CN-115108901-B - Synthesis method of alpha-hydroxycarboxylic acid compound

Abstract

The invention discloses a synthesis method of alpha-hydroxycarboxylic acid compounds, which comprises the steps of adding a reaction substrate, a photosensitizer and alkali into a dry reaction tube, adding a solvent and an additive under the atmosphere of CO 2 gas, carrying out reaction under the irradiation of visible light, carrying out acidification quenching treatment on a reaction system after the reaction is finished, separating and purifying to obtain the product alpha-hydroxycarboxylic acid compounds, wherein the photosensitizer comprises Ir (ppy) 2 (dtbbpy)PF 6 and 3DPA2FBN, the alkali is potassium tert-butoxide, cesium carbonate or potassium pivalate, the additive is N, N-diisopropylethylamine and chlorosilane, and the reaction substrate is aldehyde ketone compounds. The method for synthesizing the alpha-hydroxycarboxylic acid compound in the environment of the visible light induction and the CO 2 gas has the advantages of mild reaction conditions, wide range of reactants, good selectivity and capability of being amplified to gram scale.

Inventors

• YU DAGANG
• CAO GUANGMEI
• HU XINLONG
• LIAO LILI
• YAN SISHUN
• SONG LEI
• GONG LI

Assignees

• 四川大学
• 四川大学

Dates

Publication Date

20260421

Application Date

20210322

Priority Date

20210322

Claims (6)

1. 1. The method comprises the following steps of -A method for synthesizing hydroxycarboxylic acid compounds, comprising the steps of: S1, adding a photosensitizer and alkali into a reaction substrate, adding a solvent and an additive under a CO 2 atmosphere, and uniformly mixing to obtain a reaction solution, wherein the reaction substrate is a ketone compound, the additive is a mixture of N, N-diisopropylethylamine and chlorosilane, the photosensitizer is Ir (ppy) 2 (dtbbpy)PF 6 or 3DPA2FBN, the alkali is potassium tert-butoxide or cesium carbonate, the chlorosilane is TESCl and TMSCl, and the structural formula of the reaction substrate is shown as formula (I): Wherein R 1 is aryl, R 2 is alkyl; S2, placing the reaction liquid obtained in the step S1 at a position 1-5 cm away from a visible light source, stirring at room temperature for reaction for 0.1-48 hours, then quenching the reaction by using a quenching agent, and spin-drying the solvent to obtain a crude product; s3, purifying the crude product obtained in the step S2 by flash column chromatography to obtain -Hydroxycarboxylic acids, said The structural formula of the hydroxy carboxylic acid compound is shown as a formula (II): (II)。
2. 2. The method according to claim 1 The synthesis method of the hydroxy carboxylic acid compound is characterized in that the use level of the photosensitizer is 0.1-5 mol% of that of a reaction substrate, the addition level of the base is 1-3 times of that of the reaction substrate, the addition level of the N, N-diisopropylethylamine in the additive is 1-3 times of that of the reaction substrate, and the addition level of the chlorosilane is 1-3 times of that of the reaction substrate.
3. 3. According to claim 1 or 2 The synthesis method of the hydroxycarboxylic acid compound is characterized in that the solvent is DMF or DMA.
4. 4. According to claim 1 or 2 The synthesis method of the hydroxy carboxylic acid compound is characterized in that the quenching agent is tetrabutylammonium fluoride or hydrochloric acid aqueous solution.
5. 5. The method according to claim 1 The synthesis method of the hydroxycarboxylic acid compound is characterized in that the visible light source is a blue LED lamp with the wavelength of 30W.
6. 6. The method according to claim 1 The synthesis method of the hydroxy carboxylic acid compound is characterized in that eluent used for column chromatography purification in S3 is a mixture of petroleum ether, ethyl acetate and glacial acetic acid, wherein the volume ratio of the petroleum ether to the ethyl acetate in the mixture is 10:1, and the mass fraction of the glacial acetic acid is 0.1% -1%.

Description

Synthesis method of alpha-hydroxycarboxylic acid compound Technical Field The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of an alpha-hydroxycarboxylic acid compound. Background Alpha-hydroxy carboxylic acids (AHAs) are common building blocks in biologically active compounds and play a considerable role in the cosmetic industry. In addition, because of their strong acidity and water solubility, there are many applications in organic synthesis that they can be used as chiral ligands, solvents and building blocks for total synthesis. Finally, they are also building blocks for monomers and unnatural peptides that are common in polymerization reactions. Thus, many synthetic strategies have been developed to achieve the synthesis of this class of compounds. The most commonly used synthesis methods at present mainly comprise four steps of preparing alpha-amino acid serving as a raw material through diazotization, hydrolysis and the like, carrying out nucleophilic addition of hydrocyanic acid (salt) or tribromomethane on aldehyde, and then hydrolyzing to obtain the alpha-hydroxycarboxylic acid, and carrying out selective reduction on prochiral alpha-keto acid to obtain the alpha-hydroxycarboxylic acid, and fourth preparing the alpha-hydroxycarboxylic acid analogue through selective oxidation of 1, 2-diol compounds. There are of course other methods such as nucleophilic addition with glycidic acid or glyoxylic acid, palladium-catalyzed C-H functionalization of lactic acid derivatives, direct alpha-C-H carboxylation of primary alcohols, etc. However, many of the above processes have problems of low yields or limited availability of starting materials, and even some of the reaction conditions are severe, requiring multiple conversions or the use of highly toxic and hazardous chemicals such as cyanide. Therefore, the conventional synthesis method has a certain limitation. The research of a novel and efficient method for synthesizing the alpha-hydroxycarboxylic acid compound has important significance, such as synthesizing the alpha-hydroxycarboxylic acid compound by nucleophilic attack of CO 2 by a strategy of reversing the polarity of aldehyde ketone carbonyl compounds. In the strategy, raw materials are easy to obtain, and the greenhouse gas CO 2 can be utilized, so that the method accords with the concept of green chemistry. The clean energy source of the light source can be applied to the synthesis of the alpha-hydroxycarboxylic acid compound, so that the synthesis concept of green chemistry can be enhanced. Due to the large amount of CO 2 discharged, the global climate is increasingly warmed, the sea level is increased, the ecological environment is deteriorated, and natural disasters are frequent. Therefore, basic research on emission reduction and reasonable utilization of CO 2 is very important. If the method can realize the efficient conversion of the carboxylic acid molecules into the carboxylic acid molecules with important value and realize the industrialized mass production of the carboxylic acid molecules, not only can the chemical production industrial mode be created and the production cost be reduced, but also the utilization efficiency of CO 2 resources can be greatly improved, and a new idea is provided for solving the greenhouse effect. At present chemists have achieved some conversion of CO 2 and obtained a range of chemicals with high added value. However, the chemical utilization of CO 2, especially the part that achieves its industrialization, is only the iceberg corner, the main reason for which is due to the thermodynamic stability and kinetic inertness of CO 2. Therefore, the method explores the efficient and novel CO 2 conversion reaction, promotes the recycling utilization process of CO 2 and promotes the global carbon circulation, and has important academic value and practical significance. Disclosure of Invention The invention aims to provide a synthesis method of alpha-hydroxycarboxylic acid compounds, which has the advantages of high yield, mild reaction conditions, low toxicity of reaction reagents, low cost and the like, aiming at the limitations of the prior synthesis technology. In order to achieve the aim, the technical scheme adopted by the invention is to provide a synthesis method of an alpha-hydroxycarboxylic acid compound, which is characterized by comprising the following steps: s1, adding a photosensitizer and alkali into a reaction substrate, adding a solvent and an additive under the atmosphere of CO 2, and uniformly mixing to obtain a reaction solution, wherein the reaction substrate is an aldehyde or ketone compound, and the additive is a mixture of N, N-diisopropylethylamine and chlorosilane; s2, placing the reaction liquid obtained in the step S1 at a position 1-5cm away from a visible light source, stirring at room temperature for reaction for 0.1-48 h, then quenching the reaction by using a quenching