of dicoumarol, was deprotonated by the addition of triethylamine, yielding the respective ammonium salt which was crystallized from a methanol solution. The deprotonated dicoumarol derivative exhibits an intramolecular negative charge-assisted hydrogen bond between the deprotonated and non-deprotonated alcohol functions of the coumarol substituents.


Chemical context
Requisite chemotherapeutical treatments of cancer and inhibition of bacterial activities encourage the design of drugs that can effectively target the affected cells or respective pathogens (Nolan et al., 2007;Jung & Park, 2009). 4-Hydroxy coumarine and its derivatives have been developed and exploited by various researchers in this context (Nolan et al., 2007;Tavolari et al., 2008;Jung & Park, 2009;Li et al., 2015;David, 2017). In biological tests with 3,3 0 -[(3methoxy-4-hydroxyphenyl)methanediyl]bis(4-hydroxy-2Hchromen-2-one), much lower than expected cytotoxic activity was found (Rehman et al., 2013), which may be attributed to insufficient solubility. The hydrophobic nature of this compound is most likely due to strong intramolecular hydrogen bonding between the two coumarol moieties via two O-HÁ Á ÁO C interactions, which was confirmed for the solid state by X-ray structural analysis of this compound (Bandyopadhyay, 2015) and close relatives (Manolov et al., 2006;Stanchev et al., 2007).
Hydrophobic molecules are not only ineffective inside biological fluids but they may also accumulate inside an organism. Increasing the solubility by increasing the hydrophilicity of potentially bioactive molecules may be achieved by converting them into salts (Smith et al., 2009). Therefore, the synthesis of readily soluble ammonium salts of dicoumarol derivatives is of considerable importance. Herein, a crystallographically characterized example (being only the fourth of its kind) is discussed with a focus on its structural aspects.

Structural commentary
The molecular structure of the title compound is shown in Fig. 1. The deprotonation of one hydroxy-coumarin substituent but not the other leads to a short intramolecular negative charge-assisted hydrogen bond between the two hydroxycoumarin substituents. The formation of such intramolecular hydrogen bonds between hydroxy-coumarin substituents is rare though not unprecedented (Kolos et al., 2007;Vijayalakshmi et al., 2001;Waheed & Ahmed, 2016). Recently, Bengiat and coworkers surveyed the occurrence of negative charge-assisted hydrogen bonds (-CAHB) in the Cambridge Structural Database (Groom et al., 2016) in general (Bengiat et al., 2016a), covering 19 such compounds although excluding the report by Waheed & Ahmed (2016), which was published later that year. Bengiat et al. (2016b) also discovered the shortest distance between donor and acceptor oxygen atoms of such intermolecular interactions to be 2.404 (3) Å , whereas in all other examples the distance was given as at least 2.430 Å (Bengiat et al., 2016a). The metrical parameters of the intramolecular -CAHB in the title compound are DÁ Á ÁA 2.4139 (15) Å and D-HÁ Á ÁA 169 (2) . The distance of the freely refined hydrogen atom to its parent atom O3 is elongated to 1.18 (3) Å , while the HÁ Á ÁA hydrogen-bond length to O6 is rather short at only 1.24 (3) Å . This interaction is therefore the second shortest such -CAHB overall and the shortest intramolecular one. In the three related deprotonated dicoumarols, the DÁ Á ÁA distances range from 2.423 Å (Waheed & Ahmed, 2016) to 2.491 Å (Kolos et al., 2007). Based on the short, and hence strong, intramolecular hydrogen bond, an eight membered ring is formed (C1/C2/ C10/O3/H3O/O6/C19/C11). The distances between the alcohol oxygen atoms and bound carbon atoms are 1.3005 (16) Å (O3-C10) and 1.2939 (17) Å (O6-C19); i.e. both very similar and both significantly shorter than those reported for non-deprotonated derivatives, which range from 1.331 to 1.338 Å (Stanchev et al., 2007). This is in accordance with both alcohol functions being deprotonated and protonated to a certain extent at the same time, as was also found in one related structure of a salt (Vijayalakshmi et al., 2001) but not in the other two analogous structures (Kolos et al., 2007;Waheed & Ahmed, 2016).
structure (1.520 and 1.521 Å ) and (iii) a higher molecular symmetry including the orientation of the 4-hydroxy-3-methoxyphenyl substituent of the neutral molecule compared to the anion of the title compound, emphasized by the torsion angles between the phenyl moiety and the two benzopyrane moieties, which are much more distinct in the anion [C2-C1-C20-C25 = 124.22 (15) and C11-C1-C20-C21 = 169.11 (13) vs 153.28 and 163.81 in the neutral molecule].

Supramolecular features
The crystal packing appears to be dominated by intermolecular hydrogen-bonding interactions. No parallel alignments of the aromatic systems (phenyl, benzopyran) in a stacking fashion are observed, i.e.interactions are not present.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The three hydrogen atoms bound to heteroatoms (N1, O3, O8) were freely refined. Carbonbound hydrogen atoms were placed in calculated positions, and refined with a riding-model approximation: C-H = 0.95-1.00 Å with U iso (H) = 1.5U eq (C-methyl) and 1.2U eq (C) for other H atoms.
Hydrogen-bonding interactions were identified and analysed using PLATON (Spek, 2009) and finally calculated using the HTAB instruction in SHELXL (together with EQIV) (Sheldrick, 2015b).  SHELXL2016 (Sheldrick, 2015b); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: CIFTAB (Sheldrick, 2008) and Mercury (Macrae et al., 2006). 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.