JP3311372B2 - Method for producing 3-N, N-dialkylaminophenol derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a 3-N, N-dialkylaminophenol derivative useful as an organic industrial chemical or various dye intermediates.

[0002]

2. Description of the Related Art Conventionally, 3-aminophenol derivatives have been useful as organic industrial chemicals or various dye intermediates, and 3-N, N-dialkylaminophenol derivatives have also been known to be useful as dye intermediates. (For example, JP-B-56-52759). Also, 3-N,
It is known that N-dialkylaminophenol derivatives are produced by reacting 3-aminophenol with an alkylating agent (for example, JP-A-59-65053). In this method, approximately 1 mol of an alkyl halide is allowed to act on 1 mol of 3-aminophenol, and after alkali treatment, 3-N-monoalkylaminophenol is formed, and then an alkylating agent (dialkyl sulfate) is further added. To produce a 3-N, N-dialkylaminophenol derivative. That is, this is a method for producing a 3-N, N-dialkylaminophenol derivative in two steps using 3-aminophenol as a raw material.

In this production method, a 3-N, N-dialkylaminophenol derivative substituted with two identical alkyl groups is by-produced during the reaction of 3-aminophenol with an alkyl halide, and unreacted. 3-aminophenol remains, 3-N-monoalkylaminophenol and 3
It may be difficult to separate -N, N-dialkylaminophenol derivatives, and among the 3-N, N-dialkylaminophenol derivatives, in particular, 3-N, N-dialkylaminophenol substituted with a different alkyl group There was a major problem in producing derivatives. 2 more reactions
The operation at the time of production is complicated because it is performed in stages, and during the operation in the middle, for example, loss is likely to occur during the operation of isolating 3-N-monoalkylaminophenol, which may lead to a decrease in yield, It is not always an industrially satisfactory production method.

Further, a 3-N, N-dialkylaminophenol derivative reacts an alkylamine on resorcinol to form a 3-N-monoalkylaminophenol, and then further reacts with an alkylating agent (alkyl halide). It is also known to be manufactured (for example, JP-A-59-65053). However, the method described in the above publication is a method of producing a 3-N, N-dialkylaminophenol derivative in two steps using resorcinol as a starting material, the operation during production is complicated, and During operation, for example, loss tends to occur during the operation of isolating 3-N-monoalkylaminophenol,
In some cases, the yield may decrease, and this is not always an industrially satisfactory production method.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to improve the problems of the conventional method and to produce a high yield and high purity 3-N, N-dialkylaminophenol derivative by a simple operation. Is to provide a way.

[0006]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have reached the present invention. That is, the present invention provides a method for producing a 3-N, N-dialkylaminophenol derivative, comprising reacting an alkylamine (R ₁ NH ₂ ) with resorcinol;
The resulting 3-N-alkylaminophenol (3-N-
Without isolating the R ₁ -substituted aminophenol from the reaction solution, an alkylating agent (R ₂ agent) is added to the reaction solution to form the 3-N-alkylaminophenol (3-NR).
General formula (1) acting on _1- substituted aminophenol)
The present invention relates to a method for producing a 3-N, N-dialkylaminophenol derivative represented by the following formula (2).

[0007]

Embedded image (Wherein, R ₁ and R ₂ each independently represent an alkyl group having 1 to 20 carbon atoms)

The production method of the present invention relates to a method for producing a 3-N, N-dialkylaminophenol derivative represented by the general formula (1).
₁ and R ₂ each represent an alkyl group having 1 to 20 carbon atoms. R ₁ is preferably an alkyl group having 3 to 12 carbon atoms, for example, n-propyl group, n-butyl group, isobutyl group, n-pentyl group, isopentyl group, n-hexyl group, n-heptyl group, Examples thereof include an n-octyl group, an n-decyl group, and an n-dodecyl group. R ₂ is preferably an alkyl group having 1 to 12 carbon atoms, for example,
Methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, n
-Pentyl group, isopentyl group, n-hexyl group, n-
Examples include a heptyl group, an n-octyl group, an n-decyl group, and an n-dodecyl group.

In the present invention, the alkylamine (R ₁ N)
From H ₂₎ and resorcinol, 3-N-alkyl-aminophenol (3-N-R ₁ substituted aminophenol) alkylamine used in the first step reaction to obtain the (R ₁ N
The H _2), for example, n- propylamine, n- butylamine, isobutylamine, n- pentylamine,
Isopentylamine, n-hexylamine, n-heptylamine, n-octylamine, n-decylamine, n
-Dodecylamine and the like.

The amounts of resorcinol and alkylamine (R ₁ NH ₂ ) used are in the range of 0.8 to 2 moles, preferably 0.8 to 1.5 moles, of alkylamine per mole of resorcinol. Range. The reaction temperature is preferably in the range of 80 to 200 ° C, and 130 to 200 ° C.
C. is more preferred. The reaction time depends on the reaction temperature, but usually takes several hours to several tens of hours. In addition, at the time of this reaction, if a small amount of zinc chloride or magnesium chloride is present, the reaction can be promoted. In order to prevent coloring of the reaction solution, the reaction is preferably performed in an atmosphere of an inert gas such as nitrogen or argon. By this reaction, 3-N-alkylaminophenol (3-NR)
The reaction solution containing _{1-substituted} aminophenol) is obtained.

In the production method of the present invention, 3-N-alkylaminophenol (3-
NR ₁ -substituted aminophenol) without isolation
An alkylating agent is added to the reaction solution containing this, and the second-stage alkylation reaction is subsequently performed. From the reaction solution of the first step reaction, 3-N-alkylaminophenol (3-N-
In order to allow the alkylating agent to act without isolating the (R ₁ -substituted aminophenol), unreacted or excess alkylamine (R ₁ NH ₂ ) may be present in the reaction solution, but is preferably used. Most of the alkylamine (R ₁ NH ₂ ) contained in the reaction solution is removed from the reaction system by distillation.

Preferred examples of the alkylating agent used in the method of the present invention include a dialkyl sulfate, an alkyl halide, an alkyl-p-toluenesulfonic acid ester and a trialkyl phosphate. Specific examples include dimethyl sulfate, diethyl sulfate, di-n-propyl sulfate, di-n-butyl sulfate, methyl iodide, ethyl iodide, n-propyl bromide, isopropyl bromide, n-butyl bromide, and n-iodide. Butyl, sec-butyl bromide, n-pentyl bromide, isopentyl bromide, n-hexyl bromide, n-heptyl bromide, n-octyl bromide, n-decyl bromide, n-dodecyl bromide, methyl-p-toluenesulfonic acid ester, Ethyl-p-toluenesulfonic acid ester, n-propyl-p
-Toluenesulfonic acid ester, n-butyl-p-toluenesulfonic acid ester, n-hexyl-p-toluenesulfonic acid ester, trimethyl phosphate, triethyl phosphate, tri-n-butyl phosphate and the like. Can be.

3-N-alkylaminophenol (3-
N-R ₁ substituted aminophenol) 3-N is reacted with an alkylating agent to a reaction solution containing, in the reaction for obtaining the N- dialkylamino phenol derivative may or may not using a solvent, the solvent You can go in the presence. Examples of the solvent include benzene, toluene, xylene, chlorobenzene, and the like.When an alkyl halide is used as an alkylating agent, a polar solvent such as methanol, ethanol, isopropanol, methyl cellosolve, or dimethylformamide is used. It does not matter.
The reaction temperature of this alkylation is usually in the range of 20 to 200C, preferably in the range of 50 to 150C. The reaction time depends on the reaction temperature, but usually takes several hours to several tens of hours.

In order to obtain the desired 3-N, N-dialkylaminophenol derivative represented by the general formula (1) from the reaction solution obtained by the above reaction, the reaction mixture or the residue obtained by evaporating the solvent is used. With a base, for example, sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium acetate, potassium acetate, and the like, and then isolated. At this time, using a solvent,
The desired substance can be extracted. Further, if necessary, the product can be purified by distillation.

[0015]

EXAMPLES The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples. Example 1 (Production of 3-N, N-di-n-butylaminophenol) A mixture of 380 g (5.2 mol) of n-butylamine and 550 g (5 mol) of resorcinol was used at 140 to 150 ° C.
After stirring for 15 hours, unreacted n-butylamine was distilled off under reduced pressure (60 mmHg), 685 g (5 mol) of n-butyl bromide was added to the residue, and the mixture was further stirred at 80 to 90 ° C. for 8 hours. After the reaction, cool to room temperature and add 10% Na
After neutralization with OH water, the organic layer was separated and distilled under reduced pressure to obtain 972 g of 3-N, N-di-n-butylaminophenol as an almost colorless oil. HPLC
Was 99%, and the yield was 88%. b.
p. Was 173 to 176 ° C / 6 mmHg.

Example 2 (Production of 3-Nn-butyl-N-methylaminophenol) In Example 1, methyl-p-toluenesulfonic acid ester was used instead of using n-butylbromide. Otherwise, according to the method described in Example 1, 3-N-
n-Butyl-N-methylaminophenol was produced.
HPLC 99% purity, 87% yield, b. p.
Was 109 to 115 ° C / 1.5 mHg.

Example 3 (Production of 3-Nn-butyl-N-ethylaminophenol) In Example 1, ethyl-p-toluenesulfonic acid ester was used instead of using n-butylbromide. Otherwise, according to the method described in Example 1, 3-N-
n-Butyl-N-ethylaminophenol was produced.
99% purity by HPLC, 89% yield, b. p.
Was 108 to 114 ° C / 1.5 mmHg.

Example 4 (Production of 3-N, N-di-n-hexylaminophenol) A mixture of 520 g (5.15 mol) of n-hexylamine and 550 g (5 mol) of resorcinol was mixed with 140 to 15 parts.
After stirring at 0 ° C. for 15 hours, unreacted n-hexylamine was distilled off under reduced pressure (60 mmHg), and 825 g (5 mol) of n-hexyl bromide was added to the residue.
Stirring was performed at 8 ° C. for 8 hours. After the reaction, cool to room temperature,
After neutralization with 10% aqueous NaOH, the organic layer was separated and distilled under reduced pressure to obtain 1205 g of 3-N, N-di-n-hexylaminophenol as a nearly colorless oil. The purity by HPLC was 99% and the yield was 87%. b. p. Was 190 to 195 ° C / 3 mmHg.

Example 5 (3-Nn-hexyl-N-
Production of ethyl aminophenol) In Example 4, 3-N-hexyl bromide was used instead of ethyl-p-toluenesulfonic acid ester, except that n-hexyl bromide was used.
-N-Hexyl-N-ethylaminophenol was prepared. 99% purity by HPLC, 89% yield, b.
p. Was 139 to 141 ° C./1 mmHg.

Comparative Example 1 To 400 ml of methanol was added 109 g of 3-aminophenol and 54 g of anhydrous sodium carbonate.
184 g of butyl iodide was added dropwise over 1.5 hours.
After the dropwise addition, the mixture was stirred at the same temperature for 8 hours, filtered, and methanol was distilled off from the filtrate. The residue was analyzed by HPLC to find that the starting material, 3-aminophenol and 3-aminophenol, were obtained in addition to the desired 3-Nn-butylaminophenol.
-N, N-di-n-butylaminophenol each contained about 15%. The residue was extracted with toluene and most of the raw material 3-aminophenol was removed with warm water.
The toluene is distilled off, and the residue is distilled under reduced pressure (124 to 128 ° C).
/ 1 mmHg) to obtain 110 g of 3-N-n-butylaminophenol. The purity by HPLC was 94% and contained about 6% of 3-N, N-di-n-butylaminophenol. The yield was 67%. This 3-N
110 g of n-butylaminophenol in toluene 66
The solution was dissolved in 0 ml, water (66 ml) was added, and dimethyl sulfate (126 g) was added dropwise at 50-60 ° C. After stirring at the same temperature for 1 hour, the mixture was cooled to room temperature, neutralized with NaOH, and the toluene layer was separated.
After the toluene layer was further washed with warm water, toluene was distilled off. The residue was distilled under reduced pressure (109-115 ° C./1.5 mm
Hg) to give 81 g of the desired 3-Nn-butyl-N-methylaminophenol. The purity by HPLC was 96% and contained about 4% of 3-N, N-di-n-butylaminophenol. The yield from 3-aminophenol was 45%, and the yield described in Example 2 (8
7%).

COMPARATIVE EXAMPLE 2 A mixture of 380 g (5.2 mol) of n-butylamine and 550 g (5 mol) of resorcinol was heated at 140 to 150 ° C.
After stirring for 15 hours at room temperature and cooling to room temperature, toluene 1000
After adding toluene, the toluene layer was separated, and the toluene layer was further washed with warm water, and then toluene was distilled off under reduced pressure. The residue was distilled under reduced pressure (124 to 128 ° C / 1 mmHg) to give 3-N-n.
536 g of -butylaminophenol were obtained. 65% yield
536 g of this 3-N-n-butylaminophenol was added to 1000 ml of methyl cellosolve, and ethyl iodide 507 g was added.
g was added and the mixture was stirred at 80 to 90 ° C. for 8 hours. After the reaction, methyl cellosolve was distilled off under reduced pressure, and the residue was 10%
After neutralization with NaOH water, the organic layer was separated and distilled under reduced pressure (bp: 108 to 114 ° C./1.5 mmH) to obtain 564 g of 3-N-n-butyl-N-ethylaminophenol. I got The yield from resorcinol is 58
%, Which was lower than the yield described in Example 3 (89%).

[0022]

According to the present invention, it has become possible to obtain a highly pure 3-N, N-dialkylaminophenol derivative by a simple operation and in a high yield.

──────────────────────────────────────────────────続 き Continuation of front page (58) Field surveyed (Int. Cl. ⁷ , DB name) C07C 215/00 C07C 213/00 CA (STN)

Claims (1)

(57) [Claims] 1. A method for producing a 3-N, N-dialkylaminophenol derivative, which comprises reacting an alkylamine (excluding cyclohexylamine) with resorcinol and containing the produced 3-N-alkylaminophenol. After removing the unreacted alkylamine from the liquid by distillation, without isolating the 3-N-alkylaminophenol from the reaction solution, distilling off the unreacted alkylamine with an alkylating agent without solvent. The compound of the general formula (1), which is added to the removed reaction solution to act on the 3-N-alkylaminophenol. (Wherein, R1 has 1 to 20 carbon atoms excluding a cyclohexyl group)
Wherein R2 represents an alkyl group having 1 to 20 carbon atoms.) A method for producing a 3-N, N-dialkylaminophenol derivative represented by the formula: