5-(4,4′′-Difluoro-5′-hy­droxy-1,1′:3′,1′′-terphenyl-4′-yl)-3-(morpholin-4-ylmeth­yl)-1,3,4-oxadiazole-2(3H)-thione

Hoong-Kun Fun; Suhana Arshad; S Samshuddin; B Narayana; B K Sarojini

doi:10.1107/S1600536811048471

. 2011 Nov 19;67(Pt 12):o3372. doi: 10.1107/S1600536811048471

5-(4,4′′-Difluoro-5′-hydroxy-1,1′:3′,1′′-terphenyl-4′-yl)-3-(morpholin-4-ylmethyl)-1,3,4-oxadiazole-2(3H)-thione

Hoong-Kun Fun ^a,^*,^‡, Suhana Arshad ^a, S Samshuddin ^b, B Narayana ^b, B K Sarojini ^c

PMCID: PMC3239015 PMID: 22199864

Abstract

In the title compound, C₂₅H₂₁F₂N₃O₃S, the morpholine ring adopts a chair conformation. The 1,3,4-oxadiazole-2(3H)-thione group makes dihedral angles of 78.69 (8), 53.56 (7) and 55.30 (9)° with the benzene rings. In the crystal, O—H⋯O, C—H⋯S and C—H⋯F hydrogen bonds linked the molecules into layers lying parallel to the ab plane. Weak C—H⋯π interactions also occur.

Related literature

For pharmacological background, see: Bhatia & Gupta (2011 ▶); Liu (2006 ▶). For ring conformations, see: Cremer & Pople (1975 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₂₅H₂₁F₂N₃O₃S
M _r = 481.51
Monoclinic,
a = 16.0547 (14) Å
b = 11.4125 (11) Å
c = 25.364 (2) Å
β = 94.202 (2)°
V = 4634.9 (7) Å³
Z = 8
Mo Kα radiation
μ = 0.19 mm⁻¹
T = 296 K
0.48 × 0.25 × 0.17 mm

Data collection

Bruker SMART APEXII DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.916, T _max = 0.969
23057 measured reflections
6182 independent reflections
4139 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.143
S = 1.03
6182 reflections
311 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.24 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/S1600536811048471/hb6502sup1.cif

e-67-o3372-sup1.cif^{(23.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811048471/hb6502Isup2.hkl

e-67-o3372-Isup2.hkl^{(302.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811048471/hb6502Isup3.cml

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

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

Cg1 is the centroid of the C7–C12 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H1O3⋯O2ⁱ	0.79 (2)	1.95 (2)	2.728 (2)	167 (2)
C5—H5A⋯S1ⁱⁱ	0.93	2.80	3.639 (2)	151
C12—H12A⋯F1ⁱⁱⁱ	0.93	2.47	3.292 (2)	148
C23—H23A⋯F1^iv	0.97	2.51	3.462 (3)	167
C1—H1A⋯Cg1^v	0.93	2.91	3.414 (2)	115

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

Acknowledgments

HKF and SA thank Universiti Sains Malaysia (USM) for the Research University Grant (1001/PFIZIK/811160). SA thanks the Malaysian Government and USM for the Academic Staff Training Scheme (ASTS) award. BN thanks the UGC for financial assistance through an SAP and BSR one-time grant for the purchase of chemicals. SS thanks Mangalore University for research facilities.

supplementary crystallographic information

Comment

Substituted 1,3,4-oxadiazoles are of considerable pharmaceutical interest. For a recent review, see: Bhatia & Gupta (2011). Polysubstituted aromatics such as terphenyls exhibit considerable biological properties, e.g., potent anticoagulant, immunosuppressants, antithrombotic, neuroprotective, specific 5-lipoxygenase inhibitory and cytotoxic activities (Liu, 2006). Encouraged by these diverse biological activities of 1,3,4-oxadiazoles and terphenyls, our research group has decided to prepare terphenyl derivative bearing the oxadiazole moiety, thus bringing both types of functional groups together in a single molecule: we now report the synthesis and structure of the title compound, (I). The precursor of the title compound was prepared from 4,4'-difluorochalcone by several steps.

The molecular structure is shown in Fig. 1. The morpholine ring adopts a chair conformation with puckering parameters Q= 0.579 (2) Å, Θ= 2.9 (2)° and φ= 247 (5)° (Cremer & Pople, 1975). The 1,3,4-oxadiazole-2(3H)-thione (S1/C20/O1/C19/N1/N2) group makes dihedral angles of 78.69 (8), 53.56 (7) and 55.30 (9) ° with the benzene (C1–C6, C7–C12 & C13–C18) rings, respectively. Bond lengths (Allen et al., 1987) and angles are within normal ranges.

The crystal packing is shown in Fig. 2. Intermolecular O3—H1O3···O2, C5—H5A···S1, C12—H12A···F1 and C23—H23A···F1 hydrogen bonds (Table 1) linked the molecules into layers parallel to ab plane. C—H···π interactions (Table 1) which involves C1 and phenyl ring (Cg1 = C7–C12) further stabilize the crystal structure.

Experimental

To a solution of 5-(4,4''-difluoro-5'-hydroxy-1,1':3',1''-terphenyl-4'-yl) -1,3,4-oxadiazole-2(3H)-thione (3.82 g, 0.01 mol) in ethanol (5 ml) was added formaldehyde (0.5 ml, 37%) and morpholine (0.01 mol). The reaction mixture was stirred overnight. After cooling, the precipitate was filtered and crystallized from ethanol. Colourless blocks of (I) were grown from 1:1 mixture of ethanol and DMF by slow evaporation and the yield was 72%. M.p.: 475 K.