Crystal structure of 2,2′-oxybis(4-methylquinoline)

The title compound was unwittingly obtained from the slow evaporation of a saturated solution of commercial benserazide hydrochloride. The molecule is composed of two planar 4-methylquinoline aromatic moieties, almost perpendicular to each other, bridged by an O atom. The supramolecular organization consists of a π-bonded chain.


Chemical context
Parkinson's disease is a degenerative disorder of the central nervous system, resulting from the death of dopaminegenerating cells, mostly located in the mid-brain. The most obvious symptoms are movement-related: uncontrolled shaking, rigidity, slowness of movement and difficulty in walking. However, behavioral problems and psychiatric depression may also arise (Samii et al., 2004). Symptomatic treatment of Parkinson's disease includes daily dopamine administration, principally through l-DOPA (or levodopa) or carbidopa (both being precursors of dopamine) brain metabolization.
Benserazide [also called Serazide or Ro-4-4602, (II) in the Scheme] is an aromatic l-amino acid decarboxylase inhibitor and a DOPA decarboxylase inhibitor unable to cross the blood-brain barrier. It is used in combination with levodopa for the symptomatic management of Parkinson's disease (Clark et al., 1973;Campanella & Pennetta, 1974;Bortolanza et al., 2015). ISSN 2056-9890 As benserazide is always administered in combination therapy, it appeared to be a good candidate to search for a solid-state crystalline phase involving it with another therapeutic molecule, also active in the treatment of Parkinson's disease. However, little information could be retrieved on the structural aspects of benserazide and, as a first step, recrystallization attempts of the molecule alone have been launched. These crystallization assays have been so far fruitless, but resulted instead in the unwitting obtention of a new molecule, 2,2 0 -oxybis(4-methylquinoline) (I) with formula C 20 H 16 ON 2 , which is reported herein.

Structural commentary
The geometry of (I) is fairly predictable, with all bond lengths and valence angles being in the expected range for organic compounds (Allen et al., 1987). The molecule consists of two planar 4-methylquinoline aromatic moieties [the maximum deviations from the mean plane are 0.0104 (18) Å for C1 in the N1,C1-C9 moiety and 0.016 (2) Å for C13 in the N2,C11-C19 unit], almost perpendicular to each other [dihedral angle = 89.5 (2) ] and bound by an oxygen atom which forms an ether link ( Fig. 1).

Supramolecular features
The crystal packing organization is essentially the result of two different types of -stacking interactions involving inversionrelated molecules. Table 1 gives a survey of thesestacking interactions, in one case around ( 1 2 , 1 2 , 1 2 ) (Fig. 2) and in the other case around (0, 0, 0);(1, 1, 1) (Fig. 3). The overall effect of these interactions is the formation of chains parallel to [111] (Fig. 4). As expected from the lack of efficient hydrogen-bond donors, no significant hydrogen bonds linking the chains are present in the structure, as a result of which their mutual interaction is rather weak. The molecular structure and atom numbering of the title compound. Displacement ellipsoids for the non-H atoms are drawn at the 50% probability level. Table 1 stacking interactions (Å , ).

Synthesis and crystallization
Prismatic colourless crystals of 2,2 0 -oxybis(4-methylquinoline) were grown from a 2 ml aqueous saturated solution of benserazide hydrochloride (purchased from Sigma-Aldrich, Steinheim, Germany; purity level claimed > 98%) (9.3 mg) that was allowed to evaporate slowly at room temperature over 7 days. Several trials of slow evaporation of aqueous solutions under different temperature conditions (from 277 to 313 K) provided in all cases the same crystals, with the same unit-cell parameters. The main assumption is that the benserazide hydrochloride has undergone a fundamental structure transformation during the aqueous recrystallization assays, but work is in progress to understand the mechanism, which does not seem to be obvious. Compound (I) could also be a byproduct coming from a earlier step in the benserazide synthesis process (even if the quantity of crystalline material retrieved is relatively important). A calorimetric study has been undertaken on the crystalline material, and differential scanning calorimetry (DSC) provides an onset temperature (considered as the melting point) of 419.3 K, with no significant endo-or exothermic event before the fusion point. No spontaneous recrystallization occurs when the melt is allowed to cool down.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The methyl H atoms were located from difference Fourier maps and their positions refined freely. All other H atoms were placed at idealized positions and allowed to ride on their parent atoms, with C-H distances of 0.93 Å and with U iso (H) = 1.2U eq (C).

Figure 4
The [111] chain resulting from the two types ofinteractions.