JP2000247955A - Production of organic compound having nitroxide free radical - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce the subject compound useful as a spin label or spin probe of ESR spectrum analysis method in a good yield and in a short time by oxidizing a secondary cyclic amine with a peroxide. SOLUTION: This method for producing a nitroxide group-having organic compound of formula II (for example, 2,2,5,5-tetramethylpyrrolidine-N-oxyl) comprises reacting a sterically hindered cyclic secondary amine of formula I [T is methylene, ethylene, 0 or methyleneoxy; R is an alkyl, an aralkyl or the like; R1 to R4 are each an alkyl, an aryl, or R1 and R2 and/or R3 and R4 form together tetramethylene or the like; (n) is 0-6] (for example, 2,2,5,5- tetramethylpyrrolidine) with a peroxide (for example, hydroperoxide) in the presence of a cyano group-having organic compound (for example, acetonitrile or propionitrile) in an amount of at least 1 pt.wt. per pt.wt. of the cyclic secondary amine. The reaction is preferably carried out in a solvent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a compound represented by the general formula (2):

[0002]

Embedded image (In the formula, T represents a methylene group, an ethylene group, an oxygen atom or a methyleneoxy group, and R represents an alkyl group, an aralkyl group, an aryl group, a cycloalkyl group, an alkoxy group, an acyl group, an acyloxy group, an amino group, a hydroxy group. Or a heterocyclic group, R ¹ , R ² , R ³ and R ⁴ are the same or different and each represents an alkyl group or an aryl group, or R ¹ and R ² and / or R ³ and R ⁴ are Together represent a tetramethylene or pentamethylene group,
n is an integer of 0-6. ), An organic compound having a nitroxide free radical [hereinafter referred to as a nitroxide compound (2). ] The manufacturing method described above.

[0003] Nitroxide compounds (2) are useful as spin labels and spin probes in ESR spectroscopy, and as polymerization inhibitors for unsaturated compounds or stabilizers against thermal and photochemical decomposition of organic polymers. It is a compound useful as a co-oxidant in an oxidation reaction.

[0004]

2. Description of the Related Art It is conventionally known that an organic compound having a nitroxide free radical such as a nitroxide compound (2) can be produced by oxidizing a secondary amine having steric hindrance with a peroxide. That is, the nitroxide compound (2) has the general formula (1):

[0005]

Embedded image (Wherein T, R, R ¹ , R ² , R ³ , R ⁴ and n are as defined above) having a steric hindrance [hereinafter referred to as cyclic secondary amines (1) That. Is oxidized with a peroxide.

[0006]

However, 2,2,6,6-tetramethylpiperidine is used as the cyclic secondary amine (1), and this is oxidized with peroxide to form 2,2,6,6-tetramethylpiperidine.
When 6,6-tetramethylpiperidine-N-oxyl is produced, industrially satisfactory results are obtained, such as a low yield of the target compound and a long reaction time as shown in Comparative Examples described later. Can not.

An object of the present invention is to provide a cyclic secondary amine (1)
To provide a method for producing a nitroxide compound (2) in good yield and in a short time by oxidizing the compound with a peroxide.

[0008]

Means for Solving the Problems The present inventor has conducted intensive studies in order to solve the above problems. As a result, when the cyclic secondary amines (1) are reacted with a peroxide in the presence of at least 1 part by weight of the organic compound having a cyano group with respect to 1 part by weight of the cyclic secondary amines (1), the yield is reduced. The inventors have found that the nitroxide compound (2) can be produced efficiently and in a short time, and have completed the present invention.

That is, the present invention relates to cyclic secondary amines (1)
In the presence of at least 1 part by weight of an organic compound having a cyano group relative to 1 part by weight of the cyclic secondary amine (1),
The present invention relates to a method for producing a nitroxide compound (2), which comprises producing a nitroxide compound (2) by reacting with a peroxide.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. In the above general formula (1) showing the cyclic secondary amines used in the present invention, T represents a methylene group, an ethylene group, an oxygen atom or a methyleneoxy group, and R represents an alkyl group, an aralkyl group, an aryl group, a cycloalkyl group. , An alkoxy group,
Acyl group, an acyloxy group, an amino group, a hydroxy group or a heterocyclic group and R ^1, R ^2, R ³ and R ⁴ are the same or different or together, each represent an alkyl group or an aryl group, or R ¹ and R ² and / or R ³ and R ⁴ together represent a tetramethylene group or a pentamethylene group, and n is an integer of 0-6.

Examples of the alkyl group represented by R include linear or branched alkyl groups having 1 to 6 carbon atoms.
Specifically, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 2-methylpentyl, 3 -A methylpentyl group and a neohexyl group. Examples of the aralkyl group include an aralkyl group having 7 to 15 carbon atoms.
Benzyl, phenethyl, phenylpropyl, benzhydryl and the like. Examples of the aryl group include a phenyl group, a tolyl group, a xylyl group, and a naphthyl group. The cycloalkyl group may have 3 carbon atoms.
And cycloalkyl groups, such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group and cyclooctyl group. Examples of the alkoxy group include, for example, an alkyloxy group such as a methoxy group, an ethoxy group, and a propoxy group;
And aralkyloxy groups such as benzyloxy group. Examples of the acyl group include a linear or branched lower alkanoyl group having 1 to 6 carbon atoms such as a formyl group, an acetyl group, a propionyl group, a butyryl group, a valeryl group, a pivaloyl group and a pentanoyl group; a benzoyl group; An aroyl group such as a toluoyl group, a xyloyl group and a naphthoyl group may be mentioned. Examples of the acyloxy group include an alkanoyloxy group such as an acetoxy group and a propionyloxy group; and an aroyloxy group such as a benzoyloxy group. Further, as the heterocyclic group, for example,
Examples include thienyl group, pyrrolyl group, pyranyl group, thiopyranyl group, pyridyl group, thiazolyl group, imidazolinyl group, pyrimidinyl group, triazinyl group, indolyl group, quinolyl group, prenyl group and benzothiazolyl group. Note that R in the formula is a group that substitutes a hydrogen atom in the ring of the cyclic secondary amines (1).

The alkyl group and the aryl group represented by R ¹ , R ² , R ³ and R ⁴ in the formula are the same as those represented by R above, and preferably R ¹ , R ² , R ³ And R ⁴ each represent a methyl group.

Specific examples of the cyclic secondary amines (1) include, for example, 2,2,5,5-tetramethylpyrrolidine; an alkoxy group (methoxy Group, ethoxy group, propoxy group, benzyloxy group, etc.), acyloxy group (acetoxy group, propionyloxy group, benzoyloxy group, etc.),
2,2,5,5-tetramethylpyrrolidine derivative having a substituent such as a hydroxy group; 2,2,6,6-tetramethylpiperidine; an alkoxy group at the 4-position of 2,2,6,6-tetramethylpiperidine Having a substituent such as a methoxy group, an ethoxy group, a propoxy group, a benzyloxy group, an acyloxy group (an acetoxy group, a propionyloxy group, a benzoyloxy group), or a hydroxy group;
2,6,6-tetramethylpiperidine derivative;
4,4-tetramethyloxazolidine, 2,4,4-trimethyl-2-phenyloxazolidine or 4-aza-
4,4-dimethyloxazolidine derivatives such as 3,3-dimethyl-1-oxaspiro [4,5] decane;
5,5-tetramethylmorpholine; 3,3,5,5-tetramethylmorpholine derivatives having a substituent such as an alkyl group (such as a methyl group) at the 2-position of 3,3,5,5-tetramethylmorpholine and the like. But are not limited to these.

According to the manufacturing method of the present invention, the annular second
A nitroxide compound (2) corresponding to the amines (1) is produced. For example, 2,2,5,5-tetramethylpyrrolidine-N-oxyl and its derivatives are produced from 2,2,5,5-tetramethylpyrrolidine and its derivatives, and 2,2,6,6-tetramethylpiperidine And derivatives thereof from 2,2,6,6-tetramethylpiperidine-
N-oxyl and its derivatives are produced, 4,4-dimethyloxazolidine-N-oxyl derivatives are produced from 4,4-dimethyloxazolidine derivatives,
3,3,5,5-tetramethylmorpholine-N-oxyl and its derivatives are produced from 3,5,5-tetramethylmorpholine and its derivatives.

As the peroxide used in the present invention, any of hydrogen peroxide and organic peroxides such as hydroperoxide and peracid can be used, but from the viewpoint of economic efficiency and reduction of waste. Hydrogen oxide is preferred.

When using hydrogen peroxide, usually 5 to 7
A 0% by weight aqueous solution, preferably a 20 to 50% by weight aqueous solution is used. The amount of the peroxide used is 1.5 mol or more, preferably 1. mol, per 1 mol of the cyclic secondary amines (1).
6 to 3.5 mol.

In the present invention, the cyclic secondary amine (1) has at least 1 part by weight, preferably 1.5 to 50 parts by weight, more preferably 2 to 30 parts by weight of a cyano group per 1 part by weight of the cyclic secondary amine (1). The reaction is performed in the presence of an organic compound.
Further, at least 1.5 moles, preferably 2 to 50 moles, of cyano, based on 1 part by weight of the cyclic secondary amine (1) and 1 mole of the cyclic secondary amine (1). The reaction is preferably performed in the presence of an organic compound having a group.

The organic compound having a cyano group is not particularly limited except for a compound having a polymerizable unsaturated bond in the molecule, such as acrylonitrile, but is preferably an acetonitrile, propionitrile, butyronitrile, valeronitrile, capronitrile, or the like. And aromatic nitriles such as aliphatic nitriles, benzonitrile and tolunitrile.

When an aqueous solution of hydrogen peroxide is used as the peroxide, the organic compound having a cyano group is preferably a water-soluble organic compound, particularly preferably acetonitrile and / or propionitrile.

The present invention is performed in a solvent. The solvent is appropriately selected according to the cyclic secondary amines (1), the organic compound having a cyano group, and the nitroxide compound (2) used in the reaction, and a good solvent for the cyclic secondary amines (1) and the nitroxide compound (2). The solvent is selected from solvents which are miscible with the organic compound having a cyano group. Examples of the solvent, for example, water, methanol, ethanol, propanol, butanol, alcohols such as isopropanol, benzene, toluene, xylene, aromatic hydrocarbons such as mesitylene, diethyl ether, diisopropyl ether,
Examples include ethers such as tetrahydrofuran. Preferred are solvents that are not oxidized by nitroxide compounds (2) such as water, aromatic hydrocarbons and ethers.

When the amount of the organic compound having a cyano group is at least 2.5 parts by weight, preferably at least 3 parts by weight, based on 1 part by weight of the cyclic secondary amine (1), no solvent is used. The organic compound having the cyano group may be omitted, and serves as the solvent in the present invention.

In carrying out the process of the present invention, a catalyst can be used. Examples of the catalyst include catalysts used in a known method for producing a compound having a corresponding nitroxide free radical by oxidizing a sterically hindered secondary amine with a peroxide. Preferred catalysts are compounds containing a metal element selected from Group 6 of the Periodic Table Group, such as tungsten and molybdenum. Examples of the compound of tungsten include tungstic acid, phosphotungstic acid, paratungstic acid, and alkali metal salts thereof (sodium salt, potassium salt, etc.).
And molybdenum compounds include, for example, molybdenum acid, molybdenum oxide, molybdenum carbonyl, and alkali metal salts (such as sodium salts and potassium salts) and ammonium salts thereof. Ammonium paratungstate,
Examples include sodium tungstate, phosphotungstic acid, sodium molybdate, molybdenum trioxide, molybdenum hexacarbonyl, and the like.

The amount of the catalyst to be used is generally 0.001 to 0.1% by weight, preferably 0.01 to 0.05% by weight, based on 1 part by weight of the cyclic secondary amine (1).

The manufacturing method of the present invention will be described.
A method of reacting a mixture of the amines (1) and the organic compound having a cyano group while adding a peroxide with stirring. The reaction temperature is generally 0-75 ° C, preferably 40-65 ° C. Cyclic secondary amines (1),
After mixing the organic compound having a cyano group and the peroxide, the mixture can be reacted at the above temperature under stirring. However, the reaction is performed while adding the peroxide as described above. It is preferable because it can be produced in good yield.

The time for adding the peroxide is not particularly limited, but is usually 1 to 10 hours, preferably 3 to 6 hours.
After completion of the addition of the peroxide, the reaction is usually completed by maintaining the above temperature for 1 to 10 hours.

The nitroxide compound (2) can be isolated from the reaction mixture after completion of the reaction by a combination of unit operations such as concentration, extraction, distillation, and recrystallization.

[0027]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Example 1 In a reactor having a capacity of 100 ml, 4.3 g of 2,2,6,6-tetramethylpiperidine, 38.6 g of acetonitrile,
0.21 g of ammonium paratungstate was charged,
Under stirring, 8.8 g of 35% hydrogen peroxide was added dropwise over 3 hours while maintaining the temperature at 50 to 51 ° C., and the mixture was further stirred at the same temperature for 3 hours to carry out a reaction. When the reaction mixture after the reaction was analyzed by gas chromatography, the yield of 2,2,6,6-tetramethylpiperidine-1-oxyl was 93.5% (2,2,6,6-tetramethylpiperidine). Piperidine standard).

Example 2 The procedure of Example 1 was repeated, except that half of acetonitrile (19.3 g) was replaced by 19.3 g of tetrahydrofuran. As a result, the yield of 2,2,6,6-tetramethylpiperidine-1-oxyl was 92.3% (2,2,6,6
-Based on tetramethylpiperidine).

Example 3 In a reactor having a capacity of 100 ml, 8.5 g of 2,2,6,6-tetramethylpiperidine, 25.5 g of acetonitrile,
0.42 g of ammonium paratungstate was charged,
While stirring, the temperature was kept at 50 to 51 ° C., 17.5 g of 35% hydrogen peroxide was added dropwise over 3 hours, and the mixture was further stirred at the same temperature for 3 hours to carry out a reaction. When the reaction mixture after the reaction was analyzed by gas chromatography, the yield of 2,2,6,6-tetramethylpiperidine-1-oxyl was 90.1% (2,2,6,6-tetramethyl Piperidine standard).

Example 4 8.5 g of 2,2,6,6-tetramethylpiperidine, 12.8 g of acetonitrile were placed in a reactor having a capacity of 100 ml.
After charging 12.8 g of methanol and 0.42 g of ammonium paratungstate, 17.5 g of 35% hydrogen peroxide was added dropwise over 3 hours while maintaining the temperature at 50 to 51 ° C. with stirring, and further added at the same temperature for 3 hours. The reaction was continued while stirring for hours. When the reaction mixture after the reaction was analyzed by gas chromatography, the yield of 2,2,6,6-tetramethylpiperidine-1-oxyl was 71.2%.
(Based on 2,2,6,6-tetramethylpiperidine).

Example 5 A reaction was carried out in the same manner as in Example 3 except that ammonium paratungstate was not added. as a result,
The yield of 2,2,6,6-tetramethylpiperidine-1-oxyl was 94.4% (based on 2,2,6,6-tetramethylpiperidine).

Example 6 The amount of hydrogen peroxide was changed to 11.7 g and the dropping time was 2
The reaction was carried out in the same manner as in Example 5 except that the time was changed. As a result, the yield of 2,2,6,6-tetramethylpiperidine-1-oxyl was 93.1% (2,2,6,6
-Based on tetramethylpiperidine).

Comparative Example 1 The procedure of Example 1 was repeated except that the amount of acetonitrile used was reduced to 2.5 g and 36.1 g of methanol was used. As a result, the yield of 2,2,6,6-tetramethylpiperidine-1-oxyl was 52.0% (2,2,6,6-tetramethylpiperidine-1-oxyl).
6,6-tetramethylpiperidine).

Comparative Example 2 A reaction was carried out in the same manner as in Example 1 except that 38.6 g of tetrahydrofuran was used instead of 38.6 g of acetonitrile, hydrogen peroxide was added dropwise, and the mixture was further stirred for 10 hours to carry out the reaction. went. As a result, the yield of 2,2,6,6-tetramethylpiperidine-1-oxyl was 38.5%.
(Based on 2,2,6,6-tetramethylpiperidine).

The conditions and results of the above Examples and Comparative Examples are shown in the following table. The abbreviation TMPPR in the table indicates 2,2,6,6-tetramethylpiperidine, and THF indicates tetrahydrofuran.

[0037]

[Table 1]

Claims (4)

[Claims] 1. General formula (1): (Wherein T represents a methylene group, an ethylene group, an oxygen atom or a methyleneoxy group, and R represents an alkyl group, an aralkyl group, an aryl group, a cycloalkyl group, an alkoxy group, an acyl group, an acyloxy group, an amino group, a hydroxy group. Or R ¹ , R ² , R ³ and R ⁴ are the same or different and each represents an alkyl group or an aryl group, or R ¹ and R ² and / or R ³ and R ⁴ together Represents a tetramethylene group or a pentamethylene group, and n
Is an integer of 0 to 6. Reacting a cyclic secondary amine having steric hindrance represented by the formula (1) with a peroxide in the presence of an organic compound having a cyano group in an amount of at least 1 part by weight based on 1 part by weight of the cyclic secondary amine having steric hindrance. Let be a general formula (2): (Wherein T, R, R ¹ , R ² , R ³ , R ⁴ and n are the same as those described above), wherein an organic compound having a nitroxide free radical represented by the general formula (2) is produced. A method for producing an organic compound having a nitroxide free radical represented by the formula: 2. The method according to claim 1, wherein the reaction is carried out in the presence of a catalyst. 3. The method according to claim 2, wherein the catalyst is a compound containing a metal element belonging to Group 6 of the Periodic Table. 4. The method according to claim 1, wherein the peroxide is hydrogen peroxide.
3. The method according to any one of 3.