(7E)-5-Benzyl-7-(2-chloro­benzyl­idene)-3-(2-chloro­phen­yl)-2-phenyl-3,3a,4,5,6,7-hexa­hydro-2H-pyrazolo­[4,3-c]pyridine

N S Karthikeyan; B Uma Mahesh; K Sathiyanarayanan; P Raghavaiah; R S Rathore

doi:10.1107/S1600536810023317

. 2010 Jun 23;66(Pt 7):o1734. doi: 10.1107/S1600536810023317

(7E)-5-Benzyl-7-(2-chlorobenzylidene)-3-(2-chlorophenyl)-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine

N S Karthikeyan ^a, B Uma Mahesh ^a, K Sathiyanarayanan ^a, P Raghavaiah ^b, R S Rathore ^c,^*

PMCID: PMC3006872 PMID: 21587951

Abstract

In the title 2H-pyrazolo[4,3-c]pyridine derivative, C₃₂H₂₇Cl₂N₃, the dihydropyrazole ring adopts an envelope conformation and the piperidine fused ring a twisted-chair conformation. Two short intramolecular C—H⋯Cl contacts are observed. The crystal packing is characterized by dimeric C—Cl⋯π interactions involving the 5-benzyl ring, with Cl⋯centroid and closest atomic Cl⋯π distances of 3.778 (2) and 3.366 (4) Å, respectively.

Related literature

For the anti-inflammatory activity of 2H-pyrazolo[4,3-c]pyridine derivatives, see Krapcho & Turk (1975 ▶). For π-halogen-dimer interactions and their role in host–guest chemistry, see: Noman et al. (2004 ▶); Nagaraj et al. (2005 ▶).

Experimental

Crystal data

C₃₂H₂₇Cl₂N₃
M _r = 524.47
Monoclinic,
a = 13.7117 (7) Å
b = 15.4451 (6) Å
c = 13.6896 (9) Å
β = 113.135 (7)°
V = 2666.0 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.27 mm⁻¹
T = 294 K
0.36 × 0.26 × 0.22 mm

Data collection

Oxford Diffraction Xcalibur Eos Gemini diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009 ▶) T _min = 0.909, T _max = 0.943
11774 measured reflections
5436 independent reflections
2483 reflections with I > 2σ(I)
R _int = 0.049

Refinement

R[F ² > 2σ(F ²)] = 0.049
wR(F ²) = 0.098
S = 0.83
5436 reflections
334 parameters
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXL97 and PLATON.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810023317/ng2791sup1.cif

e-66-o1734-sup1.cif^{(25.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810023317/ng2791Isup2.hkl

e-66-o1734-Isup2.hkl^{(260.8KB, hkl)}

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
C3—H3⋯Cl1	0.98	2.61	3.101 (2)	111
C27—H27⋯Cl2	0.93	2.68	3.043 (3)	104

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Acknowledgments

The Bioinformatics Infrastructure Facility and the Single Crystal X-ray Diffractometer Facility at the University of Hyderabad are gratefully acknowledged are gratefully acknowledged for computation and data collection. RSR thanks the CSIR, New Delhi, for support under the scientist’s pool scheme and NSK thanks the CSIR, New Delhi, for a Senior Research Fellowship.

supplementary crystallographic information

Comment

Derivatives of 2H-pyrazolo[4,3-c]pyridine have been tested for anti-inflammatory activity (Krapcho & Turk, 1975). A search in Cambridge Structural Database (version 5.31) for such compounds retrieved zero hits. With a purpose to study hitherto unexplored structures of these compounds, we here report the synthesis and structural investigations on, 5-benzyl-(7E)-7-(2-chlorobenzylidene)-3-(2-chlorophenyl)-2-phenyl- 3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine, (I).

The structure of (I) with adopted atomic numbering scheme is shown in Fig 1. (I) is a racemic mixture. In the reported model, the stereogenic centers C3 and C3A possess R-configurations. The five-membered dihydropyrazole ring (N1/N2/C3/C3A/C7A) adopt an envelope conformation with atom C3 at the flap of the envelope (Ring puckering parameters are: q2 = 0.204 (2) Å, φ2 = 248.3 (6)°). The adjacent 6-membered piperidine ring (C3A/C4/N5/C6/C7/C7A) assumes a chair conformation which is substantially twisted from ideal geometry. The puckering parameters are as follows: q2 = 0.189 (2) Å, q3 = -0.468 (2) Å, θ = 158.0 (2)°, φ = 209.5 (8)°, and total puckering amplitude, Q = 0.505 (2) Å.

Two short intra-molecular contacts C3—H3···Cl1 and C27—H27···Cl2 were observed (Table 1). Intermolecular C—Halogen···π contact stabilizes the dimeric units in (I) (Fig 2). A dimer is formed by C29—Cl2···Cg5ⁱ [symmetry code (i): 1 - x, 1 - y, 1 - z]. The Cl2..Cg5 distance and C29—Cl2···Cg5 angle are 3.778 (2)Å and 141.2 (1)° respectively, whereas the minimum atomic distance in Cl2···π is 3.366 (4) Å. Cg5 is the centroid of (C21–C26) ring. The C—Halogen···π dimeric interactions [also referred as PHD; π-halogen-dimer interactions (Noman et al. 2004)] have been shown recently, to play an important role in host–guest chemistry (Nagaraj et al., 2005; references therein).

Experimental

1-benzyl-3, 5-dibenzylidenepiperidin-4-one (0.003 mol) and phenyl hydrazine (0.003 mol) were dissolved in 2-propanol. The reaction mixture was refluxed for 1–2 h on a water bath and tested with TLC at regular intervals for completeness of reaction. Following that, the resulting mixture was cooled and poured into crushed ice. The solid so obtained was separated, washed with water and subjected to column chromatography using ethyl acetate and n-hexane. Final yield 89%, m.p. 153–155° C. Suitable single crystals for data collection were grown from ethanol and tetrahydrofuran mixture in 1:1 ratio.