CN-117645529-B - Reduction method of stilbene compounds

Abstract

The invention discloses a method for reducing stilbene compounds, and belongs to the technical field of organic synthesis. The method comprises the following steps of (a) taking E-4-isopropyl-3, 5-dimethoxy-stilbene as a raw material, reducing to obtain E-4-isopropyl-3, 5-dimethoxy-stilbene, (b) taking E-4-isopropyl-3, 5-dimethoxy-stilbene as a raw material, reducing and demethylating to obtain 4-isopropyl-3, 5-dihydroxystilbene, (c) taking E-4-isopropyl-3, 5-dihydroxystilbene as a raw material, reducing to obtain 4-isopropyl-3, 5-dihydroxystilbene, wherein the reduction condition is that an alcohol solvent is taken as a solvent, formic acid or formic acid compound is taken as a hydrogen donor in the reactions (a) and (b), formic acid or formic acid amine is taken as a hydrogen donor in the reactions (c), palladium carbon and zinc powder are taken as catalysts, and the mass ratio of the palladium carbon to the zinc powder is 3-8:1.

Inventors

• WANG HAI
• YIN JUN
• GE XIANG
• LI JIANXIONG

Assignees

• 湖北英纳氏生物科技有限公司

Dates

Publication Date

20260508

Application Date

20230911

Claims (2)

1. 1. The method for reducing stilbene compounds is characterized by comprising the following reactions: (a) E-4-isopropyl-3, 5-dimethoxy-diphenylethylene is taken as a raw material, and E-4-isopropyl-3, 5-dimethoxy-diphenylethane is obtained through reduction; (b) E-4-isopropyl-3, 5-dimethoxy-stilbene is taken as a raw material, and 4-isopropyl-3, 5-dihydroxy-diphenylethane is obtained through reduction and demethylation; The reduction conditions are that the reaction (a) and (b) comprise the steps of taking E-4-isopropyl-3, 5-dimethoxy-stilbene as a raw material, taking formic acid as a hydrogen donor, taking methanol as a solvent, taking palladium carbon and zinc powder as a catalyst, carrying out reduction reaction at 60-65 ℃, filtering to remove insoluble substances after the reaction is finished, cooling to-20-5 ℃, and carrying out solid-liquid separation to obtain the E-4-isopropyl-3, 5-dimethoxy-stilbene, wherein the mass ratio of the E-4-isopropyl-3, 5-dimethoxy-stilbene to the formic acid to the palladium carbon to the zinc powder is 1:0.5:0.05:0.01.
2. 2. The method for reducing stilbene compounds according to claim 1, wherein in the reaction (b), the demethylation process comprises the steps of dissolving 4-isopropyl-3, 5 dimethoxy-diphenylethane in methylene dichloride, adding anhydrous aluminum trichloride step by step at a temperature of-20-5 ℃, stirring at room temperature for reaction, diluting with methylene dichloride after the reaction is completed, dripping the diluted solution into 0 ℃ diluted hydrochloric acid, separating the solution after the quenching reaction, washing an organic layer with water, evaporating and recrystallizing to obtain 4-isopropyl-3, 5-dihydroxy-diphenylethane, wherein the mass ratio of the anhydrous aluminum trichloride to the 4-isopropyl-3, 5 dimethoxy-diphenylethane is 0.8-1.5:1.

Description

Reduction method of stilbene compounds Technical Field The invention relates to the technical field of organic synthesis, in particular to a method for reducing stilbene compounds, and especially relates to an industrial production method of stilbene compounds. Background The styrene mod, namely 3, 5-dihydroxyl 4-isopropyl trans-stilbene, is a global first aromatic hydrocarbon receptor agonist drug, and belongs to stilbene compounds. The 3, 5-dihydroxyl 4-isopropyl diphenylethane and related compounds are novel medicines which are first created by the pharmaceutical industry of Wuhan Inna, and show great prospect in the aspects of immune system diseases and inflammations (Li Jianxiong, CN201310477097.0, a diphenylethane derivative and application thereof). The structural formula of the 3, 5-dihydroxyl 4-isopropyl diphenylethane is as follows: 。 The double bond reduction of the traditional stilbene compounds into alkyl can be completed by hydrogen under a certain pressure through palladium-carbon catalysis, the hydrogen catalytic reduction is inflammable and explosive, the industrial production needs strict approval supervision, and the investment is huge. In the industrial production, the hydrogen hydrogenation needs a special pipeline and a pressure vessel, the production can be carried out only in a special hydrogenation workshop, the safety supervision of the hydrogenation production is very complicated, and special operation evidences are needed for the safety production. Therefore, the hydrogen reduction industrialization is difficult to realize. Disclosure of Invention The patent directly uses formic acid or formic acid compounds as hydrogen donor, palladium carbon is matched with zinc powder with a certain proportion as catalyst, and the double bond of stilbene compounds can be reduced by direct heating, and other active groups are not affected, such as olefin. The method does not need hydrogen to directly reduce the benzamod to obtain 3, 5-dihydroxyl 4-isopropyl diphenylethane, or directly reduce 3,5 dimethoxy-4-isopropyl diphenylethylene to obtain 3,5 dimethoxy-4-isopropyl diphenylethane, and then demethoxy to obtain 3, 5-dihydroxyl 4-isopropyl diphenylethane. The scheme is as follows: the embodiment of the invention provides a method for reducing stilbene compounds, which comprises the following reactions: (a) E-4-isopropyl-3, 5-dimethoxy-diphenylethylene is taken as a raw material, and E-4-isopropyl-3, 5-dimethoxy-diphenylethane is obtained through reduction. (B) E-4-isopropyl-3, 5-dimethoxy-diphenyl ethylene is taken as a raw material, and 4-isopropyl-3, 5-dihydroxyl-diphenyl ethane is obtained through reduction and demethylation. (C) E-4-isopropyl-3, 5-dihydroxyl-diphenylethylene (styrene mod) is taken as a raw material, and 4-isopropyl-3, 5-dihydroxyl-diphenylethane is obtained through reduction. The reduction conditions are that alcohol solvent is used as solvent. In the reactions (a) and (b), formic acid or a formic acid compound is used as a hydrogen donor, wherein the formic acid compound is selected from ammonium formate, potassium formate, sodium formate, lithium formate, methyl formate or ethyl formate, and the like, and in the reaction (c), formic acid or an amine formate is used as a hydrogen donor. In the reaction (c), potassium formate, sodium formate, lithium formate, and the like cannot be used as hydrogen donors, and the reaction products (basicity) of the hydrogen donors may decompose the products, resulting in a large number of side reactions. The temperature of the reduction reaction is 40 ℃ to reflux, preferably the reaction temperature is 60-65 ℃. The catalyst is palladium carbon and zinc powder, the mass ratio of the raw materials of hydrogen donor to the catalyst is 1:0.3-3.5:0.03-0.2, and the mass ratio of the palladium carbon to the zinc powder is 3-8:1. The catalyst in the patent is used in a catalytic amount, palladium-carbon is used as a main catalyst, zinc powder is used as an auxiliary catalyst, and the two have unexpected effects in a synergistic effect. Wherein the alcohol solvent is selected from methanol, ethanol, propanol or isopropanol. Preferably, the alcoholic solvent is methanol. Preferably, in reactions (a), (b) and (c), the hydrogen donor is formic acid. Wherein the time of the reduction reaction is 6-12h. Preferably, in the reactions (a), (b) and (c), when the hydrogen donor is amine formate, the solvent is an alcohol-water mixture, and the volume content of water is 5 to 50% so as to avoid sublimation of the amine formate. The demethylation process includes dissolving 4-isopropyl-3, 5 dimethoxy-diphenyl ethane in dichloromethane, adding anhydrous aluminum trichloride at the temperature of-20-5 deg.c, stirring to react at room temperature, diluting with dichloromethane, quenching with dilute hydrochloric acid at the temperature of 0 deg.c (the concentration may be 10wt%, separating liquid, water washing, evaporating to dryness and re-crystallizing to obt