CN-122010701-A - Carbonyl compound and preparation method thereof

Abstract

The invention discloses a carbonyl compound and a preparation method thereof. According to the method, malonic acid derivatives are used as substrates, and under the air atmosphere and the irradiation of visible light, ferric nitrate nonahydrate is used as a catalyst to carry out photocatalytic decarboxylation oxidation reaction. After the reaction is finished, the target carbonyl compound can be obtained through separation and purification. The method has the advantages of green and mild reaction conditions, simple and convenient operation, easily obtained reagents, lower cost, good functional group compatibility and substrate applicability. The invention has potential application value in the fields of organic synthesis, pharmaceutical chemistry, bioactive molecule modification and the like.

Inventors

• CHEN JIANPING
• HE YANPING
• MENG JIE

Assignees

• 南京工业大学

Dates

Publication Date

20260512

Application Date

20260210

Claims (4)

1. 1. The preparation method of the carbonyl compound is characterized in that the carbonyl compound has a structure shown as a formula (I): In formula (I), R 1 and R 2 are each independently selected from hydrogen, C1-C6 alkyl, substituted or unsubstituted benzyl, substituted or unsubstituted phenethyl, C2-C10 hydrocarbyl containing ester groups, ether linkages, carbonyl groups, carbon-carbon double bonds or carbon-carbon triple bonds, molecular fragments derived from estrone or dehydrocholic acid, or R 1 and R 2 together with the carbon atom to which they are attached form a cyclobutane ring, pyran ring, benzo-five-membered heterocycle or N-benzoyl piperidine ring; the preparation method comprises the following steps: (1) Dissolving a malonic acid derivative shown in a formula (II) and an iron catalyst in an organic solvent in an atmosphere containing oxygen to form a reaction mixture, wherein the molar ratio of the iron catalyst to the malonic acid derivative shown in the formula (II) is 0.02-0.2:1; (2) Placing the reaction mixture obtained in the step (1) under the irradiation of blue light with the wavelength of 395-480nm and the power of 5-30W, stirring and reacting for 6-24 hours at the temperature of 30-60 ℃ to perform photocatalytic decarboxylation and oxidation; (3) After the reaction is finished, quenching, extracting, drying and concentrating the reaction system to obtain the carbonyl compound shown in the formula (I). Wherein formula (II) is: Wherein R 1 and R 2 are as defined for formula (I).
2. 2. The method according to claim 1, wherein the iron catalyst is at least one selected from the group consisting of ferric nitrate nonahydrate, ferric sulfate anhydrous, ferric acetylacetonate, ferric triflate, and ferrous sulfate heptahydrate.
3. 3. The method according to claim 1, wherein the organic solvent is at least one selected from the group consisting of N, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, N-methylpyrrolidone, and acetonitrile.
4. 4. The method of claim 1, wherein the atmosphere comprising oxygen is an oxygen or air atmosphere.

Description

Carbonyl compound and preparation method thereof Technical Field The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a preparation method of a carbonyl compound. According to the method, cheap ferric nitrate is used as a catalyst, air is used as a green oxidant, and the carbonyl compound is efficiently constructed through the free radical decarboxylation oxidation reaction of the malonic acid derivative under the driving of a visible light. Background Carbonyl compounds are core functional groups that are widely used and of critical value in organic synthesis. The importance of the material is represented in three aspects, namely, the structure is widely existing in natural products, synthetic intermediates and fine chemicals; in the reaction, the polymer is often used as a core substrate to participate in various important conversions, can be efficiently derived into various functional groups such as alcohol, amine, olefin, ester, amide and the like, provides a general and key way for the design of synthetic routes and the construction of functional molecules. The preparation method of carbonyl compounds is mature and mainly comprises the following classical pathways of oxidation of alcohols or olefins, hydration of alkynes, friedel-crafts acylation of aromatic compounds, hydrolysis after reaction of nitriles with grignard reagents, reaction of Weinreb amides with nucleophiles, and conversion of carboxylic esters under catalysis of transition metals such as organolithium reagents or palladium/nickel. Carboxylic acids are a class of compounds with wide sources, diverse structures, good stability and low cost, and carboxyl functional groups are common in natural products and various drug molecular structures, and are important raw materials in organic synthesis. Although derivatives (e.g., esters, amides) thereof are commonly used to prepare carbonyl compounds, processes for the direct conversion of carboxylic acids to carbonyl compounds have not progressed until recently. At present, the conversion mainly comprises four types of approaches, namely 1) using a stoichiometric strong oxidant, 2) using oxygen to participate in metal catalytic oxidation, 3) using oxygen to participate in photo-oxidation reduction catalysis and 4) using electrochemical decarboxylation oxidation reaction. Malonic acid derivatives are also a class of highly stable and readily available classical organic synthetic raw materials compared to monocarboxylic acids, and although decarboxylation oxidation reactions have become a research hotspot for monocarboxylic acids, to date, there has been less research on the decarboxylation oxidative conversion of malonic acid to the corresponding ketones. The malonic acid derivative can be used as a starting material and can undergo free radical decarboxylation oxidation reaction to obtain the corresponding carbonyl compound (Tetrahedron Lett.1966,7,6145) in the presence of stoichiometric lead acetate, and the malonic acid derivative can also be subjected to electrolytic decarboxylation in an ammonia methanol solution and then hydrolysis to obtain the corresponding carbonyl compound (org. Lett.2015,17,4690). The decarboxylation oxidation of malonic acid is reported to be relatively few and has a number of disadvantages, such as the need for the use of a stoichiometric amount of lead acetate which is relatively toxic or the need for electrochemical methods. In contrast to the former, electrochemical strategy is a green method for conversion to carbonyl compounds using malonic acid derivatives, but its substrate is limited and is only applicable to disubstituted malonic acid derivatives. In general, the reaction for preparing carbonyl compounds by decarboxylation oxidation of malonic acid is currently imperfect and requires further exploration and development. Considering that the carbonyl compound has very wide application in organic synthesis, pharmaceutical chemistry and industry, the invention provides a method for synthesizing the carbonyl compound by taking air as an oxidant, cheap and easily available ferric iron as a catalyst and through malonic acid free radical decarboxylation oxidation reaction, and provides a more green and efficient new way for preparing the carbonyl compound. Disclosure of Invention The invention aims to provide a preparation method of carbonyl compounds. The method aims to overcome the defects of the prior art, and utilizes a ligand-to-metal charge transfer strategy mediated by iron under the photocatalysis condition to realize the free radical decarboxylation and oxidization of malonic acid derivatives, thereby synthesizing target carbonyl compounds in a high-efficiency and green way. It is another object of the present invention to provide the use of the above method for the preparation of carbonyl compounds containing complex drug molecule fragments to demonstrate their potential in post-functionalization and drug-