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

Augusto Rivera; Diego Quiroga; Jaime Ríos-Motta; Monika Kučeraková; Michal Dušek

doi:10.1107/S1600536813000305

. 2013 Jan 12;69(Pt 2):o217. doi: 10.1107/S1600536813000305

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

Augusto Rivera ^a,^*, Diego Quiroga ^a, Jaime Ríos-Motta ^a, Monika Kučeraková ^b, Michal Dušek ^b

PMCID: PMC3569752 PMID: 23424498

Abstract

In the crystal structure of the title compound, C₂₁H₂₄F₂N₂O₂, there are two intramolecular O—H⋯N hydrogen bonds involving the N atoms of the imidazolidine ring and the hydroxy groups. The crystal studied was a meso compound obtained by the reaction of the aminal (2S,7R,11S,16R)-1,8,10,17-tetraazapentacyclo[8.8.1.1^8,17.0^2,7.0^11,16]cosane with 4-fluorophenol. The imidazolidine ring has a twisted conformation with a CH—CH—N—CH₂ torsion angle of 44.99 (14)° and, surprisingly, the lone pairs of the N atoms are disposed in a syn isomerism, making the title compound an exception to the typical ‘rabbit-ear effect’ in 1,2-diamines. In the crystal, molecules are linked via C—H⋯F hydrogen bonds, forming chains along the c-axis direction. These chains are linked via another C—H⋯F hydrogen bond, forming a three-dimensional network.

Related literature

For a related structure, see: Rivera et al. (2011 ▶). For a discussion of the ‘rabbit-ear effect’ in 1,2-diamines, see: Hutchins et al.(1968 ▶).

Experimental

Crystal data

C₂₁H₂₄F₂N₂O₂
M _r = 374.4
Orthorhombic,
a = 15.4029 (4) Å
b = 18.7822 (4) Å
c = 6.1639 (2) Å
V = 1783.22 (8) Å³
Z = 4
Cu Kα radiation
μ = 0.86 mm⁻¹
T = 120 K
0.31 × 0.15 × 0.11 mm

Data collection

Agilent Xcalibur (Atlas, Gemini ultra) diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010 ▶) T _min = 0.222, T _max = 1
40310 measured reflections
3177 independent reflections
2984 reflections with I > 3σ(I)
R _int = 0.049

Refinement

R[F ² > 2σ(F ²)] = 0.030
wR(F ²) = 0.077
S = 1.42
3177 reflections
250 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.15 e Å⁻³
Δρ_min = −0.11 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SUPERFLIP (Palatinus & Chapuis, 2007 ▶); program(s) used to refine structure: JANA2006 (Petříček et al., 2006 ▶); molecular graphics: DIAMOND (Brandenburg & Putz, 2005 ▶); software used to prepare material for publication: JANA2006.

Supplementary Material

Click here for additional data file.^{(20.9KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813000305/bx2435sup1.cif

e-69-0o217-sup1.cif^{(20.9KB, cif)}

Click here for additional data file.^{(131.2KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813000305/bx2435Isup2.hkl

e-69-0o217-Isup2.hkl^{(131.2KB, hkl)}

Click here for additional data file.^{(7.8KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813000305/bx2435Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯N1	0.85 (2)	1.89 (2)	2.6540 (17)	148 (2)
O2—H2⋯N2	0.85 (2)	1.89 (2)	2.6741 (18)	152 (2)
C13—H1C13⋯F2ⁱ	0.96	2.43	3.2645 (19)	145
C17—H2C17⋯F2ⁱⁱ	0.96	2.54	3.356 (2)	142

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors acknowledge the Dirección de Investigaciones, Sede Bogotá (DIB) de la Universidad Nacional de Colombia, for financial support of this work, as well as the Praemium Academiae project of the Academy of Sciences of the Czech Republic. DQ acknowledges the Vicerrectoría Académica de la Universidad Nacional de Colombia for a fellowship.

supplementary crystallographic information

Comment

Typically the 1,1-diamines tend to adopt a conformation in which the arrangement of electron pairs is anti periplanar. This behavior is known as `rabbit-ears' effect (Hutchins et al., 1968), however, this effect can be avoided by restriction of the 1,2-diamine in cyclic molecules. Recently, we reported the synthesis and the crystal structure of rac-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 (Rivera et al., 2011), which has trans stereochemistry in the 1,2-diamine moiety with the lone pairs located in anti disposition avoiding the repulsive interactions. Now we reported the synthesis and crystal structure of the meso diastereoisomer with absolute configuration (R,S) where surprisingly the lone pairs of the N atoms are located in syn disposition.

The molecular structure and atom-numbering scheme for (I) are shown in Fig. 1. In the molecular structure of the title compound, the two N atoms of the heterocyclic ring interact with the H atoms of the hydroxy groups by intramolecular hydrogen bonds O—H···N, with N···O interatomic distance values around 2.66 Å, as well as the values of C—O and O—H bond lengths are 1.363 (3) Å and 0.83 (3) Å, respectively. The cyclohexane ring adopts a chair conformation while the heterocyclic ring arranged diagonally respect to the cyclohexane ring with dihedral angle between planes of 25.46 (96)°. The heterocyclic ring adopts an envelope conformation according to the value of the N2—C5—N1—C16 torsion angle of -7.91°. Bond angles around the N atoms N1 and N2 show a higher sp³ character to the N1 and N2 N atoms with pyramidalization involved in the hydrogen bond type interactions [Σ(CNC) N1 = 331.3°, Σ(CNC) N2 = 330.4°]. Moreover, the benzyl groups are located in an unexpected 1,3-diequatorial syn arrangement in the heterocyclic ring with dihedral angle between the planes containing the aromatic rings of 53.80 (30)°. The nonbonding pairs of amino groups involved in the intermolecular hydrogen bonding interactions do not suffer the `rabbit-ear effect' having a syn arrangement demonstrating that the title compound is an exception of this effect.

The stability of the crystal lattice of the title compound is related with non classical intermolecular interactions C—H···F that hold molecules linked in extended chains along the c axis. There are O—H···C and C—H···F weak interactions (table 1), the latter involve halogen group in molecular contact with an electron-deficient C—H bond of the aromatic ring of a second molecule.

Experimental

To a stirred solution of (2S,7R,11S,16R)-1,8,10,17-tetraazapentacyclo[8.8.1.1.^8,170.^2,70^11,16] icosane (3) (276 mg, 1.00 mmol) in dioxane (3 ml) was added slowly dropwise p-fluorophenol (2.00 mmol) in dioxane (3 ml). After stirring for 15 min at room temperature, water (4 ml) was added and the mixture was heated at 40°C during 30 h. After cooling to room temperature, the solvent was removed in vacuo and the crude product was purified by chromatography on a silica column and subjected to gradient elution with light petroleum ether:ethyl acetate (yield 20%, m.p. = 441–443 K). Single crystals of (I) were grown from a CHCl₃ solution by slow evaporation of the solvent at room temperature over a period of about 2 weeks. FT–IR (KBr) ν_max: 3061, 2848, 1495, 1448, 1387, 1289, 1245, 1194, 1124, 1063, 979, 925, 814, 772, 737, 714, 692, 668 cm^{-1. 1}H NMR (400 MHz, CDCl₃) δ (p.p.m.): 1.36 (m, 2H), 1.55–1.79 (m, 6H), 3.11 (t, 2H, J_H,H = 4.0 Hz), 3.39 (d, 1H,²J_H,H = 6.4 Hz, NCH₂N), 3.63 (d, 2H, ²J_H,H = 14.0 Hz, ArCH₂N), 3.84 (d, 1H, ²J_H,H = 6.4 Hz, NCH₂N), 4.03 (d, 2H, ²J_H,H = 14.0 Hz, ArCH₂N), 6.70 (dd, 2H, ³J_H,F = 8.0 Hz, ⁴J_H,H = 2.8 Hz, Ar—H), 6.76 (dd, 2H, ³J_H,H = 8.0 Hz, ⁴J_H,F = 4.8 Hz, Ar—H), 6.87 (td, 2H, ³J_H,H = 8.0 Hz, ³J_H,F = 8.2 Hz, ⁴J_H,H = 3.1 Hz, Ar—H), 10.34 (s, 2H). ¹³C NMR (100 MHz, CDCl₃) δ (p.p.m.): 21.5, 24.7, 55.0, 61.1, 73.4, 114.7 (d, ²J_H,F = 23.5 Hz), 115.4 (d, ²J_H,F = 22.5 Hz), 117.0 (d, ³J_H,F = 6.3 Hz), 122.0 (d, ³J_H,F = 6.9 Hz), 153.4 (d, ⁴J_H,F = 2.0 Hz), 156.0 (d, ¹J_H,F = 236 Hz).