4-(3-Chloro­phen­yl)-3-[(2,6-difluoro­benz­yl)sulfan­yl]-5-(3,4,5-trimeth­oxy­phen­yl)-4H-1,2,4-triazole

Hoong-Kun Fun; Safra Izuani Jama Asik; B Chandrakantha; Arun M Isloor; Prakash Shetty

doi:10.1107/S1600536811048653

. 2011 Nov 25;67(Pt 12):o3422–o3423. doi: 10.1107/S1600536811048653

4-(3-Chlorophenyl)-3-[(2,6-difluorobenzyl)sulfanyl]-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole

Hoong-Kun Fun ^a,^*,^‡, Safra Izuani Jama Asik ^a, B Chandrakantha ^b, Arun M Isloor ^c, Prakash Shetty ^d

PMCID: PMC3239058 PMID: 22199906

Abstract

In the title compound, C₂₄H₂₀ClF₂N₃O₃S, the essentially planar triazole ring (r.m.s. deviation = 0.001 Å) forms dihedral angles of 22.35 (10), 68.17 (10) and 42.01 (10)° with the mean planes of the trimethoxyphenyl, chlorophenyl and difluorophenyl rings, respectively. A weak intramolecular C—H⋯π interaction occurs. In the crystal, molecules are linked into sheets lying parallel to the bc plane by C—H⋯O and C—H⋯N hydrogen bonds. The crystal packing also features weak C—H⋯π interactions.

Related literature

For the pharmacological activity of [1,2,4] triazole derivatives, see: Zhou et al. (2007 ▶); Chen et al. (2007 ▶); Isloor et al. (2010 ▶); Kalluraya et al. (2004 ▶); Sunil et al. (2009 ▶); Chandrakantha et al. (2010 ▶). For stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₂₄H₂₀ClF₂N₃O₃S
M _r = 503.94
Monoclinic,
a = 9.9867 (2) Å
b = 21.5140 (3) Å
c = 11.9793 (2) Å
β = 117.197 (1)°
V = 2289.24 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.31 mm⁻¹
T = 100 K
0.36 × 0.17 × 0.11 mm

Data collection

Bruker SMART APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.896, T _max = 0.968
26235 measured reflections
6681 independent reflections
5130 reflections with I > 2σ(I)
R _int = 0.039

Refinement

R[F ² > 2σ(F ²)] = 0.049
wR(F ²) = 0.110
S = 1.03
6681 reflections
310 parameters
H-atom parameters constrained
Δρ_max = 0.43 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811048653/hb6503sup1.cif

e-67-o3422-sup1.cif^{(23.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811048653/hb6503Isup2.hkl

e-67-o3422-Isup2.hkl^{(327KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811048653/hb6503Isup3.cml

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

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

Cg2 and Cg3 are the centroids of the C1–C6 and C9–C14 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C11—H11A⋯O2ⁱ	0.95	2.43	3.353 (2)	165
C15—H15B⋯O3ⁱⁱ	0.99	2.54	3.281 (2)	132
C24—H24A⋯N2ⁱⁱⁱ	0.98	2.49	3.189 (2)	128
C20—H20A⋯Cg2^iv	0.95	2.66	3.543 (2)	154
C1—H1A⋯Cg3	0.95	2.85	3.6138 (19)	138

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

Acknowledgments

HKF and SIJA thank the Malaysian Government and Universiti Sains Malaysia for the Research University Grants (Nos.1001/PFIZIK/811160 and 1001/PFIZIK/ 811151). AMI thanks the Board for Research in Nuclear Sciences, Department of Atomic Energy, and the Government of India for the Young Scientist award.

supplementary crystallographic information

Comment

During the last few decades, a considerable attention has been devoted to the synthesis of [1, 2, 4] triazole derivatives possessing such diverse pharmacological properties as antimicrobial, anti-inflammatory (Zhou et al., 2007), analgesic antitumorial, antihypertensive (Chen et al., 2007), anticonvulsant and antiviral activities (Isloor et al., 2010). Some 1, 2, 4-triazoles are used as DNA cleaving agents and potassium channel activators. Introduction of fluorine atom in these compounds could alter the course of the pharmacological activities (Kalluraya et al., 2004). In particular, introduction of diflurophenyl substituted group in the moiety immensely increases the pharmacological as well liphophilicity effectiveness (Sunil et al., 2009). It is also observed that the amino and mercapto groups in triazoles are readily accessible nucleophilic centers (Chandrakantha et al., 2010).

In the title compound of (I), (Fig. 1), the triazole (N1–N3/C7/C8) ring is essentially planar, with maximum deviation of 0.001 Å for C1 and N2. The dihedral angles between triazole ring and the mean plane of trimethoxyphenyl (C1–C6/C22–C24/O1–O3), chlorophenyl (C9–C14/Cl1), and difluorophenyl groups (C16–C21/F1–F2) are 22.35 (10), 68.17 (10) and 42.01 (10)° respectively.

In the crystal structure of (Fig. 2), the molecules are linked into two-dimensional network parallel to bc plane by C11—H11A···O2, C15—H15B···O3 and C24—H24A···N2 hydrogen bonds. The crystal packing is further stabilized by weak C—H···π interactions (Table 1) with distances of 3.543 (2) and 3.6138 (19) A.

Experimental

To a solution of 4-(3-chloro phenyl)-5-(3,4,5-trimethoxy phenyl) -4H-1,2,4-triazole-3-thiol (1 g, 0.0026 mol) in dry acetonitrile (20 ml) was added potassium carbonate (0.73 g, 0.0053 mol) followed by 2,6-difluorobenzyl bromide (0.58 g, 0.0029 mol) at RT. After the addition, the reaction mixture was stirred at RT for 6h. Reaction mixture was monitored by TLC. After the completion, the reaction mixture was concentrated and purified by column chromatography using pet ether, ethyl acetate as an eluent to afford title compound as colorless solid. Yield: 1.1 g, 84%. M.p. 450-453 K.