Crystal structure of 3-[(4-benzyl­piperazin-1-yl)meth­yl]-5-(thio­phen-2-yl)-2,3-di­hydro-1,3,4-oxa­diazole-2-thione

Fatmah A M Al-Omary; Ali A El-Emam; Hazem A Ghabbour; C S Chidan Kumar; Ching Kheng Quah; Hoong-Kun Fun

doi:10.1107/S2056989015002273

. 2015 Feb 13;71(Pt 3):o175–o176. doi: 10.1107/S2056989015002273

Crystal structure of 3-[(4-benzylpiperazin-1-yl)methyl]-5-(thiophen-2-yl)-2,3-dihydro-1,3,4-oxadiazole-2-thione

Fatmah A M Al-Omary ^a, Ali A El-Emam ^a,^b,^*, Hazem A Ghabbour ^c, C S Chidan Kumar ^d,^e,^‡, Ching Kheng Quah ^d, Hoong-Kun Fun ^a,^d,^*,^§

PMCID: PMC4350721 PMID: 25844234

Abstract

The title 1,3,4-oxadiazole-2-thione derivative, C₁₈H₂₀N₄OS₂, crystallized with two independent molecules (A and B) in the asymmetric unit. The 2-thienyl rings in both molecules are rotationally disordered over two orientations by approximately 180° about the single C—C bond that connects it to the oxadiazole thione ring; the ratios of site occupancies for the major and minor components were fixed in the structure refinement at 0.8:0.2 and 0.9:0.1 in molecules A and B, respectively. The 1,3,4-oxadiazole-2-thione ring forms dihedral angles of 7.71 (16), 10.0 (11) and 77.50 (12)° (molecule A), and 6.5 (3), 6.0 (9) and 55.30 (12)° (molecule B) with the major and minor parts of the disordered thiophene ring and the mean plane of the adjacent piperazine ring, respectively, resulting in approximately V-shaped conformations for the molecules. The piperazine ring in both molecules adopts a chair conformation. The terminal benzene ring is inclined towards the mean plane of the piperazine ring with N—C—C—C torsion angles of −58.2 (3) and −66.2 (3)° in molecules A and B, respectively. In the crystal, no intermolecular hydrogen bonds are observed. The crystal packing features short S⋯S contacts [3.4792 (9) Å] and π–π interactions [3.661 (3), 3.664 (11) and 3.5727 (10) Å], producing a three-dimensional network.

Keywords: crystal structure; 1,3,4-oxadiazole; piperazin-1-yl; disorder; π–π interactions; S⋯S contacts

Related literature

For the biological activity of 1,3,4-oxadiazole derivatives, see: Al-Deeb et al. (2006 ▸); El-Emam et al. (2004 ▸); Kadi et al. (2007 ▸); Padmavathi et al. (2009 ▸). For the synthesis of the title compound, see: Al-Omar (2010 ▸). For related 1,3,4-oxadiazole structures, see: El-Emam et al. (2012 ▸, 2013 ▸).

Experimental

Crystal data

C₁₈H₂₀N₄OS₂
M _r = 372.50
Monoclinic,
a = 10.6909 (5) Å
b = 29.3658 (13) Å
c = 15.6179 (6) Å
β = 130.283 (2)°
V = 3740.4 (3) Å³
Z = 8
Mo Kα radiation
μ = 0.30 mm⁻¹
T = 273 K
0.41 × 0.36 × 0.14 mm

Data collection

Bruker APEXII CCD diffractometer
88935 measured reflections
11407 independent reflections
10339 reflections with I > 2σ(I)
R _int = 0.034

Refinement

R[F ² > 2σ(F ²)] = 0.059
wR(F ²) = 0.122
S = 1.19
11407 reflections
485 parameters
18 restraints
H-atom parameters constrained
Δρ_max = 0.38 e Å⁻³
Δρ_min = −0.42 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▸); cell refinement: SAINT (Bruker, 2009 ▸); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick 2008 ▸); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015 ▸); molecular graphics: SHELXTL (Sheldrick, 2008 ▸); software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▸).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S2056989015002273/sj5443sup1.cif

e-71-0o175-sup1.cif^{(2.5MB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015002273/sj5443Isup2.hkl

e-71-0o175-Isup2.hkl^{(624.5KB, hkl)}

Click here for additional data file.^{(7.1KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015002273/sj5443Isup3.cml

Click here for additional data file.^{(1.2MB, tif)}

X Y A B . DOI: 10.1107/S2056989015002273/sj5443fig1.tif

The molecular structure of the title compound with atom labels and 50% probability displacement ellipsoids (atoms of the minor part are labelled with the suffix X and Y for molecules A and B, respectively)

Click here for additional data file.^{(1.3MB, tif)}

. DOI: 10.1107/S2056989015002273/sj5443fig2.tif

Crystal packing of the title compound, showing the S⋯S short contacts and π–π interactions as dashed lines. Only the major components of the thiophene rings are shown. All the H atoms are omitted for clarity.

CCDC reference: 1047059

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

Acknowledgments

The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this work through the Research Group Project No. RGP-274. CSCK thanks Universiti Sains Malaysia (USM) for a postdoctoral research fellowship.

supplementary crystallographic information

S1. Chemical context

Considerable attention has been devoted to 1,3,4-oxadiazole derivatives which have long been known for their diverse chemotherapeutic properties as antiviral agents against HIV-1 viruses (El-Emam et al., 2004) and to demonstrate antibacterial (Padmavathi et al., 2009) and anti-inflammatory properties (Kadi et al., 2007; Al-Deeb et al., 2006). The title compound was synthesized among a series of 2-thienyl-1,3,4-oxadiazoles and related derivatives as potential antimicrobial agents (Al-Omar, 2010).

S2. Structural commentary

The asymmetric unit of the title compound consists of two crystallographically independent molecules (A and B) as shown in Fig. 1. The thiophene rings has an approximately 180° rotational disorder (atoms of the minor part are labelled with the suffix X and Y for molecules A and B, respectively) about the C2–C3 single bond. The bond lengths and angles are within normal ranges and are comparable with those reported earlier for similar structures (El-Emam et al. 2012, 2013). The ratio of the refined site-occupancy factors of the major and minor parts of the disordered thiophene ring is 0.8: 0.2 and 0.9 : 0.1 in molecules A and B respectively. The 1,3,4-oxadiazole-2-thione (O1A/N1A/N2A/C1A/C2A and O1B/N1B/N2B/C1B/C2B) rings form dihedral angles of 7.71 (16), 10.0 (11) and 77.50 (12)° (molecule A); and 6.5 (3), 6.0 (9) and 55.30 (12)° (molecule B) with the major and minor parts of the disordered thiophene ring and the mean plane of the adjacent piperazine rings (N3A/N4A/C8A–C11A and N3B/N4B/C8B–C11B), resulting in approximately V-shaped conformations for the molecules. The piperazine adopts a chair conformation with puckering parameters: Q = 0.591 (2) Å, θ = 178.50 (19)°, and φ = 8(10)° in molecule A and Q = 0.589 (2) Å, θ = 3.10 (19)°, and φ = 178 (6)° in molecule B. The terminal benzene rings (C13A–C18A and C13B–C18B) in both the molecules are inclined towards the mean plane of the piperazine ring with torsion angles N4A–C12A–C13A–C14A of -58.2 (3)° and N4B–C12B–C13B–C18B of -66.2 (3)°.

S3. Supramolecular features

In the crystal, no significant intermolecular hydrogen bonds are observed. The crystal packing (Fig. 2) is stabilized by a short S···S contact [3.4792 (9) Å] and π–π interactions with Cg1···Cg2ⁱ distance = 3.661 (3) Å, Cg1···Cg3ⁱ distance = 3.664 (11) Å and Cg4···Cg5ⁱ distance = 3.5727 (10) Å (symmetry code: (i) X, Y, Z), producing a three-dimensional structure. Cg1–Cg5 are the centroids of the S2A/C3A/C4A/C5A/C6A, S2B/C3B/C4B/C5B/C6B, C3B/S2Y/C6Y/C5Y/C4Y, O1A/C1A/N2A/N1A/C2A and O1B/C1B/N2B/N1B/C2B rings, respectively.

S4. Synthesis and crystallization

The title compound was prepared by a literature procedure (Al-Omar, 2010) and crystallized from EtOH/CHCl₃ (1:1) to yield colorless crystals. M. P.: 101–103°C.

S5. Refinement details

All H atoms were positioned geometrically (C=H = 0.93 or 0.97 Å) and refined using a riding model with U_iso(H) = 1.2 U_eq(C). The thienyl ring is disordered over two positions and,in the final refinement cycles, the occupancy ratios were fixed in a ratio 0.8: 0.2 for molecule A and 0.9:0.1 for molecule B, respectively. Similarity and rigid-bond restraints were applied to the disordered atoms.