rac-(1S*,4aS*,8aS*)-4a-Hydroxy-2-methylperhydrospiro[isoquinoline-4,1′-cyclohexan]-2′-one

In the title compound, C15H25NO2, all three six-membered rings adopt chair conformations. The cyclohexane and piperidine rings within the perhydroisoquinoline are trans–trans fused. The N atom has a trigonal–pyramidal geometry (the sum of the bond angles is 328.0°). The methyl substituent occupies the sterically preferrable equatorial position. In the crystal, molecules form infinite [100] chains via O—H⋯N hydrogen bonds.

In the title compound, C 15 H 25 NO 2 , all three six-membered rings adopt chair conformations. The cyclohexane and piperidine rings within the perhydroisoquinoline are transtrans fused. The N atom has a trigonal-pyramidal geometry (the sum of the bond angles is 328.0 ). The methyl substituent occupies the sterically preferrable equatorial position. In the crystal, molecules form infinite [100] chains via O-HÁ Á ÁN hydrogen bonds.

Experimental
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: RK2397).

Khrustalev Comment
It is well known that 3-aroyl-4-arylpiperidin-4-ols are intermediate products in the synthesis of important antihistaminic agents (Plati & Wenner, 1950;Ellefson et al., 1978). Such piperidols can be prepared in two steps via the condensation of the corresponding acetophenones with formaldehyde and alkylamines by heating of these mixtures in 36% HCl solution and the subsequent intramolecular cyclization of the yielded double Mannich bases under action of bases (Plati & Wenner, 1949).
However, we found that use of α-tetralone -the cyclic analogue of acetophenone (Soldatenkov et al., 2008) in the analogous syntheses results in very complex multicomponent mixtures instead of the expected γ-piperidol derivatives.
These mixtures contain only trace quantities of the expected piperidols (identified by LC-MS method). It is interesing to note that heating of the analogous double Mannich base prepared from α-tetralone (Soldatenkov et al., 2009;Soldatova et al., 2010;Siaka et al., 2012) in HBr solution gives the expectable product of the cyclization, but in the dehydrated form. Its structure comprising the spiro-fused hexahydrobenzo[f]isoquinoline and tetrahydronaphthalenone systems was unambiguously established by X-ray diffraction study (Siaka et al., 2012). Thus, such a molecule appears to be much more stable than its 10b-hydroxy predecessor. Hence, we were not sure that structure of the main product would be chemically preferable in the analogous multicomponent condensation if we would use cyclohexanone as the ketone component (heating in HBr solution; Fig. 1). We have found that, in this case, 8a-hydroxy-3-methylperhydrospiro[isoquinoline-1,2′-cyclohexan]-1′-one is formed, which is very stable towards dehydration in acidic media. The first step of this cascade process is the formation of the double Mannich base, and the second one is aldol-type intramolecular cycloaddition of the two cyclohexenone moieties to each other. The structure of the spiro-derivative, C 15 H 25 NO 2 , (I) was unambiguously established by X-ray diffraction study.
The molecule of I comprises spiro-fused perhydroisoquinoline and cyclohexanone systems (Fig. 2). All the three saturated six-membered rings adopt chair conformations. The cyclohexane and piperidine rings within the perhydroisoquinoline are fused in trans-trans type. The nitrogen atom has a trigonal-pyramidal geometry (sum of the bond angles is 328.0 (2)°). The methyl substituent occupies the sterically preferrable equatorial position.
The molecule of I possesses three asymmetric centers at the C1, C4A and C8A carbon atoms and can have potentially eight diastereomers. The crystal of I is racemic and consists of enantiomeric pairs with the following relative configuration of the centers: rac-1S*,4aS*,8aS*.

Refinement
The hydrogen atom of the hydroxy group was localized in the difference Fourier map and refined isotropically with fixed isotropic displacement parameters U iso (H) = 1.5U eq (O). The other hydrogen atoms were placed in calculated positions with C-H = 0.98-1.00Å and refined in the riding model with fixed isotropic displacement parameters U iso (H) = 1.5U eq (C) for the methyl group and 1.2U eq (C) for the other groups.

Figure 1
The cascade condensation of cyclohexanone with formaldehyde and methylamine.    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 > 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.