阅读说明：本技术 一种环状（烷基）（氨基）卡宾铬络合物催化还原硝基化合物制备胺的方法 (Method for preparing amine by catalytic reduction of nitro compound by cyclic (alkyl) (amino) carbene chromium complex ) 是由 曾小明 罗美明 赵立新 于 2020-12-28 设计创作，主要内容包括：本发明从相应的配体盐、碱和CrCl-3制备环状(烷基)(氨基)卡宾铬络合物用以催化频那醇硼烷在醚溶剂中将硝基化合物在温和条件下还原生成相应的胺。用此方法制备胺具有原料廉价易得、反应条件温和、操作简单、底物适用范围广、选择性高等优点。(The invention relates to corresponding ligand salts, bases and CrCl 3 Preparation of cyclic (alkyl) (amino) carbene chromium complexes to catalyze the reduction of the nitro compounds in pinacol borane in ether solvents under mild conditions to give the corresponding amines. The method for preparing the amine has the advantages of cheap and easily obtained raw materials, mild reaction conditions, simple operation, wide substrate application range, high selectivity and the like.)

1. A method for synthesizing amine by catalytic reduction of nitro compounds is characterized in that: reacting a nitro compound with pinacolborane in an ether solvent at a temperature and under the catalysis of a cyclic (alkyl) (amino) carbene chromium complex to form the corresponding amine, wherein the method has the following reaction general formula:

in the formula R¹Is hydrogen, methoxy, methylthio, trifluoromethyl, trifluoromethoxy, amino, vinyl, styryl, phenylethynyl, phenyl, amido, hydroxyethyl, pinacolato, oxazolyl, pyrazolyl, pyridyl, thienyl, thiazolyl, furyl, pyrrolyl, morphinyl, piperidinyl, fluoro, chloro, bromo, iodo; r²Hydrogen and methyl; r³Is C₁-C₂₀Alkyl, cycloalkyl, benzyl, picolyl; the carbene chromium complex has the following structure:

wherein Dipp is 2, 6-diisopropylphenyl; r is phenyl, 2,4, 6-trimethylphenyl or 2, 6-diisopropylphenyl.

2. The method of claim 1, wherein the cyclic (alkyl) (amino) carbene chromium complex is prepared from the corresponding ligand salt, base, and CrCl₃Prepared in an ether solvent.

3. The method of claim 1, wherein the cyclic (alkyl) (amino) carbene chromium complex is present in an amount of 1 to 30 mol%.

4. The process according to claim 1, wherein the solvent used is diethyl ether, dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, or a mixture thereof.

5. The process of claim 1, wherein the reaction temperature is from 20 ℃ to 80 ℃.

6. The process according to claim 1, wherein the reaction time is from 2 to 24 hours.

7. The process according to claim 1, characterized in that the amount of pinacol borane used is 4 to 10 equivalents.

8. The method of claim 1, wherein the magnesium is present in an amount of 0.1 to 2 equivalents.

Technical Field

The invention relates to a method for preparing amine by reducing nitro compound, which takes a cyclic (alkyl) (amino) carbene chromium complex as a catalyst, and pinacol borane reacts with the nitro compound to obtain the corresponding amine.

Background

The amine is an important compound and has wide application in the fields of pesticides, medicines, materials and the like. Therefore, the development of a process for preparing amines is of great significance for the development of new pharmaceuticals and agrochemicals. At present, many popular amino-containing structural units of medicines, agrochemicals, etc. are on the market, such as the following structural formula: paracetamol, benzocaine, phenacetin and salicylic acid p (anti-tubercular prescription) and the like.

Industrially, a simple, efficient method for synthesizing amines is the direct hydrogenation reduction of nitro compounds. The method uses hydrogen to realize the reduction of nitro compounds under the action of a catalyst, for example, rhodium [ Applied Catalysis A: general2015,489(489): 280-; CN 109796346, platinum (CN 109759109), cobalt [ Catal Sci Technol 2019,9(1): 157-. The catalytic hydrogenation efficiency is high, but hydrogen is flammable gas, so that the danger is high, and the requirement on equipment is high; the selectivity to functional groups such as olefins is poor.

Nitro compounds can also be reduced to amines by hydrogen transfer. Compared with the traditional high-temperature high-pressure catalytic hydrogenation, the hydrogen transfer reduction reaction utilizes a hydrogen transfer reagent as a hydrogen source, and has the advantages of mild reaction conditions, simple and safe operation, low requirements on experimental equipment and the like [ Chem Rev, 2015,115(13): 6621-6686 ]. For example, amine borane is used as a hydrogen transfer reagent, zero-valent iron nanoparticles are used as catalysts [ Chem Commun,2012,48(64): 7982-. Molybdenum sulfide is used as a catalyst, formic acid or formate is used as a hydrogen source, and a reduced nitro compound is amine (CN 105601458A). Ni-Co loaded by titanium dioxide is used as a catalyst, hydrazine hydrate is used as a hydrogen source, and the p-nitrobenzamide is reduced to the p-aminobenzamide (CN 108456147A).

Disclosure of Invention

Compared to amine boranes, the commercialized pinacol borane is inexpensive and has been used in various other reduction reactions [ j.am.chem.soc.2015,137, 12808-12814; ACS Catal.2015,5, 4219-; nature Catalysis 2020, 3,154-162 ]. The invention provides a method for preparing amine by using carbene chromium complex as a catalyst and pinacol borane as a hydrogen transfer reagent and reducing a nitro compound through hydrogen transfer, namely, using cyclic (alkyl) (amino) carbene chromium complex to catalyze pinacol borane to reduce the nitro compound to obtain corresponding amine. The method has the advantages of high yield, wide substrate application range, mild reaction conditions, high selectivity and simple operation.

The carbene chromium complex of the invention has the following structure:

wherein Dipp is 2, 6-diisopropylphenyl; the carbene chromium complexes were prepared from the corresponding ligand salts: adding 0.5mmol ligand salt into a reaction tube, under the protection of nitrogen, adding an ether solvent and 0.5eq K [ N (SiMe) at-78 DEG C₃)₂]Stirred at room temperature for 0.5 h. Under the protection of nitrogen, 1eq CrCl was added at-78 deg.C₃And stirring at room temperature for 12h, draining the solvent, washing with n-hexane, and extracting with dichloromethane to obtain the corresponding carbene chromium complex.

The method for preparing amine has the following reaction general formula:

in the formula R¹Is hydrogen, methoxy, methylthio, trifluoromethyl, trifluoromethoxy, amino, vinyl, styryl, phenylethynyl, phenyl, amido, benzoylamino,Hydroxyethyl, pinacolato boryl, oxazolyl, pyrazolyl, pyridyl, thienyl, thiazolyl, furyl, pyrrolyl, morphinyl, piperidinyl, fluoro, chloro, bromo, iodo; r²Hydrogen and methyl; r³Is C₁-C₂₀Alkyl, cycloalkyl, benzyl, picolyl.

The solvent used according to the invention is an ethereal solvent selected from the group consisting of diethyl ether, dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, or mixtures thereof.

The reaction temperature according to the invention is between 20 ℃ and 80 ℃.

The reaction time according to the invention is between 2 and 24 hours.

The amount of catalyst used is from 1 to 30 mol%, based on the invention.

The amount of magnesium used is 0.1 to 2 equivalents, based on the invention.

The pinacol borane according to the invention is used in an amount of 4 to 10 equivalents.

Detailed Description

The specific process for preparing the amine according to the invention is described below:

in a reaction tube, a nitro compound, 0.01-0.3 times of molar amount of carbene chromium complex, 4-10 times of molar amount of pinacol borane, 0.1-2 times of molar amount of magnesium and 2 ml of solvent are added. The reaction system is placed at the temperature of 20-80 ℃ and stirred for 2-24 h. After the reaction, silica gel column chromatography is carried out, or after the catalyst and magnesium are filtered out, ethyl ether hydrochloride is added to separate out ammonium salt, and then filtration is carried out, thus obtaining the corresponding amine or amine salt compound.

Examples

The following examples are intended to illustrate the invention in detail, but are not intended to limit the invention.

Example (as shown in table one).

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