KR19990078213A - Process for preparing alpha-hydroxycarboxylate - Google Patents

Abstract

A method for efficiently and advantageously producing α-hydroxycarboxylic acid esters, which are useful as food additives, fragrances, and raw materials for various organic chemicals, including solvents, from α-hydroxycarboxylic acid amides and alcohols, has been proposed. It is.

In the present invention, α-hydroxycarboxylic acid amide and an alcohol are reacted in a liquid phase while maintaining the ammonia concentration in the reaction solution at a concentration of 0.1% by weight or less in the presence of a catalyst while discharging the generated ammonia as a gas. Provided is a method for producing hydroxycarboxylic acid ester.

Description

Production method of α-hydroxycarboxylic acid ester {PROCESS FOR PREPARING ALPHA-HYDROXYCARBOXYLATE}

The present invention relates to a method for producing α-hydroxycarboxylic acid ester.

Again, in detail, the present invention is an α- hydroxy carboxylic acid ester useful as a raw material, such as food additives, flavorings, pharmaceuticals, pesticides, industrial chemicals, degradable polymers, α-amino acids, including solvents. A method for efficiently and advantageously producing industrially from oxycarboxylic amides and alcohols.

It is known that α-hydroxycarboxylic acid ester is an industrially important compound. For example, lactic acid ester, which is a kind of high boiling point solvent, is used as a raw material for food additives, flavors, medicines, pesticides, and degradable polymers. It is used as a raw material.

In addition to being used as a solvent, the α-hydroxycarboxylic acid ester is used as a raw material such as the production of methacrylic acid esters by dehydration, especially methyl methacrylate and the production of α-amino acids due to aminolsis.

As a method for producing α-hydroxycarboxylic acid ester, a method of reacting an alcohol with nitrile in the presence of an acid catalyst is known from the example.

For example, as a method for producing lactic acid ester, Japanese Unexamined Patent Publication No. 8081/55 and Japanese Patent No. 2333/65 disclose a mixture produced by dissolving lactnitrile in alcohol and water and adding sulfuric acid to hydrolysis and esterification. A method of introducing alcohol vapor has been proposed.

As for the α-hydroxyisobutyric acid ester, a method of producing by reacting acetonecyanhydrin with an alcohol using an acid catalyst is known. For example, it is proposed in U.S. Patent No. 2041820, Japanese Patent Laid-Open No. 230241/92. have.

Since these reactions proceed spontaneously as exothermic reactions, the manufacturing apparatus may be simpler than other methods described below.

However, there is a drawback in that a large amount of salt is generated as a waste in addition to the need to use corrosion resistant materials due to the use of an acid catalyst.

As a method for producing α-hydroxycarboxylic acid ester, there is a method of reacting α-hydroxycarboxylic acid amide with an ester.

For example, Japanese Patent Laid-Open No. 178792/93 and Japanese Patent Laid-Open No. 145106/94 propose a method of producing α-hydroxyisobutyric acid ester.

This reaction is characterized by the exchange of amides and esters, no exothermic heat or endothermic, and no need to use corrosion-resistant materials.

However, there is a drawback that the reaction proceeds only up to the equilibrium composition of the amide and the ester.

Again, a method of producing α-hydroxycarboxylic acid ester by directly reacting α-hydroxycarboxylic acid amide with an alcohol is known.

This method is characterized in that no salts to be disposed of are produced and in principle there is no upper limit to the conversion of the raw amides.

For example, Japanese Patent Application Laid-Open No. 3015/1977 discloses a method of reacting in the presence of a metal carboxylic acid while purifying gas intermittently.

However, in this method, besides low yield, there were many by-products and it was not practical.

In Japanese Patent Nos. 345692/94, 258154/95, and 7373/96, the reaction is carried out in the presence of an insoluble solid acid catalyst or a metal catalyst while releasing ammonia generated by supplying a large amount of nitrogen gas. A method of making it is proposed.

As discussed by the present inventors, a large amount of nitrogen is required to prepare α-hydroxycarboxylic acid ester in high yield in this method.

Because of this, a great deal of energy is required to recover ammonia from the emitted gases.

Again, the amount of catalyst used again, the reaction takes a long time, many by-products, industrially not practical.

The present invention overcomes the drawbacks of the conventional methods for producing α-hydroxycarboxylic acid esters under such circumstances, and efficiently utilizes α-hydroxycarboxylic acid esters from α-hydroxycarboxylic acid amides and alcohols. It is an object to provide a method of manufacturing advantageously advantageously.

1 is a schematic diagram of an example of a reactor incorporating independent reactors used to practice the method of the present invention.

2 is a schematic view of a reactor used in Examples 11 to 15;

(Explanation of symbols for main parts of drawing)

1. First reactor

2. second reactor

3. third reactor

4,5,6. Liquid pipe

7,8,9. Gas conduit

10. Methanol

11. Liquid pump

12. Bottom Reactor

13. Gas Conduit

14. Liquid pipe

15. Valve

16. Chiller

17. Bottom Container

18. Gas Conduit

19. Condenser

20. Condensate Container

21.Valve

22. Liquid pump

23. Raw material solution

24. Top Reactor

In order to achieve the above object, the present inventors have conducted various studies on the following reactions carried out in a liquid phase, and as the amount of ammonia in the reaction liquid decreases, the reaction rate is improved, and high conversion and selectivity are obtained. I also found a 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)

(Wherein R ¹ and R ² represent a hydrogen atom or an alkyl group, R ³ represents an alkyl group or an aralkyl group, etc.)

Since this reaction is an equilibrium reaction, it is natural that the reaction proceeds to the production side which distills off the ammonia in the production system.

In the prior art, it is well known as described above that the pressure rise is caused by the ammonia produced and the pressure is intermittently or partially released to advance the equilibrium to the production side.

However, since ammonia is dissolved in alcohol or α-hydroxycarboxylic acid ester under pressure, the ammonia concentration in the liquid phase cannot be lowered only by this operation method.

The present inventors perform the reaction while maintaining the low ammonia concentration in the reaction solution by discharging the ammonia generated by boiling the reaction solution or bubbling inert gas into the gas phase as a gas, thereby improving the reaction rate and high conversion rate. And selectivity were obtained, and by-products were found to be small.

In particular, the present inventors found that maintaining the ammonia concentration in the reaction solution below 0.1% by weight was 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 by the following formula (2), a quaternary amine salt of α-hydroxycarboxylic acid is produced from the product α-hydroxycarboxylic acid ester and ammonia, and then Hoffman Α-hydroxycarboxylic acid (N-alkyl) amide is generated via 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)

Wherein R ¹ R ² and R ³ are as defined above.

If the ammonia concentration in the reaction solution is more than 0.1% by weight, the production of this α-hydroxycarboxylic acid (N-alkyl) amide increases and the selectivity is significantly reduced.

In addition, the present inventors have a high ammonia concentration in the reaction solution, which makes it difficult to proceed the reaction to the production system in the equilibrium reaction. It was also found that inhibition caused a decrease in reaction rate.

In other words, if the concentration of ammonia in the reaction solution is more than 0.1% by weight, the reaction will not proceed until the equilibrium conversion rate, the apparent reaction rate will be slow, and the reaction will stop.

As a means for maintaining the ammonia concentration in the reaction solution at 0.1% by weight or less, the degree of pressure release intermittently or partially caused by the ammonia generated by the ammonia generated is insufficient.

The present inventors have found that this can be easily achieved by boiling the reaction solution or by blowing the inert gas to continuously supply alcohol to the reaction liquid while distilling off ammonia and alcohol.

The present invention has been completed based on such findings.

In other words, the present invention allows the reaction of a-hydroxycarboxylic acid amide and an alcohol in a liquid phase while maintaining the ammonia concentration in the reaction solution at a concentration of 0.1% by weight or less by discharging the ammonia generated in the presence of a catalyst as a gas. It is to provide a method for producing α-hydroxycarboxylic acid ester, characterized in that.

In addition, as a preferable method for maintaining the ammonia concentration in the reaction solution to 0.1% by weight or less, the reaction solution is discharged to the gas phase as a gas by ammonia generated by boiling or bubbling an inert gas or both operations. And a method of continuously discharging ammonia generated at the same time as the alcohol is continuously supplied to the reaction solution together with the alcohol.

(Example)

The manufacturing method of the (alpha)-hydroxycarboxylic acid ester of this invention is a method of making liquid (alpha) -hydroxycarboxylic acid amide which is a raw material, and alcohol react in the presence of a catalyst.

In this method, a representative example of α-hydroxycarboxylic acid amide used as a raw material is, but is not limited to, lactamide or α-hydroxyisobutyric acid amide.

Representative alcohols include methanol, ethanol, propanol, butanol, 2-ethylhexanol, glycidyl alcohol, benzyl alcohol and the like. Of these, methanol is most suitable.

1-50 times mole is preferable with respect to (alpha) -hydroxycarboxylic acid amide, and, as for the usage-amount of alcohol, the range of 2-20 times mole is especially preferable.

The reaction temperature is usually selected in the range of 100 to 250 ° C, preferably 120 to 230 ° C.

At temperatures lower than 100 ° C, the reaction rate is too slow to be practical, and at temperatures higher than 250 ° C, by-products such as α-alkoxycarboxylic acid esters, α-hydroxycarboxylic acids, and olefin derivatives, which are dehydration products, increase. Not desirable

It is preferable that water is not present in the reaction system in the present reaction, but the reaction proceeds when the amount of water is 3 times or less with respect to α-hydroxycarboxylic acid amide.

The reaction pressure is appropriately determined depending on the type and amount of alcohol used, the reaction temperature and the like, but is usually in the range of 1 to 100 atm, preferably 5 to 50 atm. This reaction can also be carried out in the presence of a solvent.

The reaction can be carried out by any method of batch continuous.

As a catalyst in the method of the present invention, any one of a soluble metal catalyst and a solid catalyst can be used, and there is no particular limitation, for example, (1) soluble metal complex salt, (2) metal trifluoromethanesulfonate salt, (3) Insoluble metal oxides, (4) insoluble metals, and the like can be appropriately selected depending on the situation.

Examples of the soluble metal complex salt of (1) include, but are not limited to, a soluble metal complex salt made of titanium or tin or both and α-hydroxycarboxylic acid amide.

In this case, when titanium is selected as the metal type, an alkoxylate such as titanium tetraisopropoxide may be added directly to the reaction system to form a soluble complex salt of titanium and α-hydroxycarboxylic acid amide in the system. You may form a complex salt from titanium tetraisopropoxide and (alpha)-hydroxycarboxylic acid amide, and add it as a catalyst to a reaction system.

The same can be said for selecting tin as the metal type.

For example, an alkyl tin compound may be directly introduced into the reaction system to form a soluble complex salt of tin and α-hydroxycarboxylic acid amide in the system.

Examples of the alkyl tin compound in this case include tin compounds bonded to substituents such as n-butyl groups.

In addition, there is no restriction | limiting in particular about the metal compound of the catalyst raw material precursor used at this time.

The metal trifluoromethanesulfonate (also referred to as metal triflate) of the above-mentioned (2) may be soluble or insoluble, such as the Periodic Tables 1, 2, 3, 4, 11, 12, 13 and 14 The metal triplate which has as a ligand the triflate containing 1 type (s) or 2 or more types of metal elements selected from the elements which belong to a group is mentioned.

Especially Na, Li, k, Mg, Ca, Sr, Ba, Sc, y, La, Pr, Nd, Sm, Eu, Gd, Dy, Ho, Er, Tm, Yb, Lu, Hf, Cu, Ag, Zn Metal triplates containing one or two or more elements selected from among Cd, Hg, B, Al, Ga, In, Tl, Si, Ge, Sn and Pb are preferred.

Japanese Unexamined Patent Publication No. 3015/77 states that soluble metal complex salts having an anion carboxylate promote alcohol decomposition, but the use of this metal triplate accelerates the reaction compared to the case of using metal carboxylate. Fast reaction rates are obtained.

The soluble metal complex salt, especially the titanium homogeneous catalyst of the above-mentioned (1), is highly hydrolyzable and needs to control the amount of water in the raw material system.

On the other hand, in particular, the triflate of lanthanoids is prepared by hydrothermal synthesis in aqueous solution, and the hydrolyzability of lanthanoid itself is low, so that even in systems containing water, the catalyst is hydrolyzed and the reaction can proceed without loss of activity. It has a big advantage and is very suitable.

Moreover, as said inert metal oxide of (3), for example, Sb, Sc, Y, La, Ce, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Tc, Re, Fe, Co, The metal oxide containing at least 1 sort (s) of element chosen from Ni, Cu, Al, Si, Sn, Pb, and Bi is mentioned preferably.

Again, the insoluble metal of (4) is selected from, for example, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Fe, Co, Ni, Cu, Ga, In, Bi, and Te. The insoluble metal containing at least 1 sort (s) of elements mentioned above can be mentioned preferably.

One type of these catalysts may be used, or two or more types thereof may be used in combination, and any method of using a soluble or insoluble catalyst may be appropriately determined depending on the reaction type.

Again, in the case of an insoluble catalyst, it can be appropriately selected according to the method of use, which is used as a slurry or molded.

In the method of the present invention, it is necessary to react while maintaining the ammonia concentration in the reaction liquid at 0.1% by weight or less while discharging the ammonia serving as a gas phase.

In this way, the reaction rate is improved by maintaining the ammonia concentration in the reaction solution at 0.1 wt% or less, and high conversion and high selectivity are obtained, and the amount of by-products is also reduced.

As a method of maintaining the ammonia concentration in the reaction liquid at 0.1% by weight or less, for example, (1) the ammonia gas generated by boiling or bubbling an inert gas or both operations is discharged in a gaseous state. It is advantageous to carry out the method of (2) continuously supplying the alcohol to the reaction liquid or the method of continuously discharging the ammonia generated at the same time with the alcohol.

In addition, a method of using a gas dissipation device as a reaction device, supplying amide and alcohol as raw materials thereto, and reacting in the gas dissipation device while distilling off ammonia is also advantageous.

Since the composition of the liquid and gas in the reactor changes continuously or discontinuously, it is possible to increase the conversion of amide while keeping the alcohol distillation amount relatively low.

Here, the gas dissipation device is a device used industrially to divertify a desired component in a gas from the mixed liquid.

Since gas divergence is theoretically the reverse operation of gas absorption, the devices used are often equivalent to those used for gas absorption.

There are various kinds of gas dissipating devices, but any of liquid dispersing type and gas dispersing type can be applied.

Examples of the liquid dispersion type include a packed tower, a wet wall tower, a liquid column tower, a spray tower, and the like.

There are various gas dispersion types, but there are bubble towers, gas jet stirrers, shelf towers, and the like.

Among them, the packed column, bubble column, and flat column are preferred.

Fillers used in the packed column may be any of irregular fillings, regular fillings and lattice fillings.

It is also possible to mold a solid catalyst and use it as a filler.

It is a nozzle type as a bubble tower. Any of the porous plates may be used, and the packing may be filled.

The gas dispersion type device is relatively easy to flow slurry material and is suitable for the use of an insoluble catalyst.

In the case of using a homogeneous catalyst, either a liquid dispersion type or a gas dispersion type may be used.

The gas used may be not only a non-condensable gas such as nitrogen, but also a condensable gas such as vapor of alcohol.

Moreover, you may vaporize the liquid inside by heating the lower part of an apparatus, and you may use this.

When the liquid and the gas flow in the opposite direction, ammonia can be released more efficiently than the flow in the parallel direction.

In order to flow in the opposite direction, it is preferable to introduce or generate gas from the lower part of the gas dissipation device to supply the raw amide from the upper part.

Again, the following recycling method and the multistage reaction method can be adopted as a preferred form for carrying out the present invention.

First, the recycling method will be described.

In the reaction solution during or after the reaction, the boiling point is mainly in the order of low boiling point, alcohol as a raw material, α-hydroxycarboxylic acid ester as a product, α-hydroxycarboxylic acid (N-alkyl) amide as a by-product, and α-hydride as a raw material. Oxycarboxylic acid amides and catalysts.

In the recirculation method, this product is introduced into the distillation zone, and unreacted alcohol and the product? -Hydroxycarboxylic acid ester are separated as evaporated fractions.

On the other hand, part or all of the unevaporated content is recycled to a reactor as it is, and it reacts again by adding raw material (alpha)-hydroxycarboxylic acid amide and alcohol.

Since the catalyst is reusable as long as it has activity, it is possible to increase the production amount of α-hydroxycarboxylic acid ester per unit catalyst.

When the content of α-hydroxycarboxylic acid (N-alkyl) amide, which is a by-product having a lower boiling point than the raw material α-hydroxycarboxylic acid amide, has increased due to accumulation, Some or all of the α-hydroxycarboxylic acid (N-alkyl) amide is introduced as an evaporation fraction, and some or all of the evaporation fraction is recycled to the reactor.

By-products having a boiling point between the α-hydroxycarboxylic acid ester and the α-hydroxycarboxylic acid amide other than the α-hydroxycarboxylic acid (N-alkyl) amide are also removed by this operation.

In the case where there are more accumulations of by-products having a higher boiling point than α-hydroxycarboxylic acid amide, which is a raw material, some or all of the unevaporated content may be removed and discarded.

In addition, a new catalyst component equivalent to the catalyst contained in the discarded unevaporated component may be newly added to the reactor.

Distillation is carried out by a general method. Packed column, flat column, thin film distillation column and the like are appropriately selected from the conditions of use.

Either batch distillation or continuous distillation can be performed.

In particular, there is no problem even if the distillation operation is carried out without having a distillation facility independent of the reactor, and a distillation column is installed on the reactor and the production liquid is maintained in the reactor.

Distillation conditions are not particularly limited and are selected in a wide range from normal pressure to reduced pressure.

The temperature is appropriately selected from temperatures below 250 ° C. in which normal organic matter does not deteriorate.

Next, the multistage reaction method will be described.

This multistage reaction method uses a plurality of reaction zones to contact the gas containing ammonia and alcohol and the liquid containing the amide in opposite directions.

In this way,

(a) a plurality of reaction zones are arranged in series with adjacent zones using connected reactors to allow liquid and gas to flow in opposite directions;

(b) feed the raw material α-hydroxycarboxylic acid amide and alcohol into the reaction zone after the first time,

(c) maintaining each reaction zone in a boiling state, supplying gas to the preceding reaction zone from any particular reaction zone, including alcohol and by-product ammonia, and supplying the reaction liquid containing the raw materials and products of the reaction zone; Feed into the subsequent reaction zone,

(d) evacuating the gas from the first reaction zone and discharging the reaction liquid from the last reaction zone.

In each reaction zone, the reaction solution is in a boiling state.

Here, the boiling state is a state in which by-produced ammonia is evaporated in the reaction solution together with alcohol.

In each reaction zone, the raw amide is reacted with the raw alcohol to change into an ester in the presence of a catalyst.

The liquid containing the produced ester and the raw amide is distributed to the next reaction zone.

That is, the conversion of the amide increases and the ester increases as it proceeds to the last reaction zone.

Some of the ammonia generated in each reaction zone is vaporized with alcohol and fed to the previous reaction zone.

As the reaction zone proceeds from the last reaction zone to the first reaction zone, the proportion of ammonia in the distilled gas increases.

That is, the closer to the first reaction zone, the higher the ratio of ammonia, and the closer to the last reaction zone, the lower the ratio of ammonia.

As a result, in each reaction zone, the proportional relationship between the molar ratio of the raw amide and the alcohol in the liquid phase and the ammonia fraction of the distillation gas from the reaction zone is maintained.

It is possible to increase the conversion of amide without changing the distillation amount.

In order to maintain boiling in all reaction zones with less thermal energy, (a) the reaction liquid in the last reaction zone is heated to vaporize a portion of the alcohol or a mixture of alcohol and ammonia, and the steam is sequentially introduced into the reaction zone. Or (b) introducing a vapor of alcohol or a mixture of alcohol vapor and an inert gas into the last reaction zone, and subsequently introducing this gas into the preceding reaction zone, followed by a first reaction. The discharge from the zone is desirable.

The reaction zones are sufficient to be connected in series, and each one does not have to be a separate reactor.

In other words, not only a method of connecting independent reactors by pipes, but also one reactor may be partitioned into a plurality of reaction zones.

The spatial arrangement of the reaction zones is not a problem and can be connected side by side in either horizontal or vertical direction.

A step-top reactor is one type of device in which a plurality of reaction zones are vertically connected.

FIG. 1 shows a diagram of an apparatus in which three reactors are connected as an example of a method of connecting independent reactors by piping.

In FIG. 1, amide as a raw material is introduced into the first reactor 1, and gas is introduced into the third reactor 3.

Between each reactor is connected to the gas conduits (8), (9) and liquid conduits (4), (5), and the liquid is passed through the liquid conduit from the first reactor (1) to the second reactor (2) and the third reactor (3). Flows).

The gas, in contrast, flows from the third reactor 3 to the second reactor 2 and the first reactor 1 through the gas conduit.

When one reactor is partitioned and divided into a plurality of reaction zones, each reaction zone is blocked by a partition plate, and the liquid and gas flow in opposite directions.

In such a multistage reaction method, it is important to operate so that the ammonia concentration in the reaction liquid is maintained at 0.1% by weight or less in each reaction zone.

By adopting this multi-stage reaction method, high conversion and selectivity can be obtained with less energy.

According to the method of the present invention, α-hydroxycarboxylic acid ester can be industrially advantageously produced from α-hydroxycarboxylic acid amide and an alcohol with high conversion and selectivity.

Next, the present invention will be described in detail again by way of examples, but the present invention is not limited to these examples.

Example 1

63.5 g (0.634 mol) of α-hydroxyisobutyric acid amide (HBD) was dissolved in 1000 g of isopropanol.

A solution obtained by dissolving 30 g (0.106 mol) of titanium tetraisopropoxide in 1000 g of isopropanol was added thereto.

The mixed solution was concentrated to 840 g by distilling off isopropanol using a rotary evaporator.

The precipitate precipitated after standing at room temperature for one day was filtered, washed with heptane and dried in vacuo to give 37.0 g of crystals.

Elemental analysis of the obtained complex salt showed Ti: 10.5 wt%, C: 42.7 wt%, H: 7.91 wt%, and N: 12.1 wt%.

This complex salt was identified as Ti (HBD) ₄ (Elemental analysis theory: Ti: 10.4% by weight, C: 41.8% by weight, H: 7.83% by weight, N: 12.2% by weight).

30.0 g (0.291 mol) of α-hydroxyisobutyric acid amide, 100 g of methanol, and 4.85 g (0.0106 mol) of Ti (HBD) ₄ complex salt were added to a 300 ml stainless steel autoclave equipped with a jacketed reflux condenser and a stirrer. Was maintained at 3.0 MPa, and the reaction was carried out for 1.5 hours while supplying nitrogen gas to the autoclave at 190 ° C under agitation and releasing the resulting ammonia together with the nitrogen gas from the autoclave.

At this time, 185 ° C. oil was circulated and heated in the jacket of the reflux condenser, and a portion of methanol and ammonia were removed from the top of the reflux condenser at a rate of 30 g / hr and 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.

The ammonia concentration in the resulting solution was less than 0.01% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 95.3 mol%, the selectivity of α-hydroxyisobutyric acid methyl ester was 97.1 mol%, and α-hydroxyisobutyric acid (N-methyl ), The selectivity of amide was obtained at 2.9 mol%.

Comparative Example 1

Into a 300 ml stainless steel autoclave with a stirrer, 30.0 g (0.291 mol) of α-hydroxyisobutyric acid amide, 100 g of methanol and 4.85 g (0.0106 mol) of Ti (HBD) ₄ complex salt were added to maintain the pressure at 3.0 MPa. Then, the autoclave was sealed at 190 degreeC under stirring, and reaction was performed for 1.5 hours.

The ammonia concentration in the resulting solution was 1.01% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 34.9 mol%, the selectivity of α-hydroxyisobutyric acid methyl ester was 78.9 mol%, and the α-hydroxyisobutyric acid (N-methyl) 18.2 mol% of selectivity of the amide was obtained.

Comparative Example 2

30.0 g (0.291 mol) of α-hydroxyisobutyric acid amide, 100 g of methanol, and 4.85 g (0.0106 mol) of Ti (HBD) ₄ complex salt were added to a 300 ml stainless steel autoclave equipped with a jacketed reflux condenser and a stirrer. Was maintained at 3.0 MPa, and the reaction was carried out for 1.5 hours while supplying nitrogen gas to the autoclave at 190 ° C. under stirring, and releasing the resulting ammonia from the autoclave together with the nitrogen gas.

At this time, 20 degreeC cold water was circulated and cooled in the jacket of a reflux condenser, and methanol evaporated in the reactor was condensed by the reflux condenser entirely, and it returned to the reactor as methanol which melt | dissolved ammonia.

The ammonia concentration in the resulting solution was 0.59% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 56.4 mol%, the selectivity of α-hydroxyisobutyric acid methyl ester was 87.1 mol%, and α-hydroxyisobutyric acid (N-methyl) The selectivity for amide was 11.2 mol%.

Example 2

56.5 g (0.634 mole) of lactamide (LD) was dissolved in 500 g of isopropanol.

A liquid obtained by dissolving 30 g (0.106 mol) of titanium tetraisopropoxide in 150 g of isopropanol was added thereto.

The mixture was concentrated to 200 g by distilling off isopropanol using a rotary evaporator.

The precipitate precipitated by standing at room temperature for one day was filtered, washed with heptane and dried in vacuo to give 34.3 g of crystals.

An elemental analysis of the obtained complex salt showed that Ti: 11.9% by weight, C: 36.0% by weight, H: 6.84% by weight, and N: 13.6% by weight.

This complex salt was identified as Ti (HBD) ₄ (Elemental analysis theory: Ti: 11.9% by weight, C: 35.6% by weight, H: 6.93% by weight, N: 13.9% by weight).

25.9 g (0.291 mol) of lactamide, 100 g of methanol, and 4.28 g (0.0106 mol) of Ti (LD) ₄ complex salt were added to a 300 ml stainless steel autoclave equipped with a jacketed reflux condenser and agitator to maintain the pressure at 3.0 MPa. Under agitation, the reaction was carried out for 1.5 hours while supplying nitrogen gas to the autoclave at 190 ° C and releasing the resulting ammonia together with the nitrogen gas from the autoclave.

At this time, 185 ° C. oil was circulated and heated in the jacket of the reflux condenser, and a portion of methanol and ammonia were removed from the top of the reflux condenser at a rate of 30 g / hr and 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.

The ammonia concentration in the resulting solution was less than 0.01% by weight, the conversion rate of lactamide was 95.6 mol%, the selectivity of methyl lactate was 97.4 mol%, and the selectivity of lact (N-methyl) amide was 2.6 mol%.

Example 3

40 g of bismuth nitrate was dissolved in 50 ml of 10% aqueous nitric acid solution, the pH was adjusted to 8 with 28% by weight of ammonia water while stirring, and bismuth hydroxide was precipitated.

After filtering and washing this deposit, it dried at 110 degreeC for one day, and baked at 450 degreeC for 3 hours.

After the reaction, the reaction solution was cooled and analyzed by gas chromatography.

The ammonia concentration in the resulting solution was less than 0.01% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 57.3 mol%, the selectivity of α-hydroxyisobutyric acid methyl ester was 97.3 mol%, and α-hydroxyisobutyric acid (N-methyl ) Selectivity of the amide was obtained 2.7 mol%.

Comparative Example 3

3.0 g of bismuth oxide obtained in Example 3 was used as a catalyst, and esterification with methanol was carried out in the same manner as in Comparative Example 2.

The ammonia concentration in the resulting solution was 0.47% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 32.7 mol%, the selectivity of α-hydroxyisobutyric acid methyl ester was 80.3 mol%, and α-hydroxyisobutyric acid (N-methyl The selectivity of the amide was 19.7 mol%.

Example 4

200 g of cerium nitrate was dissolved in 2000 ml of water, and 5% by weight aqueous solution of ammonium carbonate was added while stirring to adjust the pH to 8 to form a precipitate.

After filtering and washing this deposit, it dried at 110 degreeC for one day, and baked at 450 degreeC 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 resulting solution was less than 0.01% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 81.7 mol%, the selectivity of α-hydroxyisobutyric acid methyl ester was 97.4 mol%, and α-hydroxyisobutyric acid (N-methyl ) 2.6 mol% of the selectivity was obtained.

Comparative Example 4

3.0 g of cerium oxide obtained in Example 4 was used as a catalyst, and esterification with methanol was carried out in the same manner as in Comparative Example 2.

The ammonia concentration in the resulting solution was 0.86% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 52.7 mol%, the selectivity of α-hydroxyisobutyric acid methyl ester was 86.5 mol%, and α-hydroxyisobutyric acid (N-methyl) The selectivity of the amide was 13.5 mol%.

Example 5

An esterification reaction with methanol was carried out in the same manner as in Example 1 except that 2.0 g of fine powder of metal bismuth was used as a catalyst.

After the reaction, the reaction solution was cooled and analyzed by gas chromatography.

The ammonia concentration in the resulting solution was less than 0.01% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 64.7 mol%, the selectivity of α-hydroxyisobutyric acid methyl ester was 97.3 mol%, and the α-hydroxyisobutyric acid (N-methyl ) Selectivity of the amide was obtained 2.7 mol%.

Comparative Example 5

Using 2.0 g of fine powder of metal bismuth as a catalyst, esterification with methanol was carried out in the same manner as in Comparative Example 2.

The ammonia concentration in the resulting solution was 0.75% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 47.4 mol%, the selectivity of α-hydroxyisobutyric acid methyl ester was 82.6 mol%, and α-hydroxyisobutyric acid (N-methyl) The selectivity of the amide was obtained at 17.4 mol%.

Example 6

[Esterification Experiment]

4.85 g of Ti (HBD) ₄ complex salt prepared in 30.0 g (0.291 mol) of α-hydroxyisobutyric acid amide, 100 g of methanol, as described in Example 1, in a 300 ml stainless steel autoclave with a jacketed reflux condenser and a stirrer. 0.0106 mol) was added to maintain the pressure at 3.0 MPa, and the reaction was carried out at 190 DEG C while supplying nitrogen gas to the autoclave at 1 L / min and releasing the resulting ammonia from the autoclave with nitrogen gas for 1.5 hours.

At this time, 185 ° C. oil was circulated and heated in the jacket of the reflux condenser, and a portion of methanol and ammonia were removed from the upper portion of the reflux condenser at a rate of 50 g / hr and methanol was supplied to the reactor at a rate of 50 g / hr.

After the reaction, the reaction solution was cooled and analyzed by gas chromatography.

The ammonia concentration in the resulting solution was less than 0.01% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 95.6 mol%, the selectivity of α-hydroxyisobutyric acid methyl ester was 98.5 mol%, and α-hydroxyisobutyric acid (N-methyl ), The selectivity for amide was obtained at 1.5 mol%.

[Recycling Experiment 1]

The reaction product obtained in the esterification experiment was removed from the reactor and distillation operation was performed.

The resulting solution was placed in a 200 ml eggplant flask, and unreacted methanol was separated as a component at 65 ° C under normal pressure.

The resulting α-hydroxyisobutyrate methyl was separated as a component at 50 ° C. under a reduced pressure of 30 mmHg.

The remaining unevaporated portion is a part of α-hydroxyisobutyrate which was not recovered as a component, α-hydroxyisobutyric acid (N-methyl) amide as a by-product, α-hydroxyisobutyric acid amide which is an unreacted raw material, and a catalyst component. It contained a metal complex salt of phosphorus titanium.

The total amount of unevaporated content was put into a reactor, and again, alpha-hydroxyisobutyric acid amide and methanol were added and esterification was performed.

At this time, the total amount of the newly added α-hydroxyisobutyric acid amide and α-hydroxyisobutyric acid amide in the unevaporated powder was 30.0 g.

This operation was repeated 10 times.

The results are shown in Table 1.

About 1.5 mol% of by-products of α-hydroxyisobutyric acid (N-methyl) amide were identified in one esterification reaction, and the reaction tended to accumulate in the method of recycling experiment 1 during repeated reactions.

HDB: α-hydroxyisobutyric acid amide

HBM: α-hydroxyisobutyrate methyl

N-Meamide: α-hydroxyisobutyric acid (N-methyl) amide

% Of HBD conversion rate = [1- (unreacted HBD mole of this batch) / (new addition HBD mole of this batch + unreacted HBD mole of last batch)] × 100

HBM Selectivity Mole% = [(Generation HBM Mole) / (Generation HBM Mole + Generation N-Meamide Mole)] × 100

N-Meamide selectivity mole% = [(current batch B- (N-Meamide mole) / (current HBM mole + current batch N-Meamide mole)] × 100

Total mole% of N-Meamide selectivity = [((N-Meamide mole / (HBM mole produced in this batch) + N-Meamide mole generated in this batch)] × 100

Example 7

The 10th production liquid of the repeated experiment of Example 6 was distilled according to the operation of recycling experiment 1 of Example 1, and the unreacted methanol and the produced alpha-hydroxyisobutyrate were separated as a component.

Discard 30% of the obtained evaporated fraction, add the remaining 70% evaporated fraction and 1.45 g (0.0032 mol) of new Ti (HBD) ₄ complex salt into the reactor, and add α-hydroxyisobutyric acid amide and methanol again. Esterification reaction was carried out.

The results are shown in Table 2.

Accumulation of α-hydroxyisobutyric acid (N-methyl) amide could be suppressed by discarding a part of unevaporated powder.

Example 8

[Recycling Experiment 2]

The eleventh production liquid of Example 7 was distilled off according to the operation of Recirculation Experiment 1 of Example 6 to separate unreacted methanol and produced α-hydroxyisobutyrate as a component. The obtained evaporated fraction was subjected to second distillation to separate α-hydroxyisobutyric acid (N-methyl) amide as a by-product as a component at 100 ° C. under a reduced pressure of 10 mmHg. The remaining unevaporated powder contained the metal complex salt of (alpha) -hydroxyisobutyric acid amide which is an unreacted raw material, and titanium which is a catalyst component.

The total amount of the remaining evaporated content was added to the reactor, and α-hydroxyisobutyric acid amide and methanol were added again to carry out the eleventh esterification reaction.

The results are shown in Table 2. The second distillation separated out the α-hydroxyisobutyric acid (N-methyl) amide, thereby preventing accumulation in the reaction system.

Example 9

Into a 300 ml stainless steel autoclave with a stirrer, 25.0 g (0.291 mol) of lactamide, 100 g of methanol, and 4.28 g (0.0106 mol) of Ti (LD) ₄ complex salt prepared in the same manner as in Example 2 were added thereto. According to the esterification reaction condition and the recycling experiment 1, the repeated reaction was carried out from 1 to 5 batches, and the 6th batch was repeated according to the recycling experiment 2 of Example 8. The results are shown in Table 3.

LD: Lactamide

LM: α-hydroxylactic acid methyl

N-Meamide: Lact (N-methyl) amide

Example 10

1800 g of methanol was added to 31.0 g (0.301 mol) of α-hydroxyisobutyric acid amide (HBD) and 30.0 g (0.120 mol) of dibutyltin oxide, and dissolved under heating and reflux.

The solution was concentrated to 150 g by distilling off methanol using a rotary evaporator. The precipitate precipitated after standing at room temperature for one day was filtered, washed with heptane and dried in vacuo to give 42.1 g of crystals.

An elemental analysis of the obtained complex salt showed that Sn: 24.5 wt%, C: 42.1 wt%, H: 816 wt%, and N: 5.97 wt%.

This complex salt was identified as (HBD) ₂ Bu ₂ Sn (Elemental Analysis Theory: Sn: 27.1 wt%, C: 43.8 wt%, H: 8.21 wt%, N: 6.38 wt%).

Into a 300 ml stainless steel autoclave with a stirrer, 30.0 g (0.291 mol) of α-hydroxyisobutyric acid amide, 100 g of methanol, and 10.57 g (0.0241 mol) of (HBD) ₂ Bu ₂ Sn complex salt were added thereto. The reaction time was changed to 2.5 hours under the esterification condition, and the reaction was repeated from 1 to 5 batches according to the recycle experiment 1.

The production solution of the fifth experiment was distilled according to the operation of Recycling Experiment 1 of Example 6 to separate unreacted methanol and produced α-hydroxyisobutyrate as a component.

50% of the obtained evaporated fraction was introduced into the reactor as it is, and the remaining 50% of the evaporated fraction was separated and removed with α-hydroxyisobutyric acid (N-methyl) amide as a component according to the distillation method of recycling experiment 2 of Example 8. The mixture was charged into a reactor as undistilled fraction of the second distillation.

Again, α-hydroxyisobutyric acid amide and methanol were added to carry out the sixth esterification reaction. The results are shown in Table 4.

Example 11

A lower reactor is heated by connecting a 150 ml SUS316 reactor (upper reactor) with an internal volume of 500 ml of SUS316 (lower reactor) with a forced stirring device to flow liquid and gas in opposite directions. The apparatus was prepared by evaporating the alcohol inside, withdrawing gas through the upper reactor, and withdrawing the liquid from the upper reactor through the lower reactor.

The schematic diagram of this reactor is shown in FIG.

The upper reactor of this reactor was supplied with? -Hydroxyisobutyric acid amide, methanol, and titanium isopropoxide as a catalyst at 50 g / hr, 100 g / hr, and 10 g / hr, respectively.

The lower reactor was heated to vaporize ammonia and methanol while the upper reactor was sufficiently kept in temperature to inhibit condensation of methanol vapor from the lower reactor as much as possible.

Distillation gas from the upper reactor is liquefied into a condenser and accumulates in the condensate container.

As such, the liquid temperature in the upper reactor and the liquid in the lower reactor are maintained at 170 ° C.

From the bottom of the bottom reactor, the reaction solution was obtained at 141 g / hr from the top reactor at 110 g / hr.

The reaction solution obtained from the bottom reactor was analyzed by gas chromatography, and the conversion of α-hydroxyisobutyric acid amide was 83 mol%, and the product of α-hydroxyisobutyrate methyl was obtained at 98 mol%.

The distilled gas was cooled and liquefied, and analyzed. As a result, 4.1% by weight of ammonia and 95.9% by weight of methanol were included.

The ammonia concentration in the reaction liquid of the lower reactor and the reaction liquid of the upper reactor was less than 0.01% by weight.

Reference Example 1

Into a 500 ml SUS316 reactor equipped with a forced stirring device, 50 g / hr, 200 g / hr and 10 g / hr of α-hydroxyisobutyric acid amide, methanol and titanium isopropoxide were introduced as catalysts, respectively.

The reactor was heated to distill off ammonia and methanol.

The reaction solution temperature was maintained at 170 ° C, the reaction solution was obtained at 141 g / hr and distillate at 110 g / hr.

The reaction solution obtained from the bottom of the reaction solution was analyzed by gas chromatography, and the conversion of α-hydroxyisobutyric acid amide was 63 mol%, and the product of α-hydroxyisobutyrate methyl was obtained at a selectivity of 98 mol%.

The distilled gas was cooled and liquefied, and analyzed. The mixture contained 3.4% by weight of ammonia and 96.6% by weight of methanol.

Example 12

The same operation as in Example 11 was carried out except that lactamide was used instead of α-hydroxyisobutyric acid amide.

The conversion rate of lactamide was 80 mol%, and the selectivity of methyl lactate was 98 mol%.

Example 13

The same operation as in Example 11 was carried out except that tributyltin oxide was used instead of titanium isopropoxide.

The conversion rate of α-hydroxyisobutyric acid amide was 70 mol% and the selectivity of α-hydroxyisobutyrate methyl was 98 mol%.

Example 14

The same operation as in Example 11 was carried out except that the lanthanum triflate was used instead of titanium isopropoxide.

The conversion rate of α-hydroxyisobutyric acid amide was 83 mol% and the selectivity of α-hydroxyisobutyrate methyl was 98 mol%.

Example 15

The same operation as in Example 11 was carried out except that bismuth oxide was used as a slurry instead of titanium isopropoxide.

The conversion of α-hydroxyisobutyric acid amide was 50 mol% and the selectivity of α-hydroxyisobutyrate methyl was 98 mol%.

Example 16

Α-hydroxyisobutyricamide 30 at a position of 50cm from the top of the tower, using a device that connected a liquid dispersing type charging tower with a diameter of 2cm and a tower length of 2m with a Dickson packing with a diameter of 3mm on top of a 100ml pressure-resistant container. 57 g / hr of a mixed liquid of 64% by weight, 64% by weight of methanol and 6% by weight of titanium isopropoxide was supplied, and 85 g / hr of methanol was supplied at a position of 50 cm from the bottom of the column. Gasification was carried out to remove methanol gas containing ammonia at 62 g / hr from the top of the column.

At this time, the pressure was maintained at 2 MPa so that the reaction liquid temperature was 170 ° C, and the reaction liquid was removed from the bottom portion of the pressure vessel so that the liquid volume in the pressure vessel was 50 ml.

The reaction solution obtained from the bottom part was analyzed by gas chromatography. The ammonia concentration in the resulting solution was less than 0.01% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 86 mol%, and the product of methyl α-hydroxyisobutyrate was Obtained with a selectivity of 97 mol%.

After distilled gas was cooled and liquefied, it was analyzed, which contained 2.7% by weight of ammonia and 97.2% by weight of methanol.

Example 17

Using a bubble column having an inner diameter of 2 cm and a length of 1 m, 57 g / of a mixed liquid of 30% by weight of α-hydroxyisobutyric acid amide, 64% by weight of methanol, and 6% by weight of titanium isopropoxide at a position of 25cm from the top of the column. hr, 85 g / hr of methanol was supplied at a position of 25 cm from the bottom of the column, the bottom of the column was heated to gasify methanol, and 60 g / hr of methanol gas containing ammonia was distilled off from the top of the column.

At this time, the pressure was maintained at 2 MPa so that the reaction liquid temperature was 170 ° C, and the reaction liquid was removed from the bottom of the column so that the liquid level was constant at a height of 10 cm from the top of the column.

The reaction solution obtained from the bottom of the column was analyzed by gas chromatography, and the concentration of ammonia in the resulting solution was less than 0.01% by weight, the conversion rate of α-hydroxyisobutyric acid amide was 82 mol%, and the product of methyl α-hydroxyisobutyrate This selectivity was obtained at 97 mol%.

After distilled gas was cooled and liquefied, it was analyzed and found to contain 2.6% by weight of ammonia and 97.3% by weight of methanol.

Example 18

The same operation as in Example 16 was carried out except that lactamide was used instead of α-hydroxyisobutyric acid amide.

The conversion rate of lactamide was 81 mol%, and the selectivity of methyl lactate was 97 mol%.

Example 19

The same operation as in Example 16 was carried out except that tributyltin oxide was used instead of titanium isopropoxide.

The conversion rate of α-hydroxyisobutyric acid amide was 69 mol% and the selectivity of α-hydroxyisobutyrate methyl was 97 mol%.

Example 20

The same operation as in Example 16 was carried out except that a lanthanum triflate was used instead of titanium isopropoxide.

The conversion rate of α-hydroxyisobutyric acid amide was 84 mol% and the selectivity of α-hydroxyisobutyrate methyl was 97 mol%.

Example 21

The same operation as in Example 17 was carried out except that bismuth oxide was used as a slurry instead of titanium isopropoxide.

The conversion of α-hydroxyisobutyric acid amide was 50 mol% and the selectivity of α-hydroxyisobutyrate methyl was 97 mol%.

Example 22

The same operation as in Example 16 was performed except that CeO ₂ molded into a diameter of 3 mm and a length of 5 mm was used as a filler for the solid catalyst without using titanium isopropoxide.

The conversion of α-hydroxyisobutyric acid amide was 50 mol% and the selectivity of α-hydroxyisobutyrate methyl was 97 mol%.

Example 23

30.0 g (0.291 mol) of α-hydroxyisobutyric acid amide, 100 g of methanol, and 4.85 g (0.0106 mol) of Ti (HBD) ₄ complex salt were added to a 300 ml stainless steel autoclave equipped with a jacketed reflux condenser and a stirrer. Was maintained at 3.0 MPa, and the reaction was carried out for 1.5 hours while supplying nitrogen gas to the autoclave at 190 ° C under agitation and releasing the resulting ammonia together with the nitrogen gas from the autoclave.

After the reaction, the reaction solution was cooled and analyzed by gas chromatography.

The ammonia concentration in the resulting solution was less than 0.01% by weight, and the conversion rate of α-hydroxyisobutyric acid amide was 78.7 mol% and the selectivity of α-hydroxyisobutyric acid methyl ester was 95.5 mol%.

Example 24

Into a 300 ml stainless steel autoclave with a stirrer, 30.0 g (0.291 mol) of α-hydroxyisobutyric acid amide, 100 g of methanol and 3.00 g (0.0106 mol) of titanium tetraisopropoxide were added to maintain the pressure at 3.0 MPa. Under agitation, the reaction was carried out for 1.5 hours while supplying nitrogen gas to the autoclave at 190 ° C and releasing the resulting ammonia together with the nitrogen gas from the autoclave.

After the reaction, the reaction solution was cooled, and a part of it was sampled and analyzed by gas chromatography to calculate reactivity. The ammonia concentration in the resulting solution was less than 0.01% by weight, and the conversion rate of α-hydroxyisobutyric acid amide was 83.0 mol%. and the selectivity of the (alpha) -hydroxyisobutyric acid methyl ester were 79.1 mol%.

The resulting solution was placed in a flask and subjected to monostillation, and methanol, α-hydroxyisobutyric acid methyl ester, and unreacted α-hydroxyisobutyric acid amide were distilled off, and 4.85 g of undistilled water remained.

Elemental analysis of the distillate showed that it was the same as Ti (HBD) ₄ .

It was found that part of the reacted α-hydroxyisobutyric acid amide was consumed in the formation of the complex salt with titanium, and was not actually involved in the production of the α-hydroxyisobutyric acid methyl ester.

Considering this, the selectivity of the α-hydroxyisobutyric acid methyl ester was 95.1 mol%.

Reference Example 2

Titanium tetraisopropoxide was added to the methanol solution of (alpha)-hydroxyisobutyric acid amide in varying ratios.

The state was kept stirring for 5 minutes, and after 5 minutes, the (alpha) -hydroxyisobutyric acid amide in the liquid mixture was quantified.

After 5 minutes, quantification of α-hydroxyisobutyric acid amide in the mixed solution was performed by an internal standard method using gas chromatography.

Α in the molar ratio of the actual amount of α-hydroxyisobutyric acid amide (HBD) to the amount of titanium tetraisopropoxide (Ti) actually used, and the gas chromatographic quantification of the amount of titanium tetraisopropoxide in the actual mixture. The molar ratio of the amount of hydroxyisobutyric acid amide was calculated. The results are shown in Table 5.

As shown in Table 5, when the molar ratio of HBD amount quantified by gas chromatography to the amount of Ti actually used is 4 or less, α-hydroxyisobutyric acid amide is not detected. Therefore, Ti (HBD) ₄ is considered to be produced. .

Example 25

10.57 g (0.0241 mol) of (HBD) ₂ Bu ₂ Sn complex salt prepared in the same manner as Example 10 in 30.0 g (0.291 mol) of α-hydroxyisobutyric acid amide, 100 g of methanol in a 300 ml stainless steel autoclave with a stirrer The reaction was carried out for 2.5 hours while the pressure was maintained at 3.0 MPa, the nitrogen gas was supplied to the autoclave at 190 ° C under stirring, and the resulting ammonia was released together with the nitrogen gas from the autoclave.

After the reaction, the reaction solution was cooled, and a portion thereof was sampled and analyzed by gas chromatography to calculate reactivity. The conversion rate of α-hydroxyisobutyric acid amide was 74.5 mol%, and the ammonia concentration in the resulting solution was less than 0.01 wt%. The selectivity of the (alpha)-hydroxyisobutyric acid methyl ester was 96.1 mol%.

Example 26

Into a 300 ml stainless steel autoclave with a stirrer, 25.9 g (0.291 mol) of α-hydroxyisobutyric acid amide, 100 g of methanol and 4.28 g (0.0106 mol) of Ti (LD) ₄ complex salt prepared in the same manner as in Example 2 were charged. The pressure was maintained at 3.0 MPa, and the reaction was carried out for 1.5 hours while supplying nitrogen gas to the autoclave at 190 ° C under agitation and releasing the resulting ammonia from the autoclave together with the nitrogen gas.

After the reaction, the reaction solution was cooled and analyzed by gas chromatography.

The ammonia concentration in the resulting solution was less than 0.01% by weight, the selectivity of lactic acid conversion 78.1 mol% and lactic acid methyl ester was 95.4 mol%.

Example 27

30.0 g (0.291 mol) of α-hydroxyisobutyric acid amide, 100 g of methanol and 6.19 g (0.0106 mol) of lanthanum triflate were added to a 300 ml stainless steel autoclave equipped with a jacketed reflux condenser and a stirrer, and the pressure was 3.0 MPa. The reaction was carried out for 1.5 hours while supplying nitrogen gas to the autoclave at 190 ° C. under agitation and releasing the resulting ammonia together with nitrogen gas from the autoclave.

At this time, 185 ° C. oil was circulated and heated in the jacket of the reflux condenser, and a portion of methanol and ammonia were removed from the top of the reflux condenser at a rate of 30 g / hr and 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.

The ammonia concentration in the resulting solution was less than 0.01% by weight, and the conversion of 98.5 mol% of α-hydroxyisobutyric acid amide and the selectivity of α-hydroxyisobutyric acid methyl ester were 98.2 mol%.

Examples 28-32

The reaction was carried out in the same manner as in Example 27, except that the various metal triflate catalysts shown in Table 6 were used. The results are shown in Table 6.

La (OTf) ₃ : Lanthanum Triflate, OTf stands for triplerate

Reference Examples 3-7

In Table 7 below, various metal carboxylates were used in the same number of moles as the metal triplate, and the reaction was carried out using a catalyst.

The reaction was carried out in the same manner as in Example 27 except for using the catalyst described.

The results are shown in Table 7.

As can be seen from Table 7, the conversion rate was higher for the metal tree plate.

La (OAc) ₃ 1.5H ₂ O: Lantancarboxylate, OAc stands for carboxylate

Reference Example 8 ( Example Using Titanium Homogeneous Catalyst)

5 wt% of water was added to the α-hydroxyisobutyric acid amide as an input, and the reaction was carried out in the same manner as in Example 27 except that 4.85 g (0.0106 mol) of Ti (HBD) ₄ complex salt was used as the catalyst.

The conversion of 80.7 mol% of the α-hydroxyisobutyric acid amide and the selectivity of the α-hydroxyisobutyric acid methyl ester were 90.2 mol% and the 8.2-% selectivity of the α-hydroxyisobutyric acid.

White precipitates precipitated in the resulting solution, and during the reaction, the Ti (HBD) ₄ complex salt was hydrolyzed to form some titanium hydroxide and titanium oxide.

For this reason, amide conversion fell, the hydrolysis of amide was also accelerated | stimulated, and ester selectivity fell.

Example 33

5 wt% of water was added to α-hydroxyisobutyric acid amide as an input, and the reaction was carried out in the same manner as in Example 27 except that 6.19 g (0.0106 mol) of La (OTf) ₃ was used as a catalyst.

97.9 mol% of the conversion rates of (alpha) -hydroxyisobutyric acid amide 98.2 mol% and the selectivity of (alpha) -hydroxyisobutyric acid methyl ester were obtained.

Hydrolysis of α-hydroxyisobutyric acid with water occurs partially in the system, but since the catalyst does not lose activity, esterification with methanol also occurs simultaneously, so no decrease in ester selectivity was observed.

Example 34

5 wt% of water was added to the α-hydroxyisobutyric acid amide as an input, and the reaction was carried out in the same manner as in Example 27 except that 6.55 g (0.0106 mol) of Yb (OTf) ₃ was used as a catalyst.

97.1 mol% of conversion rates of (alpha) -hydroxyisobutyric acid amide, and 97.1 mol% of selectivity of (alpha)-hydroxyisobutyric acid methyl ester were obtained.

Example 35

The reaction was carried out in the same manner as in Example 27, except that 25.9 g (0.291 mol) of lactamide, 100 g of methanol, and 6.19 g (0.0106 mol) of La (OTf) ₃ were used as the input.

As for the selectivity of 98.1 mol% of lactamide conversion rates, and (alpha)-hydroxyisobutyric acid methyl ester, 97.4 mol% was obtained.

Example 36

The reaction was carried out in the same manner as in Example 27, except that 25.9 g (0.291 mol) of lactamide, 100 g of methanol, and 6.55 g (0.0106 mol) of Yb (OTf) ₃ were used as the input.

96.2 mol% of lactamide conversions and 98.4 mol% of the selectivity of (alpha)-hydroxyisobutyric acid methyl ester were obtained.

Example 37

The reaction was carried out in the same manner as in Example 27, except that 25.9 g (0.291 mol) of lactamide, 100 g of methanol, and 4.40 g (0.0106 mol) of Sn (OTf) ₃ were used as an input.

97.5 mol% of lactamide conversion rates and 98.7 mol% of the selectivity of (alpha)-hydroxyisobutyric acid methyl ester were obtained.

(alpha) -hydroxycarboxylic acid ester can be manufactured from a (alpha)-hydroxycarboxylic acid amide and an alcohol with high selectivity and high yield.

Claims (16)

[alpha] -hydroxycarboxylic acid amide and alcohol are reacted in the liquid phase in the presence of alcohol and at the same time, the generated ammonia gas is discharged in the gas phase to maintain the ammonia concentration in the reaction solution at 0.1% by weight or less. Method for producing α-hydroxycarboxylic acid ester. The method of claim 1, A method for producing α-hydroxycarboxylic acid ester, characterized in that the reaction solution is boiled or the inert gas in the reaction solution is bubbled or the ammonia gas generated by both operations is discharged in the gas phase. The method of claim 1, A method for producing α-hydroxycarboxylic acid ester, characterized in that the ammonia generated simultaneously with the supply of alcohol to the reaction solution is continuously discharged together with the alcohol. The method of claim 1, A method for producing α-hydroxycarboxylic acid ester, characterized by using a gas dissipation device as a reaction device and discharging a gas containing alcohol and by-products of ammonia. The method of claim 4, wherein The gas-dispersing apparatus is a packed column, a bubble column, or a flat tower, The manufacturing method of the (alpha)-hydroxycarboxylic acid ester characterized by the above-mentioned. The method of claim 1, While discharging the generated ammonia gas into the gas phase, the reaction solution was taken out of the reactor and introduced into the distillation zone, and the unreacted alcohol and the produced α-hydroxycarboxylic acid ester were separated as evaporated fractions, and a part of the unevaporated fractions. Or a process for producing α-hydroxycarboxylic acid ester, wherein all are recycled to the reactor. The method of claim 1, While discharging the ammonia generated as a gas into the gas phase, the reaction solution was withdrawn from the reactor and introduced into the first distillation zone, and the unreacted alcohol and the resulting α-hydroxycarboxylic acid ester were separated as an evaporation component and not evaporated. A part or all of the powder is introduced into the second distillation zone, the α-hydroxycarboxylic acid (N-alkyl) amide is separated as an evaporated fraction, and some or all of the unvaporized fraction is recycled to the reactor. Method for producing α-hydroxycarboxylic acid ester. The method of claim 1, (a) using a reactor in which a plurality of reaction zones are arranged in series and connected to allow liquid and gas to flow in opposite directions between adjacent reaction zones; (b) feed the raw material α-hydroxycarboxylic acid amide and alcohol into the reaction zone after the first time, (c) maintaining each reaction zone in a boiling state, supplying gas from any particular reaction zone containing alcohol and by-product ammonia to the preceding reaction zone, containing the raw materials and products of the reaction zone; The liquid is fed to the later reaction zone, (d) A method for producing α-hydroxycarboxylic acid ester, characterized in that the gas is discharged from the first reaction zone and the reaction liquid is discharged from the last reaction zone. The method of claim 8, A method for producing α-hydroxycarboxylic acid ester, wherein any concentration of ammonia in the reaction liquid in each reaction zone is maintained at 1% by weight or less. The method of claim 1, A method for producing α-hydroxycarboxylic acid ester, wherein the α-hydroxycarboxylic acid amide is lactamide or α-hydroxyisobutyric acid amide and the alcohol is methanol. The method of claim 1, A process for producing α-hydroxycarboxylic acid ester, characterized in that the catalyst is a soluble metal complex salt made of titanium or tin or α-hydroxycarboxylic acid amides of both. The method of claim 1, A method for producing α-hydroxycarboxylic acid ester, wherein the catalyst is a metal trifluoromethanesulfonate salt. The method of claim 12, ? -Hydroxycarboxyl, characterized in that the metal constituting the metal trifluoromethanesulfonate salt is at least one selected from the elements belonging to groups 1, 2, 3, 4, 11, 12, 13 and 14 of the periodic table Production method of acid ester. The method of claim 13, A method for producing α-hydroxycarboxylic acid ester, wherein the metal constituting the metal trifluoromethanesulfonate salt is at least one selected from the lanthanoid elements. The method of claim 1, The catalyst is Sb, Sc, Y, La, Ce, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Tc, Re, Fe, Co, Ni, Cu, Al, Si, Sn, Pb, And an insoluble metal oxide containing at least one element selected from Bi. The method of claim 1, The catalyst is an insoluble metal containing at least one element selected from Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Fe, Co, Ni, Cu, Ga, In, Bi and Te. Method for producing α-hydroxycarboxylic acid ester, characterized in that.