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Acta Cryst. (2010). E66, o1235-o1236    [ doi:10.1107/S1600536810015254 ]

(E)-N'-(2,4,5-Trimethoxybenzylidene)isonicotinohydrazide dihydrate

H. S. Naveenkumar, A. Sadikun, P. Ibrahim, C. S. Yeap and H.-K. Fun

Abstract top

The asymmetric unit of the title compound, C16H17N3O4·2H2O, contains one Schiff base molecule and two water molecules. The Schiff base molecule exists in an E configuration with respect to the C=N double bond and is essentially planar, the dihedral angle between the benzene and pyridine rings being 5.48 (8)°. The three methoxy groups are also coplanar with the benzene ring [C-O-C-C torsion angles = 3.9 (2), 178.51 (15) and 0.8 (2) Å]. In the crystal structure, the water molecules link the molecules into a three-dimensional network via intermolecular N-H...O, O-H...O, O-H...N and C-H...O hydrogen bonds.

Comment top

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). As a part of a current work of synthesis of such derivatives, in this paper we present the crystal structure of the title compound which was synthesized in our lab.

The asymmetric unit consists of one Schiff base molecule and two water molecules (Fig. 1). The geometry parameters are comparable to those related structures (Naveenkumar et al., 2009, 2010a, b; Shi, 2005). The molecule exists in an E configuration with respect to the C7═N3 double bond. The molecule is essentially coplanar with dihedral angle between the benzene ring and the pyridine ring being 5.48 (8)°. The three methoxy groups are coplanar with the benzene ring [torsion angle, C14–O2–C9–C10 = 3.9 (2), C15–O3–C11–C12 = 178.51 (15), C16–O4–C12–C13 = 0.8 (2) Å]. In the crystal structure, the water molecules link the molecules into a three-dimensional network by the intermolecular N–H···O, O–H···O O–H···N and C–H···O hydrogen bonds (Fig. 2, Table 1).

Related literature top

For 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). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986).

Experimental top

The isoniazid derivative was prepared following the procedure by Lourenco et al., (2008). The title compound was prepared by reaction between 2, 4, 5-trimethoxybenzaldehyde (1.0 eq) and isoniazid (1.0 eq) in ethanol/water. After stirring for 1-3 hours at room temperature, the resulting mixture was concentrated under reduced pressure. The residue, purified by washing with cold ethanol and ethyl ether, afforded the pure derivative. The yellow single crystal suitable for X-ray analysis was obtained by recrystalization with methanol.

Refinement top

N-bound and O-bound hydrogen atoms were located from the difference Fourier map. The N-bound hydrogen atom was refined freely and the O-bound hydrogen atoms were constrained to ride on the parent atom with Uiso(H) = 1.5 Ueq(O). The rest of hydrogen 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). Rotating-group models were applied for the methyl groups. As there is not enough anomalous dispersion to determine the absolute configuration, 4136 Friedel pairs were merged before final refinement.

Computing details top

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

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound with atom labels and 50% probability ellipsoids for non-H atoms.
[Figure 2] Fig. 2. The crystal packing of the title compound, viewed down the a axis, showing the molecules linked into a 3-D network. Intermolecular hydrogen bonds are shown as dashed lines.
(E)-N'-(2,4,5-Trimethoxybenzylidene)isonicotinohydrazide dihydrate top
Crystal data top
C16H17N3O4·2H2OF(000) = 372
Mr = 351.36Dx = 1.412 Mg m−3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 6099 reflections
a = 6.8156 (4) Åθ = 3.1–37.4°
b = 14.5648 (10) ŵ = 0.11 mm−1
c = 8.5589 (5) ÅT = 100 K
β = 103.421 (2)°Block, yellow
V = 826.42 (9) Å30.50 × 0.28 × 0.19 mm
Z = 2
Data collection top
Bruker APEXII DUO CCD area-detector
diffractometer		2254 independent reflections
Radiation source: fine-focus sealed tube2171 reflections with I > 2σ(I)
graphiteRint = 0.025
φ and ω scansθmax = 29.0°, θmin = 3.1°
Absorption correction: multi-scan
(SADABS; Bruker, 2009)		h = −9→9
Tmin = 0.947, Tmax = 0.979k = −19→19
10676 measured reflectionsl = −11→11
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.034Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.126H atoms treated by a mixture of independent and constrained refinement
S = 1.17 w = 1/[σ2(Fo2) + (0.098P)2]
where P = (Fo2 + 2Fc2)/3
2254 reflections(Δ/σ)max < 0.001
233 parametersΔρmax = 0.57 e Å−3
1 restraintΔρmin = −0.56 e Å−3
Crystal data top
C16H17N3O4·2H2OV = 826.42 (9) Å3
Mr = 351.36Z = 2
Monoclinic, P21Mo Kα radiation
a = 6.8156 (4) ŵ = 0.11 mm−1
b = 14.5648 (10) ÅT = 100 K
c = 8.5589 (5) Å0.50 × 0.28 × 0.19 mm
β = 103.421 (2)°
Data collection top
Bruker APEXII DUO CCD area-detector
diffractometer		2254 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2009)		2171 reflections with I > 2σ(I)
Tmin = 0.947, Tmax = 0.979Rint = 0.025
10676 measured reflectionsθmax = 29.0°
Refinement top
R[F2 > 2σ(F2)] = 0.034H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.126Δρmax = 0.57 e Å−3
S = 1.17Δρmin = −0.56 e Å−3
2254 reflectionsAbsolute structure: ?
233 parametersFlack parameter: ?
1 restraintRogers parameter: ?
Special details top

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) top
xyzUiso*/Ueq
O10.7986 (2)0.81175 (12)1.11648 (15)0.0180 (3)
O20.6823 (2)1.23398 (11)0.79017 (15)0.0156 (3)
O30.8195 (2)1.38828 (11)1.30523 (16)0.0189 (3)
O40.89952 (19)1.23697 (11)1.45332 (14)0.0162 (3)
N10.6308 (2)0.59240 (13)0.6538 (2)0.0172 (3)
N20.7323 (2)0.91163 (13)0.90629 (17)0.0130 (3)
N30.7635 (2)0.98623 (13)1.00977 (19)0.0138 (3)
C10.7218 (3)0.65940 (15)0.9179 (2)0.0171 (4)
H1A0.75680.65051.02850.020*
C20.6821 (3)0.58454 (16)0.8141 (2)0.0206 (4)
H2A0.69170.52600.85840.025*
C30.6190 (3)0.67728 (16)0.5943 (2)0.0170 (4)
H3A0.58370.68410.48330.020*
C40.6562 (3)0.75638 (15)0.6879 (2)0.0165 (4)
H4A0.64630.81410.64030.020*
C50.7087 (2)0.74703 (14)0.8545 (2)0.0118 (4)
C60.7510 (2)0.82624 (14)0.9712 (2)0.0126 (4)
C70.7415 (2)1.06540 (15)0.9400 (2)0.0127 (3)
H7A0.71001.06850.82850.015*
C80.7652 (2)1.14993 (14)1.0336 (2)0.0117 (3)
C90.7321 (2)1.23481 (15)0.9547 (2)0.0122 (4)
C100.7488 (3)1.31661 (14)1.0429 (2)0.0131 (4)
H10A0.72421.37270.99020.016*
C110.8021 (2)1.31332 (14)1.2090 (2)0.0130 (4)
C120.8412 (2)1.22870 (15)1.2901 (2)0.0128 (4)
C130.8203 (2)1.14806 (14)1.2032 (2)0.0116 (3)
H13A0.84281.09211.25660.014*
C140.6607 (3)1.32161 (15)0.7124 (2)0.0168 (4)
H14A0.64691.31330.59910.025*
H14B0.77771.35840.75520.025*
H14C0.54301.35190.73080.025*
C150.7866 (3)1.47619 (16)1.2305 (2)0.0184 (4)
H15A0.79061.52251.31100.028*
H15B0.65711.47711.15630.028*
H15C0.89001.48821.17380.028*
C160.9457 (3)1.15432 (15)1.5425 (2)0.0176 (4)
H16A1.00341.16871.65310.026*
H16B1.04031.11911.49990.026*
H16C0.82441.11931.53480.026*
H1N20.692 (4)0.923 (2)0.803 (3)0.017 (6)*
O2W0.6218 (2)0.96947 (12)0.57107 (16)0.0189 (3)
H1W20.71450.96360.52280.028*
H2W20.52460.99580.51130.028*
O1W0.8961 (2)0.92446 (13)0.39361 (16)0.0228 (3)
H1W10.96930.88840.46000.034*
H2W10.85540.89500.30550.034*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0273 (7)0.0138 (8)0.0110 (6)0.0009 (5)0.0009 (5)0.0001 (5)
O20.0256 (6)0.0115 (7)0.0088 (6)−0.0002 (5)0.0017 (4)0.0008 (5)
O30.0313 (7)0.0101 (7)0.0128 (6)0.0004 (6)0.0003 (5)−0.0028 (5)
O40.0261 (6)0.0122 (7)0.0085 (5)0.0014 (5)0.0004 (4)0.0006 (5)
N10.0194 (6)0.0137 (9)0.0176 (8)−0.0008 (6)0.0025 (5)−0.0044 (6)
N20.0178 (6)0.0097 (8)0.0105 (6)−0.0013 (6)0.0016 (5)−0.0023 (6)
N30.0161 (6)0.0103 (8)0.0143 (6)−0.0011 (6)0.0020 (5)−0.0030 (6)
C10.0249 (8)0.0123 (10)0.0136 (8)−0.0001 (7)0.0035 (6)0.0005 (7)
C20.0328 (9)0.0099 (10)0.0185 (9)−0.0008 (8)0.0045 (7)−0.0008 (8)
C30.0202 (7)0.0144 (10)0.0148 (8)0.0010 (7)0.0010 (6)−0.0023 (7)
C40.0214 (8)0.0126 (10)0.0139 (8)0.0016 (7)0.0008 (6)0.0002 (7)
C50.0122 (6)0.0100 (10)0.0128 (7)−0.0002 (6)0.0025 (5)−0.0016 (7)
C60.0132 (7)0.0126 (10)0.0115 (7)−0.0002 (6)0.0018 (5)−0.0008 (6)
C70.0137 (6)0.0121 (9)0.0119 (7)−0.0008 (6)0.0024 (5)−0.0031 (7)
C80.0138 (7)0.0094 (9)0.0118 (8)−0.0003 (6)0.0025 (5)−0.0013 (6)
C90.0136 (7)0.0125 (9)0.0100 (7)−0.0007 (7)0.0017 (5)−0.0017 (7)
C100.0169 (7)0.0090 (9)0.0129 (7)−0.0001 (7)0.0024 (6)−0.0007 (7)
C110.0153 (7)0.0098 (10)0.0133 (8)−0.0003 (7)0.0020 (6)−0.0026 (7)
C120.0145 (6)0.0136 (10)0.0095 (7)0.0005 (7)0.0010 (5)−0.0003 (7)
C130.0126 (6)0.0098 (9)0.0121 (7)−0.0006 (6)0.0020 (5)0.0006 (6)
C140.0252 (8)0.0124 (10)0.0123 (7)0.0002 (7)0.0034 (6)0.0018 (7)
C150.0255 (8)0.0096 (9)0.0185 (8)0.0006 (7)0.0016 (6)−0.0027 (7)
C160.0244 (8)0.0154 (10)0.0129 (7)0.0018 (7)0.0042 (6)0.0042 (7)
O2W0.0265 (6)0.0172 (8)0.0127 (6)0.0040 (6)0.0039 (5)0.0029 (6)
O1W0.0282 (7)0.0261 (9)0.0118 (6)0.0080 (6)0.0002 (5)−0.0026 (6)
Geometric parameters (Å, °) top
O1—C61.228 (2)C7—H7A0.9300
O2—C91.3700 (19)C8—C91.402 (3)
O2—C141.431 (2)C8—C131.412 (2)
O3—C111.356 (2)C9—C101.401 (3)
O3—C151.426 (3)C10—C111.384 (2)
O4—C121.366 (2)C10—H10A0.9300
O4—C161.421 (2)C11—C121.410 (3)
N1—C31.332 (3)C12—C131.380 (3)
N1—C21.340 (3)C13—H13A0.9300
N2—C61.356 (3)C14—H14A0.9600
N2—N31.387 (2)C14—H14B0.9600
N2—H1N20.88 (3)C14—H14C0.9600
N3—C71.291 (3)C15—H15A0.9600
C1—C51.381 (3)C15—H15B0.9600
C1—C21.393 (3)C15—H15C0.9600
C1—H1A0.9300C16—H16A0.9600
C2—H2A0.9300C16—H16B0.9600
C3—C41.392 (3)C16—H16C0.9600
C3—H3A0.9300O2W—H1W20.8358
C4—C51.394 (2)O2W—H2W20.8306
C4—H4A0.9300O1W—H1W10.8468
C5—C61.509 (3)O1W—H2W10.8562
C7—C81.457 (3)
C9—O2—C14116.38 (15)C10—C9—C8120.44 (15)
C11—O3—C15117.89 (14)C11—C10—C9119.55 (17)
C12—O4—C16116.76 (16)C11—C10—H10A120.2
C3—N1—C2116.66 (17)C9—C10—H10A120.2
C6—N2—N3118.09 (14)O3—C11—C10124.14 (17)
C6—N2—H1N2124 (2)O3—C11—C12115.12 (15)
N3—N2—H1N2117 (2)C10—C11—C12120.74 (17)
C7—N3—N2114.86 (15)O4—C12—C13126.55 (18)
C5—C1—C2119.19 (17)O4—C12—C11113.82 (17)
C5—C1—H1A120.4C13—C12—C11119.64 (15)
C2—C1—H1A120.4C12—C13—C8120.47 (17)
N1—C2—C1123.5 (2)C12—C13—H13A119.8
N1—C2—H2A118.2C8—C13—H13A119.8
C1—C2—H2A118.2O2—C14—H14A109.5
N1—C3—C4124.15 (17)O2—C14—H14B109.5
N1—C3—H3A117.9H14A—C14—H14B109.5
C4—C3—H3A117.9O2—C14—H14C109.5
C3—C4—C5118.48 (18)H14A—C14—H14C109.5
C3—C4—H4A120.8H14B—C14—H14C109.5
C5—C4—H4A120.8O3—C15—H15A109.5
C1—C5—C4118.01 (17)O3—C15—H15B109.5
C1—C5—C6117.48 (15)H15A—C15—H15B109.5
C4—C5—C6124.52 (18)O3—C15—H15C109.5
O1—C6—N2123.39 (17)H15A—C15—H15C109.5
O1—C6—C5120.23 (18)H15B—C15—H15C109.5
N2—C6—C5116.38 (15)O4—C16—H16A109.5
N3—C7—C8120.95 (15)O4—C16—H16B109.5
N3—C7—H7A119.5H16A—C16—H16B109.5
C8—C7—H7A119.5O4—C16—H16C109.5
C9—C8—C13119.13 (16)H16A—C16—H16C109.5
C9—C8—C7119.69 (15)H16B—C16—H16C109.5
C13—C8—C7121.18 (17)H1W2—O2W—H2W2109.2
O2—C9—C10122.09 (17)H1W1—O1W—H2W1107.4
O2—C9—C8117.47 (16)
C6—N2—N3—C7−179.38 (14)C13—C8—C9—O2178.90 (14)
C3—N1—C2—C10.2 (3)C7—C8—C9—O2−1.3 (2)
C5—C1—C2—N1−0.1 (3)C13—C8—C9—C10−1.5 (2)
C2—N1—C3—C4−0.1 (3)C7—C8—C9—C10178.21 (15)
N1—C3—C4—C5−0.2 (3)O2—C9—C10—C11−179.21 (14)
C2—C1—C5—C4−0.1 (3)C8—C9—C10—C111.3 (2)
C2—C1—C5—C6179.42 (16)C15—O3—C11—C10−1.9 (2)
C3—C4—C5—C10.3 (3)C15—O3—C11—C12178.51 (15)
C3—C4—C5—C6−179.27 (16)C9—C10—C11—O3−179.05 (15)
N3—N2—C6—O1−1.7 (2)C9—C10—C11—C120.5 (2)
N3—N2—C6—C5177.93 (14)C16—O4—C12—C130.8 (2)
C1—C5—C6—O11.3 (2)C16—O4—C12—C11−178.67 (14)
C4—C5—C6—O1−179.19 (16)O3—C11—C12—O4−2.9 (2)
C1—C5—C6—N2−178.42 (15)C10—C11—C12—O4177.57 (14)
C4—C5—C6—N21.1 (2)O3—C11—C12—C13177.65 (15)
N2—N3—C7—C8178.65 (14)C10—C11—C12—C13−1.9 (2)
N3—C7—C8—C9−177.35 (15)O4—C12—C13—C8−177.80 (15)
N3—C7—C8—C132.4 (2)C11—C12—C13—C81.6 (2)
C14—O2—C9—C103.9 (2)C9—C8—C13—C120.1 (2)
C14—O2—C9—C8−176.53 (14)C7—C8—C13—C12−179.66 (14)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N2—H1N2···O2W0.88 (3)2.05 (3)2.916 (2)171 (2)
O2W—H1W2···O1W0.841.932.748 (2)167
O2W—H2W2···N1i0.832.102.887 (2)158
O1W—H1W1···O3ii0.852.182.8913 (19)141
O1W—H1W1···O4ii0.852.433.204 (2)152
O1W—H2W1···O1iii0.861.992.834 (2)170
C4—H4A···O2W0.932.343.253 (3)169
C7—H7A···O2W0.932.583.375 (2)143
C14—H14A···O4iii0.962.603.281 (2)128
Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) −x+2, y−1/2, −z+2; (iii) x, y, z−1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N2—H1N2···O2W0.88 (3)2.05 (3)2.916 (2)171 (2)
O2W—H1W2···O1W0.841.932.748 (2)167
O2W—H2W2···N1i0.832.102.887 (2)158
O1W—H1W1···O3ii0.852.182.8913 (19)141
O1W—H1W1···O4ii0.852.433.204 (2)152
O1W—H2W1···O1iii0.861.992.834 (2)170
C4—H4A···O2W0.932.343.253 (3)169
C7—H7A···O2W0.932.583.375 (2)143
C14—H14A···O4iii0.962.603.281 (2)128
Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) −x+2, y−1/2, −z+2; (iii) x, y, z−1.
Acknowledgements top

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).

references
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