JP2020132573A - Air oxidation method of benzylic position of organic compound and air oxidation catalyst - Google Patents

Abstract

To provide an air oxidation method by which a hydroxy group or oxo group can be introduced by efficient air oxidation of a benzylic position under relatively mild reaction conditions by using a metal complex as a catalyst without a joint use of an additive agent.SOLUTION: An air oxidation method is a method for carrying out air oxidation of a benzylic position of an organic compound having the benzylic position includes bringing the organic compound into contact with molecular oxygen in the presence of a catalyst that is a polynuclear metal complex including two or more kinds of metals.SELECTED DRAWING: None

Description

The present invention relates to an air oxidation method for the benzyl position of an organic compound and an air oxidation catalyst.

Various reactions for synthesizing alcohol compounds and carbonyl compounds by oxidizing the benzyl position of an organic compound having a benzyl position to introduce a hydroxyl group (-OH) or an oxo group (= O) include various electronic materials, pharmaceuticals, pesticides and the like. It is known as a basic reaction in the production of chemical products.
Air oxidation is known as a method for directly introducing a hydroxyl group or an oxo group into the benzyl position. Since the reaction of introducing a hydroxyl group or an oxo group by air oxidation generally requires high temperature and high pressure only with a catalyst, various additives are used in combination.

For example, as a method for producing benzyl alcohol and benzaldehyde, a method using titanium oxide as a catalyst and air-oxidizing the benzyl position of toluene in combination with various additives is known (Non-Patent Document 1).
However, in this method, it is necessary to carry out the reaction at a very low concentration in order to efficiently perform light irradiation, and there is a problem in productivity. In addition, since it is a method via hydroxyl radicals, not only the target compound but also a large number of by-products such as dimers and carbon dioxide are generated. Furthermore, the combined use of additives impairs the purity of the product. Therefore, a large amount of energy is required for the purification process of the product, and the labor and cost of the disposal process of the by-products of the purification process are also required.

In recent years, as a method for air-oxidizing various organic compounds under mild conditions, a method using an imide compound such as N-hydroxyphthalimide has been reported (Non-Patent Document 2, Patent Documents 1 and 2).
However, this method is industrially useful because the imide compound is consumed as a sacrificial agent and cannot be reused, the complexity of removing the decomposition product of the imide compound after the reaction, and the high price of the imide compound itself. I can't say.

Reactions using a metal complex such as a heteropolyacid or an iron complex as a catalyst are known (Non-Patent Documents 3, 4, 5). Non-Patent Document 3 reports a nitration reaction with nitric acid using a vanadium-substituted polyacid, and reports that an alcohol compound and a carbonyl compound are by-produced in the nitration reaction. Non-Patent Documents 4 to 5 report a halogenation reaction of a carbon-hydrogen bond using an iron complex, and it is reported that an alcohol compound and a carbonyl compound are by-produced in the halogenation reaction.

Japanese Unexamined Patent Publication No. 8-38909 Japanese Unexamined Patent Publication No. 9-327626

Bull. Chem. Soc. Jpn. 1982, Vol. 55, No. 3,666-671 Chem. Commun. 2001,1352-1353 Chem. Euro. J. 2004,10,6489-6494 J. Am. Chem. Soc. 2016,138,2484-2487 Angew. Chem. Int. Ed. 2016, 55, 7717-7722

However, Non-Patent Document 3 only shows that an alcohol compound or a carbonyl compound is produced as a by-product of nitric acid nitration, and cannot be said to be a direct oxidation reaction. Even in Non-Patent Document 4, some alcohol compounds and carbonyl compounds are formed as a by-product of halogenation, and it is necessary to handle the catalyst carefully in order to obtain a yield of about 50%, and the reaction temperature is −40 ° C. It requires processing at a low temperature. Also in Non-Patent Document 5, in order to promote the radicalization reaction of the carbon-hydrogen bond of the iron catalyst, a scandium compound of Lewis acid is added in addition to the iron catalyst to regulate the reaction system, and an acid as a proton source is also used. It is necessary to input more than the equivalent amount from the outside.

As described above, in the reaction using the conventional metal complex as a catalyst, the preparation of the metal complex itself as a catalyst is complicated, and it is necessary to precisely adjust the additive and the reaction temperature in order to rotate it as a catalytic cycle.
Furthermore, there is no example of an air oxidation reaction caused by the catalyst alone, and the presence of additives is required. Therefore, the catalyst and additives cannot be sufficiently removed from the product, which affects the post-process and product purity, resulting in energy saving. There are issues in terms of both quality and quality.

The present invention has been made in view of the above circumstances, in which a metal complex is used as a catalyst and the benzyl position is efficiently air-oxidized under relatively mild reaction conditions without the presence of additives to form a hydroxyl group. Alternatively, air is a metal complex capable of introducing a hydroxyl group or an oxo group by efficiently air-oxidizing the benzyl position under relatively mild reaction conditions without using an air oxidation method capable of introducing an oxo group and an additive. It is an object of the present invention to provide an oxidation catalyst.

The present invention has the following aspects.
[1] A method for air-oxidizing the benzyl position of an organic compound having a benzyl position.
A method for air oxidation, which comprises contacting the organic compound with molecular oxygen in the presence of a catalyst which is a polynuclear metal complex containing two or more kinds of metals.
[2] The air oxidation method according to claim 1, wherein the polynuclear metal complex contains a macrocycle ligand.
[3] The air oxidation method according to claim 1 or 2, wherein the two or more kinds of metals include cerium and a transition metal belonging to the fourth period of the periodic table.
[4] The air oxidation method according to any one of claims 1 to 3, wherein the polynuclear metal complex is represented by the following formula (i).

In the equation, X ¹ is a transition metal belonging to the 4th period of the periodic table.
X ² is a linking group
X ³ is a counter anion,
R ¹ and R ² are each independently a hydrogen atom, an alkyl group, an aryl group, a hydroxyl group or an amino group, or are bonded to each other to form a ring.
[5] The air oxidation method according to claim 3 or 4, wherein the transition metal belonging to the fourth period of the periodic table is at least one selected from the group consisting of manganese, copper and zinc.
[6] The air oxidation method according to any one of claims 1 to 5, wherein the amount of the catalyst used is 1 to 20% by mass with respect to the organic compound.
[7] A catalyst for air-oxidizing the benzyl position of an organic compound having a benzyl position.
An air oxidation catalyst, which is a polynuclear metal complex containing two or more kinds of metals.
[8] The air oxidation catalyst according to claim 7, wherein the polynuclear metal complex contains a macrocycle ligand.
[9] The air oxidation catalyst according to claim 7 or 8, wherein the two or more kinds of metals include cerium and a transition metal belonging to the fourth period of the periodic table.
[10] The air oxidation catalyst according to any one of claims 7 to 9, wherein the polynuclear metal complex is represented by the following formula (i).

In the formula, X ¹ is a transition metal belonging to the fourth period of the periodic table.
X ² is a linking group
X ³ is a counter anion,
R ¹ and R ² are each independently a hydrogen atom, an alkyl group, an aryl group, a hydroxyl group or an amino group, or are bonded to each other to form a ring.
[11] The air oxidation catalyst according to claim 9 or 10, wherein the transition metal belonging to the fourth period of the periodic table is at least one selected from the group consisting of manganese, copper and zinc.

According to the present invention, an air oxidation method capable of introducing a hydroxyl group or an oxo group by efficiently air-oxidizing the benzyl position under relatively mild reaction conditions without using a metal complex as a catalyst and coexisting with an additive. And, it is possible to provide an air oxidation catalyst which is a metal complex capable of efficiently air-oxidizing the benzyl position to introduce a hydroxyl group or an oxo group under relatively mild reaction conditions without coexisting an additive.

It is a figure which shows the structure of the catalyst obtained in the production example 1. FIG. It is a figure which shows the structure of the catalyst obtained in the production example 2.

Hereinafter, the present invention will be described in detail. The materials and the like exemplified in the following description are examples, and the present invention is not limited thereto, and the present invention can be appropriately modified without changing the gist thereof.
In the present specification, "~" indicating a numerical range is used to mean that numerical values described before and after the numerical range are included as a lower limit value and an upper limit value.
The "benzyl position" is the position of the carbon atom directly bonded to the carbon atom constituting the 6-membered aromatic ring.
"Air oxidation" is an oxidation reaction in which molecular oxygen acts as an oxidant.
"Transition metal" is a general term for elements of groups 3 to 12 of the periodic table.

The air oxidation method of the present invention is a method of air-oxidizing the benzyl position of an organic compound having a benzyl position. Hereinafter, the organic compound that oxidizes by air is also referred to as a "substrate".
In the air oxidation method of the present invention, the substrate is brought into contact with molecular oxygen in the presence of a catalyst (hereinafter, also referred to as "air oxidation catalyst") which is a polynuclear metal complex containing two or more kinds of metals. As a result, the benzyl position of the substrate is air-oxidized, and an organic compound having a structure in which a hydroxyl group or an oxo group is introduced into the benzyl position of the substrate is produced. For example, when the substrate has a C—H bond at the benzyl position, an alcohol compound having a C—OH bond at the benzyl position or a carbonyl compound having a C = O bond at the benzyl position when the benzyl position of the substrate is air-oxidized. Is generated.

<Air oxidation catalyst>
The air oxidation catalyst in the present invention is a polynuclear metal complex containing two or more kinds of metals. According to such an air oxidation catalyst, the benzyl position of the substrate can be efficiently air-oxidized to introduce a hydroxyl group or an oxo group under relatively mild reaction conditions without the presence of additives. Moreover, since the metal complex is not consumed (not decomposed) during air oxidation, it can be recovered and reused after the reaction.

It is preferable that the two or more kinds of metals contain at least cerium and a transition metal belonging to the fourth period of the periodic table (hereinafter, also referred to as "fourth period transition metal"). By including these metals, the stability of the complex is excellent and recovery and reuse are easy.
Cerium fluidly and stably drives trivalent and tetravalent oxidation numbers at temperatures below 100 ° C. It is considered that this property contributes to the above effect. It is considered that the fourth cycle transition metal makes the driving of trivalent and tetravalent in the oxidation number of cerium more stable, and contributes to the improvement of catalytic activity by changing the oxidation-reduction potential of cerium.

Examples of the fourth period transition metal include scandium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc and the like.
As the fourth period transition metal, at least one selected from the group consisting of manganese, copper and zinc is preferable in terms of stable driving of trivalent and tetravalent in the oxidation number of cerium and stability of the complex to be formed. , At least one selected from the group consisting of copper and zinc is more preferred.

As the ligand of the polynuclear metal complex, a macrocycle ligand is preferable in that two or more kinds of metals can be stably and effectively arranged at an appropriate distance.

A preferred embodiment of the polynuclear metal complex is a macrocycle ligand, a plurality (for example, three) fourth period transition metals arranged inside the macrocycle ligand, and the plurality of fourth period transition metals. It is a polynuclear metal complex containing a cerium arranged inside the. This polynuclear metal complex is excellent in the action of activating the CH bond at the benzyl position, and can promote air oxidation at the benzyl position with high efficiency. In addition, this polynuclear metal complex can be easily and reliably produced, and exists stably after complex formation. Due to its excellent stability, it can be easily recovered from the product after the reaction and is not easily mixed into the product. In addition, it is easy to reuse after collection.
As an example of such a polynuclear metal complex, a polynuclear metal complex represented by the following formula (i) (hereinafter, also referred to as “complex (i)”) can be mentioned.

In the equation, X ¹ is the 4th period transition metal,
X ² is a linking group
X ³ is a counter anion,
R ¹ and R ² are each independently a hydrogen atom, an alkyl group, an aryl group, a hydroxyl group or an amino group, or are bonded to each other to form a ring.

Examples of X ¹ include the same as those of the above-mentioned 4th period transition metal, and the preferred embodiment is also the same.
Examples of X ² include an alkylene group, an alicyclic group, an aromatic group and the like. The alkylene group may be linear or branched, and examples thereof include an ethylene group, a dimethylmethylene group, a trimethylene group, and a 2,2-dimethyltrimethylene group. As the alkylene group, an alkylene group having 2 to 3 carbon atoms such as an ethylene group, a dimethylmethylene group and a trimethylene group is preferable. Examples of the alicyclic group include an alicyclic group having 3 to 10 carbon atoms such as a cyclohexylene group. Examples of the aromatic group include a phenylene group such as an orthophenylene group, a 2,3-naphthalene group and the like.
X ² is typically a residue obtained by removing two amino groups from a diamine such as an aliphatic diamine or an aromatic diamine. Examples of the diamine include ethylenediamine, aliphatic diamines such as 2,2-dimethyl-1,3-propanediamine, alicyclic diamines such as 1,2-cyclohexanediamine, and aromatic diamines such as 1,2-phenylenediamine. Can be mentioned.

The X ^3, can be used various counter anion, for example, acetic acid anion, chloride ion, nitrate ion, and trifluoromethanesulfonate anion. Counteranion may be bonded to cerium and X ^1, it may not be binding.

In R ¹ and R ² , examples of the alkyl group include a linear or branched alkyl group having 1 to 15 carbon atoms. Specific examples include a methyl group, an ethyl group, a propyl group, an n-octyl group and the like. The alkyl group may have a substituent such as an aryl group or a halogen atom.
Examples of the aryl group include monocyclic, polycyclic or condensed ring aromatic hydrocarbon groups having 6 to 20 carbon atoms, preferably 6 to 14 carbon atoms. Specific examples thereof include a phenyl group, a tolyl group, a xsilyl group, an anisyl group, a nitrophenyl group, a naphthyl group, a methylnaphthyl group, an anthryl group, a phenanthryl group, a biphenyl group and the like. The aryl group may have a substituent such as an alkyl group or a halogen atom.

Bound R ¹ and R ² together, the ring formed together with the carbon atom to which R ¹ and R ² are bonded, it may be good alicyclic be an aromatic ring. Examples of the aromatic ring include a monocyclic, polycyclic or condensed ring type aromatic hydrocarbon ring having 6 to 20 carbon atoms, preferably 6 to 14 carbon atoms. Examples of the alicyclic ring include a monocyclic ring, a polycyclic ring, or a condensed ring type saturated hydrocarbon ring having 3 to 10 carbon atoms.

As the complex (i), it is preferable that X ² is an alkylene group and X ³ is an acetate anion.

The complex (i) can be produced, for example, by the following procedure.
First, in a solvent, mixing the acetate of ^{X 1,} and 2,3-dihydroxybenzene-1,4-carbaldehyde, and a cerium acetate. The mixing conditions are, for example, 25 to 80 ° C. for 1 to 4 hours. Then, diamine (H ₂ N-X ^2- NH ₂ ) is added to the obtained mixed solution and stirred. The stirring conditions are, for example, 25 to 80 ° C. for 6 to 18 hours.
After that, the formed complex can be recovered by removing the solvent. If necessary, purification treatment such as recrystallization can be performed. The structure of the obtained complex can be confirmed by, for example, single crystal X-ray crystal structure analysis.

<Substrate>
The substrate is not particularly limited as long as it is an organic compound having a benzyl position.
Substrate typically does not have a C-OH bond at the benzyl position. That is, it does not have a hydroxyl group as a substituent at the benzyl position.
As the substrate, for example, a compound represented by the following formula (1) (hereinafter, also referred to as “compound (1)”) and a compound represented by the following formula (2) (hereinafter, also referred to as “compound (2)”). Examples thereof include compounds having a CH bond at the benzyl position, such as).

In the formula, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² are independently hydrogen atom, alkyl group, cycloalkyl group and alkenyl. Shows a group, an alkynyl group, an aryl group, an aralkyl group, or a sulfinyl group. These groups may further have a substituent such as an alkyl group, an aryl group or a halogen atom.
Two locations selected from R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , and R ¹¹ may be combined to form a ring.
Two sites selected from R ⁴ , R ⁵ , and R ⁶ may be bonded to form an oxo group.
R ⁴ , R ⁵ , and R ⁶ may be combined to form an aromatic ring, and the aromatic ring may be further combined with R ⁷ or R ¹¹ to form a fused ring.

Alkyl groups that may have substituents at R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² include, for example, 1 carbon atom. Included are ~ 15 linear or branched alkyl groups. Specific examples include a methyl group, an ethyl group, a propyl group, an n-octyl group and the like.

Examples of cycloalkyl groups that may have substituents at R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² include, for example, the number of carbon atoms. Examples thereof include 3 to 10 monocyclic, polycyclic or condensed ring cycloalkyl groups. Specific examples include a cyclopropyl group, a cyclopentyl group, a cyclohexyl group, a cyclooctyl group and the like.

Examples of alkenyl groups that may have substituents at R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , and R ¹² include, for example, 3 carbon atoms. Examples include 10 to 10 alkenyl groups. Specific examples include a vinyl group, an allyl group, a hexenyl group and the like.

Examples of alkynyl groups that may have substituents at R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , and R ¹² include, for example, 3 carbon atoms. Included are 10 to 10 alkynyl groups and aryl alkynyl groups. Specific examples include an ethynyl group, a propynyl group, a hexynyl group, a phenylethynyl group and the like.

Aryl groups that may have substituents at R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , and R ¹² include, for example, 6 to 6 carbon atoms. 20, preferably 6 to 14 monocyclic, polycyclic or condensed ring aromatic hydrocarbon groups. Specific examples include a phenyl group, a tolyl group, a xsilyl group, an anisyl group, a nitrophenyl group, a naphthyl group, a methylnaphthyl group, an anthryl group, a phenanthryl group, a biphenyl group and the like.

Aralkyl groups that may have substituents at R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² include, for example, 7 carbon atoms. Examples thereof include a monocyclic, polycyclic or condensed ring type aralkyl group of ~ 20, preferably 7-14. Specific examples thereof include a benzyl group, a 1-phenylethyl group, a 1-phenylpropyl group, a 1-naphthylmethyl group, a 2-naphthylmethyl group and the like.

Sulfinyl groups that may have substituents at R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² include methyl sulfinyl groups and phenyls. Examples include a sulfinyl group.

Specific examples of the substrate include benzylphenyl ketone, 1,4-diphenyl-3-butin-2-one, toluene, о-xylene, m-xylene, p-xylene, mesitylene, pseudocumene, cumene, ethylbenzene, diphenylmethane, and fluorene. , Indan, etc.

<Air oxidation>
By contacting the substrate with molecular oxygen in the presence of an air oxidation catalyst, the air oxidation reaction at the benzyl position of the substrate proceeds.
Examples of the method of contacting the substrate with molecular oxygen in the presence of an air oxidation catalyst include a method in which the substrate, the air oxidation catalyst and, if necessary, a liquid medium are contained in a container and stirred in air. ..

Air is used, for example, in a pressure range of 1 to 10 atmospheres.
Air may be introduced into the container by utilizing diffusion depending on the shape of the container, may be introduced by using an air pump, or may be introduced by using a glassware such as a flask or a test tube with an open upper part. It may be introduced under the diffusion conditions below.

The amount of the air oxidation catalyst used is, for example, 0.01 to 20% by mass, preferably 0.01 to 10% by mass, and more preferably 0.05 to 5% by mass with respect to the substrate (100% by mass). is there.
Alternatively, the amount of the air oxidation catalyst used is, for example, 1 to 200 mg, preferably 1 to 100 mg, and more preferably 1 to 10 mg with respect to 1 mmol of the substrate.
When the amount of the air oxidation catalyst used is not less than the lower limit of the above range, the air oxidation reaction at the benzyl position of the substrate is more likely to proceed. If the amount of the air oxidation catalyst used exceeds the upper limit of the above range, the added catalyst may not be completely dissolved and the apparent catalytic activity may decrease.

As the liquid medium, all general organic solvents can be used, and examples thereof include dimethyl sulfoxide (DMSO), dichloroethane, dimethylformamide (DMF), acetonitrile, ethanol, benzene, and benzonitrile. These liquid media may be used alone or in combination of two or more.
The amount of the liquid medium used is preferably 0.1 to 1000 times, more preferably 1 to 100 times, the mass ratio with respect to the substrate.

The reaction conditions of the air oxidation reaction are not particularly limited, but the reaction temperature is preferably 0 to 150 ° C, more preferably 20 to 60 ° C.
The reaction time depends on the amount of the catalyst used, the reaction temperature, and the like, and cannot be unconditionally determined, but is usually in the range of 1 to 20 hours, preferably in the range of 2 to 6 hours.

The air oxidation reaction is preferably carried out in the absence of additives. By performing the air oxidation reaction in the absence of additives, the purity of the product is increased. In addition, the amount of energy input during purification after the reaction is completed can be reduced.
Examples of the additive include imide compounds (N-hydroxyphthalimide and the like) disclosed in JP-A-8-389909 [0014] to [0029] and JP-A-9-327626A [0030] to [0037]. ), AgBF ₄ , AgPF ₆ , NaBF ₄ , NaPF _{6, and the} like.

After completion of the reaction, the obtained product (alcohol compound, carbonyl compound, etc.) can be taken out by a usual method such as distillation, chromatographic separation, recrystallization, and sublimation.

<Product>
By air-oxidizing the benzyl position of the substrate as described above, an organic compound having a structure in which a hydroxyl group or an oxo group is introduced into the benzyl position of the substrate can be obtained.
For example, when the substrate is the compound (1), an alcohol compound represented by the following formula (3) and / or a carbonyl compound represented by the following formula (4) can be obtained.
For example, when the substrate is the compound (2), an alcohol compound represented by the following formula (5) and / or a carbonyl compound represented by the following formula (6) can be obtained.

In the formula, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² are synonymous with the above, respectively.

Specific examples of the obtained alcohol compound or carbonyl compound include benzyl alcohol, 2-methylbenzyl alcohol, 3-methylbenzyl alcohol, 4-methylbenzyl alcohol benzyl, 3,5-dimethylbenzyl alcohol, 1-phenylethanol and diphenylmethanol. , Fluolenol, 1-indanol, benzyl, benzoic acid, 2-methylbenzoic acid, 3-methylbenzoic acid, 4-methylbenzoic acid, 3,5-dimethylbenzoic acid, acetphenone, benzophenone, fluorenone, 1-indanone, etc. Can be mentioned.

In the present invention described above, by using the above-mentioned air oxidation catalyst, the benzyl position can be efficiently air-oxidized under relatively mild conditions without the presence of additives, and the benzyl position of the substrate can be used. An organic compound having a structure in which a hydroxyl group or an oxo group is introduced can be obtained in high yield. Moreover, since molecular oxygen is used as an oxidizing agent, an alcohol compound or a carbonyl compound can be produced while discharging only water as a by-product.
Further, since the above-mentioned air oxidation catalyst is a metal complex, it can be reused without being decomposed when the benzyl position is air-oxidized.
In particular, the catalyst (i) described above can be easily and reliably produced, and exists stably after complex formation. Therefore, it is possible to avoid the use of a ligand which is complicated and costly to produce as used in a conventional metal complex and may be decomposed during or after production.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples. Room temperature is 25 ° C. unless otherwise specified.
The conversion rate and yield in air oxidation were calculated by the following formulas based on the results analyzed by gas chromatography.
Conversion rate (%) = (1-Number of moles of remaining raw material / Number of moles of raw material used) x 100
Yield (%) = (number of moles of target compound / number of moles of raw material used) x 100

(Manufacturing Example 1)
Zinc acetate dihydrate (manufactured by Wako Pure Chemical Industries, Ltd.) (274 mg, 1.25 mmol) in methanol solution (50 mL) and 2,3-dihydroxybenzene-1,4-dicarbaldehyde (208 mg, 1.25 mmol) Chloroform solution (75 mL) of cerium acetate monohydrate (manufactured by Kishida Chemical Co., Ltd.) (139.8 mg, 0.416 mmol) in a methanol / water mixed solvent (methanol: water = 2: 1 (mass ratio)). It was added to the solution (75 mL) and stirred for 30 minutes at room temperature. Then, a chloroform solution (75 mL) of 2,2-dimethyl-1,3-propanediamine (manufactured by Tokyo Chemical Industry Co., Ltd.) (148 mg, 1.45 mmol) was added, and the mixture was stirred at room temperature for 18 hours. After distilling off the solvent with a rotary evaporator, it was vacuum dried under 0.05 mmHg, recrystallized in a three-layer system of methanol / diethyl ether / hexane, represented by the above formula (i), and X ^{1 in} the formula was expressed. A complex (379 mg, 0.315 mmol, yield 76%) in which zinc and X ² were dimethylmethylene groups and X ³ was an acetate anion was obtained.
A single crystal X-ray crystal structure analysis was performed on the obtained complex, and from the results, it was confirmed that the obtained complex had the structure shown in FIG.

(Manufacturing Example 2)
2,3-Dihydroxy in a methanol solution (25 mL) of cupric acetate (Aldrich) (55.3 mg, 0.304 mmol) and cerium nitrate hexahydrate (Aldrich) (43.7 mg, 0.101 mmol). A methanol solution (5 mL) of benzene-1,4-dicarbaldehyde (50.7 mg, 0.305 mmol) was added, and the mixture was stirred at room temperature for 4 hours. Then, a methanol solution (5 mL) of 2,2-dimethyl-1,3-propanediamine (manufactured by Tokyo Chemical Industry Co., Ltd.) (35.6 mg, 0.350 mmol) was added, and the mixture was stirred at room temperature for 17 hours. The solvent was distilled off and dried under 0.05 mmHg, and recrystallization was performed in a two-layer system of pyridine / toluene, which was represented by the above formula (i), where X ¹ was copper and X ² was a dimethyl methylene group. , X ³ is an acetate anion complex (379 mg, 0.315 mmol, yield 76%).
A single crystal X-ray crystal structure analysis was performed on the obtained complex, and from the results, it was confirmed that the obtained complex had the structure shown in FIG.

(Manufacturing Example 3)
Zinc acetate dihydrate (manufactured by Wako Pure Chemical Industries, Ltd.) (109.8 mg, 0.500 mmol) is dissolved by adding methanol (20 mL) and water (10 mL) to dissolve 2,3-dihydroxybenzene-1,4-di. A chloroform solution (10 mL) of carboaldehyde (83.1 mg, 0.500 mmol) was added, and the mixture was stirred at room temperature for 17 hours. After distilling off the solvent and drying under reduced pressure, methanol (30 mL) was added, cerium (III) chloride (anhydrous) (manufactured by Tokyo Chemical Industry Co., Ltd.) (41.1 mg, 0.166 mmol) was added, and the mixture was stirred at room temperature for 1 hour. .. Then, a methanol solution (3 mL) of 2,2-dimethyl-1,3-propanediamine (manufactured by Tokyo Chemical Industry Co., Ltd.) (52.8 mg, 0.516 mmol) was added, and the mixture was stirred at room temperature for 17 hours. Under 0.05 mmHg, the solvent was distilled off and dried, dissolved in methanol (6 mL), and the solution was added dropwise to diethyl ether (200 mL) to reprecipitate the complex. By filtering and drying the obtained powder, a complex represented by the above formula (i), in which X ¹ is zinc, X ² is a dimethylmethylene group, and X ³ is a chlorine ion (132 mg, 0. 117 mmol, yield 70%) was obtained. The structure of the obtained complex was confirmed by mass spectrometry.

(Manufacturing Example 4)
Zinc nitrate hexahydrate (manufactured by Nacalai Tesque) (148.6 mg, 0.500 mmol), cerium acetate monohydrate (manufactured by Kishida Chemical Co., Ltd.) (55.9 mg, 0.166 mmol) and methanol (20 mL) Water (10 mL) was added to dissolve the mixture, a chloroform solution (10 mL) of 2,3-dihydroxybenzene-1,4-dicarbaldehyde (83.1 mg, 0.500 mmol) was added, and the mixture was stirred at room temperature for 17 hours. After distilling off the solvent and drying under reduced pressure, methanol (20 mL) was added, and the mixture was stirred at room temperature for 1 hour. Then, a methanol solution (3 mL) of 2,2-dimethyl-1,3-propanediamine (manufactured by Tokyo Chemical Industry Co., Ltd.) (52.8 mg, 0.516 mmol) was added, and the mixture was stirred at room temperature for 17 hours. Under 0.05 mmHg, the solvent was evaporated to dryness, dissolved in methanol (6 mL) and the solution was added dropwise to diethyl ether (200 mL) to reprecipitate the complex. By filtering and drying the obtained powder, a complex represented by the above formula (i), in which X ¹ is zinc, X ² is a dimethyl methylene group, and X ³ is a nitrate ion (197 mg, 0. 162 mmol, yield 98%) was obtained. The structure of the obtained complex was confirmed by mass spectrometry.

(Manufacturing Example 5)
The above formula (i) is the same as in Production Example 4 except that zinc trifluoromethanesulfonate (II) and cerium trifluoromethanesulfonate (III) are used instead of zinc nitrate hexahydrate and cerium acetate monohydrate. ), X ¹ is zinc, X ² is a dimethyl methylene group, and X ³ is a trifluoromethanesulfonic acid anion (hereinafter, also referred to as “OTf”) (221 mg, 0.15 mmol, yield). 90%) was obtained. The structure of the obtained complex was confirmed by mass spectrometry.

(Example 1)
Put the stirrer chip in a 25 mL round bottom flask, put 6.0 mg of the complex obtained in Production Example 1, 19.6 mg of benzyl phenyl ketone (manufactured by Tokyo Kasei Kogyo Co., Ltd.) as a substrate, and DMSO (Nacalai Tesque) as a liquid medium. 2 mL (manufactured by Co., Ltd.) was added, connected to a reflux tube, and stirred at 90 ° C. under air at 1 atm for 18 hours. Then, 22.5 mg (0.0921 mmol) of triphenylmethane (manufactured by Nacalai Tesque, Inc.) was added as an internal standard, and gas chromatography measurement was performed. As a result, the conversion rate was 97%, the yield of diketone (A in the reaction formula below) was 59%, and 2-hydroxy-1,2-diphenylethanone (B in the reaction formula below) was not detected. It was.

(Example 2)
The reaction was carried out under the same conditions as in Example 1 except that dichloroethane was used instead of DMSO. As a result, the conversion was 81%, the yield of diketone was 28%, and the yield of 2-hydroxy-1,2-diphenylethanone was 16%.

(Example 3)
The reaction was carried out under the same conditions as in Example 1 except that dimethylformamide was used instead of DMSO. As a result, the conversion rate was 94%, the yield of diketone was 40%, and the yield of 2-hydroxy-1,2-diphenylethanone was 8%.

(Example 4)
The reaction was carried out under the same conditions as in Example 1 except that acetonitrile was used instead of DMSO. As a result, the conversion was 89%, the yield of diketone was 48%, and the yield of 2-hydroxy-1,2-diphenylethanone was 16%.

(Example 5)
The complex obtained in Production Example 3 in place of the complex obtained in Production Example 1 (X ³ are chloride ions) as a catalyst, except that acetonitrile was used instead of DMSO to conduct the reaction under the same conditions as in Example 1 It was. As a result, the conversion was 64%, the yield of diketone was 19%, and the yield of 2-hydroxy-1,2-diphenylethanone was 30%.

(Example 6)
The complex obtained in Production Example 4 in place of the complex obtained in Production Example 1 (X ³ is OTf) with a catalyst, except that acetonitrile was used instead of DMSO Reaction was carried out under the same conditions as in Example 1. As a result, the conversion was 59%, the yield of diketone was 20%, and the yield of 2-hydroxy-1,2-diphenylethanone was 22%.

(Comparative Example 1)
The reaction was carried out under the same conditions as in Example 1 except that acetonitrile was used instead of DMSO without using a catalyst. As a result, the conversion rate was 0%, and diketone and 2-hydroxy-1,2-diphenylethanone were not detected.

(Comparative Example 2)
The reaction was carried out under the same conditions as in Example 1 except that cerium acetate monohydrate was used instead of the complex obtained in Production Example 1 and acetonitrile was used instead of DMSO. As a result, the conversion rate was 0%, and diketone and 2-hydroxy-1,2-diphenylethanone were not detected.

(Comparative Example 3)
The reaction was carried out under the same conditions as in Example 1 except that zinc acetate dihydrate was used in place of the complex obtained in Production Example 1 and acetonitrile was used in place of DMSO. As a result, the conversion rate was 0%, and diketone and 2-hydroxy-1,2-diphenylethanone were not detected.

(Comparative Example 4)
The reaction was carried out under the same conditions as in Example 1 except that cerium acetate monohydrate and zinc acetate dihydrate were used instead of the complex obtained in Production Example 1 and acetonitrile was used instead of DMSO. As a result, the conversion rate was 0%, and diketone and 2-hydroxy-1,2-diphenylethanone were not detected.

(Example 7)
Put the stirrer chip in a 25 mL round bottom flask, put 1.29 mg of the complex obtained in Production Example 1, put 3 mL of ethylbenzene (manufactured by Sigma-Aldrich), connect to a reflux tube, and connect to a reflux tube at 140 ° C. at 140 ° C. at 1 atm. Stirred for hours. Then, 22.3 mg (0.0913 mmol) of triphenylmethane (manufactured by Nacalai Tesque, Inc.) was added as an internal standard, and gas chromatography measurement was performed. As a result, the yield of 1-phenylethanol (B in the following reaction formula) was 3.4%, and the yield of acetophenone (A in the following reaction formula) was 0.8%.

(Example 8)
Put the stirrer chip in a 25 mL round bottom flask, put 1.2 mg of the complex obtained in Production Example 2, put 3 mL of ethylbenzene (manufactured by Sigma-Aldrich), connect to a reflux tube, and connect to a reflux tube at 140 ° C. at 140 ° C. at 1 atm. Stirred for hours. Then, 22.9 mg (0.0928 mmol) of triphenylmethane (manufactured by Nacalai Tesque, Inc.) was added as an internal standard, and gas chromatography measurement was performed. As a result, the yield of 1-phenylethanol was 1.5%, and the yield of acetophenone was 0.8%.

(Comparative Example 5)
The reaction was carried out under the same conditions as in Example 7 except that no catalyst was used. As a result, only trace amounts of acetophenone and 1-phenylethanol were observed.

(Comparative Example 6)
The reaction was carried out under the same conditions as in Example 7 except that cerium acetate monohydrate was used instead of the complex obtained in Production Example 1. As a result, the yield of acetophenone was 0.3%, and the yield of 1-phenylethanol was 1.3%.

(Comparative Example 7)
The reaction was carried out under the same conditions as in Example 7 except that zinc acetate dihydrate was used instead of the complex obtained in Production Example 1. As a result, the yield of acetophenone was 0.5%, and the yield of 1-phenylethanol was 1.7%.

(Comparative Example 8)
The reaction was carried out under the same conditions as in Example 7 except that cerium acetate monohydrate and zinc acetate dihydrate were used instead of the complex obtained in Production Example 1. As a result, the yield of acetophenone was 0.2%, and the yield of 1-phenylethanol was 0.9%.

(Comparative Example 9)
The reaction was carried out under the same conditions as in Example 7 except that ammonium hexanitratocerium (IV) (CAN) was used instead of the complex obtained in Production Example 1. As a result, the yield of acetophenone was 0.5%, and the yield of 1-phenylethanol was 2.2%.

(Comparative Example 10)
The reaction was carried out under the same conditions as in Example 7 except that 30 μmol of acetic acid was used instead of the complex obtained in Production Example 1. As a result, the yield of acetophenone was 0.1%, and the yield of 1-phenylethanol was 0.5%.

Table 1 shows the results of Examples 1 to 6 and Comparative Examples 1 to 4 using benzylphenyl ketone as a substrate.
Table 2 shows the results of Examples 7 to 8 and Comparative Examples 5 to 10 using ethylbenzene as a substrate. In Table 2, the addition amount indicates the amount of the catalyst used per 3 mL of ethylbenzene.

From the comparison of Examples 1 to 6 and Comparative Examples 1 to 4, in Examples 1 to 6 in which a polynuclear metal complex containing two or more kinds of metals was used as a catalyst, Comparative Example 1 and other catalysts without a catalyst were used. It can be confirmed that the benzyl position of the substrate can be more efficiently air-oxidized as compared with Comparative Examples 2 to 4 used, and an organic compound having a structure in which a hydroxyl group or an oxo group is introduced into the benzyl position of the substrate can be obtained in a high yield. It was.
Similar results were confirmed in the comparison between Examples 7 to 8 and Comparative Examples 5 to 10.

By directly oxidizing the benzyl position by air oxidation and introducing a hydroxyl group or an oxo group, an industrially important alcohol compound or carbonyl compound can be obtained as an intermediate for pharmaceuticals, agricultural chemicals and the like, a raw material for a resin, and the like. According to the present invention, an alcohol compound or a carbonyl compound can be efficiently produced by using air as an oxidizing agent, using only water as an by-product, and a simple catalyst mixing. Therefore, the present invention relates to pharmaceuticals, pesticides, etc. It can be widely used mainly in fields such as intermediates and raw materials for resins.

Claims (11)

A method of air-oxidizing the benzyl position of an organic compound having a benzyl position.
A method for air oxidation, which comprises contacting the organic compound with molecular oxygen in the presence of a catalyst which is a polynuclear metal complex containing two or more kinds of metals. The air oxidation method according to claim 1, wherein the polynuclear metal complex contains a macrocycle ligand. The air oxidation method according to claim 1 or 2, wherein the two or more kinds of metals include cerium and a transition metal belonging to the fourth period of the periodic table. The air oxidation method according to any one of claims 1 to 3, wherein the polynuclear metal complex is represented by the following formula (i).

In the equation, X ¹ is a transition metal belonging to the 4th period of the periodic table.
X ² is a linking group
X ³ is a counter anion,
R ¹ and R ² are each independently a hydrogen atom, an alkyl group, an aryl group, a hydroxyl group or an amino group, or are bonded to each other to form a ring. The air oxidation method according to claim 3 or 4, wherein the transition metal belonging to the fourth period of the periodic table is at least one selected from the group consisting of manganese, copper and zinc. The air oxidation method according to any one of claims 1 to 5, wherein the amount of the catalyst used is 1 to 20% by mass with respect to the organic compound. A catalyst for air-oxidizing the benzyl position of an organic compound having a benzyl position.
An air oxidation catalyst, which is a polynuclear metal complex containing two or more kinds of metals. The air oxidation catalyst according to claim 7, wherein the polynuclear metal complex contains a macrocycle ligand. The air oxidation catalyst according to claim 7 or 8, wherein the two or more metals include cerium and a transition metal belonging to the fourth period of the periodic table. The air oxidation catalyst according to any one of claims 7 to 9, wherein the polynuclear metal complex is represented by the following formula (i).

In the equation, X ¹ is a transition metal belonging to the 4th period of the periodic table.
X ² is a linking group
X ³ is a counter anion,
R ¹ and R ² are each independently a hydrogen atom, an alkyl group, an aryl group, a hydroxyl group or an amino group, or are bonded to each other to form a ring. The air oxidation catalyst according to claim 9 or 10, wherein the transition metal belonging to the fourth period of the periodic table is at least one selected from the group consisting of manganese, copper and zinc.

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