Alaptide from synchrotron powder diffraction data

The title compound [systematic name: (8S)-8-methyl-6,9-diazaspiro[4.5]decane-7,10-dione], C9H14N2O2, consists of two connected rings, viz. a piperazine-2,5-dione (DKP) ring and a five-membered ring. The DKP ring adopts a slight boat conformation and the bonded methyl group is in an equatorial position. The five-membered ring is in an envelope conformation. In the crystal structure, intermolecular N—H⋯O hydrogen bonds link molecules into chains running parallel to the c axis.

The title compound [systematic name: (8S)-8-methyl-6,9diazaspiro[4.5]decane-7,10-dione], C 9 H 14 N 2 O 2 , consists of two connected rings, viz. a piperazine-2,5-dione (DKP) ring and a five-membered ring. The DKP ring adopts a slight boat conformation and the bonded methyl group is in an equatorial position. The five-membered ring is in an envelope conformation. In the crystal structure, intermolecular N-HÁ Á ÁO hydrogen bonds link molecules into chains running parallel to the c axis.
during the last twenty years has shown a positive effect of alaptide and its derivatives on the memory of animals and on healing of burns (Hliňák et al., 1996).
The molecular structure of the title compound is shown in Fig. 1. The crystal structure contains two types of intermolecular N-H···O hydrogen bonds between DKP rings. The DKP ring adopts a slight boat conformation and is connected via the spiro junction to a five-membered carbon ring which is in an envelope conformation. The methyl group bonded to the dipeptide ring is in an equatorial position. A search in the Cambridge Structural Database (Allen, 2002) found the crystal structure of a similar type of molecule, namely: (8S)-8-Hydroxymethyl-6,9-diazaspiro[4.5]decane-7,10-dione (CSD refcode FEPFOV; Symerský et al., 1987). This structure has the same spacegroup and comparable unit-cell parameters as the reported structure of the title copmound. Two similar hydrogen bonds N-H···O connecting DKP rings of neighboring molecules occur in both crystal structures. In both structures, the hydrogen bonding connects molecules to form one-dimensional chains. The third hydrogen bond O-H···O is missing in the structure of alaptide, which causes a different formation of extended chains in these structures, see Fig. 2.

Experimental
The title compound was synthesized according to the procedure of Sturc & Kacafirek (1992). Alaptide was crystallized from various solvents in order to check polymorphism, but only one solid form was found (Maixner et al., 2009). The sample for measurement was recrystallized from methanol by slow evaporation technique.

Refinement
X-Ray diffraction data were collected on the high resolution diffractometer ID31 of the European Synchrotron Radiation Facility. The monochromatic wavelength was fixed at 0.79984 (4) Å. Si (111) crystal multi-analyzer combined with Si (111) monochromator was used (beam offset angle α = 2°). A rotating 1-mm-diameter borosilicate glass capillary with alaptide powder was used for the experiment. Data were measured from 1.002° 2θ to 48.012° 2θ at the room temperature, steps scans were set to 0.003° 2θ.
All non-hydrogen atoms were found in the structure solution process. Hydrogen atoms were placed in their theoretical positions and structure was refined by Rietveld method as implemented in GSAS (Larson & Von Dreele, 1994). Bonds, angles and planar group restraints were used during refinement. At final stages atomic coordinates and U iso parameters of supplementary materials sup-2 non-hydrogen atoms were refined to the final agreement factors R p = 0.059 and R wp = 0.089. The diffraction profiles and differences between the measured and calculated profiles are shown in Fig. 3.
The isotropic displacement parameters of atoms C10, C11 and C12 are large compared to those of the other atoms. A disorder model was attempted but this did not improve the refinement and therefore was not used. Fig. 1. The molecular structure of alaptide showing the atomic numbering. Displacement spheres are drawn at 30% probability level.