阅读说明：本技术 一种基于电化学合成异喹啉酮类化合物的方法 (Method for synthesizing isoquinolone compound based on electrochemistry ) 是由 *** 唐海涛 潘英明 钟媛芳 于 2019-11-13 设计创作，主要内容包括：本发明公开了一种基于电化学合成异喹啉酮类化合物的方法。这种方法在温和的电化学条件下,通过苯甲酰胺化合物和炔烃进行两次分子间(4+2)环化合成了高度官能团化的异喹啉酮类化合物。这种方法反应条件温和,这种方法合成步骤简单,所合成的产品异喹啉酮类化合物的区域选择性好、具有较好的抗肿瘤活性。(The invention discloses a method for electrochemically synthesizing isoquinolinone compounds. The method synthesizes the highly functionalized isoquinolone compound by performing intermolecular cyclization (4+2) twice through benzamide compound and alkyne under mild electrochemical conditions. The method has mild reaction conditions, simple synthesis steps, and good regioselectivity and anti-tumor activity of the synthesized isoquinolone compound.)

1. A method for synthesizing isoquinolone compounds based on electrochemistry is characterized in that

The general formula of the synthesis method is as follows:

in the general formula, R¹= aromatic or aliphatic radical,

wherein, the catalyst is: dichlorobis (4-methylisopropylphenyl) ruthenium (II); the electrolyte is as follows: tetrabutylammonium perchlorate; the solvent is as follows: isopropanol and water; the alkali is: sodium pivalate; the anode is: a reticular glassy carbon sheet; the cathode is: a platinum sheet.

2. The method for electrochemically synthesizing isoquinolinone compounds according to claim 1, characterised in that said method comprises: 0.2mmol of benzamide, 0.6mmol of alkyne, 5 mol% of catalyst dichlorobis (4-methylisopropylphenyl) ruthenium (II) and 1 equivalent of electrolyte tetrabutylperchloroAdding ammonium sulfate and 1 equivalent of sodium pivalate as alkali into 10mL three-neck flask, dissolving in 10mL solvent containing isopropanol/water = 3/1, using Reticular Vitreous Carbon (RVC) as anode and platinum sheet as cathode, stirring under constant current of 10mA and under protection of argon gas at 100 deg.C, monitoring reaction progress by TLC, extracting with ethyl acetate 10mL, drying organic layer with anhydrous sodium sulfate, drying solvent under reduced pressure, and performing column chromatography (SiO)₂Petroleum ether/ethyl acetate = 40:1-10: 1) to purify the residue to give the product.

Technical Field

The invention relates to chemical synthesis, in particular to a method for synthesizing isoquinolinone compounds based on electrochemistry.

Background

Amides, which play an important role in life activities as a key component of proteins, are also widely present in natural products, commercially available drugs, and polymeric materials, and therefore, functionalization of amides is of great interest to chemists, and C — H activation of amides is widely used for synthesis of nitrogen-containing heterocyclic compounds. The most amide C-H activation reported so far is the synthesis of polycyclic isoquinolinones by reacting amides with protecting groups with one molecule of alkyne (org. Lett.2017,19, 5348-; chem. Eur.J.2016,22, 5899-.

In general, most amide activations require protection of the amino group, one C — H activation is achieved, the resulting product is less selective, and a large amount of source oxidant needs to be added. Therefore, the research of realizing the two-time C-H activation of the amide by a green, simple and convenient organic synthesis method which accords with sustainable development has important significance and application value.

Disclosure of Invention

The invention aims to overcome the defects in the prior art and provides a method for electrochemically synthesizing isoquinolone compounds. The method has mild reaction conditions, simple synthesis steps, and good regioselectivity and anti-tumor activity of the synthesized isoquinolone compound.

The technical scheme for realizing the purpose of the invention is as follows:

the difference of the electrochemical synthesis method of isoquinolone compounds from the prior art is that the general formula of the synthesis method is as follows:

in the general formula, R¹Either an aromatic group or an aliphatic group,

wherein, the catalyst is: dichlorobis (4-methylisopropylphenyl) ruthenium (II); the electrolyte is as follows: tetrabutylammonium perchlorate; the solvent is as follows: isopropanol and water; the alkali is: sodium pivalate; the anode is: a reticular glassy carbon sheet; the cathode is: a platinum sheet.

The method for synthesizing the isoquinolone compound comprises the following steps: respectively adding 0.2mmol of benzamide, 0.6mmol of alkyne, 5mol percent of catalyst dichlorobis (4-methyl isopropylphenyl) ruthenium (II), 1 equivalent of electrolyte tetrabutylammonium perchlorate and 1 equivalent of alkali sodium pivalate into a 10mL three-neck flask, adding 10mL of solvent for dissolving, wherein isopropanol/water in the solvent is 3/1, taking Reticular Vitreous Carbon (RVC) as an anode and a platinum sheet as a cathode, carrying out stirring reaction under the conditions of 10mA constant current, argon protection and 100 ℃, monitoring the reaction process by TLC, extracting the mixture by using 10mL of ethyl acetate after the reaction is finished, and using anhydrous sodium sulfate for an organic layerDrying, spin-drying the solvent under reduced pressure, and purifying by column chromatography (SiO)₂Petroleum ether/ethyl acetate 40:1-10: 1) to afford the product.

The technical scheme synthesizes the polycyclic isoquinolone compound through two times of C-H activation through the electrochemical-driven amide and alkyne dehydrocyclization reaction, does not need an external oxidant in the reaction, realizes the circulation of a ruthenium catalyst by electricity, and has the most remarkable characteristic that the regioselectivity of a product can be effectively improved under the mild electrolysis condition.

Detailed Description

The present invention will be further illustrated with reference to the following examples, but is not limited thereto.