3-(Adamantan-1-yl)-4-ethyl-1-{[4-(2-meth­oxy­phen­yl)piperazin-1-yl]meth­yl}-1H-1,2,4-triazole-5(4H)-thione

Ali A El-Emam; Hanaa M Al-Tuwaijri; Ebtehal S Al-Abdullah; C S Chidan Kumar; Hoong-Kun Fun

doi:10.1107/S1600536813032789

. 2013 Dec 7;70(Pt 1):o25–o26. doi: 10.1107/S1600536813032789

3-(Adamantan-1-yl)-4-ethyl-1-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-1H-1,2,4-triazole-5(4H)-thione

Ali A El-Emam ^a,^‡, Hanaa M Al-Tuwaijri ^a, Ebtehal S Al-Abdullah ^a, C S Chidan Kumar ^b, Hoong-Kun Fun ^a,^*,^§

PMCID: PMC3914072 PMID: 24526973

Abstract

In the title compound, C₂₆H₃₇N₅OS, the piperazine ring adopts a chair conformation. The triazole ring forms dihedral angles of 67.85 (9) and 59.41 (9)° with the piperazine and benzene rings, respectively, resulting in an approximate V-shaped conformation for the molecule. An intramolecular C—H⋯O hydrogen bond generates an S(6) ring motif. The crystal structure features C—H⋯π interactions, producing a two-dimensional supramolecular architecture.

Related literature

For the pharmacological activity of adamantane derivatives and adamantyl-1,2,4-triazoles, see: Togo et al. (1968 ▶); El-Emam et al. (2004 ▶, 2013 ▶); Al-Deeb et al. (2006 ▶); Kadi et al. (2007 ▶, 2010 ▶). For related adamantyl-1,2,4-triazole structures, see: Al-Abdullah et al. (2013 ▶); Al-Tamimi, Alafeefy et al. (2013 ▶); Al-Tamimi, Al-Abdullah et al. (2013 ▶); El-Emam et al. (2012 ▶). For the synthesis of the starting material, see: El-Emam & Ibrahim (1991 ▶). For ring conformations and ring puckering analysis, see: Cremer & Pople (1975 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). graphic file with name e-70-00o25-scheme1.jpg

Experimental

Crystal data

C₂₆H₃₇N₅OS
M _r = 467.67
Monoclinic,
a = 19.8170 (3) Å
b = 11.9384 (3) Å
c = 21.7807 (4) Å
β = 107.886 (2)°
V = 4903.90 (17) Å³
Z = 8
Cu Kα radiation
μ = 1.39 mm⁻¹
T = 296 K
0.98 × 0.62 × 0.41 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.344, T _max = 0.599
15455 measured reflections
4029 independent reflections
3606 reflections with I > 2σ(I)
R _int = 0.033

Refinement

R[F ² > 2σ(F ²)] = 0.043
wR(F ²) = 0.115
S = 1.05
4029 reflections
308 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.27 e Å⁻³

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

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813032789/rz5099sup1.cif

e-70-00o25-sup1.cif^{(35.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813032789/rz5099Isup2.hkl

e-70-00o25-Isup2.hkl^{(197.6KB, hkl)}

Click here for additional data file.^{(10.1KB, cml)}

Supporting information file. DOI: 10.1107/S1600536813032789/rz5099Isup3.cml

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

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

Cg is the centroid of the C1–C6 benzene ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C11—H11A⋯O1	0.97	2.26	2.903 (2)	123
C18—H18A⋯Cg ⁱ	0.97	2.81	3.748 (2)	162

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Symmetry code: (i) Inline graphic .

Acknowledgments

The financial support of the Deanship of Scientific Research and the Research Center for Female Scientific and Medical Colleges, King Saud University, is greatly appreciated. CSCK thanks Universiti Sains Malaysia for a postdoctoral research fellowship.

supplementary crystallographic information

1. Comment

Derivatives of adamantane have long been known for their diverse biological activities including antiviral activity against influenza (Togo et al., 1968) and HIV viruses (El-Emam et al., 2004). Moreover, adamantane derivative were reported to exhibit marked antibacterial and anti-inflammatory activities (Kadi et al., 2007, 2010; El-Emam et al., 2013). In continuation of our interest in the chemical and pharmacological properties of adamantane derivatives, and as part of our on-going structural studies of adamantane derivatives (Al-Abdullah et al., 2013); Al-Tamimi, Alafeefy et al., 2013; Al-Tamimi, Al-Abdullah et al., 2013; El-Emam et al., 2012), we have synthesized the title compound (I) as a potential chemotherapeutic agent.

In the crystal structure of the title compound (Fig. 1), the piperazine (N1–N2/C8–C11) ring adopts a chair conformation with puckering parameters: Q = 0.5783 (18) Å, θ = 178.03 (17)°, and φ = 25 (5)° (Cremer & Pople, 1975). The dihedral angle between the piperazine ring and the triazole ring (N3–N5/C13/C14) is 67.85 (9)°. The triazole ring forms a dihedral angle of 59.41 (9)° with the benzene ring (C1—C6), resulting in an approximate V-shape conformation of the molecule. An intramolecular C–H···O hydrogen bond generates an S(6) ring motif (Bernstein et al., 1995). The crystal structure features an intermolecular C–H···π interaction with a H18A···Cg distance of 2.81 Å, where Cg is the centroid of the benzene ring (C1—C6).

2. Experimental

A mixture of 527 mg (2 mmol) of 3-(1-adamantyl)-4-ethyl-4H-1,2,4- triazole-5-thiol (El-Emam & Ibrahim, 1991), 1-(2-methoxyphenyl)piperazine (383 mg, 2 mmol) and 37% formaldehyde solution (1 ml) in ethanol (8 ml) was heated under reflux for 15 min until a clear solution was obtained. Stirring was continued for 12 h at room temperature and the mixture was allowed to stand overnight. Cold water (5 ml) was added slowly and the mixture was stirred for 20 min. The precipitated crude product were filtered, washed with water, dried, and crystallized from ethanol to yield 860 mg (92%) of the title compound (C₂₆H₃₇N₅OS) as colourless needle crystals. M.p.: 477–479 K. Single plate-shaped crystals suitable for X-ray analysis were obtained by slow evaporation of a CHCl₃:EtOH solution (1:1 v/v; 5 ml) at room temperature.

¹H NMR (CDCl₃, 500.13 MHz): δ 1.32 (t, 3H, CH₂CH₃, J = 7.0 Hz), 1.71–1.76 (m, 6H, Adamantane-H), 1.98–2.12 (m, 9H, Adamantane-H), 3.08 (s, 8H, Piperazine-H), 3.81 (s, 3H, OCH₃), 4.15 (q, 2H, CH₂CH₃, J = 7.0 Hz), 5.15 (s, 2H, CH₂), 6.79–7.01 (m, 4H, Ar—H). ¹³C NMR (CDCl₃, 125.76 MHz): δ 13.76 (CH₂CH₃), 27.92, 35.32, 36.48, 39.83 (Adamantane-C), 43.83 (CH₂CH₃), 47.40, 50.18 (Piperazine-C), 55.48 (OCH₃), 72.58 (CH₂), 111.43, 118.38, 121.12, 123.55, 152.13, 152.26 (Ar—C), 156.57 (Triazole C-5), 167.34 (C=S).