JP5552550B1 - Oxidation catalyst and method for producing oxidation reaction product - Google Patents

Abstract

（式中、Ｍは鉄、マンガン又はコバルトであり、Ｌは任意の配位子であり、Ｘは対イオンであり、ｎは０、１又は２である。）
【選択図】 なしThe present invention provides a method for oxidizing an sp ³ C—H bond that enables high selectivity and catalyst rotation speed.
The sp ³ C—H bond oxidation method according to the present invention is characterized by oxidizing a sp ³ C—H bond using a metal complex catalyst represented by the following general formula (1) as an oxidation catalyst. .
[Chemical 1]

(In the formula, M is iron, manganese or cobalt, L is an arbitrary ligand, X is a counter ion, and n is 0, 1 or 2.)
[Selection figure] None

Description

The present invention relates to an oxidation catalyst for oxidizing an inactive sp ³ C—H bond and a method for producing an oxidation reaction product .

The sp ³ C—H bond is inactive and is generally difficult to oxidize, but in the living body, such an oxidation reaction proceeds under mild conditions. In vivo oxidation reactions involving cytochrome 450 and methane monooxygenase are good examples.
Various attempts have been made to design metal complex catalysts that catalyze the oxidation of sp ³ C—H bonds based on the mechanism of the oxidation reaction of sp ³ C—H bonds in vivo (for example, Patent Document 1). reference).
In addition, the present inventors have used 2- [bis (pyridin-2-ylmethyl)] amino-N-quinoline-8 as a metal complex catalyst for selectively hydroxylating an alkane C—H bond with hydrogen peroxide. -It has been reported that the iron (III) complex of yl-acetamidate is excellent (see Non-Patent Document 1).

US Patent Application Publication No. 2009/0221083

Hitomi Hitomi, 3 others, “An Iron (III) Monoamidate Complex Catalyst for Selective Hydroxylation of Alkane C-H Bonds with Hydrogen Peroxide”, Angewandte Chemie International Edition, 2012, 51 (14), p.3448-3452

However, the conventional metal complex catalyst still has room for improvement in the selectivity of the oxidation reaction of the sp ³ C—H bond.
In addition to selectivity, it is also important to improve the catalyst rotation speed.

Then, this invention aims at providing the manufacturing method of the oxidation catalyst and oxidation reaction product which enable high selectivity and catalyst rotation speed.

  As a result of intensive studies in order to solve the above problems, the present inventors have found that if a specific metal complex catalyst is used as an oxidation catalyst, high selectivity and catalyst rotation speed can be exhibited. The present invention has been completed.

That is, the oxidation catalyst of the present invention is characterized in that it consists of a metal complex catalyst represented by the following general formula (1).
In the method for producing an oxidation reaction product according to the present invention, the sp ³ C—H bond is oxidized by oxidizing the compound having the sp ³ C—H bond with an oxidizing agent capable of oxidizing the sp ³ C—H bond. In the method for producing an oxidation reaction product, the oxidation is performed using a metal complex catalyst represented by the following general formula (1) as an oxidation catalyst.
In the following, the oxidation using the oxidation catalyst according to the present invention may be referred to as “ the oxidation method of sp ³ C—H bond according to the present invention” or “the oxidation method of the present invention”.

(In the formula, M is iron, manganese or cobalt, L is an arbitrary ligand, X is a counter ion, and n is 0, 1 or 2.)

According to the present invention, the oxidation of sp ³ C—H bond can be performed with high selectivity and high catalyst rotation speed.

Hereinafter, embodiments of the method for oxidizing sp ³ C—H bonds according to the present invention will be described in detail. However, the scope of the present invention is not limited to these descriptions, and the present invention is not limited to the following examples. Changes can be made as appropriate without departing from the spirit of the invention.

[Metal complex catalyst]
The metal complex catalyst used in the oxidation reaction of the present invention is represented by the following general formula (1).

In the above formula (1), M is iron, manganese or cobalt, preferably iron.
L is an arbitrary ligand that coordinates to M in addition to the heterocyclic compound that is a tetradentate ligand, and examples thereof include acetonitrile, hydroxo, chloride, triflate, and aqua.
X is a counterion, preferably ClO ₄ ^- is.
n is 0, 1 or 2.

[Method for producing metal complex catalyst]
Although an example of a preferable manufacturing method is given about the said metal complex catalyst, the metal complex catalyst used by this invention is not limited to what is obtained with the following manufacturing method.

  For example, the following synthetic scheme using a proline in which an amino group is protected with a protecting group and 8-aminoquinoline as starting materials can be suitably employed.

  In the above, P is a protecting group, and may be a known group used for protecting an amino group, such as a Boc group (tert-butoxycarbonyl group) or a Z group (benzyloxycarbonyl group).

  Next, the target metal complex catalyst is obtained by coordinating the heterocyclic compound obtained as described above to a metal. The method is not particularly limited, and a conventionally known method can be employed.

  For example, the heterocyclic compound and a predetermined metal ion may be allowed to coexist in a solvent under conditions capable of forming a complex. Specifically, the heterocyclic compound is dissolved in a solvent together with a basic compound, In addition, a complex crystallite can be formed by adding a predetermined metal ion solution.

  Here, as said solvent, polar organic solvents, such as methanol and acetonitrile, are suitable. As the basic compound, triethylamine, N, N-diisopropylethylamine and the like are suitable.

  After the complex formation, a high-purity metal complex catalyst can be obtained by washing with a solvent such as methanol.

[Oxidation of sp ³ CH bond by metal complex catalyst]
In the oxidation method of the present invention, the sp ³ C—H bond is oxidized using the metal complex catalyst as an oxidation catalyst.
Preferably, the oxidation reaction is performed in the presence of carboxylic acid. This is because in the coexistence of carboxylic acid, the effect of improving the selectivity and the number of rotations of the catalyst is further improved.

According to the oxidation method of the present invention, it is possible to selectively oxidize sp ³ C—H bonds. Here, “selective” specifically refers to specific sp ³ C—H bonds other than It means that it is oxidized in preference to the sp ³ C—H bond. At this time, which sp ³ C—H bond is oxidized among a plurality of sp ³ C—H bonds is usually determined by the magnitude of bond dissociation energy in each sp ³ C—H bond. That is, normally, sp ³ C—H bonds having low bond dissociation energy are preferentially oxidized.

  In the oxidation method of the present invention, when carboxylic acid is allowed to coexist, for example, acetic acid, propionic acid, trichloroacetic acid, trifluoroacetic acid and the like are preferably used, and acetic acid is particularly preferable.

  Examples of the oxidizing agent for performing the oxidation reaction include hydrogen peroxide, ozone, m-chloroperbenzoic acid (mCPBA), 2-iodoxybenzoic acid ester (IBX ester), t-butyl hydroperoxide, cumene hydroperoxide, and the like. Is mentioned. Hydrogen peroxide and ozone are preferred because the by-products are those that have a low environmental load such as oxygen and water.

  Examples of the solvent in the oxidation reaction include acetonitrile and dimethylacetamide. Among them, acetonitrile is preferable because of its high activity.

Since the oxidation method of the present invention is excellent in selectivity and has a sufficient number of catalyst rotations, the oxidation reaction can be carried out efficiently and economically with a small amount of addition.
For example, although depending on the oxidation conditions and the type of raw material, the metal complex catalyst: substrate (substance to be oxidized) = 1: 200 can be set on the molar basis.

According to the oxidation method of the present invention, for example, alcohol can be produced. Further, the ketone can be produced by further proceeding the oxidation reaction.
In particular, alcohols can be easily produced as derivatives such as esters and ethers using the hydroxyl group as a reactive base, and can also be developed as monomers by esterification with an acid having a vinyl group. Various application development can be expected. Thus, the significance of synthesizing alcohol directly and highly selectively from alkanes is extremely significant.

  To give more specific examples, for example, adamantane derivatives are attracting attention for their usefulness in applications such as pharmaceuticals and photoresist materials. However, according to the oxidation method of the present invention, 1-adamantanol is converted from adamantane. It can be selectively obtained in a high yield, and various adamantane derivatives can be efficiently produced using the hydroxyl group as a reactive base point.

  EXAMPLES Hereinafter, although the oxidation method of this invention is demonstrated using an Example, this invention is not limited to these Examples.

(Synthesis example)
<Synthesis Example 1>
Compound (A1) was synthesized by the following reaction.

Specifically, first, Boc-L-proline (0.40 g, 1.86 mmol) was added to the Schlenk tube and purged with nitrogen, and then 5 mL of anhydrous tetrahydrofuran was added. In the ice bath, ethyl chloroformate (0.18 ml, 1.86 mmol) was added over 15 minutes and a white precipitate formed. Further, after stirring for 1 hour, 8-aminoquinoline (0.268 g, 1.86 mmol) was added and stirred overnight at room temperature. Furthermore, after heating and refluxing for 3 hours, 2 mL of ethyl acetate was added, and a few drops of triethylamine were added. Thereafter, the reaction mixture containing the precipitate was filtered through Celite, and the filtrate was concentrated to dryness using an evaporator. As a result, a light pink solid was obtained. This solid was dissolved in ethyl acetate, washed with a saturated aqueous NH ₄ Cl solution by a liquid separation operation, the organic layer was dried using Na ₂ SO ₄ , and then concentrated to dryness. The obtained solid was purified by column chromatography (silica, ethyl acetate: hexane = 3: 1) to obtain a white solid.
The obtained white solid had a yield of 0.51 g and a yield of 80%, and it was confirmed from the following identification result that it was the compound (A1).
¹ H NMR (500 MHz, DMSO-d ₆ , δ): 10.4, 10.3 (s, 1H), 8.91 (d, J = 7.5 Hz, 1H), 8.66 (d, J = 7.5 Hz, 1 H), 8.43 (dd, J = 1.7, 8.6 Hz, 1 H), 7.69 (d, J = 8.0 Hz, 1 H), 7.65 (dd, J = 4 .3, 8.3 Hz, 1H), 7.60 (t, J = 7.1 Hz, 1H), 4.51 (dd, J = 8.3, 4.3 Hz, 1H), 3.41-3. 54 (m, 2H), 2.10 to 2.30 (m, 1H), 2.00 to 2.12 (m, 1H), 1.86 to 1.94 (m, 2H), 1.46 1.23 (s, 9H).

<Synthesis Example 2>
The following compound (A2) was synthesized by the following reaction using the above compound (A1).

Specifically, first, the compound (A1) (0.30 g, 0, 88 mmol) was added to a Schlenk tube, dissolved in dichloromethane (1 mL), and bathed in an ice bath. Slow addition of trifluoroacetic acid (1 mL) turned the solution orange. After stirring for 1 hour, the reaction mixture was concentrated to dryness using an evaporator. The obtained solid was dissolved in dichloromethane, and a liquid separation operation was performed using a saturated NaOH aqueous solution and a saturated NaCl aqueous solution. The organic layer was dried using Na ₂ SO ₄ and then concentrated to dryness to obtain a white solid.
The obtained white solid had a yield of 0.20 g and a yield of 96%, and it was confirmed from the following identification result that it was the compound (A2).
¹ H NMR (500 MHz, DMSO-d ₆ , δ): 11.2 (s, 1H), 8.97 (s, 1H), 8.65 (dd, J = 2.3, 7.5 Hz, 1H) , 8.44 (dd, J = 1.7, 8.0 Hz, 1H), 7.74 (dd, J = 2.0, 8.3 Hz, 1H), 7.67 (dt, J = 4.0) , 8.0 Hz, 1H), 7.62 (dt, J = 3.4, 8.0 Hz, 1H), 4.48 (s, 1H), 3.19 (m, 2H), 2.36 (m , 1H), 2.00 (m, 1H), 1.86 (m, 2H).
¹³ C NMR (125.8 MHz, DMSO-d ₆ , δ): 169.7 (s), 149.1 (s), 138.4 (s), 136.5 (s), 133.9 (s) , 127.9 (s), 126.8 (s), 122.6 (s), 122.2 (s), 117.2 (s), 60.3 (s), 39.8 (s), 30.1 (s), 24.4 (s).

<Synthesis Example 3>
Using the compound (A2), a compound (A3) (hereinafter simply referred to as “H-ppaq”) was synthesized by the following reaction.

Specifically, first, the compound (A2) (0.20 g, 0.84 mmol), Na ₂ CO ₃ (0.45 g, 4.2 mmol), 2- (chloromethyl) pyridine hydrochloride (0.14 g, 0.84 mmol) was added to a 30 ml two-necked eggplant flask and purged with nitrogen. 10 mL of anhydrous CH ₃ CN was added, and the mixture was heated to reflux for 3 hours. Furthermore, 2- (chloromethyl) pyridine hydrochloride (0.04 g) and potassium iodide (0.03 g) were added, and the mixture was heated to reflux for 2 hours. The reaction mixture was filtered through Celite, and the filtrate was concentrated using an evaporator. The obtained crude product was purified by column chromatography (Al ₂ O ₃ , ethyl acetate: hexane = 2: 1) to obtain a yellow oily substance.
The obtained yellow oily substance had a yield of 0.15 g and a yield of 55%, and was confirmed to be H-ppaq from the following identification results.
¹ H NMR (500 MHz, DMSO-d ₆ , δ): 11.6 (s, 1H), 9.01 (dd, J = 1.7, 4.0 Hz, 1H), 8.74 (dd, J = 1.4, 7.7 Hz, 1 H), 8.47 (dd, J = 1.7, 4.0 Hz, 1 H), 8.43 (dd, J = 1.7, 8.6 Hz, 1 H), 8 .11 (d, J = 7.5 Hz, 1H), 7.91 (dt, J = 1.7, 7.4 Hz, 1H), 7.68 (dd, J = 1.4, 8.3 Hz, 1H) ), 7.67 (dd, J = 4.0, 8.0 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.27 (ddd, J = 1.2, 5.). 2,7.4 Hz, 1H), 4.18 (d, J = 13.8 Hz, 1H), 3.78 (d, J = 13.8 Hz, 1H), 3.52 (dd, J = 5.2). , 10.3Hz, 1H , 3.12 (ddd, J = 2.6, 6.9, 9.4 Hz, 1H), 2.49 (dt, J = 6.7, 9.6 Hz, 1H), 2.32 (dq, J = 9.4, 12.8 Hz, 1H), 1.95 (dq, J = 4.5, 8.9 Hz, 1H), 1.84 (m, 1H), 1.76 (m, 1H).
¹³ C NMR (125.8 MHz, DMSO-d ₆ , δ): 172.5 (s), 158.5 (s), 148.9 (s), 148.5 (s), 137.9 (s) , 136.6 (s), 136.5 (s), 134.0 (s), 127.8 (s), 127.0 (s), 122.9 (s), 122.2 (s), 122.2 (s), 121.7 (s), 115.3 (s), 67.0 (s), 61.2 (s), 53.5 (s), 30.3 (s), 23 .9 (s).

<Synthesis Example 4>
Using the above H-ppaq (compound (A3)), the following compound (A4) (iron complex of H-ppaq. Hereinafter, simply referred to as “Fe (III) -ppaq”) was synthesized by the following reaction.

Specifically, first, H-ppaq (0.13 g, 0.40 mmol) and Fe (ClO ₄ ) ₃ .nH ₂ O (0.25 g, 0.47 mmol) were weighed in separate sample bottles. Each was dissolved in a small amount of methanol. Triethylamine (0.05 mL, 0.40 mmol) was added to the sample bottle in which H-ppaq was dissolved, and when the solution was slowly added to a methanol solution of Fe (ClO ₄ ) ₃ · 9H ₂ O, the solution turned dark brown did. It was allowed to stir overnight and the solution was concentrated. The crude product was dissolved in acetonitrile and recrystallized by gas-liquid diffusion using diethyl ether as a poor solvent to obtain Fe (III) -ppaq as a black solid.
The identification results by elemental analysis are as follows.
Calculated _{(C 24 H 26 Cl 2 FeN} 6 O 9.5): C, 42.56; H, 3.87; N, 12.41
Measurement: C, 42.74; H, 3.73; N, 12.4

[Comparative Synthesis Example 1]
<Comparative Synthesis Example 1-1>
The following compound (B1) was synthesized by the following reaction.

Specifically, first, 2-picolylamine (4.01 g, 37.0 mmol) purified by Kugelrohr was weighed into a 100 ml two-necked eggplant flask, and 50 ml of toluene was added. Further, formic acid (3.48 g, 74.0 mmol) was added, and a din stack tube was attached, followed by heating to reflux at 110 ° C. The solution accumulated in the Dinstack tube was removed and toluene was added several times. After 5 hours, the completion of the reaction was confirmed by TLC (Al ₂ O ₃ , ethyl acetate: hexane = 10: 1). After concentration, liquid separation was performed with an aqueous sodium carbonate solution and dichloromethane, and the organic phase was concentrated to obtain a brown oily substance.
The resulting brown oily substance had a yield of 3.15 g and a yield of 56.7%, and it was confirmed from the following identification result that it was the compound (B1).
¹ H NMR (500 MHz, CDCl ₃ , δ): 8.54 (d, J = 4.6 Hz, 1H), 8.33 (s, 1H), 7.68 (dt, J = 7.7, 1. 7 Hz, 1 H), 7.28 (d, J = 7.5 Hz, 1 H), 7.22 (dd, J = 7.5, 5.2 Hz, 1 H), 7.03 (br, 1 H), 4. 62 (d, J = 5.2 Hz, 2H).
¹³ C NMR (125.8 MHz, CDCl ₃ , δ): 161.5 (s), 156.2 (s), 149.0 (s), 137.0 (s), 122.5 (s), 122 .1 (s), 43.1 (s).

<Comparative Synthesis Example 1-2>
The following compound (B2) was synthesized by the following reaction using the compound (B1).

Specifically, first, the compound (B1) was placed in a 500 ml three-necked eggplant flask, and further 150 ml of dry tetrahydrofuran was added and the atmosphere was replaced with nitrogen. Thereafter, when sodium hydride (1.68 g, 69.6 mmol) was added, the solution turned white. After 1.5 hours, iodomethane (2.2 mL, 34.7 mmol) was added slowly using a syringe. Over the course of several hours, the color of the solution gradually changed to brown. After stirring overnight, the completion of the reaction was confirmed by TLC (Al ₂ O ₃ , ethyl acetate: hexane = 10: 1), 40 ml of distilled water and 30 ml of methanol were added, and 4.04 g of sodium hydroxide was added. Refluxed overnight. Then, after confirming the completion of the reaction by TLC (Al ₂ O ₃ , ethyl acetate: hexane = 10: 1), the mixture was concentrated and subjected to a liquid separation operation with an aqueous sodium chloride solution and dichloromethane, and the organic phase was concentrated to obtain a brown oil Obtained material.
The obtained brown oily substance was 2.29 g in yield and 80.8% in yield, and it was confirmed from the following identification result that it was the above compound (B2).
¹ HNMR (500 MHz, CDCl ₃ , δ): 8.56 (d, J = 5.2 Hz, 1H), 7.65 (dt, J = 7.6, 1.9 Hz, 1H), 7.31 (d , J = 7.5 Hz, 1H), 7.16 (dd, J = 7.7, 4.9 Hz, 1H), 3.88 (s, 1H), 2.49 (s, 1H), 1.97. (Br, 1H).

<Comparative Synthesis Example 1-3>
Using the compound (B2), the following reaction was sequentially performed to synthesize the following compound (B3) (hereinafter simply referred to as “H-mpaq”).

  Specifically, first, 8-aminoquinoline (2.70 g, 18.7 mmol) and sodium carbonate (2.79 g, 26.2 mmol) were added to a 300 ml two-necked eggplant flask, and after nitrogen substitution, 100 ml of dehydrated acetonitrile was added. added. After an ice bath, bromoacetyl bromide (2.0 ml, 22.5 mmol) was added slowly and the solution turned yellow and a solid formed. Then it gradually turned red. After 3 hours, the completion of the reaction was confirmed by TLC (silica, ethyl acetate: hexane = 1: 3), and the solid product was removed by Celite filtration and concentrated to obtain a red needle-like solid.

Next, sodium carbonate (2.79 g, 26.2 mmol) and the above compound (B2) (18.7 g, 2.29 mmol) were added to a 300 ml three-necked eggplant flask, and nitrogen substitution was performed. Thereafter, 100 ml of dehydrated acetonitrile was added, followed by ice bathing. To this, 4.99 g of the red needle solid was slowly added and stirred overnight. Then, after confirming the completion of the reaction by TLC (Al ₂ O ₃ , ethyl acetate: hexane = 10: 1), the solid product was removed by Celite filtration and concentrated to obtain a red oily substance. The product was purified by column chromatography (Al ₂ O ₃ , ethyl acetate: hexane = 2: 1). Since the solution was divided into a solution containing impurities and a solution containing no impurities, they were concentrated separately, and the obtained solid was recrystallized from acetonitrile to obtain a pale yellow solid.

The finally obtained pale yellow solid had a yield of 2.51 g and a yield of 43.7%, and it was confirmed from the following identification result that it was H-mpaq.
¹ H NMR (500 MHz, CDCl ₃ , δ): 11.5 (s, 1H), 8.90 (dd, J = 4.0, 1.7 Hz, 1H), 8.81 (dd, J = 6. 9, 1.7 Hz, 1 H), 8.55 (dd, J = 4.3, 1.4 Hz, 1 H), 8.18 (dd, J = 8.0, 1.7 Hz, 1 H), 8.07 (D, J = 8.0 Hz, 1H), 7.73 (dd, J = 7.7, 1.7 Hz, 1H), 7.54 (m, 2H), 7.48 (dd, J = 8. 3, 4.3 Hz, 1H), 7.19 (dd, J = 6.9, 5.2 Hz, 1H), 3.95 (s, 2H), 3.42 (s, 2H), 2.50 ( s, 3H).
¹³ C NMR (125.8 MHz, CDCl ₃ δ): 169.6 (s), 158.9 (s), 149.1 (s), 148.4 (s), 139.1 (s), 136. 7 (s), 136.4 (s), 134.4 (s), 128.2 (s), 127.5 (s), 123.2 (s), 122.4 (s), 121.8 (S), 121.6 (s), 116.7 (s), 64.3 (s), 62.6 (s), 43.6 (s).

<Comparative Synthesis Example 1-4>
Using the above H-mpaq (compound (B3)), the following compound (B4) (an iron complex of H-mpaq. Hereinafter, simply referred to as “Fe (III) -mpaq”) was synthesized by the following reaction.

Specifically, first, H-mpaq (0.1 g, 0.33 mmol) and Fe (ClO ₄ ) ₃ .9H ₂ O (0.20 g, 0.39 mmol) were weighed in separate sample bottles. Both materials were dissolved in a small amount of methanol. Triethylamine (0.04 ml, 0.33 mmol) is added to the sample bottle in which H-mpaq is dissolved, and when the solution is slowly added to a methanol solution of Fe (ClO ₄ ) ₃ · 9H ₂ O, the solution turns dark green did. The mixture was allowed to stir overnight, and the solution was filtered through a membrane filter to obtain a dark blue solid. The yield was 0.21g.
The analysis results of ESI-MS are as follows.
ESI-MS: Positive mode: m / z 391.98 [Fe (III) -mpaq (CH ₃ O)] ⁺

[Comparative Synthesis Example 2]
<Comparative Synthesis Example 2-1>
Compound (C1) (hereinafter referred to as “H-dpaq”) was synthesized by the following reaction.

Specifically, sodium carbonate (2.02 g, 19.4 mmol) and 8-aminoquinoline (2.00 g, 13.9 mmol) were added to the reaction vessel, and after being placed in an argon atmosphere, 40 mL of dehydrated acetonitrile was added. The reaction vessel was brought to 0 ° C. in an ice bath, and bromoacetyl bromide (3.36 mL, 16.6 mmol) was added over 10 minutes with stirring. After 20 minutes, the white solid was removed by suction filtration using “Celite 500” (registered trademark), and the filtrate was concentrated by an evaporator and then vacuum-dried to obtain a pink solid.
The obtained pink solid (3.54 g) and sodium carbonate (2.06 g, 19.4 mmol) were put in a reaction vessel and brought to an argon atmosphere, and then 40 mL of dehydrated acetonitrile was added. After bringing the temperature to 0 ° C. in an ice bath, 2,2′-dipiconylamine (3.31 mL, 16.6 mmol) was added over 20 minutes with stirring. After stirring overnight, the white solid was removed by suction filtration using Celite, and the filtrate was concentrated by an evaporator and dried in vacuo. The crude product was purified with an alumina column (ethyl acetate: hexane = 1: 1) to obtain a white solid.

The obtained white solid had a yield of 4.6 g and a yield of 86%, and was confirmed to be H-dpaq from the following identification results.
^The identification result by ¹ HNMR (500 MHz, CDCl ₃ ) is as follows.
δ3.53 (s, 2H), 4.01 (s, 4H), 7.14 (dd, J = 4.9 Hz, J = 7.2 Hz, 2H), 7.55-7.50 (m, 3H) ), 7.64 (ddd, J = 1.5 Hz, J = 7.5 Hz, 2H), 7.97 (d, J = 8.0 Hz, 2H), 8.19 (dd, J = 1.2 Hz, J = 8.6 Hz, 1H), 8.51 (d, J = 5.1 Hz, 2H), 8.76 (dd, J = 2.6 Hz, J = 6.0 Hz, 1H), 8.93 (dd , J = 1.4 Hz, J = 4.3 Hz, 1H), 11.6 (s, 1H)
^The identification result by ¹³ CNMR (125.8 MHz, CDCl ₃ ) is as follows.
δ 59.6 (s), 61.3 (s), 116.8 (s), 121.8 (s), 121.9 (s), 122.6 (s), 123.6 (s), 127 .7 (s), 128.3 (s), 134.7 (s), 136.6 (s), 136.8 (s), 139.1 (s), 148.3 (s), 149. 4 (s), 158.5 (s), 169.8 (s)
The identification results by elemental analysis are as follows.
Calculated _{(C 23 H 21 N 5 O} ): C, 72.04; H, 5.52; N, 18.26
Measurement: C, 72.25; H, 5.45; N, 18.36

<Comparative Synthesis Example 2-2>
Using the above H-dpaq (compound (C1)), the following compound (C2) (iron complex of H-dpaq. Hereinafter, simply referred to as “Fe (III) -dpaq”) was synthesized.

That is, H-dpaq (0.10 g, 0.26 mmol) and triethylamine (0.03 g, 0.30 mmol) were dissolved in 1.0 mL of methanol, and ferric perchlorate (Fe (ClO ₄ ) ₃ · 6H ₂ O, 0.11 g, 0.31 mmol) in methanol (1.0 mL) was added. The reaction solution turned green. After stirring for 2 hours, the precipitate was collected using a membrane filter and vacuum-dried to obtain a greenish black solid. When the obtained solid was dissolved in acetonitrile and recrystallized by a gas-liquid diffusion method using ethyl acetate as a poor solvent, a blocky green-black crystal stable in the air was obtained. The yield was 0.14 g and the yield was 78%.

[Example 1]
Using Fe (III) -ppaq obtained in Synthesis Example 1 as an oxidation catalyst, an adamantane oxidation reaction was performed by the following reaction.

Specifically, 500 equivalents of adamantane with respect to the complex was added to 1 ml (0.5 mM, 0.5 μmol) of Fe (III) -ppaq in acetonitrile under aerobic conditions at room temperature, and after stirring for a while, peroxidation was performed. Hydrogen in acetonitrile (0.5 ml, 0.02 M, 10 μmol) was added over 30 minutes and stirred for 5 minutes. A solution of nitrobenzene in acetonitrile was added as an internal standard, and the composition of the solution was measured by gas chromatography.
Instrument: Gas chromatograph “GC2014” (manufactured by Shimadzu Corporation)
Column: Capillary column “InertCap” (60 m × 0.25 mm) (manufactured by GL Sciences Inc.)
Measurement conditions: hold at initial temperature of 100 ° C. for 5 minutes, then increase to 220 ° C. at 10 ° C./min, reach 220 ° C. and hold for 11 minutes

[Example 2]
After adding adamantane and stirring for a while, the adamantane oxidation reaction was carried out in the same manner as in Example 1 except that acetic acid (100 equivalents) was added before adding the acetonitrile solution of hydrogen peroxide. In the measurement of the solution composition by gas chromatography, 20 minutes after the measurement, the composition of the solution was measured again by gas chromatography. As a result, the number of oxidized substrates in the solution to which acetic acid was added was increased. The mixture was stirred overnight, and the composition of the solution was measured by gas chromatography.

[Comparative Example 1]
Instead of 1 ml (0.5 mM, 0.5 μmol) of an acetonitrile solution of Fe (III) -ppaq, 1 ml (0.5 mM, 0.5 μmol) of an acetonitrile solution of Fe (III) -mpaq obtained in Comparative Synthesis Example 1 The adamantane oxidation reaction was carried out in the same manner as in Example 1 except that was used.

[Comparative Example 2]
Instead of 1 ml (0.5 mM, 0.5 μmol) of an acetonitrile solution of Fe (III) -ppaq, 1 ml (0.5 mM, 0.5 μmol) of an acetonitrile solution of Fe (III) -mpaq obtained in Comparative Synthesis Example 1 An adamantane oxidation reaction was carried out in the same manner as in Example 2 except that was used.

[Comparative Example 3]
Instead of 1 ml (0.5 mM, 0.5 μmol) of an acetonitrile solution of Fe (III) -ppaq, 1 ml (0.5 mM, 0.5 μmol) of an acetonitrile solution of Fe (III) -dpaq obtained in Synthesis Example 2 for comparison The adamantane oxidation reaction was carried out in the same manner as in Example 1 except that was used.

[Results of oxidation reaction]
In each of the oxidation reactions in Examples 1 and 2 and Comparative Examples 1 to 3, 1-adamantanol (target product) produced by oxidizing the C—H bond of the tertiary carbon, C of the secondary carbon -Mole amounts of 2-adamantanol and 2-adamantanone (byproduct) produced by oxidation of -H bond and selectivity calculated from these values (3 ° / 2 °), 1-adamantanol The production rate and catalyst rotation speed (TON) are shown in the table below.

The selectivity (3 ° / 2 °) represents how much the oxidation of the C—H bond of the tertiary carbon proceeds with respect to the oxidation of the C—H bond of the secondary carbon. Since there are 4 tertiary carbon C—H bonds and 12 secondary carbon C—H bonds per molecule of adamantane, the following formula is calculated from the molar amount of each product. .
3 ° / 2 ° = 3 × {[1-adamantanol] / ([2-adamantanol] + [2-adamantanone])}
The production rate (%) of 1-adamantanol is a value calculated by the following equation from the molar amounts of 1-adamantanol and hydrogen peroxide.
Production rate (%) = 100 × [1-adamantanol] / [hydrogen peroxide]
The catalyst rotation speed (TON) is a value calculated by the following formula from each molar ratio of the oxidation product of adamantane and the catalyst.
Catalyst rotational speed (TON) = [oxidation product of adamantane] / [catalyst]

From Table 1 above, in Examples 1 and 2 using the metal complex catalyst of the present invention as an oxidation catalyst, high selectivity is exhibited compared to Comparative Example 3 using Fe (III) -dpaq. I understand.
Furthermore, in Comparative Examples 1 and 2 using Fe (III) -mpaq, although the selectivity is higher than that in Comparative Example 3, the catalyst rotation speed is slightly lower. On the other hand, in Examples 1 and 2 using the metal complex catalyst of the present invention as an oxidation catalyst, selectivity is higher than Comparative Examples 1 and 2 and the number of catalyst rotations is also high.
In addition, from the comparison of the results of Examples 1 and 2, it can be seen that selectivity and catalyst rotation speed are higher when carboxylic acid is present together.

The oxidation method of the present invention can be suitably used as a method for selectively oxidizing sp ³ C—H bonds in adamantane and the like that have been difficult to oxidize conventionally.

Claims (6)

An oxidation catalyst comprising a metal complex catalyst represented by the following general formula (1).

(In the formula, M is iron, manganese or cobalt, L is an arbitrary ligand, X is a counter ion, and n is 0, 1 or 2.) M is iron, X is ClO ₄ ^- is, n is 2, the oxidation catalyst according to claim 1. sp ^Three Sp by an oxidant capable of oxidizing the C—H bond. ^Three Oxidizing a compound having a C—H bond to sp ^Three In the method for producing an oxidation reaction product in which a C—H bond is oxidized, the oxidation is performed using a metal complex catalyst represented by the following general formula (1) as an oxidation catalyst. Product manufacturing method.

(In the formula, M is iron, manganese or cobalt, L is an arbitrary ligand, X is a counter ion, and n is 0, 1 or 2.) The oxidation reaction product according to claim 3, wherein the oxidizing agent is selected from hydrogen peroxide, ozone, m-chloroperbenzoic acid, 2-iodoxybenzoic acid ester, t-butyl hydroperoxide and cumene hydroperoxide. Manufacturing method. Sp in the presence of carboxylic acid ^Three The method for producing an oxidation reaction product according to claim 3 or 4, wherein a compound having a C-H bond is oxidized. M is iron and X is ClO _Four ^- The method for producing an oxidation reaction product according to any one of claims 3 to 5, wherein n is 2.