2-(5-Meth­oxy-2-methyl-1H-indol-3-yl)-N′-[(1E,2E)-3-phenyl­prop-2-en-1-yl­idene]acetohydrazide

Mehmet Akkurt; Joel T Mague; Shaaban K Mohamed; Mustafa R Albayati; Mahmoud A A El-Remaily

doi:10.1107/S1600536813023805

. 2013 Aug 31;69(Pt 9):o1493. doi: 10.1107/S1600536813023805

2-(5-Methoxy-2-methyl-1H-indol-3-yl)-N′-[(1E,2E)-3-phenylprop-2-en-1-ylidene]acetohydrazide

Mehmet Akkurt ^a, Joel T Mague ^b, Shaaban K Mohamed ^c,^d, Mustafa R Albayati ^e,^*, Mahmoud A A El-Remaily ^f,^g

PMCID: PMC3884474 PMID: 24427110

Abstract

The title compound, C₂₁H₂₁N₃O₂, adopts a J-shaped conformation which 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 into R ₂ ²(8) and R ₂ ²(14) cyclic dimers, which form a chain running parallel to the b axis.

Related literature

For general background to side-effect toxicity of non-steroidal anti-inflammatory drugs (NSAIDs), see: Agrawal et al. (2010 ▶); Champion et al. (1997 ▶); Allan & Fletcher (1990 ▶). For reduction of GI toxicity attributed to NSAIDs, see: Halen et al. (2009 ▶); Schoen & Vender (1989 ▶); Mitchell & Warner (1999 ▶). For hydrogen-bond motifs, see: Etter et al. (1990 ▶).

Experimental

Crystal data

C₂₁H₂₁N₃O₂
M _r = 347.41
Triclinic,
a = 8.2786 (9) Å
b = 10.1194 (11) Å
c = 11.7739 (13) Å
α = 93.001 (2)°
β = 108.993 (2)°
γ = 105.578 (2)°
V = 887.76 (17) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 150 K
0.26 × 0.13 × 0.08 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2013 ▶) T _min = 0.78, T _max = 0.99
16303 measured reflections
4574 independent reflections
3675 reflections with I > 2σ(I)
R _int = 0.041

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.126
S = 1.08
4574 reflections
245 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.36 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: APEX2 (Bruker, 2013 ▶); cell refinement: SAINT (Bruker, 2013 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: WinGX (Farrugia, 2012 ▶) and PLATON.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813023805/qm2100sup1.cif

e-69-o1493-sup1.cif^{(27.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813023805/qm2100Isup2.hkl

e-69-o1493-Isup2.hkl^{(250.8KB, hkl)}

Click here for additional data file.^{(7.3KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813023805/qm2100Isup3.cml

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	0.891 (18)	2.093 (18)	2.9841 (14)	178.1 (9)
N2—H2⋯O2ⁱⁱ	0.903 (16)	2.012 (16)	2.9055 (13)	170.0 (14)
C7—H7⋯N3	0.95	2.54	3.3609 (15)	145

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

Acknowledgments

Manchester Metropolitan University, Tulane University and Erciyes University are gratefully acknowledged for supporting this study.

supplementary crystallographic information

1. Comment

Indomethacin as other common anti-inflammatory drugs (NSAIDs) which are widely employed in the treatment of pain and inflammation has been reported to be associated with a number of undesirable effects, in particular gastrointestinal (GI) toxicity and ulceration (Agrawal et al., 2010; Champion et al., 1997; Allan & Fletcher, 1990) which represent a still unsolved therapeutic problem. Topical irritation by the free carboxylic group of Indomethacin is considered an important factor in establishing superficial stomach erosion (Schoen & Vender, 1989; Mitchell & Warner, 1999). Considerable attention has been focused on the development of bio-reversible derivatives of such pro-drugs to temporarily mask the acidic group as a promising means of reducing or abolishing the GI toxicity due to the local action mechanism (Halen et al., 2009). Based on such facts and continue to our on-going study in functionalization of NSAIDs we herein report the synthesis and crystal structure of the title compound.

The molecular conformation adopted by I in the crystal is "J" shaped (Fig. 1) and appears to be at least partially directed by a weak, intramolecular C7—H7···N3 hydrogen bond. The indole ring system is almostly planar [maximum deviations = -0.046 (1) Å for N1, -0.036 (1) Å for C2 and 0.035 (1) Å for C4] and the dihedral angle between it and the terminal phenyl ring is 79.10 (5)°.

In the crystal structure, the N—H···O hydrogen bonding consists of R²₂(8) rings (Etter et al., 1990) with 2 N2—H2···O2 contacts and R²₂(14) rings with 2 N1—H1···O2 contacts which form a chain running parallel to the b axis (Table 1, Figs. 2 & 3).

2. Experimental

A mixture of 233 mg (1 mmol) 2-(5-methoxy-2-methyl-1H-indole-3-yl)acetohydrazide and 132 mg (1 mmol) of (2E)-3-phenylprop-2-enal in 50 ml of ethanol containing a few drops of glacial acetic acid was refluxed for 6 hrs. The mixture was cooled to room temperature and the excess solvent was evaporated under vacuum. The resulting solid was collected, washed with ethanol and recrystalized from dioxan to give colourless tablets (M.p. 410–413 K) suitable for X-ray analysis.

IR (KBr cm^-1): (C=O amide 1661), (NH 3301), (C=N 1606) (C—H, Ar 3021–3072), (C—H aliphatic 2836–2957). ¹H-NMR: (DMSO-d₆) δ at 3.6(s, 3H, –OCH₃), 2.3(s, 3H, CH₃), 3.4(s, 2H, –CH₂), 6.5(d,1H, –CH= alkene), 6.6(d,1H, –CH= alkene), 8.2(d, 1H, –CH=N), 11.8(s, 1H, –NH amide), the aromatic protons of indole nuclei and benzene ring were appeared in the range of 7.0–7.9. ¹³C-NMR: 161(C=O amide), 149(–CH=N), 55(–OCH₃), 10(1 C, CH₃), 136(–C=C alkene), 125(–C=C alkene).