3-Hydroxy-2,2-bis(1H-pyrazol-1-yl)cyclopentanone

The title compound, C11H12N4O2, was unexpectedly obtained in the reaction of α,α′-disubstituted cyclopentanone with 1,1,3,3-tetramethoxypropane in the presence of dioxane saturated with HCl. It belongs to a previously unknown class of gem-bihetaryl ketones which may be useful for screening of new substances with biological activity. In the studied structure, the cyclopentanone moiety adopts an envelope conformation, with the hydroxy-bearing C atom as the flap [deviation from basal plane = 0.643 (3) Å]. The dihedral angle between the two pyrazole rings is 80.02 (8)°. In the crystal, inversion dimers are formed via a pair of O—H⋯N hydrogen bonds.

The title compound, C 11 H 12 N 4 O 2 , was unexpectedly obtained in the reaction of , 0 -disubstituted cyclopentanone with 1,1,3,3-tetramethoxypropane in the presence of dioxane saturated with HCl. It belongs to a previously unknown class of gem-bihetaryl ketones which may be useful for screening of new substances with biological activity. In the studied structure, the cyclopentanone moiety adopts an envelope conformation, with the hydroxy-bearing C atom as the flap [deviation from basal plane = 0.643 (3) Å ]. The dihedral angle between the two pyrazole rings is 80.02 (8) . In the crystal, inversion dimers are formed via a pair of O-HÁ Á ÁN hydrogen bonds.

Related literature
For the medicinal chemistry of chiral carbo-and heterocyclic substituents of pyrazole, see: Bennani et al. (2007); Srivastava et al. (2007). For the -amination of carbonyl compounds, see: List (2002). For standard values of bond lengths in organic compounds, see: Allen et al. (1987).
Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999 The pyrazole derivatives with chiral carbo-and heterocyclic substituents at the nitrogen atom have great importance for medicinal chemistry (Bennani et al., 2007;Srivastava et al., 2007). The substituted hydrazine derivatives are suitable and accessible reagents in the reactions with 1,3-dicarbonilyl compounds or their masked forms for the preparation of various N-substituted pyrazoles. We have used for the synthesis of starting hydrazine the reaction of direct stereoselective αamination of cyclopentanone catalyzed by L-proline with azadicarboxylates as the source of nitrogen (List, 2002). Under these conditions the reaction of α-amination affords to bis-α,α′-aminated ketone derivative 2 ( Fig. 1) as a main product, which was transformed to 2,5-di-1H-pyrazol-1-ylcyclopentanone 3 ( Fig. 1) by further cyclization with 1,1,3,3-tetramethoxypropane. However, in reaction mixture we have found also two unexpected compounds 4 and 5 (Fig. 1). Formation of the compound 4 can be explained by the competitive intramolecular cyclization of 2 with the participation of ketone group. Appearance of compound 5, which structure was determined by X-ray analysis, is totally unexpected and unusual.
It is assumed that such product results from the unusual intermediate formed via uncommon α,α-diamination, that hasn't been previously described, instead of usual α,α′-diamination. The mechanism of formation of 5 is currently under investigation and will be discussed in a further paper.
Compound 5 was obtained by chromatographic separation of complex reaction mixture formed due to the catalyzed by L-proline α-amination of cyclopentanone 1 ( Fig. 1) with azadicarboxylates. Chromatographic separation was carried out using a combination of column with silica gel and PTLC. A gradient elution system was developed enabling the resolution of mixture of compounds 4 and 5 and pure product 2,5-di-(1H-pyrazol-1-yl)cyclopentanone 3. Further PTLC of mixture of compounds 4 and 5 afforded to obtain both pure products as individual compounds.

Figure 1
Synthetic path for title compound.

Figure 2
The structure of the title molecule with the atom numbering scheme. Displacement ellipoids are drawn at the 30% probability level. H atoms are presented as small spheres of arbitrary radius.

3-Hydroxy-2,2-bis(1H-pyrazol-1-yl)cyclopentanone
Crystal data C 11 H 12 N 4 O 2 M r = 232.25 Monoclinic, P2 1 /c Hall symbol: -P 2ybc a = 11.4360 (11) Å b = 9.5925 (9) Å c = 11.5968 (11) Å β = 117.25 (2) Special details Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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.