6-(4-Amino­phen­yl)-2-eth­oxy-4-(2-thien­yl)nicotinonitrile

Hoong-Kun Fun; Suchada Chantrapromma; Thawanrat Kobkeatthawin; Mahesh Padaki; Arun M Isloor

doi:10.1107/S160053681002369X

. 2010 Jun 26;66(Pt 7):o1811–o1812. doi: 10.1107/S160053681002369X

6-(4-Aminophenyl)-2-ethoxy-4-(2-thienyl)nicotinonitrile

Hoong-Kun Fun ^a,^*,^‡, Suchada Chantrapromma ^b,^§, Thawanrat Kobkeatthawin ^b, Mahesh Padaki ^c, Arun M Isloor ^c

PMCID: PMC3006713 PMID: 21588020

Abstract

In the title nicotinonitrile derivative, C₁₈H₁₅N₃OS, the central pyridyl ring makes dihedral angles of 25.22 (10) and 24.80 (16)° with the 4-aminophenyl and thiophene rings, respectively. The thiophene ring is disordered over two orientations by rotation around the C(thiophene)—C(pyridine) bond; the occupancies are 0.858 (2) and 0.142 (2). The ethoxy group is slightly twisted from the attached pyridyl ring [C—O—C—C torsion angle = 171.13 (16)°]. In the crystal structure, molecules are linked by N—H⋯N hydrogen bonds into chains along [010]. These chains are stacked along the a axis. C—H⋯π weak interactions involving the thiophene ring are observed.

Related literature

For reference bond-length data, see: Allen et al. (1987 ▶). For the synthesis and applications of nicotinonitrile derivatives, see: Amr & Abdulla (2006 ▶); Borgna et al. (1993 ▶); Fun et al. (2009 ▶); Goda et al. (2004 ▶); Kamal et al. (2007 ▶); Malinka et al. (1998 ▶). For related structures, see: Chantrapromma et al. (2009 ▶, 2010 ▶); Fun et al. (2009 ▶). For the stability of the temperature controller used in the data collection, see Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₁₈H₁₅N₃OS
M _r = 321.38
Orthorhombic,
a = 7.0751 (12) Å
b = 20.843 (4) Å
c = 20.983 (4) Å
V = 3094.3 (9) Å³
Z = 8
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 100 K
0.35 × 0.11 × 0.04 mm

Data collection

Bruker APEXII DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.928, T _max = 0.992
34805 measured reflections
3045 independent reflections
2188 reflections with I > 2σ(I)
R _int = 0.092

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.085
S = 1.05
3045 reflections
233 parameters
88 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.32 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/S160053681002369X/wn2394sup1.cif

e-66-o1811-sup1.cif^{(22.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053681002369X/wn2394Isup2.hkl

e-66-o1811-Isup2.hkl^{(149.5KB, hkl)}

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

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

Cg1 is the centroid of the major disorder component of the thiophene ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H1N2⋯N3ⁱ	0.92 (2)	2.29 (2)	3.197 (3)	168.2 (19)
C3—H3A⋯Cg1ⁱⁱ	0.93	2.93	3.566 (6)	127
C12—H12A⋯Cg1ⁱⁱⁱ	0.93	2.78	3.430 (3)	128

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

Acknowledgments

The authors thank the Thailand Research Fund (TRF) and Prince of Songkla University for a research grant. AMI is grateful to the Head of the Department of Chemistry and the Director, NITK-Surathkal, India, for providing research facilities. The authors also thank Universiti Sains Malaysia for the Research University Golden Goose grant No. 1001/PFIZIK/811012.

supplementary crystallographic information

Comment

Heterocyclic compounds containing the pyridine ring are reported to possess a diverse range of biological activities such as antimicrobial, antitumor and anti-inflammatory (Amr & Abdulla, 2006; Borgna et al., 1993; Goda et al., 2004; Kamal et al., 2007; Malinka et al., 1998) properties. Our research is aimed at the synthesis and preliminary biological (in vitro) and pharmacological (in vivo) screening, together with enzyme inhibitory activity, of the nicotinonitrile derivatives. The title compound, which is a substituted pyridine compound, was synthesized by cyclization of our previous chalcone derivative (Fun et al., 2009) and malononitrile.

The molecule of the title compound, C₁₈H₁₅N₃OS, is not planar (Fig. 1). The central pyridyl ring is inclined to the 4-aminophenyl and thiophene rings with dihedral angles of 25.22 (10)° and 24.80 (16)°, respectively. The thiophene ring is disordered over two orientations by rotation around the C4—C5 bond, with occupancies of 0.858 (2) and 0.142 (1). The ethoxy group is twisted slightly from the attached pyridyl ring, as indicated by the torsion angles C14—O1—C16—C17 = 171.13 (16)° and C16—O1—C14—C15 = 179.01 (16) °. The bond distances agree with the literature values (Allen et al., 1987) and are comparable with those for related structures (Chantrapromma et al., 2009; 2010).

In the crystal structure, (Fig. 2), the molecules are linked by weak intermolecular N2—H1N2···N3 hydrogen bond (Table 1) into chains along [010]. These chains are stacked along the a axis. The crystal structure is further stabilized by C—H···π interactions (Table 1); Cg₁ is the centroid of the C1–C4/S1 ring (major disorder component).

Experimental

(2E)-1-(4-Aminophenyl)-3-(2-thienyl)prop-2-en-1-one (0.34 g, 0.0015 mole) which was synthesized according to a previous procedure (Fun et al., 2009) was added with continuous stirring to a freshly prepared sodium alkoxide solution (0.0014 mole of sodium in 100 ml of ethanol). Malononitrile (1.30 g, 0.02 mol) was then added with continuous stirring at room temperature until the precipitate separated out. The resulting solid was filtered (yield 68%). Yellow plate-shaped single crystals of the title compound suitable for X-ray structure determination were recrystalized from ethanol by the slow evaporation of the solvent at room temperature over several days. Mp. 470–471 K.