阅读说明：本技术 一种制备β-羰基砜的方法 (Method for preparing β -carbonyl sulfone ) 是由 万小兵 王航航 郑永高 廉鹏程 李晶晶 于 2019-11-29 设计创作，主要内容包括：本发明公开了一种制备β-羰基砜的方法。以α-羰基重氮化合物和芳基亚磺酸钠为反应底物,以廉价的硝酸银为最优催化剂,1,10-菲啰啉为配体,过硫酸钾为氧化剂,在乙腈与水的混合溶剂中经过偶联反应得到β-羰基砜化合物。与现有技术相比较,本发明方法具有以下优点：反应底物范围广,反应时间短,反应产率比较高,反应条件温和等优点。本发明使用无毒无害的试剂为反应原料,对环境没有危害,符合当代绿色化学发展的要求。反应后处理比较简单,便于分离提纯。此外,该反应能够实现克级规模合成,为实际应用奠定基础。(The invention discloses a method for preparing β -carbonyl sulfone, which comprises the steps of taking α -carbonyl diazo compound and sodium arylsulfinate as reaction substrates, taking cheap silver nitrate as an optimal catalyst, taking 1, 10-phenanthroline as a ligand and taking potassium persulfate as an oxidant, and carrying out coupling reaction in a mixed solvent of acetonitrile and water to obtain a β -carbonyl sulfone compound.)

1. A process for preparing β -carbonyl sulfone, which comprises reacting α -carbonyl diazo compound and sodium arylsulfinate,N,Nreacting a bidentate compound serving as a ligand and peroxide serving as an oxidant in a mixed solvent of an organic solvent and water in the presence of a metal compound catalyst to obtain β -carbonyl sulfone compound;

the α -carbonyl diazo compound has the following chemical structural formula:

in the formula, R¹Selected from methyl, ethyl or hydrogen; r²Is an alkoxy group;

the chemical structural formula of the sodium arylsulfinate is as follows:

in the formula, Ar is benzene or substituted benzene;

the β -carbonyl sulfone has the following chemical structural formula:

2. the method for preparing β -carbonyl sulfone of claim 1, wherein the reaction temperature is 40-90 ℃ and the reaction time is 4-12 hours.

3. The method of claim 1, wherein the metal compound is a silver compound or a copper compound, the peroxide is potassium persulfate, sodium persulfate, or ammonium persulfate;N,Nthe-bidentate compound is 1, 10-phenanthroline, 2' -bipyridine, 4, 7-dimethoxy-1, 10-phenanthroline, 4, 7-diphenylOne of 1, 10-phenanthroline, 3, 8-dibromo-1, 10-phenanthroline.

4. The method for preparing β -carbonyl sulfone according to claim 1, wherein the amount of the catalyst is 10% of the molar amount of the sodium arylsulfinate, the amount of the oxidant is 0.2-2 times of the molar amount of the sodium arylsulfinate, the amount of the ligand is 10% of the molar amount of the sodium arylsulfinate, and the amount of the α -carbonyl diazo compound is 2 times of the molar amount of the sodium arylsulfinate.

5. The method of claim 1 for preparing β -carbonyl sulfone, wherein the reaction is carried out in air.

6. The method of claim 1, wherein the organic solvent is acetonitrile.

7. The application of the metal compound as a catalyst in catalyzing the reaction of α -carbonyl diazo compound and sodium arylsulfinate to prepare β -carbonyl sulfone is characterized in that the metal compound is a silver compound or a copper compound.

8. Use according to claim 7, characterized in that: the reaction is carried out inN,NThe preparation method comprises the following steps of (1) carrying out reaction in a mixed solvent of an organic solvent and water in the presence of a bidentate compound and a peroxide, wherein the using amount of the metal compound is 10% of the molar amount of the sodium arylsulfinate, and the using amount of the α -carbonyl diazo compound is 2 times of the molar amount of the sodium arylsulfinate.

9. Use according to claim 8, characterized in that: the using amount of the peroxide is 0.2-2 times of the molar amount of the sodium arylsulfinate; said is atN,NThe bidentate compound is used in an amount of 10% of the molar amount of sodium arylsulphinate.

10. The β -carbonyl sulfone compound prepared according to the process of claim 1 for preparing β -carbonyl sulfone.

Technical Field

The invention relates to a method for preparing β -carbonyl sulfone, belonging to the technical field of organic synthesis.

Background

The sulfone skeleton compound has wide application, and the sulfone skeleton compound is also an important reaction intermediate in organic synthetic chemistry, for example, the sulfone skeleton compound can be converted into a corresponding target molecule through Julia alkenylation, Ramberg-Bäcklund reaction and Smiles rearrangement, because of the wide application, a series of methods for synthesizing the sulfone skeleton compound have been developed in the past decades, β -carbonyl sulfone compound has special interest among numerous sulfone group compounds, the compound has wide activity and is often used for the total synthesis of natural products and the synthesis of heterocyclic compounds, therefore, the compound has important significance for the synthesis of β -carbonyl sulfone compound, and the literature investigation shows that the current synthesis method for β -carbonyl sulfone has some defects, such as harsh reaction conditions, poor atom economy, narrow substrate range, complex operation and the like.

(1) Karl Anker J ø rgensen et al report the use of a thiol compound to react with a α -bromocarbonyl compound under basic conditions to first obtain a thioether followed by H₅IO₆And catalytic amount of CrO₃Oxidation gives the corresponding β -carbonyl sulfone compound but requires multiple reactions and the use of large excesses of oxidizing agent (see k.a. Jorgensen.Eur. J. Org. Chem.2011,2011, 47）；

(2) Knospe, r.h. et al reported that the synthesis of β -carbonyl sulfone compound was achieved using Claisen condensation reaction strategy, but the reaction had disadvantages in that it required the use of strong base sodium ethoxide, it was not environmentally friendly, and the reaction steps were cumbersome, and the substrate range was also narrow (see Knospe, r.h).J. Am. Chem. Soc. 1955,77, 5063）；

(3) Chen Zhen-Chu uses ketone compound and PhI (OH) OTs to carry out reflux operation in acetonitrile solvent to obtain α -p-toluenesulfonyloxy substituted ketone substance, and then carries out reflux operation with sodium benzene sulfinate in mixed solvent of acetonitrile and water to obtain corresponding β -carbonyl sulfone compound.

In conclusion, the methods for synthesizing β -carbonyl sulfone reported at present have obvious disadvantages, such as high cost, complicated reaction operation, harsh reaction conditions, poor atom economy, narrow substrate range and the like, so that it is important to develop a method with rich raw material sources, high reaction activity, low cost, safety, environmental protection and simple operation to effectively synthesize the β -carbonyl sulfone compound.

Disclosure of Invention

The invention aims to provide a method for preparing β -carbonyl sulfone compounds, which has the advantages of abundant sources of reaction raw materials, wide universality of reaction substrates, mild reaction conditions and simple and convenient operation.

In order to achieve the purpose of the invention, the technical scheme adopted by the invention is as follows:

a process for preparing β -carbonyl sulfone comprises reacting α -carbonyl diazo compound and sodium arylsulfinate,N,Nthe β -carbonyl sulfone compound is obtained by reacting a bidentate compound serving as a ligand and peroxide serving as an oxidant in a mixed solvent of an organic solvent and water in the presence of a metal compound catalyst.

The invention discloses application of a metal compound serving as a catalyst in catalyzing reaction of α -carbonyl diazo compound and sodium arylsulfinate to prepare β -carbonyl sulfone, wherein the metal compound is a silver compound or a copper compound.

In the invention, the α -carbonyl diazo compound has the following chemical structural formula:

in the formula, R¹Selected from methyl, ethyl or hydrogen; r²Is an alkoxy group;

the chemical structural formula of the sodium arylsulfinate is as follows:

in the formula, Ar is benzene or substituted benzene;

the metal compound is a silver compound or a copper compound, preferably a silver compound such as silver nitrate;

the peroxide is potassium persulfate, sodium persulfate or ammonium persulfate, preferably potassium persulfate;

N,Nthe-bidentate compound is one of 1, 10-phenanthroline, 2' -bipyridine, 4, 7-dimethoxy-1, 10-phenanthroline, 4, 7-diphenyl-1, 10-phenanthroline, 3, 8-dibromo-1, 10-phenanthroline, and preferably 1, 10-phenanthroline;

the β -carbonyl sulfone has the following chemical structural formula:

。

in the invention, the reaction temperature is 40-90 ℃ and the reaction time is 4-12 hours; preferably, the reaction temperature is 70 ℃ and the reaction time is 4 hours.

According to the invention, the dosage of the catalyst is 10% of the molar weight of sodium arylsulfinate, the dosage of the oxidant is 0.2-2 times, preferably 0.5 times of the molar weight of sodium arylsulfinate, the dosage of the ligand is 10% of the molar weight of sodium arylsulfinate, and the dosage of the α -carbonyl diazo compound is 2 times of the molar weight of sodium arylsulfinate.

In the present invention, the reaction is carried out in air.

In the present invention, the organic solvent is acetonitrile, and preferably, the volume ratio of acetonitrile to water is 10: 1.

After the reaction is finished, quenching the reaction system by using saturated sodium sulfite solution, extracting for 3 times by using ethyl acetate, combining organic layers, drying by using anhydrous sodium sulfate, removing a solvent, adsorbing by using silica gel, and then carrying out column chromatography to obtain the β -carbonyl sulfone product.

Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:

1. according to the invention, silver nitrate is preferably used as a catalyst, 1, 10-phenanthroline is used as a ligand, and 0.5 equivalent of potassium persulfate is used as an oxidant, so that the reaction of sodium benzene sulfinate and α -carbonyl diazo compound is realized to prepare the β -carbonyl sulfone compound.

2. Compared with the prior art, the method does not need to be carried out under the strong alkaline condition, and the used reagent is non-toxic and harmless and has no harm to the environment.

3. The diazo compound can be prepared from various alcohols including biologically active alcohols, so that the corresponding β -carbonyl sulfone compound can be prepared by cross coupling with sodium aryl sulfinate, and the substrate universality is good.

Detailed Description

The invention is further described below with reference to the following examples:

the invention discloses a making method of β -carbonyl sulfone, which comprises the following steps that α -carbonyl diazo compound and aryl sodium sulfinate are used as reaction substrates,N,Nthe β -carbonyl sulfone compound is obtained by reacting a bidentate compound serving as a ligand and peroxide serving as an oxidant in a mixed solvent of an organic solvent and water in the presence of a metal compound catalyst.

The catalyst, the oxidant, the ligand, the sodium benzene sulfinate, the sodium 4-methyl benzene sulfinate, the sodium 4-fluorobenzene sulfinate, the sodium 4-chlorobenzene sulfinate and the organic solvent are all commercial products and can be directly purchased and obtained. The diazo compound is prepared by taking corresponding alcohols or amines as starting materials according to different structures.