阅读说明：本技术 双芳基衍生物的制备、双芳基衍生物及应用 (Preparation of diaryl derivative, diaryl derivative and application ) 是由 朱勍 窦言东 蔡春晖 章苗 于 2019-08-30 设计创作，主要内容包括：本发明涉及一种双芳基衍生物及其制备方法与应用,所述双芳基衍生物结构如式(II)所示。本发明提供了双芳基衍生物及铜催化芳基偶联合成双芳基的方法,操作过程简单,原料都已商品化容易得到,催化剂廉价易得且环境友好,反应条件温和,位点选择性高,反应高效,只需一步便可制得双芳基类生物。此外,该反应利用表面活性剂作为辅助溶剂,使该反应可以在水溶液中进行,克服了传统双芳基偶联反应对酸和有机溶剂的需求。<Image he="273" wi="700" file="DDA0002185852720000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention relates to a diaryl derivative and a preparation method and application thereof, wherein the structure of the diaryl derivative is shown as a formula (II). The invention provides a method for synthesizing diaryl by combining a diaryl derivative and a copper-catalyzed aryl pair, which has the advantages of simple operation process, easily obtained commercialized raw materials, cheap and easily obtained catalyst, environmental friendliness, mild reaction conditions, high site selectivity and high reaction efficiency, and the diaryl organisms can be prepared by only one step. In addition, the reaction utilizes a surfactant as an auxiliary solvent, so that the reaction can be carried out in an aqueous solution, and the requirements of the traditional biaryl coupling reaction on acid and an organic solvent are overcome.)

1. A process for the preparation of a bisaryl derivative, the process comprising: dissolving a compound shown as a formula (I) in water, adding an oxidant, a copper catalyst and an additive, reacting completely at normal temperature, and separating and purifying reaction liquid to obtain an aryl coupling compound shown as a formula (II); the oxidant is one of the following: potassium persulfate, manganese dioxide, iodobenzene diacetate and benzoquinone; the copper catalyst is one of the following: copper acetate, copper chloride, copper diacetone; the additive is one of the following: silver acetate, silver carbonate, silver triflate;

in the formulas (I) and (II), R is H, halogen, C1-C7 alkyl, C1-C7 alkoxy or substituted aryl, and the substituent of the substituted aryl is H, halogen, methoxy or C1-C7 alkyl.

2. The method according to claim 1, wherein a surfactant is further added to the reaction solution, and the surfactant is polyethylene glycol octyl phenyl ether.

3. The method according to claim 1, wherein the separation and purification method comprises: adding saturated NaCl water solution into the reaction solution, extracting with dichloromethane, drying the organic layer with magnesium sulfate, filtering, and rotary evaporating at normal temperature to remove solvent to obtain crude product; and (3) performing silica gel column chromatography on the crude product, wherein the volume ratio is 1: and (3) taking a solution of ethyl acetate and petroleum ether of 3-10 as a mobile phase, tracking and collecting the eluent with Rf value of 0.3-0.5 by TLC, decompressing and removing the solvent from the collected eluent, and drying to obtain the aryl coupling compound.

4. The method of claim 1, wherein R is phenyl, m-methylphenyl, p-chlorophenyl, p-nitrophenyl, o-fluorophenyl, p-methoxyphenyl, C6 aliphatic cyclic group, C4 aliphatic alkyl, or C4 alkoxy.

5. The method of claim 1, wherein said bisaryl derivative is one of:

6. a bisaryl derivative prepared according to the process of claim 1, having the structure of one of the following formulae:

7. use of the biaryl derivatives of claim 5 in the preparation of antitumor drugs.

(I) technical field

The invention relates to a preparation method of a diaryl derivative, the diaryl derivative and application.

(II) background of the invention

Diaryl compounds, especially bisphenols and binaphthols, are a very valuable class of organic molecules found in a variety of bioactive molecules, natural products, and functional materials. In addition, curcumin and other compounds containing two phenolic hydroxyl groups have effective antioxidant and anti-inflammatory activities. Bisphenols are used as preservatives and disinfectants in addition to industrial uses because of their bactericidal and bactericidal properties. On the other hand, enantioselective aryl-aryl cross-couplings, such as binaphthol, provide the most direct access to atropine bisaryl, and have significant application potential in the field of chemical science. However, they are most important as chiral ligands or catalysts in asymmetric syntheses. Therefore, it is very urgent to develop a new and efficient synthesis method of bisphenol and binaphthol.

Disclosure of the invention

The invention aims to provide a novel method for coupling diaryl compounds in an aqueous phase, a diaryl derivative obtained by the method and application thereof.

The technical scheme adopted by the invention is as follows:

a process for the preparation of a bisaryl derivative, the process comprising: dissolving a compound shown as a formula (I) in water, adding an oxidant, a copper catalyst and an additive, reacting completely at normal temperature, and separating and purifying reaction liquid to obtain an aryl coupling compound shown as a formula (II); the oxidant is one of the following: potassium persulfate, manganese dioxide, iodobenzene diacetate and benzoquinone; the copper catalyst is one of the following: copper acetate, copper chloride, copper diacetone; the additive is one of the following: silver acetate, silver carbonate, silver triflate;

in the formulas (I) and (II), R is H, halogen, C1-C7 alkyl, C1-C7 alkoxy or substituted aryl, and the substituent of the substituted aryl is H, halogen, methoxy or C1-C7 alkyl. Or R is phenyl, m-methylphenyl, p-chlorophenyl, p-nitrophenyl, o-fluorophenyl, p-methoxyphenyl, C6 aliphatic cyclic group, C4 aliphatic alkyl or C4 alkoxy.

The reaction liquid can also be added with a surfactant, the surfactant is polyethylene glycol octyl phenyl ether, and the addition amount of the surfactant in the reaction liquid is 1-5% (w/w), preferably 2%.

The method has the advantages of cheap and easily-obtained catalyst, environmental friendliness, mild reaction conditions, high site selectivity and high reaction efficiency. The use of the surfactant enables the reaction to overcome the requirements on strong acid and organic solvent, and is more environment-friendly. In addition, the reaction breaks through the bottleneck of the non-para-bisphenol ortho-coupling.

The catalyst is preferably copper acetate; the oxidant is preferably potassium persulfate; further, the additive is silver acetate; the ratio of the amounts of the oxidizing agent, the additive, the catalyst and the substance of the phenol compound (I) is preferably 1.2:1.2:0.2: 1.

The separation and purification method comprises the following steps: adding saturated NaCl water solution into the reaction solution, extracting with dichloromethane, drying the organic layer with magnesium sulfate, filtering, and rotary evaporating at normal temperature to remove solvent to obtain crude product; and (3) performing silica gel column chromatography on the crude product, wherein the volume ratio is 1: and (3) taking a solution of ethyl acetate and petroleum ether of 3-10 as a mobile phase, tracking and collecting the eluent with Rf value of 0.3-0.5 by TLC, decompressing and removing the solvent from the collected eluent, and drying to obtain the aryl coupling compound.

The R is preferably phenyl, m-methylphenyl, p-chlorophenyl, p-nitrophenyl, o-fluorophenyl, p-methoxyphenyl, C6 aliphatic cyclic group, C4 aliphatic alkyl or C4 alkoxy.

More preferably, the bisaryl derivative is one of the following:

the invention also relates to a diaryl derivative prepared according to the method, which has one of the following structures:

the invention also relates to application of the diaryl derivative in preparing antitumor drugs.

The invention has the following beneficial effects: (1) the invention provides a novel diaryl compound, which has certain anti-tumor activity and provides a basis for screening tumor drugs; (2) the invention provides a method for synthesizing diaryl by coupling aryl under the catalysis of copper, which has the advantages of simple operation process, easily obtained commercialized raw materials, cheap and easily obtained catalyst, environmental friendliness, mild reaction conditions, high site selectivity and high reaction efficiency, and the diaryl organisms can be prepared by only one step. In addition, the reaction utilizes a surfactant as an auxiliary solvent, so that the reaction can be carried out in an aqueous solution, and the requirements of the traditional biaryl coupling reaction on acid and an organic solvent are overcome.

(IV) description of the drawings

FIG. 1 is a hydrogen spectrum of compound (II-1);

FIG. 2 is a carbon spectrum of compound (II-1);

FIG. 3 is a mass spectrum of compound (II-1);

FIG. 4 is a graph showing the antitumor activity of Compound (II-1).

(V) detailed description of the preferred embodiments

The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto: