JPH05996A - Production of isoamyl glycolic acid - Google Patents

Abstract

PURPOSE:To enable to safely and massively produce isoamyl glycolic acid useful as a synthetic intermediate for perfume compounds from isoamyl alcohol as a raw material without metal sodium. CONSTITUTION:Isoamyl alcohol is reacted in the presence of a quaternary ammonium or a compound capable of forming the quaternary ammonium in the reaction system and a metal hydroxide salt, while removing by-produced water, and subsequently reacted with a monohalogenated acetic acid, thereby permitting to produce isoamyl glycolic acid in a high purity and in a high yield.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel process for producing isoamyl glycolic acid, which is extremely useful as a synthetic intermediate for perfume compounds for cosmetics, pharmaceuticals and foods and drinks, and more specifically, without using metallic sodium. A safe and industrial process of reacting isoamyl alcohol with a phase transfer catalyst or a compound capable of forming a phase transfer catalyst in the reaction system in the presence of a metal hydroxide salt to form an isoamyl alkoxide, and then reacting with a monohalogenated acetic acid. Relates to a highly advantageous method for producing isoamyl glycolic acid.

[0002]

2. Description of the Related Art Isoamyl glycolic acid is an important synthetic intermediate for fragrance compounds. However, there has been little research on a method for producing such branched alkoxyacetic acids, for example, a branched alcohol is converted to sodium alkoxide by using metallic sodium. Method for synthesizing branched alkoxyacetic acid by desalting reaction between sodium alkoxide and monochloroacetic acid (Suzuka National College of Technology, 21 (1), 109-113
(1988) is known.

[0003]

However, the reaction using metallic sodium is dangerous and is difficult to manufacture on a large scale. Further, the reaction yield is low and the price is very expensive, which is an industrial method. There are many challenges.

[0004]

[Means for Solving the Problems] The inventors of the present invention have made extensive studies to solve such problems. As a result, a compound capable of forming a phase transfer catalyst with isoamyl alcohol or a compound capable of forming a phase transfer catalyst in the reaction system is reacted in the presence of a metal hydroxide salt to form an isoamyl alkoxide, and an unreacted metal hydroxide salt can be reacted. It was found that the target isoamyl glycolic acid can be synthesized with high purity and high yield by reacting with monohalogenated acetic acid. According to the method of the present invention, the conventional dangers can be completely avoided without using metallic sodium, and industrially extremely advantageous and large-scale production is possible. A typical reaction formula of this step is as follows.

[0005]

[Figure 1]

Next, an embodiment of the present invention will be specifically described according to the reaction formula of FIG. First, isoamyl alcohol is reacted with a phase transfer catalyst or a compound capable of forming a phase transfer catalyst in the reaction system in the presence of metal hydroxide salts. The reaction is carried out with 1 mol of isoamyl alcohol and, for example, triethylbenzylammonium chloride,
About 0.01 to about 0.1% by weight of a phase transfer catalyst such as quaternary ammonium such as triethyloctyl ammonium chloride, or alternatively, as a compound capable of forming a phase transfer catalyst in the reaction system, for example, triethylamine, Amine such as trimethylamine, tributylamine, trioctylamine, etc. is added to isoamyl alcohol at about 0.0
1 to 10% by weight, preferably about 0.1 to about 5% by weight and about 0.0% of an organic halide such as benzyl chloride, benzyl bromide, butyl chloride and butyl iodide.
1 to about 10% by weight, preferably about 0.1 to about 5% by weight, added to about 0 ° C to about 200 ° C, preferably about 50 to about 150 ° C.
The quaternary ammonium can be formed by heating and reacting at 0 ° C. for about 10 to about 60 minutes.

After cooling to about 0 to about 100 ° C., preferably about room temperature, for example, about 0.1 to about 1 mol of metal hydroxide salts such as sodium hydroxide, potassium hydroxide, barium hydroxide and calcium hydroxide. Is added for about 1 to about 60 minutes, preferably about 1 to about 30 minutes to form the isoamyl alkoxide. At this time, it is desirable to forcibly remove the water generated along with the formation of the alkoxide out of the system to reduce unreacted metal hydroxide salts as much as possible. Any known means can be used to remove water outside the reaction system, and examples thereof include a heating distillation method, a reduced pressure distillation method, and an azeotropic distillation method in which a solvent that is azeotropic with water is added. However, an azeotropic distillation method capable of carrying out the reaction at a relatively low temperature can be preferably mentioned. As a specific example of the azeotropic distillation method, for example, a solvent such as cyclohexane, benzene, toluene, and xylene which is azeotropic with water is added in an amount of about 0.1 to about 100% by weight with respect to the reaction mixture.
An example is a method of efficiently forming an isoamyl alkoxide by azeotropic distillation at 0 to about 140 ° C., preferably about 120 to about 130 ° C. for about 2 to about 10 hours to remove water.

To the resulting reaction mixture is added about 0.01 to about 1 mol of at least one monohalogenated acetic acid selected from monochloroacetic acid, monobromoacetic acid, ethyl monochloroacetate, isoamyl monochloroacetate, etc.
Add at 0 ° C., preferably about 40 to about 80 ° C. for about 5 minutes to about 3 hours, preferably about 10 minutes to about 30 minutes, and further under reflux conditions for about 1 to about 50 hours, generally about Let react for 2 to about 40 hours. After completion of the reaction, excess isoamyl alcohol was recovered under normal pressure conditions, and about 1.5 times by weight of water of the isoamyl alcohol used was dropped into the reaction solution and azeotroped with water to completely remove the isoamyl alcohol. By recovering, an alkali metal salt of isoamyl glycolic acid can be obtained.

The alkali metal salt of isoamyl glycolic acid utilizes a known desalting reaction. For example, a free acid is formed by adding an inorganic acid such as hydrochloric acid, sulfuric acid, phosphoric acid or the like to make it acidic, and for example toluene, benzene, Isoamyl glycolic acid can be obtained by extraction with a solvent such as xylene or cyclohexane. The carboxylic acid can be further purified by vacuum distillation or the like.

The above reaction can also be carried out by reacting isoamyl alcohol with a phase transfer catalyst or a compound capable of forming a phase transfer catalyst in the reaction system and a monohalogenated acetic acid in the presence of a metal hydroxide salt. However, in that case, the metal hydroxide salts and the monohalogenated acetic acid react with each other to form monohydroxyacetic acid, which causes a significant decrease in yield, which is not preferable. Hereinafter, embodiments of the present invention will be described in more detail with reference to Examples.

[0011]

Example 1 352 g of isoamyl alcohol in a 1-liter 4-diameter flask
(4 mol), 3 g of triethylamine and 2.5 g of benzyl chloride were charged and reacted by heating at about 110 ° C. for 30 minutes, cooled to 80 ° C. or lower and 48 g of sodium hydroxide (1.
2 mol) was added in 10 minutes. Then attach a side tube with a condenser and heat the mixture to about 135-145 ° C to about 10
The water was distilled over time. Cool the reaction mixture to about 55
47.3 g of monochloroacetic acid (0.
5 mol) was added dropwise over about 10 minutes, and after the addition was completed, the reaction was further continued at about 120 to about 130 ° C. for 3 hours. After completion of the reaction, excess isoamyl alcohol was recovered, and water 25
0 ml was added and isoamyl alcohol was removed azeotropically. After cooling, 250 ml of water was added, acidified with concentrated hydrochloric acid, and then extracted with 150 ml of toluene. Toluene was removed from the extract, and then crude distillation was performed to give a boiling point of 93-9.
Isoamyl glycolic acid fraction of 8 ° C./2 mmHg 65.
9 g was obtained (yield 90.3%). [0012]

Example 2 A 5 l 4-diameter flask was charged with 2816 g (32 mol) of isoamyl alcohol, 24 g of triethylamine and 20 g of benzyl chloride, and the mixture was heated at about 110 ° C. for 30 minutes.
The mixture was heated and reacted for 1 minute, cooled to 80 ° C. or lower, and 384 g (9.6 mol) of sodium hydroxide was added over 30 minutes. Then, a side tube equipped with a condenser was attached, 350 ml of toluene was added, and then the mixture was heated to about 125 to 130 ° C. and water was distilled out over about 10 hours. Cool the reaction mixture to about 55-65
While maintaining the temperature at ℃, 378 g (4 mol) of monochloroacetic acid was added dropwise over about 10 minutes.
The reaction was carried out at about 130 ° C for 12 hours. After completion of the reaction, excess isoamyl alcohol was recovered, and 2.5 l of water was further added to remove isoamyl alcohol by azeotropic distillation. After cooling, 1.5 l of water was added, acidified with concentrated hydrochloric acid, and then extracted with toluene. Toluene was removed from the extract, and then crude distillation was performed to obtain 505 g of an isoamyl glycolic acid fraction having a boiling point of 93 to 98 ° C / 2 mmHg (yield 87
%).

[0013]

Comparative Example 1 In the same manner as in Example 1, 352 g (4 mol) of isoamyl alcohol, 3 g of triethylamine and 2.5 g of benzyl chloride were charged into a 1-liter four-diameter flask, and the mixture was heated at about 110 ° C. for 30 minutes to react at 80 ° C. or lower. After cooling, 48 g (1.2 mol) of sodium hydroxide was added over 10 minutes. Then a reflux condenser was attached and the mixture was heated to about 135
It was heated to 145 ° C. and reacted for about 10 hours without distilling water. While cooling the reaction mixture and maintaining it at about 55 to 65 ° C, about 47.3 g (0.5 mol) of monochloroacetic acid was added to about 1
Drop it over 0 minutes and add about 120-
The reaction was carried out at about 130 ° C. for 3 hours. After completion of the reaction, excess isoamyl alcohol was recovered, and 250 ml of water was further added to remove isoamyl alcohol by azeotropic distillation. After cooling,
After adding 250 ml of water and acidifying with concentrated hydrochloric acid, toluene 1
Extracted with 50 ml. Toluene is removed from the extract, and then crude distillation is carried out to give a boiling point of 93 to 98 ° C / 2 mmHg.
39 g (yield 53%) of isoamyl glycolic acid were obtained.

[0014]

According to the present invention, when isoamyl alcohol and a phase transfer catalyst or a compound capable of forming a phase transfer catalyst in a reaction system are reacted in the presence of a metal hydroxide salt to form an isoamyl alkoxide, By carrying out the reaction while removing the produced water, the unreacted metal hydroxide salts are extremely reduced, and then by reacting with monohalogenated acetic acid, the desired isoamyl glycolic acid can be obtained with high purity and high yield. Can be synthesized. Furthermore, according to the present invention, large-scale production, which has been impossible with the conventional high-risk method using metallic sodium or sodium alkoxide, etc., becomes possible, and the raw material cost and the production cost are significantly increased as compared with the conventional method. It can be reduced. The isoamyl glycolic acid obtained by the present invention is extremely useful as a synthetic intermediate for a fragrance compound.

Claims (1)

Claim: What is claimed is: 1. An isoamyl alcohol and a phase transfer catalyst or a compound capable of forming a phase transfer catalyst in a reaction system are reacted in the presence of a metal hydroxide salt to form an isoamyl alkoxide. A method for producing isoamyl glycolic acid, which comprises reacting with halogenated acetic acid.