3-Amino-4-(1,3-benzoxazol-2-yl)-5-(cyclo­hexyl­amino)­thio­phene-2-carbo­nitrile

Chiraz Youssef; Mohamed Belhouchet; Hamed Ben Ammar; Ridha Ben Salem

doi:10.1107/S1600536813019880

. 2013 Jul 27;69(Pt 8):o1339. doi: 10.1107/S1600536813019880

3-Amino-4-(1,3-benzoxazol-2-yl)-5-(cyclohexylamino)thiophene-2-carbonitrile

Chiraz Youssef ^a, Mohamed Belhouchet ^b,^*, Hamed Ben Ammar ^a, Ridha Ben Salem ^a

PMCID: PMC3793821 PMID: 24109408

Abstract

In the title compound, C₁₈H₁₈N₄OS, the cyclohexyl ring adopts a chair conformation. The other rings of this compound lie almost in the same plane, with a mean deviation of 0.03 (2) Å from the least-squares plane defined by the 14 constituent atoms. There are intramolecular N—H⋯N and N—H⋯O hydrogen bonds, as well as intermolecular N—H⋯N hydrogen bonds, which link the molecules into centrosymmetric dimers.

Related literature

For the pharmacological and biological activities of benzoxazole derivatives, see: Isomura et al. (1983 ▶); Cheng et al.(1993 ▶); Koci et al. (2002 ▶); Hoffman et al. (1993 ▶); Arpaci et al. (2002 ▶). For the synthesis and a similar structure, see: Youssef et al. (2011 ▶); Belhouchet et al. (2012 ▶). graphic file with name e-69-o1339-scheme1.jpg

Experimental

Crystal data

C₁₈H₁₈N₄OS
M _r = 338.42
Monoclinic,
a = 24.270 (5) Å
b = 6.193 (5) Å
c = 23.578 (5) Å
β = 107.554 (5)°
V = 3379 (3) Å³
Z = 8
Mo Kα radiation
μ = 0.20 mm⁻¹
T = 293 K
0.3 × 0.25 × 0.22 mm

Data collection

Bruker APEXII area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.655, T _max = 0.746
13506 measured reflections
2961 independent reflections
1904 reflections with I > 2σ(I)
R _int = 0.049

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.112
S = 1.01
2961 reflections
230 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; 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 ▶) and DIAMOND (Brandenburg, 1998 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813019880/bv2222sup1.cif

e-69-o1339-sup1.cif^{(20.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813019880/bv2222Isup2.hkl

e-69-o1339-Isup2.hkl^{(142.5KB, hkl)}

Click here for additional data file.^{(6.6KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813019880/bv2222Isup4.cml

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
N2—H1N2⋯O1	0.92 (3)	2.13 (3)	2.783 (4)	127 (2)
N2—H2N2⋯N1ⁱ	0.86 (3)	2.25 (3)	3.088 (4)	166 (3)
N3—H1N3⋯N4	0.86 (2)	2.12 (3)	2.787 (3)	135 (2)

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Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

Substituted thiophenes have attracted considerable interest because they are endowed with variety of biological activities and have wide range of therapeutic properties. The Literature survey indicates that benzoxazole derivatives possess different pharmacological and biological activities (Isomura et al., 1983) which of most potent activity such as anti-tumor (Cheng et al. 1993), anticancer (Koci et al., 2002), antiviral (Hoffman et al., 1993), or antimicrobial (Arpaci et al., 2002) properties. For these reasons we thought to synthesize thiophene system incorporating benzoxazole.

The present report describes the molecular structure of 3-amino-4-benzo[d]oxazol-2-yl-5-(cyclohexylamino) thiophène-2-carbonitrile. The crystal structure of this compound is built up from two fused five(O1/C6/N4/C12/C7) and six membered (C7—C11) rings linked to five (C2—C5/S1) membered ring via C6—C4 bond. The built planar entity (with a mean deviation of 0.03 (2) Å from the least square plane defined by the fourteen constituted atoms) is linked to the cyclohexyl ring (adopting a chair conformation) via two C—N bonds (C5—N3 and C13-N3) as shown in Figure 1. All bond lengths are normal and are comparable with those reported for a similar structure (Belhouchet et al., 2012). There are intramolecular N—H···N and N—H···O hydrogen bonds as well as intermolecular N—H···N hydrogen bonds which link the molecules into centrosymmetric dimers (Figure 2 and Table 1). There are no other intermolecular interactions present.

Experimental

Previously, we investigated the reaction of benzoxazole with active methylene compounds and aldehyde in alkaline medium, which has proved to be a convenient route for the synthesis of pyridobenzoxazole ring systems (Youssef et al.,2011). Now, we have extended our synthetic program to the synthesis of thiophenes ring system, utilizing benzoxazol-2-cyanomethyle as a key starting material.

To a cold suspension of potassium tertio-butylate (25 mmol) in THF (30 ml) benzoxazol-2-cyanomethyl was added (22 mmol) and followed by cyclohexyl isothiocyanate (22 mmol). The mixture was stirred overnight at room temperature and treated with the chloroacetone (22 mmol), stirring was continued for 4 h. The reaction mixture was poured onto ice cold water. Acidification using dilute HCl until the medium becomes acidic gave the synthesized solid product which was filtered off, washed with water, dried and recrystallized from aqueous ethanol solution to give single-crystal suitable for the X-ray diffraction.)