Synthesis method of benzoxepine compound

A technology for benzoxa and salt compounds, which is applied in the field of synthesis of benzoxa compounds, can solve problems such as low efficiency and harsh reaction conditions, and achieve high total yield, simple reaction system, and simple post-treatment Effect

Active Publication Date: 2020-05-08
ZHEJIANG UNIV OF TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reaction is simple in operation and convenient in post-treatment, which solves the problems of low efficiency and harsh reaction conditions in previous synthesis methods.

Method used

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  • Synthesis method of benzoxepine compound
  • Synthesis method of benzoxepine compound
  • Synthesis method of benzoxepine compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Synthesis of 2-iodo-2'-phenoxy-1,1'-biphenyl

[0029] Phenol (45.2mg, 0.48mmol), [1,1'-biphenyl]-cyclic iodonium trifluoromethanesulfonate (171.1mg, 0.4mmol), copper trifluoromethanesulfonate (14.5mg, 0.04mmol ), potassium carbonate (110.5mg, 0.8mmol) were dissolved in 2mL of dichloromethane and placed in a 35mL pressure tube, and the solution was stirred at 100°C for 18h. Concentrate, and go through silica gel column chromatography, eluting with petroleum ether / ethyl acetate = 100:1, and concentrate to obtain 139.5 mg of the product with a yield of 94%. 1 H NMR (500MHz, CDCl 3 )δ7.91(dd, J=8.0,1.1Hz,1H),7.40–7.32(m,2H),7.31(dd,J=7.6,2.1Hz,1H),7.29–7.25(m,3H),7.20 (td,J=7.5,1.2Hz,1H),7.05(tt,J=7.3,1.1Hz,1H),7.03–7.00(m,1H),7.00–6.97(m,3H)ppm; 13C NMR (126MHz, CDCl 3 )δ157.0, 154.1, 143.0, 138.9, 135.8, 131.7, 130.6, 129.5, 129.4, 128.9, 127.7, 123.1, 123.0, 119.1, 118.7, 100.1ppm; HRMS m / z (EI) calcd for C 18 h 13 IO[M] + 372.0011, found: 371.9994. The structural...

Embodiment 2

[0032] Synthesis of Tribenzo[b,d,f]oxepatriene

[0033] 2-iodo-2'-phenoxy-1,1'-biphenyl (74.4mg, 0.2mmol), triphenylphosphine (5.2mg, 0.02mmol), palladium pivalate (3.1mg, 0.01mmol) , potassium acetate (58.8mg, 0.6mmol), and pivalic acid (12.3mg, 0.12mmol) were dissolved in 2mL of N-methylpyrrolidone, and stirred at 130°C for 8h under nitrogen protection. Extraction, concentration, and silica gel column chromatography, eluting with petroleum ether / ethyl acetate = 100:1, and concentration gave 43.2 mg of the product with a yield of 88%. 1 H NMR (500MHz, CDCl 3 )δ7.67(dd, J=5.8,3.4Hz,2H),7.60(dd,J=7.7,1.5Hz,2H),7.52(dd,J=5.8,3.3Hz,2H),7.40–7.33(m ,4H),7.27(ddd,J=7.7,6.6,2.0Hz,2H)ppm; 13 C NMR (126MHz, CDCl 3 )δ160.2, 136.6, 132.9, 129.7, 129.4, 129.3, 128.1, 125.5, 120.9ppm. The structural formula of the product is:

[0034]

Embodiment 3

[0036] Synthesis of 2-iodo-2'-(m-tolyloxy)-1,1'-biphenyl

[0037] According to the method described in Example 1, except that the hydroxyl substrate used was m-cresol (52.0 mg, 0.48 mmol), 150.6 mg of the product was obtained with a yield of 97%. 1 H NMR (500MHz, CDCl 3 )δ7.92(dd,J=7.9,1.1Hz,1H),7.41–7.31(m,3H),7.31–7.27(m,1H),7.23–7.13(m,2H),7.04–6.97(m, 2H), 6.87(ddt, J=7.5, 1.7, 0.9Hz, 1H), 6.83–6.78(m, 2H), 2.31(s, 3H)ppm; 13 C NMR (126MHz, CDCl 3 )δ156.9, 154.2, 143.0, 139.6, 138.9, 135.7, 131.6, 130.6, 129.3, 129.2, 128.8, 127.7, 123.9, 122.8, 119.8, 118.6, 116.1, 100.0, 21.3ppm; HRMS m / z (for C) 19 h 15 IO[M] + 386.0168, found: 386.0158. The structural formula of the product is:

[0038]

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Abstract

The invention provides a synthesis method of a benzoxepine compound. A diarylether compound is efficiently synthesized through a reaction of a diaryl cyclic iodonium salt compound and a substrate containing a hydroxyl group, and the benzoxepine compound is obtained through intramolecular cyclization. The reaction operation is simple, the post-treatment is convenient, and the problems of low efficiency, harsh reaction conditions and the like of a conventional synthesis method are solved; the atom economy of the substrate is fully utilized; and the diarylether compound is efficiently obtained byusing the hydroxyl-containing compound and the diaryl cyclic iodonium salt at a certain temperature under the catalysis of cheap metal copper, intramolecular cyclization is carried out through further reaction, the highest yield of the obtained diarylether compound is 99%, and the highest yield of the benzoxepine compound is 95%.

Description

technical field [0001] The present invention relates to a kind of benzoxa The synthesis method of the compound, that is, through the reaction of the diaryl cyclic iodonium salt compound and the substrate containing the phenolic hydroxyl group to realize the arylation of the oxygen atom and then the cyclization through the activation of the carbon-hydrogen bond, the efficient synthesis of benzoxepal method of compounds. Background technique [0002] Aryl ethers are important structures in many natural products and pharmaceuticals, and heteroatom arylation and alkylation are the most common transformations in the synthesis of drug candidates (J. Med. Chem. 2011, 54, 3451–3479; Org. Biomol. Chem. 2006, 4, 2337–2347). Diaryl ethers are common structural features in many natural products and bioactive compounds (Chem. Rev. 2008, 108, 3054; Angew. Chem. Int. Ed. 2003, 42, 5400). The structure of diaryl ether is included in the total synthesis of vancomycin, glycopeptide antib...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D313/06C07D491/044C07D495/04
CPCC07D313/06C07D491/044C07D495/04
Inventor 张逢质方琪
Owner ZHEJIANG UNIV OF TECH
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