(E)-4-[(4-Fluoro­benzyl­idene)amino]-3-[1-(4-isobutyl­phen­yl)eth­yl]-1-(morpholino­meth­yl)-1H-1,2,4-triazole-5(4H)-thione methanol hemisolvate

Jia Hao Goh; Hoong-Kun Fun; A C Vinayaka; B Kalluraya

doi:10.1107/S1600536810015217

. 2010 Apr 30;66(Pt 5):o1233–o1234. doi: 10.1107/S1600536810015217

(E)-4-[(4-Fluorobenzylidene)amino]-3-[1-(4-isobutylphenyl)ethyl]-1-(morpholinomethyl)-1H-1,2,4-triazole-5(4H)-thione methanol hemisolvate

Jia Hao Goh ^a,^‡, Hoong-Kun Fun ^a,^*,^§, A C Vinayaka ^b, B Kalluraya ^b

PMCID: PMC2979111 PMID: 21579255

Abstract

In the title compound, C₂₆H₃₂FN₅OS·0.5CH₄O, the methyl group of the methanol solvent molecule is disordered over two sites with equal occupancies and the solvent is further disordered about a crystallographic twofold rotation axis. The organic molecule exists in a trans configuration with respect to the acyclic C=N bond. An intramolecular C—H⋯S hydrogen bond generates an S(6) ring motif. The morpholine ring adopts a chair conformation. The essentially planar 1,2,4-triazole ring [maximum deviation = 0.013 (2) Å] forms dihedral angles of 11.21 (10) and 67.53 (11)°, respectively, with the fluorophenyl unit and the isobutyl-substituted benzene ring. The crystal structure is stabilized by a weak intermolecular C—H⋯π interaction.

Related literature

For general background to and applications of 1,2,4-triazole derivatives, see: Calhoun et al. (1995 ▶); Pandeya et al. (1999 ▶, 2000 ▶); Sujith et al. (2009 ▶). For graph-set descriptions of hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For closely related structures, see: Goh et al. (2010a ▶,b ▶). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₂₆H₃₂FN₅OS·0.5CH₄O
M _r = 497.65
Monoclinic,
a = 40.186 (3) Å
b = 4.7840 (3) Å
c = 30.073 (2) Å
β = 116.112 (2)°
V = 5191.5 (6) Å³
Z = 8
Mo Kα radiation
μ = 0.16 mm⁻¹
T = 100 K
0.31 × 0.16 × 0.06 mm

Data collection

Bruker APEXII DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.951, T _max = 0.990
24705 measured reflections
5921 independent reflections
4378 reflections with I > 2σ(I)
R _int = 0.056

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.149
S = 1.04
5921 reflections
337 parameters
H-atom parameters constrained
Δρ_max = 0.63 e Å⁻³
Δρ_min = −0.22 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 datablocks global, I. DOI: 10.1107/S1600536810015217/lh5026sup1.cif

e-66-o1233-sup1.cif^{(27.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810015217/lh5026Isup2.hkl

e-66-o1233-Isup2.hkl^{(290KB, hkl)}

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

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

Cg1 is the centroid of the 1,2,4-triazole ring (N2/C8/N3/N4/C9).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H7A⋯S1	0.93	2.51	3.221 (2)	133
C22—H22A⋯Cg1ⁱ	0.97	2.64	3.492 (2)	146

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank Universiti Sains Malaysia (USM) for the Research University Golden Goose grant (No. 1001/PFIZIK/811012). JHG also thanks USM for the award of a USM fellowship.

supplementary crystallographic information

Comment

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used. Despite their large therapeutic applications, they have several undesired, often serious side effects (Calhoun et al., 1995). Therefore, long term administration is not advisable. The need for new anti-inflammatory drugs is obvious and accordingly, there have been renewed interest in anti-inflammatory agents endowed with potent biological activity. In this context, it has been shown that some Mannich bases find applications as anti-inflammatory, analgesic agents (Sujith et al., 2009) and anti-microbial properties (Pandeya et al., 1999, 2000).

The asymmetric unit of the title 1,2,4-triazole compound (Fig. 1) comprises of a (E)-4-[(4-fluorobenzylidene)amino]-3-[1-(4-isobutylphenyl)ethyl] -1-(morpholinomethyl)-1H-1,2,4-triazole-5(4H)-thione molecule and a methanol molecule of crystallization, which is partially occupied with a fixed occupancy of 0.5. The atom C27 of the methanol solvent molecule is disordered over two sites with an equal occupancy of 0.25. Both the disordered components are further disordered over a crystallographic two-fold rotation [symmetry code to generate equivalent atoms: -x, y, -z + 1/2]. The main molecule exists in an E configuration with respect to the acyclic C7═N1 double bond [bond length of C7═N1 = 1.276 (2) Å and torsion angle of C6–C7–N1–N2 of 176.41 (16)°]. An intramolecular C7—H7A···S1 hydrogen bond generates a six-membered ring, producing an S(6) ring motif (Bernstein et al., 1995). The morpholino unit adopts a chair conformation, with puckering parameters of Q = 0.580 (2) Å, θ = 178.2 (2)° and φ = 126 (6)°. The 1,2,4-triazole ring (N2/C8/N3/N4/C9) is essentially planar, with maximum deviation of -0.013 (2) Å for atom N2. The 1,2,4-triazole ring is inclined at dihedral angles of 11.21 (10) and 67.53 (11)°, respectively, with fluorophenyl group (C1-C6/F1) and isobutyl-substituted benzene ring (C11-C16). The bond lengths and angles are consistent to those observed in closely related structures (Goh et al., 2010a,b).

In the crystal structure, no significant intermolecular hydrogen bonds are observed. The crystal structure is stabilized by a weak intermolecular C22—H22A···Cg1 interactions (Table 1) involving the 1,2,4-triazole ring.

Experimental

A mixture of Schiff base (0.01 mol) and formaldehyde (40 %, 2 ml) in ethanol (15 ml) was taken to this solution morpholine (0.01 mol) was added. The reaction mixture was stirred at room temperature for two days. The solid product obtained was collected by filtration, washed with ethanol and dried. Colourless single crystals suitable for X-ray analysis were obtained from a 1:2 mixture of N,N-dimethylformamide and methanol by slow evaporation.