supplementary materials


sj5357 scheme

Acta Cryst. (2013). E69, o1660-o1661    [ doi:10.1107/S1600536813027050 ]

N'-[(E)-4-Meth­oxy­benzyl­idene]-2-(5-meth­oxy-2-methyl-1H-indol-3-yl)acetohydrazide

M. Akkurt, J. T. Mague, S. K. Mohamed, A. A. Abelhamid and M. R. Albayati

Abstract top

The conformation adopted by the title compound, C20H21N3O3, in the crystal is `J'-shaped and appears to be at least partially directed by a weak intra­molecular C-H...N hydrogen bond. In the crystal, mol­ecules are linked by N-H...O hydrogen bonds, forming dimers with R22(8) motifs. Furthermore, these dimers connect to each other via C-H...O and N-H...O hydrogen bonds to form a three-dimensional network.

Comment top

Indomethacin like other non-steroidal anti-inflammatory drugs (NSAIDs) is widely used in treatment of pain, fever, and inflammation (Richy et al., 2004). Prolonged administration of such drugs is commonly associated with several undesired side-effects. The most common of these are gastrointestinal hemorrhage, ulceration, and decreased renal function (Allison et al., 1992; McMahon 2001; Rocha et al., 2001). The existence of a free carboxylic acid group in the parent drug has been considred to be the major factor in establishing superficial stomach erosion, particularly in the corpus region of the stomach (Halen et al., 2009). Thus, it was considered essential to mask or to remove this functional group in order to produce a safer and more tolerant prodrug profile. Following this reasoning, we report here the synthesis and crystal structure of the title compound.

The "J" shaped conformation of the title molecule (I) is shown in Fig. 1. The bond lengths and bond angles of (I) compare well with those in related compounds (Mague et al., 2013).

In the crystal, the molecules form inversion dimers with R22(8) motifs (Bernstein et al., 1995) through N—H···O hydrogen bonds (Fig. 2, Table 1). In addition, the dimers are linked by C—H···O and N—H···O hydrogen bonds (Table 1), forming a three-dimensional network.

Related literature top

For general medical applications of non-steriodal anti-inflammatory drugs (NSAIDs), see: Richy et al. (2004). For the undesirable side effects of such drugs, see: Allison et al. (1992); McMahon (2001); Rocha et al. (2001); Halen et al. (2009). For a similar structure, see: Mague et al. (2013). For hydrogen-bond motifs, see: Bernstein et al. (1995).

Experimental top

A mixture of 233 mg (1 mmol) 2-(5-methoxy-2-methyl-1H-indol-3-yl)acetohydrazide and 136 mg (1 mmol) of 4-methoxybenzaldehyde in 30 ml ethanol containing few drops of glacial acetic acid was refluxed for 5 h. The reaction mixture was allowed to cool to room temperature and the excess solvent was evaporated under vacuum. The residual solid was collected, washed with cold ethanol and recrystallized from ethanol. Colourless blocks of X-ray quality were obtained. M.p. 453–455 K.

Refinement top

The H atoms of the amino group were found in the difference Fourier maps, and were refined freely. C-bound H atoms were placed geometrically and refined using a riding model with C—H = 0.95 - 0.99 Å, and with Uiso(H) = 1.2 or 1.5Uiso(C).

Computing details top

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: WinGX (Farrugia, 2012) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. Perspective view of the title compound with 50% probability displacement ellipsoids.
[Figure 2] Fig. 2. Packing viewed along a showing the hydrogen bonds as dotted lines.
N'-[(E)-4-Methoxybenzylidene]-2-(5-methoxy-2-methyl-1H-indol-3-yl)-acetohydrazide top
Crystal data top
C20H21N3O3Z = 2
Mr = 351.40F(000) = 372
Triclinic, P1Dx = 1.336 Mg m3
Hall symbol: -P 1Cu Kα radiation, λ = 1.54178 Å
a = 7.1894 (2) ÅCell parameters from 6305 reflections
b = 10.4055 (3) Åθ = 3.8–68.2°
c = 12.4403 (4) ŵ = 0.74 mm1
α = 107.983 (2)°T = 100 K
β = 92.451 (2)°Block, colourless
γ = 97.882 (2)°0.14 × 0.12 × 0.08 mm
V = 873.24 (5) Å3
Data collection top
Bruker D8 VENTURE PHOTON 100 CMOS
diffractometer
3121 independent reflections
Radiation source: INCOATEC IµS micro–focus source2579 reflections with I > 2σ(I)
Mirror monochromatorRint = 0.029
Detector resolution: 10.4167 pixels mm-1θmax = 68.2°, θmin = 3.8°
ω scansh = 88
Absorption correction: multi-scan
(SADABS; Bruker, 2013)
k = 1112
Tmin = 0.85, Tmax = 0.94l = 1412
8928 measured reflections
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.036 w = 1/[Σ2(Fo2) + (0.0398P)2 + 0.2493P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.090(Δ/σ)max = 0.001
S = 1.04Δρmax = 0.19 e Å3
3121 reflectionsΔρmin = 0.18 e Å3
246 parameters
Crystal data top
C20H21N3O3γ = 97.882 (2)°
Mr = 351.40V = 873.24 (5) Å3
Triclinic, P1Z = 2
a = 7.1894 (2) ÅCu Kα radiation
b = 10.4055 (3) ŵ = 0.74 mm1
c = 12.4403 (4) ÅT = 100 K
α = 107.983 (2)°0.14 × 0.12 × 0.08 mm
β = 92.451 (2)°
Data collection top
Bruker D8 VENTURE PHOTON 100 CMOS
diffractometer
3121 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2013)
2579 reflections with I > 2σ(I)
Tmin = 0.85, Tmax = 0.94Rint = 0.029
8928 measured reflectionsθmax = 68.2°
Refinement top
R[F2 > 2σ(F2)] = 0.036H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.090Δρmax = 0.19 e Å3
S = 1.04Δρmin = 0.18 e Å3
3121 reflectionsAbsolute structure: ?
246 parametersAbsolute structure parameter: ?
0 restraintsRogers parameter: ?
Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > σ(F2) is used only for calculating -R-factor-obs 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
O10.71418 (17)0.52381 (11)0.54515 (9)0.0430 (4)
O20.98707 (13)0.84392 (9)1.03898 (8)0.0292 (3)
O30.13304 (14)0.95693 (11)0.60125 (9)0.0371 (3)
N10.79353 (17)0.35490 (13)0.91900 (12)0.0351 (4)
N20.76381 (16)0.90476 (12)0.94351 (10)0.0260 (3)
N30.58416 (16)0.88308 (12)0.89050 (9)0.0265 (3)
C10.7349 (3)0.44162 (19)0.43283 (14)0.0480 (6)
C20.7324 (2)0.46796 (15)0.63133 (13)0.0345 (5)
C30.7787 (2)0.33672 (16)0.61512 (15)0.0388 (5)
C40.7991 (2)0.28921 (15)0.70661 (15)0.0384 (5)
C50.7752 (2)0.37351 (15)0.81367 (14)0.0326 (4)
C60.72832 (19)0.50583 (14)0.83158 (13)0.0296 (4)
C70.7039 (2)0.55117 (15)0.73782 (13)0.0310 (4)
C80.7797 (2)0.48079 (17)1.12353 (14)0.0379 (5)
C90.76673 (19)0.47320 (15)1.00178 (14)0.0317 (5)
C100.72383 (19)0.56677 (14)0.95159 (12)0.0281 (4)
C110.67910 (19)0.70663 (14)1.01121 (12)0.0284 (4)
C120.82053 (19)0.82164 (14)0.99829 (11)0.0256 (4)
C130.5515 (2)0.97217 (14)0.84341 (11)0.0272 (4)
C140.3702 (2)0.96285 (14)0.78169 (11)0.0269 (4)
C150.2179 (2)0.86146 (14)0.77499 (12)0.0290 (4)
C160.0484 (2)0.85462 (15)0.71417 (12)0.0302 (4)
C170.0283 (2)0.95182 (15)0.66076 (12)0.0296 (4)
C180.1787 (2)1.05399 (15)0.66754 (12)0.0322 (5)
C190.3475 (2)1.05862 (15)0.72627 (12)0.0305 (5)
C200.2801 (2)0.84238 (17)0.57471 (14)0.0380 (5)
H10.855 (3)0.295 (2)0.9360 (16)0.052 (5)*
H1A0.862200.417700.428900.0720*
H1B0.714900.492700.380100.0720*
H1C0.641900.357800.412000.0720*
H20.847 (2)0.9799 (18)0.9426 (14)0.037 (4)*
H30.796000.280500.541100.0470*
H40.829000.200300.696100.0460*
H70.668200.638300.747300.0370*
H8A0.663100.432101.139700.0570*
H8B0.797800.576801.171400.0570*
H8C0.886700.438401.139600.0570*
H11A0.674200.717901.093000.0340*
H11B0.552600.713700.980900.0340*
H130.648101.046500.848800.0330*
H150.230200.795900.812600.0350*
H160.053500.783800.709100.0360*
H180.165001.120900.631500.0390*
H190.450101.128000.729200.0370*
H20A0.232100.759600.531700.0570*
H20B0.384500.857400.529100.0570*
H20C0.325000.831300.645100.0570*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0543 (7)0.0399 (6)0.0312 (6)0.0116 (5)0.0040 (5)0.0044 (5)
O20.0263 (5)0.0249 (5)0.0361 (5)0.0024 (4)0.0050 (4)0.0112 (4)
O30.0322 (6)0.0354 (6)0.0412 (6)0.0052 (5)0.0101 (5)0.0103 (5)
N10.0263 (7)0.0250 (7)0.0565 (9)0.0034 (5)0.0021 (6)0.0177 (6)
N20.0243 (6)0.0238 (6)0.0290 (6)0.0014 (5)0.0035 (5)0.0091 (5)
N30.0257 (6)0.0267 (6)0.0251 (6)0.0044 (5)0.0018 (5)0.0060 (5)
C10.0488 (11)0.0495 (10)0.0348 (9)0.0063 (8)0.0034 (8)0.0016 (8)
C20.0298 (8)0.0309 (8)0.0389 (8)0.0030 (6)0.0015 (6)0.0063 (7)
C30.0322 (8)0.0288 (8)0.0469 (9)0.0022 (6)0.0044 (7)0.0007 (7)
C40.0269 (8)0.0232 (8)0.0604 (11)0.0041 (6)0.0038 (7)0.0064 (7)
C50.0217 (7)0.0253 (7)0.0494 (9)0.0010 (6)0.0006 (6)0.0117 (7)
C60.0201 (7)0.0245 (7)0.0421 (8)0.0007 (5)0.0014 (6)0.0093 (6)
C70.0271 (8)0.0257 (7)0.0383 (8)0.0038 (6)0.0007 (6)0.0079 (6)
C80.0301 (8)0.0363 (9)0.0516 (10)0.0003 (6)0.0071 (7)0.0240 (8)
C90.0199 (7)0.0287 (8)0.0469 (9)0.0017 (6)0.0035 (6)0.0159 (7)
C100.0212 (7)0.0250 (7)0.0388 (8)0.0006 (5)0.0021 (6)0.0131 (6)
C110.0266 (7)0.0280 (8)0.0312 (7)0.0028 (6)0.0002 (6)0.0113 (6)
C120.0275 (8)0.0227 (7)0.0246 (7)0.0053 (6)0.0004 (6)0.0044 (6)
C130.0298 (8)0.0240 (7)0.0266 (7)0.0031 (6)0.0004 (6)0.0072 (6)
C140.0297 (8)0.0257 (7)0.0237 (7)0.0063 (6)0.0006 (6)0.0049 (6)
C150.0323 (8)0.0250 (7)0.0301 (7)0.0063 (6)0.0008 (6)0.0089 (6)
C160.0284 (8)0.0257 (7)0.0336 (8)0.0026 (6)0.0015 (6)0.0060 (6)
C170.0296 (8)0.0303 (8)0.0264 (7)0.0094 (6)0.0022 (6)0.0042 (6)
C180.0362 (8)0.0313 (8)0.0316 (8)0.0066 (6)0.0019 (6)0.0136 (7)
C190.0298 (8)0.0301 (8)0.0316 (8)0.0026 (6)0.0004 (6)0.0111 (6)
C200.0293 (8)0.0443 (9)0.0367 (8)0.0029 (7)0.0040 (6)0.0098 (7)
Geometric parameters (Å, º) top
O1—C11.422 (2)C14—C151.393 (2)
O1—C21.3776 (19)C15—C161.388 (2)
O2—C121.2422 (17)C16—C171.390 (2)
O3—C171.3653 (18)C17—C181.389 (2)
O3—C201.425 (2)C18—C191.377 (2)
N1—C51.386 (2)C1—H1A0.9800
N1—C91.383 (2)C1—H1B0.9800
N2—N31.3818 (16)C1—H1C0.9800
N2—C121.3475 (19)C3—H30.9500
N3—C131.2810 (19)C4—H40.9500
N1—H10.88 (2)C7—H70.9500
N2—H20.920 (18)C8—H8A0.9800
C2—C31.406 (2)C8—H8B0.9800
C2—C71.382 (2)C8—H8C0.9800
C3—C41.384 (2)C11—H11A0.9900
C4—C51.383 (2)C11—H11B0.9900
C5—C61.415 (2)C13—H130.9500
C6—C101.434 (2)C15—H150.9500
C6—C71.400 (2)C16—H160.9500
C8—C91.490 (2)C18—H180.9500
C9—C101.369 (2)C19—H190.9500
C10—C111.501 (2)C20—H20A0.9800
C11—C121.514 (2)C20—H20B0.9800
C13—C141.460 (2)C20—H20C0.9800
C14—C191.398 (2)
C1—O1—C2118.05 (13)C14—C19—C18121.03 (14)
C17—O3—C20117.85 (13)O1—C1—H1A109.00
C5—N1—C9109.09 (13)O1—C1—H1B109.00
N3—N2—C12122.52 (12)O1—C1—H1C109.00
N2—N3—C13114.94 (12)H1A—C1—H1B109.00
C9—N1—H1120.9 (12)H1A—C1—H1C109.00
C5—N1—H1126.0 (13)H1B—C1—H1C109.00
N3—N2—H2118.7 (10)C2—C3—H3120.00
C12—N2—H2118.8 (10)C4—C3—H3120.00
O1—C2—C3123.67 (14)C3—C4—H4121.00
O1—C2—C7115.23 (14)C5—C4—H4121.00
C3—C2—C7121.10 (15)C2—C7—H7120.00
C2—C3—C4120.20 (16)C6—C7—H7120.00
C3—C4—C5118.84 (15)C9—C8—H8A109.00
C4—C5—C6121.74 (15)C9—C8—H8B109.00
N1—C5—C6107.17 (14)C9—C8—H8C110.00
N1—C5—C4131.07 (15)H8A—C8—H8B109.00
C5—C6—C10107.06 (13)H8A—C8—H8C109.00
C7—C6—C10134.17 (14)H8B—C8—H8C109.00
C5—C6—C7118.73 (14)C10—C11—H11A109.00
C2—C7—C6119.35 (15)C10—C11—H11B109.00
N1—C9—C8120.08 (14)C12—C11—H11A109.00
N1—C9—C10109.40 (14)C12—C11—H11B109.00
C8—C9—C10130.47 (15)H11A—C11—H11B108.00
C6—C10—C11126.49 (13)N3—C13—H13119.00
C9—C10—C11126.29 (13)C14—C13—H13119.00
C6—C10—C9107.22 (13)C14—C15—H15119.00
C10—C11—C12113.58 (12)C16—C15—H15119.00
N2—C12—C11119.29 (12)C15—C16—H16120.00
O2—C12—N2118.72 (13)C17—C16—H16120.00
O2—C12—C11121.97 (13)C17—C18—H18120.00
N3—C13—C14121.97 (13)C19—C18—H18120.00
C13—C14—C19119.12 (13)C14—C19—H19119.00
C15—C14—C19118.23 (13)C18—C19—H19119.00
C13—C14—C15122.65 (13)O3—C20—H20A110.00
C14—C15—C16121.06 (14)O3—C20—H20B109.00
C15—C16—C17119.73 (14)O3—C20—H20C109.00
O3—C17—C16124.68 (14)H20A—C20—H20B109.00
C16—C17—C18119.73 (13)H20A—C20—H20C109.00
O3—C17—C18115.59 (14)H20B—C20—H20C109.00
C17—C18—C19120.21 (15)
C1—O1—C2—C33.0 (2)C10—C6—C7—C2174.92 (15)
C1—O1—C2—C7177.73 (15)C7—C6—C10—C9177.33 (16)
C20—O3—C17—C18169.28 (13)C5—C6—C7—C22.2 (2)
C20—O3—C17—C1611.6 (2)C5—C6—C10—C90.04 (16)
C9—N1—C5—C62.29 (16)C8—C9—C10—C110.6 (3)
C5—N1—C9—C102.37 (17)N1—C9—C10—C61.46 (16)
C9—N1—C5—C4176.09 (16)N1—C9—C10—C11178.14 (13)
C5—N1—C9—C8179.76 (13)C8—C9—C10—C6179.03 (15)
C12—N2—N3—C13179.16 (13)C6—C10—C11—C1264.10 (18)
N3—N2—C12—C115.17 (19)C9—C10—C11—C12116.38 (16)
N3—N2—C12—O2176.44 (12)C10—C11—C12—O265.23 (17)
N2—N3—C13—C14178.67 (12)C10—C11—C12—N2116.43 (14)
O1—C2—C3—C4178.35 (14)N3—C13—C14—C19176.06 (13)
C7—C2—C3—C40.9 (2)N3—C13—C14—C153.6 (2)
C3—C2—C7—C62.4 (2)C13—C14—C19—C18179.70 (13)
O1—C2—C7—C6176.95 (13)C15—C14—C19—C180.7 (2)
C2—C3—C4—C50.7 (2)C13—C14—C15—C16179.08 (13)
C3—C4—C5—N1177.38 (15)C19—C14—C15—C160.6 (2)
C3—C4—C5—C60.8 (2)C14—C15—C16—C171.3 (2)
N1—C5—C6—C7179.22 (13)C15—C16—C17—C180.8 (2)
C4—C5—C6—C70.7 (2)C15—C16—C17—O3178.29 (13)
C4—C5—C6—C10177.19 (14)O3—C17—C18—C19179.57 (13)
N1—C5—C6—C101.37 (16)C16—C17—C18—C190.4 (2)
C7—C6—C10—C113.1 (3)C17—C18—C19—C141.2 (2)
C5—C6—C10—C11179.56 (13)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.88 (2)2.04 (2)2.9212 (17)174.0 (18)
N2—H2···O2ii0.920 (18)1.988 (18)2.9025 (16)171.9 (15)
C4—H4···O3iii0.952.503.410 (2)161
C11—H11B···N30.992.362.8373 (19)109
C20—H20A···O1iv0.982.493.215 (2)131
Symmetry codes: (i) x+2, y+1, z+2; (ii) x+2, y+2, z+2; (iii) x+1, y1, z; (iv) x1, y, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.88 (2)2.04 (2)2.9212 (17)174.0 (18)
N2—H2···O2ii0.920 (18)1.988 (18)2.9025 (16)171.9 (15)
C4—H4···O3iii0.95002.50003.410 (2)161.00
C11—H11B···N30.99002.36002.8373 (19)109.00
C20—H20A···O1iv0.98002.49003.215 (2)131.00
Symmetry codes: (i) x+2, y+1, z+2; (ii) x+2, y+2, z+2; (iii) x+1, y1, z; (iv) x1, y, z.
Acknowledgements top

The authors are deeply grateful to Tulane University, Erciyes University and Manchester Metropolitan University for supporting this study.

references
References top

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