New Short Strategy for the Synthesis of the Dibenz[b,f]oxepin Scaffold

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David R. R. Moreno 1, Giorgio Giorgi 2, Cristian O. Salas 1 and Ricardo A. Tapia 1,*
1 Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de
Chile, Santiago 7820436, Chile; E-Mails: (D.R.R.M.); (C.O.S.)

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2 Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia,
Universidad Complutense, Madrid 28040, Spain;E-Mail:

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* Author to whom correspondence should be addressed; E-Mail:;
Tel.: +56-2-2354-4429; Fax: +56-2-2354-4744.

Molecules 201318(12), 14797-14806; doi:10.3390/molecules181214797

Download PDF Full-text (257 KB) |  Supplementary Files

(This article belongs to the Section Organic Synthesis)
 In this report a short and efficient synthesis of the dibenz[b,f]oxepin framework through intramolecular SNAr and McMurry reactions is described. The diaryl ethers required for the McMurry reaction have been obtained in good yields under microwave-assisted conditions of the reaction of salicylaldehydes with fluorobenzaldehydes without catalysts. Application of an intramolecular McMurry reaction to the synthesized diarylethers using TiCl4/Zn in THF gave the target dibenzo[b,f]oxepin system in 53%–55% yields.
Molecules 2013, 18, 14797-14806; doi:10.3390/molecules181214797

In conclusion, we have developed a short synthesis of dibenzo[b,f]oxepin derivatives using SNAr
and intramolecular McMurry reactions. An efficient process to obtain diarylethers through SNAr
reaction of salicylaldehydes with fluorobenzaldehydes using microwave irradiation is described.
McMurry reaction of diarylethers using TiCl4 and Zn in THF afforded the target tricyclic system in
reasonable yields (53%–55%). Further work on the synthesis of natural and pharmacologically active
dibenzo[b,f]oxepins are under way.

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Supplementary Files   DOWNLOAD


compd 5a


Dibenz[b,f]oxepin (5a).

Stilbene 3 (215 mg, 0.5 mmol) was added to a solution of KOH (900 mg,
16 mmol) in a mixture of EtOH (15 mL) and H2O (15 mL) and the suspension was heated under reflux
for 1 h. After cooling, the reaction mixture was acidified with aqueous HCl (10%) to pH 4 and
extracted with CH2Cl2 (3 × 25 mL). The combined organic extracts were washed with saturated
aqueous NaHCO3, dried, and filtered through a short column of silica gel. After the removal of the
solvent, the residue was dissolved in DMSO (5.0 mL) and Cs2CO3 (651.6 mg, 2.0 mmol) was added.
The reaction mixture was heated in a microwave reactor at 180 °C for 15 min. After cooling, the
solvent was evaporated under reduced pressure and the crude product was purified by flash column
chromatography (silica gel, EtOAc-hexanes; 1:9) to afford 5a (70 mg, 72%),

mp 108.5–109.5 °C
(Lit. 106–108 °C [34], 110–111 °C [35]).

IR (KBr): 􀟥􀷤 max 3069, 3044, 1483, 798 cm−1.
1H-NMR (acetone-d6) δ 6.82 (s, 2H, Two protons of -CH=CH- ), 7,19 (t, J = 7,8 Hz, 2H), 7.25 (d, J = 7.8 Hz, 2H), 7.30 (d, J = 7.8 Hz,2H), 7.38 (t, J = 7.8 Hz, 2H).

13C-NMR (acetone-d6) δ 122.9, 126.6, 131.1, 131.6, 131.7, 132.3, 159.1.

The Mapuche people were the original inhabitants of southern and central Chile.

Fighting during the War of the Pacific: The Battle of Iquique on 21 May 1879.

Parinacota volcano in northern Chile

Araucanian Indians and Huasos in Chile, 19th century

The Catholic Monarchs in the Capitulation of Granada, the end of the Reconquista and the unification of the kingdoms forming actual Spain.




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