Method for synthesizing isoflavone by nickel-catalyzed Negishi cross coupling reaction at room temperature

Abstract

The invention belongs to the technical field of heterocyclic compounds, and particularly relates to a heterocyclic non-hydrogenated heterocyclic compound containing a six-membered ring and taking an oxygen atom as the only heteroatom and condensed with other rings. The invention provides a new method for synthesizing isoflavone by a nickel-catalyzed Negishi cross coupling reaction at room temperature, which comprises the following steps of: adding reactants (substituted) 3-iodine chromone or (substituted) 3-bromine chromone and an aryl zinc reagent into a solvent, and performing a nickel-catalyzed reaction at room temperature; and after the reaction, performing column chromatographic separation and purification to obtain a pure product of the compound isoflavone. The method provided by the invention is used for preparing medical isoflavones such as ipriflavone, formononetin, isoflavoues aglycone, genistein, puerarin and the like, provides a new technical way to the industrial production of the medicines, and is also used for preparing a series of new isoflavone compounds with potential physiological activity.

Description

technical field [0001] The invention belongs to the technical field of heterocyclic compounds, and specifically relates to a heterocyclic compound containing a six-membered ring without hydrogenation, which has an oxygen atom as the only ring heteroatom and is fused with other rings. Background technique [0002] Isoflavones are phenolic compounds based on benzochromone rings formed by cyclization of cinnamoyl-CoA side chains during the metabolism of phenylalanine in plants. The 3-phenyl derivatives are isoflavones, which belong to plants secondary metabolites. Modern pharmacological studies have shown that isoflavones play a role in the cardiovascular system, endocrine system, central nervous system, immune system and anti-tumor, anti-oxidation and free radical scavenging effects, estrogen-like effects, anti-inflammatory and anti-allergic effects, antibacterial and antiviral effects etc. have obvious pharmacological effects. For example, formononetin which can prevent and...

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Problems solved by technology

Ib Thomsen etc. have also reported that isoflavones are synthesized by reacting salicylaldoxime and enamine (N-styrylmarin), and can obtain isoflavones through acetylation, reduction, and ring closure reactions, and the yield is 37%. The reaction process Complex, low yield and separation and purification by thin-layer chromatography, so the industrial application value is low

[0007] In the 1970s, the synthesis of isoflavones by the chalcone route appeared, mainly using substituted acetophenones and substituted benzaldehydes as raw materials, which were condensed by Claisen-Schemidt to generate corresponding chalcones. The role of chalcones in heavy metal thallium salts Under the following conditions, the rearrangement reaction is used to synthesize isoflavones. The yield of this method is low and a large amount of toxic thallium salts are used in the production process; and the improved method for preparing isoflavones through oxidative rearrangement of chalcones has a low yield.

The currently reported synthesis of isoflavones using Suzuki coupling reaction, Stille organotin coupling reaction, Stille organobismuth coupling and Negishi organozinc coupling reaction are all expensive palladium catalysts, palladium catalysts are prone to produce palladium in the reaction Black, reducing catalytic efficiency, and the formed palladium black is not easy to remove, affecting product purity and quality

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