JP2022040918A - α-METHYLENE GROUP CONVERSION COMPOUND OF ALKYL AMINE HAVING METHYLENE GROUP AT α-POSITION, PRODUCTION METHOD OF AMIDES, AND PRODUCTION METHOD OF PROPARGYLAMINES - Google Patents

Abstract

To provide a compound that can solve problems of conventional catalysts using Au nano particles, exhibits high catalyst activity not only in production of amides by α-methylene group selective oxygenation reaction of an alkyl amine having a methylene group at an α-position but also in production of propargylamines by α-methylene group selective alkynyl reaction of the alkyl amine, and efficiently produce amides or propargylamines, and to provide a production method of amides using the compound, and a production method of propargylamines using the compound.SOLUTION: There is provided an α-methylene group conversion compound of an alkyl amine having a methylene group at an α-position, in the compound, Au nano particles are carried to a ZnO and/or Co3O4 carrier. Under presence of the compound, an amide is produced by α-methylene group selective oxygenation reaction of an alkyl amine having a methylene group at an α-position. Under presence of the compound, a propargylamine is produced by α-methylene group selective alkynyl reaction of an alkyl amine having a methylene group at an α-position.SELECTED DRAWING: None

Description

There is an application for exception of loss of novelty

The present invention relates to a method for producing amides or propargylamines by an α-methylene group selective oxygenation reaction or an α-methylene group selective alkynylation reaction using an alkylamine having a methylene group at the α-position as a raw material. The present invention also relates to an α-methylene group conversion compound of an alkylamine having a methylene group at the α-position, which exhibits excellent catalytic action in the α-methylene group selective oxygenation reaction and the α-methylene group selective alkynylation reaction. ..

Alkylamine is a universal and easily available compound, and since alkylamine and its derivatives are contained in various useful compounds from basic compound raw materials to pharmaceuticals and natural products, alkylamines having a methylene group at the α-position are used. The method of oxidatively functionalizing the α-methylene group position-selectively without changing the basic skeleton is effective for improving the production efficiency of existing useful compounds and for producing new useful compounds. Regarding the selective functionalization of the α-methylene group of an alkylamine having a methylene group at the α-position, if an aryl group such as a benzene ring is further attached to the carbon of the methylene group at the α-position, the reactivity becomes higher. Although many have been reported, when the aryl group is not attached, the α-methylene group of the alkylamine having a methylene group at the α-position is relatively poor in reactivity, and it is difficult to selectively functionalize the α-methylene group. Met. Therefore, an α-methylene group selective functionalization method applicable to such general alkylamines has been desired.

Amides are widely used as intermediates for organic synthesis, raw materials for engineering plastics, enhancers for fragrances, coloring pigments for inks, anti-adhesive agents, detergents, circulating agents, etc., and are extremely important compounds in the industry.

Conventionally, amides have been used for nucleophilic addition / desorption of carboxylic acid derivatives (acidides, anhydrides, esters, etc.) with amines, condensation of amines and carboxylic acids using condensing agents such as carbodiimides, or hydration of nitriles. Although they have been produced by Beckmann rearrangement and the like, these methods have problems such as the use of toxic reagents in a chemical amount and the generation of a large amount of waste. Therefore, various studies and proposals have been made on a method for producing an amide as an alternative to such a method for producing an amide.

Non-Patent Document 1 describes alkyl through the following steps in the presence of a compound in which gold (Au) nanoparticles (average particle size of Au nanoparticles of 4.9 nm) are supported on alumina (Al ₂ O ₃ ). Methods for producing amides from amines have been proposed.

This method utilizes the specific oxygenation-catalyzing action of an alkylamine on an α-methylene group of a compound supporting Au nanoparticles on alumina, and oxygen is generated by the progress of the reaction as follows. It is presumed that introduced (oxygenated) amides are produced. First, Au abstracts (oxidizes) hydrogen from the α-methylene group of the alkylamine and becomes an Au hydride species. Next, water is added to the obtained compound (hydration). The Au hydride species returns to Au by oxygen, and the Au abstracts hydrogen from the intermediate hemiacetal produced by the hydration to form an amide. In addition, oxygen reacts with the regenerated Au hydride species to produce water. Since water is the only theoretical by-product in this reaction, it is expected to be put into practical use as an environmentally friendly method.

On the other hand, propargylamines are important compounds as useful compounds such as pharmaceuticals and pesticides and their synthetic intermediates. Conventionally, as a method for producing propargyl amines, a method of aminating a propargyl chloride compound and a method of nucleophilic coupling of an alkyne to an imine formed by reacting an aldehyde and an amine are generally known. With these methods, it is difficult to produce an alkynylated form of the α-methylene group of the cyclic amine, and the propargylamine that can be produced is limited.

Angew. Chem. Int. Ed. 2016, 55, 7212-7217 Xiongjie Jin et al. "Supported gold nanoparticles for efficient α-oxygenation of secondary and tertiary amines to amides"

Au nanoparticles used as a catalytically active ingredient in Non-Patent Document 1 have poor stability and have a problem of a decrease in activity due to sintering. In addition, there is also a problem that the Au hydride species produced as a result of Au oxidizing an alkylamine has a slow rate of being oxidized by oxygen and returning to Au and a rate of adsorbing intermediates to Au, and the overall reaction rate is low. ..
Further, Non-Patent Document 1 describes only the production of an amide by α-methylene group selective oxygenation of an alkylamine, and is applicable to the production of propargylamine by α-methylene group selective alkynylization. No suggestion has been made.

The present invention solves the problem of a catalyst using conventional Au nanoparticles, and not only produces amides by α-methylene group selective oxygenation reaction of an alkylamine having a methylene group at the α-position, but also at the α-position. A specific carrier capable of efficiently producing amides or propargylamines, which also exhibits high catalytic activity in the production of propargylamines by α-methylene group selective alkynylation reaction of alkylamines having a methylene group. It is an object of the present invention to provide a compound supporting Au nanoparticles, a method for producing an amide using this compound, and a method for producing propargylamines.

As a result of repeated studies to solve the above problems, the present inventor has improved the stability of Au nanoparticles by supporting Au nanoparticles on a ZnO and / or _{Co3 O4} carrier, and Au hydride. It has been found that the above-mentioned problems can be solved by the effect of improving the oxidation rate of seeds. Further, by using a compound in which Au nanoparticles and Pd nanoparticles are supported on a ZnO and / or Co ₃ O ₄ carrier, a selective oxygenation reaction of an α-methylene group of an alkylamine having a methylene group at the α-position is further carried out. It was found that the reaction activity of methylene can be enhanced.
That is, the gist of the present invention is as follows.

[1] An α-methylene group conversion compound of an alkylamine having a methylene group at the α-position, which comprises Au nanoparticles supported on a ZnO and / or Co ₃ O ₄ carrier.

[2] The compound for α-methylene group conversion of an alkylamine having a methylene group at the α-position according to [1], wherein the conversion is oxygenation.

[3] The compound for α-methylene group conversion of an alkylamine having a methylene group at the α-position according to [1], wherein the conversion is alkynylation.

[4] The compound for converting an α-methylene group of an alkylamine having a methylene group at the α-position according to [2], which further supports Pd nanoparticles.

[5] An α-methylene group of an alkylamine having a methylene group at the α-position in the presence of a compound in which Au nanoparticles or Au nanoparticles and Pd nanoparticles are supported on a ZnO and / or Co _{3 O4} carrier. A method for producing amides, which produces amides by a selective oxygenation reaction.

[6] Propargylamine by a selective alkynylation reaction of the α-methylene group of an alkylamine having a methylene group at the α-position in the presence of a compound in which Au nanoparticles are carried _on a ZnO and / or _Co3O4 carrier. A method for producing propargylamines.

[7] The method for producing propargylamines according to [6], wherein the selective alkynylation reaction is carried out in the presence of the compound and a zinc salt.

According to the present invention, by supporting Au nanoparticles on a ZnO and / or Co ₃ O ₄ carrier, the problem of instability of conventional Au nanoparticles can be solved, and nanoparticles can be sintered even during repeated use. It can be prevented and the catalytic activity can be maintained high. Further, a compound obtained by supporting Au nanoparticles and Pd nanoparticles on a ZnO and / or Co ₃ O ₄ carrier can obtain high α-methylene group selective oxygenation activity.
In addition, the oxidation rate of Au hydride species by oxygen and the adsorption rate of intermediates to Au can be improved, the overall reaction rate can be increased, and the reaction efficiency can be significantly improved.
Moreover, the compound of the present invention not only produces amides by an α-methylene group selective oxygenation reaction of an alkylamine having a methylene group at the α-position, but also has an α-methylene group of an alkylamine having a methylene group at the α-position. Since high catalytic activity is exhibited in the production of propargylamines by selective alkynylation reaction, the present invention provides not only an efficient method for producing amides but also an efficient method for producing propargylamines. can do.

The best mode for carrying out the present invention will be described in detail below, but the description of the constituent elements described below is a representative example of the embodiment of the present invention, and the present invention is limited to these contents. It's not a thing. In addition, in this invention, "-" is used in the meaning which includes the numerical values described before and after it as the lower limit value and the upper limit value.

[A compound for converting an alkylamine having a methylene group at the α-position to an α-methylene group]
The compound for converting an α-methylene group of an alkylamine having a methylene group at the α-position of the present invention (hereinafter, may be referred to as “compound of the present invention”) is an Au nano on a ZnO and / or Co ₃ O ₄ carrier. It is a compound that carries particles. Examples of the compound include a compound in which Au nanoparticles are carried on a ZnO carrier (hereinafter, may be referred to as “Au / ZnO”), and a compound in which Au nanoparticles are carried on a Co ₃ O ₄ carrier (hereinafter, referred to as “Au / ZnO”). May be referred to as "Au / Co ₃ O ₄ "), a mixture of Au / ZnO and Au / Co ₃ O ₄ (hereinafter, may be referred to as "Au / ZnO + Au / Co ₃ O ₄ "), ZnO and Examples thereof include a compound in which Au nanoparticles are carried on a carrier containing Co ₃ O ₄ (hereinafter, may be referred to as “Au / (ZnO + Co ₃ O ₄ )”).
Further, in the α-methylene group selective oxygenation reaction of an alkylamine having a methylene group at the α position, the compound of the present invention preferably carries Pd nanoparticles in addition to Au nanoparticles.

_In the present invention, Au nanoparticles or Pd nanoparticles (hereinafter referred to as “metal nanoparticles”) are referred to as Au nanoparticles or Pd nanoparticles (hereinafter referred to as “metal nanoparticles”” by using ZnO and / or _Co3O4 as a carrier for supporting Au nanoparticles or Au nanoparticles and Pd nanoparticles. ) Can be strongly supported on the carrier, preventing aggregation of the carried metal nanoparticles during the reaction and maintaining the size of the metal nanoparticles, that is, maintaining a large specific surface area and maintaining catalytic activity. Can be maintained.
Further, by using ZnO and / or Co ₃ O ₄ as a carrier, the metal nanoparticles become more cationic and the reaction rate can be increased. In addition, when _D2O , which is a stable isotope, is used as a solvent in the α-methylene group selective oxygenation reaction _, the kinetic isotope effect is not observed when the conventional _Al2O3 carrier is used. In particular, in the Co ₃ O ₄ carrier, a decrease in the reaction rate is confirmed due to the kinetic isotope effect. Therefore, in the conventional Al ₂ O ₃ carrier, the oxidation step of Au hydride is the rate-determining step. It can be seen that in the Co ₃ O ₄ carrier, the deprotoning step from the intermediate hemiaminoal is the rate-determining step. That is, the Co ₃ O ₄ carrier improves the oxidation rate of Au hydride species, and the deprotonation step from the intermediate hemiaminal changes to the rate-determining step. Therefore, by using the Co ₃ O ₄ carrier, oxygen can be activated and the oxidation of Au hydride species can be promoted.

The average particle size of the metal nanoparticles supported on the ZnO and / or Co ₃ O ₄ carrier is preferably 1 to 10 nm, particularly preferably 2 to 7 nm. When the average particle size is 10 nm or less, the surface area of the nanoparticles can be increased to increase the catalytic activity points, and the catalytic activity can be enhanced to obtain a large reaction rate. If the average particle size is 1 nm or more, it can be easily prepared.
Here, the average particle size of the metal nanoparticles is an average value of the particle size of each particle measured by a transmission electron microscope (hereinafter referred to as TEM).

As described above, when the compound of the present invention is used for the α-methylene group selective oxygenation reaction of an alkylamine having a methylene group at the α position, Au nanoparticles are added to the ZnO and / or Co ₃ O ₄ carrier. In addition, it is preferable that Pd nanoparticles are further supported. In this case, amides can be efficiently produced by the α-methylene group selective oxygenation reaction of the raw material alkylamine at a reaction rate significantly superior to that of the conventional Au nanoparticles-supporting compound. The Au / Pd weight ratio is preferably 9/1 or more, and more preferably 9/1 to 20/1. By supporting Au nanoparticles and Pd nanoparticles, the adsorption force of the intermediate to the surface becomes larger than that of Au alone, and the overall reaction rate increases due to the improvement of the adsorption rate, but the amount of Pd becomes excessive. If it is too large, the original catalytic activity of Au may be impaired. Considering the number of Au active sites and control of side reactions, the Au / Pd weight ratio is particularly preferably in the range of 13/1 to 19/1.

Further, the carrier supporting the metal nanoparticles according to the present invention may further contain an inorganic carrier other than _ZnO and _Co3O4 . In this case, as the other inorganic carrier, any inorganic carrier capable of supporting catalytically active metal nanoparticles can be used, and for example, carbonaceous carriers such as activated carbon, graphite, and mesoporous-carbon; SiO ₂ . , Al ₂ O ₃ , MgO, TiO ₂ , ZrO ₂ , CeO ₂ , CaO, Cs ₂ O, Sc ₂ O ₃ , Y ₂ O ₃ , La ₂ O ₃ , Sm ₂ O ₃ , Yb ₂ O ₃ , zeolite, etc. Metal oxides; mesoporous materials (eg, mesoporous-alumina, mesoporous-silica, etc.); composite oxides such as SiO ₂ -Al ₂ O ₃ , MgO-SiO ₂ , SiO ₂ -TiO ₂ ; carbides such as SiC; Nitridees such as Si ₃ N ₄ ; layered compounds such as montmorillonite, kaolinite, hydrotalcite, hydroxyapatite and the like can be mentioned.
Only one of these other inorganic carriers may be used, or two or more of them may be mixed and used.
However, from the viewpoint of effectively obtaining the effect of the present invention by using ZnO and / or Co ₃ O ₄ carrier, when Zn O and / or other inorganic carriers other than Co ₃ O ₄ are used, Zn O and / in the total amount of the carrier are used. Alternatively, the ratio of Co ₃ O ₄ is preferably 90 to 100% by weight.

The amount of Au nanoparticles or Au nanoparticles and Pd nanoparticles supported on the ZnO and / or Co ₃ O ₄ carrier is the Zen O and / or Co ₃ O ₄ carrier (if other inorganic carriers are included, other inorganic carriers). The supported amount in terms of Au is preferably 0.01 to 10% by weight, particularly preferably 0.1 to 2.5% by weight, based on the total carrier weight including the above. When the amount of Au nanoparticles or Au nanoparticles and Pd nanoparticles supported is at least the above lower limit, the amount of effective catalytically active component in the compound of the present invention can be increased to obtain high catalytic activity. When the supported amount is not more than the above upper limit, the stabilizing effect by supporting Au nanoparticles or Au nanoparticles and Pd nanoparticles on the ZnO and / or Co ₃ O ₄ carrier can be effectively obtained.

The compound of the present invention, which comprises supporting Au nanoparticles on a ZnO and / or Co ₃ O ₄ carrier, can be produced, for example, by the following step I.
Step I: Disperse ZnO and / or _Co3O4 in an aqueous solution of a water _- soluble Au reagent dissolved in pure water, and adjust the pH to basic by adding ammonia water or urea to obtain Au. To carry. Then, filtration / washing / drying, that is, for example, the liquid is filtered, the obtained powder is washed with pure water, and then dried under reduced pressure at room temperature. A compound in which Au nanoparticles are supported on a ZnO and / or Co ₃ O ₄ carrier by using a method of calcining dried powder at a high temperature in air or a method of reducing it with sodium borohydride or hydrogen gas. To get.

Compounds in which Au nanoparticles and Pd nanoparticles are supported on a ZnO and / or Co ₃ O ₄ carrier can be produced, for example, in the following steps II-1 and 2.
Step II-1: A water-soluble palladium reagent is dissolved in pure water _, and ZnO and / or _Co3O4 is dispersed therein. Then, the pH is adjusted to be basic using a basic aqueous solution, and palladium is supported _on the ZnO and / or _Co3O4 carrier by a precipitation precipitation method in which the mixture is stirred for a long time.
Step II-2: A method in which the powder obtained in Step II-1 is filtered, washed, and dried, and then the water-soluble Au reagent is redispersed in an aqueous solution dissolved in pure water, and ammonia water or urea is added. The pH is adjusted to be basic by such means as carrying Au. After filtration, washing and drying, the compound is obtained by carrying Au nanoparticles and Pd nanoparticles _on a ZnO and / or Co3O4 carrier by high _- temperature firing in air.

According to the compound of the present invention, as described later, the α-methylene group selective oxygenation reaction of the raw material alkylamine has a reaction rate significantly superior to that of the conventional compound in which Au nanoparticles are supported on Al ₂ O ₃ . Therefore, amides can be efficiently produced.
Further, according to the compound of the present invention, as described later, propargylamines useful as various agents or intermediates thereof by the selective alkynylation reaction of the α-methylene group of the alkylamine from various raw material alkylamines. Can be synthesized directly.

[Method for producing amides]
The method for producing amides of the present invention selects an α-methylene group of an alkylamine having a methylene group at the α-position (hereinafter, may be referred to as “raw material alkylamine”) in the presence of the above-mentioned compound of the present invention. It is characterized in that amides are produced by a target oxygenation reaction.

The raw material alkylamine for the method for producing amides of the present invention is not particularly limited, and the alkyl group or amino group of the alkylamine is substituted with a hydroxy group, a carbonyl group, an alkoxy group, an ester group, a cyano group, a chloro group or the like. Even in this case, the α-methylene group selective oxygenation reaction in the production of the amides of the present invention proceeds satisfactorily.

Examples of the raw material alkylamine include cyclic secondary amines such as piperidine, pyrrolidine, azepan, morpholin, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, dibenzylamine and dioctyl. Examples thereof include chain secondary amines such as amines, N-substituted cyclic amines such as N-substituted pyrrolidine and N-substituted piperidine, and chain tertiary amines such as dimethyloctylamine and dioctylmethylamine.

Of these, as the raw material alkylamine, it is preferable to use N-substituted cyclic amines such as N-substituted pyrrolidine and N-substituted piperidine from the viewpoint of reactivity. Examples of the N-substituted group of these N-substituted cyclic amines include an alkyl group having 1 or more carbon atoms such as a methyl group, an ethyl group, a methoxy group, an ethoxy group, a phenyl group and a benzyl group, an alkoxy group and an aryl group. Can be mentioned.

Although it is possible to use two or more kinds of these raw material alkylamines, usually only one kind of raw material alkylamine is used.

In the method for producing amides of the present invention, an α-methylene group selective oxygenation reaction is carried out using oxygen as an oxidizing agent.
The oxygen concentration in the gas phase of the reaction system is arbitrarily selected in the range of 1 to 100% by volume, but from the viewpoint of reactivity, it is preferably 3 to 100% by volume, particularly preferably 5 to 100% by volume.

The amount of the compound of the present invention used varies depending on the reaction type, the amount of Au nanoparticles or Au nanoparticles and Pd nanoparticles supported on the compound, other reaction conditions, etc., but for example, in the case of a batch type, 1 mol of the raw material alkylamine is used. On the other hand, it is preferable to use about 1 to 20 g.

The reaction temperature of the α-methylene group selective oxygenation reaction is preferably 0 to 100 ° C, particularly preferably 20 to 80 ° C. When the reaction temperature is at least the above lower limit, the reaction proceeds rapidly, and when it is at least the above upper limit, deterioration of the compound of the present invention due to sintering can be suppressed.

The reaction time varies depending on the reaction conditions such as the catalytic activity of the raw material alkylamine and the compound of the present invention used, the reaction temperature and the oxygen concentration, but is usually about 1 to 24 hours.

In the α-methylene group selective oxygenation reaction of the raw material alkylamine, it is preferable to allow water to be present in the reaction system for the addition reaction of water after the oxidation reaction. In this case, the amount of water may be not less than the reaction equivalent, but for example, it is preferable to use about 0.1 to 1 L with respect to 1 mol of the raw material alkylamine. Further, an organic solvent may be used.

According to the method for producing amides of the present invention, the α-methylene group is converted to a carbonyl group by the selective oxygenation reaction of the α-methylene group of the raw material alkylamine, and the corresponding amides are efficiently produced at a high reaction rate. Can be manufactured as a target.

[Manufacturing method of propargyl amines]
The method for producing propargylamines of the present invention is a propargylamine by an α-methylene group selective alkynylation reaction of an alkylamine having a methylene group at the α-position in the presence of the compound of the present invention, usually in the presence of a reaction solvent. It is characterized by producing a kind.

Examples of the raw material alkylamine in the method for producing propargylamines of the present invention include tertiary amines exemplified as the raw material alkylamine in the above-mentioned method for producing amides of the present invention, and preferred ones are also the same.

The substrate alkyne may be a compound having a terminal alkynyl group and is not particularly limited, but may be phenylacetylene, ethynylthiophene, propargyl alcohol, fluorogroup, chloro group, bromo group, alkoxy group, cyano group, nitro group, etc. Examples thereof include compounds such as aryl acetylene having an alkyl group and alkyl acetylene such as 1-octyne.
Two or more kinds of these alkynes may be used, but usually only one kind is used.
The amount of alkyne used may be not less than the reaction equivalent, but is preferably 1 to 2 equivalents with respect to the raw material alkylamine, for example.

The amount of the compound of the present invention used varies depending on the reaction type, the amount of Au nanoparticles supported, other reaction conditions, and the like, but for example, in the case of a batch type, it is preferable to use about 10 to 200 g per 1 mol of the raw material alkylamine.

As the reaction solvent in the α-methylene group selective alkynylation reaction, an aromatic solvent such as benzotrifluoride, toluene, mesitylene and chlorobenzene, an ether solvent such as 1,4-dioxane, an ester solvent such as butyl acetate and the like are used. Can be done. One of these solvents may be used alone, or two or more of them may be mixed and used.
Of these solvents, aromatic solvents such as benzotrifluoride, toluene, mesitylene, and chlorobenzene are preferable from the viewpoint of solubility of the raw material alkylamine.
Further, aromatic hydrocarbon solvents such as toluene and mesitylene can raise the reaction temperature at a high boiling point, which is effective in improving the yield.

It is preferable to use about 0.1 to 5 L of these solvents with respect to 1 mol of the raw material alkylamine from the viewpoint of operability and economy.

Further, the α-methylene group selective alkynylation reaction is preferably carried out in the presence of oxygen for the oxidation of Au hydride species, and the oxygen concentration in the gas phase of the reaction system is 1 to 100% by volume, particularly 5 to 100. The volume is preferably%.

Further, in the α-methylene group selective alkynylation reaction according to the present invention, hydrogen of the α-methylene group of the alkylamine is selectively extracted by Au by coexisting a zinc salt together with the compound of the present invention in the reaction system. Propargylamines can be produced with high selectivity and high yield by the action of nucleophilic addition of alkyne by zinc salt (oxidation).

As the zinc salt, for example, one kind or two or more kinds of zinc halide such as zinc bromide, zinc chloride and zinc fluoride, and zinc trifluoromethanesulfonate can be used.

It is preferable to use about 0.01 to 0.2 mol of these zinc salts with respect to 1 mol of the raw material alkylamine. When the amount of zinc salt is at least the above lower limit, the effect of improving the yield by using the zinc salt can be effectively obtained. On the other hand, if the amount of zinc salt is not more than the above upper limit, the product recovery step can be easily performed.

The reaction temperature of the α-methylene group selective alkynylation reaction is preferably 60 to 160 ° C, particularly preferably 90 to 110 ° C. If the reaction temperature is at least the above lower limit, the reaction proceeds rapidly, and if it is at least the above upper limit, side reactions such as alkyne dimerization can be suppressed.

The reaction time varies depending on the reaction conditions such as the catalytic activity of the raw material alkylamine and the compound of the present invention used, the reaction temperature, the presence or absence of a zinc salt, and the oxygen concentration, but is usually about 1 to 24 hours.

According to the method for producing propargylamines of the present invention, the corresponding propargylamines having an alkynyl group introduced at the α-methylene position can be produced at a high reaction rate by selective alkynylation of the α-methylene group of the raw material alkylamine. It can be manufactured efficiently.

Hereinafter, the present invention will be described in more detail with reference to production examples and examples.
Further, in the following, a compound in which Au nanoparticles or Au nanoparticles and Pd nanoparticles are carried on a carrier may be simply referred to as a “carrier”.

The yield was calculated from the amount of substance of the compound produced by the internal standard method in gas chromatography (hereinafter, may be simply referred to as "product") and the ratio of the raw material amine to the amount of substance.
Yield (%) = (Amount of substance of product) x 100 / (Amount of substance of raw material amine)
The catalyst rotation frequency was calculated from the amount of substance of the product and the reaction time with respect to the amount of substance of Au contained in the carrier used.
Catalyst rotation frequency (h ^-1 ) = {(amount of substance of product) / (amount of substance of Au in carrier)} / (reaction time)

[Manufacturing of carrier]
<Production Example 1: Production of carrier A>
By the following method, a carrier A was produced in which Au nanoparticles (average particle size = 3.15 nm, standard deviation = 1.03 nm) were supported on a ZnO carrier by 0.8% by weight as the amount of Au supported on the carrier.
1 g of ZnO was added to an aqueous solution of 25.7 mg of HAuCl _{4.4H 2O} in 100 mL of pure water, and the mixture was stirred for 15 minutes, and then 0.3 g of urea was added. After stirring at 80 ° C. for 20 hours, washing with pure water, filtration, suction drying, and firing at 300 ° C. in air for 2 hours may be referred to as carrier A (hereinafter, “Au / ZnO”). ) Was manufactured.

<Production Example 2: Production of carrier B>
Au nanoparticles (average particle size = 2.62 nm, standard deviation = 0.94 nm) were added to the Co ₃ O ₄ carrier in the same manner as in Production Example 1 except that Co ₃ O ₄ was used instead of Zn O as the carrier. , A carrier B (hereinafter, may be referred to as “Au / Co ₃ O ₄ ”) supported by 0.8% by weight as the amount of Au supported on the carrier was produced.

<Production Example 3: Production of carrier C>
A carrier C in which Au nanoparticles and Pd nanoparticles (Au / Pd weight ratio = 13/1) were supported on a Co ₃ O ₄ carrier by 0.8% by weight as the amount of Au supported on the carrier was produced by the following method.
Co ₃ O ₄ 3 g, PdCl ₂
4.6 mg and 7.5 mg of KCl were added to an aqueous solution of 150 mL of pure water, and the mixture was stirred for 15 minutes, the pH was adjusted to 10 with a 1 mol / L NaOH aqueous solution, and the mixture was stirred for 20 hours. After filtering, washing and drying the precipitated precipitate, 1 g of the obtained powder was added to an aqueous solution of 25.7 mg of HAuCl _{4.4H 2} O in 100 mL of pure water, and the mixture was stirred for 15 minutes. .. Then, 0.3 g of urea was added, and the mixture was stirred at 80 ° C. for 20 hours, washed with pure water, filtered, and suction-dried, and calcined in air at 300 ° C. for 2 hours. -Pd / Co ₃ O ₄ "may be described.) Was manufactured.

<Production Example 4: Production of carrier a>
Au nanoparticles (average particle size 2.6 nm, standard deviation 0.69 nm) were added to the Al ₂ O ₃ carrier in the same manner as in Production Example 1 except that Al ₂ O ₃ was used instead of ZnO as the carrier. A carrier a (hereinafter, may be referred to as “Au / Al ₂ O ₃ ”) supported in an amount of 1% by weight based on Au was produced.

<Production Example 5: Production of carrier b>
A carrier b in which Au nanoparticles were supported on the Al ₂ O ₃ carrier in an amount of 1% by weight as the amount of Au supported on the carrier, in the same manner as in Production Example 1 except that TiO ₂ was used instead of Al ₂ O ₃ as the carrier. (Hereinafter, it may be referred to as "Au / TiO ₂ ".) Was manufactured.

[Manufacturing of amide]
<Example 1>
Carrier A (5 mg), N-methylpyrrolidine (1 mmol), H ₂ O (0.4 mL) was placed in a 20 mL volume test tube, O ₂ was allowed to flow into the test tube for 1 minute, and then the lid was closed (O ₂ ). When the reaction was carried out at 40 ° C. for 21 hours at a concentration of 100% by volume), the α-methylene group oxygenation reaction proceeded selectively, and the target N-methyl-2-pyrrolidone was obtained in a yield of 60% in the following reaction. Obtained. When the Au nanoparticle size of the carrier A after use was measured with a transmission electron microscope, the average particle size was 2.63 nm.
The catalyst rotation frequency (TOF) per Au corresponding to the overall reaction rate was 114h ^-1 .

<Example 2>
When the reaction was carried out under the same conditions as in Example 1 using the carrier B instead of the carrier A, N-methylpyrrolidone was obtained in a yield of 79%. When the Au nanoparticle size of the carrier B after use was measured with a transmission electron microscope, the average particle size was 2.84 nm.
The catalyst rotation frequency (TOF) per Au corresponding to the overall reaction rate was 150 h ^-1 .

<Example 3>
When the reaction was carried out under the same conditions as in Example 1 using the carrier C instead of the carrier A except that the reaction time was set to 3 hours, N-methylpyrrolidone was obtained in a yield of 80%. ..
The catalyst rotation frequency (TOF) per Au corresponding to the overall reaction rate was 1333h ^-1 .

<Comparative Example 1>
When the reaction was carried out under the same conditions as in Example 1 using the carrier a instead of the carrier A, N-methylpyrrolidone was obtained in a yield of 38%. When the Au nanoparticle size of the carrier a after use was measured with a transmission electron microscope, the average particle size was 9.9 nm.
The catalyst rotation frequency (TOF) per Au corresponding to the overall reaction rate was 72h ^-1 .

<Comparative Example 2>
When the reaction was carried out under the same conditions as in Example 1 using the carrier b instead of the carrier A, N-methylpyrrolidone was obtained in a yield of 5%.
The catalyst rotation frequency (TOF) per Au corresponding to the overall reaction rate was 9.5 h ^-1 .

The results of Examples 1 to 3 and Comparative Examples 1 and 2 are summarized in Table 1 below.

From the results of Examples 1 to 3 and Comparative Examples 1 and 2, according to the compound of the present invention, the yield and reaction rate of the α-methylene group selective oxygenation reaction of the alkylamine were significantly improved and supported. It can be seen that the stability of the body is also improved.

[Manufacturing of Propargyl Amine]
<Example 4>
20 mL of carrier A, N-methylpiperidine (0.5 mmol), phenylacetylene (0.5 mmol), zinc bromide (0.05 mmol), and benzotrifluoride (2 mL) with Au carried in an amount of 1.5% by weight. When placed in a test tube having a volume, O ₂ was allowed to flow into the test tube for 1 minute, the lid was closed (O ₂ concentration 100% by volume), and the reaction was carried out at 95 ° C. for 20 hours. It proceeded selectively, and the desired 1-methyl-2-phenylethynylpiperidine was obtained in a yield of 58% by the following reaction.
The catalyst rotation frequency (TOF) per Au corresponding to the overall reaction rate was 1.9 h ^-1 .

<Example 5>
When the reaction was carried out under the same conditions as in Example 4 using the carrier B instead of the carrier A, the desired 1-methyl-2-phenylethynylpiperidin was obtained in a yield of 72%.
The catalyst rotation frequency (TOF) per Au corresponding to the overall reaction rate was 2.4 h ^-1 .

<Comparative Example 3>
When the reaction was carried out under the same conditions as in Example 4 using the carrier a having an Au loading amount of 1.8% by weight instead of the carrier A, the desired 1-methyl-2-phenylethynylpiperidin was obtained. It was obtained with a yield of 44%.
The catalyst rotation frequency (TOF) per Au corresponding to the overall reaction rate was 1.5 h ^-1 .

<Comparative Example 4>
When the reaction was carried out under the same conditions as in Example 4 using a carrier b having an Au loading amount of 1.6% by weight instead of the carrier A, the yield of the desired 1-methyl-2-phenylethynylpiperidin was obtained. Obtained at 26%.
The catalyst rotation frequency (TOF) per Au corresponding to the overall reaction rate was 0.9h ^-1 .

The results of Examples 4 and 5 and Comparative Examples 3 and 4 are summarized in Table 2 below.

From the results of Examples 4 and 5 and Comparative Examples 3 and 4, according to the compound of the present invention, the yield and reaction rate of the α-methylene group-selective alkynylation reaction of the alkylamine were significantly improved, and the catalyst was also used. It can be seen that the stability of the carrier is also improved because the rotation frequency is improved.

Claims (7)

A compound for converting an α-methylene group of an alkylamine having a methylene group at the α-position, which comprises Au nanoparticles supported on a ZnO and / or Co ₃ O ₄ carrier. The compound for α-methylene group conversion of an alkylamine having a methylene group at the α-position according to claim 1, wherein the conversion is oxygenation. The compound for α-methylene group conversion of an alkylamine having a methylene group at the α-position according to claim 1, wherein the conversion is alkynylation. The compound for converting an α-methylene group of an alkylamine having a methylene group at the α-position according to claim 2, further comprising Pd nanoparticles. Selective oxygen of the α-methylene group of an alkylamine having a methylene group at the α position in the presence of a compound consisting of Au nanoparticles or Au nanoparticles and Pd nanoparticles supported on a ZnO and / or Co ₃ O ₄ carrier. A method for producing amides, which produces amides by a chemical reaction. Propargylamine is produced by a selective alkynylation reaction of the α-methylene group of an alkylamine having a methylene group at the α-position in the presence of a compound in which Au nanoparticles are carried _on a ZnO and / or _Co3O4 carrier. A method for producing propargylamines. The method for producing propargylamines according to claim 6, wherein the selective alkynylation reaction is carried out in the presence of the compound and a zinc salt.