4,4′-Difluoro-2,2′-{[(3aRS,7aRS)-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene)]}diphenol

In the crystal structure of the title compound, C21H24F2N2O2, the two N atoms of the imidazolidine moiety are linked to the hydroxy groups by intramolecular O—H⋯N hydrogen-bonding interactions. The crystal studied was a racemic mixture of RR and SS enatiomers. The cyclohexane ring adopts a chair conformation and the imidazolidine group to which it is fused has a twisted envelope conformation.

In the crystal structure of the title compound, C 21 H 24 F 2 N 2 O 2 , the two N atoms of the imidazolidine moiety are linked to the hydroxy groups by intramolecular O-HÁ Á ÁN hydrogenbonding interactions. The crystal studied was a racemic mixture of RR and SS enatiomers. The cyclohexane ring adopts a chair conformation and the imidazolidine group to which it is fused has a twisted envelope conformation.

Comment
The title compound was obtained by a Mannich type reaction between the aminal (2R,7R,11S,16S)-1, 8,10,17tetraazapentacyclo[8.8.1.1 8,17 .0 2,7 .0 11,16 ]icosane and p-fluorophenol. The crystal structure of the title compound was determined as a racemic mixture having (R,R) or (S,S) configurations at the two stereogenic centers and it crystallizes in a centrosymmetric space group. The chiral centers were not affected when the aminal cage reacted, so the title compound is a trans-rac mixture. The molecular structure and atom-numbering scheme for the title compound are shown in Fig. 1 (Rivera, et al. 2010b and2011), showing a decrease in hydrogen-bonding strength. The slight elongation of the C-O bond in the title compound could be explained by the presence of a fluorine substituent, since theoretical results using MP2 and density functional (B3LYP) methods showed that the chlorine and bromine substituents caused a shortening of this bond by a presumable contribution of these halogens in a quinoid-type structure by resonance (mesomeric) effects (Zierkiewicz,et al. 2003), and an electron donation from the pz-orbital on the oxygen atom to π* acceptor orbitals in the ring, which was not observed in p-fluorophenol where an inductive effect and a strong delocalization of electron density from the pz-orbital on the F atom to π* acceptor orbitals in the ring are predominant, leading to a suppression of electron donation from the pz-orbital on the oxygen atom to the aromatic ring (Zierkiewicz, et al. 2004).
The crystal structure showed an angular deformation in the phenol ring which is caused by the presence of the fluorine atom: the C12-C13-C14 and C19-C20-C21 internal ring angles [both 122.7 (1) °] increase by about 3.53° compared to the value of the corresponding angles in the phenol derivative (Rivera, et al. 2010a). The structural changes of the aromatic ring are governed chiefly by the electronegativity of the fluorine substituent (inductive electron withdrawal), which is reflected in an elongation of C-O bond.

Physical Measurements
The melting point was determined with an Electrothermal apparatus, and it has not been corrected. IR spectrum was recorded as KBr pellets at 292 K on a Perkin-Elmer Paragon FT-IR instrument. NMR spectra were performed in CDCl 3 at room temperature on a Bruker AMX 400 Avance spectrometer.

Preparation
of 4,3,3a,4,5,6,7, dioxane (3 ml) and water (4 ml) in a two-necked round-bottomed flask, prepared beforehand following previously described procedures, was added dropwise a dioxane solution (3 ml) containing two equivalents of p-fluorophenol (224 mg, 2.00 mmol). The mixture was refluxed for about 6 h. The solvent was evaporated under reduced pressure until a sticky residue appeared. The product was purified by chromatography on a silica column, and subjected to gradient elution with benzene:ethyl acetate (yield 25%, m.p. = 443-447 K). Single crystals were grown from a CHCl 3 solution by slow evaporation of the solvent at room temperature over a period of about 2 weeks.

Refinement
All hydrogen atoms were discernible in difference Fourier maps and could be refined to reasonable geometry. According to common practice H atoms attached to C atoms were nevertheless kept in ideal positions during the refinement. The isotropic atomic displacement parameters of hydrogen atoms were evaluated as 1.2*U~eq~ of the parent atom. Fig. 1. Displacement elipsoid plot of the title compound, drawn at 50% probability level. Refinement. The refinement was carried out against all reflections. The conventional R-factor is always based on F. The goodness of fit as well as the weighted R-factor are based on F and F 2 for refinement carried out on F and F 2 , respectively. The threshold expression is used only for calculating R-factors etc. and it is not relevant to the choice of reflections for refinement.

Figures
The program used for refinement, Jana2006, uses the weighting scheme based on the experimental expectations, see _refine_ls_weighting_details, that does not force S to be one. Therefore the values of S are usually larger than the ones from the SHELX program.