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Preparation method of benzo 1, 3-dioxin-4 ketone acetal compound

A compound and benzo-based technology are applied in the field of preparation of benzo-1,3-dioxin-4 ketone acetal compounds to achieve the effects of wide substrate range, efficient green synthesis and simple operation

Pending Publication Date: 2018-08-10
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] In summary, in the current methods for synthesizing the skeleton of benzo1,3-dioxin-4-one compounds, commonly used methods such as trifluoroacetic acid / acetone, photoreaction, and metal-catalyzed ring-closing strategies, due to the reaction Limitations of conditions (strong acid / strong base / metal catalysis / high temperature / anhydrous and oxygen-free conditions, etc.), there are many defects

Method used

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  • Preparation method of benzo 1, 3-dioxin-4 ketone acetal compound
  • Preparation method of benzo 1, 3-dioxin-4 ketone acetal compound
  • Preparation method of benzo 1, 3-dioxin-4 ketone acetal compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1: Synthesis of 2-(2-carbonylpropyl)-2-phenyl-4-hydrogen-benzo[d][1,3]dioxin-4-one:

[0035] The structural formula of this example is as follows:

[0036]

[0037] To a dichloromethane solution (2 mL) of salicylic acid (0.3 mmol) and 4-phenyl-3-butyn-2-one (0.3 mmol), tetrahydropyrrole (10 mol%) was added dropwise under stirring conditions, and room temperature (25°C) to react overnight. The reaction solution was spin-dried and purified by column chromatography to obtain the target product 2-(2-carbonylpropyl)-2-phenyl-4-hydrogen-benzo[d][1,3]dioxin-4-one: 77.08 mg, yield: 91%, yellow oily liquid. 1 H NMR (400 MHz, CDCl 3 )δ: 7.81 (dd, J=7.8, 1.6Hz, 1H), 7.52 (ddd, J=7.6, 7.1, 1.5Hz, 3H), 7.32 (ddd, J=9.7, 5.5, 2.4Hz, 3H), 7.12 (d,J=8.3Hz, 1H),7.07–6.99(m,1H),3.38–3.20(m,2H),2.32(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ:202.39,160.47,155.93,138.59,136.70,129.84,129.48,128.83,126.30,123.23,117.40,114.61,105.60,55.32,31.85. HR-MS: C 17 h 14 o 4 ,[M+Na] + ...

Embodiment 2

[0038] Example 2: Synthesis of 7-bromo-2-(2-carbonylpropyl)-2-phenyl-4-hydrogen-benzo[d][1,3]dioxin-4-one

[0039]

[0040] To a methanol solution (2 mL) of 4-bromosalicylic acid (0.3 mmol) and 4-phenyl-3-butyn-2-one (0.3 mmol), morpholine (20 mol%) was added dropwise with stirring, React overnight at room temperature (25°C). The reaction solution was spin-dried and purified by column chromatography to obtain the target product 7-bromo-2-(2-carbonylpropyl)-2-phenyl-4-hydrogen-benzo[d][1,3]dioxin- 4-Keto: 80.19 mg, yield: 74%, yellow oily liquid. 1 H NMR (400MHz, CDCl3) δ: 7.68 (d, J = 8.4Hz, 1H), 7.49 (dd, J = 7.8, 1.5Hz, 2H), 7.39–7.32 (m, 4H), 7.19 (dd, J = 8.4,1.7Hz,1H),3.28(d,J=3.2Hz,2H),2.31(s,3H). 13 C NMR(101MHz,CDCl3)δ:201.91,159.81,156.20,138.12,131.13,130.94,129.72,128.99,126.90,126.24,120.73,113.47,106.07,55.04,31.84.HR-MS:C17 +, Calcd.: 382.9889, Found: 382.9884.

Embodiment 3

[0041] Example 3: Synthesis of 7-methyl-2-(2-carbonylpropyl)-2-phenyl-4-hydrogen-benzo[d][1,3]dioxin-4-one

[0042]

[0043] To a solution (2 mL) of 4-methylsalicylic acid (0.3 mmol) and 4-phenyl-3-butyn-2-one (0.3 mmol) in tetrahydrofuran (2 mL), piperidine (5 mol%) was added dropwise with stirring, React overnight at room temperature (25°C). The reaction solution was spin-dried and purified by column chromatography to obtain the target product 7-methyl-2-(2-carbonylpropyl)-2-phenyl-4-hydrogen-benzo[d][1,3]dioxin -4-Kone: 66.62 mg, yield: 75%, colorless oily liquid. 1 H NMR (400MHz, CDCl3) δ: 7.73 (dd, J=8.2, 0.7Hz, 1H), 7.54–7.48 (m, 2H), 7.37–7.29 (m, 3H), 6.62–6.52 (m, 2H), 3.86(s,3H),3.25(q,J=14.5Hz,2H),2.32(s,3H). 13 C NMR (101MHz, CDCl3) δ: 202.62, 166.49, 160.32, 157.83, 138.82, 131.44, 129.42, 128.82, 126.11, 110.85, 107.23, 105.54, 101.31, 55.83, 565.39HR-31.87. Na] + ,Calcd.:319.0941,Found:319.0939

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Abstract

The invention discloses a preparation method of a benzo 1, 3-dioxin-4 ketone acetal compound. The method comprises the steps that salicylic acid or substituted salicylic acid on a benzene ring, and substituted 3-alkynyl-2-butanone are used as reaction substrates; a secondary amine type compound is used as a catalyst; in solvent environment, through a cascade reaction path of catalytic double-Michael addition, the racemic benzo 1, 3-dioxin-4 ketone acetal compound is obtained by a one-pot method. The method has the advantages that the substrate range is wide; the operation is simple; the conditions are mild; the product can be easily separated; the reaction is relatively fast; the yield is high; the metal catalysis is not needed, so that the metal residue in the product is avoided; the process is green and achieves an environment-friendly effect, and the like. Meanwhile, the reaction does not have special requirements on used substrates and catalysts; the substrates and the catalysts can be obtained through low-cost purchase or simple synthesis, so that the molecule compound library is greatly expanded; the efficient green synthesis of the target compound is realized.

Description

technical field [0001] The invention belongs to the field of organic synthesis, in particular to a preparation method of benzo-1,3-dioxin-4-ketone acetal compounds. Background technique [0002] The benzo1,3-dioxin skeleton is an important component of several classes of pharmacologically active molecules. It is also the core structure of several important natural products ((a), US Pat., US2003013660(A1), 2003; (b) WO 2006 / 010642A1, 2007; (c) H.Lin, T.Annamalai, P. ( f) G. Xu, A. Kannan, T.L. Hartman, et al. Bioorg. Med. Chem., 2002, 10(8): 2807-2816.). Therefore, the method of synthesizing such molecules has increasingly become one of the research directions in the field of organic synthesis. [0003] The reaction to construct this type of skeleton is generally to obtain the corresponding product under the catalysis of salicylic acid and acetone under strong acidic conditions such as trifluoroacetic acid, or to obtain the corresponding product from thionyl chloride (SOCl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D319/08
CPCC07D319/08
Inventor 邱立勤何雪峰王猛
Owner SUN YAT SEN UNIV