(Z)-1-Di­phenyl­methyl-4-(3-phenyl­prop-2-en­yl)piperazine

S Shivaprakash; G Chandrasekara Reddy; Jerry P Jasinski

doi:10.1107/S1600536814008289

. 2014 Apr 18;70(Pt 5):o576. doi: 10.1107/S1600536814008289

(Z)-1-Diphenylmethyl-4-(3-phenylprop-2-enyl)piperazine

S Shivaprakash ^a, G Chandrasekara Reddy ^a, Jerry P Jasinski ^b,^*

PMCID: PMC4011253 PMID: 24860379

Abstract

In the title compound, C₂₆H₂₈N₂, the piperazine group adopts a chair conformation with the exocyclic N—C bonds in equatorial orientations. The dihedral angle between the geminal benzene rings is 80.46 (12)° and the C=C—C—N torsion angle is 145.9 (2)°. In the crystal, weak C—H⋯π interactions link the molecules into [100] chains.

Related literature

For the use of cinnerizine as an antihistamine, see: Paton & Webster (1985 ▶). For synthetic methods of (E)-isomers of 1-benzhydryl-4-cinnamyl piperazines, see: Cignarella & Testa (1968 ▶). For the synthesis of the Z-isomer of cinnerizine, see: Shivaprakash & Chandrasekara Reddy (2014 ▶). graphic file with name e-70-0o576-scheme1.jpg

Experimental

Crystal data

C₂₆H₂₈N₂
M _r = 368.50
Monoclinic,
a = 8.7823 (3) Å
b = 9.6068 (3) Å
c = 12.4894 (4) Å
β = 94.834 (3)°
V = 1049.97 (6) Å³
Z = 2
Cu Kα radiation
μ = 0.52 mm⁻¹
T = 173 K
0.42 × 0.38 × 0.32 mm

Data collection

Agilent Eos Gemini diffractometer
Absorption correction: multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012 ▶) T _min = 0.907, T _max = 1.000
6399 measured reflections
3316 independent reflections
3177 reflections with I > 2σ(I)
R _int = 0.027

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.096
S = 1.05
3316 reflections
254 parameters
2 restraints
H-atom parameters constrained
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.14 e Å⁻³
Absolute structure: Flack parameter determined using 1186 quotients [(I ⁺)−(I ⁻)]/[(I ⁺)+(I ⁻)] (Parsons et al., 2013 ▶)
Absolute structure parameter: 0.1 (4)

Data collection: CrysAlis PRO (Agilent, 2012 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis RED (Agilent, 2012 ▶); program(s) used to solve structure: SUPERFLIP (Palatinus & Chapuis, 2007 ▶; Palatinus & van der Lee, 2008 ▶; Palatinus et al., 2012 ▶); program(s) used to refine structure: SHELXL2012 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶); software used to prepare material for publication: OLEX2.

Supplementary Material

Crystal structure: contains datablock(s) I. DOI: 10.1107/S1600536814008289/hb7219sup1.cif

e-70-0o576-sup1.cif^{(29.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814008289/hb7219Isup2.hkl

e-70-0o576-Isup2.hkl^{(182KB, hkl)}

Click here for additional data file.^{(8.1KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814008289/hb7219Isup3.cml

CCDC reference: 997025

Additional supporting information: crystallographic information; 3D view; checkCIF report

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

Cg1 is the centroid of the C15–C20 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C24—H24⋯Cg1ⁱ	0.95	2.70	3.629 (3)	164

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Symmetry code: (i) Inline graphic .

Acknowledgments

We express our sincere thanks to Dr Anil Kush, Director, VMSRF, for his keen interest and support throughout this work. JPJ acknowledges the NSF–MRI program (grant No. CHE-1039027) for funds to purchase the X-ray diffractometer.

supplementary crystallographic information

1. Comment

Cinnerizine: (E)-1-(Diphenyl)methyl)-4-(3-phenyl-2-propenyl)piperazine is marketed as stugeron which is used as antihistamine (Paton & Webster, 1985). Because of greater biological importance of (E)-isomers of 1-benzhydryl-4-cinnamyl piperazines, several synthetic methods are described (Cignarella & Testa, 1968). But only recently the synthesis of (Z)-1-(Diphenylmethyl)-4-(3-phenyl-2-propenyl)piperazine is reported (Shivaprakash & Chandrasekara Reddy, 2014).

The title compound, C₂₆H₂₈N₂, (I), is a close analogue of an existing drug viz., Cinnarizine, which has (E) geometry. We have prepared for the first time the (Z) isomer to study the structure activity relationship. However there is no report of any crystallographic data for this molecule so far. Hence this study was performed to confirm its structure. This compound exists as solid in free base form which could be crystallized easily. In continuation of our work in this area, we report here the crystal structure of (I).

In (I), the piperazine group adopts a slightly distorted chair conformation (puckering parameters Q, θ, and φ = 0.597 (2)Å, 3.95 (19)° and 168 (3)°, respectively (Fig. 1). The dihedral angles between the mean planes of the two methyl diphenyl groups (C15–C20 and C21–C26) with that of the 2-propenyl phenyl group (C8–C13) are 35.2 (1)° and 45.8 (8)°, respectively. The two methyl phenyl groups are separated by 80.4 (6)° with respect to each other.

2. Experimental

To a solution of 1-benzhydryl-4-(2-acetaldehyde) piperazine (5.0 g, 17.0 mmol) in dichloromethane (50 ml) under N₂ atmosphere was added benzyltriphenyl phosphonium chloride (6.9 g, 17.9 mmol). The mixture was cooled to 278°K and t-BuOK (4.6 g, 41.3 mmol) was added under stirring. After completion, the reaction mass was quenched into water (100 ml). The organic layer was separated, dried over anhydrous sodium sulphate and concentrated under vacuum which was then subjected to column chromatography over silica gel with a EtOAc/Hexane mixture to afford the pure form of (Z)-1-benzhydrl-4-cinnamylpiperazine which was crystallized using absolute ethanol, white solid, mp: 363-365 K.