3-(Adamantan-1-yl)-4-methyl-1-({4-[3-
(trifluoromethyl)phenyl]piperazin-1-yl}-methyl)-4,5-dihydro-1
H
-1,2,4-triazole-5-thione
Ali A. El-Emam,a‡ Abdul-Malek S. Al-Tamimi,bKhalid A. Alrashood,aSeik Weng Ngc,dand Edward R. T. Tiekinkc*
aDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud
University, Riyadh 11451, Saudi Arabia,bDepartment of Pharmaceutical Chemistry,
College of Pharmacy, Salman bin Abdulaziz University, Alkharj 11942, Saudi Arabia,
cDepartment of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia,
anddChemistry Department, Faculty of Science, King Abdulaziz University, PO Box
80203 Jeddah, Saudi Arabia
Correspondence e-mail: edward.tiekink@gmail.com
Received 8 April 2013; accepted 8 April 2013
Key indicators: single-crystal X-ray study;T= 295 K; mean(C–C) = 0.006 A˚;
Rfactor = 0.058;wRfactor = 0.151; data-to-parameter ratio = 15.2.
In the title compound, C25H32F3N5S, two independent
mol-ecules 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 inter-actions. 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-Deebet al.(2006); Al-Omaret al.(2010). For a related adamantanyl structure, see: El-Emamet al.(2012).
Experimental
Crystal data
C25H32F3N5S
Mr= 491.62
Orthorhombic,Pna21
a= 28.8100 (15) A˚
b= 6.6052 (4) A˚
c= 25.7717 (14) A˚
V= 4904.2 (5) A˚3
Z= 8
MoKradiation
= 0.18 mm1
T= 295 K
0.400.300.20 mm
Data collection
Agilent SuperNova Dual diffractometer with an Atlas detector
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)
Tmin= 0.878,Tmax= 1.000
19420 measured reflections 9351 independent reflections 6701 reflections withI> 2(I)
Rint= 0.038
Refinement
R[F2> 2(F2)] = 0.058
wR(F2) = 0.151
S= 1.03 9351 reflections 616 parameters 1 restraint
H-atom parameters constrained
max= 0.37 e A˚
3
min=0.28 e A˚
3
Absolute structure: Flack (1983), 3730 Friedel pairs
[image:1.610.313.565.530.596.2]Flack parameter: 0.27 (9)
Table 1
Hydrogen-bond geometry (A˚ ,).
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 Cg1iv
0.97 2.97 3.723 (5) 135 C45—H45 Cg2v 0.93 2.97 3.708 (5) 137 Symmetry codes: (i)xþ1
2;y 1
2;z; (ii)xþ 1 2;yþ
1
2;z; (iii)xþ1;y;z 1 2; (iv)
xþ1;yþ1;z1 2; (v)xþ
1 2;yþ
1 2;zþ
1 2.
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).
The financial support of the Deanship of Scientific Research Acta Crystallographica Section E
Structure Reports
Online
Ministry of Higher Education (Malaysia) for funding struc-tural studies through the High-Impact Research scheme (UM.C/HIR-MOHE/SC/03).
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HG5307).
References
Agilent (2011).CrysAlis PRO. Agilent Technologies, Yarnton, England.
Al-Deeb, O. A., Al-Omar, M. A., El-Brollosy, N. R., Habib, E. E., Ibrahim, T. M. & El-Emam, A. A. (2006).Arzneim. Forsch. Drug. Res.56, 40–47. Al-Omar, M. A., Al-Abdullah, E. S., Shehata, I. A., Habib, E. E., Ibrahim,
T. M. & El-Emam, A. A. (2010).Molecules,15, 2526–2550.
Brandenburg, K. (2006).DIAMOND. Crystal Impact GbR, Bonn, Germany. El-Emam, A. A., Al-Omar, M. A., Al-Tamimi, A.-M. S., Ng, S. W. & Tiekink,
E. R. T. (2012).Acta Cryst.E68, o1772–o1773. Farrugia, L. J. (2012).J. Appl. Cryst.45, 849–854. Flack, H. D. (1983).Acta Cryst.A39, 876–881.
Gans, J. & Shalloway, D. (2001).J. Mol. Graph. Model.19, 557–559. Sheldrick, G. M. (2008).Acta Cryst.A64, 112–122.
supporting information
Acta Cryst. (2013). E69, o695–o696 [https://doi.org/10.1107/S1600536813009495]
3-(Adamantan-1-yl)-4-methyl-1-({4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}methyl)-4,5-dihydro-1
H
-1,2,4-triazole-5-thione
Ali A. El-Emam, Abdul-Malek S. Al-Tamimi, Khalid A. Alrashood, Seik Weng Ng and Edward R. T.
Tiekink
S1. 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-S2-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.
S2. 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
S3. Refinement
The H-atoms were placed in calculated positions [and C—H = 0.93 to 0.98 Å, Uiso(H) = 1.2–1.5Ueq(C)] and were
[image:4.610.134.475.141.502.2]included in the refinement in the riding model approximation. The crystal is an inversion twin with the fractional contribution of the minor component being 0.27 (9).
Figure 1
Figure 2
Figure 3
View of the unit-cell contents in projection down the b axis of (I). The C—H···π contacts are shown as purple dashed lines.
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
Crystal data
C25H32F3N5S
Mr = 491.62
Orthorhombic, Pna21
Hall symbol: P 2c -2n
a = 28.8100 (15) Å
b = 6.6052 (4) Å
c = 25.7717 (14) Å
V = 4904.2 (5) Å3
Z = 8
F(000) = 2080
Dx = 1.332 Mg m−3
Mo Kα radiation, λ = 0.71073 Å Cell parameters from 4723 reflections
θ = 2.9–27.5°
µ = 0.18 mm−1
T = 295 K Prism, colourless 0.40 × 0.30 × 0.20 mm
Data collection
Agilent SuperNova Dual
diffractometer with an Atlas detector Radiation source: SuperNova (Mo) X-ray
Source
Mirror monochromator
Detector resolution: 10.4041 pixels mm-1
ω scan
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)
19420 measured reflections 9351 independent reflections 6701 reflections with I > 2σ(I)
Rint = 0.038
θmax = 27.6°, θmin = 2.9°
h = −28→37
k = −8→6
l = −27→33
Refinement
Refinement on F2
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.058
wR(F2) = 0.151
S = 1.03 9351 reflections 616 parameters 1 restraint
Primary atom site location: structure-invariant direct methods
Secondary atom site location: difference Fourier map
Hydrogen site location: inferred from neighbouring sites
H-atom parameters constrained
w = 1/[σ2(F
o2) + (0.0676P)2 + 1.2433P]
where P = (Fo2 + 2Fc2)/3
(Δ/σ)max = 0.001
Δρmax = 0.37 e Å−3
Δρmin = −0.28 e Å−3
Absolute structure: Flack (1983), 3730 Friedel pairs
Absolute structure parameter: 0.27 (9)
Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2,
conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used
only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2
are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x y z Uiso*/Ueq
C42 0.50745 (15) −0.1556 (6) 0.41217 (17) 0.0639 (11) H42A 0.4910 −0.2022 0.4428 0.077* H42B 0.5289 −0.2610 0.4018 0.077* C43 0.47310 (14) −0.1184 (6) 0.36896 (17) 0.0616 (10) H43A 0.4895 −0.0819 0.3374 0.074* H43B 0.4555 −0.2408 0.3623 0.074* C44 0.57378 (12) 0.0090 (5) 0.45413 (13) 0.0466 (8) C45 0.60424 (14) −0.1533 (7) 0.44725 (15) 0.0598 (10) H45 0.5962 −0.2562 0.4243 0.072* C46 0.64559 (15) −0.1659 (7) 0.47321 (16) 0.0683 (12) H46 0.6651 −0.2755 0.4670 0.082* C47 0.65905 (15) −0.0202 (7) 0.50823 (17) 0.0679 (12) H47 0.6870 −0.0298 0.5261 0.082* C48 0.62912 (12) 0.1419 (6) 0.51580 (14) 0.0524 (9) C49 0.58751 (12) 0.1560 (6) 0.49019 (13) 0.0499 (9) H49 0.5680 0.2652 0.4969 0.060* C50 0.64274 (15) 0.2985 (7) 0.55468 (18) 0.0658 (11)
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
C10 0.058 (2) 0.060 (2) 0.075 (3) 0.022 (2) 0.017 (2) 0.019 (2) C11 0.066 (2) 0.060 (2) 0.083 (3) 0.029 (2) 0.023 (2) 0.012 (2) C12 0.074 (3) 0.067 (3) 0.091 (4) −0.007 (3) 0.031 (3) −0.029 (3) C13 0.0418 (18) 0.109 (4) 0.071 (3) 0.012 (2) 0.012 (2) 0.006 (3) C14 0.0447 (18) 0.087 (3) 0.048 (2) 0.001 (2) 0.0070 (17) 0.016 (2) C15 0.058 (2) 0.069 (2) 0.0442 (19) 0.016 (2) −0.0020 (18) −0.0016 (19) C16 0.057 (2) 0.067 (2) 0.055 (2) 0.012 (2) −0.0048 (18) −0.006 (2) C17 0.059 (2) 0.056 (2) 0.077 (3) −0.006 (2) −0.007 (2) 0.011 (2) C18 0.063 (2) 0.055 (2) 0.064 (2) −0.002 (2) −0.008 (2) −0.001 (2) C19 0.0498 (18) 0.054 (2) 0.0357 (17) 0.0056 (17) 0.0058 (15) 0.0063 (16) C20 0.062 (2) 0.071 (2) 0.045 (2) 0.018 (2) −0.0023 (18) −0.0123 (19) C21 0.075 (3) 0.087 (3) 0.063 (3) 0.036 (3) −0.008 (2) −0.010 (2) C22 0.061 (2) 0.103 (3) 0.047 (2) 0.027 (3) −0.007 (2) 0.001 (2) C23 0.0509 (18) 0.064 (2) 0.0378 (17) 0.0008 (19) 0.0024 (15) 0.0036 (17) C24 0.0486 (17) 0.0510 (19) 0.044 (2) 0.0026 (17) 0.0028 (16) 0.0032 (17) C25 0.0488 (19) 0.075 (3) 0.065 (3) 0.003 (2) −0.005 (2) −0.002 (2) C26 0.071 (2) 0.053 (2) 0.072 (3) 0.008 (2) 0.012 (2) 0.003 (2) C27 0.0356 (15) 0.0478 (18) 0.0411 (17) −0.0002 (16) −0.0042 (14) 0.0005 (15) C28 0.0376 (16) 0.067 (2) 0.0410 (18) −0.0030 (18) −0.0015 (14) −0.0073 (18) C29 0.0352 (14) 0.0461 (17) 0.0395 (17) −0.0078 (15) 0.0025 (14) −0.0009 (15) C30 0.0486 (17) 0.064 (2) 0.046 (2) −0.0010 (18) −0.0008 (16) −0.0075 (18) C31 0.072 (2) 0.088 (3) 0.044 (2) 0.006 (3) −0.002 (2) −0.012 (2) C32 0.102 (3) 0.075 (3) 0.057 (3) 0.013 (3) 0.035 (3) 0.010 (2) C33 0.070 (3) 0.067 (3) 0.094 (4) −0.032 (2) 0.038 (3) −0.016 (3) C34 0.062 (2) 0.065 (3) 0.070 (3) −0.022 (2) 0.016 (2) −0.019 (2) C35 0.058 (2) 0.068 (3) 0.059 (2) 0.021 (2) 0.0180 (19) 0.014 (2) C36 0.056 (2) 0.063 (2) 0.073 (3) 0.017 (2) 0.020 (2) 0.003 (2) C37 0.080 (3) 0.065 (2) 0.065 (3) −0.003 (2) 0.022 (2) −0.017 (2) C38 0.0426 (19) 0.125 (4) 0.086 (3) −0.006 (3) 0.021 (2) −0.014 (3) C39 0.0468 (19) 0.102 (3) 0.048 (2) 0.005 (2) 0.0094 (17) 0.021 (2) C40 0.061 (2) 0.068 (2) 0.046 (2) 0.021 (2) −0.0017 (18) −0.004 (2) C41 0.060 (2) 0.077 (3) 0.048 (2) 0.026 (2) −0.0053 (18) −0.012 (2) C42 0.065 (2) 0.056 (2) 0.070 (3) −0.003 (2) −0.003 (2) 0.012 (2) C43 0.060 (2) 0.065 (2) 0.059 (2) −0.002 (2) −0.0061 (19) 0.001 (2) C44 0.0502 (19) 0.055 (2) 0.0349 (16) 0.0071 (18) 0.0105 (14) 0.0031 (15) C45 0.065 (2) 0.066 (2) 0.048 (2) 0.020 (2) 0.0000 (18) −0.0140 (18) C46 0.066 (2) 0.080 (3) 0.059 (2) 0.031 (2) −0.003 (2) −0.013 (2) C47 0.060 (2) 0.087 (3) 0.057 (2) 0.022 (2) −0.004 (2) −0.012 (2) C48 0.0524 (18) 0.062 (2) 0.0427 (19) 0.0056 (19) −0.0013 (16) −0.0028 (17) C49 0.0551 (19) 0.052 (2) 0.0424 (19) 0.0124 (18) 0.0083 (16) 0.0015 (16) C50 0.066 (3) 0.070 (3) 0.061 (3) 0.005 (2) −0.005 (2) −0.010 (2)
Geometric parameters (Å, º)
C8—H8 0.9800 C40—H40B 0.9700 C9—H9A 0.9700 C41—H41A 0.9700 C9—H9B 0.9700 C41—H41B 0.9700 C10—C11 1.540 (6) C42—C43 1.510 (6) C10—H10A 0.9700 C42—H42A 0.9700 C10—H10B 0.9700 C42—H42B 0.9700 C11—C12 1.505 (7) C43—H43A 0.9700 C11—C13 1.516 (6) C43—H43B 0.9700 C11—H11 0.9800 C44—C45 1.397 (5) C12—H12A 0.9700 C44—C49 1.400 (5) C12—H12B 0.9700 C45—C46 1.369 (6) C13—H13A 0.9700 C45—H45 0.9300 C13—H13B 0.9700 C46—C47 1.375 (6) C14—H14A 0.9700 C46—H46 0.9300 C14—H14B 0.9700 C47—C48 1.388 (6) C15—C16 1.520 (5) C47—H47 0.9300 C15—H15A 0.9700 C48—C49 1.372 (5) C15—H15B 0.9700 C48—C50 1.493 (6) C16—H16A 0.9700 C49—H49 0.9300
C17—C18—H18A 109.9 C46—C47—C48 117.2 (4) N4—C18—H18B 109.9 C46—C47—H47 121.4 C17—C18—H18B 109.9 C48—C47—H47 121.4 H18A—C18—H18B 108.3 C49—C48—C47 121.8 (4) C20—C19—C24 116.6 (3) C49—C48—C50 120.4 (4) C20—C19—N5 120.8 (3) C47—C48—C50 117.7 (3) C24—C19—N5 122.4 (3) C48—C49—C44 121.3 (3) C21—C20—C19 121.2 (4) C48—C49—H49 119.4 C21—C20—H20 119.4 C44—C49—H49 119.4 C19—C20—H20 119.4 F6—C50—F5 103.8 (4) C22—C21—C20 121.7 (4) F6—C50—F4 106.4 (4) C22—C21—H21 119.1 F5—C50—F4 106.8 (4) C20—C21—H21 119.1 F6—C50—C48 112.4 (4) C21—C22—C23 118.0 (4) F5—C50—C48 113.0 (4) C21—C22—H22 121.0 F4—C50—C48 113.8 (4)
C24—C23—C25—F1 98.6 (5) C47—C48—C50—F5 46.2 (6) C22—C23—C25—F2 158.9 (5) C49—C48—C50—F4 −14.2 (6) C24—C23—C25—F2 −22.0 (7) C47—C48—C50—F4 168.2 (4)
Hydrogen-bond geometry (Å, º)
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···Cg1iv 0.97 2.97 3.723 (5) 135
C45—H45···Cg2v 0.93 2.97 3.708 (5) 137
