Pimobendan B from powder diffraction data

The title molecule, C19H18N4O2 {systematic name: (RS)-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one}, adopts an extended conformation. The dihedral angles between the central benzimidazole ring sytem and the pendant methoxyphenyl and pyridazinone residues are 1.41 (18) and 9.7 (3)°, respectively. In the crystal, N—H⋯N hydrogen bonds link the imadazole groups into [001] chains, and pairs of N—H⋯O hydrogen bonds link the pyridazinone groups into dimers. Together, these generate a two-dimensional supramolecular structure parallel to (010). The layers are linked by C—H⋯π interactions.


Related literature
For general information about pimobendan, see: Gordon et al. (2006). For related crystalline forms, see: Boeren et al. (2011). Semi-empirical calculations were carried out with HYPERCHEM Professional (Hypercube, 2010). Refinement of lattice parameters and peak profile determination were performed by Le Bail profile fitting (Le Bail et al., 1988) Experimental Crystal data  Table 1 Hydrogen-bond geometry (Å , ).
The compositions of unit cell and the values of Z were determined in all cases from the unit cell volume.
Refinement of lattice parameters and peak profile determination were performed by Le Bail profile fitting (Le Bail et al., 1988) using FOX. Structures were determined with FOX by parallel tempering algorithm. The best cost function values were reached by using automatic temperature schedule and Cauchy-type displacement amplitude schedule.
The input model of pimobendan molecule was obtained from semiempirical calculations by HYPERCHEM Professional (Hypercube, 2010) for both -R and S enentiomer. The molecules were described in terms of Fenske-Hall Z-matrix format ans structure solutions The dihedral angles C21-C22-O7-C25; N11-C8-C20-C15 and C2-C6-C14-N4 were defined as intramolecular degrees of freedom and were varied during the structure determinations.

Synthesis and crystallization
Pimobendan form B was prepared in three steps. At the first step, its dioxane solvate was held in a thermostat at 100°C for one day. At the second step obtained powder were suspended in methanol and suspension were hold in a dry box while all methanol evaporates. At the end obtained methanol solvate were desolvatated at 100°C.

Results and discussion
Several crysltalline forms of pimobendan and its preparation are patented (Boeren et al., 2011) but there are no crystal data for these polymorphs or pseudopolymorhs. This article is focused on the structure determination from powder data and description of the pimobendan B form.
Modeling with PLATON (Spek, 2009) showed that the crystal structure contain voids ( 69Å 3 ) accessible to solvent molecules. Since pimobendan B form are obtained from its methanol solvate by desolvation at 100°C, these voids may be result of desolvation at temperature that is almost twice as large as boiling point this solvent. Pimobendan B form at ambient conditions tends to form monohydrate. Unstabilty of pimobendane B form at ambient conditions may be explained by penetration of water molecules into voids of crystal structure.

Figure 1
The molecular structure of the title compound showing 50% probability ellipsoids and hydrogen atoms are shown as small spheres of arbitrary radii.    Scattered X-ray intensities of title compound at ambient conditions as a function of diffraction angle 2θ. The observed pattern (red dots), the best Rietveld fit profiles (line) and the difference curve between the observed and calculated profiles (below) are shown. Hydrogen site location: inferred from neighbouring sites H-atom parameters not refined (Δ/σ) max = 0.01 Background function: linear extrapolation Special details Refinement. Rietveld refinement for the final structure was performed by Fullprof. Hydrogen atoms were added with Crystals according to the molecular geometry and their positions were not refined, but final refinement was performed with hydrogen atoms. Since the bond lengths and angles departed to unacceptable values, atomic parameters for (N3, N4, C5, O9, C14, C16, C17,C23), (N1, N11, C2, C6, C8, C10, C13, C18, C19) and (O7, C12, C15, C20, C21, C22, C24, C25) were refined as rigid bodies.