Stable polymorph of morphine1

In the stable polymorph of the title compound, C17H19NO3 [systematic name: (5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol], the molecular conformation is in agreement with the characteristics of previously reported morphine forms. The molecule displays the typical T-shape and its piperidine ring adopts a slightly distorted chair conformation. Intermolecular O—H⋯O hydrogen bonds link the molecules into helical chains parallel to the b axis. Intramolecular O—H⋯O hydrogen bonds are also observed.

In the stable polymorph of the title compound, C 17 H 19 -NO 3 [systematic name: (5,6)-7,8-didehydro-4,5-epoxy-17methylmorphinan-3,6-diol], the molecular conformation is in agreement with the characteristics of previously reported morphine forms. The molecule displays the typical T-shape and its piperidine ring adopts a slightly distorted chair conformation. Intermolecular O-HÁ Á ÁO hydrogen bonds link the molecules into helical chains parallel to the b axis. Intramolecular O-HÁ Á ÁO hydrogen bonds are also observed.
According to Kofler (1933), morphine can exist in two distinct polymorphic modifications, and the characteristics of the crystals investigated by us match Kofler's description of the stable form. Our thermomicroscopy experiments have shown that the investigated crystals melt under decomposition at 254 °C (the applied heating rate was 5 °C per minute). This behaviour is in agreement with reports given by Kofler (1933) and Kuhnert-Brandstätter et al. (1975).
The geometry of the molecular morphine scaffold ( Figure 1) with its five rings agrees with the characteristics of the related salt and free base structures mentioned above. The title structure displays two sets of O-H···O bonds, one of which is intramolecular and the other is intermolecular (Table 1). Intermolecular hydrogen bonds link the morphine molecules into an infinite helical chain that propagates parallel to the b-axis ( Figure 2).
The packing of the geometrically inflexible morphine moieties in the title structure was compared with corresponding packing arrangements present in the six morphine forms mentioned above (Bye, 1976;Gelbrich et al., 2012;Gylbert, 1973;Mackay & Hodgkin, 1955;Lutz & Spek, 1998;Wongweichintana et al., 1984), using the program XPac (Gelbrich & Hursthouse, 2005). These comparisons have shown that the packing mode of morphine molecules in the stable form is unique and has no supramolecular constructs in common with any of the other structures in this group.

Experimental
Morphine was obtained from Heilmittelwerke Wien, Austria. Very thin, plate-shaped crystals of the stable polymorph were yielded from a sublimation experiment carried out on a Kofler hot bench at approximately 150 °C, using two glass slides separated by a spacer ring of 1 cm height.

Refinement
All H atoms were identified in a difference map. Methyl H atoms were idealized and included as rigid groups allowed to atoms they were set to U iso (H) = 1.2 U eq (C or O).

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.
The Flack x parameter (Flack, 1983) and the Hooft y parameter (Hooft et al., 2008) were both indeterminate due to a lack of significant resonant scattering. Accordingly, Friedel opposites were merged prior to the final refinement. [Flack, H. D. (1983)