3-(Adamantan-1-yl)-1-[(4-ethyl­piperazin-1-yl)meth­yl]-4-[(E)-(4-hy­droxy­benzyl­idene)amino]-1H-1,2,4-triazole-5(4H)-thione

Ali A El-Emam; Khalid A Alrashood; Abdul-Malek S Al-Tamimi; Seik Weng Ng; Edward R T Tiekink

doi:10.1107/S1600536812005107

. 2012 Feb 10;68(Pt 3):o657–o658. doi: 10.1107/S1600536812005107

3-(Adamantan-1-yl)-1-[(4-ethylpiperazin-1-yl)methyl]-4-[(E)-(4-hydroxybenzylidene)amino]-1H-1,2,4-triazole-5(4H)-thione

Ali A El-Emam ^a,^‡, Khalid A Alrashood ^a, Abdul-Malek S Al-Tamimi ^a, Seik Weng Ng ^b,^c, Edward R T Tiekink ^b,^*

PMCID: PMC3295449 PMID: 22412560

Abstract

In the title thione, C₂₆H₃₆N₆OS, the 1,2,4-triazole ring is planar (r.m.s. deviation = 0.020 Å) and the benzene ring is twisted out of this plane [dihedral angle = 62.35 (12)°]. Supramolecular zigzag chains feature in the crystal packing. These are sustained by O—H⋯N(piperazine) hydrogen bonds, and are connected into the three-dimensional crystal structure by C—H⋯S and C—H⋯O interactions. The crystal studied was a racemic twin.

Related literature

For the biological activity of adamantyl derivatives, see: Vernier et al. (1969 ▶); El-Emam et al. (2004 ▶); Kadi et al. (2007 ▶, 2010 ▶); Al-Omar et al. (2010 ▶). For related adamantane structures, see: Al-Tamimi et al. (2010 ▶); Kadi et al. (2011 ▶).

Experimental

Crystal data

C₂₆H₃₆N₆OS
M _r = 480.67
Monoclinic,
a = 16.1006 (6) Å
b = 14.2182 (5) Å
c = 11.4641 (4) Å
β = 92.440 (4)°
V = 2622.00 (16) Å³
Z = 4
Mo Kα radiation
μ = 0.15 mm⁻¹
T = 100 K
0.25 × 0.20 × 0.15 mm

Data collection

Agilent SuperNova Dual diffractometer with Atlas detector
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T _min = 0.963, T _max = 0.977
12526 measured reflections
4840 independent reflections
4374 reflections with I > 2σ(I)
R _int = 0.036

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.100
S = 1.03
4840 reflections
312 parameters
3 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.18 e Å⁻³
Absolute structure: Flack (1983 ▶), with 1811 Friedel pairs
Flack parameter: 0.06 (7)

Data collection: CrysAlis PRO (Agilent, 2011 ▶); 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 DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812005107/hg5175sup1.cif

e-68-0o657-sup1.cif^{(25.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812005107/hg5175Isup2.hkl

e-68-0o657-Isup2.hkl^{(237.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812005107/hg5175Isup3.cml

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
O1—H1O⋯N6ⁱ	0.85 (1)	1.86 (1)	2.699 (3)	170 (5)
C13—H13B⋯S1ⁱⁱ	0.99	2.72	3.700 (2)	170
C22—H22⋯O1ⁱⁱⁱ	0.95	2.33	3.149 (3)	145

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

The financial support of the Deanship of Scientific Research and the Research Center of the College of Pharmacy, King Saud University is greatly appreciated. We also thank the Ministry of Higher Education (Malaysia) for funding structural studies through the High-Impact Research Scheme (grant No. UM.C/HIR/MOHE/SC/12).

supplementary crystallographic information

Comment

Derivatives of adamantane have long been known for their diverse biological activities including anti-viral activity against the influenza (Vernier et al., 1969) and HIV viruses (El-Emam et al., 2004). Moreover, adamantane derivative were recently reported to exhibit marked anti-bacterial and anti-inflammatory activities (Kadi et al., 2007, 2010). In continuation of our interest in the chemical and pharmacological properties of adamantane derivatives, and as a part of on-going structural studies of adamantane derivatives (Kadi et al., 2011; Al-Tamimi et al., 2010) we synthesized the title compound (I) as potential chemotherapeutic agent.

The structure determination of (I), Fig. 1, confirms the presence of the thione in the solid-state. The central 1,2,4-triazole ring is planar [r.m.s. deviation = 0.020 Å] and the benzene ring is twisted out of this plane [dihedral angle = 62.35 (12)°]. Globally, the plane of the five-membered ring bisects the adamantyl group with the benzene and piperazine substituents lying to one side.

In the crystal packing, supramolecular zigzag chains are formed via O—H···N(piperazine) hydrogen bonds, Fig. 2 and Table 1. These are connected into the three-dimensional crystal structure by C—H···S and C—H···O interactions, Fig. 3 and Table 1.

Experimental

A mixture of 709 mg (2 mmol) of 3-(1-adamantyl)-4-(4-hydroxybenzylideneamino)-4H-1,2,4-triazole-5-thiol (Al-Omar et al., 2010), 1-ethylpiperazine (228 mg, 2 mmol) and 37% formaldehyde solution (1 ml), in ethanol (8 ml) was heated under reflux for 15 min when 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 and the mixture was stirred for 20 min. The precipitated crude product were filtered, washed with water, dried, and crystallized from ethanol to yield 425 mg (44%) of the title compound (I) as colourless crystals. m.p. 436–438 K. ¹H NMR (CDCl₃): δ 1.18 (t, 3H, CH₃, J = 6.5 Hz), 1.69–1.76 (m, 6H, adamantane-H), 1.95 (s, 6H, adamantane-H), 2.03 (s, 3H, adamantane-H), 2.56 (q, 2H, CH₂CH₃, J = 6.5 Hz), 2.85–3.90 (m, 8H, piperazine-H), 5.18 (s, 2H, CH₂), 6.75 (d, 2H, Ar—H, J = 8.0 Hz), 7.67 (d, 2H, Ar—H, J = 8.0 Hz), 9.21 (s, 1H, CH═N). ¹³C NMR: δ 11.11 (CH₃), 27.84, 35.09, 36.48, 38.39 (adamantane-C), 49.50 (CH₂CH₃), 52.29, 58.43 (piperazine-C), 68.56 (CH₂), 116.53, 123.49, 130.87, 161.53 (Ar—C), 154.94 (triazole C-3), 163.34 (CH═N), 164.65 (C═ S).