阅读说明：本技术 一种合成多取代α,β不饱和酮的方法 (Method for synthesizing polysubstituted α unsaturated ketone ) 是由 魏颢 姜城 鲁鸿 于 2019-11-07 设计创作，主要内容包括：本发明具体涉及一种合成多取代α,β不饱和酮的方法,该方法包括：步骤一：将Ni(cod)<Sub>2</Sub>、氮杂环类卡宾配体、Cs<Sub>2</Sub>CO<Sub>3</Sub>和β,γ不饱和酮加入非极性非质子有机溶剂中,进行混合,制得混合物；步骤二：将步骤一中的混合物加入干燥后的容器中进行反应,反应温度120～180℃,反应时间10～40小时,反应结束后冷却至室温,制得粗产物；步骤三：提纯。该方法采用了廉价的Ni(cod)<Sub>2</Sub>作为催化剂,通过过渡金属来活化碳碳键,双键的异构化为该反应提供了动力,合成方法简单,底物稳定廉价,反应受底物限制性少,且底物适用性范围广。(The invention relates in particular to a synthesisA process for polysubstituted α unsaturated ketone includes such steps as mixing Ni (cod) 2 Nitrogen heterocyclic carbene ligands, Cs 2 CO 3 β, adding gamma unsaturated ketone into nonpolar aprotic organic solvent, mixing to obtain a mixture, adding the mixture obtained in the step one into a dried container for reaction at 120-180 ℃ for 10-40 hours, cooling to room temperature after the reaction to obtain a crude product, and purifying in the step three, wherein the method adopts cheap Ni (cod) 2 As a catalyst, carbon-carbon bonds are activated by transition metals, and the isomerization of double bonds provides power for the reaction, the synthetic method is simple, the substrate is stable and cheap, the reaction is less limited by the substrate, and the substrate has wide applicability.)

1. A method for synthesizing polysubstituted α unsaturated ketone is characterized by comprising the following steps:

the method comprises the following steps: mixing Ni (cod)₂Nitrogen heterocyclic carbene ligands, Cs₂CO₃β, adding gamma unsaturated ketone into nonpolar aprotic organic solvent, and mixing to obtain mixture;

step two: and (3) adding the mixture obtained in the step one into a dried container for reaction at the temperature of 120-180 ℃ for 10-40 hours, and cooling to room temperature after the reaction is finished to obtain a crude product.

2. The method for synthesizing polysubstituted α unsaturated ketone according to claim 1, further comprising the steps of, filtering the crude product obtained in step two, vacuum concentrating the filtrate to obtain a residue, and purifying the residue by silica gel column chromatography to obtain α unsaturated ketone.

3. The method for synthesizing polysubstituted α unsaturated ketones according to claim 1, wherein said azacyclo-carbene ligand is 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride, 1, 3-bis- (2, 6-diisopropylphenyl) imidazolium chloride, 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride or 1, 3-dicyclohexylimidazolium chloride.

4. The method of synthesizing a polysubstituted α unsaturated ketone according to claim 1, wherein said non-polar aprotic organic solvent is dioxane, toluene or xylene.

5. The method for synthesizing polysubstituted α unsaturated ketone according to claim 1, wherein said Ni (cod)₂And the nitrogen heterocyclic carbene ligand is prepared from the following raw materials in a molar ratio of 1: 2.

6. the method for synthesizing polysubstituted α unsaturated ketone according to claim 1, wherein said Ni (cod)₂The content of (a) is 5-15 mol%, the content of the azacyclo-carbene ligand is 10-30 mol%, and the content of Cs is₂CO₃The content of (B) is 20 to 35 mol%.

7. The method of synthesizing polysubstituted α unsaturated ketones according to claim 6, wherein said Ni (cod)₂The content of (A) is 10 mol%, the content of the azacyclo-carbene ligand is 20 mol%, and the content of Cs is₂CO₃The content of (B) is 30 mol%.

8. The method of claim 7, wherein the reaction temperature is 150 ℃ and the reaction time is 24 hours.

9. The method for synthesizing polysubstituted α unsaturated ketones according to any one of claims 1-8, wherein the reaction formula is represented by formula (A):

wherein R is: phenyl, 2-methylphenyl, 3-methylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-cyanophenyl, 4-ethylphenyl, 4-methoxyphenyl, phenol, 4-isopropylphenyl, 4-tert-butylphenyl, 4-phenylphenyl, 2-naphthyl, 2-furyl, 2-thienyl, a phenyl five-membered cyclic group, 2- (2-propenyl) phenyl or phenethyl.

10. The method for synthesizing polysubstituted α unsaturated ketones according to any one of claims 1-8, wherein the reaction formula is represented by formula (B):

wherein R is¹、R²、R³Respectively selected from any one of ethyl, phenyl, methyl, n-hexyl, phenethyl, five-membered (benzo) ring to eight-membered ring, androsteronyl, heptyl or nonyl.

Technical Field

The invention belongs to the technical field of chemical industry, and particularly relates to a method for synthesizing polysubstituted α unsaturated ketone.

Background

The traditional method for synthesizing the compound is greatly limited by substrates, and requires that two ketones participating in the reaction are the same compound or one ketone does not have a hydrogen atom at α, so that the compound cannot participate in the reaction as an electrophilic reagent.

In addition, foreign literature reports new methods for synthesizing these compounds.A new method for synthesizing these compounds by ring opening of cyclopropane is reported, for example, in (J.Am. chem. Soc.1981,103,2404-2405), but this method requires the use of an unstable three-membered ring as a substrate for the reaction, and the synthesis of the three-membered ring itself has a great difficulty.A three-component reaction involving a allene is reported, for example, in (J.Am. chem. Soc.2003,125,12576-12583), but this reaction also uses a highly active allene as a substrate, and for this reason, it is necessary to invent a new method for synthesizing α unsaturated ketones.

Disclosure of Invention

In order to solve the problems in the prior art, the invention provides a method for synthesizing polysubstituted α unsaturated ketoneThe method of (1), which uses inexpensive Ni (cod)₂As a catalyst, carbon-carbon bonds are activated by transition metals, and the isomerization of double bonds provides power for the reaction, the synthetic method is simple, the substrate is stable and cheap, the reaction is less limited by the substrate, and the substrate has wide applicability.

The technical problem to be solved by the invention is realized by the following technical scheme:

a method of synthesizing a polysubstituted α unsaturated ketone, comprising the steps of:

the method comprises the following steps: mixing Ni (cod)₂Nitrogen heterocyclic carbene ligands, Cs₂CO₃β, adding gamma unsaturated ketone into nonpolar aprotic organic solvent, and mixing to obtain mixture;

step two: and (3) adding the mixture obtained in the step one into a dried container for reaction at the temperature of 120-180 ℃ for 10-40 hours, and cooling to room temperature after the reaction is finished to obtain a crude product.

Preferably, the method for synthesizing the polysubstituted α unsaturated ketone further comprises a third step of filtering the crude product obtained in the second step, concentrating the filtrate in vacuum to obtain filter residue, and purifying the filter residue by using a silica gel column chromatography to obtain α unsaturated ketone.

Preferably, the nitrogen heterocyclic carbene ligand is 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride, 1, 3-bis- (2, 6-diisopropylphenyl) imidazolium chloride, 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride or 1, 3-dicyclohexylimidazole chloride.

Preferably, the nonpolar aprotic organic solvent is dioxane, toluene, or xylene.

Preferably, the above-mentioned Ni (cod)₂And the nitrogen heterocyclic carbene ligand is prepared from the following raw materials in a molar ratio of 1: 2.

preferably, the above-mentioned Ni (cod)₂The content of (a) is 5-15 mol%, the content of the azacyclo-carbene ligand is 10-30 mol%, and the content of Cs is₂CO₃The content of (B) is 20 to 35 mol%.

Preferably, the above-mentioned Ni (cod)₂The content of (a) is 10 mol%, and the content of the nitrogen heterocyclic carbene ligand20 mol% of the total amount of the above-mentioned Cs₂CO₃The content of (B) is 30 mol%.

Preferably, the reaction temperature is 150 ℃ and the reaction time is 24 hours.

Preferably, the reaction formula of the method for synthesizing the polysubstituted α unsaturated ketone is shown as the formula (A):

wherein R is: phenyl, 2-methylphenyl, 3-methylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-cyanophenyl, 4-ethylphenyl, 4-methoxyphenyl, phenol, 4-isopropylphenyl, 4-tert-butylphenyl, 4-phenylphenyl, 2-naphthyl, 2-furyl, 2-thienyl, a phenyl five-membered cyclic group, 2- (2-propenyl) phenyl or phenethyl.

Preferably, the reaction formula of the method for synthesizing the polysubstituted α unsaturated ketone is shown as the formula (B):

wherein R is¹、R²、R³Respectively selected from any one of ethyl, phenyl, methyl, n-hexyl, phenethyl, five-membered (benzo) ring to eight-membered ring, androsteronyl, heptyl or nonyl.

Compared with the prior art, the invention has the beneficial effects that:

1. the reaction system is simple, only a catalyst and a ligand need to be added in the reaction, and the adopted α -site acyl-substituted olefin compound substrate is obtained, so that the substrate is stable and easy to obtain, and the preparation cost is low;

2. the reaction system is clean, the conversion rate is high, the catalyst in the system is only required to be filtered, and the product is easy to separate;

3. the process of the present invention is widely applicable, most common functional groups are applicable to the process, substrates are widely applicable, and cyclic α unsaturated ketones and acyclic α unsaturated ketones can be prepared according to the process.

Drawings

FIG. 1 is a drawing of the product of example 1¹H NMR spectrum.

FIG. 2 is a photograph of the product of example 1¹³C NMR spectrum.

FIG. 3 is an X-RAY spectrum of the product of example 1.

FIG. 4 is β of example 1, a process for preparing gamma-unsaturated ketones¹H NMR spectrum.

FIG. 5 is β of example 1, a process for preparing gamma-unsaturated ketones¹³C NMR spectrum.

FIG. 6 is the HRMS spectrum of β, a gamma unsaturated ketone, from example 1.

Detailed Description

The present invention will be described in further detail with reference to specific examples, but the embodiments of the present invention are not limited thereto.

The invention provides a method for synthesizing α unsaturated ketone, which comprises the following steps:

the method comprises the following steps: 5 to 15 mol% of Ni (cod)₂10-30 mol% of nitrogen heterocyclic carbene ligand and 20-35 mol% of Cs₂CO₃β, adding gamma unsaturated ketone into nonpolar aprotic organic solvent, and mixing to obtain mixture;

step two: adding the mixture obtained in the step one into a dried container for reaction, wherein the reaction temperature is 120-180 ℃, the reaction time is 10-40 hours, and cooling to room temperature after the reaction is finished to obtain a crude product;

and step three, filtering the crude product in the step two, concentrating the filtrate in vacuum to obtain filter residue, and purifying the filter residue by using a silica gel column chromatography method to obtain α unsaturated ketone.

Wherein the nitrogen heterocyclic carbene ligand can be 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride, 1, 3-bis- (2, 6-diisopropylphenyl) imidazolium chloride, 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride or 1, 3-dicyclohexyl imidazolium chloride, and the nitrogen heterocyclic carbene ligand can adjust the electronic effect and the stereoscopic effect of a catalyst Ni center. Ni (cod)₂And the nitrogen heterocyclic carbene ligand is prepared from the following raw materials in a molar ratio of 1: 2, 1 mol of Ni(cod)₂Coordinated to 2 moles of azacyclo-carbene ligand. In view of the solubility of the substrate and the catalyst, the nonpolar aprotic organic solvent is selected for the method, and dioxane, toluene or xylene is selected for the nonpolar aprotic organic solvent in the embodiment.

The method of the invention can synthesize α unsaturated ketone of non-cyclic product and α unsaturated ketone of cyclic product by the same mechanism according to different reaction substrate structures.

(1) The reaction formula for the synthesis of the α unsaturated ketone for the acyclic product is as follows:

wherein R is: phenyl, 2-methylphenyl, 3-methylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-cyanophenyl, 4-ethylphenyl, 4-methoxyphenyl, phenol, 4-isopropylphenyl, 4-tert-butylphenyl, 4-phenylphenyl, 2-naphthyl, 2-furyl, 2-thienyl, a phenyl five-membered cyclic group, 2- (2-propenyl) phenyl or phenethyl.

The structural formula of the product is as follows:

(2) the reaction formula for the synthesis of the α unsaturated ketone for the acyclic product is as follows:

wherein R is¹、R²、R³Respectively selected from any one of ethyl, phenyl, methyl, n-hexyl, phenethyl, five-membered (benzo) ring to eight-membered ring, androsteronyl, heptyl or nonyl.

The structural formula of the product is as follows: