Ethyl 2-(5-meth­oxy-2-methyl-1H-indol-3-yl)acetate

Shaaban K Mohamed; Joel T Mague; Mehmet Akkurt; Alaa A Hassan; Mustafa R Albayati

doi:10.1107/S1600536813018618

. 2013 Jul 13;69(Pt 8):o1242. doi: 10.1107/S1600536813018618

Ethyl 2-(5-methoxy-2-methyl-1H-indol-3-yl)acetate

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

PMCID: PMC3793745 PMID: 24109332

Abstract

In the title compound, C₁₄H₁₇NO₃, the nine-membered 1H-indole ring system is essentially planar [maximum deviation = 0.019 (1) Å]. In the crystal, molecules are linked via N—H⋯O hydrogen bonds, forming chains along [001]. These chains are linked via C—H⋯O hydrogen bonds and C—H⋯π interactions, forming a two-dimensional network lying parallel to the ac plane.

Related literature

For medicinal applications of the drug indomethacin (systematic name: 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid), see: Paneth (1995 ▶); McIntyre et al. (2001 ▶); Abou-Ghannam et al. (2012 ▶). For the synthesis and reactions of indomethacin with other non-steroidal anti-inflammatory molecules, see: Mohamed et al. (2012 ▶). graphic file with name e-69-o1242-scheme1.jpg

Experimental

Crystal data

C₁₄H₁₇NO₃
M _r = 247.29
Monoclinic,
a = 7.8117 (5) Å
b = 17.1953 (12) Å
c = 9.9003 (7) Å
β = 106.756 (1)°
V = 1273.39 (15) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 150 K
0.23 × 0.21 × 0.06 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2013 ▶) T _min = 0.84, T _max = 1.00
22947 measured reflections
3374 independent reflections
2889 reflections with I > 2σ(I)
R _int = 0.043

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.117
S = 1.08
3374 reflections
170 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.31 e Å⁻³
Δρ_min = −0.24 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 DIAMOND (Brandenburg & Putz, 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/S1600536813018618/su2618sup1.cif

e-69-o1242-sup1.cif^{(23.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813018618/su2618Isup2.hkl

e-69-o1242-Isup2.hkl^{(185.2KB, hkl)}

Click here for additional data file.^{(5.3KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813018618/su2618Isup3.cml

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

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

Cg1 is the centroid of the C1–C6 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O2ⁱ	0.914 (18)	2.013 (18)	2.8987 (14)	162.7 (16)
C7—H7B⋯O2ⁱⁱ	0.98	2.57	3.4271 (18)	146
C13—H13A⋯O1ⁱⁱⁱ	0.99	2.55	3.4236 (16)	148
C7—H7A⋯Cg1^iv	0.98	2.99	3.9550 (16)	169

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

Acknowledgments

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

supplementary crystallographic information

Comment

Indomethacin, chemically named 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid is a non-steroidal drug (NSAID) and is commonly used as an anti-inflammatory drug by inhibiting cyclooxygenase (COX) 1 and 2 enzymes. It also clinically used as a tocolytic agent to delay premature labor (preterm birth; PTB), reduce amniotic fluid in polyhydramnios, and to close patent ductus arteriosus (PDA). PTB is a major cause of neonatal morbidity and mortality worldwide (Paneth, 1995; McIntyre et al., 2001; Abou-Ghannam et al., 2012). In view of these facts and as part of our ongoing study incorporating NSAID's as a substructure in the synthesis of potential bio-active pharmacophors (Mohamed et al., 2012), indomethacin has been hydrolysed during its esterification in acidic medium with ethanol to afforded the title corresponding ethyl ester.

In the title compound, Fig. 1, the nine-membered 1H-indole ring system (N1/C1–C6/C8/C9) is essentially planar with a maximum deviation of 0.019 (1) Å for N1. The C2–C3–O1–C7, C1–C9–C8–C10, C1–C9–C11–C12, C9–C11–C12–O2, C11–C12–O3–C13 and C12–O3–C13–C14 torsion angles are -6.53 (18), -177.77 (12), 117.42 (13), -69.51 (15), 177.50 (9) and 171.98 (10)°, respectively.

In the crystal, molecules are linked via N-H···O hydrogen bonds forming chains along [001]. These chains are linked via C-H···O hydrogen bonds and C-H···π interactions forming a two-dimensional network lying parallel to the ac plane (Fig. 2 and Table 1).

Experimental

A mixture of 0.03 mol indomethacin (10.57 g m) in 150 ml of absolute ethanol and 6 ml of concentrated H₂SO₄ was refluxed for 6 h. The mixture was cooled to room temperature and neutralized with NaHCO₃ solution. The ester was separated as an organic layer, washed with water and extracted with diethyl ether (3 × 50mL). The combined ether layers were dried over MgSO₄, filtered and left for 3–4 days until brown crystals formed. The solid was collected and recrystallized from cyclohexane to give the pure ester as silver-coloured crystals (m.p. 347–350 K) suitable for X-ray diffraction. Spectroscopic data for the title compound are available in the archived CIF.