3-(2,4-Dimeth­oxy­anilino)-8-meth­oxy­dibenz[b,e]oxepin-11(6H)-one

Benjamin Baur; Dieter Schollmeyer; Stefan Laufer

doi:10.1107/S1600536811002637

. 2011 Jan 26;67(Pt 2):o487. doi: 10.1107/S1600536811002637

3-(2,4-Dimethoxyanilino)-8-methoxydibenz[b,e]oxepin-11(6H)-one

Benjamin Baur ^a, Dieter Schollmeyer ^b, Stefan Laufer ^a,^*

PMCID: PMC3051661 PMID: 21523143

Abstract

In the title compound, C₂₃H₂₁NO₅, the two benzene rings of the tricyclic unit are oriented at a dihedral angle of 37.5 (8)°. The 2,4-dimethoxyanilino residue is oriented at a dihedral angle of 60.2 (8)° towards the phenoxy ring. In the crystal, the central carbonyl O atom accepts two hydrogen bonds from the N—H and C—H groups. A further intermolecular C—H⋯O interaction involving one of the methoxy O atoms is also observed.

Related literature

For palladium-catalysed amination reactions of aryl halides with anilines, see: Jensen et al. (2004 ▶). For p38 MAP kinase inhibitors based on dibenzo[b,e]oxepin-11(6H)-one, see: Laufer et al. (2006 ▶).

Experimental

Crystal data

C₂₃H₂₁NO₅
M _r = 391.41
Monoclinic,
a = 9.3277 (9) Å
b = 25.8290 (8) Å
c = 7.9519 (6) Å
β = 98.914 (3)°
V = 1892.7 (2) Å³
Z = 4
Cu Kα radiation
μ = 0.80 mm⁻¹
T = 193 K
0.50 × 0.10 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
3847 measured reflections
3578 independent reflections
3041 reflections with I > 2σ(I)
R _int = 0.021
3 standard reflections every 60 min intensity decay: 1%

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.111
S = 1.06
3578 reflections
265 parameters
H-atom parameters constrained
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ▶); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811002637/nc2218sup1.cif

e-67-0o487-sup1.cif^{(21.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811002637/nc2218Isup2.hkl

e-67-0o487-Isup2.hkl^{(175.5KB, 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
N12—H12⋯O23ⁱ	0.87	2.08	2.9403 (18)	168
C4—H4⋯O23ⁱ	0.95	2.57	3.3000 (19)	134
C20—H20B⋯O21ⁱⁱ	0.98	2.56	3.496 (3)	160

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

supplementary crystallographic information

Comment

Based on dibenzo[b,e]oxepin-11(6H)-one (Laufer et al. 2006) as novel p38 MAP kinase inhibitors, our intent was to synthesize new oxepin derivatives. The title compound was synthesized in the course of an ongoing study to insert hydrophilic residues at position 8. The two phenyl rings of the tricyclid unit are oriented at a dihedral angle of 37.5 (8°). The 2,4-dimethoxyphenylamino residue is oriented at a dihedral angel of 60.2 (8°) towards the phenoxy ring. The crystal stucture is characterized by several hydrogen bonds. The central carboxyl group O(23) forms two hydrogen bonds towards N(12)—H (2.08 Å) and C(4)—H (2.57 Å) and O(21) forms a hydrogen bond towards C(20)—H (2.56 Å) (Tab. 1).

Experimental

The preparation of the title compound was achieved by using a palladium catalyzed amination reaction (Jensen et al. (2004)).

A mixture of 200 mg (0.73 mmol) 3-chloro-9-methoxy-dibenzo[b,e]oxepin-11(6H)-one, 120 mg (0.78 mmol) 2–4-dimethoxyaniline, 1.10 g (3.37 mmol) Cs₂CO₃, 45 mg (0.10 mmol) 2-(dicyclohexylphosphino)-2`-4`-6`-triisopropylbiphenyl and 20 mg (0.09 mmol) Pd(OAc)₂ in 2 ml absolute tert-butanol and 10 ml absolute 2.4-dioxane was stirred for 1 h at 284 K under an argon atmosphere. The mixture was then filtered and evaporated under pressure. The residue was purified by column chromatography (SiO_2,n-hexane / ethyl acetate 1 + 1). Crystals of the title compound were obtained by slow evaporation of the solvent from a solution of the title compound in diethylether / n-hexane.

¹H NMR (200 MHz, DMSO) δ in p.p.m. 3.75 (s, 3 H), 3.77 (s, 3 H), 3.84 (s, 3 H), 5.10 (s, 2 H), 6.11 (d, J=2.27 Hz, 1 H), 6.52 (m, 2 H), 6.66 (m, 1 H), 7.07 (m, 3 H), 7.82 (d, J=7.96 Hz, 1 H), 7.95 (d, J=8.97 Hz, 1 H), 8.17 (s, 1 H)

¹³C NMR (50 MHz, DMSO) δ in p.p.m. 55.7, 55.9, 55.9, 73.4, 100.0, 101.0, 105.1, 109.6, 113.2, 114.6, 116.2, 121.7, 126.7, 132.0, 132.9, 133.6, 138.9, 153.8, 154.9, 158.2, 162.6, 163.1, 185.4