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

Mehmet Akkurt; Joel T Mague; Shaaban K Mohamed; Antar A Abelhamid; Mustafa R Albayati

doi:10.1107/S1600536813027050

. 2013 Oct 19;69(Pt 11):o1660–o1661. doi: 10.1107/S1600536813027050

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

Mehmet Akkurt ^a, Joel T Mague ^b, Shaaban K Mohamed ^c,^d, Antar A Abelhamid ^e, Mustafa R Albayati ^f,^*

PMCID: PMC3884321 PMID: 24454097

Abstract

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 R ₂ ²(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.

Related literature

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 ▶). graphic file with name e-69-o1660-scheme1.jpg

Experimental

Crystal data

C₂₀H₂₁N₃O₃
M _r = 351.40
Triclinic,
a = 7.1894 (2) Å
b = 10.4055 (3) Å
c = 12.4403 (4) Å
α = 107.983 (2)°
β = 92.451 (2)°
γ = 97.882 (2)°
V = 873.24 (5) Å³
Z = 2
Cu Kα radiation
μ = 0.74 mm⁻¹
T = 100 K
0.14 × 0.12 × 0.08 mm

Data collection

Bruker D8 VENTURE PHOTON 100 CMOS diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2013 ▶) T _min = 0.85, T _max = 0.94
8928 measured reflections
3121 independent reflections
2579 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.036
wR(F ²) = 0.090
S = 1.04
3121 reflections
246 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: APEX2 (Bruker, 2013 ▶); cell refinement: SAINT (Bruker, 2013 ▶); data reduction: SAINT; 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 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813027050/sj5357sup1.cif

e-69-o1660-sup1.cif^{(27.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813027050/sj5357Isup2.hkl

e-69-o1660-Isup2.hkl^{(171.4KB, hkl)}

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

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O2ⁱ	0.88 (2)	2.04 (2)	2.9212 (17)	174.0 (18)
N2—H2⋯O2ⁱⁱ	0.920 (18)	1.988 (18)	2.9025 (16)	171.9 (15)
C4—H4⋯O3ⁱⁱⁱ	0.95	2.50	3.410 (2)	161
C11—H11B⋯N3	0.99	2.36	2.8373 (19)	109
C20—H20A⋯O1^iv	0.98	2.49	3.215 (2)	131

Open in a new tab

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

Acknowledgments

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

supplementary crystallographic information

1. Comment

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.

2. Experimental

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.