JPH0920734A - Production of aminophenol derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a high-purity aminophenol derivative by a simple method. SOLUTION: The method for producing an aminophenol derivative contains (a) a step for reacting a dihydric phenol derivative with a primary amine derivative and obtaining a reaction mixture containing an N-mono-substituted aminophenol derivative, (b) a step for alkylating the reaction mixture containing the N-mono-substituted aminophenol derivative and obtaining a reaction mixture containing an N, N-di-substituted aminophenol derivative, (c) a step for bringing the reaction mixture containing the N,N-di-substituted aminophenol derivative into contact with a base in the presence of water to convert the N,N-di- substituted aminophenol derivative into a water-soluble basic salt and separating water phase containing the basic salt and (d) a step for bringing water phase containing the water-soluble basic salt of the N, N-di-substituted aminophenol derivative into contact with an acid to neutralize the water phase and separating the N,N-di-substituted aminophenol derivative isolated.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing an aminophenol derivative. More specifically, for example,
The present invention relates to a method for producing an aminophenol derivative, which is a useful raw material when producing an electron-donating color forming compound for a recording material (for example, a heat-sensitive recording material, a pressure-sensitive recording material).

[0002]

2. Description of the Related Art Conventionally, a method for producing an aminophenol derivative from a dihydric phenol derivative and an amine derivative has been known (for example, JP-A-48-28429 and JP-A-51-1429). U.S. Pat. No. 237
6112).

A reaction mixture produced from a dihydric phenol derivative and an amine derivative usually contains an unreacted dihydric phenol derivative and a by-product (for example, a phenylenediamine derivative) together with an aminophenol derivative. ing. A method for separating and producing an aminophenol derivative from this reaction mixture has been proposed.

For example, in a method for producing an N-alkylaminophenol derivative by reacting a dihydric phenol derivative with an alkylamine derivative, the reaction mixture is treated with an acid to give an acid salt of the N-alkylaminophenol derivative. The unreacted dihydric phenol derivative is extracted and separated with an organic solvent, the remaining acid salt of the N-alkylaminophenol derivative is neutralized with an alkaline aqueous solution, and the separated organic phase is distilled to obtain N-alkylaminophenol. A method for producing a derivative has been proposed (JP-A-3-202).
No. 48).

According to the production method described in JP-A-3-20248, the unreacted dihydric phenol derivative is separated and removed by the extraction and separation operation with an organic solvent after the acid treatment. The product N, N′-dialkylphenylenediamine derivative is not separated or removed by the extraction / separation operation with an organic solvent after the acid treatment and the subsequent neutralization treatment operation.

Thereafter, the N-alkylaminophenol derivative containing the N, N'-dialkylphenylenediamine derivative is further purified by distillation.
However, it is often difficult to separate and remove the N, N′-dialkylphenylenediamine derivative even by the distillation operation.

In the method of producing an N-alkylaminophenol derivative by reacting a dihydric phenol derivative with an alkylamine derivative, the reaction mixture is treated with an alkali to convert the unreacted dihydric phenol derivative into an alkali salt. After that, the N-alkylaminophenol derivative is extracted and separated with an organic solvent, and the separated organic phase is distilled,
A method for producing an N-alkylaminophenol derivative has been proposed (JP-A-3-20249).

According to the method described in JP-A-3-20249, an unreacted dihydric phenol is present in the organic phase together with the N-alkylaminophenol derivative by the extraction and separation operation with an organic solvent after the alkali treatment. The derivative and the by-product N, N′-dialkylphenylenediamine derivative are mixed. Then, this mixture is purified by distillation. However, the dihydric phenol derivative and / or N, N 'can be obtained by the distillation operation.
It is often difficult to separate and remove the dialkylphenylenediamine derivative.

Generally, N-alkyl-m-aminophenol derivatives are alkylated to give N, N-dialkyl-
2- (4′-N, N-dialkylamino-2′-hydroxy), which is an intermediate for producing a fluorane compound for a recording material, after being led to an m-aminophenol derivative and further reacted with phthalic anhydride. (Phenylcarbonyl) benzoic acid derivative (for example, Japanese Patent Publication No. 2-48537)
Japanese Patent Publication No. 2-48538).

However, the N-alkyl-m-aminophenol derivative produced by the method described in JP-A-3-20248 or JP-A-3-20249, for example, contains N, N'-as impurities. Dialkyl-m-
A phenylenediamine derivative or the like is often mixed.
As a result, the N, N-dialkyl-m-aminophenol derivative produced by alkylating the N-alkyl-m-aminophenol derivative produced by these known methods was added to N, N, N'-tri Alkyl-m-phenylenediamine derivative or / and N, N, N ′, N ′
There is a problem that it is not possible to prevent the tetraalkyl-m-phenylenediamine derivative from being mixed.

Furthermore, N, N, N'-trisubstituted-m-phenylenediamine derivatives or / and N, N, N ',
When an N, N-disubstituted-m-aminophenol derivative containing a large amount of N′-tetra-substituted-m-phenylenediamine derivative is used and a reaction with phthalic anhydride is carried out, the reason is not clear, but the desired product is obtained. It was found that the by-product rhodamine compound is often produced in a large amount together with the 2- (4′-N, N-disubstituted amino-2′-hydroxyphenylcarbonyl) benzoic acid derivative that is .

At present, a method for producing a highly pure aminophenol derivative by a simple method is desired.

[0013]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for producing a highly pure aminophenol derivative by a simple method.

[0014]

Means for Solving the Problems The present inventor has completed the present invention as a result of extensive studies on a method for producing an aminophenol derivative in order to meet the above-mentioned demand.

That is, in the present invention, (a) a step of reacting a dihydric phenol derivative with a primary amine derivative to obtain a reaction mixture containing an N-mono-substituted aminophenol derivative, (b) the reaction mixture and alkylation React the agent,
A step of obtaining a reaction mixture containing the N, N-disubstituted aminophenol derivative, (c) contacting the reaction mixture containing the N, N-disubstituted aminophenol derivative with a base in the presence of water to obtain N, N- A step of separating the di-substituted aminophenol derivative into a water-soluble basic salt and separating an aqueous phase containing the basic salt, and (d) a water-soluble basic salt of the N, N-disubstituted aminophenol derivative. A process for producing an N, N-disubstituted aminophenol derivative, which comprises a step of contacting an aqueous phase containing OH with an acid to separate the N, N-disubstituted aminophenol derivative released. .

Further, N, N obtained by the manufacturing method
The present invention relates to a method for producing a 2- (N, N-disubstituted amino-hydroxyphenylcarbonyl) benzoic acid derivative by reacting a disubstituted aminophenol derivative with phthalic anhydride.

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION The manufacturing method of the present invention will be described in detail below.

[Step (a)] The dihydric phenol derivative according to the present invention is preferably a compound represented by the general formula (1).

[0019]

Embedded image In the compound represented by the general formula (1), X represents a hydrogen atom or an alkyl group, more preferably a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and particularly preferably a hydrogen atom.

Specific examples of the dihydric phenol derivative include:
For example, hydroquinone, resorcin, catechol, 2
-Methyl hydroquinone, 2-ethyl hydroquinone,
4-methylresorcin, 5-methylresorcin, 5-ethylresorcin, 5-n-propylresorcin, 5-isopropylresorcin, 5-n-butylresorcin, 5
-Sec-butylresorcin, 5-tert-butylresorcin, 3-methylcatechol, 4-methylcatechol, 4
-Ethylcatechol, 4-isopropylcatechol, 4
Examples thereof include -n-butylcatechol and 4-tert-butylcatechol, more preferably hydroquinone or resorcin, and particularly preferably resorcin.

As the primary amine derivative according to the present invention,
For example, the compound represented by general formula (2) can be mentioned.

H ₂ N—R ₁ (2) In the compound represented by the general formula (2), R ₁ represents an alkyl group, an alkenyl group, an alkoxyalkyl group, an aryl group or an aralkyl group, more preferably carbon. A chain alkyl group having 1 to 16 carbon atoms, a cycloalkyl group having 5 to 16 carbon atoms, an alkenyl group having 2 to 16 carbon atoms, and 2 to 2 carbon atoms
It represents an alkoxyalkyl group having 16 carbon atoms, an aryl group having 6 to 10 carbon atoms or an aralkyl group having 7 to 10 carbon atoms.

Specific examples of the primary amine derivative include, for example, methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, isobutylamine, sec-butylamine, tert-butylamine,
n-pentylamine, isopentylamine, 2,2-dimethylpropylamine, 1-ethylpropylamine, n
-Hexylamine, 1-methylpentylamine, n-heptylamine, 2-methylhexylamine, 1-ethylpentylamine, n-octylamine, 1,4-dimethylpentylamine, 2-methylheptylamine, 2-ethylhexylamine , N-nonylamine, n-decylamine, n-undecylamine, n-dodecylamine, n
-N such as tetradecylamine and n-hexadecylamine
-Chain alkylamine derivative,

For example, cyclopentylamine, cyclohexylamine, (4'-methylcyclohexyl) amine, cycloheptylamine, cyclooctylamine, cyclodecylamine, cyclotetradecylamine and the like N-
N-alkylamine derivatives such as cycloalkylamine derivatives such as allylamine, β-butenylamine,
N-alkenylamine derivatives such as β-n-pentenylamine, for example, 2-methoxyethylamine, 2-ethoxyethylamine, 2-n-propoxyethylamine, 2
-Isopropoxyethylamine, 2-n-butoxyethylamine, 2-n-pentyloxyethylamine, 2-
n-hexyloxyethylamine, 2-n-octyloxyethylamine, 3-methoxypropylamine, 3-
Ethoxypropylamine, 3-n-propoxypropylamine, 3-isopropoxypropylamine, 3-n-
Butoxypropylamine, 3-isobutoxypropylamine, 3-n-pentyloxypropylamine, 3-n
-N-alkoxyalkylamine derivatives such as hexyloxypropylamine, 3- (2'-ethylhexyloxy) propylamine, 3-n-decyloxypropylamine, 4-methoxybutylamine, 5-ethoxypentylamine, tetrahydrofurfurylamine,

For example, aniline, 3-methylaniline,
N-arylamine derivatives such as 4-methylaniline, 4-ethylaniline and 4-methoxyaniline, for example, N- such as benzylamine, 2-phenylethylamine, 3-phenylpropylamine and 4-phenylbutylamine.
Examples thereof include aralkylamine derivatives. A more preferable primary amine derivative is an N-alkylamine derivative in which R ₁ is an alkyl group in the compound represented by the general formula (2), and an N-chain alkylamine derivative is particularly preferable. N-chain alkylamine derivatives of the numbers 1 to 6 are preferred.

The N-mono-substituted aminophenol derivative produced in step (a) is preferably a compound represented by the general formula (3),

[0027]

Embedded image (In the formula, X and R ₁ have the same meanings as described above.) More preferably, the compound is represented by formula (3-A).

[0028]

Embedded image (In the formula, R ₁ has the same meaning as described above.)

The amount of the primary amine derivative used is not particularly limited, but is generally 0.5 to 2.5 mol, and more preferably, 1 mol of the dihydric phenol derivative.
0.7 to 2.0 mol, particularly preferably 0.8 to 1.5
Is a mole.

The reaction between the dihydric phenol derivative and the primary amine derivative is usually about 110 to 240 ° C, more preferably about 130 to 220 ° C, and particularly preferably 140 to 40 ° C.
It is carried out at a temperature of about 200 ° C.

The reaction between the dihydric phenol derivative and the primary amine derivative is generally preferably carried out under a pressure of from normal pressure to 50 kg / cm ² .

The reaction time depends on various conditions such as reaction temperature and reaction pressure, but is generally about 1 to 30 hours, more preferably about 2 to 20 hours.

The reaction between the dihydric phenol derivative and the primary amine derivative can be carried out in the absence of an organic solvent, but can be carried out in the presence of an organic solvent if desired. As such an organic solvent, any organic solvent inert to the reaction can be used. More preferably, it is an organic solvent which is excellent in solubility of the N-mono-substituted aminophenol derivative produced and is hardly soluble in water.

Specific examples of the organic solvent include, for example, benzene, toluene, o-xylene, m-xylene, p-xylene, ethylbenzene, p-diethylbenzene, 1,
Aromatic hydrocarbon solvents such as 2,4-trimethylbenzene, 1,3,5-trimethylbenzene, tetralin and α-methylnaphthalene, for example, chlorobenzene, o-chlorotoluene, m-chlorotoluene, p-chlorotoluene, o-difluorobenzene, o-dichlorobenzene,
Aromatic halogenated hydrocarbon solvents such as m-dichlorobenzene and p-dichlorobenzene, for example, hydrocarbon solvents such as aliphatic hydrocarbon solvents such as heptane, octane, decane and decalin, such as anisole and diphenyl ether. Examples of the ether solvents include n-hexanol, n-heptanol, n-octanol, 2-ethylhexanol, n-decanol and cyclohexanol.
These organic solvents may be used alone or in combination. Particularly preferable organic solvents are hydrocarbon solvents, and among them, aromatic hydrocarbon solvents are preferable.

The amount of the organic solvent used is not particularly limited and is generally 10% by weight or more with respect to the weight of the dihydric phenol derivative. Use of an excessive amount itself lowers production efficiency and the like. Is caused, preferably 10 to 10,000% by weight, more preferably 2
0-5000% by weight, particularly preferably 50-3000
% By weight.

The reaction between the dihydric phenol derivative and the primary amine derivative can be carried out in the absence of a catalyst (reaction accelerator), but can also be carried out in the presence of a catalyst if desired.

Examples of such catalysts include metals (eg, copper, cobalt, zinc, nickel, magnesium,
Halides of tin, antimony, vanadium, iron, etc.,
Ammonium halide salts of metals (eg, copper, cobalt, nickel, etc.), metals (eg, gallium, silicon,
Zinc, molybdenum, tungsten, antimony, vanadium, iron, aluminum, etc. oxides, metals (eg,
Phosphates of zinc, nickel, etc., organic carboxylic acids (eg, acetic acid, propionic acid, caproic acid, palmitic acid,
Stearic acid, succinic acid, malonic acid, adipic acid, glutaric acid, benzoic acid, phenylacetic acid, naphthoic acid, phthalic acid, etc.), phosphoric acid, polyphosphoric acid, phosphorous acid, phosphorous acid ester (eg, trialkylphosphite, triphenyl) Phosphite) and the like. The amount of the catalyst used is not particularly limited and may be an amount that exerts a desired reaction promoting effect, and is generally about 1 to 30 mol% based on the number of moles of the dihydric phenol derivative. .

The reaction method of the dihydric phenol derivative and the primary amine derivative is not particularly limited, but for example,
If desired, a divalent phenol derivative and a primary amine derivative are collectively inserted into a reaction apparatus in the presence of an organic solvent and / or a catalyst to react, and the divalent phenol derivative is continuously charged with the primary amine derivative, or It is possible to apply a method of reacting while supplying intermittently. Of course, it is needless to say that other modification methods that are possible in process engineering can be applied.

When the primary amine derivative is supplied, it may be supplied neat or as a solution of the organic solvent mentioned in the step (a).

The reaction between the dihydric phenol derivative and the primary amine derivative may be carried out while removing the produced water outside the reaction system.

Since the progress of the reaction can be monitored by an analytical means such as high performance liquid chromatography or gas chromatography, the post-treatment operation can be carried out at a desired reaction rate.

The reaction mixture produced by the reaction of the dihydric phenol derivative and the primary amine derivative generally includes the target N-mono-substituted aminophenol derivative, unreacted dihydric phenol derivative, and by-products. [For example, N, N'-di-substituted phenylenediamine derivatives and the like]
Is included.

When the reaction mixture contains unreacted primary amine derivative, it can be used in the next step (b) without removing the primary amine derivative. It is preferred to remove most of the primary amine derivative out of the reaction system by the method described above and then subject it to the step (b).

When the reaction mixture obtained in the step (a) is subjected to the step (a-1) described later, when unreacted primary amine derivative is contained, for example, a method such as distillation. After the removal of most of the primary amine derivative outside the reaction system, or by using an acid such as hydrochloric acid or sulfuric acid, the pH of the reaction system is adjusted to about 4 to about 9, preferably about 5 to about 5.
After adjusting to about 8, it is preferable to provide to the step (a-1).

When the step (a) is carried out in the presence of a catalyst or / and an organic solvent, the reaction mixture may be subjected to the step (b) after removing the catalyst or / and the organic solvent, Alternatively, the reaction mixture may be used in step (b) without removing the catalyst and organic solvent.

In the production method of the present invention, step (a)
The unreacted dihydric phenol derivative in the reaction mixture produced in the step (d) is separated and removed in the step (d) through the steps (b) and (c). For the purpose of further increasing the concentration, the reaction mixture produced in step (a) is contacted with water before being subjected to step (b), and then the aqueous phase is removed to obtain an N-monosubstituted aminophenol derivative. It is preferred to subject the organic phase containing the to step (b).

Next, the step of bringing the reaction mixture obtained in step (a) into contact with water and then removing the aqueous phase [hereinafter referred to as step (a-1)] will be described.

[Step (a-1)] In the step (a-1),
First, water is contacted with a reaction mixture containing an N-monosubstituted aminophenol derivative. The main purpose of step (a-1) is to remove the unreacted divalent phenol derivative in the reaction mixture.

The amount of water used is not particularly limited as long as it is sufficient to dissolve the dihydric phenol derivative, and the use of an excessive amount itself causes a reduction in production efficiency. Generally, it is preferably 50 to 10000% by weight, more preferably 100 to 5000% by weight, based on the weight of the dihydric phenol derivative.

The water to be used is not particularly limited, but tap water, distilled water or ion-exchanged water can be used, for example. The water may contain an inorganic salt such as sodium chloride, sodium sulfate or potassium sulfate, and the water neutralized in step (d) can be reused. Further, the neutralized water and tap water, distilled water, or ion-exchanged water can be mixed and used. Also, if desired, deoxygenated water or water saturated with an inert gas such as nitrogen gas can be used.

Contact with water is carried out, for example, with hydrochloric acid if the primary amine derivative used in step (a) remains.
The pH of the aqueous phase is adjusted to about 4 to about 9, more preferably about 5 to about 8 with an acid such as sulfuric acid.

It is preferable to carry out the step (a-1) in the presence of an organic solvent in order to improve the separation efficiency between the organic phase containing the N-monosubstituted aminophenol derivative and the aqueous phase. That is. As such an organic solvent, N-
An organic solvent which is excellent in solubility of the mono-substituted aminophenol derivative and hardly soluble in water is preferable. Specific examples of the organic solvent include, for example, benzene, toluene, o-xylene,
m-xylene, p-xylene, ethylbenzene, p-diethylbenzene, 1,2,4-trimethylbenzene,
Aromatic hydrocarbon solvents such as 1,3,5-trimethylbenzene, tetralin and α-methylnaphthalene, for example,
Chlorobenzene, o-chlorotoluene, m-chlorotoluene, p-chlorotoluene, o-difluorobenzene,
Aromatic halogenated hydrocarbon solvents such as o-dichlorobenzene, m-dichlorobenzene and p-dichlorobenzene, for example, aliphatic hydrocarbon solvents such as pentane, hexane, heptane, octane, decane, cyclohexane, decalin, etc. , Dichloromethane, chloroform, tetrachloromethane, tetrachloroethylene, 1,
2-dichloroethane, 1,1,1-trichloroethane,
Hydrocarbon-based solvents such as aliphatic halogenated hydrocarbon-based solvents such as 1,1,2-trichloroethane and 1,1,2,2-tetrachloroethane,

For example, a ketone solvent such as methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone,
For example, diethyl ether, diisopropyl ether,
Ether-based solvents such as di-n-butyl ether, anisole and diphenyl ether, for example, ester-based solvents such as ethyl acetate, butyl acetate and amyl acetate, for example n
Examples thereof include alcohol solvents such as -hexanol, n-heptanol, n-octanol, 2-ethylhexanol, n-decanol, and cyclohexanol. These organic solvents may be used alone,
Alternatively, a plurality may be used in combination. More preferred organic solvent is
A hydrocarbon-based solvent, particularly preferably an aromatic hydrocarbon-based solvent or an aliphatic hydrocarbon-based solvent, among which,
Aromatic hydrocarbon solvents are preferred.

The amount of the organic solvent used is not particularly limited, and generally 10% by weight or more based on the weight of the N-monosubstituted aminophenol derivative,
The use of an excessively large amount itself causes a reduction in production efficiency and the like, and is preferably 10 to 10000% by weight, more preferably 20 to 5000% by weight.

It is also preferable to carry out step (a-1) in the presence of a reducing agent such as sodium sulfite or sodium hydrosulfite.

The method of contacting the reaction mixture containing the N-mono-substituted aminophenol derivative with water is not particularly limited, but, for example, it may contain the N-mono-substituted aminophenol derivative in the presence of an organic solvent, if desired. A method of charging the reaction mixture and water all together, a method of mixing the reaction mixture containing the N-mono-substituted aminophenol derivative and water in a parallel flow, a reaction mixture containing the N-mono-substituted aminophenol derivative A method of mixing water in a countercurrent, or the like can be applied. Furthermore, a method combining these methods can be applied. Of course, it is needless to say that other modification methods that are possible in process engineering can be applied.

When the reaction mixture containing the N-monosubstituted aminophenol derivative and water are brought into contact with each other in order to obtain a desired effect, for example, in a batch system (batch system),
The contact operation can be performed multiple times. Further, the dihydric phenol derivative extracted in the aqueous phase can be recovered and reused in the step (a).

After contact with water, the organic phase containing the N-monosubstituted aminophenol derivative is separated from the aqueous phase.
The separation method is not particularly limited,
It can be carried out by a known method, for example, a filtration operation or a liquid separation operation.

The step (a-1) is usually carried out at a temperature of about 0 to 100 ° C, preferably about 20 to 80 ° C.

When the step (a-1) is carried out in the presence of an organic solvent, the organic solvent is removed from the organic phase containing the N-monosubstituted aminophenol derivative after separation from the aqueous phase, and It may be used in the step (b), or the organic phase (organic solvent solution) containing the N-monosubstituted aminophenol derivative may be used in the step (b) without removing the organic solvent.

[Step (b)] In step (b), the N-monosubstituted aminophenol derivative is alkylated to give N, N-
A disubstituted aminophenol derivative is prepared.

The method for carrying out the alkylation is not particularly limited, and a method and a reagent capable of N-alkylating the N-monosubstituted aminophenol derivative can be arbitrarily selected and carried out. .

As a preferable alkylation method, for example, a method of reacting an N-monosubstituted aminophenol derivative with an alkylating agent [hereinafter referred to as (bA) method],
Alternatively, a method of reductively alkylating an N-mono-substituted aminophenol derivative [hereinafter referred to as (b-B) method] can be mentioned, and a method of acting an alkylating agent is particularly preferable.

[(B-A) Method] The alkylating agent used in the (b-A) method is not particularly limited, and N is N.
The mono-substituted aminophenol derivative can be selected from any compound as long as it is a compound having the ability to N-alkylate. Examples of preferable alkylating agents include compounds represented by general formula (4-A) or general formula (4-B).

R ₂ —Z (4-A) (R ₂ O) ₂ SO ₂ (4-B)

General formula (4-A) and general formula (4-B)
In the compound represented by, R ₂ represents an alkyl group,
It is preferably an alkyl group having 1 to 16 carbon atoms, more preferably an alkyl group having 1 to 10 carbon atoms, and particularly preferably an alkyl group having 1 to 6 carbon atoms.

In the compound represented by formula (4-A), Z represents a leaving group. The leaving group is not particularly limited, and may be selected from any group as long as it is a group that leaves upon alkylation when the N-mono-substituted aminophenol derivative is subjected to alkylation. it can. As the leaving group, for example, a chlorine atom, a bromine atom, a halogen atom such as an iodine atom, an arylsulfonyloxy group,
Examples thereof include a substituted sulfonyloxy group such as an alkylsulfonyloxy group.

Specific examples of the alkylating agent include, for example,
Methyl bromide, methyl iodide, ethyl bromide,
Ethyl iodide, n-propyl chloride, n-propyl bromide, iodo-n-propyl, isopropyl chloride, isopropyl bromide, n-butyl chloride, n-butyl bromide, i-n-butyl, isobutyl chloride, isobutyl bromide, sec-Butyl bromide, tert-butyl chloride, n-pentyl bromide, isopentyl bromide, 2,2-dimethylpropyl bromide, 1-ethylpropyl bromide, n-hexyl bromide, 1-methylpentyl bromide, n-heptyl bromide, 2 -Methylhexyl bromide, 1-ethylpentyl bromide, n-octyl bromide, 1,4-dimethylpentyl bromide, 2-methylheptyl bromide, 2-ethylhexyl bromide, n-nonyl Bromide, n-decyl bromide, n-undecyl bromide, n-dodecyl bromide, n-tetradecyl bromide, n-hexadecyl bromide, cyclopentyl bromide, cyclohexyl chloride, cyclohexyl bromide, (4'-
Methyl cyclohexyl) bromide, cycloheptyl bromide, cyclooctyl bromide, cyclodecyl bromide, cyclohexylmethyl bromide, 2-cyclohexylethyl bromide, and other halogenated alkyl derivatives,

For example, benzenesulfonic acid methyl ester, o-toluenesulfonic acid methyl ester, p-
Toluenesulfonic acid methyl ester, β-naphthalenesulfonic acid methyl ester, benzenesulfonic acid ethyl ester, o-toluenesulfonic acid ethyl ester, p-toluenesulfonic acid ethyl ester, p-toluenesulfonic acid-n-propyl ester, p-toluene Isopropyl sulfonic acid, benzenesulfonic acid-n-butyl ester, o-toluenesulfonic acid-n-butyl ester, p-toluenesulfonic acid-n-butyl ester, p-toluenesulfonic acid isobutyl ester, p-toluenesulfonic acid- sec-butyl ester, p-toluenesulfonic acid-n-pentyl ester, p-toluenesulfonic acid isopentyl ester, p-toluenesulfonic acid-2,2-dimethylpropyl ester, - toluenesulfonic acid 1-ethylpropyl ester,

Benzenesulfonic acid-n-hexyl ester, p-toluenesulfonic acid-n-hexyl ester, p-toluenesulfonic acid-1-methylpentyl ester, p-toluenesulfonic acid-n-heptyl ester, p-toluenesulfone Acid-2-methylhexyl ester, p-toluenesulfonic acid-1-ethylpentyl ester, p-toluenesulfonic acid-n-octyl ester, p-toluenesulfonic acid-1,4-dimethylpentyl ester, p-toluenesulfonic acid -2
-Methylheptyl ester, p-toluenesulfonic acid-2-ethylhexyl ester, p-toluenesulfonic acid-n-nonyl ester, p-toluenesulfonic acid-n-decyl ester, p-toluenesulfonic acid-n
-Undecyl ester, p-toluenesulfonic acid-n
-Dodecyl ester, p-toluenesulfonic acid-n-
Tetradecyl ester, p-toluenesulfonic acid-n
-Hexadecyl ester,

P-Toluenesulfonic acid cyclopentyl ester, p-toluenesulfonic acid cyclohexyl ester, p-toluenesulfonic acid- (4'-methylcyclohexyl) ester, p-toluenesulfonic acid cycloheptyl ester, p-toluenesulfonic acid cyclooctyl ester. Ester, p-toluenesulfonic acid cyclodecyl ester, p-toluenesulfonic acid cyclohexylmethyl ester, p-toluenesulfonic acid- (2
-Cyclohexylethyl) ester or the like aryl sulfonic acid alkyl ester derivative,

For example, methanesulfonic acid methyl ester, ethanesulfonic acid methyl ester, n-butanesulfonic acid methyl ester, n-hexanesulfonic acid methyl ester, methanesulfonic acid ethyl ester, ethanesulfonic acid ethyl ester, methanesulfonic acid- n-propyl ester, methanesulfonic acid isopropyl ester, methanesulfonic acid-n-butyl ester, ethanesulfonic acid-n-butyl ester,
Methanesulfonic acid isobutyl ester, methanesulfonic acid-sec-butyl ester, methanesulfonic acid-
n-Pentyl ester, methanesulfonic acid isopentyl ester, methanesulfonic acid-2,2-dimethylpropyl ester, methanesulfonic acid-1-ethylpropyl ester, methanesulfonic acid-n-hexyl ester, methanesulfonic acid-1-methyl Pentyl ester, methanesulfonic acid-n-heptyl ester, p-
Toluene sulfonic acid-2-methylhexyl ester,
p-toluenesulfonic acid-1-ethylpentyl ester, methanesulfonic acid-n-octyl ester, methanesulfonic acid-2-ethylhexyl ester, methanesulfonic acid-n-decyl ester, methanesulfonic acid-n-dodecyl ester, methanesulfone Acid-n-
Hexadecyl ester,

Methanesulphonic acid cyclopentyl ester, methanesulphonic acid cyclohexyl ester, ethanesulphonic acid cyclohexyl ester, methanesulphonic acid- (4'-methylcyclohexyl) ester, methanesulphonic acid cycloheptyl ester, methanesulphonic acid cyclooctyl ester, methanesulphone Alkyl sulfonic acid alkyl ester derivatives such as acid cyclodecyl ester, methanesulfonic acid cyclohexylmethyl ester, methanesulfonic acid- (2-cyclohexylethyl) ester,

Examples thereof include dimethylsulfate, diethylsulfate, di-n-propylsulfate, diisopropylsulfate, di-n-butylsulfate and other dialkyl sulfate derivatives. These alkylating agents may be used alone. For example, in the case of the same alkyl group, a plurality of alkylating agents of different types are used in combination (for example, n-butyl bromide and p-toluenesulfonic acid-n. -Butyl ester may be used together).

The amount of the alkylating agent used is not particularly limited, and is generally 0.8 to 3.0 mol, more preferably 0.9 to 3.0 mol, based on 1 mol of the N-monosubstituted aminophenol derivative. 2.0 mol, particularly preferably 1.0 to
1.5 mol.

The reaction between the N-monosubstituted aminophenol derivative and the alkylating agent is usually carried out at a temperature of about 0 to 200 ° C, more preferably about 20 to 180 ° C.

The reaction between the N-monosubstituted aminophenol derivative and the alkylating agent is generally from atmospheric pressure to 50 kg / cm ^2.
Preference is given to working under moderate pressure.

The reaction time depends on various conditions such as reaction temperature and reaction pressure, but is generally about 30 minutes to 20 hours, more preferably about 1 to 15 hours.

The reaction between the N-monosubstituted aminophenol derivative and the alkylating agent can be carried out in the absence of water or an organic solvent, but is preferably carried out in the presence of water or an organic solvent. As such an organic solvent, any organic solvent inert to the reaction can be used.

Specific examples of the organic solvent include benzene, toluene, o-xylene, m-xylene, p-xylene, ethylbenzene, p-diethylbenzene, 1, and the like.
Aromatic hydrocarbon solvents such as 2,4-trimethylbenzene, 1,3,5-trimethylbenzene, tetralin and α-methylnaphthalene, for example, chlorobenzene, o-chlorotoluene, m-chlorotoluene, p-chlorotoluene, o-difluorobenzene, o-dichlorobenzene,
Aromatic halogenated hydrocarbon solvents such as m-dichlorobenzene and p-dichlorobenzene, for example, aliphatic hydrocarbon solvents such as pentane, hexane, heptane, octane, decane, cyclohexane and decalin, such as dichloromethane and chloroform. Tetrachloromethane, tetrachloroethylene, 1,2-dichloroethane, 1,
Hydrocarbon-based solvents such as aliphatic halogenated hydrocarbon-based solvents such as 1,1-trichloroethane, 1,1,2-trichloroethane and 1,1,2,2-tetrachloroethane,

For example, acetone, methyl ethyl ketone,
Methyl isobutyl ketone, a ketone solvent such as cyclohexanone, for example, an ether solvent such as diethyl ether, diisopropyl ether, di-n-butyl ether, anisole, diphenyl ether, tetrahydrofuran, dioxane, for example, ethyl acetate, butyl acetate,
Ester type solvents such as amyl acetate, for example, methanol, ethanol, n-propanol, isopropanol, n-butanol, n-pentanol, n-hexanol, n-octanol, 2-ethylhexanol, cyclohexanol, methyl cellosolve, ethyl cellosolve. , Alcohol solvents such as ethylene glycol, propylene glycol, glycerol,

For example, acetonitrile, N, N-dimethylformamide, N, N-dimethylacetamide, N-
Examples thereof include aprotic polar solvents such as methyl-2-pyrrolidone, N, N′-dimethyl-2-imidazolidinone, dimethylsulfoxide, and sulfolane. These organic solvents may be used alone or in combination of two or more, and may also be used in combination with water.

The amount of water or / and the organic solvent used is not particularly limited, and generally 10% by weight based on the weight of the N-monosubstituted aminophenol derivative.
It is sufficient if the above is satisfied, and use of an excessive amount itself causes only a decrease in production efficiency, and preferably 10 to 100.
The amount is 00% by weight, more preferably 20 to 5000% by weight.

The reaction between the N-mono-substituted aminophenol derivative and the alkylating agent is further carried out by a phase transfer catalyst such as benzyltrialkylammonium chloride or tetra-n-butylammonium bromide, and further potassium iodide or sodium iodide. It can also be carried out in the presence of

The reaction method of the N-mono-substituted aminophenol derivative and the alkylating agent is not particularly limited, but, for example, if desired, in the presence of water or / and an organic solvent, the N-mono-substituted aminophenol derivative and It is possible to apply a method in which an alkylating agent is charged all at once into a reaction apparatus and reacted, a method in which an alkylating agent is reacted with an N-monosubstituted aminophenol derivative continuously or intermittently, and the like. it can. Of course, it is needless to say that other modification methods that are possible in process engineering can be applied.

When the alkylating agent is supplied, it may be supplied neat or as a solution of the organic solvent mentioned in the method (b-A).

Since the progress of the reaction can be monitored by an analytical means such as high performance liquid chromatography or gas chromatography, the post-treatment operation can be carried out at a desired reaction rate.

The reaction of the N-monosubstituted aminophenol derivative with the alkylating agent produces a salt of the N, N-disubstituted aminophenol derivative. By reacting the salt of the N, N-disubstituted aminophenol derivative with a base (deoxidizing agent), the liberated N, N-disubstituted aminophenol derivative can be obtained.

Examples of the base include lithium hydroxide, potassium hydroxide, sodium hydroxide, potassium carbonate,
Alkali metal bases such as sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, for example, inorganic bases such as calcium hydroxide, magnesium hydroxide, calcium carbonate, alkaline earth metal bases such as magnesium oxide, for example, ammonia, methylamine, Organic amine bases such as ethylamine, propylamine, butylamine, dimethylamine, diethylamine, triethylamine, pyridine, N, N-dimethylaniline and morpholine, for example, organic bases such as alkali metal bases of organic carboxylic acids such as sodium acetate and potassium acetate. And so on. These bases may be used alone or in combination. More preferable bases are inorganic bases or organic amine bases, particularly preferably inorganic bases, and among them, alkali metal bases are preferable.

The base may be used neat (solid, liquid or gaseous state) or in the form of an aqueous solution. When used in the form of an aqueous solution, the concentration of the base is not particularly limited, and generally 5 to 80.
It is preferably used as an aqueous solution of about wt%.

The amount of the base used is not particularly limited, and may be an amount sufficient to deoxidize the salt of the N, N-disubstituted aminophenol derivative and convert it into the N, N-disubstituted aminophenol derivative. Generally, an equivalent amount, preferably about 0.9 to 1.5 equivalents, more preferably 1.0 to 1.2 equivalents, relative to the salt of the N, N-disubstituted aminophenol derivative. Use to some extent.

The base can appropriately act on the reaction mixture in which the N-monosubstituted aminophenol derivative and the alkylating agent are reacting. Moreover,
It is also possible to act a base after the reaction of the N-monosubstituted aminophenol derivative and the alkylating agent.

The action of the base on the salt of the N, N-disubstituted aminophenol derivative is usually carried out at a temperature of about 0 to 100 ° C, preferably about 20 to 80 ° C.

When the base is allowed to act on the salt of the N, N-disubstituted aminophenol derivative obtained after the reaction between the N-monosubstituted aminophenol derivative and the alkylating agent, unreacted or / and The alkylating agent present in excess is separated by distillation or extraction with an organic solvent (for example, hexane, heptane, octane, toluene, xylene, di-n-butyl ether, etc.), separated and removed from the reaction system, and then the base is reacted. Preferably.

When the method (bA) is carried out in the presence of an organic solvent, a base can be allowed to act without removing the organic solvent, and a base can be allowed to act after the organic solvent is removed. You can also

For example, when an aqueous solution of a base is allowed to act on a salt of an N, N-disubstituted aminophenol derivative in the presence of an organic solvent such as an aromatic hydrocarbon solvent or an aliphatic hydrocarbon solvent. In particular, the liberated N, N-disubstituted aminophenol derivative is extracted in an organic solvent and separated from the aqueous phase. Furthermore, the extracted N, N-disubstituted aminophenol derivative can be used in the next step (c) in a state of an organic solvent solution without removing the organic solvent.

[(B-B) Method] The reductive alkylation of the (b-B) method means to react an N-monosubstituted aminophenol derivative with an aldehyde derivative in the presence of hydrogen and a reducing catalyst in an organic solvent. And N-alkylation.

The aldehyde derivative is not particularly limited, but the compound represented by the general formula (5) is preferable.

R ₃ —CHO (5) In the compound represented by the general formula (5), R ₃ represents a hydrogen atom or an alkyl group, preferably a hydrogen atom or an alkyl group having 1 to 16 carbon atoms, It is more preferably a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and particularly preferably a hydrogen atom or an alkyl group having 1 to 6 carbon atoms.

Specific examples of the aldehyde derivative include formaldehyde, acetaldehyde, propylaldehyde, n-butyraldehyde, isobutyraldehyde, n-pentylaldehyde, isopentylaldehyde, n-hexylaldehyde, n-heptylaldehyde, n-octyl. Aldehyde, n-nonyl aldehyde,
n-decyl aldehyde, n-dodecyl aldehyde, n-
Examples thereof include tetradecyl aldehyde, n-hexadecyl aldehyde, cyclopentyl aldehyde, cyclohexyl aldehyde, cycloheptyl aldehyde and cyclooctyl aldehyde.

The amount of the aldehyde derivative used is not particularly limited, but is generally 0.9 to 2.0 mol, and more preferably 1.0 to 2.0 mol, based on 1 mol of the N-monosubstituted aminophenol derivative. 1.5 mol, particularly preferably,
It is 1.0 to 1.2 mol.

As the reduction catalyst used for the reductive alkylation, for example, a metal of Group VIII of the periodic table such as Pt, Pd, Rh, Co, Ni and Ru is supported on activated carbon, alumina, barium sulfate and the like. Examples thereof include those in which Pt is supported on activated carbon. The amount of the reducing catalyst used is not particularly limited, and may be any amount that exerts a catalytic effect, and is generally about 0.1 to 20% by weight based on the weight of the N-monosubstituted aminophenol derivative. , And more preferably about 0.5 to 10% by weight.

Specific examples of the organic solvent include aromatic hydrocarbon solvents such as benzene, toluene, o-xylene, m-xylene and p-xylene, such as methanol, ethanol, n-propanol, isopropanol and n. -Alcoholic solvents such as butanol, isobutanol, n-pentanol, n-hexanol, cyclohexanol, methyl cellosolve, ethyl cellosolve, ethylene glycol, propylene glycol, eg
Examples thereof include ester solvents such as ethyl acetate, butyl acetate and amyl acetate. These organic solvents are
They may be used alone or in combination. A particularly preferable organic solvent is an alcohol solvent.

The amount of the organic solvent used is not particularly limited, and the use of an excessive amount itself causes a reduction in production efficiency and the like, and generally, relative to the weight of the N-monosubstituted aminophenol derivative, It is about 50 to 10000% by weight, more preferably about 100 to 5000% by weight.

The amount of hydrogen involved in the reaction is a theoretical amount, and 1 mol of hydrogen is used for the reaction per 1 mol of N-monosubstituted aminophenol derivative, but hydrogen is excessively present in the reaction system. However, it does not adversely affect the reaction, for example, by monitoring the consumption of hydrogen,
Since the progress of the reaction can be known, the reaction can be carried out in the presence of excess hydrogen.

The reductive alkylation reaction is generally carried out at atmospheric pressure to 5
It is carried out under a pressure of about 0 kg / cm ² , preferably in a hydrogen atmosphere.

The reaction is generally carried out at a temperature of about 0 to 100 ° C, more preferably about 20 to 80 ° C.

In the reductive alkylation using the N-monosubstituted aminophenol derivative and the aldehyde derivative, further, for example, acetic acid, propionic acid, butyric acid, benzoic acid,
It can also be carried out in the presence of an organic carboxylic acid derivative such as oxalic acid, succinic acid, malonic acid and maleic acid, for example, a trialkylamine such as trimethylamine, triethylamine and tributylamine.

The method of reductively alkylating the N-monosubstituted aminophenol derivative is not particularly limited, but, for example, in a hydrogen atmosphere, a mixture of the N-monosubstituted aminophenol derivative, the reducing catalyst and the organic solvent is added to the mixture. Method of reacting by continuously or intermittently supplying aldehyde derivative, method of reacting, N-mono-substituted aminophenol derivative, reducing catalyst, hydrogen and aldehyde derivative are continuously or intermittently supplied to a mixture of organic solvents. , Reaction method, etc. can be applied. Of course, it is needless to say that other modification methods that are possible in process engineering can be applied.

When supplying the aldehyde derivative, the aldehyde derivative may be supplied neat or as a solution of the organic solvent mentioned in the method (b-B). The supply time of the aldehyde derivative is not particularly limited, and is generally about 10 minutes to 5 hours.

Since the progress of the reaction can be monitored by an analytical means such as high performance liquid chromatography or gas chromatography, the post-treatment operation can be carried out at a desired reaction rate.

Generally, after the reaction, the reduction catalyst is filtered and separated from the reaction mixture. The separated reduction catalyst is (b-
B) Can be reused in the law.

The N, N-disubstituted aminophenol derivative can be isolated by distilling off the unreacted aldehyde compound and the organic solvent from the filtrate.

The N, N-disubstituted aminophenol derivative produced by alkylating the N-monosubstituted aminophenol is preferably a compound represented by the general formula (6):

[0115]

Embedded image (In the formula, X and R ₁ have the same meanings as described above, and R ₄ is R
₂ or -CH ₂ R ₃ ) is more preferable, and the compound represented by formula (6-A) is more preferable.

[0116]

Embedded image (In the formula, R ₁ represents the same meaning as described above, and R ₄ represents R ₂ or —CH ₂ R _3. )

[Step (c)] In step (c), first,
The reaction mixture containing the N, N-disubstituted aminophenol derivative (organic phase) and the base are contacted in the presence of water,
The N, N-disubstituted aminophenol derivative is a water-soluble basic salt.

Examples of the base include alkali metal bases such as lithium hydroxide, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, potassium hydrogencarbonate and sodium hydrogencarbonate, and alkaline earth bases such as calcium hydroxide. Examples thereof include inorganic bases such as metal bases, and organic bases such as ammonia, methylamine, ethylamine, propylamine, butylamine, dimethylamine, diethylamine, triethylamine, morpholine. These bases may be used alone or in combination. More preferable bases are inorganic bases, particularly preferably alkali metal bases, and among them, sodium hydroxide is preferable.

The base may be used neat (solid, liquid or gaseous state) or in the form of an aqueous solution. When used in the form of an aqueous solution, the concentration of the base is not particularly limited, and generally 5 to 80.
It is preferably used as an aqueous solution of about wt%.

The amount of the base used may be an amount sufficient to convert the N, N-disubstituted aminophenol derivative into a water-soluble basic salt, and is generally used with respect to the N, N-disubstituted aminophenol derivative. It is sufficient to use at least equivalent amount, and excessive use itself causes only a decrease in production efficiency and the like, preferably about 1.0 to 1.5 equivalents, more preferably 1.0 to 1.2 equivalents. Use about equivalent amount.

If the mixture containing the N, N-disubstituted aminophenol derivative used in step (c) contains an unreacted dihydric phenol derivative, 2
It is preferable to make the dihydric phenol derivative water-soluble basic by further using an equivalent amount of a base with respect to the dihydric phenol derivative.

The amount of water used is not particularly limited, and the water-soluble basic salt of the N, N-disubstituted aminophenol derivative may be used in an amount sufficient to dissolve it, and an excessive amount should be used. As such, it merely causes a decrease in production efficiency and the like, and is generally about 50 to 10000% by weight, more preferably about 100 to 5000% by weight, based on the weight of the N, N-disubstituted aminophenol derivative.

The water to be used is not particularly limited, but tap water, distilled water or ion-exchanged water can be used, for example. The water may contain an inorganic salt such as sodium chloride, sodium sulfate and potassium sulfate. Also, if desired, deoxygenated water or water saturated with an inert gas such as nitrogen gas can be used.

The amount of water used includes the amount of water of the basic aqueous solution when the base is used in the form of an aqueous solution.

It is preferable to carry out step (c) in the presence of an organic solvent in order to improve production efficiency and the like. As such an organic solvent, an organic solvent that is sparingly soluble in water is preferable, and the organic solvent mentioned in the step (b-1) can be exemplified as a specific example. A hydrocarbon solvent is more preferable, an aromatic hydrocarbon solvent or an aliphatic hydrocarbon solvent is particularly preferable, and an aromatic hydrocarbon solvent is particularly preferable.

The amount of the organic solvent used is not particularly limited and is generally 10% by weight or more based on the weight of the N, N-disubstituted aminophenol derivative. It only causes a decrease in production efficiency, and preferably 10 to 10000% by weight,
More preferably, it is 20 to 5000% by weight.

It is also preferable to carry out step (c) in the presence of a reducing agent such as sodium sulfite or sodium hydrosulfite.

The method of contacting the organic phase containing the N, N-disubstituted aminophenol derivative with a base in the presence of water is not particularly limited, but, for example, if desired, in the presence of an organic solvent, N, N -A method in which an organic phase containing a di-substituted aminophenol derivative, a base and water are collectively charged and mixed, an organic phase containing an N, N-di-substituted aminophenol derivative, and a basicity consisting of a base and water Applying a method of mixing the aqueous solution in parallel flow, a method of mixing the organic phase containing the N, N-disubstituted aminophenol derivative and a basic aqueous solution consisting of a base and water in countercurrent, etc. You can Furthermore, a method combining these methods can be applied. Of course, it is needless to say that other modification methods that are possible in process engineering can be applied.

The contact of the organic phase containing the N, N-disubstituted aminophenol derivative with a base in the presence of water is carried out in order to obtain a desired effect, for example, in a batch system.
The contact operation can be performed multiple times.

The aqueous phase containing the water-soluble basic salt of the N, N-disubstituted aminophenol derivative is separated from the organic phase. The separation method is not particularly limited, and a known method such as liquid separation operation can be used.

Step (c) is usually about 0 to 100 ° C.,
It is preferably carried out at a temperature of about 20 to 80 ° C.

When step (c) is carried out in the presence of an organic solvent, the organic solvent is, after separation with an aqueous phase containing a water-soluble basic salt of an N, N-disubstituted aminophenol derivative, It can be reused in the step (a-1) or / and the step (c) and the like. Furthermore, the organic solvent is purified by a method such as distillation, and then the step (a-1) or / and the step (c). ) Etc. can be reused.

[Step (d)] In step (d), first,
An acid is contacted with an aqueous phase containing a water-soluble basic salt of an N, N-disubstituted aminophenol derivative to neutralize the acid.

The acid is not particularly limited, but an acid capable of neutralizing a water-soluble basic salt of an N, N-disubstituted aminophenol derivative and converting it into an N, N-disubstituted aminophenol derivative. If so, it can be used arbitrarily.

Specific examples of the acid include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, p-toluenesulfonic acid, methanesulfonic acid, acetic acid and the like. These acids may be used alone or in combination of two or more.

The acid may be used neat or in the form of an aqueous solution. When used in the form of an aqueous solution, the concentration of the acid is not particularly limited and is generally used as an aqueous solution of about 5 to 80% by weight.

Generally, the pH of the aqueous phase is adjusted to about 4 to about 9, preferably about 5 by contacting the acid with an aqueous phase containing a water-soluble basic salt of an N, N-disubstituted aminophenol derivative.
The basic salt can be liberated (converted) to an N, N-disubstituted aminophenol derivative by adjusting the amount to about 8.

The amount of the acid used is such that the water-soluble basic salt of the N, N-disubstituted aminophenol derivative is neutralized and N, N-
It may be an amount sufficient for conversion into a di-substituted aminophenol derivative, and is generally equivalent to the basic salt, preferably 1.0 to 1.5 equivalents, more preferably 1 equivalent. Use about 0 to 1.2 equivalents.

It is preferable to carry out step (d) in the presence of an organic solvent in order to improve production efficiency and the like. As such an organic solvent, an organic solvent which is excellent in solubility of the N, N-disubstituted aminophenol derivative and hardly soluble in water is preferable, and for example, the organic solvent mentioned in the step (a-1) is exemplified as a specific example. can do. A more preferable organic solvent is a hydrocarbon solvent, particularly preferably an aromatic hydrocarbon solvent or an aliphatic hydrocarbon solvent, and among them, an aromatic hydrocarbon solvent is preferable.

The amount of the organic solvent used is not particularly limited, and generally 10% by weight or more based on the weight of the N, N-disubstituted aminophenol derivative is sufficient. It only causes a decrease in production efficiency, and preferably 10 to 10000% by weight,
More preferably, it is 20 to 5000% by weight.

The acid is contacted with an aqueous phase containing a water-soluble basic salt of an N, N-disubstituted aminophenol derivative,
The method of neutralization is not particularly limited, but for example, in the presence of an organic solvent, an acid is supplied to an aqueous phase containing a water-soluble basic salt of an N, N-disubstituted aminophenol derivative, if desired. , A method of mixing and neutralizing, a method of mixing and neutralizing the aqueous phase containing the water-soluble basic salt of the N, N-disubstituted aminophenol derivative and the acid in a cocurrent manner, N, A method in which an aqueous phase containing a water-soluble basic salt of an N-disubstituted aminophenol derivative and an acid are countercurrently mixed and neutralized can be applied. Furthermore, a method combining these methods can be applied. Of course, it is needless to say that other modification methods that are possible in process engineering can be applied.

Upon neutralization, the liberated N, N-disubstituted aminophenol derivative is separated from the aqueous phase. The separation method is not particularly limited, and a known method such as filtration operation or liquid separation operation can be used.

Step (d) is usually about 0 to 100 ° C.,
It is preferably carried out at a temperature of about 20 to 80 ° C.
The separated N, N-disubstituted aminophenol derivative may be further washed with water, if desired.

The N, N-disubstituted aminophenol derivative produced by the method of the present invention has a practically sufficient purity, but if desired, it may be subjected to a purification operation such as recrystallization or / and distillation. Good.

When step (d) is carried out in the presence of an organic solvent, the N, N-disubstituted aminophenol derivative should be subjected to the desired reaction in the state of an organic solvent solution without removing the organic solvent. You can

As described above, the N, N-disubstituted aminophenol derivative produced by the method of the present invention contains the N, N, N'-trisubstituted phenylenediamine derivative or / and N, N, N 'as impurities. It contains almost no N'-tetra-substituted phenylenediamine derivative (usually 2
Wt% or less). When the N, N-disubstituted aminophenol derivative is reacted with phthalic anhydride to produce 2- (N, N-disubstituted amino-hydroxyphenylcarbonyl) benzoic acid, the reason is not clear, but It was found to be low in products (eg rhodamine derivatives).

N, N- used for reaction with phthalic anhydride
As the di-substituted aminophenol derivative, preferably,
It is a compound represented by the general formula (6), more preferably a compound represented by the general formula (6-A).

As the 2- (N, N-disubstituted amino-hydroxyphenylcarbonyl) benzoic acid derivative,
Preferably, the compound represented by the general formula (7) is

[0149]

[Chemical 6] (In the formula, X, R ₁ and R ₄ have the same meanings as described above.)

More preferred is a compound represented by the general formula (7-A) which is 2- (4'-N, N-disubstituted amino-2'-hydroxyphenylcarbonyl) benzoic acid.

[0151]

Embedded image (In the formula, R ₁ and R ₄ have the same meanings as described above.)

The amount of phthalic anhydride used is not particularly limited, but is usually about 0.8 to 3.0 mol, and more preferably about 1 mol of N, N-disubstituted aminophenol derivative. , About 1.0 to 2.0 mol.

The reaction between the N, N-disubstituted aminophenol derivative and phthalic anhydride is usually about 40 to 180 ° C, more preferably about 50 to 150 ° C, and particularly preferably
It is carried out at a temperature of about 60 to 130 ° C.

The reaction between the N, N-disubstituted aminophenol derivative and phthalic anhydride can be usually carried out under normal pressure, but if desired, it can also be carried out under pressure up to about 50 kg / cm ^2. .

While the reaction time depends on various conditions such as reaction temperature and reaction pressure, it is generally about 1 to 40 hours, more preferably about 2 to 30 hours.

The reaction of the N, N-disubstituted aminophenol derivative and phthalic anhydride can be carried out in the absence of an organic solvent, but is preferably carried out in the presence of an organic solvent. As such an organic solvent, any organic solvent that is inert to the reaction can be used. Specific examples of the organic solvent include, for example, benzene, toluene, o
-Aromatic hydrocarbon solvents such as xylene, m-xylene, p-xylene, ethylbenzene, p-diethylbenzene, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene, tetralin and α-methylnaphthalene, For example, chlorobenzene, o-chlorotoluene, m
-Aromatic halogenated hydrocarbon solvents such as -chlorotoluene, p-chlorotoluene, o-difluorobenzene, o-dichlorobenzene, m-dichlorobenzene and p-dichlorobenzene, for example, pentane, hexane, heptane, octane, decane , Cyclohexane, decalin and other aliphatic hydrocarbon solvents such as dichloromethane, chloroform, tetrachloromethane, tetrachloroethylene, 1,2-dichloroethane, 1,1,1-trichloroethane, 1,1,2-trichloroethane, 1,1 , 2,
A hydrocarbon solvent such as an aliphatic halogenated hydrocarbon solvent such as 2-tetrachloroethane,

For example, an ether solvent such as diethyl ether, diisopropyl ether, di-n-butyl ether, anisole, diphenyl ether, tetrahydrofuran, dioxane, etc., an ester solvent such as ethyl acetate, butyl acetate, amyl acetate, etc., acetic acid,
Examples thereof include aliphatic carboxylic acid type solvents such as propionic acid and butyric acid. These organic solvents may be used alone or in combination. A particularly preferable organic solvent is a hydrocarbon solvent, and among them, an aromatic hydrocarbon solvent or an aliphatic hydrocarbon solvent is preferable.

The amount of the organic solvent used is not particularly limited, and generally 10% by weight or more based on the weight of the N, N-disubstituted aminophenol derivative is sufficient. It merely causes a decrease in production efficiency and the like, and is preferably 10 to 1000% by weight, more preferably 20 to 500% by weight.

The progress of the reaction can be monitored by analytical means such as high performance liquid chromatography and gas chromatography.
Post-treatment operations can be performed.

After the reaction, the 2- (N, N-disubstituted amino-hydroxyphenylcarbonyl) benzoic acid derivative can be obtained by a known method, for example, a method in which crystals are filtered from the reaction system,
Alternatively, the alkali metal base of the 2- (N, N-disubstituted amino-hydroxyphenylcarbonyl) benzoic acid derivative (for example, sodium hydroxide, potassium hydroxide) in the reaction system is allowed to act to cause the alkali metal of the benzoic acid derivative. After conversion to a salt, the alkali metal salt of the benzoic acid derivative can be separated, neutralized with an acid, and then isolated by a method such as filtration.

After isolation, if desired, an aromatic hydrocarbon solvent such as toluene or xylene, an alcohol solvent such as methanol, ethanol, isopropanol or n-butanol, or a mixed solvent of an alcohol solvent and water may be used. Recrystallization or / and washing may be performed.

In the production method of the present invention, each step is carried out under an atmospheric pressure atmosphere in producing the N, N-disubstituted aminophenol derivative and the 2- (N, N-disubstituted amino-hydroxyphenylcarbonyl) benzoic acid derivative. However, preferably, an inert gas (for example,
Gas such as nitrogen, argon, helium, etc.).

The reaction used in the preparation of N, N-disubstituted aminophenol derivatives [steps (a) to (d)] and 2- (N, N-disubstituted amino-hydroxyphenylcarbonyl) benzoic acid derivatives. The type and form of the apparatus are not particularly limited, but generally, a tank type, a tube type, or a column type reaction apparatus can be used. Of course, different reactors can be used in each step.

In the method for producing an N, N-disubstituted aminophenol derivative, these reactors are arbitrarily combined and the steps (a) to (d) are carried out in a batch system (batch system). be able to. Furthermore, step (a)
It is also possible to carry out through a plurality of steps of (d) or continuously through all the steps.

The reaction apparatus used in each step can be equipped with various stirring devices. Examples of such a stirring device include a paddle type stirrer, a propeller type stirrer, a turbine type stirrer, a high speed stirrer such as a homogenizer, a homomixer, a line mixer, a line homomixer, and a static mixer, a colloid mill, an orifice mixer. , A flow jet mixer and the like.

[0166]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the present invention is limited thereto.

Example 1 Step (a) A 2 liter glass container was charged with 550 g (5 mol) of resorcin and 365 g (5 mol) of n-butylamine,
The mixture was heated to 160 ° C. under a nitrogen atmosphere and stirred at the same temperature for 15 hours. Unreacted n-butylamine was distilled off under reduced pressure. As a result of analysis by high performance liquid chromatography, the reaction mixture contained 490 g of Nn-butyl-m-aminophenol (yield based on resorcinol was 59 mol%) and 193 g of resorcinol (conversion rate of resorcinol was 65%).
%, And 60 g of N, N'-di-n-butyl-m-phenylenediamine (the yield based on resorcin was 5.5 mol%).

Step (b) To the mixture obtained in Step (a), under a nitrogen atmosphere, 750 g of isopropanol and 615 g of n-butyl bromide.
(4.5 mol) was added, and the mixture was stirred at 70 ° C. for 10 hours. After the reaction, isopropanol and unreacted n-butyl bromide were distilled off under reduced pressure. Toluene 1500 in the residue
g and 10% by weight aqueous sodium hydroxide solution were added to adjust the pH of the aqueous phase to 6, and the organic phase was separated. The separated organic phase was further washed twice with water (500 g) twice.

As a result of high performance liquid chromatography analysis, the organic phase was found to contain 654 g of N, N-di-n-butyl-m-aminophenol and N, N, N'-tri-n-butyl-m-phenylenediamine. And N, N, N'N'-tetra-n-butyl-m-phenylenediamine mixture 8
It contained 9 g. Resorcin was extracted in the separated and removed aqueous phase.

Step (c) To the organic phase obtained in the step (b), 1 g of sodium hydrosulfite, 1000 g of water and 1200 g of 10% by weight sodium hydroxide aqueous solution were added under a nitrogen atmosphere, and the mixture was heated to 30 ° C.
After stirring for 30 minutes at rt, the aqueous phase was separated.

Incidentally, N, N, N'-tri-n-butyl-m
The mixture of phenylenediamine and N, N, N'N'-tetra-n-butyl-m-phenylenediamine had been extracted into the separated and removed organic phase.

Step (d) 550 g of 20% by weight hydrochloric acid was added to the aqueous phase obtained in step (c) under a nitrogen atmosphere, and the mixture was stirred at 30 ° C. for 30 minutes, and then the organic phase was separated. The organic phase contains N, N-di-n-butyl-
It contained 650 g of m-aminophenol (purity 97% by weight).

Of course, the organic phase contains resorcin, N, N,
N'-tri-n-butyl-m-phenylenediamine and N, N, N'N'-tetra-n-butyl-m-phenylenediamine were not included.

Example 2 Step (a) A 2 liter glass container was charged with 550 g (5 mol) of resorcin and 295 g (5 mol) of n-propylamine, and the mixture was heated to 160 ° C. under a nitrogen atmosphere. While removing by-produced water out of the system, the mixture was stirred at the same temperature for 7 hours. Unreacted n-propylamine was distilled off under reduced pressure.

As a result of analysis by high performance liquid chromatography, the reaction mixture contained 513 g of Nn-propyl-m-aminophenol (the yield based on resorcin was 68 mol%) and 130 g of resorcin (the conversion of resorcin was 76).
Mol%), 58 g of N, N'-di-n-propyl-m-phenylenediamine (the yield based on resorcin is 6 mol%).
Was contained.

To this mixture, 1500 g of toluene and 50 parts of water were added.
After adding 0 g and stirring at 50 ° C. for 30 minutes, the aqueous phase was separated and removed. The separated organic phase is further separated by water (500
g) The washing operation was repeated twice. The organic phase contains Nn
It contained 509 g of -propyl-m-aminophenol, 3 g of resorcin and 58 g of N, N'-di-n-propyl-m-phenylenediamine.

Step (b) N-n obtained by heating 504 g (4 mol) of dimethylsulfate to 50 ° C. and distilling toluene from the organic phase produced in step (a) under a nitrogen atmosphere. A mixture of 509 g of -propyl-m-aminophenol (3.4 mol), 3 g of resorcin and 58 g of N, N'-di-n-propyl-m-phenylenediamine was fed in for 1 hour. Furthermore, the reaction mixture was stirred at 50 ° C. for 10 hours. Then 25
After cooling to ℃ and adding 1500 g of toluene to the reaction mixture, 1520 g of 28 wt% sodium carbonate aqueous solution was added to
It was fed over time and the organic phase was separated. The separated organic phase was further washed twice with water (500 g) twice.

As a result of high performance liquid chromatography analysis, the organic phase was found to be Nn-propyl-N-methyl-m-.
Aminophenol 544 g, N, N′-di-n-propyl-N-methyl-m-phenylenediamine and N,
It contained 66 g of a mixture of N'-di-n-propyl-N, N'-dimethyl-m-phenylenediamine.
Resorcin was extracted in the separated and removed aqueous phase.

Step (c) To the organic phase obtained in step (b), 1 g of sodium hydrosulfite and 1320 g of a 10% by weight sodium hydroxide aqueous solution were added under a nitrogen atmosphere, and the mixture was stirred at 30 ° C. for 30 minutes, then, the aqueous phase was added. Was separated and subjected to step (c).

N, N'-di-n-propyl-N-methyl-m-phenylenediamine and N, N'-di-n
The mixture of -propyl-N, N'-dimethyl-m-phenylenediamine had been extracted into the separated and removed organic phase.

Step (d) To the aqueous phase obtained in step (c), 605 g of 20 wt% hydrochloric acid was added under a nitrogen atmosphere, and the mixture was stirred at 30 ° C. for 30 minutes, and then the organic phase was separated.

The organic phase contained 540 g of Nn-propyl-N-methyl-m-aminophenol (purity: 97% by weight).
Was contained. Of course, the organic phase contains resorcin and N, N'-di-n-propyl-N-methyl-m-phenylenediamine and N, N'-di-n-propyl-.
It did not contain N, N'-dimethyl-m-phenylenediamine.

Example 3 In step (a) of Example 2, n-propylamine 2
Example 2 except that 495 g (5 mol) of cyclohexylamine was used instead of using 95 g (5 mol).
750 g of N-cyclohexyl-N-methyl-m-aminophenol according to the operation of steps (a) to (d) described in 1.
A toluene solution containing (purity 97% by weight) was obtained. Of course, resorcin, N, N'-dicyclohexyl-N-methyl-m-phenylenediamine and N, N'-dicyclohexyl-N, N'-dimethyl-m-phenylenediamine were not included.

Example 4 Step (a) A 2 liter glass container was charged with 550 g (5 mol) of resorcin, 435 g (5 mol) of isopentylamine, and 500 g of 1,2,4-trimethylbenzene, and the atmosphere was nitrogen. Under heating the mixture to 170 ° C. for 12 hours,
The mixture was stirred at the same temperature. 1,2,4-Trimethylbenzene and unreacted isopentylamine were distilled off under reduced pressure.

As a result of analysis by high performance liquid chromatography, the reaction mixture contained 564 g of N-isopentyl-m-aminophenol (yield based on resorcin was 63 mol%) and 156 g of resorcin (conversion rate of resorcin was 71).
%, And 74 g of N, N′-diisopentyl-m-phenylenediamine (yield based on resorcinol is 6 mol%).

Step (b) Toluene 1 was added to the mixture obtained in Step (a) under a nitrogen atmosphere.
000 g and 800 g (4 mol) of p-toluenesulfonic acid ethyl ester were added, and the mixture was stirred at 90 ° C for 12 hours. After the reaction, the upper toluene layer was removed, and toluene 1 was added.
The pH of the aqueous phase was adjusted to 7 by adding 000 g and a 5 wt% sodium hydrogen carbonate aqueous solution, and the organic phase was separated. The separated organic phase was further washed twice with water (500 g) twice. As a result of analysis by high performance liquid chromatography,
The organic phase contains 635 g of N-isopentyl-N-ethyl-m-aminophenol, N, N'-diisopentyl-N.
It contained 89 g of a mixture of -ethyl-m-phenylenediamine and N, N'-diisopentyl-N, N'-diethyl-m-phenylenediamine.

Step (c) To the organic phase obtained in step (b), 1 g of sodium hydrosulfite, 1000 g of water and 1240 g of a 10% by weight sodium hydroxide aqueous solution were added under a nitrogen atmosphere, and the mixture was heated to 30 ° C.
After stirring for 30 minutes at rt, the aqueous phase was separated.

The N, N'-diisopentyl-N-ethyl-m-phenylenediamine and N, N'-diisopentyl-N, N'-diethyl-m-phenylenediamine were extracted into the separated and removed organic phase. It had been.

Step (d) To the aqueous phase obtained in Step (c), toluene 10 was added under a nitrogen atmosphere.
Add 00 g and 380 g of 40 wt% sulfuric acid aqueous solution, and add 3
After stirring for 30 minutes at 0 ° C., the organic phase was separated. The organic phase contained 630 g of N-isopentyl-N-ethyl-m-aminophenol (purity 98% by weight).

Of course, the organic phase contains resorcin, N, N '.
-Diisopentyl-N-ethyl-m-phenylenediamine and N, N'-diisopentyl-N, N'-diethyl-m-phenylenediamine were not included.

Example 5 In step (a) of Example 4, isopentylamine 4
Instead of using 35 g, isobutylamine 365 g
Toluene containing 580 g (purity 97%) of N-isobutyl-N-ethyl-m-aminophenol according to the operations of steps (a) to (d) described in Example 4 except that (5 mol) was used. A solution was obtained.

Of course, the organic phase contains resorcin, N, N '.
-Diisobutyl-N-ethyl-m-phenylenediamine and N, N'-diisobutyl-N, N'-diethyl-
It contained no m-phenylenediamine.

Comparative Example 1 N, N-di-n-butyl-m-aminophenol 654 g, N, N, N 'prepared by repeating the procedure described in step (a) and step (b) of Example 1. -Tri-n-butyl-m-phenylenediamine and N, N, N'N'-
Toluene was distilled off under reduced pressure from the organic phase containing 89 g of a mixture of tetra-n-butyl-m-phenylenediamine. After adding 360 g of 98% by weight sulfuric acid to the residue,
340 g of water was added, and the mixture was stirred at 30 ° C for 30 minutes. To this solution, 450 g of methyl isobutyl ketone was added, and the organic phase was separated and removed. Furthermore, the extraction operation with methyl isobutyl ketone (450 g) was repeated 5 times. Then, the aqueous phase was added with a 25 wt% sodium hydroxide aqueous solution 115.
After adding 5 g, the organic phase was separated.

The organic phase contains N, N-di-n-butyl-m.
-Aminophenol 653 g, N, N, N'-tri-n
-Butyl-m-phenylenediamine and N, N, N '
It contained 89 g of a mixture of N'-tetra-n-butyl-m-phenylenediamine.

Example 6 Step (a) According to the method described in step (a) of Example 1, 490 g (3 mol) of Nn-butyl-m-aminophenol, 193 g of resorcin and N, N-di-n. A reaction mixture containing 60 g of -butyl-m-phenylenediamine was prepared.

Step (b) In an autoclave, under a nitrogen atmosphere, 490 g (3 mol) of Nn-butyl-m-aminophenol obtained in step (a), 193 g of resorcinol and N, N-di-n-butyl. A mixture of 60 g of m-phenylenediamine, 1500 g of methanol and 2% by weight of Pt on activated carbon 3
0 g was charged. Then, after replacing the system with hydrogen, 7
The pressure was increased to kg / cm ² . While maintaining the hydrogen pressure constant, at 30 to 35 ° C., n-butyraldehyde 252 g
(3.5 mol) was fed in 4 hours. Then 0 ℃
After cooling to room temperature, the pressure in the system was released, and the reaction mixture was filtered.

As a result of high performance liquid chromatography analysis, N, N-di-n-butyl-m- was found in the organic phase of the filtrate.
Aminophenol 633 g, resorcin 192 g and N, N, N'-tri-n-butyl-m-phenylenediamine and N, N, N'N'-tetra-n-butyl-m
Contained 89 g of a mixture of phenylenediamines.

Step (c) From the organic phase obtained in step (b), methanol was distilled off under reduced pressure. Under a nitrogen atmosphere, 1 g of sodium hydrosulfite and 2600 g of a 10 wt% sodium hydroxide aqueous solution were added to the residue, and the mixture was stirred at 30 ° C. for 30 minutes, and then the aqueous phase was separated. In addition, N, N, N'-tri-n-butyl-
A mixture of m-phenylenediamine and N, N, N'N'-tetra-n-butyl-m-phenylenediamine is
It was extracted into the separated and removed organic phase.

Step (d) 1190 g of 20 wt% hydrochloric acid was added to the aqueous phase obtained in step (c) under a nitrogen atmosphere, and the mixture was stirred at 30 ° C. for 30 minutes, and then the organic phase was separated.

The organic phase contains N, N-di-n-butyl-m.
630 g of aminophenol (purity 96% by weight) were contained. Of course, the organic phase contains resorcin, N, N,
N'-tri-n-butyl-m-phenylenediamine and N, N, N'N'-tetra-n-butyl-m-phenylenediamine were not included.

Example 7 Partial amount of N, N-di-n-butyl-m- obtained by distilling toluene from the organic phase prepared in step (d) of Example 1
221 g (1 mol) of aminophenol and 1 phthalic anhydride
78 g (1.2 mol) of toluene 20 under nitrogen atmosphere
Stir in 0 g at 90 ° C. for 12 hours. The production rate of the rhodamine derivative in the obtained reaction mixture was 4 mol% (N,
N-di-n-butyl-m-aminophenol). To the reaction mixture, 200 g of toluene and 30 warm water
After adding 0 g and stirring at 80 degreeC for 30 minutes, the water phase was isolate | separated and removed. After cooling the organic phase to 20 ° C., the precipitated crystals were filtered. Further, the crystal was added to methanol 1300
Recrystallization from g, filtration, and methanol 100
After washing with g, it was dried and as light yellow crystals, 296 g of 2- (4′-N, N-di-n-butylamino-2′-hydroxyphenylcarbonyl) benzoic acid containing no rhodamine derivative (yield 80 %) Was obtained.

Example 8 A portion of N-isopentyl-N-ethyl-m-aminophenol 207 g (1 mol) obtained by distilling toluene from the organic phase prepared in step (d) of Example 4 And 178 g (1.2 mol) of phthalic anhydride were stirred under nitrogen atmosphere in 280 g of toluene at 90 ° C. for 18 hours. The production rate of the rhodamine derivative in the obtained reaction mixture was 4 mol%.
(N-isopentyl-N-ethyl-m-aminophenol standard). 780 g of a 15 wt% sodium hydroxide aqueous solution was added to the reaction mixture, and the mixture was stirred at 70 ° C. for 30 minutes. The aqueous phase was separated, cooled to 10 ° C., and the precipitated sodium salt was filtered. The obtained sodium salt was added to water 1
It was dissolved in 000 g and neutralized by adding 20 wt% sulfuric acid. The precipitated crystals were filtered and dried, and as light yellow crystals, 296 g of 2- (4′-N-isopentyl-N-ethylamino-2′-hydroxyphenylcarbonyl) benzoic acid containing no rhodamine derivative (yield 80% ) Got.

Comparative Example 2 221 g (1 mol) of N, N-di-n-butyl-m-aminophenol obtained by distilling toluene off the organic phase prepared in Comparative Example 1 and N, N, N'-tri-n-butyl-m-phenylenediamine and N, N, N ',
N'-tetra-n-butyl-m-phenylenediamine 3
0.1 g mixture and 178 g phthalic anhydride (1.2 g
Mol) in a nitrogen atmosphere in 200 g of toluene at 90 ° C.
It was stirred for 12 hours. The production rate of the rhodamine derivative in the obtained reaction mixture was 10 mol% (based on N, N-di-n-butyl-m-aminophenol). To the reaction mixture, 200 g of toluene and 300 g of warm water were added,
After stirring at 0 ° C. for 30 minutes, the aqueous phase was separated and removed. After cooling the organic phase to 20 ° C., the precipitated crystals were filtered.
The crystals were recrystallized from 1300 g of methanol, filtered, washed with 100 g of methanol, and dried to give 2- (4′-N, N-di-n-as pale pink crystals.
Butylamino-2'-hydroxyphenylcarbonyl)
236 g (64% yield) of benzoic acid was obtained. The crystals still contained 5000 ppm of the rhodamine derivative.

[0204]

Industrial Applicability According to the present invention, it is possible to produce a highly pure aminophenol derivative by a simple method.

Claims (2)

[Claims] 1. A step of (a) reacting a dihydric phenol derivative with a primary amine derivative to obtain a reaction mixture containing an N-monosubstituted aminophenol derivative, and (b) containing an N-monosubstituted aminophenol derivative. Alkylating the reaction mixture to obtain a reaction mixture containing the N, N-disubstituted aminophenol derivative, (c) the reaction mixture containing the N, N-disubstituted aminophenol derivative and the base in the presence of water. A step of bringing the N, N-disubstituted aminophenol derivative into a water-soluble basic salt by contact, and separating an aqueous phase containing the basic salt; and (d) N, N
A step of contacting an acid with an aqueous phase containing a water-soluble basic salt of a di-substituted aminophenol derivative to neutralize and separating the liberated N, N-di-substituted aminophenol derivative. -A method for producing a di-substituted aminophenol derivative. 2. N obtained by the manufacturing method according to claim 1,
A method for producing a 2- (N, N-disubstituted amino-hydroxyphenylcarbonyl) benzoic acid derivative, which comprises reacting an N-disubstituted aminophenol derivative with phthalic anhydride.