JP2011012053A - Method for preparing n-alkylamino phenol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for preparing an N-alkylamino phenol without using gaseous monoalkylamine.SOLUTION: The method for preparing the N-lower alkylamino phenol represented by formula (III) comprises contacting dihydric phenols represented by formula (I) with an aqueous solution of a lower alkylamine in the presence of zinc halide. In the formulas, Ris a hydrogen atom or the like, and Ris a 1-3C alkyl group.

Description

  The present invention relates to a method for producing N-alkylaminophenol and the like.

  After enclosing resorcin in an autoclave, heating and pressurizing, N-ethyl-3-aminophenol, which is one of N-alkylaminophenols, is collected by contacting gaseous ethylamine as a monoalkylamine. Patent Document 1 describes that it can be manufactured at a rate of 64.1%.

JP-A-6-271515 (Example 1)

At present, gaseous ethylamine is not commercially available, and in order to produce N-ethyl-3-aminophenol by the production method described in the above publication, it is necessary to prepare gaseous ethylamine, which is complicated to produce. Met.
An object of the present invention is to provide a method for producing N-alkylaminophenol without using a gaseous monoalkylamine.

（式中、Ｒ_１は水素原子又はメチル基を表す。）
で表される２価フェノール類と、式（II）
Ｒ_２-ＮＨ_２ (II)
（式中、Ｒ_２は炭素数１〜３のアルキル基を表す。）
で表されるアミン化合物の水溶液とを
ハロゲン化亜鉛存在下、接触させることを特徴とする式（III）

で表されるＮ−アルキルアミノフェノールの製造方法； Under such circumstances, as a result of intensive studies by the present inventors, the present invention has been achieved. That is, the present invention
[1]: Formula (I)

(In the formula, R ₁ represents a hydrogen atom or a methyl group.)
A dihydric phenol represented by the formula (II)
R ₂ -NH ₂ (II)
(In the formula, R ₂ represents an alkyl group having 1 to 3 carbon atoms.)
And an aqueous solution of an amine compound represented by formula (III):

A process for producing an N-alkylaminophenol represented by formula:

[2]: The amount of the amine compound represented by the formula (II) is 0.7 mol or more with respect to 1 mol of the dihydric phenol represented by the formula (I) [1] ] The manufacturing method of description;
[3]: The production method according to [1] or [2], wherein the amount of zinc halide used is 0.03 mol or more based on the amine compound represented by the formula (II);
[4]: The production method according to any one of [1] to [3], wherein the amine compound represented by the formula (II) is ethylamine;

[5]: A reaction mixture containing an N-alkylaminophenol represented by formula (III) obtained by the production method according to any one of [1] to [4] and an acid are mixed to form formula (III) A mixture of an organic layer containing N-alkylaminophenol represented by the formula and a weakly acidic aqueous layer having a pH of 4 to 5, and then separating the mixture into an organic layer and an aqueous layer to recover the organic layer A method for purifying N-alkylaminophenol, comprising:
[6]: A reaction mixture containing an N-alkylaminophenol represented by the formula (III) obtained by the production method according to any one of [1] to [4] and an acid are mixed to produce an acid having a pH of 3 or less. A first recovery step for recovering the aqueous layer;
The acidic aqueous layer obtained in the first recovery step, the organic solvent and the base are mixed to adjust the pH of the aqueous layer to 4 or more, and the resulting mixture is separated into an organic layer and an aqueous layer to separate the organic layer. A second recovery step to recover;
A method for purifying N-alkylaminophenol, comprising:
It is.

  According to the production method of the present invention, it is possible to provide a production method of N-alkylaminophenol without using a gaseous monoalkylamine.

Hereinafter, the present invention will be described in detail.
Examples of the dihydric phenols represented by the formula (I) (hereinafter sometimes referred to as dihydric phenols (I)) include resorcin, 5-methylresorcin, hydroquinone, 2-methylhydroquinone and the like. be able to.
As the dihydric phenol (I), it is preferable to use one compound, but two or more compounds may be used.
As the dihydric phenol (I), resorcin is preferable.

Examples of the amine compound represented by the formula (II) (hereinafter sometimes referred to as amine compound (II)) include methylamine, ethylamine, n-propylamine, isopropylamine and the like.
As the amine compound (II), one compound is preferably used, but two or more compounds may be used.
As the amine compound (II), ethylamine is preferable.
The amount of the amine compound (II) to be used is preferably 0.7 mol or more, more preferably 0.8 to 2.5 mol, per mol of the dihydric phenol (I).
The concentration of the amine compound (II) in the aqueous solution of the amine compound (II) is preferably about 30 to 70% by weight.

The present invention is a production method characterized by contacting an aqueous solution of a dihydric phenol (I) and an amine compound (II) in the presence of zinc halide.
Examples of the zinc halide used in the present invention include zinc chloride, zinc bromide, zinc iodide and the like. Preferably, zinc chloride etc. are mentioned.

（式中、Ｒ_１及びＲ_２は前記と同じ意味を表す。）
で示されるＮ，Ｎ’−ジアルキルフェニレンジアミン（以下、ジアミン（IV）と記すことがある。）の副生を抑制する傾向がある。 The amount of zinc halide used is preferably 0.03 mol or more and more preferably 0.1 mol to 0.12 mol with respect to 1 mol of the amine compound (II).
When the amount of zinc halide used is 0.03 mol or more with respect to 1 mol of the amine compound (II), the formula (IV)

(In the formula, R ₁ and R ₂ represent the same meaning as described above.)
There is a tendency to suppress the by-product of N, N′-dialkylphenylenediamine (hereinafter sometimes referred to as diamine (IV)).

  In the production method of the present invention, the mixing method of the dihydric phenols (I), the aqueous solution of the amine compound (II), and the zinc halide is not limited. As a preferable mixing method, for example, a method in which zinc halide is mixed in a mixed solution of an aqueous solution of a dihydric phenol (I) and an amine compound (II) at once or intermittently can be exemplified.

  Examples of the reaction temperature for bringing the dihydric phenol (I) and the aqueous solution of the amine compound (II) into contact in the presence of zinc halide include 150 to 200 ° C. Preferably, 160-180 degreeC etc. can be mentioned.

  Examples of the contact time when the dihydric phenol (I) and the aqueous solution of the amine compound (II) are contacted in the presence of zinc halide include 2 to 12 hours. Preferably, it can be 3 to 8 hours.

  When the dihydric phenol (I) and the aqueous solution of the amine compound (II) are contacted in the presence of zinc halide, for example, a hydrocarbon solvent such as toluene, for example, ether such as diethyl ether, tetrahydrofuran, propylene glycol dimethyl ether, etc. An organic solvent such as an ester solvent such as ethyl acetate, butyl acetate, and propylene glycol dimethyl ester, for example, a ketone solvent such as acetone, methyl ethyl ketone, and methyl isobutyl ketone may be coexistent. It is preferred that substantially no organic solvent is used. Here, “substantially not use” means that the amount of the organic solvent used is preferably 5 parts by weight or less with respect to a total of 100 parts by weight of the aqueous solution of the dihydric phenol (I) and the amine compound (II). Preferably it means 1 part by weight or less.

  When the dihydric phenol (I) and the aqueous solution of the amine compound (II) are contacted in the presence of zinc halide, water may be added from other than the aqueous solution of the amine compound (II). As content of water in this case, the total weight part combined with water derived from the aqueous solution of the amine compound (II) is, for example, 30 to 250 parts by weight with respect to 100 parts by weight of the amine compound (II). Can be mentioned.

The reaction performed by contacting the aqueous solution of the dihydric phenol (I) and the amine compound (II) in the presence of zinc halide is preferably performed under an inert gas atmosphere such as nitrogen and sealed in an autoclave or the like. . When carried out in a sealed state without applying pressure, the pressure is usually about 0 to 1 MPa, preferably about 0.1 to 0.8 MPa.
The production method of the present invention can be carried out in a sealed state without particularly applying pressure.

  When the dihydric phenol (I) and the aqueous solution of the amine compound (II) are contacted in the presence of zinc halide, the conversion rate of the dihydric phenol (I) is, for example, about 70 to 90%. be able to. Here, the conversion rate is obtained by subtracting the value obtained by subtracting the unreacted dihydric phenol (I) from the dihydric phenol (I) used before the reaction by the divalent phenol (I) used before the reaction. Means the percentage of the value.

  When contacting the aqueous solution of the dihydric phenol (I) and the amine compound (II) in the presence of zinc halide, ammonium salts such as ammonium chloride and ammonium phosphate may be present, but substantially It is preferable not to contain. Specifically, the amount is adjusted to 0.3 mol or less, more preferably 0.1 mol or less, and more preferably 0.01 mol or less with respect to 1 mol of the dihydric phenol (I).

  Examples of the N-alkylaminophenol represented by the formula (III) obtained by the production method of the present invention (hereinafter sometimes referred to as compound (III)) include N-methyl-3-aminophenol, N-ethyl-3-aminophenol, Nn-propyl-3-aminophenol, N-isopropyl-3-aminophenol, N-methyl-3-amino-5-methylphenol, N-ethyl-3-amino- 5-methylphenol, Nn-propyl-3-amino-5-methylphenol, N-isopropyl-3-amino-5-methylphenol, N-methyl-4-aminophenol, N-ethyl-4-aminophenol N-propyl-4-aminophenol, N-isopropyl-4-aminophenol, N-methyl-2-methyl-4-aminophenol Le, N- ethyl-2-methyl-3-aminophenol, N-n-propyl-2-methyl-3-aminophenol, can be mentioned N- isopropyl-2-methyl-3-aminophenol. Preferred examples include N-methyl-3-aminophenol, N-ethyl-3-aminophenol, Nn-propyl-3-aminophenol, N-isopropyl-3-aminophenol, and more preferably N-methyl-3-aminophenol. -Ethyl-3-aminophenol and the like.

A dihydric phenol (I) and an aqueous solution of an amine compound (II) are contacted in the presence of zinc halide to obtain a reaction mixture containing the compound (III).
In addition to the compound (III), the reaction mixture usually contains zinc halide, unreacted dihydric phenol (I), diamine (IV) and the like.
Among them, diamine (IV) is difficult to remove by a purification method described later, but the production method of the present invention is preferable because by-product of diamine (IV) tends to be suppressed.

Next, a method for purifying the compound (III) contained in the reaction mixture will be described below.
First, a method for removing zinc halide from the reaction mixture will be described. For example, the reaction mixture and an acid are mixed in the presence of an organic solvent as necessary to obtain a compound (III) and a weakly acidic aqueous layer having a pH of 4 to 5, preferably 4.0 to 5.0. Examples thereof include a purification method including a step of obtaining a mixture and then separating the mixture into an organic layer and an aqueous layer and recovering the organic layer (hereinafter sometimes referred to as a water washing step).
Zinc halide is usually distributed in the aqueous layer.
Here, examples of the organic solvent include those exemplified above, and an ester solvent is preferable.
Examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, and organic acids such as acetic acid. These acids are preferably aqueous solutions, and more preferably sulfuric acid aqueous solutions. The concentration of the sulfuric acid aqueous solution is preferably 10 to 90% by weight.
Such a purification method may further include a step of neutralizing the organic layer recovered as described above with a base.
Examples of the base include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal bicarbonates such as sodium carbonate and potassium carbonate, and alkali metal carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate. A salt etc., for example, ammonia etc. can be mentioned. Preferably, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide are used.

Next, a method for removing unreacted dihydric phenols (I) from the reaction mixture will be described. For example, the above reaction mixture and acid are mixed to recover an acidic aqueous layer having a pH of 3 or less, preferably 0.1 to 2, an acidic aqueous layer obtained in the first recovery step, an organic solvent, and And a purification method including a second recovery step of mixing the base to adjust the pH of the aqueous layer to 4 or more, separating the resulting mixture into an organic layer and an aqueous layer and recovering the organic layer. .
In the first recovery step, the dihydric phenol (I) is usually distributed mainly in the organic layer. Compound (III) is usually distributed to the aqueous layer in the first recovery step and recovered as an organic layer in the second recovery step. The reaction mixture used in the first recovery step may have undergone the water washing step.
Examples of the organic solvent, acid and base used in the first recovery step and the second recovery step are the same as those obtained in the water washing step.

  The purification method of the present invention may include a step of obtaining the compound (III) by concentrating the organic layer containing the recovered compound (III), a step of distilling the compound (III), and the like.

Hereinafter, the present invention will be described in more detail with reference to examples.
Example 1
In an autoclave, 80 g (0.727 mol, 1 mol ratio) of resorcin and 49.1 g (0.763 mol, 1.05 mol ratio) of an aqueous solution containing 70% by weight of ethylamine were mixed and stirred until uniform. Subsequently, 11.9 g (0.087 mol, 0.12 molar ratio) of zinc chloride was charged into the autoclave, and the gas phase portion of the autoclave was purged with nitrogen, followed by sealing. The contents in the autoclave were stirred for 5 hours while maintaining the temperature of the contents at 175 ° C. The maximum pressure during stirring was 0.62 MPa (gauge pressure).
Subsequently, the contents were cooled and the inside of the autoclave was opened to atmospheric pressure, and the obtained crude product was analyzed using liquid chromatography (Shimadzu LC10A) equipped with a detector having a wavelength of 270 nm. The results of area percentage of the obtained chromatograph are as follows: N-ethyl-3-aminophenol 75.4%, resorcin 19.2%, 3-aminophenol 0.07%, N, N′-diethylphenylenediamine 29%. From these results, the selectivity of N-ethyl-3-aminophenol (75.4 / [75.4 + 0.07 + 0.29] × 100) with respect to the total product obtained was 99.5%, and the obtained N- The by-product rate of N, N′-diethylphenylenediamine with respect to ethyl-3-aminophenol (0.29 × 75.4 × 100) was 0.4%.
Further, using the same liquid chromatography, the content of N-ethyl-3-aminophenol in the crude product was analyzed by an internal standard method (internal standard material: phenol), and N-ethyl-3-amino was determined from the content. The yield of phenol (resorcin basis) was 74.6 mol%.

(Examples 2 to 5, Reference Example 1)
The same procedure as in Example 1 was carried out except that the amount charged and the reaction conditions were as shown in Table 1. The obtained crude product was analyzed by liquid chromatography. The survival rate was calculated. The results are shown in Table 1 together with Example 1.
N-ethyl-3-aminophenol is obtained as the crude product, and the by-product of N, N′-diethylphenylenediamine is suppressed to less than 0.5%.

(Removal of zinc chloride from the reaction mixture)
To the reaction mixture obtained in Example 1, 120 ml of ethyl acetate and 80 ml of water were mixed, and then 78% sulfuric acid aqueous solution and 25% aqueous sodium hydroxide solution were added to adjust the aqueous layer to pH 5.0. The aqueous layer is separated to remove most of the zinc chloride, and the resulting organic layer is washed with brine, followed by the addition of a 25% aqueous sodium hydroxide solution and brine to bring the brine layer to pH 7. Thus, an organic layer from which zinc chloride was removed was obtained. This organic layer was analyzed by liquid chromatography. As a result, N-ethyl-3-aminophenol 75.23%, resorcin 18.12%, 3-aminophenol 0.12%, N, N′-diethylphenylenediamine 0.12%, 27%.

(Resorcin removal)
To the reaction mixture obtained in Example 1, 120 ml of ethyl acetate and 160 ml of water were mixed, and subsequently 78% sulfuric acid was added to adjust the aqueous layer to pH 1.5. To the aqueous layer obtained by liquid separation, 240 ml of ethyl acetate was added and stirred, and then the step of removing the ethyl acetate layer to obtain a liquid separation aqueous layer was repeated twice. After neutralizing the separated aqueous layer, 240 ml of ethyl acetate was added, and the obtained ethyl acetate layer was analyzed by liquid chromatography. As a result, N-ethyl-3-aminophenol 92.96%, resorcin 0.12%, They were 0.12% 3-aminophenol and 0.27% N, N′-diethylphenylenediamine.

  According to the production method of the present invention, it is possible to provide a production method of N-alkylaminophenol without using a gaseous monoalkylamine.

Claims (6)

Formula (I)

(In the formula, R ₁ represents a hydrogen atom or a methyl group.)
A dihydric phenol represented by the formula (II)
R ₂ -NH ₂ (II)
(In the formula, R ₂ represents an alkyl group having 1 to 3 carbon atoms.)
And an aqueous solution of an amine compound represented by formula (III):

The manufacturing method of N-alkylaminophenol represented by these.   2. The production according to claim 1, wherein the amount of the amine compound represented by the formula (II) is 0.7 mol or more with respect to 1 mol of the dihydric phenol represented by the formula (I). Method.   The production method according to claim 1 or 2, wherein the amount of zinc halide used is 0.03 mol or more based on the amine compound represented by the formula (II).   The production method according to any one of claims 1 to 3, wherein the amine compound represented by the formula (II) is ethylamine.   A reaction mixture containing an N-alkylaminophenol represented by the formula (III) obtained by the production method according to any one of claims 1 to 4 and an acid are mixed to produce an N- represented by the formula (III). Obtaining a mixture of an organic layer containing an alkylaminophenol and a weakly acidic aqueous layer having a pH of 4 to 5, and then separating the mixture into an organic layer and an aqueous layer to recover the organic layer, A method for purifying N-alkylaminophenol. A reaction mixture containing an N-alkylaminophenol represented by formula (III) obtained by the production method according to any one of claims 1 to 4 and an acid are mixed to recover an acidic aqueous layer having a pH of 3 or less. 1 recovery process;
The acidic aqueous layer obtained in the first recovery step, the organic solvent and the base are mixed to adjust the pH of the aqueous layer to 4 or more, and the resulting mixture is separated into an organic layer and an aqueous layer to separate the organic layer. A second recovery step to recover;
A process for purifying N-alkylaminophenol, comprising: