CN-122010881-A - Synthesis method of 3-phenoxy-2-arylbenzofuran compound

Abstract

The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of a 3-phenoxy-2-arylbenzofuran compound. In nitrogen atmosphere, 1-fluoro-2- (phenoxymethyl) benzene compounds shown in formulas 1 and 4 and N-methyl-N-methylbenzamide compounds shown in formulas 2 and 5 are mixed with tetrahydrofuran in the presence of bistrimethylsilylamincesium to synthesize 3-phenoxy-2-arylbenzofuran compounds shown in formulas 3 and 6. The synthesis method is simple, economical and more widely applicable, is suitable for large-scale production, and has important influence on synthesizing furan compounds.

Inventors

• MAO JIANYOU
• YU RUI
• XIONG DAN

Assignees

• 南京工业大学

Dates

Publication Date

20260512

Application Date

20260113

Claims (4)

1. 1. A method for synthesizing 3-phenoxy-2-arylbenzofuran compounds is characterized in that: In nitrogen atmosphere, mixing and heating 1-fluoro-2- (phenoxymethyl) benzene compounds shown in formulas 1 and 4 and N-methyl-N-methylbenzamide compounds shown in formulas 2 and 5 with tetrahydrofuran in the presence of bistrimethylsilylamincesium to synthesize 3-phenoxy-2-arylbenzofuran compounds shown in formulas 3 and 6; Wherein R 1 is selected from any one of phenoxy, 4-methylphenoxy, 4-fluorophenoxy, 4-tert-butylphenoxy and 4-1,1' -biphenyloxy, and R 2 is selected from any one of 3-methylphenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 4-N, N-dimethylaminophenyl and 4-methylthiophenyl.
2. 2. The method of claim 1, wherein the gas is nitrogen.
3. 3. The synthetic method of claim 1 wherein the reaction temperature is 110 ℃.
4. 4. The synthesis method according to claim 1, wherein the 1-fluoro-2- (phenoxymethyl) benzene compound, the N-methyl-N-methylbenzamide compound and the 3-phenoxy-2-arylbenzofuran compound are one of the following tables:

Description

Synthesis method of 3-phenoxy-2-arylbenzofuran compound Technical Field The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing a 3-phenoxy-2-arylbenzofuran compound. Background Benzofurans are widely used in the pharmaceutical field due to their wide range of biological activities. They are also substrates for many reactions in organic synthesis. Despite extensive research on their synthesis, challenges remain, including the need for harsh or dangerous reaction conditions and the use of expensive or unstable reagents. Its unique biological activity has attracted considerable attention from organic chemists. In general, conventional methods for synthesizing benzofurans include Perkin rearrangement, madelung cyclization, condensation cyclization of phenols with α -halocarbonyl compounds, and the like. However, these methods are generally harsh in reaction conditions, require heavy metal catalysts, and have a relatively limited substrate range. Therefore, the development of a novel and efficient synthesis method of the benzofuran compounds has great significance and value. Disclosure of Invention The invention provides a method for synthesizing benzofuran compounds by a one-pot method under the condition of no transition metal. A series of 3-phenoxy-2-arylbenzofuran compounds are synthesized. The synthesis method provides a high-efficiency direct, mild-condition and simple-operation method through seldom-used CsN (SiMe 3)2 realizes selective deprotonation at a benzyl position: In the nitrogen atmosphere, 1-fluoro-2- (phenoxymethyl) benzene compounds shown in formulas 1 and 4, N-methyl-N-methylbenzamide compounds shown in formulas 2 and 5, strong alkali and an organic solvent are adopted to mix and heat so as to synthesize 3-phenoxy-2-arylbenzofuran compounds shown in formulas 3 and 6; Wherein R 1 is selected from any one of phenoxy, 4-methylphenoxy, 4-fluorophenoxy, 4-tert-butylphenoxy and 4-1,1' -biphenyloxy, and R 2 is selected from any one of 3-methylphenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 4-N, N-dimethylaminophenyl and 4-methylthiophenyl. The method of the invention uses alkali metal to realize high-efficiency synthesis of 3-phenoxy-2-aryl benzofuran compounds, the raw materials used in the synthesis method are cheap and easy to obtain, and R 1、R2 in the invention can be selected from a plurality of types, so that the applicability is wider. Preferably, the reaction is carried out under a nitrogen atmosphere. Preferably, the synthesis occurs in the presence of a strong base and an organic solvent. Preferably, the strong base is cesium bistrimethylsilylamino. Preferably, the organic solvent is tetrahydrofuran. Preferably, the reaction temperature is 110 ℃. Preferably, by the method of the present invention, 3-phenoxy-2-arylbenzofurans of the following structure can be synthesized: The 3-phenoxy-2-arylbenzofuran compound is finally synthesized by mixing 1-fluoro-2- (phenoxymethyl) benzene compound and N-methyl-N-methoxybenzamide compound with organic solvent tetrahydrofuran in the presence of equivalent bis (trimethylsilyl) aminocesium to react. The technical scheme of the invention can at least achieve one of the following beneficial effects: The raw materials 1 and 4 adopted by the synthesis method are easy to prepare, and the raw materials 2 and 5 are cheap and easy to obtain; The method has the advantages that the required operation steps are simple and convenient, the reaction can be carried out only under normal pressure without extreme temperature rise or temperature reduction, and the method is safe and convenient; R 1、R2 in the invention can be selected from a plurality of types, so that the substrate has wider applicability, and can synthesize various 3-phenoxy-2-arylbenzofuran compounds; Compared with the traditional method, the method has the advantages of high yield, mild condition, simple operation and the like. Drawings The figures are the hydrogen spectrum and the carbon spectrum of the product of each example, the figure numbers correspond to the example numbers, the figure A is the hydrogen spectrum, the figure B is the carbon spectrum, the figure 1A is the hydrogen spectrum, the figure 1B is the carbon spectrum, the figure 2A is the hydrogen spectrum, the figure 2B is the carbon spectrum, the figure 3A is the hydrogen spectrum, the figure 3B is the carbon spectrum, the figure 4A is the hydrogen spectrum, the figure 4B is the carbon spectrum, the figure 5A is the hydrogen spectrum, the figure 5B is the carbon spectrum, the figure 6A is the hydrogen spectrum, the figure 6B is the carbon spectrum, the figure 7A is the figure 8A is the figure 9, the figure 8A is the figure 9, the figure 8B is the figure 8A is the figure 8. DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION The following is a further description of the inventive concept in connection with examples to facilitate understanding by those skilled in the art. The followin