N-(4-Bromo­phen­yl)-2-[(1-cyclo­hexyl­meth­yl-1H-1,2,4-triazol-3-yl)sulfanyl]­acetamide

Yue-Ping Wang; Wan-Lu Yan; Qiong Guo; Yan-Ping He

doi:10.1107/S1600536812015991

. 2012 Apr 21;68(Pt 5):o1495. doi: 10.1107/S1600536812015991

N-(4-Bromophenyl)-2-[(1-cyclohexylmethyl-1H-1,2,4-triazol-3-yl)sulfanyl]acetamide

Yue-Ping Wang ^a, Wan-Lu Yan ^b,^*, Qiong Guo ^b, Yan-Ping He ^b

PMCID: PMC3344604 PMID: 22590366

Abstract

The title compound, C₁₇H₂₁BrN₄OS, was synthesized as a potential reverse transcriptase (RT) inhibitor of the human immunodeficiency virus type 1 (HIV-1). In the molecule, there is an N—H⋯S hydrogen bond making a five-membered ring. In the crystal, molecules are connected into centrosymmetric dimers via pairs of N—H⋯N and weak C—H⋯N hydrogen bonds. The crystal structure also features C—H⋯O interactions.

Related literature

The 1,2,4-triazole scaffold and its analogues are important pharmacophores that can be found in biologically active compounds across a number of different therapeutic areas, see: Lin et al. (2005 ▶); Naito et al. (1996 ▶); Sui et al. (1998 ▶); Tafi et al. (2002 ▶).

Experimental

Crystal data

C₁₇H₂₁BrN₄OS
M _r = 409.35
Triclinic,
a = 7.2061 (8) Å
b = 9.521 (1) Å
c = 14.2862 (16) Å
α = 104.132 (1)°
β = 90.804 (1)°
γ = 95.820 (1)°
V = 944.84 (18) Å³
Z = 2
Mo Kα radiation
μ = 2.30 mm⁻¹
T = 298 K
0.25 × 0.16 × 0.12 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1998 ▶) T _min = 0.597, T _max = 0.770
8793 measured reflections
4076 independent reflections
2644 reflections with I > 2σ(I)
R _int = 0.025

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.092
S = 1.01
4076 reflections
217 parameters
H-atom parameters constrained
Δρ_max = 0.34 e Å⁻³
Δρ_min = −0.42 e Å⁻³

Data collection: SMART (Bruker, 1998 ▶); cell refinement: SAINT (Bruker, 1998 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812015991/bq2348sup1.cif

e-68-o1495-sup1.cif^{(20.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812015991/bq2348Isup2.hkl

e-68-o1495-Isup2.hkl^{(199.7KB, hkl)}

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
N4—H4⋯S1	0.86	2.61	3.096 (2)	117
N4—H4⋯N1ⁱ	0.86	2.55	3.339 (3)	153
C1—H1⋯O1ⁱⁱ	0.93	2.29	3.214 (3)	171
C13—H13⋯N1ⁱ	0.93	2.48	3.342 (3)	153

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

Acknowledgments

This work was supported by the Fund for Fostering Talents of Kunming University of Science and Technology (grant No. 14118149) and the Natural Science Foundation of Yunnan Province (grant No. 619120090059 to YPW) and the Western Light Talent Culture Project of the Chinese Academy of Sciences (grant No. W8090303 to YPH).

supplementary crystallographic information

Comment

The 1,2,4-triazole scaffold and its analogues are important pharmacophores that can be found in biologically active compounds across a number of different therapeutic areas; these include antifungal (Tafi, et al., 2002), antibacterial (Sui, et al., 1998), antiasthmatic (Naito, et al., 1996) and anticancer activities (Lin, et al., 2005), etc. In the course of our search for new anti-HIV-1 agents, we have synthesized a new series of 1,2,4-triazole analogues, including the title compound, (I), as potential HIV-1 inhibitors.

The chemical structure of (I) is shown in Fig.1. The molecule is stabilized by a weak intramolecular N4—H4···S1 hydrogen bond (Table 1). The cyclohexyl ring adopts the lowest energy chair conformation. The torsion angle (C1—N3—C2—C3), which describes the arrangement between the cyclohexyl ring and the triazole moiety, is -112.1 (3) °; the torsion angle C12—N4—C11—O1, which characterizes the location of the CONH₂ group relative to the phenyl ring, is 3.5 (4) °.

In the crystal structure, centrosymmetric dimmers are formed by pairs of N4—H4···N1ⁱ and C13—H13···N1ⁱ hydrogen bonds [symmetry code: (i) -x + 1, -y + 2,-z + 1]. These dimmers are further linked into chains by weak C—H···O interactions (Table 1, Fig.2).

Experimental

To a stirred solution of 2-((1H-1,2,4-triazol-3-yl)thio)-N-(4-bromophenyl)acetamide (3.12 g, 10 mmol) in anhydrous EtOH (75 ml) was added K₂CO₃ (1.38 g, 0.01 mol) under a nitrogen atmosphere. The mixture was stirred at 298 K for 15 min, then (bromomethyl)cyclohexane (0.53 g, 0.03 mol) was added, and the reaction mixture was refluxed for 8 h under a nitrogen atmosphere. The reaction mixture was poured into cold H₂O (80 ml), then the aqueous phase was extracted with EtOAc (3×50 ml). The combined organic layer was washed with H₂O (3×50 ml), dried (Mg₂SO₄), filtered and concentrated in vacuo to give the crude product, which was purified by chromatography (eluent EtOAc/PE 100:25) to afford the title compound (yield: 23%; m.p. 398.7–398.9 K). Single crystals of (I) suitable for X-ray diffraction were grown from a solution in EtOAc by slow evaporation. The product was characterized by IR, MS, ¹H NMR and ¹³C NMR.