JP2000281624A - Method for producing α-hydroxy acid esters - Google Patents

Abstract

(57) [Summary] [Object] To provide a method for producing α-hydroxy acid esters with good operability and high yield. A method for producing an α-hydroxy acid ester comprising the following steps (1) to (3). (1) a step of reacting ketones with hydrogen cyanide to form α-cyanhydrins;
(2) The α-cyanhydrins are hydrolyzed with mineral acid to form α-cyanhydrins.
(3) a step of esterifying the α-hydroxy acids in the presence of an inorganic salt to form α-hydroxy acids;

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION [0002] α-Hydroxy acid esters are important synthetic intermediates such as pharmaceutical intermediates for treating urinary incontinence and hypertension, liquid crystal materials, optical resolving agents and the like. The present invention relates to a method for producing α-hydroxy acid esters in a simple and high yield by using inexpensive hydrogen cyanide and ketones having simple chemical structures as raw materials.

[0002]

2. Description of the Related Art As a method for producing .alpha.-hydroxy acid esters, (1) a method comprising reacting an aqueous solution of hydrochloric acid with .alpha.-hydroxy acid methyl ester as a raw material and then esterifying the resulting .alpha.-hydroxy acid again, "J. Org.
USSR (Engl. Transl.), 23 <198
7> 7, 1298-1303 ", (2) a method of reacting ammonia using α-hydroxy acid methyl ester as a raw material and then esterifying the obtained α-hydroxy acid amide“ J. Chem. Soc., <1951> 2329,2
331 "and the like are known as known documents. on the other hand,
The method for producing α-hydroxy acid esters using ketones as a raw material is as follows: (3) After reacting sodium cyanide on ketones, then reacting aqueous solution of sulfuric acid on the obtained α-cyanohydrins, -Esterification of -hydroxy acids or α-hydroxy acid amides [J.
m. Soc. , <1951> 2329, 2331 ",
"Chem. Lett., <1992> 2, 251-2.
52 ", (4) after reacting sodium cyanide on ketones, after reacting ammonium sulfite on the obtained α-cyanohydrins, and then reacting α-hydroxythioamide obtained with an aqueous hydrochloric acid solution to obtain α-hydroxythioamide. Method for esterifying an acid “J. Chem. Soc., 2329, 2331 <
1951>"is known as a known document. The method for producing α-cyanhydrins, which are intermediates for the synthesis of α-hydroxy acid esters using ketones as raw materials, includes (5) a method of reacting sodium cyanide on ketones “J. Org. Chem. ., <1969>
34, no. 9, 2543-2549 "is known as a known document.

Since both methods (1) and (2) use an expensive α-hydroxy acid methyl ester as a starting material because of its complicated chemical structure, an industrially inexpensive method for producing an α-hydroxy acid ester is required. Can not be. On the other hand, method (3)
In (4) and (5), ketones having a simple chemical structure are used as starting materials, but since sodium cyanide is used,
During the reaction, some of the α-cyanohydrins caused polymerization. For this reason, there are difficulties such as a decrease in the quality of α-cyanohydrins and a decrease in the reaction yield, and the solidification of the reaction solution for the synthesis of α-cyanhydrins, such that the operability is extremely poor. -Hydroxy acid esters could not be obtained. When the corresponding α-hydroxy acids are produced by reacting the α-hydroxy acids obtained by the methods (1) to (5) with a poorly water-soluble saturated alkyl alcohol, If a large excess of saturated alkyl alcohol is not used, the esterification reaction liquid will not be uniform, and if the amount of saturated alkyl alcohol is reduced, unreacted α-hydroxy acid will remain in the aqueous phase. The reaction yield was reduced. For the above reasons, none of the methods (1) to (5) was an industrially satisfactory method for producing α-hydroxy acid esters.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to react ketones having a simple chemical structure with inexpensive ketones as a raw material, thereby producing α-cyanohydrins without polymerization and consolidation of the reaction solution. -After the production of cyanohydrins, they are formed into α-hydroxy acids by a hydrolysis reaction, and in the presence of an inorganic salt, an esterification reaction is carried out to improve the operability and the yield of α-hydroxy acids.
An object of the present invention is to provide a method for producing hydroxy acid esters.

[0005]

Means for Solving the Problems The present inventors have conducted intensive studies on a method for producing industrially advantageous α-hydroxy acid esters, and as a result, when hydrogen cyanide acts on ketones, α-cyanhydrins are produced. It has been found that α-cyanhydrins can be produced with high operability and high yield without involving polymerization and consolidation of the reaction solution. The obtained α-cyanhydrins were subjected to a conventional esterification reaction of α-hydroxy acid after mineral acid hydrolysis. -Despite the difficulty in reconciling the conditions for improving the conversion of the hydroxy acid, if appropriate conditions are selected in the presence of the inorganic salt, the α-hydroxy acid ester can be efficiently produced without much by-product of the alkyl ether. Have been found to be able to produce the same, leading to the present invention.

[0006] That is, the present invention provides a method comprising the steps of:
(3) A method for producing α-hydroxy acid esters. Step (1) The following general formula [I]

Embedded image (Wherein, R ₁ and R ₂ represent a halogen or a branched or straight-chain saturated or unsaturated alkyl group having 1 to 6 carbon atoms which may be substituted with an alkoxy group having 1 to 4 carbon atoms. , R ₁ and R ₂ are not simultaneously methyl groups,
R ₁ and R ₂ may combine to form a ring. A) reacting hydrogen cyanide with a ketone represented by the formula (1) in the presence of a base catalyst to obtain an α-cyanhydrin represented by the following general formula [II].

Embedded image (In the formula, R ₁ and R ₂ are the same as described above.) Step (2) A step of hydrolyzing the α-cyanhydrins in the presence of a mineral acid catalyst to form α-hydroxy acids represented by the following general formula [III]. .

Embedded image (In the formula, R ₁ and R ₂ are the same as described above.) Step (3) The α-hydroxy acids are reacted with a branched or straight-chain saturated alkyl alcohol having 4 to 8 carbon atoms in the presence of an inorganic salt. A step of forming an α-hydroxy acid ester represented by the following general formula [IV].

Embedded image (In the formula, R ₁ and R ₂ are the same as above, and R ₃ represents a branched or straight-chain saturated alkyl group having 4 to 8 carbon atoms.) ”.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.

The ketones used in the step (1) of the present invention include, specifically, methyl ethyl ketone, 2-pentanone, 3-pentanone, 3-methyl-2-butanone,
-Hexanone, 3-hexanone, 2-heptanone, 3-
Heptanone, cyclobutanone, cyclopentanone, cyclohexanone, trans-4-methoxy-3-buten-2-one, acetophenone, 1,1,1-trifluoroacetone, 1,1-dichloroacetone, 1,1,1-
Examples include, but are not limited to, trichloroacetone, 1,1,3-trichloroacetone, α, α, α-trifluoroacetophenone.

Specific examples of the basic catalyst used in the step (1) of the present invention include basic compounds containing an alkali metal such as sodium carbonate, potassium carbonate, sodium acetate, potassium acetate, sodium hydroxide, and hydroxide. Examples thereof include alkali metal hydroxides such as potassium, and basic alkylamines such as diethylamine and triethylamine.

The amount of hydrogen cyanide used for the ketones in the step (1) of the present invention varies depending on the type of ketones, but is usually preferably 1 to 5 equivalents. The reaction temperature is in the range of 0 to 85 ° C.,
5 ° C. is preferred. The reaction time varies depending on the reaction temperature, but is usually applied within 4 hours, in the range of 0.2 to 24 hours. Isolation and purification of α-cyanhydrins from the reaction-finished solution can be performed by a general method such as solvent extraction, crystallization, salting out, or distillation, but directly without isolation and purification of α-cyanhydrins, Step (2) for the reaction completed solution
You can also do

[0011] Specific examples of the mineral acid catalyst used in the step (2) of the present invention include sulfuric acid, hydrochloric acid, nitric acid and the like.

The amount of the mineral acid catalyst used for the α-cyanhydrins in the step (2) of the present invention varies depending on the types of the α-cyanhydrins and the mineral acid catalyst, but is usually preferably 0.5 to 5 equivalents. . In addition, the amount of water used for the α-cyanhydrins is usually preferably 2 to 5 equivalents. The reaction temperature is applied in the range of 20 to 200 ° C, preferably 80 to 100 ° C. The reaction time is
Although it varies depending on the reaction temperature, it is usually within 8 hours, and the reaction is carried out at 0.1.
It is applied in the range of 2 to 24 hours. Α from reaction end solution
-Hydroxy acids are isolated and purified by solvent extraction, crystallization, salting out,
It can be carried out by a general method such as distillation.
Step (3) can also be performed directly on the reaction-terminated liquid without isolating and purifying the hydroxy acids.

The inorganic salt used in the step (3) of the present invention may be any one of an alkali metal or an alkaline earth metal such as Na ⁺ , K ⁺ , Mg ²⁺ and Cl ⁻ , I ⁻ , SO ⁴² , PO ₄ .
₄ ³ inorganic salt comprising a combination of any of the anions and the like. Specifically, sodium chloride,
Examples thereof include sodium iodide, sodium sulfate, sodium phosphate, potassium chloride, potassium iodide, potassium sulfate, potassium phosphate, magnesium chloride, magnesium iodide, magnesium sulfate, and magnesium phosphate.

The alcohols used in step (3) of the present invention include, specifically, n-butanol, n-pentanol, n-heptanol, n-hexanol, 1-octanol, sec-butyl alcohol, isobutyl alcohol Alcohol, tert-butyl carbinol, 2-octanol and the like can be mentioned.

The amount of the alcohol to be used with respect to the α-hydroxy acid in the step (3) of the present invention varies depending on the combination of the α-hydroxy acid and the alcohol.
Although it is applied in the range of ５5 equivalents, it is preferred that the amount is 1１〜３3 equivalents. Further, the amount of the inorganic salt used for the α-hydroxy acids may be usually added in a range where the inorganic salt concentration of the aqueous phase generated by the esterification reaction becomes a saturated concentration,
0.05 to 1 equivalent is preferred, more preferably 0.05
~ 0.5 equivalents. The reaction temperature is 20 to 200
Although it applies in the range of ° C, 70-90 ° C is especially preferred for avoiding by-product of alkyl ether. The reaction time varies depending on the reaction temperature, but is usually within 8 hours, 0.2 to
Applicable for 24 hours. The α-hydroxy acid esters can be isolated and purified from the reaction completed solution by a general method such as solvent extraction, crystallization, salting out, concentration, and distillation.

[0016]

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 Synthesis of 2-trifluoromethyl-2-hydroxypropionitrile 60 wt% 1,1,1-trifluoroacetone aqueous solution 3
2.2 g of sodium carbonate was added to 950 g, and the internal temperature was set to 1
While controlling at 0 ° C., 686 g of hydrogen cyanide was added dropwise. Thereafter, the mixture was heated and stirred at 30 ° C. for 3.0 hours. About aging solution, "Aso, Analytical Chemistry Baifukan p2
49 <1950>. "Quantification of cyanide" and "Hiroshi Namiki,
Detailed explanation Factory drainage test method Daiichi Printing Press p213-216
<1982>. A cyan titration analysis was carried out according to the method described in "Silver nitrate titration method".
%, And free cyanide content of 2.45 wt%. From the above results, 4628 g of a 62.2 wt% solution of 2-trifluoromethyl-2-hydroxypropionitrile was obtained.
98% was added to 4618 g of the obtained 62.2 wt% solution of 2-trifluoromethyl-2-hydroxypropionitrile.
After adding 6.72 g of sulfuric acid and 212.7 g of sodium chloride and stirring, the phases were separated to obtain oily oil having a purity of 78.3 wt%.
There were obtained 3,885 g of a trifluoromethyl-2-hydroxypropionitrile solution (lower phase). At this time, the acquisition yield of 2-trifluoromethyl-2-hydroxypropionitrile in terms of pure content was 98.1%.

Example 2 Synthesis of 2-trifluoromethyl-2-hydroxypropionic acid 3648 g of 78.3 wt% 2-trifluoromethyl-2-hydroxypropionitrile solution obtained in Example 1
While controlling the internal temperature to 70 ° C, 98% sulfuric acid 39
31 g and 1150 g of pure water were sequentially dropped. Then 95
The mixture was heated and stirred at 7.5 ° C. for 7.5 hours. The oily matured solution was subjected to cyan titration analysis by the method described in Example 1 to obtain 8511 g of a hydrolysis reaction completed solution containing 152 ppm of all cyan ions. From the above results, the conversion of 2-trifluoromethyl-2-hydroxypropionitrile was 99.8%. In addition, HPLC analysis of the hydrolysis-terminated liquid showed that the selectivity to 2-trifluoromethyl-2-hydroxypropionic acid was 99.
6%.

Example 3 Synthesis of 2-trifluoromethyl-2-hydroxypropionic acid-n-butyl ester To 2123 g of the reaction solution obtained in Example 2, 59.3 g of sodium chloride was added, and then n-butanol was added. 72
Extraction and phase separation were performed with 7 g to obtain 1,686 g of a 48.4 wt% 2-trifluoromethyl-2-hydroxypropionic acid n-butanol solution (upper phase). After adding 36.3 g of sodium chloride to the obtained upper phase, the mixture was heated and stirred at 80 ° C. for 4.0 hours. The oily matured liquid was subjected to phase separation to obtain 1603 g of crude 2-trifluoromethyl-2-hydroxypropionic acid-n-butyl ester (upper phase). 1603 g of the obtained 2-trifluoromethyl-2-hydroxypropionic acid-n-butyl ester (upper phase)
Was distilled under reduced pressure to obtain 1081 g of an oily product, 2-trifluoromethyl-2-hydroxypropionic acid-n-butyl ester. As a result of performing gas chromatography analysis on the obtained product, product 2-trifluoromethyl-2-
The GC purity of hydroxypropionic acid-n-butyl ester was 97.0%. Also, from the results of Examples 1 to 3, it was found that 1,1,1-trifluoroacetone
Trifluoromethyl-2-hydroxypropionic acid-n
Acquisition yield in terms of pure content up to -butyl ester is 93.8%
Met.

Example 4 Synthesis of 2-trifluoromethyl-2-hydroxypropionic acid-sec-butyl ester 727 g of sec-butanol instead of n-butanol
The same operation as in Example 3 was carried out using
-Trifluoromethyl-2-hydroxypropionic acid-
1035 g of sec-butyl ester was obtained. The obtained product was analyzed by gas chromatography. As a result, it was found that the product, 2-trifluoromethyl-2-hydroxypropionic acid-sec-
The GC purity of the butyl ester was 97.3%. In addition, from 1,1,1-trifluoroacetone, 2-trifluoromethyl-2-hydroxypropionic acid-sec-
The acquisition yield in terms of pure content up to butyl ester was 90.1%.

Example 5 Synthesis of 2-trifluoromethyl-2-hydroxypropionic acid-2-octyl ester 1279 g of 2-octanol instead of n-butanol
And the same operation as in Example 3 was carried out to obtain 1321 g of a product 2-trifluoromethyl-2-hydroxypropionic acid-2-octyl ester. As a result of performing gas chromatography analysis on the obtained product, GC purity of the product 2-trifluoromethyl-2-hydroxypropionic acid-2-octyl ester was 95.0%. Also, 1,1,
The acquisition yield in terms of pure content from 1-trifluoroacetone to 2-trifluoromethyl-2-hydroxypropionic acid-2-octyl ester was 89.0%.

Example 6 Synthesis of 2-trichloromethyl-2-hydroxypropionitrile Instead of the aqueous solution of 60 wt% 1,1,1-trifluoroacetone described in Example 1, an aqueous solution of 60 wt% 1,1,1-trichloroacetone was used. The same operation as in Example 1 was performed using 5687 g, and a 2-trichloromethyl-2-hydroxypropionitrile solution having a purity of 80.0 wt% (lower phase)
4631 g were obtained. At this time, 2-trichloromethyl-2
-Acquisition yield of hydroxypropionitrile in terms of pure content is 9
3.0%.

Example 7 Synthesis of 2-trichloromethyl-2-hydroxypropionic acid The solution obtained in Example 6 was used instead of the 78.3 wt% 2-trifluoromethyl-2-hydroxypropionitrile solution described in Example 2. The same operation as in Example 2 was performed using 4585 g of a 80.0 wt% 2-trichloromethyl-2-hydroxypropionitrile solution to obtain a total cyanide ion of 5%.
9448 g of a hydrolysis reaction completed solution containing 10 ppm was obtained. From the above results, the conversion of 2-trichloromethyl-2-hydroxypropionitrile was 99.0%. In addition, HPLC analysis of the solution after the completion of the hydrolysis reaction revealed that the selectivity to 2-trichloromethyl-2-hydroxypropionic acid was 99.5%.

Example 8 2-Trichloromethyl-2-hydroxypropionic acid
Example 7 Synthesis of n-butyl ester Instead of the hydrolysis reaction termination solution described in Example 3, Example 7 was used.
The same operation as in Example 3 was performed using 2336 g of the hydrolysis reaction completed solution obtained in the above, to obtain the product 2-trichloromethyl-2-hydroxypropionic acid-n-butyl ester 1
266 g were obtained. As a result of performing gas chromatography analysis on the obtained product, the GC purity of the product 2-trichloromethyl-2-hydroxypropionic acid-n-butyl ester was 9
8.0%. Further, from the results of Examples 6 to 8, the acquisition yield in terms of pure content from 1,1,1-trichloroacetone to 2-trichloromethyl-2-hydroxypropionic acid-n-butyl ester was 91.0%. Met.

Example 9 Synthesis of 2-n-butyl-2-hydroxybutyrotrile 97% by weight of 3-heptanone 24 instead of the 60% by weight aqueous solution of 1,1,1-trifluoroacetone described in Example 1
The same operation as in Example 1 was carried out using a mixed solution of 88 g and 1535 g of pure water, and a 2-n-butyl-2-hydroxybutyrotrile solution (lower phase) having a purity of 87.0 wt% (lower phase) 3250 was used.
g was obtained. At this time, the acquisition yield of 2-n-butyl-2-hydroxybutyrotrile in terms of pure content was 94.7%.

Example 10 Synthesis of 2-n-butyl-2-hydroxybutyric acid Obtained in Example 9 instead of the 78.3 wt% 2-trifluoromethyl-2-hydroxypropionitrile solution described in Example 2. The same operation as in Example 2 was performed by using 3240 g of an 87.0 wt% 2-n-butyl-2-hydroxybutyrotrile solution to obtain 8103 g of a hydrolysis reaction completed solution containing 347 ppm of all cyan ions. From the above results, the conversion of 2-n-butyl-2-hydroxybutyrotrile was 99.4%. In addition, HPLC analysis of the hydrolysis reaction completed solution revealed that 2-n-butyl-
The selectivity to 2-hydroxybutyric acid was 98.5%.

Example 11 Synthesis of 2-n-butyl-2-hydroxybutyric acid-n-butyl ester In place of the hydrolysis reaction solution described in Example 3, Example 1 was used.
The same operation as in Example 3 was carried out using 2026 g of the hydrolysis reaction completed solution obtained in Step 0 to obtain the product 2-n-butyl-2.
1063 g of -hydroxybutyric acid-n-butyl ester was obtained. As a result of performing gas chromatography analysis on the obtained product,
The GC purity of the product 2-n-butyl-2-hydroxybutyric acid-n-butyl ester was 97.2%. Also, from the results of Example 9 to Example 11, 3-heptanone was converted to 2-heptanone.
The acquisition yield in terms of pure content up to n-butyl-2-hydroxybutyric acid-n-butyl ester was 90.7%.

Example 12 Synthesis of 2-trifluoromethyl-2-hydroxy-2-phenylacetonitrile Instead of the 60 wt% aqueous solution of 1,1,1-trifluoroacetone described in Example 1, 98 wt% α, α, α- The same operation as in Example 1 was performed using a mixed solution of 901 g of trifluoroacetophenone and 571 g of pure water, and the purity was 85.0.
wt% 2-trifluoromethyl-2-hydroxy-2
1073 g of a phenylacetonitrile solution (lower phase) was obtained. At this time, the acquisition yield of 2-trifluoromethyl-2-hydroxy-2-phenylacetonitrile in terms of pure content was 8%.
It was 9.4%.

Example 13 Synthesis of 2-trifluoromethyl-2-hydroxy-2-phenylacetic acid To 1063 g of 2-trifluoromethyl-2-hydroxy-2-phenylacetonitrile having a purity of 85.0 wt% obtained in Example 12 While controlling the internal temperature to 70 ° C., 860 g of 98% sulfuric acid and 252 g of pure water were sequentially dropped. Thereafter, the same operation as in Example 2 was performed, and all the cyan ions 1
2121 g of a hydrolysis reaction completed solution containing 83 ppm was obtained. From the above results, the conversion of 2-trifluoromethyl-2-hydroxy-2-phenylacetonitrile was 9
9.7%. In addition, the HPL of the hydrolysis reaction end solution
When C analysis was performed, 2-trifluoromethyl-2-
97.7% selectivity for hydroxy-2-phenylacetic acid
Met.

Example 14 Synthesis of 2-trifluoromethyl-2-hydroxy-2-phenylacetic acid-n-butyl ester Example 1 was used in place of the hydrolysis reaction end solution described in Example 3.
The same operation as in Example 3 was performed using 2100 g of the hydrolysis reaction completed liquid obtained in 3 to obtain 1185 g of product 2-trifluoromethyl-2-hydroxy-2-phenylacetic acid-n-butyl ester. As a result of performing gas chromatography analysis on the obtained product, product 2-trifluoromethyl-
The GC purity of 2-hydroxy-2-phenylacetic acid-n-butyl ester was 98.2%. Example 12
-From the results of Example 14, the acquisition yield in terms of pure content from α, α, α-trifluoroacetophenone to 2-trifluoromethyl-2-hydroxy-2-phenylacetic acid-n-butyl ester was 84.7%. Met.

Comparative Example 1 Synthesis of 2-trifluoromethyl-2-hydroxypropionitrile 60 wt% 1,1,1-trifluoroacetone aqueous solution 3
20w while controlling the internal temperature to 10 ° C to 950g
6220 g of a t% aqueous sodium cyanide solution was added dropwise. Thereafter, the mixture was heated and stirred at 30 ° C. for 3.0 hours. A cyan titration analysis was performed on the aging solution having increased viscosity by the method described in Example 1, and it was found that all the cyan ions were 6.63 wt.
%, And free cyanide was contained at 3.04% by weight. Cyan titration analysis confirmed that the reaction yield was low. When the mixture was further heated and stirred at 30 ° C. for 9.0 hours, the reaction solution was solidified. When the obtained condensed product after completion of ripening was subjected to cyan titration analysis again, it was found that total cyan ion content was 6.62 wt% and free cyan content was 2.92 wt%. From the above results, it was found that 19.8% by weight of 19.8% by weight of 2-trifluoromethyl-2-hydroxypropionitrile 99
67 g were obtained. In addition, the obtained 2-trifluoromethyl-
Because 2-hydroxypropionitrile was a solidified product,
2-trifluoromethyl-2 from the condensate by phase separation
-Hydroxypropionitrile could not be purified.
At this time, the acquisition yield of 2-trifluoromethyl-2-hydroxypropionitrile in terms of pure content was 67.1%.

Comparative Example 2 Synthesis of 2-trifluoromethyl-2-hydroxypropionic acid-n-butyl ester Hydrolysis reaction completed solution 2 obtained in the same manner as in Example 2
After charging 59.3 g of sodium chloride to 123 g, extraction and phase separation were performed with 727 g of n-butanol, and 48.7 wt%.
1676 g of n-butanol solution (upper phase) of 2-trifluoromethyl-2-hydroxypropionic acid was obtained. 3. At 80 ° C. without adding sodium chloride to the upper phase obtained.
Heating and stirring were performed for 0 hours. The oily ripened liquid is subjected to phase separation to give crude 2-trifluoromethyl-2-hydroxypropionic acid-n-butyl ester (upper phase) 1230
g was obtained. The obtained 2-trifluoromethyl-2-hydroxypropionic acid-n-butyl ester (upper phase) 12
Vacuum distillation was performed on 30 g to obtain 824 g of an oily product, 2-trifluoromethyl-2-hydroxypropionic acid-n-butyl ester. As a result of performing gas chromatography analysis on the obtained product, product 2-trifluoromethyl-
G of 2-hydroxypropionic acid-n-butyl ester
C purity was 97.7%. The acquisition yield in terms of pure content from 1,1,1-trifluoroacetone to 2-trifluoromethyl-2-hydroxypropionic acid-n-butyl ester was 72.0%.

[0033]

According to the method of the present invention, operability is improved without the polymerization of α-cyanohydrins and the consolidation of the reaction solution by reacting hydrogen cyanide with an inexpensive ketone having a simple chemical structure as a raw material. Α-Cyanhydrins could be produced in high yield after production. Also, the present invention provides a method for producing α-hydroxy acid esters with good operability and high yield by conducting an esterification reaction of α-hydroxy acids obtained by hydrolysis reaction of α-cyanhydrins in the presence of an inorganic salt. We were able to.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Haruo Sakai 20-1 Miyukicho, Otake City, Hiroshima Prefecture Mitsubishi Rayon Co., Ltd. Otake Works F-term (reference) 4H006 AA02 AC25 AC41 AC48 AC54 BA66 BA69 BC10 BD70 BE06 BE60 BE61 BE63 BE90 BN10 BS10 KA06

Claims (7)

[Claims] 1. The method comprising the steps of (1) to (3):
A method for producing hydroxy acid esters. Step (1) The following general formula [I] (Wherein, R ₁ and R ₂ represent a halogen or a branched or straight-chain saturated or unsaturated alkyl group having 1 to 6 carbon atoms which may be substituted with an alkoxy group having 1 to 4 carbon atoms. , R ₁ and R ₂ are not simultaneously methyl groups;
₁ and R ₂ may combine to form a ring. A) reacting hydrogen cyanide with a ketone represented by the formula (1) in the presence of a base catalyst to obtain an α-cyanhydrin represented by the following general formula [II]. Embedded image (In the formula, R ₁ and R ₂ are the same as described above.) Step (2) A step of hydrolyzing the α-cyanhydrins in the presence of a mineral acid catalyst to form α-hydroxy acids represented by the following general formula [III]. . Embedded image (Wherein R ₁ and R ₂ are the same as above). Step (3) The α-hydroxy acids are reacted with a branched or straight-chain saturated alkyl alcohol having 4 to 8 carbon atoms in the presence of an inorganic salt to obtain the following. A step of forming an α-hydroxy acid ester represented by the general formula [IV]. Embedded image (In the formula, R ₁ and R ₂ are the same as above, and R ₃ represents a branched or straight-chain saturated alkyl group having 4 to 8 carbon atoms.) 2. In general formulas [I] to [IV], R ₁ is a methyl group, R ₂ is a trifluoromethyl group, and R ₃
Is a n-butyl group. The method for producing α-hydroxy acid esters according to claim 1, wherein 3. The method according to claim 1, wherein in step (1), the reaction solvent is water, a branched or straight-chain saturated alkyl alcohol having 1 to 8 carbon atoms, a branched or straight-chain saturated alkyl nitrile having 1 to 8 carbon atoms, A branched or straight-chain saturated alkyl ester having 1 to 8 carbon atoms, and a branched or straight-chain saturated alkyl ester having 1 to 8 carbon atoms which may be substituted by halogen or an alkoxy group having 1 to 4 carbon atoms. The method for producing α-hydroxy acid esters according to claim 1 or 2, wherein the method is at least one selected from the group consisting of unsaturated hydrocarbons. 4. The reaction temperature in the step (3) is 20 to 1
The method for producing α-hydroxy acid esters according to any one of claims 1 to 3, wherein the temperature is in the range of 00 ° C. 5. The method according to claim 1, wherein the inorganic salt used in the step (3) is Cl ⁻ , I ⁻ , S
O 4 ^_2-, method for producing α- hydroxy acid esters of PO ₄ ^3- either an anion combination consisting of an inorganic salt of claims 1 to 4 set forth in any one. 6. The method according to claim 1, wherein the amount of the inorganic salt used in the step (3) is such that the concentration of the inorganic salt in the aqueous phase becomes 0.05 to 1 equivalent of the saturated concentration. A method for producing α-hydroxy acid esters. 7. The method for producing α-hydroxy acid esters according to claim 1, wherein the esterification reaction is carried out without distilling off water produced as a by-product in step (3) outside the reaction vessel.