(E)-N′-(2,4,6-Trimethyl­benzyl­idene)isonicotinohydrazide

H S Naveenkumar; Amirin Sadikun; Pazilah Ibrahim; Jia Hao Goh; Hoong-Kun Fun

doi:10.1107/S1600536810019446

. 2010 May 29;66(Pt 6):o1493. doi: 10.1107/S1600536810019446

(E)-N′-(2,4,6-Trimethylbenzylidene)isonicotinohydrazide

H S Naveenkumar ^a, Amirin Sadikun ^a,^‡, Pazilah Ibrahim ^a, Jia Hao Goh ^b,^§, Hoong-Kun Fun ^b,^*,^¶

PMCID: PMC2979577 PMID: 21579555

Abstract

The title isoniazid derivative, C₁₆H₁₇N₃O, exists in an E configuration with respect to the Schiff base C=N bond. The pyridine ring is essentially planar [maximum deviation = 0.009 (3) Å]. The mean plane through the hydrazide unit forms dihedral angles of 38.38 (16) and 39.42 (16)°, respectively, with the pyridine and benzene rings. In the crystal structure, symmetry-related molecules are linked via intermolecular N—H⋯O hydrogen bonds into chains along [100]. The crystal structure is further stabilized by weak intermolecular C—H⋯π interactions.

Related literature

For general background to and applications of isoniazid derivatives, see: Janin (2007 ▶); Maccari et al. (2005 ▶); Slayden & Barry (2000 ▶); Kahwa et al. (1986 ▶). For the preparation of the title compound, see: Lourenco et al. (2008 ▶). For related structures, see: Naveenkumar et al. (2009 ▶, 2010a ▶,b ▶); Shi (2005 ▶).

Experimental

Crystal data

C₁₆H₁₇N₃O
M _r = 267.33
Monoclinic,
a = 4.7966 (7) Å
b = 34.268 (7) Å
c = 8.3795 (14) Å
β = 96.203 (14)°
V = 1369.3 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 100 K
0.35 × 0.10 × 0.07 mm

Data collection

Bruker APEXII DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.971, T _max = 0.994
12980 measured reflections
3127 independent reflections
2043 reflections with I > 2σ(I)
R _int = 0.070

Refinement

R[F ² > 2σ(F ²)] = 0.074
wR(F ²) = 0.160
S = 1.11
3127 reflections
188 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.48 e Å⁻³
Δρ_min = −0.30 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/S1600536810019446/lh5051sup1.cif

e-66-o1493-sup1.cif^{(18.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810019446/lh5051Isup2.hkl

e-66-o1493-Isup2.hkl^{(153.4KB, hkl)}

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

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

Cg1 is the centroid of the C1-C5/N1 pyridine ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H1N2⋯O1ⁱ	0.93 (3)	1.97 (3)	2.844 (3)	157 (3)
C16—H16B⋯Cg1ⁱ	0.96	2.96	3.551 (3)	121

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Symmetry code: (i) Inline graphic .

Acknowledgments

This research was supported by Universiti Sains Malaysia (USM) under the Fundamental Research Grant Scheme (203/PFARMASI/671157). HSN and JHG are grateful to USM for USM Fellowships. HKF and JHG thank USM for the Research University Golden Goose Grant (1001/PFIZIK/811012).

supplementary crystallographic information

Comment

In the search of new compounds, isoniazid derivatives have been found to possess potential tuberculostatic activity (Janin, 2007; Maccari et al., 2005; Slayden & Barry, 2000). Schiff bases have attracted much attention because of their biological activity (Kahwa et al., 1986). As part of our current work on the synthesis of (E)-N'-substituted isonicotinohydrazide derivatives, in this paper we report the crystal structure of the title isoniazid derivative.

The title isoniazid derivative (Fig. 1) exists in an E configuration with respective to the Schiff base C7═N3 bond [C7═N3 = 1.280 (3) Å; torsion angle N2–N3–C7–C8 = 179.4 (2)°]. The pyridine ring with atom sequence C1/C2/N1/C3/C4/C5 is essentially planar, with a maximum deviation of 0.009 (3) Å at atom C4. The mean plane through the hydrazide unit (O1/C6/N2/N3/C7) forms dihedral angles of 38.38 (16) and 39.42 (16)°, respectively, with the pyridine and benzene (C8-C13) rings. The bond lengths and angles are consistent to those observed in closely related structures (Naveenkumar et al., 2009; 2010a,b; Shi, 2005).

In the crystal structure (Fig. 2), adjacent molecules are linked into one-dimensional chains along the [100] direction via intermolecular N2—H1N2···O1ⁱ hydrogen bonds (Table 1). The crystal structure is further stabilized by weak intermolecular C16—H16B···Cg1ⁱ interactions (Table 1) involving the centroid of the pyridine ring.

Experimental

The title isoniazid derivative was prepared following the procedure by Lourenco et al., (2008). The title derivative was prepared by the reaction between 2,4,6-trimethylbenzaldehyde (1.0 eq) with isoniazid (1.0 eq) in ethanol/water. After stirring for 1-3 h at room temperature, the resulting mixture was concentrated under reduced pressure. The residue was purified by washing with cold ethanol and ethyl ether to afford the pure derivative. Colourless single crystals suitable for X-ray analysis were obtained by slow evaporation with dimethyl sulfoxide.