N-(4-Chloro­phen­yl)-5-(4,5-dihydro-1H-imidazol-2-yl)thieno[2,3-b]pyridin-4-amine

Alice M R Bernardino; Luiz C S Pinheiro; Edward R T Tiekink; James L Wardell; Solange M S V Wardell

doi:10.1107/S160053681202658X

. 2012 Jun 20;68(Pt 7):o2135–o2136. doi: 10.1107/S160053681202658X

N-(4-Chlorophenyl)-5-(4,5-dihydro-1H-imidazol-2-yl)thieno[2,3-b]pyridin-4-amine

Alice M R Bernardino ^a, Luiz C S Pinheiro ^b, Edward R T Tiekink ^c,^*, James L Wardell ^d,^‡, Solange M S V Wardell ^e

PMCID: PMC3393946 PMID: 22798811

Abstract

In the title compound, C₁₆H₁₃ClN₄S, the thienopyridine fused-ring system is nearly planar (r.m.s. deviation = 0.0333 Å) and forms a dihedral angle of 4.4 (3)° with the attached dihydroimidazole ring (r.m.s. deviation = 0.0429 Å) allowing for the formation of an intramolecular (exocyclic amine)N—H⋯N(imine) hydrogen bond. The benzene rings of the disordered (50:50) –N(H)—C₆H₄Cl residue form dihedral angles of 59.1 (3) and 50.59 (15)° with the fused ring system. In the crystal, (imidazole amine)N—H⋯N(pyridine) hydrogen bonds lead to a supramolecular helical chain along the b axis. The chains assemble into layers (ab plane) with inter-digitation of the chlorobenzene rings which results in weak C—H⋯Cl interactions in the c-axis direction.

Related literature

For the synthesis and biological activity of thienopyridine derivatives, see: Kaigorodova et al. (2000 ▶); Moloney (2001 ▶); Bernardino et al. (2004 ▶, 2006 ▶); Leal et al. (2008 ▶); Pinheiro et al. (2008a ▶); El-Kashef et al. (2010 ▶); Testa et al. (2010 ▶); Panchamukhi et al. (2011 ▶). For the anti-leishmanial activity of 5-(4,5-dihydro-1H-imidazol-2-yl)-4-(arylamino)thieno[2,3-b]pyridine, see: Pinheiro et al. (2012 ▶).

Experimental

Crystal data

C₁₆H₁₃ClN₄S
M _r = 328.81
Monoclinic,
a = 17.784 (3) Å
b = 6.2264 (4) Å
c = 13.6226 (18) Å
β = 102.700 (4)°
V = 1471.5 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.40 mm⁻¹
T = 120 K
0.25 × 0.15 × 0.03 mm

Data collection

Bruker–Nonius Roper CCD camera on κ-goniostat diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2007 ▶) T _min = 0.639, T _max = 1.000
9375 measured reflections
2591 independent reflections
1106 reflections with I > 2σ(I)
R _int = 0.138

Refinement

R[F ² > 2σ(F ²)] = 0.079
wR(F ²) = 0.217
S = 0.99
2591 reflections
191 parameters
2 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.42 e Å⁻³

Data collection: COLLECT (Hooft, 1998 ▶); cell refinement: DENZO (Otwinowski & Minor, 1997 ▶) and COLLECT; data reduction: DENZO and COLLECT; 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, 1997 ▶) and DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S160053681202658X/xu5563sup1.cif

e-68-o2135-sup1.cif^{(22.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681202658X/xu5563Isup2.hkl

e-68-o2135-Isup2.hkl^{(124.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S160053681202658X/xu5563Isup3.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—H2n⋯N3	0.88 (10)	1.87 (11)	2.578 (18)	136 (10)
N2′—H2n’⋯N3	0.88 (10)	2.04 (11)	2.740 (15)	135 (7)
N4—H4n⋯N1ⁱ	0.88 (3)	2.10 (3)	2.956 (8)	167 (5)
C6—H6⋯Cl1′ⁱⁱ	0.95	2.74	3.559 (10)	146

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

Acknowledgments

The use of the EPSRC X-ray crystallographic service at the University of Southampton, England, and the valuable assistance of the staff there is gratefully acknowledged. JLW acknowledges support from CAPES (Brazil). We also thank the Ministry of Higher Education (Malaysia) for funding structural studies through the High-Impact Research scheme (UM.C/HIR/MOHE/SC/12).

supplementary crystallographic information

Comment

Thienopyridine derivatives have been synthesized by a variety of routes (Kaigorodova et al., 2000; Bernardino et al., 2006; Pinheiro et al., 2008; El-Kashef et al., 2010; Testa et al., 2010). A primary motivation for the preparation of these compounds is their biological activity, viz. anti-viral (Bernardino et al., 2004), anti-inflammatory (Moloney, 2001), anti-bacterial (Leal et al., 2008; Pinheiro et al., 2008; Panchamukhi et al., 2011) and anti-parasitic (Bernardino et al., 2006). Recently, the anti-leishmanial activity of a family of 5-(4,5-dihydro-1H-imidazol-2-yl)-4-(arylamino)thieno[2,3-b]pyridine derivatives was reported (Pinheiro et al., 2012). We now wish to report the crystal structure determination of a related derivative, namely 5-(4,5-dihydro-1H-imidazol-2-yl)-4-(4'-chlorophenylamino)-thieno[2,3-b]pyridine, (I).

In (I), Fig. 1, the nine non-hydrogen atoms of the thienopyridine ring are planar, having a r.m.s. deviation = 0.0333 Å and maximum deviations of 0.051 (5) Å [for the C7 atom] and -0.038 (5) Å [C6]. The imidazolyl ring is approximately planar [r.m.s. deviation = 0.0429 Å] and is co-planar with the fused ring system forming a dihedral angle of 4.4 (3)°. The imine-N3 atom of the imidazolyl ring is orientated towards the exocyclic amine so that an intramolecular hydrogen bond is formed, Table 1. There are two orientations for the disordered —N(H)—C₆H₄Cl residue of equal weight. The benzene rings of this residue are approximately co-planar (dihedral angle = 8.7 (5)°) and slightly displaced from each other. The dihedral angles between each orientation and the fused ring system are 59.1 (3) and 50.59 (15)°.

The most prominent feature of the crystal packing is the formation of N—H···N hydrogen bonds between the imidazolyl-amine and the pyridyl-N atom which lead to supramolecular helical chains along the b axis, Fig. 2 and Table 1. These assemble into layers in the ab plane allowing for inter-digitation of the chlorobenzene rings which in turn, allows for the formation of weak C—H···Cl interactions, Table 1. For the illustrated orientation of disordered benzene ring, Fig. 3, the H6···Cl1 separation is 2.95 Å.

Experimental

Following general procedures (Bernardino et al., 2006; Pinheiro et al., 2012), a solution of 4-(4'-chlorophenylamino)thieno[2,3-b]pyridine-5-carbonitrile (1.5 mmol) in ethylenediamine (5 ml) was cooled at 273 K, carbon disulfide (8 drops) was added and the reaction mixture heated at 373 for 24 h. The resulting mixture was cooled, treated with water and filtered to give a brown crystalline solid, which was collected and dried. The sample used in the structure determination was grown from CHCl₃ solution. IR (KBr, cm^-1): ν NH 3225, ν C═N 1591). ¹H NMR (300 MHz, CDCl₃, TMS, δ in p.p.m.) 7.09 (d, 6.0, 1H, H2); 6.50 (d, 6.0, 1H, H3); 8.51 (s, 1H, H6); 7.29 (d, 8.7, 2H, Ar—H); 7.09 (d, 8.7, 2H, Ar—H); 3.83 (s, 4H, CH₂). ¹³C NMR (75 MHz, DMSO-d6, TMS, δ in p.p.m.) 164.4; 164.1; 146.9; 146.6; 140.0; 129.3; 128.8; 125.4; 123.6; 121.3; 119.4; 105.4. ESI-(+)-MS [M+H]+ - 329.051 (100).