Method for synthesizing 3,5-diphenyl phenol

Abstract

The invention discloses a method for synthesizing 3,5-diphenyl phenol in one pot by two steps. The method comprises the following steps: by taking ethyl acetoacetate as a raw material, fluorinating by using a fluorinating agent SelectfluorTM; cyclizing with chalcone Robinson to generate a fluorine-containing cyclohexenone midbody; subsequently continuously performing dehydrofluorination, aromatization and hydrolysis decarboxylation to generate a final product 3,5-diphenyl phenol. The method is simple to operate, capable of reducing the difficulty of after-treatment, high in reaction selectivity, cheap in raw material, good in substrate adaptability and capable of shortening the total reaction time of a traditional method from 30h to 4h and increasing the total yield from 20% to above 80%. A 3,5-diaryl phenol derivative is an important medicine midbody, and the special molecular structure thereof has quite important bioactivity and can be used for preparing 'Molecular Harpoon'.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a novel and efficient synthesis method for synthesizing 3,5-diphenylphenol in one pot by using acetoacetate and chalcone as raw materials, undergoing fluorination and dehydrofluorination processes. Background technique [0002] Whether it is in the field of medicine or polymer, phenol is the precursor or core structural unit of some commonly used industrial compounds, and it has always been a very challenging task to introduce some special functional groups at specific positions on the phenol ring. . Among all substituted derivatives of phenol, 3,5-diaryl substituted derivatives have very important biological activities and can be used to prepare "molecular harpoons". Some important such intermediates are listed in the following formula, such as 1a and 1b are intermediates of EGF-stimulated cell proliferation inhibitors and anti-cell proliferation drugs, 1c is CD40 function inhi...

AI Technical Summary

Problems solved by technology

However, the strong electron-guiding effect in these reactions limits the synthesis of ortho-substituted derivatives, such as 3,5-disubstituted phenol series compounds

[0005] There are difficulties in the synthesis of 3,5-diarylphenol series compounds. Although this has attracted the investment and enthusiasm of a large number of scientific researchers, and new synthetic methods have emerged in an endless stream. However, in the past, these ketones were used as raw materials to synthesize 3,5- The methods of diarylphenol compounds often have problems such as low yield, limited selection of raw materials, and easy formation of isomers.

This method is very constructive, but the conversion rate is not high

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