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Acta Crystallogr Sect E Struct Rep Online. 2010 May 1; 66(Pt 5): o1231–o1232.
Published online 2010 April 30. doi:  10.1107/S1600536810015266
PMCID: PMC2979288

(E)-N’-(2,3,4-Trimethoxy­benzyl­idene)isonicotinohydrazide

Abstract

In the title compound, C16H17N3O4, the mol­ecule exists in an E configuration with respect to the C=N double bond. The mol­ecule is not planar, the dihedral angle between the pyridine and benzene rings being 71.67 (8)°. In the crystal structure, mol­ecules are linked into chains along the b axis by bifurcated N—H(...)O and C—H(...)O hydrogen bonds. These chains are linked into a three-dimensional network by C—H(...)O and C—H(...)π inter­actions.

Related literature

For applications of isoniazid derivatives, see: Janin (2007 [triangle]); Maccari et al. (2005 [triangle]); Slayden & Barry (2000 [triangle]); Kahwa et al. (1986 [triangle]). For preparation of the compound, see: Lourenco et al. (2008 [triangle]). For related structures, see: Naveenkumar et al. (2009 [triangle], 2010a [triangle],b [triangle]); Shi (2005 [triangle]). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o1231-scheme1.jpg

Experimental

Crystal data

  • C16H17N3O4
  • M r = 315.33
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1231-efi1.jpg
  • a = 14.246 (3) Å
  • b = 9.397 (2) Å
  • c = 12.098 (3) Å
  • β = 109.245 (6)°
  • V = 1529.1 (6) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 100 K
  • 0.38 × 0.33 × 0.14 mm

Data collection

  • Bruker APEXII DUO CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2009 [triangle]) T min = 0.963, T max = 0.986
  • 14341 measured reflections
  • 3482 independent reflections
  • 2988 reflections with I > 2σ(I)
  • R int = 0.030

Refinement

  • R[F 2 > 2σ(F 2)] = 0.047
  • wR(F 2) = 0.159
  • S = 1.10
  • 3482 reflections
  • 215 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.57 e Å−3
  • Δρmin = −0.38 e Å−3

Data collection: APEX2 (Bruker, 2009 [triangle]); cell refinement: SAINT (Bruker, 2009 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810015266/tk2657sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810015266/tk2657Isup2.hkl

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

Acknowledgments

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

supplementary crystallographic information

Comment

In the search of new compounds of pharmaceutical importance, 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 a part of on-going work into the synthesis of (E)-N'-substituted isonicotinohydrazide derivatives, in this paper we present the crystal structure of the title compound (I).

The geometric parameters of (I) are comparable to those in related structures (Naveenkumar et al., 2009, 2010a, 2010b; Shi, 2005). The molecule exists in an E configuration with respect to the C7═N3 double bond (Fig. 1). The isoniazid group is twisted away with the torsion angle of C1–C5–C6–N2 being -149.60 (15)°. The dihedral angle between the pyridine ring and the benzene ring is 71.67 (8)°. One of the methoxy group is coplanar with the benzene ring whereas the other two are twisted away from the benzene ring [torsion angles: C16–O4–C11–C12 = -3.8 (2), C15–O3–C10–C11 = -97.83 (17), C14–O2–C9–C10 = 73.23 (19) °]. A weak intramolecular C14–H14C···O3 hydrogen bond stabilizes the molecular structure (Table 1). In the crystal structure, the molecules are linked into one-dimensional chains along the b axis by the bifurcated intermolecular N2–H1N2···O1 and C4–H4A···O1 hydrogen bonds (Table 1). These chains are linked into a three-dimensional network by C15–H15C···O2, C16–H16A···O3 and C14–H14B···Cg1 interactions (Fig. 2, Table 1).

Experimental

The isoniazid derivative (I) was prepared following the procedure by Lourenco et al. (2008). 2,3,4-Trimethoxybenzaldehyde (1.0 eq) was reacted with isoniazid (1.0 eq) in ethanol/water. After stirring for 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, affording the pure derivative. The colourless crystals were obtained by recrystallization from a methanol solution of (I).

Refinement

The H1N2 H atom was located from a difference Fourier map and refined freely. The remaining H atoms were positioned geometrically [C–H = 0.93 or 0.96 Å] and refined using a riding model, with Uiso(H) = 1.2 or 1.5 Ueq(C). A rotating-group model was applied for the methyl groups.

Figures

Fig. 1.
The molecular structure of (I) with atom labels and 50% probability ellipsoids for non-H atoms.
Fig. 2.
The crystal packing of (I), viewed down the c axis, showing the molecules are linked into a 3-D network. Intermolecular contacts are shown as dashed lines.

Crystal data

C16H17N3O4F(000) = 664
Mr = 315.33Dx = 1.370 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 5847 reflections
a = 14.246 (3) Åθ = 2.8–33.0°
b = 9.397 (2) ŵ = 0.10 mm1
c = 12.098 (3) ÅT = 100 K
β = 109.245 (6)°Block, colourless
V = 1529.1 (6) Å30.38 × 0.33 × 0.14 mm
Z = 4

Data collection

Bruker APEXII DUO CCD area-detector diffractometer3482 independent reflections
Radiation source: fine-focus sealed tube2988 reflections with I > 2σ(I)
graphiteRint = 0.030
[var phi] and ω scansθmax = 27.5°, θmin = 2.6°
Absorption correction: multi-scan (SADABS; Bruker, 2009)h = −17→18
Tmin = 0.963, Tmax = 0.986k = −11→12
14341 measured reflectionsl = −15→15

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.047Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.159H atoms treated by a mixture of independent and constrained refinement
S = 1.10w = 1/[σ2(Fo2) + (0.0903P)2 + 0.7464P] where P = (Fo2 + 2Fc2)/3
3482 reflections(Δ/σ)max < 0.001
215 parametersΔρmax = 0.56 e Å3
0 restraintsΔρmin = −0.38 e Å3

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O10.01090 (9)0.86823 (12)−0.28320 (11)0.0286 (3)
O20.36424 (9)0.41851 (12)−0.00731 (10)0.0232 (3)
O30.47223 (8)0.40332 (13)0.23303 (10)0.0235 (3)
O40.41436 (9)0.55428 (13)0.38640 (10)0.0245 (3)
N1−0.18863 (12)0.63126 (17)−0.66119 (13)0.0302 (4)
N20.05989 (10)0.63755 (14)−0.24901 (12)0.0207 (3)
N30.11895 (10)0.66421 (14)−0.13400 (11)0.0208 (3)
C1−0.08316 (12)0.79807 (18)−0.52380 (15)0.0238 (3)
H1A−0.05570.8888−0.50980.029*
C2−0.14580 (13)0.76010 (19)−0.63502 (15)0.0277 (4)
H2A−0.15870.8275−0.69440.033*
C3−0.16847 (13)0.53782 (19)−0.57329 (15)0.0278 (4)
H3A−0.19830.4487−0.58940.033*
C4−0.10626 (12)0.56370 (17)−0.45947 (15)0.0231 (3)
H4A−0.09420.4937−0.40210.028*
C5−0.06239 (11)0.69824 (17)−0.43404 (14)0.0204 (3)
C60.00512 (11)0.74314 (16)−0.31422 (14)0.0203 (3)
C70.18304 (11)0.56473 (17)−0.09093 (13)0.0200 (3)
H7A0.19100.4914−0.13870.024*
C80.24315 (11)0.56734 (16)0.03316 (14)0.0198 (3)
C90.33100 (11)0.48599 (16)0.07346 (13)0.0184 (3)
C100.38660 (11)0.48299 (16)0.19251 (13)0.0188 (3)
C110.35435 (12)0.56152 (17)0.27246 (14)0.0205 (3)
C120.26610 (12)0.63962 (17)0.23309 (15)0.0233 (3)
H12A0.24380.68950.28600.028*
C130.21207 (12)0.64218 (17)0.11454 (14)0.0229 (3)
H13A0.15370.69510.08860.027*
C140.35843 (15)0.26623 (19)−0.00823 (17)0.0325 (4)
H14A0.37680.2297−0.07230.049*
H14B0.29170.2376−0.01710.049*
H14C0.40290.22940.06410.049*
C150.55771 (13)0.4749 (2)0.22131 (17)0.0324 (4)
H15A0.61520.41520.25160.049*
H15B0.56820.56260.26440.049*
H15C0.54680.49450.14010.049*
C160.38727 (14)0.6398 (2)0.46951 (15)0.0308 (4)
H16A0.43430.62480.54630.046*
H16B0.32210.61320.46900.046*
H16C0.38730.73840.44880.046*
H1N20.0529 (18)0.544 (3)−0.270 (2)0.038 (6)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0297 (6)0.0180 (6)0.0300 (6)0.0029 (5)−0.0011 (5)−0.0029 (5)
O20.0270 (6)0.0225 (6)0.0204 (6)0.0008 (4)0.0083 (5)−0.0008 (4)
O30.0192 (6)0.0264 (6)0.0232 (6)0.0059 (4)0.0047 (4)0.0030 (4)
O40.0264 (6)0.0278 (6)0.0176 (6)0.0044 (5)0.0048 (5)−0.0011 (4)
N10.0324 (8)0.0321 (8)0.0239 (7)0.0010 (6)0.0062 (6)−0.0048 (6)
N20.0224 (7)0.0167 (6)0.0202 (6)0.0005 (5)0.0032 (5)−0.0022 (5)
N30.0217 (6)0.0189 (6)0.0200 (6)−0.0027 (5)0.0045 (5)−0.0024 (5)
C10.0234 (7)0.0205 (8)0.0288 (8)0.0018 (6)0.0104 (6)0.0013 (6)
C20.0306 (9)0.0289 (9)0.0244 (8)0.0040 (7)0.0101 (7)0.0026 (6)
C30.0276 (8)0.0244 (8)0.0285 (8)−0.0007 (7)0.0055 (7)−0.0062 (7)
C40.0214 (7)0.0200 (8)0.0272 (8)0.0014 (6)0.0071 (6)0.0000 (6)
C50.0181 (7)0.0197 (7)0.0243 (8)0.0031 (6)0.0080 (6)−0.0013 (6)
C60.0178 (7)0.0172 (7)0.0257 (8)0.0011 (6)0.0069 (6)−0.0006 (6)
C70.0201 (7)0.0191 (7)0.0201 (7)−0.0028 (6)0.0054 (6)−0.0004 (5)
C80.0192 (7)0.0175 (7)0.0211 (7)−0.0023 (6)0.0044 (6)0.0028 (5)
C90.0198 (7)0.0160 (7)0.0197 (7)−0.0020 (5)0.0069 (6)0.0004 (5)
C100.0175 (7)0.0170 (7)0.0212 (7)0.0014 (5)0.0054 (6)0.0021 (5)
C110.0222 (7)0.0195 (7)0.0192 (7)−0.0006 (6)0.0059 (6)0.0013 (6)
C120.0242 (8)0.0227 (8)0.0236 (8)0.0035 (6)0.0088 (6)−0.0016 (6)
C130.0216 (7)0.0199 (8)0.0259 (8)0.0026 (6)0.0061 (6)0.0019 (6)
C140.0394 (10)0.0229 (9)0.0378 (10)0.0001 (7)0.0165 (8)−0.0068 (7)
C150.0205 (8)0.0433 (11)0.0336 (9)0.0019 (7)0.0092 (7)0.0000 (8)
C160.0330 (9)0.0381 (10)0.0211 (8)0.0055 (8)0.0086 (7)−0.0035 (7)

Geometric parameters (Å, °)

O1—C61.228 (2)C5—C61.512 (2)
O2—C91.3733 (19)C7—C81.463 (2)
O2—C141.433 (2)C7—H7A0.9300
O3—C101.3765 (18)C8—C131.395 (2)
O3—C151.438 (2)C8—C91.409 (2)
O4—C111.3634 (19)C9—C101.397 (2)
O4—C161.436 (2)C10—C111.409 (2)
N1—C31.335 (2)C11—C121.397 (2)
N1—C21.346 (2)C12—C131.387 (2)
N2—C61.345 (2)C12—H12A0.9300
N2—N31.3910 (18)C13—H13A0.9300
N2—H1N20.91 (3)C14—H14A0.9600
N3—C71.290 (2)C14—H14B0.9600
C1—C51.391 (2)C14—H14C0.9600
C1—C21.394 (2)C15—H15A0.9600
C1—H1A0.9300C15—H15B0.9600
C2—H2A0.9300C15—H15C0.9600
C3—C41.391 (2)C16—H16A0.9600
C3—H3A0.9300C16—H16B0.9600
C4—C51.399 (2)C16—H16C0.9600
C4—H4A0.9300
C9—O2—C14115.72 (13)O2—C9—C8118.64 (14)
C10—O3—C15112.99 (13)C10—C9—C8120.32 (14)
C11—O4—C16117.16 (13)O3—C10—C9120.87 (14)
C3—N1—C2116.26 (15)O3—C10—C11119.46 (13)
C6—N2—N3119.77 (13)C9—C10—C11119.68 (14)
C6—N2—H1N2124.0 (15)O4—C11—C12124.39 (15)
N3—N2—H1N2115.3 (15)O4—C11—C10115.49 (14)
C7—N3—N2112.81 (13)C12—C11—C10120.11 (15)
C5—C1—C2119.00 (16)C13—C12—C11119.48 (15)
C5—C1—H1A120.5C13—C12—H12A120.3
C2—C1—H1A120.5C11—C12—H12A120.3
N1—C2—C1123.62 (16)C12—C13—C8121.61 (15)
N1—C2—H2A118.2C12—C13—H13A119.2
C1—C2—H2A118.2C8—C13—H13A119.2
N1—C3—C4124.95 (16)O2—C14—H14A109.5
N1—C3—H3A117.5O2—C14—H14B109.5
C4—C3—H3A117.5H14A—C14—H14B109.5
C3—C4—C5117.92 (16)O2—C14—H14C109.5
C3—C4—H4A121.0H14A—C14—H14C109.5
C5—C4—H4A121.0H14B—C14—H14C109.5
C1—C5—C4118.23 (15)O3—C15—H15A109.5
C1—C5—C6117.70 (15)O3—C15—H15B109.5
C4—C5—C6124.06 (15)H15A—C15—H15B109.5
O1—C6—N2123.99 (15)O3—C15—H15C109.5
O1—C6—C5121.16 (14)H15A—C15—H15C109.5
N2—C6—C5114.79 (14)H15B—C15—H15C109.5
N3—C7—C8119.94 (14)O4—C16—H16A109.5
N3—C7—H7A120.0O4—C16—H16B109.5
C8—C7—H7A120.0H16A—C16—H16B109.5
C13—C8—C9118.77 (14)O4—C16—H16C109.5
C13—C8—C7121.20 (14)H16A—C16—H16C109.5
C9—C8—C7119.90 (14)H16B—C16—H16C109.5
O2—C9—C10120.87 (13)
C6—N2—N3—C7−165.58 (14)C7—C8—C9—O27.4 (2)
C3—N1—C2—C10.3 (3)C13—C8—C9—C10−1.2 (2)
C5—C1—C2—N10.5 (3)C7—C8—C9—C10−177.24 (14)
C2—N1—C3—C4−1.0 (3)C15—O3—C10—C982.69 (18)
N1—C3—C4—C51.0 (3)C15—O3—C10—C11−97.83 (17)
C2—C1—C5—C4−0.5 (2)O2—C9—C10—O3−5.1 (2)
C2—C1—C5—C6−179.50 (14)C8—C9—C10—O3179.63 (14)
C3—C4—C5—C1−0.2 (2)O2—C9—C10—C11175.45 (14)
C3—C4—C5—C6178.75 (15)C8—C9—C10—C110.2 (2)
N3—N2—C6—O17.8 (2)C16—O4—C11—C12−3.8 (2)
N3—N2—C6—C5−175.09 (13)C16—O4—C11—C10176.28 (14)
C1—C5—C6—O127.6 (2)O3—C10—C11—O41.7 (2)
C4—C5—C6—O1−151.38 (17)C9—C10—C11—O4−178.79 (13)
C1—C5—C6—N2−149.60 (15)O3—C10—C11—C12−178.17 (14)
C4—C5—C6—N231.5 (2)C9—C10—C11—C121.3 (2)
N2—N3—C7—C8−172.80 (13)O4—C11—C12—C13178.42 (15)
N3—C7—C8—C1322.4 (2)C10—C11—C12—C13−1.7 (2)
N3—C7—C8—C9−161.70 (15)C11—C12—C13—C80.6 (2)
C14—O2—C9—C1073.23 (19)C9—C8—C13—C120.8 (2)
C14—O2—C9—C8−111.40 (16)C7—C8—C13—C12176.81 (15)
C13—C8—C9—O2−176.62 (14)

Hydrogen-bond geometry (Å, °)

Cg1 is centroid of the C1/C2/N1/C3/C4/C5 ring.
D—H···AD—HH···AD···AD—H···A
N2—H1N2···O1i0.91 (3)2.09 (3)2.7987 (19)134 (2)
C4—H4A···O1i0.932.463.348 (2)159
C14—H14C···O30.962.553.113 (2)118
C15—H15C···O2ii0.962.493.292 (2)141
C16—H16A···O3iii0.962.573.518 (2)167
C14—H14B···Cg1i0.962.813.719 (3)159

Symmetry codes: (i) −x, y−1/2, −z−1/2; (ii) −x+1, −y+1, −z; (iii) −x+1, −y+1, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: TK2657).

References

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