3-(Adamantan-1-yl)-4-[(E)-(2,6-difluoro­benzyl­idene)amino]-1-[(4-phenyl­piperazin-1-yl)meth­yl]-1H-1,2,4-triazole-5(4H)-thione

Ali A El-Emam; Ebtehal S Al-Abdullah; Nasser R El-Brollosy; Seik Weng Ng; Edward R T Tiekink

doi:10.1107/S1600536812025135

. 2012 Jun 13;68(Pt 7):o2031. doi: 10.1107/S1600536812025135

3-(Adamantan-1-yl)-4-[(E)-(2,6-difluorobenzylidene)amino]-1-[(4-phenylpiperazin-1-yl)methyl]-1H-1,2,4-triazole-5(4H)-thione

Ali A El-Emam ^a,^‡, Ebtehal S Al-Abdullah ^a, Nasser R El-Brollosy ^a, Seik Weng Ng ^b,^c, Edward R T Tiekink ^b,^*

PMCID: PMC3393300 PMID: 22807857

Abstract

The imine residue [C=N = 1.268 (3) Å; conformation = E] is twisted [N—N—C—N = 87.8 (2)°] out of the plane (r.m.s. deviation = 0.016 Å) of the central 1,2,4-triazole ring in the title compound, C₃₀H₃₄F₂N₆S. A small twist also occurs between the imine and terminal benzene rings [N—C—C—C = −169.8 (2)°]. The piperazine ring (chair conformation) occupies a position almost normal to the central plane [N—N—C—N = 87.8 (2)°]. In the crystal, the molecules are consolidated into a three-dimensional architecture via C—H⋯S, C—H⋯π and π–π interactions, the latter between centrosymmetrically related difluorobenzene rings [inter-centroid distance = 3.9389 (18) Å].

Related literature

For a related structure and background to the biological activity of adamantane derivatives, see: El-Emam et al. (2012 ▶). For further synthetic details, see: Al-Omar et al. (2010 ▶).

Experimental

Crystal data

C₃₀H₃₄F₂N₆S
M _r = 548.69
Monoclinic,
a = 17.2712 (3) Å
b = 7.7141 (1) Å
c = 21.3157 (4) Å
β = 95.245 (2)°
V = 2828.04 (8) Å³
Z = 4
Cu Kα radiation
μ = 1.38 mm⁻¹
T = 294 K
0.35 × 0.30 × 0.25 mm

Data collection

Agilent SuperNova Dual diffractometer with Atlas detector
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012 ▶) T _min = 0.702, T _max = 1.000
20801 measured reflections
5884 independent reflections
4712 reflections with I > 2σ(I)
R _int = 0.027

Refinement

R[F ² > 2σ(F ²)] = 0.053
wR(F ²) = 0.161
S = 1.04
5884 reflections
352 parameters
H-atom parameters constrained
Δρ_max = 0.70 e Å⁻³
Δρ_min = −0.42 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2012 ▶); 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/S1600536812025135/hb6828sup1.cif

e-68-o2031-sup1.cif^{(27.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812025135/hb6828Isup2.hkl

e-68-o2031-Isup2.hkl^{(288.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812025135/hb6828Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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

Cg1 is the centroid of the C25–C30 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C20—H20B⋯S1ⁱ	0.97	2.86	3.397 (2)	116
C28—H28⋯Cg1ⁱⁱ	0.93	2.99	3.832 (3)	151

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

Acknowledgments

The financial support of the Research Center for Female Scientific and Medical Colleges, 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 (UM.C/HIR/MOHE/SC/12).

supplementary crystallographic information

Comment

In continuation to our interest in the chemical and pharmacological properties of adamantane derivatives, and as part of on-going structural studies (El-Emam et al., 2012), the title compound (I) was synthesized as potential chemotherapeutic agent (Al-Omar et al., 2010).

In (I), the central 1,2,4-triazole ring (r.m.s. deviation = 0.016 Å) is twisted with respect to the adjacent imine bond (1.268 (3) Å; conformation = E) as seen in the value of the C13—N1—N2—C11 torsion angle of 148.49 (19)°. There is a small twist between the latter and the connected benzene ring with the N1—C13—C14—C15 torsion angle being -169.8 (2)°. The piperazine ring (chair conformation) projects nearly normal to the central plane [N3—N4—C20—N5 = 87.8 (2)°].

Molecules are consolidated in the crystal packing by a combination of C—H···S and C—H···π interactions, Table 1, as well as weak π—π interactions between centrosymmetrically related C(14—C19) benzene rings [inter-centroid distance = 3.9389 (18) Å for 1 - x, 1 - y, 1 - z], Fig. 2.

Experimental

A mixture of the 5-(adamantan-1-yl)-4-(2,6-difluorobenzylideneamino)-4H-1,2,4-triazole-3-thiol (347 mg, 1 mmol), 1-phenylpiperazine (162 mg, 1 mmol) and 37% formaldehyde solution (0.5 ml), in ethanol (8 ml), was heated under reflux for 15 min. after which 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 a further 20 min. The precipitated crude product was filtered, washed with water, dried, and crystallized from ethanol to yield 434 mg (79%) of the title compound (I) as crystals. M.pt: 424–426 K. Light yellow prisms were obtained by slow evaporation of CHCl₃:EtOH (1:1; 5 ml) solution at room temperature. ¹H NMR (DMSO-d₆, 500.13 MHz): δ 1.80 (s, 6H, adamantane-H), 2.10 (s, 3H, adamantane-H), 2.19 (s, 6H, adamantane-H), 3.04 (s, 4H, piperazine-H), 3.23 (s, 4H, piperazine-H), 5.24 (s, 2H, CH₂), 6.89 (t, 1H, Ar—H, J = 7.0 Hz), 6.94 (d, 2H, Ar—H, J = 8.0 Hz), 7.03 (t. 2H, Ar—H, J = 8.5 Hz), 7.26–7.28 (m, 2H, Ar—H), 7.47–7.50 (m. 1H, Ar—H), 10.67 (s, 1H, CH=N). ¹³C NMR (DMSO-d₆, 125.76 MHz): δ 28.0, 35.56, 36.46, 38.37 (adamantane-C), 49.41, 50.55 (piperazine-C), 68.82 (CH₂), 110.76, 112.19, 116.31, 119.88, 129.10, 133.27, 151.38, 152.24 (Ar—C), 155.64, 161.06 (triazole C-5 & CH=N), 163.22 (C=S).