JPH11292824A - Production of alpha-hydroxycarboxylate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing α-hydroxycarboxylate by reacting α-hydroxycarboxylic acid with an alcohol in high selectivity and high yield. SOLUTION: An α-hydroxycarboxylate is produced by reacting α- hydroxycarboxylic acid amide with an alcohol in liquid phase in the presence of a catalyst while distilling ammonia generated as gas off vapor phase so as to maintain the concentration of ammonia at the level of 0.1 wt.% or below.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing an α-hydroxycarboxylic acid ester from an α-hydroxycarboxylic acid amide and an alcohol. α-Hydroxycarboxylic acid esters, for example, lactic acid esters are used as high-boiling solvents, and are used as food additives, flavors, raw materials for medical and agricultural chemicals, and raw materials for biodegradable polymers. Also,
α-Hydroxyisobutyric acid ester is an industrially important compound that is used as a solvent and as a raw material for producing methacrylic acid ester, particularly methyl methacrylate by dehydration, and producing α-amino acid by aminolysis.

[0002]

2. Description of the Related Art As a method for producing an α-hydroxycarboxylic acid ester, a method using an acid catalyst has been known for a long time. For example, as a method for producing methyl α-hydroxyisobutyrate, methyl α-hydroxyisobutyrate has been obtained directly from acetone cyanohydrin using an acid catalyst. U.S. Pat. No. 2,041,820 discloses a method in which acetone cyanohydrin, sulfuric acid, and methanol are hydrolyzed and esterified at a temperature of 100 ° C. or less, and then anhydrous sodium sulfate is added thereto for distillation. However, in this method, a large amount of ammonium sulfate is produced as a by-product, and the treatment requires a great deal of cost. In addition, since sulfuric acid is used, the reactor must use expensive corrosion-resistant materials.

As a method for producing an α-hydroxycarboxylic acid ester from an α-hydroxycarboxylic acid amide and an alcohol, JP-A-52-3015 discloses a method in which a reaction is carried out in the presence of a metal carboxylate. I have. In this, a method has been proposed in which the alcoholysis is carried out in a pressure reactor at a temperature above the boiling point of the alcohol, whereby the reactor is intermittently or partially depressurized to remove the ammonia produced. I have. However, this method is not practical because the yield is low and there are many by-products.
JP-A-6-345492, JP-A-7-25815
No. 4 and JP-A-8-73408 propose a method of reacting in the presence of an insoluble solid acid catalyst or metal catalyst. However, the present inventors have studied that, in order to produce α-hydroxycarboxylic acid ester in high yield, a large amount of catalyst is used, a long time is required for the reaction, many by-products are produced, and Was not practical.

[0004]

In the prior art, α
-When producing a hydroxycarboxylic acid ester, a large amount of auxiliary materials such as sulfuric acid are required, or even when a catalyst is used, the amount used is large, the reaction takes a long time, the by-product is large, It was not industrially practical.
An object of the present invention is to provide a method capable of industrially and advantageously performing the production of an α-hydroxycarboxylic acid ester from an α-hydroxycarboxylic acid amide and an alcohol using a catalyst. To solve the conventional problems by changing the method and conditions of the above.

[0005]

The present inventors have conducted various studies on the reaction of the following formula carried out in the liquid phase. As a result, the smaller the amount of ammonia in the reaction solution, the higher the reaction rate and the higher the reaction rate. It was found that conversion and selectivity were obtained, and that there were few by-products. This reaction is represented by the following formula (1). R ¹
R ² C (OH) CONH ₂ + R ³ OH = R ¹ R ² C (OH) COOR ³ + NH ₃
(1) (R ¹ and R ² are hydrogen or alkyl groups; R ³ OH is an alcohol.) Since this reaction is an equilibrium reaction, it is natural that the reaction proceeds to the production side when ammonia in the production system is distilled off. It is. It is known in the prior art that, as described above, the pressure generated by the produced ammonia is increased intermittently or partially and the equilibrium is advanced to the production side. However, since ammonia dissolves in alcohol or α-hydroxycarboxylic acid ester under pressure, the ammonia concentration in the liquid phase cannot be reduced only by this operation method. By boiling the reaction solution and / or bubbling an inert gas, the researchers distill off the generated ammonia as a gas into the gas phase and maintain the reaction while keeping the ammonia concentration in the reaction solution low. It has been found that by carrying out, the reaction rate is improved, a high conversion and selectivity are obtained, and the amount of by-products is small. In particular, the present researchers have found that keeping the ammonia concentration in the reaction solution at 0.1% by weight or less is effective in suppressing by-products that no one has pointed out so far.

As a by-product, when ammonia is present in the reaction solution as shown in the following formula (2), a quaternary amine salt of α-hydroxycarboxylic acid is formed from the product α-hydroxycarboxylic acid ester and ammonia Then, α-hydroxycarboxylic acid (N-alkyl) amide is generated via Hoffman decomposition. R ¹ R ² C (OH) COOR ³ + NH ₃ = [R ¹ R ² C (OH) COO] ^- [R ³ NH ₃ ] ⁺ = R ¹ R ² C (OH) CONR ³ H + H ₂ O ( 2) If the ammonia concentration in the reaction solution is more than 0.1% by weight,
The formation of the α-hydroxycarboxylic acid (N-alkyl) amide increases, and the selectivity is significantly reduced.

[0007] In addition, if the concentration of ammonia in the reaction solution is high, the present researchers not only make it difficult for the reaction to proceed to the production system by the equilibrium reaction, but also coordinate or adsorb ammonia to the catalyst, and It has also been found that the coordination or adsorption of a certain α-hydroxycarboxylic acid amide is significantly inhibited, leading to a reduction in the reaction rate. That is, when the ammonia concentration in the reaction solution is more than 0.1% by weight, the reaction does not proceed to the equilibrium conversion rate, the apparent reaction rate becomes slow, and the reaction stops.

The concentration of ammonia in the reaction solution is 0.1% by weight.
As a means for keeping the pressure below, it is not sufficient to release the pressure increase caused by the generated ammonia intermittently or partially. The researchers easily achieved this by boiling the reaction solution and / or bubbling an inert gas and continuously supplying alcohol to the reaction solution phase while distilling off ammonia and alcohol. I found what I could do. In the method of the present invention, the alcohol is always continuously supplied to the reaction liquid phase forcibly, and the alcohol is continuously distilled off, thereby promoting the gasification and removal of ammonia from the liquid phase.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION Representative examples of α-hydroxycarboxylic acid amide used in this reaction are lactamamide and α-hydroxycarboxylic acid amide.
Hydroxyisobutyric acid amide, but is not limited thereto. Representative examples of alcohol include methanol, ethanol, propanol, butanol, 2-ethylhexanol, glycidyl alcohol, benzyl alcohol and the like. The alcohol is used in an amount of 1 to 50 times, preferably 2 to 20 times the mole of the α-hydroxycarboxylic acid amide.

The reaction temperature is in the range of 100 to 250 ° C., preferably 120 to 230 ° C. At a temperature lower than 100 ° C., the reaction rate decreases, and at a temperature higher than 250 ° C., α-alkoxycarboxylic acid ester, α
-The amount of by-products such as hydroxycarboxylic acid and olefin derivatives which are dehydration products increases, which is not preferable. In this reaction, it is preferable that water is not present in the reaction system, but the reaction proceeds when the amount of water is 3 times or less the molar amount of α-hydroxycarboxylic acid amide.

The reaction pressure is determined as appropriate depending on the type and amount of the alcohol used, the reaction temperature and the like.
It is good to carry out at 0 atm, preferably at 5 to 50 atm. This reaction can also be performed in the presence of a solvent. The reaction can be performed in any of a batch system and a continuous system.

The catalyst used in the present invention may be soluble or insoluble in the reaction solution under the reaction conditions. As the soluble catalyst, use of a metal species which forms a complex with α-hydroxycarboxylic acid amide is preferable, and titanium and tin are particularly suitable, but not limited thereto. When titanium is selected as the metal species, an alkoxylate such as titanium tetraisopropoxide may be directly charged into the reaction system to form a complex of soluble titanium and α-hydroxycarboxylic acid amide in the system. Alternatively, a complex may be separately formed from titanium tetraisopropoxide and α-hydroxycarboxylic acid amide outside the system, and this may be added to the reaction system as a catalyst. The same can be said for the case of selecting tin, and the metal compound of the catalyst raw material precursor is not particularly limited.

As the insoluble catalyst, Sb, Sc, Y, L
a, Ce, Ti, Zr, Hf, V, Nb, Ta, Cr,
Mo, W, Tc, Re, Fe, Co, Ni, Cu, A
a metal oxide containing at least one element selected from the group consisting of 1, Si, Sn, Pb and Bi;
i, Zr, Hf, V, Nb, Ta, Cr, Mo, W, F
Insoluble metals containing at least one element selected from the group consisting of e, Co, Ni, Cu, Ga, In, Bi and Te are preferred.

The method of using both the soluble catalyst and the insoluble catalyst is appropriately determined depending on the reaction type. Whether the insoluble catalyst is used in a slurry or formed and used is determined according to the method of use.

[0015]

The method of the present invention will be described in more detail with reference to the following examples. Example 1 65.3 g of α-hydroxyisobutyric acid amide (HBD)
(0.634 mol) was dissolved in 1000 g of isopropanol. Here titanium tetraisopropoxide 30
g (0.106 mol) in 1000 g of isopropanol
Was added. Isopropanol was distilled off from the mixture using a rotary evaporator, and the mixture was concentrated to 840 g. Leave it at room temperature for 24 hours to filter out the deposited precipitate,
After washing with heptane, vacuum drying gave 37.0 g of crystals. Elemental analysis of the obtained complex revealed that Ti: 10.5
wt%, C: 42.7 wt%, H: 7.91 wt%, N: 12.1 wt%. This complex was identified as Ti (HBD) ₄ (theoretical element analysis: Ti: 1
0.4wt%, C: 41.8wt%, H: 7.83wt%, N: 12.2wt%). 300ml internal volume with jacketed reflux condenser and stirrer
30.0 g (0.291 mol) of α-hydroxyisobutyric amide, 100 g of methanol, 4.85 g of Ti (HBD) ₄ complex (0.0106 mol) in a stainless steel autoclave
l), the pressure is maintained at 3.0 MPa, and 1
Nitrogen gas was fed into the autoclave at 90 ° C., and the reaction was carried out for 1.5 hours while releasing the produced ammonia together with the nitrogen gas from the autoclave. At this time, oil at 185 ° C. was circulated through the jacket of the reflux condenser and heated, and a portion of methanol was removed from the top of the reflux condenser together with ammonia at a rate of 30 g / hr, and at the same time, 30 g / hr of methanol was introduced into the reactor. Feeded at speed. After the reaction, the reaction solution was cooled and analyzed by gas chromatography.
The ammonia concentration in the product solution is 0.01 wt% or less, and the conversion of α-hydroxyisobutyric acid amide is 95.3 mol.
1%, α-hydroxyisobutyric acid methyl ester selectivity 9
7.1 mol% and α-hydroxyisobutyric acid (N-methyl) amide selectivity of 2.9 mol% were obtained.

Comparative Example 1 30.0 g of α-hydroxyisobutyric acid amide was placed in a 300 ml stainless steel autoclave equipped with a stirrer.
(0.291 mol), 100 g of methanol, Ti (HBD) ₄
4.85 g (0.0106 mol) of the complex was charged, the pressure was maintained at 3.0 MPa, and the autoclave was closed at 190 ° C. with stirring to carry out a reaction for 1.5 hours. The ammonia concentration in the product solution was 1.01% by weight, α-hydroxyisobutyric acid amide conversion was 34.9 mol%, α-hydroxyisobutyric acid methyl ester selectivity was 78.9 mol%, and α-hydroxyisobutyric acid methyl ester was 78.9 mol%.
Hydroxyisobutyric acid (N-methyl) amide selectivity
2 mol% was obtained.

Comparative Example 2 Internal volume 30 with jacket-type reflux condenser and stirrer
In a 0 ml stainless steel autoclave, 30.0 g (0.291 mol) of α-hydroxyisobutyric acid amide, 100 g of methanol, 4.85 g of Ti (HBD) ₄ complex (0.010 mol)
6 mol), the pressure was maintained at 3.0 MPa, and nitrogen gas was fed into the autoclave at 190 ° C. with stirring.
The reaction was carried out for 1.5 hours while releasing generated ammonia together with nitrogen gas from the autoclave. At this time, chilled water of 20 ° C. was circulated through the jacket of the reflux condenser to cool it.
All the methanol evaporated in the reactor was condensed in a reflux condenser, and returned to the reactor as methanol in which ammonia was dissolved. The ammonia concentration in the product liquid is 0.59w
% of α-hydroxyisobutyric acid amide conversion 5
6.4 mol%, α-hydroxyisobutyric acid methyl ester selectivity of 87.1 mol%, and α-hydroxyisobutyric acid (N-methyl) amide selectivity of 11.2 mol% were obtained.

Example 2 Lactamide (LD) 56.5 g (0.634 mol)
Was dissolved in 500 g of isopropanol. Here, 30 g (0.106 mol) of titanium tetraisopropoxide
Was dissolved in 150 g of isopropanol.
Isopropanol was distilled off from the mixture using a rotary evaporator and concentrated to 200 g. The precipitate was left standing overnight at room temperature, and the precipitate was filtered, washed with heptane, and dried under vacuum to obtain 34.3 g of crystals. When the elemental analysis of the obtained complex was performed, Ti: 11.9 wt%, C: 36.0 wt%, H: 6.84 wt%
%, N: 13.6 wt%. This complex was identified as Ti (LD) ₄ (theoretical elemental analysis: Ti: 11.9 wt%, C: 35.6 wt%, H: 6.93 w
t%, N: 13.9 wt%). 25.9 g (0.291 mol) of lactamide, 100 g of methanol, 4.28 g of Ti (LD) ₄ complex were placed in a 300 ml stainless steel autoclave equipped with a jacket-type reflux condenser and a stirrer.
06 mol), the pressure was maintained at 3.0 MPa, a nitrogen gas was fed into the autoclave at 190 ° C. with stirring, and the reaction was carried out for 1.5 hours while releasing the produced ammonia together with the nitrogen gas from the autoclave. On this occasion,
The oil at 185 ° C. was circulated through the jacket of the reflux condenser and heated.
The methanol was withdrawn from the upper part of the reflux condenser at a rate of hr, and at the same time, methanol was supplied to the reactor at a rate of 30 g / hr. After the reaction, the reaction solution was cooled and analyzed by gas chromatography. Ammonia concentration in product solution is 0.01wt
% Or less, and a lacroamide conversion rate of 95.6 mol%,
α-Hydroxyisobutyric acid methyl ester selectivity 97.4
mol%, a selectivity for α-hydroxyisobutyric acid (N-methyl) amide of 2.6 mol% was obtained.

Example 3 Bismuth nitrate (40 g) was dissolved in a 10% aqueous nitric acid solution (50 ml), and the pH was adjusted to 28 with 28% aqueous ammonia while stirring to precipitate bismuth hydroxide. Filter this precipitate,
After washing with water, it was dried at 110 ° C. all day and night, and baked at 450 ° C. for 3 hours. An esterification reaction with methanol was carried out in the same manner as in Example 1 except that 3.0 g of the obtained oxide was used as a catalyst. After the reaction, the reaction solution is cooled,
The analysis was performed by gas chromatography. The ammonia concentration in the product solution is 0.01 wt% or less, the conversion of α-hydroxyisobutyric amide is 57.3 mol%,
Hydroxyisobutyric acid methyl ester selectivity 97.3mo
1% and a selectivity of α-hydroxyisobutyric acid (N-methyl) amide of 2.7 mol% were obtained.

Comparative Example 3 Using 3.0 g of bismuth oxide obtained in Example 3 as a catalyst, an esterification reaction with methanol was carried out in the same manner as in Comparative Example 2. The ammonia concentration in the product liquid is 0.4
Α-hydroxyisobutyric acid amide conversion rate of 32.7 mol%, α-hydroxyisobutyric acid methyl ester selectivity of 80.3 mol%, and α-hydroxyisobutyric acid (N-methyl) amide selectivity of 19.7 mol%. Obtained.

Example 4 200 g of cerium nitrate was dissolved in 2000 ml of water, and a 5% aqueous solution of ammonium carbonate was added thereto with stirring to adjust the pH to 8, thereby producing a precipitate. After the precipitate was filtered and washed with water, it was dried at 110 ° C. all day and night and calcined at 450 ° C. for 3 hours. An esterification reaction with methanol was carried out in the same manner as in Example 1 except that 3.0 g of the obtained oxide was used as a catalyst. After the reaction, the reaction solution was cooled and analyzed by gas chromatography. The ammonia concentration in the product solution is 0.01 wt% or less, α-hydroxyisobutyric acid amide conversion is 81.7 mol%, α-hydroxyisobutyric acid methyl ester selectivity is 97.4 mol%, α
-Hydroxyisobutyric acid (N-methyl) amide selectivity 2.
6 mol% was obtained.

Comparative Example 4 Using 3.0 g of the cerium oxide obtained in Example 4 as a catalyst, an esterification reaction with methanol was carried out in the same manner as in Comparative Example 2. The ammonia concentration in the product liquid is 0.8
Α-hydroxyisobutyric acid amide conversion rate of 52.7 mol%, α-hydroxyisobutyric acid methyl ester selectivity of 86.5 mol%, and α-hydroxyisobutyric acid (N-methyl) amide selectivity of 13.5 mol%. Obtained.

Example 5 An esterification reaction with methanol was carried out in the same manner as in Example 1, except that 2.0 g of a fine powder of metallic bismuth was used as a catalyst. After the reaction, the reaction solution was cooled and analyzed by gas chromatography. The ammonia concentration in the product solution is 0.01 wt% or less, the conversion of α-hydroxyisobutyric acid amide is 64.7 mol%, the selectivity of α-hydroxyisobutyric acid methyl ester is 97.3 mol%,
Hydroxyisobutyric acid (N-methyl) amide selectivity 2.7
mol% was obtained.

Comparative Example 5 An esterification reaction with methanol was carried out in the same manner as in Comparative Example 2, using 2.0 g of a fine powder of metallic bismuth as a catalyst. The ammonia concentration in the product solution was 0.75 wt%, and the α-hydroxyisobutyric acid amide conversion was 47.4 mo.
1%, α-hydroxyisobutyric acid methyl ester selectivity 8
2.6 mol% and a selectivity of α-hydroxyisobutyric acid (N-methyl) amide of 17.4 mol% were obtained.

[0025]

According to the present invention, an α-hydroxycarboxylic acid ester can be produced from an α-hydroxycarboxylic acid amide and an alcohol in a high selectivity and a high yield.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI // C07B 61/00 300 C07B 61/00 300

Claims (7)

[Claims] 1. A method according to claim 1, wherein the generated ammonia is distilled off as a gas in the gas phase in the presence of a catalyst from an α-hydroxycarboxylic acid amide and an alcohol to keep the ammonia concentration in the reaction solution at 0.1% by weight or less. A method for producing an α-hydroxycarboxylic acid ester, which comprises reacting in a liquid phase. 2. The method according to claim 1, wherein ammonia generated by bringing the reaction solution into a boiling state and / or bubbling an inert gas is distilled off as a gas into a gas phase. 3. The production method according to claim 1, wherein the alcohol is continuously distilled while continuously supplying the alcohol to the reaction liquid phase. 4. The method according to claim 1, wherein the α-hydroxycarboxylic acid amide is lactoamide or α-hydroxyisobutyric acid amide, and the alcohol is methanol. 5. The process according to claim 1, wherein the catalyst is a metal complex comprising soluble titanium and / or tin and α-hydroxycarboxylic acid amide. 6. A catalyst comprising Sb, Sc, Y, La, Ce,
Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W,
Tc, Re, Fe, Co, Ni, Cu, Al, Si, S
at least one selected from the group consisting of n, Pb and Bi
Claim 1 which is an insoluble metal oxide containing a kind element.
5. The production method according to 2, 3 or 4. 7. The method according to claim 1, wherein the catalyst is Ti, Zr, Hf, V, Nb,
Ta, Cr, Mo, W, Fe, Co, Ni, Cu, G
2. An insoluble metal containing at least one element selected from the group consisting of a, In, Bi and Te.
5. The production method according to 2, 3 or 4.