阅读说明：本技术 一种酮芳基化制备取代芳基酮的方法 (Method for preparing substituted aryl ketone by ketone arylation ) 是由 陆辉扬 沈安 曹育才 李永清 倪晨 胡宇才 于 2019-11-23 设计创作，主要内容包括：本发明提供一种酮芳基化制备取代芳基酮的方法,在碱性条件下,采用饱和氮杂环卡宾结构的氮杂环卡宾催化剂,在含氧气氛中,催化芳基卤化物或类卤化物和羰基α-位的分子内或分子间的偶联反应,制备得到取代芳基酮,本发明提供的方法,采用新的催化体系,氮杂环卡宾催化剂中的金属钯配合物采用饱和氮杂环卡宾结构,具有更好的稳定性,可在极低催化剂用量以及在含有氧气气氛的条件下高效制备各种取代α-芳基酮,适合工业化生产。(The invention provides a method for preparing substituted aryl ketone by ketone arylation, which adopts a nitrogen heterocyclic carbene catalyst with a saturated nitrogen heterocyclic carbene structure to catalyze coupling reaction between aryl halide or similar halide and carbonyl α -position molecules or between the molecules in an oxygen-containing atmosphere to prepare the substituted aryl ketone.)

1. A method for preparing substituted aryl ketone by ketone arylation is characterized in that a substituted aryl ketone (D) is prepared by the following reaction in an oxygen-containing atmosphere by using a nitrogen heterocyclic carbene catalyst shown in formula (A):

in the above reaction formula:

R¹、R²、R³、R⁴、R⁵、R⁶、R⁷、R⁸each independently represents hydrogen, alkyl, heteroalkyl, alkenyl or aryl, and two adjacent groups can form a cyclic group, and the groups can be further fused with a benzene ring to form a multi-aromatic ring;

x is fluorine, chlorine, bromine or iodine;

the N-heterocyclic carbene catalyst shown in the formula (A) has the following structural characteristics:

in the above structure:

R⁹、R¹⁰、R¹¹each independently represents an alkyl, heteroalkyl, alkenyl or aryl group;

R¹²、R¹³、R¹⁴、R¹⁵、R¹⁶each independently represents hydrogen, alkyl, heteroalkyl, alkenyl or aryl, and two adjacent groups can form a cyclic group, and the groups can be further fused with a benzene ring to form a multi-aromatic ring;

y is selected from fluorine, chlorine, bromine, iodine or acetoxy;

m is a transition metal.

2. The method of claim 1, wherein the aryl ketone is a substituted aryl ketone,

R¹、R²、R³、R⁴、R⁵、R⁶、R⁷、R⁸、R¹²、R¹³、R¹⁴、R¹⁵、R¹⁶each independently represents hydrogen or C₁-C₁₅Alkyl radical, C₁-C₁₅Alkoxy, silyl, C₁-C₁₅Heteroalkyl group, C₁-C₁₅Alkenyl or C₁-C₂₈Aryl, wherein two adjacent groups can form a cyclic group, and the groups can be further fused with a benzene ring to form a multi-aromatic ring;

R⁹、R¹⁰、R¹¹each independently represents C₁-C₁₅Alkyl radical, C₁-C₁₅Alkoxy, silyl, C₁-C₁₅Heteroalkyl group, C₁-C₁₅Alkenyl or C₁-C₄₀An aryl group;

m is selected from chromium, iron, nickel, copper, zinc, silver, palladium, rhodium, ruthenium, iridium and platinum.

3. The method of claim 1, wherein R is R¹、R²、R³、R⁴、R⁵、R⁶、R⁷、R⁸、R¹²、R¹³、R¹⁴、R¹⁵、R¹⁶Each independently selected from the group consisting of H, methyl, methoxy, ethyl, ethoxy, propyl, isopropyl, propoxy, butyl, isobutyl, butoxy, pentyl, isopentyl, cyclopentyl, pentyloxy, hexyl, hexyloxy, cyclohexyl, phenyl, phenoxy, heptyl, heptyloxy, methylphenyl, methylphenoxy, octyl, octyloxy, dimethylphenyl, ethylphenyl, dimethylphenoxy, ethylphenoxy, nonyl, nonyloxy, trimethylphenyl, methylethylphenyl, propylphenyl, trimethylphenoxy, methylethylphenoxy, propylphenoxy, decyl, decyloxy, tetramethylphenyl, dimethylethylphenyl, methylpropylphenyl, diethylphenyl, butylphenyl, tetramethylphenoxy, dimethylethylphenoxy, methylpropylphenoxy, diethylphenoxy, naphthyl, naphthyloxy, methylnaphthyl, isopentylphenoxy, pentylphenoxy, hexyloxy, phenyl, hexyloxy, methylphenyl, hexyloxy, dimethylphenyl, Methylnaphthoxy, ethenyl, propenyl, butenyl, isobutenyl, pentenyl, isopentenyl, hexenyl, azodimethyl, azodiethyl, trimethylsilyl, trimethylsilyloxy, triethylsilyl, triethylsilyloxy, tert-butyldimethylsilyl, triphenylsilyl, triphenylsilyloxy, wherein two adjacent groups may constitute a cyclic group.

4. The method of claim 1, wherein the aryl ketone is substituted with a substituted aryl ketoneCharacterized in that R is⁹、R¹⁰、R¹¹Each independently selected from the group consisting of methyl, methoxy, ethyl, ethoxy, propyl, isopropyl, propoxy, butyl, isobutyl, butoxy, pentyl, isopentyl, cyclopentyl, pentyloxy, hexyl, hexyloxy, cyclohexyl, phenyl, phenoxy, heptyl, heptyloxy, methylphenyl, methylphenoxy, octyl, octyloxy, dimethylphenyl, ethylphenyl, dimethylphenoxy, ethylphenoxy, nonyl, nonyloxy, trimethylphenyl, methylethylphenyl, propylphenyl, dipropylphenyl, trimethylphenoxy, methylethylphenoxy, propylphenoxy, decyl, decyloxy, tetramethylphenyl, dimethylethylphenyl, methylpropylphenyl, diethylphenyl, butylphenyl, tetramethylphenoxy, dimethylethylphenoxy, methylpropylphenoxy, diethylphenoxy, butylphenoxy, naphthyl, naphthyloxy, isopentyloxy, pentyloxy, hexyloxy, octyloxy, Methylnaphthyl, methylnaphthoxy, ethenyl, propenyl, butenyl, isobutenyl, pentenyl, isopentenyl, hexenyl, azodimethyl, azodiethyl, trimethylsilenyl, trimethylsilyloxy, triethylsilyl, triethylsiloxy, tert-butyldimethylsilyl, triphenylsilyl, triphenylsiloxy, dipentylphenyl, diphenylmethylphenyl.

5. The process of claim 1, wherein the solvent used in the reaction is selected from the group consisting of water, an alkane, an aromatic hydrocarbon, and a mixture of one or more alcohol ether organic solvents.

6. The method of claim 1, wherein the base used in the reaction is one or two of organic base or inorganic base selected from alkali metal, alkaline earth metal organic base or inorganic base, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium hydride, calcium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium tert-butoxide, potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, potassium hydrogen sulfate, sodium persulfate, magnesium ethoxide, magnesium butyl chloride, magnesium butyl bromide, and magnesium methyl butyl.

7. The method for preparing substituted aryl ketone by arylating ketone according to claim 1, wherein the reaction temperature is-80 ℃ to 150 ℃, and the molar ratio of reactants (B) to (C) is 0.01 to 99.

8. The method of claim 1, wherein the oxygen content of the oxygen-containing atmosphere is 1% to 40% (by volume).

9. The method of claim 1, wherein Y is one of chlorine, bromine, and acetoxy, and M is one of nickel, palladium, and platinum.

10. The method of claim 1, wherein R is R⁹、R¹⁰、R¹¹Each independently selected from trimethylphenyl, dipropylphenyl, dipentylphenyl and diphenylmethylphenyl.

Technical Field

The invention relates to the technical field of organic compounds, in particular to a method for preparing substituted aryl ketone by ketone arylation.

Background

α -arylcarbonyl functional groups are important components of not only many natural products (Chin.J.org.chem.2005,25(3): 282-.

The preparation of α -arylcarbonyl compounds by ketone α -arylation is the most efficient method, i.e. intramolecular or intermolecular coupling reaction of aryl halide or pseudohalide and carbonyl α -position is catalyzed by transition metal under basic condition, although the method of preparing substituted aryl ketone by transition metal palladium has achieved some achievements (U.S. Pat. No. 20060287544A 1; CN.patent 201310437. X), for example, the conventional transition metal phosphine ligand is changed into azacyclo-carbene ligand (NHCs), the sensitivity of the reaction system to water and oxygen is reduced (J.Org.Chem.2005,690, 5832-5840; the problem of severe usage of noble metal palladium in industrial production is not solved, only the problem of severe usage of noble metal palladium is reported by Nolan < 1% under the condition of catalyzing benzene-carbene-aryl ketone under the condition, No. 1722-1722. the above mentioned catalyst can be used under the condition of no-methoxy group under the condition of benzene-aryl ketone synthesis and no-aryl group under the condition (E.S. 1722-1722. under the condition of no-methoxy group under the condition of benzene-carbene-aryl ketone under the condition and no-aryl group under the condition of benzene-carbazole.

It can be seen from the above literature reports that it is of great practical significance to greatly reduce the amount of catalyst required for preparing substituted aryl ketones and avoid harsh reaction operating conditions, and to develop a method suitable for the industrial production of substituted aryl ketones.

Disclosure of Invention

The invention aims to solve the problem that the prior art cannot provide a ketone arylation reaction with low catalytic dosage completely in an oxygen-containing atmosphere, and provides a method for preparing substituted aryl ketone by ketone arylation, which can prepare various substituted α -aryl ketones efficiently under the conditions of extremely low catalyst dosage and oxygen-containing atmosphere.

The purpose of the invention is realized by the following technical scheme:

the invention provides a method for preparing substituted aryl ketone by ketone arylation, which uses an N-heterocyclic carbene catalyst shown in formula (A) to obtain substituted aryl ketone (D) by the following reaction process in an oxygen-containing atmosphere:

in the above reaction formula: r¹、R²、R³、R⁴、R⁵、R⁶、R⁷、R⁸Each independently represents hydrogen, alkyl, heteroalkyl, alkenyl or aryl, and two adjacent groups can form a cyclic group, and the groups can be further fused with a benzene ring to form a multi-aromatic ring; x is fluorine, chlorine, bromine or iodine; the oxygen content level of the atmosphere is 1-40% (volume ratio);

the N-heterocyclic carbene catalyst shown in the formula (A) has the following structural characteristics:

in the above structure R⁹、R¹⁰、R¹¹Each independently represents an alkyl, heteroalkyl, alkenyl or aryl group; r¹²、R¹³、R¹⁴、R¹⁵、R¹⁶Each independently represents hydrogen, alkyl, heteroalkyl, alkenyl or aryl, and two adjacent groups can form a cyclic group, and the groups can be further fused with a benzene ring to form a multi-aromatic ring; y is selected from fluorine, chlorine, bromine, iodine or acetoxy, and M is a transition metal.

Preferably, R¹、R²、R³、R⁴、R⁵、R⁶、R⁷、R⁸、R¹²、R¹³、R¹⁴、R¹⁵、R¹⁶Each independently represents hydrogen or C₁-C₁₅Alkyl radical, C₁-C₁₅Alkoxy, silyl, C₁-C₁₅Heteroalkyl group, C₁-C₁₅Alkenyl or C₁-C₁₈Aryl radical, R⁹、R¹⁰、R¹¹Each independently represents C₁-C₁₅Alkyl radical, C₁-C₁₅Alkoxy, silyl, C₁-C₁₅Heteroalkyl group, C₁-C₁₅Alkenyl or C₁-C₄₀Aryl, each independently represents hydrogen, C₁-C₁₅Alkyl radical, C₁-C₁₅Alkoxy, silyl, C₁-C₁₅Heteroalkyl group, C₁-C₁₅Alkenyl or C₁-C₂₈And M is selected from chromium, iron, nickel, copper, zinc, silver, palladium, rhodium, ruthenium, iridium and platinum.

Preferably, R¹、R²、R³、R⁴、R⁵、R⁶、R⁷、R⁸、R¹²、R¹³、R¹⁴、R¹⁵、R¹⁶Each independently selected from the group consisting of H, methyl, methoxy, ethyl, ethoxy, propyl, isopropyl, propoxy, butyl, isobutyl, butoxy, pentyl, isopentyl, cyclopentyl, pentyloxy, hexyl, hexyloxy, cyclohexyl, phenyl, phenoxy, heptyl, heptyloxy, methylphenyl, methylphenoxy, octyl, octyloxy, dimethylphenyl, ethylphenyl, dimethylphenoxy, ethylphenoxy, nonyl, nonyloxy, trimethylphenyl, methylethylphenyl, propylphenyl, trimethylphenoxy, methylethylphenoxy, propylphenoxy, decyl, decyloxy, tetramethylphenyl, dimethylethylphenyl, methylpropylphenyl, diethylphenyl, butylphenyl, tetramethylphenoxy, dimethylethylphenoxy, methylpropylphenoxy, diethylphenoxy, naphthyl, naphthyloxy, methylnaphthyl, isopentylphenoxy, pentylphenoxy, hexyloxy, phenyl, hexyloxy, methylphenyl, hexyloxy, dimethylphenyl, Methylnaphthoxy, ethenyl, propenyl, butenylIsobutylene, pentenyl, isopentenyl, hexenyl, azodimethyl, azodiethyl, trimethylsilyl, trimethylsilyloxy, triethylsilyl, tert-butyldimethylsilyl, triphenylsilyl, wherein two adjacent groups may constitute a cyclic group.

Preferably, R⁹、R¹⁰、R¹¹Each independently selected from the group consisting of methyl, methoxy, ethyl, ethoxy, propyl, isopropyl, propoxy, butyl, isobutyl, butoxy, pentyl, isopentyl, cyclopentyl, pentyloxy, hexyl, hexyloxy, cyclohexyl, phenyl, phenoxy, heptyl, heptyloxy, methylphenyl, methylphenoxy, octyl, octyloxy, dimethylphenyl, ethylphenyl, dimethylphenoxy, ethylphenoxy, nonyl, nonyloxy, trimethylphenyl, methylethylphenyl, propylphenyl, dipropylphenyl, trimethylphenoxy, methylethylphenoxy, propylphenoxy, decyl, decyloxy, tetramethylphenyl, dimethylethylphenyl, methylpropylphenyl, diethylphenyl, butylphenyl, tetramethylphenoxy, dimethylethylphenoxy, methylpropylphenoxy, diethylphenoxy, butylphenoxy, naphthyl, naphthyloxy, isopentyloxy, pentyloxy, hexyloxy, octyloxy, Methylnaphthyl, methylnaphthoxy, ethenyl, propenyl, butenyl, isobutenyl, pentenyl, isopentenyl, hexenyl, azodimethyl, azodiethyl, trimethylsilenyl, trimethylsilyloxy, triethylsilyl, triethylsiloxy, tert-butyldimethylsilyl, triphenylsilyl, triphenylsiloxy, dipentylphenyl, diphenylmethylphenyl.

Preferably, the solvent used for the reaction is selected from one or more of water, alkane, aromatic hydrocarbon or alcohol ether organic solvent, preferably one or more of water, toluene, xylene, n-hexane, cyclohexane, n-heptane, dichloromethane, 1, 2-dichloroethane, tetrahydrofuran, pyrrolidine, methanol, ethanol, isopropanol, n-butanol, tert-butanol, cyclohexanol, dioxane, dimethylformamide, dimethylacetamide, diethyl ether, isopropyl ether, methyl tert-butyl ether, methyl cyclopentyl ether and ethylene glycol dimethyl ether.

Preferably, the base used in the reaction is an organic base or an inorganic base, preferably an organic base or an inorganic base selected from alkali metals, alkaline earth metals, one or two of sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium hydride, calcium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium tert-butoxide, potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, potassium hydrogen sulfate, sodium persulfate, magnesium ethoxide, magnesium butyl chloride, magnesium butyl bromide and magnesium methyl butyl.

Preferably, the reaction temperature is-80 ℃ to 150 ℃, and further preferably-20 ℃ to 150 ℃; the molar ratio of the reactants (B) to (C) is 0.01 to 99, and more preferably 0.1 to 10.

Preferably, the atmosphere has an oxygen content level of 5% to 25% (by volume).

Preferably, Y is one of chlorine, bromine or acetoxy, and M is one of nickel, palladium and platinum.

Preferably, R⁹、R¹⁰、R¹¹Each independently selected from trimethylphenyl, dipropylphenyl, dipentylphenyl and diphenylmethylphenyl.

The method for preparing substituted aryl ketone by ketone arylation adopts a new catalytic system, a metal palladium complex in an N-heterocyclic carbene catalyst adopts a saturated N-heterocyclic carbene structure, unsaturated double bonds are reduced into saturated single bonds, the carbon-carbon bond length is increased, and the five-membered N-heterocyclic tension is favorably reduced, so that the coordination capacity of a ligand is increased, and the N-heterocyclic carbene ligand with lower rigidity can be better coordinated with metal atoms in the catalytic cycle process, so that the N-heterocyclic carbene ligand has better stability than unsaturated N-heterocyclic carbene.

The method has simple reaction operation conditions, can realize the reaction under the condition of oxygen-containing atmosphere by utilizing the catalytic system, greatly simplifies the operation steps, saves the equipment cost and is beneficial to the industrialized implementation.

The invention has high catalytic activity, can realize the yield of 99 percent at most by using 0.1 percent of mol of catalyst at least aiming at the ketone arylation reaction with more side reactions and complexity, and has obvious technical advancement.

Detailed Description

The present invention is described in detail below with reference to specific examples, but the present invention is not limited thereto in any way.