6,9-Dimeth­oxy-3,4-dihydro-1H-1,4-oxazino[4,3-a]indol-1-one

Cristian O Salas; Ricardo A Tapia; Yolanda Prieto

doi:10.1107/S1600536811000249

. 2011 Jan 12;67(Pt 2):o318. doi: 10.1107/S1600536811000249

6,9-Dimethoxy-3,4-dihydro-1H-1,4-oxazino[4,3-a]indol-1-one

Cristian O Salas ^a,^*, Ricardo A Tapia ^a, Yolanda Prieto ^a

PMCID: PMC3051655 PMID: 21523004

Abstract

The title compound, C₁₃H₁₃NO₄, is one cyclization product of the reaction of ethyl 1-(2-bromoethyl)-4,7-dimethoxy-1H-indole-2-carboxylate with sodium azide in refluxing dioxane and was synthesized with the aim of finding new compounds with biological properties. Bond lengths and angles are within the expected values and confirm the bond orders giving in the scheme. The shortest contacts between molecules are set along the a axis, where stacked molecules related by an inversion center form an ABAB array through π–π stacking interactions with centroid–centroid distances ranging from 3.922 (2) to 4.396 (2) Å. Weak C—H⋯O hydrogen bonds further stabilize the structure.

Related literature

For background to oxazinoindoles as intermediates in the chemistry of bioactive compounds, see: Demerson et al. (1975 ▶); Fedouloff et al. (2001 ▶); Shchekotikhin et al. (2004 ▶). Several synthetic strategies for the preparation of oxazinoindoles have been reported, for some examples, see: Abbiati et al. (2005 ▶); Brudeli et al. (2010 ▶); Fu et al. (2010 ▶).

Experimental

Crystal data

C₁₃H₁₃NO₄
M _r = 247.24
Monoclinic,
a = 8.414 (2) Å
b = 6.9722 (19) Å
c = 19.331 (5) Å
β = 101.276 (4)°
V = 1112.1 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 100 K
0.72 × 0.27 × 0.26 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ▶) T _min = 0.925, T _max = 0.972
10088 measured reflections
2277 independent reflections
1922 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.102
S = 1.06
2277 reflections
165 parameters
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811000249/sj5085sup1.cif

e-67-0o318-sup1.cif^{(18.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811000249/sj5085Isup2.hkl

e-67-0o318-Isup2.hkl^{(109.6KB, 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
C2—H2a⋯O16	0.99	2.40	2.9776 (18)	117
C3—H3B⋯O14ⁱ	0.99	2.56	3.2524 (19)	127 (4)
C15—H15B⋯O5ⁱⁱ	0.98	2.56	3.493 (2)	159 (4)
C17—H17A⋯O5ⁱⁱⁱ	0.98	2.59	3.484 (2)	151 (4)

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

Acknowledgments

We gratefully acknowledge the Unidade de Raios X, RIAIDT, University of Santiago de Compostela, Spain.

supplementary crystallographic information

Comment

Oxazinoindoles are very important as precursors of a wide range of natural and synthetic products with relevant biological properties such as antidepressant activity (Demerson et al., 1975), 5-HT4 Receptor Antagonist (Fedouloff et al., 2001), antiproliferative activity (Shchekotikhin et al., 2004). The oxazinoindolone 2 is the product of the cyclization of ethyl 1-(2-bromoethyl)-4,7-dimethoxy-1H-indole-2-carboxylate mediated by the azido intermediate in dioxane at reflux (Fig. 2). Other efficient cyclizations have been reported also (Abbiati et al.,2005; Brudeli et al., 2010; Fu et al., 2010). The molecular structure of the title compound is represented in Fig. 1. Bond lengths and angles are within the expected values and confirm the bond orders giving in the Scheme. The e.s.d. for the molecular plane, as well as the bond distances and angles for the indol fragment, are within the expected values for bicyclic aromatic systems [r.m.s deviation = 0.006 (1) Å]. The shortest contacts between molecules are set along the crystallographic axis a, where the stacked molecules related by an inversion center form an ABAB array. Centroid to centroid distances range from 3.922 (2) to 4.396 (2)Å (Table 2). Weak C–H···O hydrogen bonds further stabilize the structure (Table 1).

Experimental

6,9-Dimethoxy-3,4-dihydro-1H-[1,4]oxazino[4,3-a]indol-1-one (2)

Sodium azide (40 mg, 0.62 mmol) was added to a solution of ethyl 1-(2-bromoethyl)-4,7-dimethoxy-1H-indole-2-carboxylate 1 (100 mg, 0.28 mmol) in dioxane (5.0 ml) and the mixture was stirred at reflux for 4 days. The suspension was filtered and the solvent was removed in vacuum to give a residue, which was purified by flash column chromatography (CH₂Cl₂) to give 6,9-dimethoxy-3,4-dihydro-1H-[1,4]oxazino[4,3-a]indol-1-one (2) (27 mg, 39%) as a white solid. mp: 419.0–419.5 K (Fig. 3).