JP5324298B2 - Process for producing hydroxyalkylaminophenol derivatives - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for preparing a hydroxyalkyl aminophenol derivative etc., which is excellent in economical efficiency, operability and ease of waste liquid treatment and is capable of yielding the product with high purity. <P>SOLUTION: The method for preparing the hydroxyalkyl aminophenol derivative represented by the formula (wherein R1 is a hydrogen atom, 1-4C alkyl group or the like; R2 is a hydrogen atom, 1-4C alkyl group or the like; R3 is a hydrogen atom, 1-2C alkyl group or the like; R5 is a 2-6C hydroxyalkyl group; provided that the R1, R2 and amino group are situated on the ortho, meta or para positions relative to the hydroxy group without overlapping each other) comprises: making an aminophenol derivative react with chloroalkyl chlorocarbonate in a solvent having an alcoholic hydroxy group so as to obtain a corresponding carbamate derivative; and treating the carbamate derivative with alkali hydroxide. <P>COPYRIGHT: (C)2011,JPO&amp;INPIT

Description

The present invention relates to a method for producing a hydroxycarboxylic alkyl aminophenol derivative. The present invention is useful for producing a hair dye.

  Oxidative dyes are often used in dyeing hair. Hair dyed with an oxidative dye is excellent in light resistance and friction resistance and is robust. In addition, since the oxidation dye is excellent in covering property, once it is dyed on keratin, further oxidation is gradually advanced by oxygen in the air, and there is a strong tendency to darken. Ordinary dyes fade over time and behave in contrast to flow with each shampoo. Resorcinol and hydroxyalkylaminophenol derivatives are often used as toning agents necessary for coloring by combining with dyes for dyeing keratin and the like and dye precursor amines such as p-phenylenediamine. ing.

  A typical method for producing a hydroxyalkylaminophenol derivative consists of two steps (Patent Documents 1 to 3). That is, in the first step, the aminophenol derivative and chloroalkyl chloroformate are reacted in an aprotic solvent to obtain a carbamate derivative. In the second step, the carbamate derivative obtained in the first step is treated with a strong alkali in a water solvent to which a protic solvent is added to cause a rearrangement reaction (decarboxylation) to obtain a hydroxyalkylaminophenol derivative. Examples of the aprotic solvent used in the first step include dioxane, triol, chlorobenzole, dimethoxyethane, diethoxyethane, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, dioxane, tetrahydrofuran, monoethylene glycol dimethyl ether, and methyl-t-butyl ether. It is illustrated (patent documents 1 to 3).

  As described above, in the prior art, the first step is performed in an aprotic solvent. Here, the protic solvent is a solvent having a proton donating property, and examples thereof include alcohols, carboxylic acids, and phenols. Protic solvents also have the property of accepting protons (Lewis basic). Protic solvents have relatively highly acidic hydrogen bonded to oxygen or nitrogen atoms, but at the same time oxygen or nitrogen also has unshared electron pairs, so hydrogen bonds are formed between solvent molecules with protic solvents. It can be said that it is a solvent. Therefore, in the first step, it is common technical knowledge to increase the purity of the product to suppress the production of by-products by eliminating the protic solvent that can interfere with the reaction as much as possible from the reaction system. The reason why the first step is performed in an aprotic solvent in the prior art is considered to be based on this common general knowledge.

Japanese Patent Publication No. 61-33801 Japanese Patent Publication No. 3-80182 JP-A-7-149696

  However, many aprotic solvents are expensive, which is disadvantageous in terms of economy. Although it is possible to devise such as changing the solvent to an inexpensive one in the second step, the operation becomes complicated. Further, when an aprotic solvent is used, there is a problem that it takes time to process the waste liquid.

An object of the present invention, economics, operability, and is excellent in processability of the waste, it is to provide a manufacturing how hydroxyalkyl aminophenol derivatives which can be obtained product with high purity.

（式中、Ｒ１は水素原子、Ｃ１−Ｃ４のアルキル基、又はハロゲン原子を表し、Ｒ２は水素原子、Ｃ１−Ｃ４のアルキル基、Ｃ１−Ｃ４のアルキルアミノ基、ニトロ基、又はハロゲン原子を表し、Ｒ３は水素原子、又はＣ１−Ｃ２のアルキル基を表す。ここで、Ｒ１、Ｒ２、及びアミノ基は、互いに重複することなくＯＲ３に対してオルト、メタ、又はパラの位置にある。）
で表される化合物と、
一般式（２）

（式中、Ｒ４はＣ２−Ｃ６のクロロアルキル基を表す。）
で表される化合物とをアルコール性のヒドロキシ基を有する溶媒中で反応させて、一般式（３）

（式中、Ｒ１，Ｒ２，Ｒ３は一般式（１）と同様の意味を有し、Ｒ４は一般式（２）と同様の意味を有する。）
で表されるカルバマート誘導体を得る第一工程と、第一工程で得られたカルバマート誘導体を水酸化アルカリで処理する第二工程とを包含する、
一般式（６）

（式中、Ｒ１，Ｒ２，Ｒ３は一般式（１）と同様の意味を有し、Ｒ５はＣ２−Ｃ６のヒドロキシアルキル基を表す。）
で表されるヒドロキシアルキルアミノフェノール誘導体の製造方法である。 The invention described in claim 1 for solving the above-described problem is represented by the general formula (1).

(Wherein R1 represents a hydrogen atom, a C1-C4 alkyl group, or a halogen atom, and R2 represents a hydrogen atom, a C1-C4 alkyl group, a C1-C4 alkylamino group, a nitro group, or a halogen atom. , R3 represents a hydrogen atom or a C1-C2 alkyl group, wherein R1, R2, and an amino group are in an ortho, meta, or para position with respect to OR3 without overlapping each other.
A compound represented by
General formula (2)

(In the formula, R4 represents a C2-C6 chloroalkyl group.)
Is reacted with a compound represented by the formula (3) in a solvent having an alcoholic hydroxy group.

(In the formula, R1, R2 and R3 have the same meaning as in general formula (1), and R4 has the same meaning as in general formula (2).)
A first step of obtaining a carbamate derivative represented by: and a second step of treating the carbamate derivative obtained in the first step with an alkali hydroxide.
General formula (6)

(In the formula, R1, R2 and R3 have the same meaning as in the general formula (1), and R5 represents a C2-C6 hydroxyalkyl group.)
It is a manufacturing method of the hydroxyalkylaminophenol derivative represented by these.

The present invention relates to a method for producing a hydroxyalkylaminophenol derivative represented by the general formula (6), which is represented by the compound represented by the general formula (1) and the general formula (2). The first step of reacting the compound with a solvent having an alcoholic hydroxy group to obtain the carbamate derivative represented by the general formula (3), and the carbamate derivative obtained in the first step with an alkali hydroxide A second step of processing. The carbamate derivative represented by the general formula (3) is an intermediate formed in the first step when producing a hydroxyalkylaminophenol derivative useful as a hair dye. According to the present invention, the first step can be performed without using an aprotic solvent. Therefore, the production method of the hydroxyalkyl-aminophenol derivative of the present invention, economical, have excellent processability of the operability, and waste.

The invention according to claim 2 is the method for producing a hydroxyalkylaminophenol derivative according to claim 1, wherein the solvent is a primary alcohol or a secondary alcohol.

  With such a configuration, it is possible to provide a method for producing a hydroxyalkylaminophenol derivative that is more excellent in economy, operability, and waste liquid treatability.

（式中、ｍは０〜２の整数を表す）
で表されるクロロアルキル基である構成が好ましい（請求項３）。 R4 is the general formula (4)

_{- (CH 2) n -Cl (} 4)

(In the formula, n represents an integer of 2 to 6)
Or general formula (5)

(In the formula, m represents an integer of 0 to 2)
The structure which is a chloroalkyl group represented by (Claim 3) is preferable.

（式中、ｍは一般式（５）と同様の意味を有する。）
で表されるヒドロキシアルキル基である構成が好ましい（請求項４）。 R5 is the general formula (7)

— (CH ₂ ) _n —OH (7)

(In the formula, n has the same meaning as in the general formula (4).)
Or general formula (8)

(In the formula, m has the same meaning as in the general formula (5).)
The structure which is a hydroxyalkyl group represented by (Claim 4 ) is preferable.

Invention of Claim 5 transfers to a 2nd process, without isolate | separating the carbamate derivative obtained at the 1st process, The hydroxyalkylaminophenol derivative in any one of Claims 1-4 characterized by the above-mentioned. It is a manufacturing method.

  According to the present invention, a hydroxyalkylaminophenol derivative useful as a hair dye can be produced with high economic efficiency, operability, and waste liquid treatability, and a product can be obtained with high purity.

The first step in the present invention is to produce the carbamate derivative represented by the above general formula (3), and the aminophenol derivative represented by the above general formula (1) and the above general formula (2). The chloroalkyl chloroformate is reacted in a “solvent having an alcoholic hydroxy group”. Examples of the “solvent having an alcoholic hydroxy group” include aliphatic alcohols such as methanol, ethanol, propanol, butanol, pentanol, hexanol and octanol; cyclic alcohols such as cyclopentanol and cyclohexanol; ethylene glycol and diethylene glycol And glycols such as propylene glycol; cellosolves such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, and ethylene glycol monobutyl ether. Regarding alcohol, primary alcohols such as ethanol, n-propanol, n-butanol and isobutanol; secondary alcohols such as isopropanol and sec-butanol; tertiary alcohols such as tert-butanol are used. Although possible, primary and secondary alcohols are particularly preferred. In addition, both monohydric alcohols and dihydric or higher polyhydric alcohols (such as glycerin) can be used. Furthermore, both lower alcohols and higher alcohols can be used. About these solvents, only 1 type may be used and you may use in combination of multiple types.

  Although there is no limitation in particular as molar ratio at the time of making the said aminophenol derivative and chloroalkyl chloroformate react, For example, chloroalkyl chloroformate is 0.5 mol-1.5 mol with respect to 1 mol of aminophenol derivatives. Can be moles. The reaction between the aminophenol derivative and chloroalkyl chloroformate is preferably performed in a weak alkaline base atmosphere. Examples of the base include alkali metal hydrogen carbonates such as sodium hydrogen carbonate; alkaline earth metal carbonates such as calcium carbonate and magnesium carbonate; oxides of alkaline earth metals such as calcium oxide and magnesium oxide. It is done. About these bases, only 1 type may be used and you may use in combination of multiple types. Moreover, the usage-amount of these bases is 0.2-2.5 mol with respect to 1 mol of aminophenol derivatives of General formula (1), Preferably it is 0.4-1.5 mol.

  As temperature at the time of making the said aminophenol derivative and chloroalkyl chloroformate react, the range of 0 degreeC-100 degreeC can be employ | adopted, for example, Preferably it is the range of 10 degreeC-90 degreeC. Similarly, the pH value can be in the range of 3.0 to 10.0, preferably 6.0 to 8.0. Similarly, as the reaction time, for example, a range of 5 minutes to 6 hours can be employed.

The method for producing a hydroxyalkylaminophenol derivative of the present invention relates to a method for producing a hydroxyalkylaminophenol derivative represented by the above general formula (6), and the aminophenol derivative represented by the above general formula (1). And a chloroalkyl chloroformate represented by the general formula (2) to obtain a carbamate derivative represented by the general formula (3), and a carbamate derivative obtained in the first step. And a second step of treating with an alkali hydroxide. Examples of the alkali hydroxide employed in the second step include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide. The amount of these alkali hydroxides to be used can be, for example, 1 mol to 8 mol, preferably 1.5 mol to 5 mol, relative to 1 mol of the carbamate derivative. The reaction temperature may be, for example, 0 ° C. to 110 ° C., and the reaction time may be, for example, 10 minutes to 5 hours.

  When shifting from the first step to the second step, the carbamate derivative obtained in the first step may be isolated once by filtration or the like and then used for the second step, but without being isolated, the second step is performed as it is. You can also migrate.

  The following are examples of hydroxyalkylaminophenol derivatives that can be produced according to the present invention, the types of R1 to R5 in the above general formula, and the positions of R1, R2, and amino groups (the position of -OR3 is the 1st position) Indicates.

5- (β-hydroxyethyl) amino-2-methylphenol • amino group: 5-amino • R1, R2: hydrogen atom, 2-methyl • R3: hydrogen atom • R4: β-chloroethyl • R5: β-hydroxyethyl

5- (γ-hydroxypropyl) amino-2-methylphenol amino group: 5-amino R1, R2: hydrogen atom, 2-methyl R3: hydrogen atom R4: γ-chloropropyl R5: γ-hydroxy Propyl

4- (β-hydroxyethyl) amino-3-nitrophenol amino group: 4-amino, R1: hydrogen atom, R2: 3-nitro, R3: hydrogen atom, R4: β-chloroethyl, R5: β-hydroxyethyl

4- (γ-hydroxypropyl) amino-3-nitrophenol amino group: 4-amino, R1: hydrogen atom, R2: 3-nitro, R3: hydrogen atom, R4: γ-chloropropyl, R5: γ-hydroxy Propyl

4- (β-hydroxypropyl) amino-3-nitrophenol amino group: 4-amino, R1: hydrogen atom, R2: 3-nitro, R3: hydrogen atom, R4: β-chloropropyl, R5: β-hydroxy Propyl

4- (β-hydroxyethyl) amino-6-methyl-3-nitrophenol amino group: 4-amino, R1: 6-methyl, R2: 3-nitro, R3: hydrogen atom, R4: β-chloroethyl, R5 : Β-hydroxyethyl

4- (γ-hydroxypropyl) amino-6-methyl-3-nitrophenol amino group: 4-amino, R1: 6-methyl, R2: 3-nitro, R3: hydrogen atom, R4: γ-chloroepropyl R5: γ-hydroxypropyl

3- (β-hydroxyethyl) amino-2,6-dimethylphenol • amino group: 3-amino • R1, R2: 2-methyl, 6-methyl • R3: hydrogen atom • R4: β-chloroethyl • R5: β -Hydroxyethyl

6-chloro-4- (β-hydroxyethyl) amino-3-nitrophenol amino group: 4-amino, R1: 6-chloro, R2: 3-nitro, R3: hydrogen atom, R4: β-chloroethyl, R5 : Β-hydroxyethyl

6-chloro-4- (β-hydroxypropyl) amino-3-nitrophenol amino group: 4-amino R1: 6-chloro R2: 3-nitro R3: hydrogen atom R4: β-chloropropyl R5: β-hydroxypropyl

6-bromo-4- (β-hydroxyethyl) amino-3-nitrophenol amino group: 4-amino, R1: 6-bromo, R2: 3-nitro, R3: hydrogen atom, R4: β-chloroethyl, R5 : Β-hydroxyethyl

4- (β-hydroxyethyl) amino-2-nitroanisole, amino group: 4-amino, R1: hydrogen atom, R2: 2-nitro, R3: methyl, R4: β-chloroethyl, R5: β-hydroxyethyl

4- (β-hydroxypropyl) amino-2-nitroanisole, amino group: 4-amino, R1: hydrogen atom, R2: 2-nitro, R3: methyl, R4: β-chloropropyl, R5: β-hydroxypropyl

  Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.

Production of 5- (β-hydroxyethyl) amino-2-methylphenol [1]

(1) First step 0.5 mol (61.5 g) of 5-amino-2-methylphenol and 200 mL of ethanol were mixed and cooled to 5 ° C. To this was added 0.51 mol (42.8 g) of sodium hydrogen carbonate, and 0.5 mol (71.5 g) of chloroethyl chloroformate was added dropwise over 1 hour with stirring. Stirring was continued after completion of the addition, and when cooling water was added after a while, it solidified and became a white slurry. This was filtered at a low temperature to obtain white crystals containing β-chloroethyl-N- (3-hydroxy-4-methylphenyl) carbamate.

(2) Second Step The obtained white crystals were added to ethanol as a wet cake without drying. With the air shut off, 465 mL of a 23.5% aqueous sodium hydroxide solution was added dropwise at room temperature. Next, the temperature was raised to 50 ° C. and the reaction was performed for 5 hours, followed by hot filtration to remove insoluble matters. Concentrated hydrochloric acid was added dropwise to the filtrate for neutralization, followed by cooling to precipitate crystals. After filtration once, recrystallization was performed from ion-exchanged water to obtain 5- (β-hydroxyethyl) amino-2-methylphenol crystals. The obtained crystals were dried at low temperature or reduced pressure. Crystals having a liquid chromatography purity of 99% or more and a melting point of 90 to 92 ° C. were obtained in a yield of 90%. The results of crystal analysis are shown below.
- composition analysis (as _{C 9 H 13 N 1 O 2} )
Calculated values: C64.65, H7.84, N8.38
Analytical value: C64.51, H7.63, N8.39
UV-visible spectrophotometer (λmax): 295 nm, 244 nm, 206 nm

  From the above, β-chloroethyl-N- (3-hydroxy-4-methylphenyl) carbamate can be obtained by reacting 5-amino-2-methylphenol and chloroethyl chloroformate in ethanol, and It is shown that 5- (β-hydroxyethyl) amino-2-methylphenol can be obtained by treating the obtained β-chloroethyl-N- (3-hydroxy-4-methylphenyl) carbamate with alkali hydroxide. It was done.

Production of 5- (β-hydroxyethyl) amino-2-methylphenol [2]

(1) First Step In the same manner as in Example 1, 5-amino-2-methylphenol and chloroethyl chloroformate are reacted in ethanol to give β-chloroethyl-N- (3-hydroxy-4-methyl. A white slurry containing phenyl) carbamate was obtained.

(2) Second Step Ethanol and 465 mL of a 23.5% aqueous sodium hydroxide solution were added dropwise without filtering the white slurry obtained. Thereafter, the same operation as in Example 1 was performed to obtain 5- (β-hydroxyethyl) amino-2-methylphenol crystals. The obtained crystals were dried at low temperature or reduced pressure. Crystals having a liquid chromatography purity of 99% or more and a melting point of 90 to 92 ° C. were obtained in a yield of 91%. The results of crystal analysis are shown below.
UV-visible spectrophotometer (λmax): 295 nm, 245 nm, 206 nm

  From the above, without shifting β-chloroethyl-N- (3-hydroxy-4-methylphenyl) carbamate when moving from the first step to the second step, 5- (β-hydroxyethyl) amino-2- Methylphenol could be obtained.

Production of 5- (β-hydroxyethyl) amino-2-methylphenol [3]

  The same operation as in Example 1 was performed except that methanol was used in place of ethanol in the first step to obtain 5- (β-hydroxyethyl) amino-2-methylphenol crystals.

  From the above, β-chloroethyl-N- (3-hydroxy-4-methylphenyl) carbamate can be obtained by reacting 5-amino-2-methylphenol and chloroethyl chloroformate in methanol, and It is shown that 5- (β-hydroxyethyl) amino-2-methylphenol can be obtained by treating the obtained β-chloroethyl-N- (3-hydroxy-4-methylphenyl) carbamate with alkali hydroxide. It was done.

Preparation of 4- (β-hydroxyethyl) amino-3-nitrophenol

(1) First step 0.5 mol (77.0 g) of 4-amino-3-nitrophenol and 0.53 mol (44.5 g) of sodium hydrogen carbonate were added to 100 g of isopropanol and heated to 70 ° C. While stirring, 0.52 mol (74.4 g) of chloroethyl chloroformate was slowly added dropwise to solidify into a slurry. Thereafter, the mixture was ice-cooled, water was poured in at around 50 ° C., and the precipitated crystals were filtered at room temperature, and the crystals were washed well with water. As a result, yellow crystals of β-chloroethyl-N- (4-hydroxy-2-nitrophenyl) carbamate having a melting point of 137 to 138 ° C. were obtained in a yield of 96%.

(2) Second step The crystals obtained in the first step are added as they are to the methanol in the form of a wet cake without drying, and 213 mL of a 47% sodium hydroxide aqueous solution is added in a state where the air is shut off. For several hours. After completion of the reaction, the pH was adjusted to 8.0 with hydrochloric acid. The solution was cooled to 15 ° C., filtered with suction, washed with water, and dried. As a result, dark red crystals of 4- (β-hydroxyethyl) amino-3-nitrophenol having a liquid chromatography purity of 98% or more and a melting point of 142 to 143 ° C. were obtained in a yield of 90%. The results of crystal analysis are shown below.
Composition analysis (as C ₈ H ₁₀ N ₂ O ₄ )
Calculated value: C48.44, H5.05, N14.13
Analytical value: C48.30, H5.06, N13.98

  From the above, β-chloroethyl-N- (4-hydroxy-2-nitrophenyl) carbamate can be obtained by reacting 4-amino-3-nitrophenol and chloroethyl chloroformate in isopropanol, and It is shown that 4- (β-hydroxyethyl) amino-3-nitrophenol can be obtained by treating the obtained β-chloroethyl-N- (4-hydroxy-2-nitrophenyl) carbamate with alkali hydroxide. It was done.

  Preparation of 4- (γ-hydroxypropyl) amino-3-nitrophenol

(1) First Step The same operation as in the first step of Example 1 was performed except that chloropropyl chloroformate was used instead of chloroethyl chloroformate. Yellow crystals of γ-chloropropyl-N- (3-hydroxy-4-methylphenyl) carbamate were obtained with a yield of 93%.

(2) Second Step The same operation as in the second step of Example 1 was performed on the yellow crystals obtained in the first step. As a result, dark red crystals of 4- (γ-hydroxypropyl) amino-3-nitrophenol having a liquid chromatography purity of 98% or more and a melting point of 110 to 112 ° C. were obtained in a yield of 90%. The results of crystal analysis are shown below.
- composition analysis (as _{C 9 H 12 N 2 O 4} )
Calculated values: C50.94, H5.70, N13.20
Analytical value: C50.90, H5.51, N13.21

  From the above, by reacting 4-amino-3-nitrophenol and chloropropyl chloroformate in isopropanol, γ-chloropropyl-N- (3-hydroxy-4-methylphenyl) carbamate is obtained, and 4- (γ-hydroxypropyl) amino-3-nitrophenol can be obtained by treating the obtained γ-chloropropyl-N- (3-hydroxy-4-methylphenyl) carbamate with alkali hydroxide. It has been shown.

Preparation of 4- (β-hydroxyethyl) amino-6-methyl-3-nitrophenol

(1) First step The same procedure as in the first step of Example 4 was performed except that 4-amino-6-methyl-3-nitrophenol was used instead of 4-amino-3-nitrophenol, and β-chloroethyl was used. Crystals of -N- (4-hydroxy-5-methyl-2-nitrophenyl) carbamate were obtained.

(2) Second Step The crystal obtained in the first step is treated in the same manner as in the second step of Example 4, and 4- (β-hydroxyethyl) amino-6 having a melting point of 172 ° C. to 174 ° C. Crystals of methyl-3-nitrophenol were obtained. The analysis results of the obtained crystals are shown below.
- composition analysis (as _{C 9 H 12 N 2 O 4} )
Calculated values: C50.94, H5.70, N13.20
Analytical value: C51.01, H5.61, N13.20

  From the above, by reacting 4-amino-6-methyl-3-nitrophenol and chloroethyl chloroformate in isopropanol, β-chloroethyl-N- (4-hydroxy-5-methyl-2-nitrophenyl) is obtained. Carbamate is obtained, and the resulting β-chloroethyl-N- (4-hydroxy-5-methyl-2-nitrophenyl) carbamate is treated with alkali hydroxide to give 4- (β-hydroxyethyl) Amino-6-methyl-3-nitrophenol was shown to be obtained.

Preparation of 4- (β-hydroxypropyl) amino-3-nitrophenol

(1) First Step The same procedure as in the first step of Example 4 was performed except that chloroformate-β-chloropropyl was used instead of chloroethyl chloroformate, and β-chloropropyl-N- (2-nitro Crystals of -4-hydroxyphenyl) carbamate were obtained.

(2) Second Step The crystal obtained in the first step is treated in the same manner as in the second step of Example 4, and 4- (β-hydroxypropyl) amino-3- having a melting point of 146 ° C. to 148 ° C. Nitrophenol crystals were obtained. The results of crystal analysis are shown below.
- composition analysis (as _{C 9 H 12 N 2 O 4} )
Calculated values: C50.94, H5.70, N13.20
Analytical value: C50.89, H5.61, N13.22

  From the above, β-chloropropyl-N- (2-nitro-4-hydroxyphenyl) carbamate can be obtained by reacting 4-amino-3-nitrophenol and chloroformate-β-chloropropyl in isopropanol. And the obtained β-chloropropyl-N- (2-nitro-4-hydroxyphenyl) carbamate was treated with an alkali hydroxide to give 4- (β-hydroxypropyl) amino-3-nitrophenol. It was shown that

Preparation of 4- (β-hydroxyethyl) amino-2-nitroanisole

(1) First step 0.5 mol (77.0 g) of 4-amino-2-nitroanisole and 0.53 mol (44.5 g) of sodium hydrogen carbonate were added to 100 g of isopropanol and heated to 77 ° C. or higher. . While stirring, 0.52 mol (74.4 g) of chloroethyl chloroformate was slowly added dropwise to solidify into a slurry. Thereafter, the mixture was ice-cooled, water was poured in the vicinity of 50 ° C., and the precipitated crystals were filtered at room temperature. The crystals were washed well with water. As a result, yellow crystals of β-chloroethyl-N- (3-nitro-4-methoxyphenyl) carbamate having a melting point of 83 to 84 ° C. were obtained with a yield of 95%.

(2) Second Step The same operation as in the second step of Example 4 was performed on the obtained yellow crystals. As a result, orange crystals of 4- (β-hydroxyethyl) amino-2-nitroanisole having a liquid chromatography purity of 98% or more and a melting point of 81 to 83 ° C. were obtained in a yield of 85%. The results of crystal analysis are shown below.
- composition analysis (as _{C 9 H 12 N 2 O 4} )
Calculated values: C50.94, H5.70, N13.20
Analytical values: C51.00, H5.70, N13.15

  From the above, β-chloroethyl-N- (3-nitro-4-methoxyphenyl) carbamate can be obtained by reacting 4-amino-2-nitroanisole with chloroethyl chloroformate in isopropanol, and It is shown that 4- (β-hydroxyethyl) amino-2-nitroanisole can be obtained by treating the obtained β-chloroethyl-N- (3-nitro-4-methoxyphenyl) carbamate with alkali hydroxide. It was done.

Preparation of 6-chloro-4- (β-hydroxyethyl) amino-3-nitrophenol

(1) First step The same procedure as in the first step of Example 4 was performed except that 4-amino-6-chloro-3-nitrophenol was used instead of 4-amino-3-nitrophenol, and β-chloroethyl was used. A red color of -N- (5-chloro-4-hydroxy-2-nitrophenyl) carbamate was obtained.

(2) Second Step The crystal obtained in the first step is treated in the same manner as in the second step of Example 4, and 6-chloro-4- having a melting point of 171 ° C. to 173 ° C. (ethanol recrystallization melting point). Crystals of (β-hydroxyethyl) amino-3-nitrophenol were obtained. The analysis results of the obtained crystals are shown below.
Composition analysis (as C ₈ H ₉ N ₂ O ₄ Cl)
Calculated value: C41.31, H3.90, N12.04, Cl 115.24
Analytical values: C41.38, H3.81, N12.09, Cl 115.10

  From the above, by reacting 4-amino-6-chloro-3-nitrophenol and chloroethyl chloroformate in isopropanol, β-chloroethyl-N- (5-chloro-4-hydroxy-2-nitrophenyl) is obtained. Carbamate is obtained, and the resulting β-chloroethyl-N- (5-chloro-4-hydroxy-2-nitrophenyl) carbamate is treated with alkali hydroxide to give 6-chloro-4- (β It was shown that -hydroxyethyl) amino-3-nitrophenol is obtained.

Using 5- (β-hydroxyethyl) amino-2-methylphenol produced in Example 1, a hair dye was prepared by the following procedure.
5- (β-hydroxyethyl) amino-2-methylphenol 0.7 part 4-N- (β-hydroxyethyl) amino-aniline sulfate 0.2 part Ethanol 30 parts Surfactant 3 parts Water 55 parts + α
And triethanolamine was further added to make 100 parts to prepare a hair dye having a pH of 7.0 to 7.5. This hair dye was mixed with 3% hydrogen peroxide and applied to half-white gray hair. After 20 minutes, the hair was washed with water, further washed with shampoo and dried. As a result, the gray hair was colored dark red-purple.

Claims (5)

General formula (1)

(Wherein R1 represents a hydrogen atom, a C1-C4 alkyl group, or a halogen atom, and R2 represents a hydrogen atom, a C1-C4 alkyl group, a C1-C4 alkylamino group, a nitro group, or a halogen atom. , R3 represents a hydrogen atom or a C1-C2 alkyl group, wherein R1, R2, and an amino group are in an ortho, meta, or para position with respect to OR3 without overlapping each other.
A compound represented by
General formula (2)

(In the formula, R4 represents a C2-C6 chloroalkyl group.)
Is reacted with a compound represented by the formula (3) in a solvent having an alcoholic hydroxy group.

(In the formula, R1, R2 and R3 have the same meaning as in general formula (1), and R4 has the same meaning as in general formula (2).)
A first step of obtaining a carbamate derivative represented by: and a second step of treating the carbamate derivative obtained in the first step with an alkali hydroxide.
General formula (6)

(In the formula, R1, R2 and R3 have the same meaning as in the general formula (1), and R5 represents a C2-C6 hydroxyalkyl group.)
The manufacturing method of the hydroxyalkylaminophenol derivative represented by these. The method for producing a hydroxyalkylaminophenol derivative according to claim 1, wherein the solvent is a primary alcohol or a secondary alcohol. R4 is the general formula (4)

_{- (CH 2) n -Cl (} 4)

(In the formula, n represents an integer of 2 to 6.)
Or general formula (5)

(In the formula, m represents an integer of 0 to 2.)
The method for producing a hydroxyalkylaminophenol derivative according to claim 1, wherein the chloroalkyl group is represented by the formula: R5 is the general formula (7)

— (CH ₂ ) _n —OH (7)

(In the formula, n has the same meaning as in the general formula (4).)
Or general formula (8)

(In the formula, m has the same meaning as in the general formula (5).)
Method for producing a hydroxyalkyl-aminophenol derivative as claimed in claim 1, characterized in that in a hydroxyalkyl group represented. The process for producing a hydroxyalkylaminophenol derivative according to any one of claims 1 to 4, wherein the carbamate derivative obtained in the first step is transferred to the second step without separation.