2,4,6,8-Tetra­kis(4-chloro­phen­yl)-3,7-diaza­bicyclo­[3.3.1]nonan-9-one O-benzyl­oxime acetone monosolvate

Dong Ho Park; V Ramkumar; P Parthiban

doi:10.1107/S1600536812016509

. 2012 Apr 21;68(Pt 5):o1481. doi: 10.1107/S1600536812016509

2,4,6,8-Tetrakis(4-chlorophenyl)-3,7-diazabicyclo[3.3.1]nonan-9-one O-benzyloxime acetone monosolvate

Dong Ho Park ^a, V Ramkumar ^b, P Parthiban ^a,^*

PMCID: PMC3344591 PMID: 22590353

Abstract

In the title compound, C₃₈H₃₁Cl₄N₃O·C₃H₆O, the 3,7-diaza-bicycle exists in a chair–boat conformation. The 4-chlorophenyl groups attached to the chair form are equatorially oriented at an angle of 18.15 (3)° with respect to each other, whereas the 4-chlorophenyl groups attached to the boat form are oriented at an angle of 32.64 (3)°. In the crystal, molecules are linked by N—H⋯π and C—H⋯O interactions.

Related literature

For the synthesis and stereochemistry of 3,7-diazabicyclo[3.3.1]nonan-9-one derivatives, see: Parthiban et al. (2008 ▶). For the biological activity of 3,7-diazabicyclo[3.3.1]nonan-9-one derivatives and related structures, see: Parthiban et al. (2009 ▶, 2010 ▶); Asakawa (1995 ▶); Jayaraman & Avila (1981 ▶). For ring puckering parameters, see: Cremer & Pople (1975 ▶); Nardelli (1983 ▶); Luger & Bülow (1983 ▶).

Experimental

Crystal data

C₃₈H₃₁Cl₄N₃O·C₃H₆O
M _r = 745.54
Monoclinic,
a = 14.9237 (5) Å
b = 10.5064 (3) Å
c = 24.6015 (7) Å
β = 93.116 (1)°
V = 3851.7 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.35 mm⁻¹
T = 293 K
0.20 × 0.16 × 0.16 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2004 ▶) T _min = 0.934, T _max = 0.947
35931 measured reflections
7173 independent reflections
4263 reflections with I > 2σ(I)
R _int = 0.040

Refinement

R[F ² > 2σ(F ²)] = 0.062
wR(F ²) = 0.188
S = 1.03
7173 reflections
475 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.89 e Å⁻³
Δρ_min = −0.29 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT-Plus (Bruker, 2004 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SIR92 (Altomare et al., 1993) ▶; program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812016509/hb6689sup1.cif

e-68-o1481-sup1.cif^{(29.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812016509/hb6689Isup2.hkl

e-68-o1481-Isup2.hkl^{(343.9KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812016509/hb6689Isup3.cml

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

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

Cg3 is the centroid of the C8–C13 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C13—H13⋯O2	0.93	2.52	3.441 (6)	172
N2—H2A⋯Cg3ⁱ	0.88 (3)	2.85 (3)	3.637 (3)	150 (3)

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Symmetry code: (i) Inline graphic .

Acknowledgments

This research was supported by the National Research Foundation (NRF) of Korea.

supplementary crystallographic information

Comment

The 3,7-diazabicyclo[3.3.1] nonan-9-one nucleus is widely present in Lupin alkaloids and are displaying various biological actions (Parthiban et al., 2009, 2010, Asakawa, 1995, Jayaraman & Avila, 1981). In fact, the biological activities mainly depends on the nature of the substituents and their positions on the nucleus. Since C=N—O-R is an important class of pharmacophore by displaying biological actions, we have synthesized the title molcule by the condensation of 3,7-diazabicyclo[3.3.1]nonan-9-one and O-benzyl moiety to make the biologically potent oxime derivative. Because the biological actions mainly depend on the stereochemistry of the molecule, we undertaken the title molecule for the present study to explore its stereochemistry.

The crystallographic parameters viz., torsion angles, asymmetry parameters and ring puckering parameters calculated for the title compound shows that one of the piperidone rings, N(1)—C(1)—C(2)—C(7)—C(5)—C(6) adopts a near ideal chair conformation, according to Cremer & Pople and Nardelli. The total puckering amplitude, Q_T is 0.606 (3) Å, the phase angle θ is 2.7 (3)° and phi is 261 (6)° (Cremer & Pople, 1975). The smallest displacement asymmetry parameters q₂ and q₃ are 0.031 (3) and 0.605 (3) Å, respectively (Nardelli, 1983). On the otherhand, another piperidone ring N(2)—C(3)—C(2)—C(7)—C(5)—C(4) exists in the boat conformation according to C&P by Q_T = 0.764 (3), θ = 91.9 (2)° and phi = 357.0 (3)° as well as Nardelli by q₂ = 0.764 (3) and q₃ = -0.025 (3)°.

An equatorial orientation of the 4-chlorophenyl groups attached on the chair form piperidone is supported by the angles of C(1)—C(8) and C(6)—C(26) on the C&P plane normal as 70.85 (19) and 75.04 (19)°, respectively (Luger & Bülow, 1983). The equatorial orientations of the aryl groups are further supported by thier torsion angles; the C8—C1—C2—C7 is 178.4 (3)° and C26—C6—C5—C7 is 177.0 (3)°. The 4-chlorophenyl groups attached on the boat form of the piperidone have angles with C&P plane normal are C(3)—C(14) = 57.34 (19)° and C(4)—C(20) = 61.70 (19)°, they are respectively in bisectional and equatorial orientations according to Luger & Bulow. In fact, both lies on the boundary of bisectional and this is further supported by their torsion angles as follows: C7—C2—C3—C14 = 115.5 (3)° and C20—C4—C5—C7 = -121.6 (3)°.

The 4-chlorophenyl groups attached on the chair form are equatorially oriented at an angle of 18.15°, respect to each other, whereas, the 4-chlorophenyl groups attached to the boat form are oriented at an angle of 32.64° between them.

Based on the above analysis, it is clear that the title compound exists in the chair-boat conformation with an equatorial orientation of the 4-chlorophenyl groups on both sides of the secondary amino group of the piperidone in the chair conformation.

The crystal packing is stabilized by weak intermolecular N—H···π (C14—C19) and C—H···O interactions.

Experimental

The 2,4,6,8-tetrakis(4-chlorophenyl)-3,7-diazabicyclo[3.3.1]nonan-9-one was synthesized by a modified Mannich condensation in one-pot, using 4-chlorobenzaldehyde (0.2 mol, 28.12 g), acetone (0.05 mol, 3.7 ml) and ammonium acetate (0.1 mol, 7.7 g) in a 50 ml of absolute ethanol (Parthiban et al., 2008). The mixture was gently warmed on a hot plate at 303 K (30° C) with moderate stirring till the complete consumption of the starting materials, which was monitored by TLC. At the end, the crude 3,7-diazabicycle was separated by filtration and gently washed with 1:5 cold ethanol-ether mixture. The pure 2,4,6,8-tetrakis(4-chlorophenyl)-3,7-diazabicyclo[3.3.1]nonan-9-one (0.01 mol, 5.823 g) was condensed with O-benzylhydroxylamine hydrochloride (0.012 mol, 1.915 g) using sodium acetate trihydrate (0.03 mol, 3.06 g) as base in ethanol-chloroform 1:1 mixture to obtain the title oxime ether. Colourless prisms were obtained by slow evaporation of an acetone solution.