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

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

doi:10.1107/S1600536813009495

. 2013 Apr 13;69(Pt 5):o695–o696. doi: 10.1107/S1600536813009495

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

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

PMCID: PMC3648232 PMID: 23723852

Abstract

In the title compound, C₂₅H₃₂F₃N₅S, two independent molecules comprise the asymmetric unit and are related across a pseudo-centre of inversion. The piperazine rings have chair conformations with each N-bound substituent occupying an equatorial position so that the dihedral angles between the planes of the triazole and benzene ring are 78.20 (19) and 79.10 (19)° for the two independent molecules, indicating that the molecules have an L-shape. In the crystal, a three-dimensional architecture is stabilized by C—H⋯π interactions. The crystal studied was an inversion twin with the fractional contribution of the minor component being 0.27 (9).

Related literature

For the diverse biological activities of adamantane derivatives, see: Al-Deeb et al. (2006 ▶); Al-Omar et al. (2010 ▶). For a related adamantanyl structure, see: El-Emam et al. (2012 ▶). graphic file with name e-69-0o695-scheme1.jpg

Experimental

Crystal data

C₂₅H₃₂F₃N₅S
M _r = 491.62
Orthorhombic,
a = 28.8100 (15) Å
b = 6.6052 (4) Å
c = 25.7717 (14) Å
V = 4904.2 (5) Å³
Z = 8
Mo Kα radiation
μ = 0.18 mm⁻¹
T = 295 K
0.40 × 0.30 × 0.20 mm

Data collection

Agilent SuperNova Dual diffractometer with an Atlas detector
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T _min = 0.878, T _max = 1.000
19420 measured reflections
9351 independent reflections
6701 reflections with I > 2σ(I)
R _int = 0.038

Refinement

R[F ² > 2σ(F ²)] = 0.058
wR(F ²) = 0.151
S = 1.03
9351 reflections
616 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.28 e Å⁻³
Absolute structure: Flack (1983 ▶), 3730 Friedel pairs
Flack parameter: 0.27 (9)

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 for Windows (Farrugia, 2012 ▶), QMol (Gans & Shalloway, 2001 ▶) and DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Click here for additional data file.^{(41.4KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813009495/hg5307sup1.cif

e-69-0o695-sup1.cif^{(41.4KB, cif)}

Click here for additional data file.^{(457.4KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813009495/hg5307Isup2.hkl

e-69-0o695-Isup2.hkl^{(457.4KB, hkl)}

Click here for additional data file.^{(9.9KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813009495/hg5307Isup3.cml

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

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

Cg1–Cg4 are the centroids of the N1–N3,C2,C3, C19–C24, N6–N8,C27,C28 and C44–C49 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C6—H6⋯Cg2ⁱ	0.98	2.95	3.817 (4)	148
C13—H13B⋯Cg3ⁱⁱ	0.97	2.86	3.782 (4)	158
C31—H31⋯Cg4ⁱⁱⁱ	0.98	2.94	3.873 (5)	159
C38—H38B⋯Cg1^iv	0.97	2.97	3.723 (5)	135
C45—H45⋯Cg2^v	0.93	2.97	3.708 (5)	137

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

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 (UM.C/HIR-MOHE/SC/03).

supplementary crystallographic information

Comment

In connection with the biological activities of adamantane derivatives (Al-Deeb et al., 2006; Al-Omar et al., 2010) and complementary structural studies (El-Emam et al., 2012), the title compound was synthesized and characterized, including by X-ray crystallography.

Two independent molecules comprise the crystallographic asymmetric unit of (I), Fig. 1. The molecules are related across a pseudo centre of inversion. As shown in Fig. 2, the best fit between the molecules occurs when the inverted S2-containing molecule is superimposed upon the S1-containing molecule. Each piperazinyl ring has a chair conformation with the respective N-bound methylene and benzene ring substituents in equatorial positions. With respect to the triazole ring, the piperazinyl ring lies completely to one side with the N2—N3—C14—N4 torsion angle being -58.5 (5)°; for the S2-containing molecule, the equivalent N7—N8—C39—N9 torsion angle is 63.9 (5)°. The dihedral angles between the triazole and benzene rings are 78.20 (19) and 79.10 (19)° for the S1- and S2-containing molecules, respectively, so that overall, each molecule approximates the shape of the letter L.

The crystal packing of (I) is dominated by C—H···π interactions, Table 1, where the triazole and benzene rings of both independent molecules function as the π-systems; the benzene ring of the S1-containing molecule is bifurcated. These interactions result in a three-dimensional architecture, Fig. 3.

Experimental

A mixture of 5-(adamantan-1-yl)-4-methyl-4H-1,2,4-triazole-3-thiol (499 mg, 2 mmol), 1-(3-trifluoromethylphenyl)piperazine (460 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 slowly added and the mixture was stirred for 20 min. The precipitated crude product were filtered, washed with water, dried, and crystallized from aqueous ethanol to yield 551 mg (56%) of the title compound as colourless crystals. M.pt: 459–461 K. Single crystals suitable for X-ray analysis were obtained by slow evaporation of its CHCl₃:EtOH solution (1:1, 5 ml) at room temperature. ¹H NMR (CDCl₃, 500.13 MHz): δ 1.76–1.84 (m, 6H, adamantane-H), 2.07 (s, 6H, adamantane-H), 2.13 (s, 3H, adamantane-H), 2.98 (s, 4H, piperazine-H), 3.24 (s, 4H, piperazine-H), 3.80 (s, 3H, CH₃), 5.19 (s, 2H, CH₂), 7.03–7.10 (m, 3H, Ar—H), 7.32–7.35 (m, 1H, Ar—H). ¹³C NMR (CDCl₃, 125.76 MHz): δ 27.82, 35.10, 36.29, 39.02 (adamantane-C), 33.98 (CH₃), 48.79, 50.21 (piperazine-C), 69.15 (CH₂), 112.33, 115.89, 118.83, 123.21, 125.38, 129.54, 151.38 (Ar—C & CF₃), 156.38 (triazole C-5), 169.58 (C═S).