JP5858386B2 - Organic hybrid catalyst - Google Patents

Description

  The present invention relates to an organic hybrid catalyst, and more particularly to an organic hybrid catalyst for achieving an oxidation reaction of alcohols excellent in environmental harmony.

Aldehydes, ketones, carboxylic acids and their derivatives are the main constituent substituents of the chemical structures of many organic natural products and pharmaceuticals, and are constructed by oxidation reactions of primary alcohols or secondary alcohols.
Therefore, these oxidation reactions are the most important reactions in the production of organic compounds.
Further, these oxidation reactions are one of basic reactions in organic synthetic chemistry, and classically, heavy metal oxidizing agents such as chromium (VI) compounds have been used.
In addition, compounds using transition metals such as ruthenium, manganese and vanadium have been developed.
However, the use of metal compounds has problems such as adverse environmental effects and the incorporation of trace metals into products.
In particular, in the manufacture of pharmaceuticals, cosmetics, agricultural chemicals, foods and the like, improvement of environmental harmony and improvement of safety are the most important issues from an industrial viewpoint.

In recent years, 2,2,6,6-tetramethylpiperidine-1-oxyl (hereinafter referred to as TEMPO) instead of conventional oxidizing agents using heavy metals Is widely used as an oxidation catalyst for alcohols.
TEMPO is a low environmental impact organic oxidizer compared to heavy metals, but it is expensive, so it is used after being reoxidized to the oxidized form with another oxidant that coexists with the reductant generated after the end of the oxidation reaction. Combinations with various coexisting oxidants have been tried.

On the other hand, the coexisting oxidant used with TEMPO is also desired to be inexpensive and have a low environmental load.
Coexisting oxidants that have been used so far include organic oxidants such as m-chloroperbenzoic acid (mCPBA), trichloroisocyanuric acid, iodobenzene diacetate, N-chlorosuccinimide, sodium hypochlorite, Inorganic chlorine-based oxidizing agents such as sodium chlorite.
The use of molecular oxygen, the ultimate environmentally friendly oxidant, was also considered, but catalytic amounts of transition metal compounds such as manganese and cobalt were required.

Although a method using a hypervalent iodine compound as a coexisting oxidant is known, this method has a high functional group selectivity in the reaction, and is widely used for synthesizing natural products having a complicated structure at the laboratory level. However, it is not industrially preferable from the viewpoint of economy and waste.
Therefore, a method using a catalytic amount of an iodine compound while retaining the characteristics of this method has been proposed (Non-Patent Document 1).

Tetrahedron Lett., 47, 13 (2006)

Peracetic acid is an environmentally friendly oxidant comparable to molecular oxygen because it is inexpensive and available in large quantities, has reactivity as an oxidant, and becomes acetic acid after completion of the oxidation reaction.
However, application as a coexisting oxidant in TEMPO oxidation has not been successful so far.

Since peracetic acid oxidizes iodobenzene to iodobenzene diacetate in acetic acid, and since iodobenzene diacetate is used in natural product synthesis as a coexisting oxidant for TEMPO oxidation, TEMPO and iodobenzene As a hybrid catalyst, we devised a new oxidation reaction using peracetic acid as a coexisting oxidant.
In the reaction of the present invention, peracetic acid oxidizes iodobenzene to iodobenzene diacetate, which oxidizes TEMPO to its oxidized form, which oxidizes alcohols.
Furthermore, by combining the TEMPO part and the iodobenzene part with a covalent bond and consolidating them into one molecule, it is possible to improve the efficiency of the catalytic action and simplify the recovery and reuse of the catalyst.
Hereinafter, the present invention will be described in detail.

In the present invention, unless otherwise specified, alkylene is a linear or branched C _1-6 alkylene group such as methylene, ethylene and propylene, and alkenylene is a linear chain such as vinylene, 1-propynylene and isopropenylene. A branched or branched C _2-6 alkenylene group, a saturated 5- to 6-membered carbocyclic group is a group derived from cyclopentane, cyclohexane or cycloheptane; an unsaturated 5- to 6-membered carbon The cyclic group is a group derived from cyclopentene, cyclohexene, or cycloheptene, the amino acid residue is a group obtained by removing an amino group and a carboxyl group from an amino acid, and the ester residue is -CO (O)-. , Meaning each.

The present invention relates to a general formula [1]

（式［１１］中、Ｘ^ａは、酸素原子またはイミノ基、ｍは０，１，２のいずれかである。）
または、式［１２］であり；

（式［１２］中、Ｘ^aは、酸素原子またはイミノ基、Ｗはアルキレン基、ｍは０，１，２のいずれかである。）
Ｙは、酸素原子、イミノ基または式［１３］のいずれかであり；

（式［１３］中、Ｗはアルキレン基、Ｙ^ａは酸素原子またはイミノ基である。）
Ｚはアルキレン、アルケニレン、フェニレンまたは飽和もしくは不飽和の５〜７員の炭素環基のいずれかであり；ｎは０または１である。」で表される、２，２，６，６−テトラメチルピペリジン−１−オキシル誘導体である。“In the formula [1], X represents the formula [11]

(In Formula [11], ^Xa is an oxygen atom or an imino group, and m is 0, 1, or 2.)
Or Formula [12];

(In the formula [12], X ^a is an oxygen atom or an imino group, W is an alkylene group, and m is 0, 1, or 2.)
Y is any of an oxygen atom, an imino group, or a formula [13];

(Wherein [13], W is an alkylene group, ^{Y a} is oxygen atom or imino group.)
Z is any one of alkylene, alkenylene, phenylene or a saturated or unsaturated 5- to 7-membered carbocyclic group; n is 0 or 1. 2,2,6,6-tetramethylpiperidine-1-oxyl derivative represented by

  The present invention is an organic compound oxidation catalyst comprising the 2,2,6,6-tetramethylpiperidine-1-oxyl derivative represented by the above general formula [1].

  In the present invention, an alcohol is oxidized in the presence of the 2,2,6,6-tetramethylpiperidine-1-oxyl derivative represented by the above general formula [1] and a co-oxidant, and the corresponding oxo It is an oxidation method of alcohols characterized by synthesizing a body.

When a new hybrid catalyst having both a TEMPO part and an iodobenzene part of the present invention is used, alcohols can be oxidized using peracetic acid, which is not effective as a coexisting oxidant in the conventional TEMPO oxidation.
Further, the catalyst itself can be recovered.
In the oxidation of primary alcohols, direct oxidation to carboxylic acids can be performed.
In addition, ketones can be obtained by oxidation of secondary alcohols.
The hybrid catalyst according to the present invention is recovered and reused after use.

  The 2,2,6,6-tetramethylpiperidine-1-oxyl derivative of the present invention can be produced by the following method.

<Production method 1>

（式［１１］中、Ｘ^ａは、酸素原子、イミノ基、ｍは０，１，２のいずれかである。）または、式［１２］であり；

（式［１２］中、Ｘ^aは、酸素原子またはイミノ基、Ｗはアルキレン基、ｍは０，１，２のいずれかである。）
式［２］中、Ｙ^aは酸素原子またはイミノ基；ｎは０または１である。」
また、式［３］中、Ｚはアルキレン、アルケニレン、フェニレンまたは飽和もしくは不飽和の５〜７員の炭素環基をのいずれかである。“In the formula [1a], X represents the formula [11]

(. Wherein [11], ^{X a} is an oxygen atom, an imino group, m is 0, 1, or 2), or is Formula [12];

(In the formula [12], X ^a is an oxygen atom or an imino group, W is an alkylene group, and m is 0, 1, or 2.)
In the formula [2], Y ^a is an oxygen atom or an imino group; n is 0 or 1. "
In the formula [3], Z is any one of alkylene, alkenylene, phenylene, or a saturated or unsaturated 5- to 7-membered carbocyclic group.

The compound of general formula [4a] can be produced by reacting the compound of general formula [2] with the compound of general formula [3] in a solvent in the presence of a base.
Although the base used for this reaction will not be specifically limited if it is used as a base in a normal reaction, For example, N-methylmorpholine, a triethylamine, a diisopropylethylamine, a tributylamine, 1,8- diazabicyclo [5.4. 0] undec-7-ene, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [5.4.0] undec-7-ene, pyridine, 4- (N , N-dimethylamino) pyridine, or an organic base such as picoline, or an inorganic base such as sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide, or sodium hydride.
The solvent used in this reaction is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane, and pyridine also used as a base. These solvents may be used alone or in combination.
This reaction may be performed at 20 ° C. to 60 ° C. for 30 minutes to 20 hours.

The compound of general formula [1a] can be produced by reacting the compound of general formula [4a] with the compound of general formula [5a] or [5b].
This reaction may be carried out in a solvent such as benzene in the presence of a base such as dimethylaminopyridine, an acid catalyst such as camphorsulfonic acid, and a dehydrating agent such as N, N-dicyclohexylcarbodiimide.
This reaction may be performed at 20 ° C. to 40 ° C. for 30 minutes to 2 hours.

<Production method 2>

（式［１１］中、Ｘ^ａは酸素原子またはイミノ基、ｍは０，１，２のいずれかである。）または、式［１２］である。

（式［１２］中、Ｘ^ａは、酸素原子またはイミノ基、Ｗはアルキレン基、ｍは０，１，２のいずれかである。）；Ｙ^ａは酸素原子またはイミノ基；
ｎは０または１である。」“In the formula [1b], X represents [11]

(Wherein [11], ^{X a} is an oxygen atom or an imino group, m is 0, 1 or 2..) Or a formula [12].

(Wherein [12], ^{X a} is an oxygen atom or an imino group, W is an alkylene group, m is either 0, 1, 2.); ^{Y a} represents an oxygen atom or an imino group;
n is 0 or 1. "

A compound of the general formula [6] can be produced by subjecting the compound of the general formula [5a] or the general formula [5b] and the compound of the general formula [3] to an esterification reaction or an amidation reaction.
For the esterification reaction and the amidation reaction, a known reaction or the method described in the above production method 1 may be used.

The compound of the general formula [8] can be produced by subjecting the compound of the general formula [6] and the compound of the general formula [7] to an amidation reaction.
A known reaction or the method described in the above production method 1 may be used.

A compound of the general formula [1b] can be produced by subjecting the compound of the general formula [8] and the compound of the general formula [2] to an esterification reaction.
For the esterification reaction, a known reaction may be used.

The compounds of the above general formulas [4a], [6] and [8] may be used as they are in the next reaction without isolation.
The compounds of the general formulas [1a] and [1b] thus obtained can be isolated and purified by ordinary methods such as extraction, crystallization, distillation and column chromatography.

Preferred examples of the organic hybrid catalyst of the present invention include compounds of the following general formula [1c].

  "In the formula [1c], m is 0, 1, or 2, n is 0 or 1, Z is alkylene, alkenylene, phenylene, or a saturated or unsaturated 5- to 7-membered carbocyclic group. Either. "

  More preferable organic hybrid catalysts include 2,2,6,6-tetramethylpiperidine-1-oxyl derivatives in which, in the general formula [1c], Z is phenylene or alkylene, m is 0 or 1, and n is 0.

  EXAMPLES The present invention will be described more specifically with reference to the following examples, but the present invention is not limited thereto.

<Synthesis of hybrid catalyst>

(1) To a solution of 517 mg (3 mmol) of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl in 10 mL of pyridine, 2.132 g (15 mmol) of phthalic anhydride, 4- (N, N-dimethyl) Amino) pyridine (183 mg, 1.5 mmol) was added, and the mixture was stirred at room temperature for 1 hour.
The reaction mixture was concentrated under reduced pressure, and the residue was filtered through silica gel to obtain 982 mg of crude monoester “4- (2-carbobenzoyloxy) -2,2,6,6-tetramethylpiperidin-1-oxyl” as an orange crystalline substance.

(2a) Under nitrogen atmosphere at 5 ° C., crude monoester 982 mg, 4-iodobenzyl alcohol 772 mg (3.3 mmol), 4- (N, N-dimethylamino) pyridine 73 mg (0.6 mmol), camphorsulfonic acid 70 mg ( 0.3 mmol) in 70 mL of benzene was added 1.237 g (6 mmol) of N, N-dicyclohexylcarbodiimide, and the mixture was stirred at room temperature for 30 minutes.
Diethyl ether was added to the reaction solution, filtered through celite, and the filtrate was concentrated under reduced pressure.
The residue was purified by silica gel column chromatography (eluent: hexane containing 50% ethyl acetate), and the product [1e] “4- (2-((4-iodobenzyloxy) carbonyl) benzoyloxy) -2,2,6,6 -Tetramethylpiperidin-1-oxyl "1.216 g was obtained as an orange crystalline material.
Melting point: 127-129 ° C. (recrystallization solvent: hexane containing 20% ethyl acetate)

(2b) N, N-dicyclohexylcarbodiimide in a 20 mL benzene solution of 160 mg of crude monoester, 140 mg of 4-iodophenol, 12 mg of 4- (N, N-dimethylamino) pyridine and 12 mg of camphorsulfonic acid at 5 ° C. in a nitrogen atmosphere 206 mg was added and stirred at room temperature for 30 minutes.
Diethyl ether was added to the reaction solution, filtered through celite, and the filtrate was concentrated under reduced pressure.
The residue was purified by silica gel column chromatography (eluent: hexane containing 20% ethyl acetate), and the product [1f] “4- (2-((4-iodophenoxy) carbonyl) benzoyloxy) -2,2,6,6 182 mg of “-tetramethylpiperidin-1-oxyl” was obtained as an orange crystalline material.
Melting point: 142-144 ° C. (recrystallization solvent: hexane containing 20% ethyl acetate)

<Synthesis of hybrid catalyst 2>

(1) To a solution of 517 mg (3 mmol) of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl in 10 mL of pyridine, 1.501 g (15 mmol) of succinic anhydride, 4- (N, N-dimethyl) After adding 183 mg (1.5 mmol) of amino) pyridine and stirring at room temperature for 3 hours, the reaction solution was distilled off under reduced pressure.
The residue was purified by silica gel column chromatography (eluent: ethyl acetate), and 854 mg of crude monoester “4- (2-carbopropypropyoxy) -2,2,6,6-tetramethylpiperidin-1-oxyl” as an orange crystalline substance Obtained.

(2a) 278 mg of crude monoester “4- (2-carboxypropionyloxy) -2,2,6,6-tetramethylpiperidin-1-oxyl” at 5 ° C. in a nitrogen atmosphere, 280 mg (1.2 mmol) of 4-iodobenzyl alcohol, To 40 mL of a benzene solution of 24 mg (0.2 mmol) of 4- (N, N-dimethylamino) pyridine and 23 mg (0.1 mmol) of camphorsulfonic acid, 412 mg (2.0 mmol) of N, N-dicyclohexylcarbodiimide was added at room temperature. Stir for 45 minutes.
Diethyl ether was added to the reaction solution, filtered through Celite, and the filtrate was distilled off under reduced pressure.
The residue was purified by silica gel column chromatography (eluent: 20% ethyl acetate-containing hexane), and the product [1 g] “4- (2-((4-iodobenzyloxy) carbonyl) propionyloxy) -2,2,6,6 426 mg of “tetramethylpiperidin-1-oxyl” was obtained as an orange crystalline substance.
Melting point: 95-97 ° C. (recrystallization solvent: 10% ethyl acetate-containing hexane)

(2b) 278 mg of crude monoester “4- (2-carbopropypropyoxy) -2,2,6,6-tetramethylperperdin-1-oxyl” at 5 ° C. under an atmosphere of atmosphere, 264 mg (1.2 mmol) of 4-iodophenol, 4 -412 mg (2.0 mmol) of N, N-dicyclohexylcarbodiimide was added to 40 mL of a benzene solution of 24 mg (0.2 mmol) of (N, N-dimethylamino) pyridine and 23 mg (0.1 mmol) of camphorsulfonic acid, and 30 minutes at room temperature. Stir.
Diethyl ether was added to the reaction solution, filtered through Celite, and the filtrate was distilled off under reduced pressure.
The residue was purified by silica gel column chromatography (eluent: hexane containing 10% ethyl acetate), and the product [1h] “4- (2-((4-iodophenoxy) carbonyl) propionyloxy) -2,2,6,6 -Tetramethylperidin-1-oxyl "413 mg was obtained as an orange crystalline material.
Melting point: 69-71 ° C. (recrystallization solvent: hexane containing 20% ethyl acetate)

<Oxidation of primary alcohol>

Hybrid catalyst “4- (2-((4-iodobenzoyl) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperdin-1-oxyl” in 27 mg of peracetic acid (9232% acetic acid solution 4232 mg) in 4-nitrobenzyl 77 mg (0.5 mmol) of alcohol was added and stirred at room temperature for 24 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to recover 19 mg of catalyst.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 82 mg of 4-nitrobenzoic acid (yield 99%). It was.

Hybrid catalyst “4- (2-((4-iodobenzyloxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylpiperidin-1-oxyl” 27 mg of peracetic acid (9232% acetic acid solution 4232 mg) in benzyl alcohol 54 mg ( 0.5 mmol) was added and stirred at room temperature for 24 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to obtain 15 mg (28% yield) of benzaldehyde and recover 15 mg of the catalyst.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 36 mg of benzoic acid (yield 59%).

Hybrid catalyst “4- (2-((4-iodobenzyloxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperdin-1-oxyl” 27 mg of peracetic acid (9% acetic acid solution, 4232 mg) in 4-methyl 61 mg (0.5 mmol) of benzyl alcohol was added and stirred at room temperature for 24 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to obtain 33 mg (yield 55%) of p-tolualdehyde, and 21 mg of the catalyst was recovered.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 25 mg (yield 37%) of p-toluic acid. It was.

Hybrid catalyst “4- (2-((4-iodobenzyloxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperdin-1-oxyl” in 27 mg of peracetic acid (9% acetic acid solution 6348 mg) in 2-nitrobenzyl 77 mg (0.5 mmol) of alcohol was added and stirred at room temperature for 48 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to obtain 4 mg of 2-nitrobenzaldehyde (yield 5%), and 20 mg of the catalyst was recovered.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 76 mg of 2-nitrobenzoic acid (yield 92%). It was.

Hybrid catalyst “4- (2-((4-iodobenzoyl) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperdin-1-oxyl” in 27 mg of peracetic acid (9% acetic acid solution 6348 mg) in 3-nitrobenzyl 77 mg (0.5 mmol) of alcohol was added and stirred at room temperature for 48 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to recover 18 mg of catalyst.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 78 mg of 3-nitrobenzoic acid (yield 94%). It was.

Hybrid catalyst “4- (2-((4-iodobenzyloxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperidin-1-oxyl” in 27 mg of peracetic acid (9% acetic acid solution 6348 mg) in 4-chlorobenzyl 71 mg (0.5 mmol) of alcohol was added and stirred at room temperature for 48 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to obtain 14 mg of 4-chlorobenzaldehyde (yield 20%), and 22 mg of the catalyst was recovered.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 44 mg of 4-chlorobenzoic acid (yield 56%). It was.

Hybrid catalyst “4- (2-((4-iodobenzyloxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylpiperidin-1-oxyl” 27 mg of peracetic acid (9% acetic acid solution 6348 mg) in 4-fluorobenzyl 65 mg (0.5 mmol) of alcohol was added and stirred at room temperature for 48 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to obtain 12 mg (yield 19%) of 4-fluorobenzaldehyde, and 16 mg of the catalyst was recovered.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 47 mg of 4-fluorobenzoic acid (yield 67%). It was.

Hybrid catalyst “4- (2-((4-iodobenzyloxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylpiperidin-1-oxyl” in a solution of 27 mg peracetic acid (9348% acetic acid solution 6348 mg) in 2,4- Dichlorobenzyl alcohol 88 mg (0.5 mmol) was added, and the mixture was stirred at room temperature for 48 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to obtain 11 mg (yield 13%) of 2,4-dichlorobenzaldehyde, and 19 mg of the catalyst was recovered.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to yield 74 mg of 2,4-dichlorobenzoic acid (yield 78%). was gotten.

Hybrid catalyst “4- (2-((4-iodobenzoyl) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperidin-1-oxyl” in 27 mg of peracetic acid (9% acetic acid solution 6348 mg) in 3,4- Difluorobenzyl alcohol 72 mg (0.5 mmol) was added, and the mixture was stirred at room temperature for 48 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to obtain 13 mg of 3,4-difluorobenzaldehyde (yield 18%), and 15 mg of the catalyst was recovered.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give 49 mg of 3,4-difluorobenzoic acid (yield 62%). was gotten.

Hybrid catalyst “4- (2-((4-iodobenzyloxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylpiperidin-1-oxyl” in 80 mg of peracetic acid (9% acetic acid solution, 4232 mg) in 3-phenyl 68 mg (0.5 mmol) of -1-propanol was added, and the mixture was stirred at room temperature for 17 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to recover 61 mg of catalyst.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 72 mg of 3-phenylpropanoic acid (yield 96%). It was.

Hybrid catalyst “4- (2-((4-iodobenzyloxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperdin-1-oxyl” in a solution of 80 mg of peracetic acid (9232% acetic acid solution 4232 mg) with 57 mg of cyclohexyl methanol ( 0.5 mmol) was added and stirred at room temperature for 24 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to recover 60 mg of the catalyst.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 64 mg of cyclohexylcarboxylic acid (yield 100%). .

4- (2-((4-iodophenoxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperdin-1-oxyl in 26 mg (0.05 mmol) of peracetic acid (9232% acetic acid solution 4232 mg) in 4-nitro 77 mg (0.5 mmol) of benzyl alcohol was added and stirred at room temperature for 24 hours.
Ethyl acetate was added, washed with 50% aqueous potassium carbonate solution, and extracted with ethyl acetate.
The extract was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to obtain 3 mg (yield 4%) of 4-nitrobenzaldehyde and 20 mg (77%) of the catalyst was recovered.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give 78 mg (yield 94%) of 4-nitrobenzoic acid.

4- (2-((4-iodophenoxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylpiperidin-1-oxyl in 26 mg (0.05 mmol) of peracetic acid (9% acetic acid solution 6348 mg) in 2-nitro 77 mg (0.5 mmol) of benzyl alcohol was added and stirred at room temperature for 48 hours.
Ethyl acetate was added, washed with 50% aqueous potassium carbonate solution, and extracted with ethyl acetate.
The extract was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to obtain 6 mg (yield 8%) of 4-nitrobenzaldehyde and 16 mg (62%) of the catalyst was recovered.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give 71 mg (yield 86%) of 2-nitrobenzoic acid.

4- (2-((4-iodophenoxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperdin-1-oxyl in 26 mg (0.05 mmol) of peracetic acid (9% acetic acid solution 6348 mg) was added to 3-nitro 77 mg (0.5 mmol) of benzyl alcohol was added and stirred at room temperature for 48 hours.
Ethyl acetate was added, washed with 50% aqueous potassium carbonate solution, and extracted with ethyl acetate.
The extract was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to recover 15 mg (58%) of the catalyst.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 83 mg of 3-nitrobenzoic acid (yield 100%).

4- (2-((4-iodophenoxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperdin-1-oxyl 78 mg (0.15 mmol) in peracetic acid (9% acetic acid solution 4232 mg) was added to 3-phenyl -1-Propanol 68 mg (0.5 mmol) was added, and the mixture was stirred at room temperature for 20 hours.
Ethyl acetate was added, washed with 50% aqueous potassium carbonate solution, and extracted with ethyl acetate.
The extract was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography, and 57 mg (73%) of the catalyst was recovered.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give 72 mg (yield 96%) of 3-phenylpropanoic acid.

4- (2-((4-iodophenoxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperdin-1-oxyl 78 mg (0.15 mmol) in peracetic acid (9% acetic acid solution 4232 mg) in cyclohexyl methanol 57 mg (0.5 mmol) was added and stirred at room temperature for 26 hours.
Ethyl acetate was added, washed with 50% aqueous potassium carbonate solution, and extracted with ethyl acetate.
The extract was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to recover 59 mg (76%) of the catalyst.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 62 mg (97% yield) of cyclohexylcarboxylic acid.

Hybrid catalyst “4- (2-((4-iodobenzyloxy) carbonyl) benzoyloxy) -2,2,6,6-tetramethylpiperidin-1-oxyl” in a solution of 27 mg of peracetic acid (9232% acetic acid solution 4232 mg) with 1-phenyl- 1-ethanol 61 mg (0.5 mmol) was added, and the mixture was stirred at room temperature for 19 hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to recover 23 mg of catalyst.
The aqueous layer was acidified with a 10% aqueous hydrochloric acid solution, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 55 mg of acetophenone (yield 92%).

Hybrid catalyst “4- (2-((4-iodobenzoyl) carbonyl) benzoyloxy) -2,2,6,6-tetramethylperperdin-1-oxyl” in a solution of 27 mg of peracetic acid (9% acetic acid solution, 4232 mg) in 92 mg of diphenylmethanol (0.5 mmol) was added, and the mixture was stirred at room temperature for 28 hours, diluted with 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to recover 24 mg of catalyst.
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 86 mg of benzophenone (yield 95%).

(Reference example)
To a solution of 16 mg (0.05 mmol) of 4-benzoyloxyiodobenzene and 8 mg (0.05 mmol) of TEMPO in peracetic acid (4232 mg of 9% acetic acid solution), 77 mg (0.5 mmol) of 4-nitrobenzyl alcohol was added. Stir for hours.
The reaction solution was diluted by adding 20 mL of ethyl acetate, and partitioned by adding 10 mL of 50% aqueous potassium carbonate solution.
The organic layer was washed with a saturated aqueous solution of sodium thiosulfate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was separated and purified by silica gel column chromatography to recover 26 mg of raw 4-nitrobenzyl alcohol (recovery rate 34%) and 6 mg of 4-nitrobenzaldehyde (yield 8%).
The aqueous layer was acidified with 10% aqueous hydrochloric acid, extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 40 mg of 4-nitrobenzoic acid (yield 48%). It was.

  The organic hybrid catalyst of the present invention can be used in the oxidation process of alcohols in the production of fine chemicals such as pharmaceuticals and agricultural chemicals, and can achieve the construction of a green industrial plant with little waste.

Claims (7)

Represented by the following general formula [1],

“In the formula [1], X represents the formula [11]

(In Formula [11], ^Xa is an oxygen atom or an imino group, and m is 0, 1, or 2.)
Or Formula [12];

(In the formula [12], X ^a is an oxygen atom or an imino group, W is an alkylene group, and m is 0, 1, or 2.)
Y is any of an oxygen atom, an imino group, or a formula [13];

(Wherein [13], W is an alkylene group, ^{Y a} is oxygen atom or imino group.)
Z is any one of alkylene, alkenylene, phenylene or a saturated or unsaturated 5- to 7-membered carbocyclic group; n is 0 or 1. 2,2,6,6-tetramethylpiperidine-1-oxyl derivative represented by The 2,2,6,6-tetramethylpiperidine-1-oxyl derivative according to claim 1, wherein ^{X a} and Y is an oxygen atom, m is the 1, n is 0.   The 2,2,6,6-tetramethylpiperidine-1-oxyl derivative according to claim 1 or 2, wherein Z is phenylene. Represented by the following general formula [1],

“In the formula [1], X represents the formula [11]

(In Formula [11], ^Xa is an oxygen atom or an imino group, and m is 0, 1, or 2.)
Or Formula [12];

(In the formula [12], X ^a is an oxygen atom or an imino group, W is an alkylene group, and m is 0, 1, or 2.)
Y is any of an oxygen atom, an imino group, or a formula [13];

(Wherein [13], W is an alkylene group, ^{Y a} is oxygen atom or imino group.)
Z is any one of alkylene, alkenylene, phenylene or a saturated or unsaturated 5- to 7-membered carbocyclic group; n is 0 or 1. And a 2,2,6,6-tetramethylpiperidine-1-oxyl derivative represented by the formula:   The oxidation catalyst according to claim 4, wherein the organic compound is an alcohol. Represented by the following general formula [1],

“In the formula [1], X represents the formula [11]

(In Formula [11], ^Xa is an oxygen atom or an imino group, and m is 0, 1, or 2.)
Or Formula [12];

(In the formula [12], X ^a is an oxygen atom or an imino group, W is an alkylene group, and m is 0, 1, or 2.)
Y is any of an oxygen atom, an imino group, or a formula [13];

(Wherein [13], W is an alkylene group, ^{Y a} is oxygen atom or imino group.)
Z is either alkylene, alkenylene, phenylene or a saturated or unsaturated 5- to 7-membered carbocyclic group;
n is 0 or 1. In the presence of a 2,2,6,6-tetramethylpiperidine-1-oxyl derivative and a coexisting oxidant, and the corresponding oxo form is synthesized. Method for oxidizing alcohols.   The method for oxidizing alcohols according to claim 6, wherein the coexisting oxidizing agent is peracetic acid.