WO2008018121A1 - Process for producing 2-hydroxy ester compound - Google Patents

Abstract

It is intended to provide a process for producing a 2-hydroxy ester compound at a high yield from a liquid reaction mixture containing an ammonium salt. Namely, a process for producing 2-hydroxy ester compound represented by the general formula (1) which comprises: the step of distilling off an alcohol from a liquid mixture containing the above-described 2-hydroxy ester compound, the alcohol, an organic solvent and an ammonium salt; the step of adding water to the liquid residue obtained in the step of distilling off the alcohol and then separating the mixture into an organic solvent layer and an aqueous layer; and the step of distilling theorganic solvent layer obtained in the separation step to thereby purify the 2-hydroxy ester compound. [Chemical formula 1] R1-CH(OH)-COOR2 (1) Wherein R1 represents a hydrogen atom, a substituted or unsubstituted aliphatic hydrocarbon group having from 1 to 12 carbon atoms and optionally containing an oxygen atom, a sulfur atom or a nitrogen atom, a substituted or unsubstituted alicyclic hydrocarbon group having from 3 to 6 carbon atoms and optionally containing an oxygen atom, a sulfur atom or a nitrogen atom, or a substituted or unsubstituted aryl or aralkyl group having from 3 to 14 carbon atoms and optionally containing an oxygen atom, a sulfur atom or a nitrogen atom; and R2 represents an alkyl group having from 1 to 12 carbon atoms and optionally containing an oxygen atom, a sulfur atom or a nitrogen atom.

Description

 Specification

 Method for producing 2-hydroxyester compound

 Technical field

 [0001] The present invention removes a reaction liquid ammonia salt containing 2-hydroxyester compound and an ammonia salt alcohol and the like, and efficiently purifies the 2-hydroxyester compound. The present invention relates to a method for producing a 2-hydroxyester compound.

 Background art

 [0002] 2-Hydroxyester compounds are industrially important compounds as intermediates for raw materials for pharmaceuticals and agricultural chemicals and photographic materials. As starting materials, there are a method using amide, alcohol and formic acid ester, a method using 2-hydroxycarboxylic acid and alcohol, and a method using cyanohydrin and alcohol. Above all, since cyanohydrin can be easily prepared from aldehyde and hydrocyanic acid, various methods for producing 2-hydroxy ester compounds starting from cyanohydrin have been proposed! Speak.

 [0003] For example, a ketone cyanohydrin and sulfuric acid are reacted to esterify the reaction product and an alcohol, and an anhydrous sulfate such as an alkali metal is added thereto to add a 2-hydroxy fatty acid ester. There is a manufacturing method (US Pat. No. 20,418,820).

 [0004] Further, in the first step, cyanohydrin was reacted with an acid such as salt or hydrogen in an alcohol solvent to synthesize iminoether hydrochloride, and in the second step, unreacted acid was removed. There is also a method for producing a 2-hydroxyester compound by high-yield by adding water later (Japanese Patent Laid-Open No. 4-230241). This reaction is shown below using R and R ′ as alkyl groups. If the second step is followed by the second step, 2-hydroxyesters can be synthesized in a high yield and in a short time! .

[0005] [Chemical 1] First step

 OH OH NH · HC1

 R— CR '-CN + HC1 + R "0H ^-R— CR' -C-OR" Second step

 OH NH-HC1 OH

R— CR * -C— 0R "+ H ₂ 0 ^ ^ R— CR '-C00R" + NH ₄ C1

[0006] There is also a method of reacting water and phosphoric acid with a specific cyanohydrin and adding alcohol to the reaction product to carry out esterification (Japanese Patent Laid-Open No. 6-247895). In this method, when a strong acid such as sulfuric acid or hydrochloric acid is used as an acid, it is inevitable that the etherification reaction of the product hydroxycarboxylic acid ester and alcohol is avoided, and the reaction product contains an alkoxy as a by-product. This was made in view of the point that carboxylic acid ester is mixed, and is characterized in that phosphoric acid is used. When the reaction is carried out using phosphoric acid, side reactions that produce etherified products are suppressed, and the reaction proceeds with high selectivity. The reaction is shown below. The reaction is carried out by reacting cyanhydrin with water and phosphoric acid, followed by esterification with alcohol.

 [0007] [Chemical 2]

 OH OH

H— CH-CN + H ₂ 0 + H ₃ P0 ₄ ~~-H— CH-CONH ₂ · H3PO,

OH OH

H— CH— CONH ₂ · H ₃ P0 ₄ + ROH ~ HCH— COOR + NH ^ PC ^

[0008] There is also a method of reacting a specific cyanohydrin with a specific amount of water and a specific amount of sulfuric acid and adding alcohol to the reaction product to carry out esterification (Japanese Patent Laid-Open No. 6-247896). Cyanhydrin is allowed to react with water and sulfuric acid to amidate, and then esterified with alcohol, and the reaction mixture is continuously supplied with hydrous alcohol to simultaneously distill the hydroxycarboxylic acid ester produced. In this case, it is possible to suppress the side reaction to produce an etheric compound and to proceed the reaction with high selectivity. [0009] When cyanohydrin is used as a raw material, nitrogen atoms constituting cyanide are reduced and finally discharged as ammonia. Therefore, ammonium sulfate is used depending on the type of acid used. Ammonium, ammonium nitrate, ammonium phosphate, ammonium chloride are by-produced. As a method for fractionating such ammonium salt, for example, a method in which sodium sulfate is added to a reaction liquid slurry containing ammonium salt, alcohol, 2-hydroxyester, etc., and 2-hydroxyester is recovered by distillation. (U.S. Pat. No. 20,418,820) and a method of solid-liquid separation of a reaction liquid slurry (Japanese Patent Laid-Open No. 4-230241).

 Disclosure of the invention

 Problems to be solved by the invention

 [0010] However, for example, when 2-hydroxybutanoic acid methyl (hereinafter abbreviated as MHBA) is taken as an example of the 2-hydroxyester compound, MHBA dissolves ammonia salts such as ammonium chloride. Therefore, the filtrate after the solid-liquid separation contains a considerable amount of salt ammonia. When the filtrate is heated to purify MHBA by distillation, MHBA undergoes thermal decomposition due to the presence of salt ammonium and the yield decreases. Also, in order to improve the yield, a large amount of solvent is required when trying to drain the MHBA contained in the solid ammonium liquid solid-liquid separated.

 [0011] In view of the above situation, the present invention provides a reaction solution slurry force containing ammonia salt, alcohol, 2-hydroxyester, etc. 2-hydroxyester compound that removes ammonia salt by a simple method. The manufacturing method of a thing is provided.

 [0012] In particular, the present invention suppresses dissolution of a 2-hydroxyester compound in a separated water layer in a method for producing a relatively high water-soluble 2-hydroxyester compound such as MHBA. It is possible to provide a method for efficiently recovering the 2-hydroxyester compound in the separated water layer.

 Means for solving the problem

[0013] As a method for efficiently separating an ammonium salt and a 2-hydroxyester compound contained in a reaction solution, the present inventors added ammonia in the presence of an organic solvent to add ammonia. -Dissolve -um salt and separate it into two layers, so that ammonium salt can be recovered in the separated aqueous layer. It was found that the concentration of ammonia salt contained in the organic solvent can be reduced. In this water layer

Since the 2-hydroxyester compound is dissolved, it is necessary to recover the 2-hydroxyester compound by distilling the aqueous layer. The 2-hydroxyester compound is hydrolyzed in the presence of water, and the 2-hydroxyesteri compound is hydrolyzed when the separated aqueous layer is distilled immediately. As a result of diligent studies aimed at suppressing this hydrolysis, it is clear that when the aqueous layer is adjusted to pH 3-8 and then distilled, it can be recovered by azeotroping with water while suppressing decomposition of the 2-hydroxyester compound. became. When the distillate is reused as added water in the subsequent step of separating the organic solvent layer and the aqueous layer, the 2-hydroxyester can be efficiently recovered and the yield is further improved. This invention was completed based on the above findings.

 [0014] That is, the present invention is a method for producing a 2-hydroxyester compound, which comprises the 2-hydroxyester compound, an alcohol, an organic solvent, and an ammonium salt. A step of distilling alcohols from the solution, a step of adding water to the residual liquid obtained in the step of distilling off the alcohols to separate the organic solvent layer and the aqueous layer, and an organic matter obtained in the step of separating. This is a method for producing a 2-hydroxyester compound, which comprises the step of distilling the solvent layer to purify the 2-hydroxyester compound.

 The invention's effect

 [0015] According to the present invention, the 2-hydroxyester compound and the ammonium salt can be easily separated. Since the obtained organic solvent layer has a small amount of ammonium salt, a 2-hydroxyester compound can be easily produced in a high yield by distillation.

 [0016] Further, the 2-hydroxyester compound contained in the aqueous layer after the two-layer separation can be recovered together with water by distillation under specific conditions. If this is reused in the purification process, the recovery rate can be further improved.

 BEST MODE FOR CARRYING OUT THE INVENTION

[0017] A first aspect of the present invention is a process for producing a 2-hydroxyester compound represented by the general formula (1), wherein the 2-hydroxyester compound, the alcohol, the organic solvent, and the ammonia- A process of distilling off alcohol, which is a mixed liquid containing um salt,

Water is added to the residual liquid obtained in the step of distilling off the alcohols to obtain an organic solvent layer and an aqueous layer. Separating into, and

 It is a method for producing a 2-hydroxy ester compound by distillation of the organic solvent layer obtained in the separating step to purify the 2-hydroxy ester compound.

[0018] [Chemical 3]

R ¹ — CH (OH)-COOR ² (1)

[0019] In the formula, R ¹ is a hydrogen atom, a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 12 carbon atoms and including an oxygen atom, a sulfur atom, or a nitrogen atom, or 3 to 3 carbon atoms. 6 or a substituted or unsubstituted alicyclic hydrocarbon group which may contain an oxygen atom, a sulfur atom or a nitrogen atom, or has 3 to 14 carbon atoms and contains an oxygen atom, a sulfur atom or a nitrogen atom R ² is an alkyl group which has 1 to 12 carbon atoms and may contain an oxygen atom, a sulfur atom or a nitrogen atom.

 [0020] When the 2-hydroxyester compound in the mixed solution is distilled as it is, the 2-hydroxyester compound is decomposed by the ammonium salt contained in the mixed solution in a slurry state. Therefore, alcohols are removed from the liquid mixture by distillation in advance, ammonia salts, etc. are removed by adding two layers by adding water, and then an organic solvent containing only the 2-hydroxyester compound is recovered. To do. When the organic solvent is distilled, the decomposition of the 2-hydroxyester compound can be suppressed and a 2-hydroxyester compound can be produced. Hereinafter, the present invention will be described in detail.

 [0021] (1) Mixed liquid

 The object of the present invention is a 2-hydroxyester compound represented by the general formula (1).

 [0022] The 2-hydroxyester compound is produced by using an alcohol on a cyanohydrin shown below.

 [0023] [Chemical 4]

R ¹ -CH (OH) (CN) (2)

[0024] In the formula, R ¹ is a hydrogen atom, a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 12 carbon atoms, which may contain an oxygen atom, a sulfur atom, or a nitrogen atom, or 3 to 3 carbon atoms. 6 Substituted or unsubstituted alicyclic hydrocarbon group which may contain oxygen atom, sulfur atom or nitrogen atom, or has 3 to 14 carbon atoms and may contain oxygen atom, sulfur atom or nitrogen atom, substituted Alternatively, it represents an unsubstituted aryl group or aralkyl group.

[0025] The corresponding alcohol is represented by R¾H, and R ² is the same as R ² in the above formula (1).

 [0026] The mixed solution used in the present invention is prepared by any reaction system as long as it contains the above-mentioned 2 hydroxyester compound, alcohol, organic solvent, and ammonium salt. May be. Also, the ammonium salt is not limited to the case where it is a by-product of the production process of the 2-hydroxyester compound. For example, when an ammonium salt is by-produced in the process of producing cyanohydrin, and cyanohydrin containing such an ammonium salt is used as a raw material, such a reaction solution used in the present invention has such a reaction. Ammonium salt of origin may be included. Therefore, ammonium salts such as ammonium sulfate, ammonium nitrate, ammonium chloride, and ammonium phosphate can be targeted.

[0027] The organic solvent contained in the mixed solution is an inert solvent that does not cause a side reaction when the alcohols are distilled off, and a solvent having a solubility in water of 8% by mass or less is used. For example, aromatic hydrocarbons having 6 to 12 carbon atoms such as benzene, toluene, xylene and black benzene, aliphatic hydrocarbons having 6 to 18 carbon atoms such as hexane and heptane, ethyl acetate, butyl acetate, etc. It is preferable to use at least one selected from the group consisting of the following esters: ethers such as jetyl ether, methyl t-butyl ether, and chlorinated hydrocarbons such as methylene chloride and chloroform. Since both are reaction-inert solvents, the degradation of cyanohydrin, which is an unstable raw material, can be suppressed. Moreover, since the solubility with respect to water is low, two-layer separation with an aqueous layer is easy. In addition, since the target 2-hydroxyester compound is excellent in solubility, it can be easily separated from the ammonium salt. More preferred are aromatic hydrocarbons having 6 to 12 carbon atoms, saturated aliphatic hydrocarbons having 6 to 18 carbon atoms, and chlorinated hydrocarbons. In particular, it is preferable to use toluene since the solubility of the 2-hydroxyester compound is high and the solubility in water is low, the recovery is easy, and the inertness is inactive. [0028] On the other hand, the composition of the mixed solution used in the present invention is different in the reaction system as described above and is intended to produce 2-hydroxy ester compound, and therefore, generally, an organic solvent and 2- The weight ratio with respect to the hydroxy ester compound (organic solvent: 2-hydroxy ester compound) is preferably 1:10 to L0: 1, more preferably 1: 3 to 3: 1. The ratio of 2-hydroxyester compounds contained in the aqueous layer is sufficiently low in the separation step because the amount of 2-hydroxyester compounds is less than the weight ratio of 1:10. Therefore, recovery of the 2-hydroxyester compound is facilitated. Further, when the 2-hydroxyester compound is more than the weight ratio of 10: 1, the amount of the organic solvent is relatively small, so that productivity is improved and the recovery cost of the organic solvent can be kept low. . The weight ratio of the slightly water-soluble organic solvent to the ammonium salt (organic solvent: ammonium salt) is preferably 1:10 to: L0: 1, more preferably 1: 5 to 5: 1. Particularly preferred is 1: 3 to 3: 1. When there are more poorly water-soluble organic solvents than the weight ratio of 1:10, recovery of 2-hydroxyester compounds is facilitated, as is the weight ratio between organic solvents and 2-hydroxyester compounds. Further, if the organic solvent is less than the weight ratio of 10: 1, productivity is improved, and the recovery cost of the poorly water-soluble organic solvent can be kept low. Furthermore, the weight ratio of alcohols to organic solvent (alcohols: organic solvent) is preferably 10: 1 to 1:10, more preferably 5: 1 to 1: 5, particularly preferably 3: 1 to 1: 3. Alcohol strength When the ratio is less than 10: 1 with respect to the organic solvent, the operability in the step of distilling off alcohols is improved, and the recovery cost of alcohols is further reduced. Further, it is preferable that the amount of alcohol is more than 1:10 with respect to the organic solvent because the yield of 2-hydroxyester is increased and the recovery cost of the organic solvent can be suppressed.

 [0029] On the other hand, even when an organic solvent is not used during the synthesis reaction of the 2-hydroxyester compound, an organic solvent can be added during the reaction or after the reaction to obtain the above mixed solution. Examples of the mixed solution that can be used in the present invention include the reaction solution obtained in the above-mentioned US Pat. No. 20,41820, JP-A-4-230241, JP-A-6-247896, and the like, and further an organic solvent, etc. There is what added.

[0030] A method for producing a 2-hydroxyester compound containing an ammonium salt used in the present invention is not particularly limited, but an acid is mixed with a mixture of cyanohydrin, a corresponding alcohol, a solvent and water. The reaction solution thus obtained was mixed with the 2-hydroxyester compound, alcohol It can be used as a mixed solution containing alcohols, organic solvent, and ammonium salt. The reaction solution can be prepared simply by charging cyanohydrin, alcohol, solvent, and water, then mixing the acid and heating, eliminating the need for operations such as solid-liquid separation, distillation, and concentration for intermediate separation. Thus, since the reaction can be carried out under normal pressure, a pressure reaction device such as autoclave is not necessary, and it can be easily prepared. In addition, the yield of ester candy is high.

 [0031] Specifically, a 2-hydroxyester compound is produced in one step without adding an acid to the mixture obtained by adding the above alcohol, solvent and water to the above cyanohydrin. To do. The acid to be used is not particularly limited, and examples thereof include inorganic acids such as hydrogen chloride gas, hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid, and organic acids such as p-toluenesulfonic acid, methanesulfonic acid, formic acid and acetic acid.

 [0032] [Chemical 5]

OH _{HC 1} OH 0

R ¹ -CH-CN + H ₂ 0 + R ² OH ^ R ^ CH— C-0R ² + NH ₄ C1

[0033] As the solvent to be used, a solvent which is inert to the reaction and has a solubility in water of 8% by mass or less can be used. For example, benzene, toluene, xylene, black benzene and the like have 6 carbon atoms. ~ 12 aromatic hydrocarbons, hexane, heptane and other aliphatic hydrocarbons having 6-18 carbon atoms, chlorinated hydrocarbons such as methylene chloride and black mouth form, and jetyl ether, methyl-t-butyl ether, etc. Any one of these ethers is preferably at least one kind. More preferred are aromatic hydrocarbons having 6 to 12 carbon atoms, saturated aliphatic hydrocarbons having 6 to 18 carbon atoms, and chlorinated hydrocarbons. In particular, it is preferable to use toluene since the solubility of the 2-hydroxyester compound is high and the solubility in water is low, and furthermore, the recovery is easy and it is inert. Esters such as ethyl acetate and butyl acetate are active under the reaction conditions, and side reactions such as hydrolysis and transesterification may occur.

[0034] The concentration of cyanohydrin contained in the solvent varies depending on the amounts of water and alcohol to be added, but is generally preferably 5.0 to 60.0% by mass, more preferably 20.0% in the mixed solution. -40. 0 mass _^0/0, particularly preferably at 26. 0-37. 0 wt _^0/0. 60. When 0 mass _^0/0 Ru exceeded, solid content formed during Iminoeterui spoon is too large, the stirring of the slurry It becomes difficult. On the other hand, if it is less than 5.0% by mass, the solvent recovery step becomes complicated and disadvantageous.

[0035] The alcohol to be added is theoretically 1 to 5 mol, more preferably 1.5 to 4 mol, especially considering the force reaction yield of 1 mol per 1 mol of cyanohydrin. Preferably it is 2-4 mol. If the amount is less than 1 mol, the yield decreases. On the other hand, if the amount exceeds 5 mol, the operation for removing the excessively added alcohol becomes complicated and disadvantageous.

[0036] In consideration of the reaction yield, which is theoretically 1 mol of water per 1 mol of cyanohydrin, water is preferably from 0.7 to 2 monolayer, more preferably from 0.8 to 8 1.5 monole, particularly preferably ί or 0.8 to 1.2 mol. If the amount is less than 0.7 mol, the yield decreases. On the other hand, if it exceeds 2 mol, the yield decreases, which is disadvantageous. In particular, when water is added in the above range before the acid is added, the fluidity of the reaction liquid slurry during imino etherification is improved, stirring is facilitated, and the reactivity and operability are further improved. The concentration of the cyanohydrin in the mixed solution can be adjusted by appropriately selecting the amount of solvent in consideration of the water and alcohol to be added.

[0037] The acid to be used is preferably 1 to 1.5 mol, more preferably 1.05 to L 25 mol per 1 mol of cyanohydrin. If the amount is less than 1 mol, the reaction promoting effect decreases, whereas if it exceeds 1.5 mol, the yield decreases, which is disadvantageous. However, the acid contained in the molecule (for example, nitrogen atom of amine in the molecule) and an acid capable of forming a salt are not included in the above-mentioned introduction amount of the acid.

 [0038] The liquid temperature at the time of acid introduction is preferably 0 to 80 ° C, more preferably 25 to 60 ° C, and particularly preferably 35 to 45 ° C. Below 0 ° C, the reaction time becomes longer, which is disadvantageous. On the other hand, if it exceeds 80 ° C, the raw material alcohol and acid may react to form a by-product, which is disadvantageous. When using an aqueous hydrochloric acid solution as the acid, it is preferable to adjust the temperature to the above temperature range. The introduction time of the acid can be arbitrarily selected depending on the productivity and the heat removal efficiency of the reaction heat, but is 1 to 20 hours, particularly 1 to 15 hours.

[0039] After the addition of the acid, the reaction solution is allowed to react for 0 to 20 hours in the range of 0 ° C to reflux temperature under normal pressure. The ability to obtain the target 2-hydroxyester compound is obtained at different temperatures. It is more preferable to perform the first aging and the second aging. For example, after the addition of the acid, the reaction solution is aged at a temperature ranging from 0 ° C to the reflux temperature under normal pressure, preferably 35-45 ° C, more than 0 hours and 4 hours or less, more preferably 1-2 hours. . This is referred to as first aging. Next, return at 20 ° C to normal pressure Aging is carried out in the range of the flow temperature, preferably at the reflux temperature under normal pressure, for more than 0 hours and not more than 15 hours, more preferably for 4 to 12 hours. This is called second aging. By changing the temperature in this way, in the first ripening, side reactions can be suppressed, and most of the charged acid can be reacted to reduce acid and alcohol consumption and improve yield. By increasing the reaction temperature in the second aging, the reaction time can be shortened, the yield can be improved, and the reaction time can be shortened. In the present invention, since the slurry is formed according to the formation of the target product, it is preferable to stir the reaction liquid during the first aging and the second aging. In the present invention, since the reaction solution contains a solvent, water and alcohol, and the amount of the solution is large, stirring is also easy.

 [0040] The weight ratio of the components in the reaction solution obtained by the above method is preferably 1: 6 to 3: 1, more preferably 2: 3 to 5: the weight ratio of the organic solvent to the 2-hydroxyester compound. 3. Particularly preferred is 5: 6 to 5: 4. The weight ratio of the organic solvent to the ammonium salt is preferably 1: 3 to 6: 1, more preferably 4: 3 to: LO: 3, particularly preferably 5: 6 to 5: 4. The ratio of alcohols to organic solvent is preferably 5: 1 to 1:10, more preferably 1: 1 to 1:10.

 [0041] (2) Alcohol distillation step

 In the present invention, alcohols are distilled off from the mixed solution containing the 2-hydroxyester compound and the ammonium salt. By removing the alcohols contained in the organic solvent in advance, the 2-hydroxyester compound can be produced with high purity from the organic solvent in the purification step of the 2-hydroxyester compound.

 [0042] In the distillation of the alcohol, the distillation should be carried out under conditions that allow the alcohols to be distilled. In general, the distillation temperature is preferably 60 to 130 ° C, more preferably. 60 to 100 ° C, particularly preferably 70 to 90 ° C. In particular, when the alcohol is methanol or ethanol contained in the mixed solution, it can be easily distilled from the mixed solution within the above temperature range. If the temperature exceeds 130 ° C, the 2-hydroxyester compound contained in the mixed solution may be decomposed by the action of water or ammonia salt, which is disadvantageous. Excessive decompression conditions are required. The pressure is within a known range as long as the alcohol can be distilled!

[0043] The alcohol distilled off in the step of distilling off the alcohol is 2-hydroxyl It can also be used as a raw material for the production of steril compounds.

 [0044] (3) Two-layer separation process

 Water is added to the residual liquid after the alcohols are distilled off to separate the organic solvent layer and the aqueous layer. Simply separating the ammonium salt contained in the residual liquid by solid-liquid separation does not prevent the ammonium salt from dissolving in the organic solvent, but after adding water, the organic solvent layer and the aqueous layer are separated. By separating into two layers, the concentration of ammonia salt contained in the organic solvent can be efficiently reduced. In the organic solvent layer, the 2-hydroxyester compound is mainly dissolved, and in the aqueous layer, a part of the 2-hydroxyester compound in which the ammonium salt is mainly dissolved is also included in the aqueous layer.

 [0045] Since the ammonium salt contained in the residual liquid is insoluble in the organic solvent, the ammonium salt is dissolved in water by adding force water that exists in the form of a slurry in the residual liquid. Therefore, the organic solvent power can also remove ammonia salts. Therefore, the amount of water to be added needs to be an amount sufficient to dissolve the contained ammonium salt and can be separated into two layers with an organic solvent. Preferably, it is 2.6 to 5.0 mass times, more preferably 2.6 to 3.0 mass times, and particularly preferably 2.6 to 2.8 mass times that of salt ammonium. Since 2-hydroxy ester compound is soluble in water, the recovery rate of 2-hydroxy ester compound may decrease if the amount of water added exceeds 5.0 mass times. On the other hand, when the amount is less than 2.6 mass times, the ammonium salt is not completely dissolved, resulting in an obstacle to the liquid separation operation.

 [0046] Since the residual liquid after distillation of alcohol shows the same high temperature as the distillation temperature immediately after distillation, water is preferably added when the temperature is 70 ° C or lower, more preferably 40 ° C or lower. . If water is added above 70 ° C, the 2-hydroxyester compound may be hydrolyzed by water due to the effect of temperature. The temperature of water to be added is not limited, but is preferably 0 to 40 ° C, more preferably 20 to 40 ° C. If the temperature of the added water exceeds 40 ° C, depending on the pH of the reaction solution, the 2-hydroxyester compound may be hydrolyzed by water. On the other hand, below 0 ° C, the solubility of ammonia salt may decrease.

[0047] Further, the water in the kettle may be neutralized after the addition of water. The pH of the liquid in the kettle is preferably 3 to 9, more preferably 5 to 8, particularly preferably 6.5 to 7.5. If the pH exceeds 9, Hydrolysis can occur even at warm temperatures. When the pH is less than 3, decomposition of the 2-hydroxyester compound may be accelerated when heating in the step (4) of recovering 2-hydroxyester from the organic solvent layer. The pH in the present invention refers to the pH at a temperature of 25 ° C.

 [0048] (4) Step of purifying 2-hydroxyester compound from organic solvent layer

 In the present invention, the organic solvent layer after the two-layer separation obtained in the step (3) is distilled to produce a 2-hydroxyester compound. Since the solvent layer is one in which the content of water and ammonia salt is extremely reduced by the step (3) above, the organic solvent layer is heated to the distillation temperature of the 2-hydroxyester compound. However, they are not hydrolyzed by these, and the 2-hydroxyester compound can be produced with high yield.

[0049] (5) 2-hydroxyester compound recovery process with water layer strength

 The water layer separated in the above two-layer separation process also contains a force-soluble 2-hydroxyester compound containing an ammonium salt. In the present invention, it is confirmed that the pH of the aqueous layer is 3 to 8, and after adjusting to Z or PH 3 to 8, the aqueous layer is distilled to recover water and 2 hydroxyester compound. To do.

[0050] As described above, since the water layer also contains a water-soluble 2-hydroxyester compound, discarding the water layer as it is decreases the yield. On the other hand, when this is recovered by distillation, the 2-hydroxyester compound is easily hydrolyzed by heating, and the recovery efficiency decreases. In particular, in the production process of 2-hydroxyester compound, an acid is often added to the reaction system for hydrolysis, and the resulting aqueous layer may be strongly acidic. It is hydrolyzed by heating. However, the present inventors have found that when the pH of the aqueous layer is adjusted to 3 to 8, decomposition of the 2-hydroxyester compound can be avoided even under heating conditions. _P H of the aqueous layer, more preferably 4-7, particularly preferably 5-6. The pH of the aqueous layer is not limited in time if it is adjusted before distillation. For example, in the aforementioned two-layer separation process, sodium hydroxide or the like is added to the mixed solution before the alcohol is distilled off. Then, the pH may be adjusted to 3-8, or when adding water to the residual liquid after the alcohol has been distilled off, or before adding water to the residual liquid. As a result, the two-layer separated aqueous layer can be adjusted to pH 3-8. To adjust the pH, Sodium, potassium hydroxide or alkali metal or alkaline earth metal carbonates, organic acid salts such as sodium acetate, and phosphates can be used. If the pH of the aqueous layer shows pH 3 to 8 without any adjustment, just distill it as is!

[0051] In this step, water and the 2-hydroxyester compound are also recovered by distillation. The 2-hydroxyester compound may be recovered alone, but when the 2-hydroxyester compound forms an azeotropic composition with water, the two are recovered by azeotropic distillation. In this case, it is preferable that the distillation conditions are such that hydrolysis of the 2-hydroxyester compound can be avoided and that strong water and the 2-hydroxyester compound can be azeotroped, for example, at a temperature of 10 ° C. Distill at ~ 100 ° C, more preferably 20 ° C-90 ° C, particularly preferably 30 ° C-80 ° C. The pressure is normal pressure or lower, preferably 1.2 kPa to 101.3 kPa, more preferably 2.3 kPa to 70.1 kPa, particularly preferably 4.2 kPa to 47.4 kPa. In particular, the 2-hydroxy ester compound shown by the general formula (1) Contact !, Te, R ¹ and R ² are methyl or Echiru, these 2-hydroxy ester Louis匕合was and high water-solubility This is preferred because it easily forms an azeotropic composition with water.

 [0052] If the distillate is reused in the following two-layer separation step in the following production process, water can be reused as added water, and the 2-hydroxyester compound is obtained. The yield can be improved because it is not discarded but reused in the manufacturing process.

 According to the present invention, the 2-hydroxyester compound represented by the general formula (1) is mixed with a mixture containing a 2-hydroxyester compound, an alcohol, an organic solvent, and an ammonium salt. Ammonium salt can also be separated efficiently and easily in terms of liquid mixture power. After obtaining an organic solvent that mainly dissolves the 2-hydroxyester compound, this is distilled to easily produce the target product. Can do.

 [0054] Further, when an aqueous layer containing a 2-hydroxyester compound and water is distilled, both of them are azeotroped. Therefore, when the 2-hydroxyester compound is reused in the next production process, the yield is reduced. Can be improved.

[0055] The production method of the present invention can be applied regardless of the reaction step of the 2-hydroxyester compound, and it is particularly easy to prepare a reaction solution containing an organic solvent and add water thereto. In addition, it can be used to dissolve ammonium salt in the water layer, so its application range is wide. Example

 Next, the present invention will be specifically described with reference to examples, but these examples do not limit the present invention at all.

[Example 1]

Stirrer, thermocouple thermometer, and a container of 1L of the container receiving steam condenser heat exchanger and distillate Connect the toluene 29.5 wt _^0/0, methyl 2-hydroxybutanoate 30.7 mass

% Methanol 20.2 wt _^0/0, Shioi匕ammoxidation - were charged ester containing © arm 16.5 mass _^0/0, etc. Kahan reaction solution 600 g. The liquid in the container was heated, and methanol was distilled off by simple distillation until the temperature in the container reached 90 ° C.

[0058] Thereafter, the liquid in the container was cooled to 40 ° C, and 314 g of water and 4.2 g of sodium hydroxide were added. As a result, the pH of the liquid water layer in the container was adjusted to 7.1, and the salt ammonia was dissolved in water.

[0059] Subsequently to carry out a liquid separation operation, toluene 39.7 wt _^0/0, methyl 2-hydroxybutanoate 38. and the organic layer 352g containing 6 wt%, methyl 2-hydroxybutanoate 9.5 wt%, etc. A water layer containing 49 lg was obtained.

 [0060] The water obtained in the above two-layer separation process in a 1 L vessel having a stirrer, thermocouple thermometer, heat exchanger for vapor condensation, a vessel for receiving a distillate, and piping connected to a vacuum pump All layers were charged. It was pH 6.5 when pH of the prepared water layer was confirmed. The pH was then adjusted to 5.1 with 36% aqueous hydrochloric acid. After pH adjustment, the pressure in the distillation system was reduced to 26.7 kPa and the liquid in the vessel was heated to recover water and methyl 2-hydroxybutanoate. In this step, 266 g of a distillate containing 16.5% by mass of methyl 2-hydroxybutanoate was obtained. The recovery rate of methyl 2-hydroxybutanoate by the above process was 94.2% and the yield of raw material was 20.9%.

[0061] A 500 mL container having a stirrer, a thermocouple thermometer, a heat exchanger for vapor condensing, a container for receiving a distillate, and a pipe connected to a vacuum pump was obtained in the above two-layer separation process. The entire layer was charged and the pressure in the distillation system was reduced to 26.7 kPa. The liquid in the container was heated and toluene was recovered by distillation. Then, it was once cooled and the pressure in the distillation system was reduced to 2.7 kPa. The solution in the container was heated to the heat and distilled to obtain 107.6 g of methyl 2-hydroxybutanoate. The yield of methyl 2-hydroxybutanoate by the above process was 51.3%. Separate the separated aqueous and organic layers The total yield of methyl 2-hydroxybutanoate obtained was 72.2%.

 [Example 2]

Stirrer, thermocouple thermometer, and a container 10L having connection with pipes in a container for receiving vapor condenser heat exchanger and distillate, toluene 29.5 wt _^0/0, 2-hydroxy butane Sanme Chill 30.7 mass _^0/0, methanol 20.2 wt _^0/0, chloride ammonium - a © arm 16.5 mass _^0/0, etc. were charged including Esuterui spoon reaction 6304G. The liquid in the container was heated, and methanol was distilled off by simple distillation until the temperature in the container reached 90 ° C.

 [0063] Thereafter, the liquid in the container was cooled to 40 ° C, 3357 g of water was added, and the salt ammonia contained therein was dissolved in water.

[0064] Subsequently to carry out a liquid separation operation, toluene 57.3 wt _^0/0, 2-hydroxyethyl and the organic layer 3214g containing butanoate 32.5 wt%, methyl 2-hydroxybutanoate 9.6 wt%, etc. An aqueous layer containing 5743 g was obtained.

 [0065] The water obtained in the above-mentioned two-layer separation process in a 10-L container having a stirrer, thermocouple thermometer, heat exchanger for vapor condensation, a container for receiving a distillate, and piping connected to a vacuum pump All layers were charged. It was pH 6.5 when pH of the prepared water layer was confirmed. The pH was then adjusted to 5.4 with 36% aqueous hydrochloric acid. After pH adjustment, the pressure in the distillation system was reduced to 26.7 kPa, and the liquid in the vessel was heated to recover water and methyl 2-hydroxybutanoate. In this step, 3722 g of a distillate containing 13.6% by mass of methyl 2-hydroxybutanoate was obtained. The recovery rate of methyl 2-hydroxybutanoate by the above process was 91.8%, and the yield of raw material was 27.4%.

[0066] The organic material obtained in the above two-layer separation process in a 6L container having a stirrer, a thermocouple thermometer, a heat exchanger for vapor condensation, a container for receiving a distillate, and piping connected to a vacuum pump All layers were charged. Thereto, 31 g of a 20% sodium hydroxide aqueous solution was added, and the pH of the liquid water layer in the container was adjusted to 6.8. Subsequently, a liquid separation operation was performed, and the aqueous layer was taken out of the system. The pressure in the distillation system was reduced to 26.7 kPa. The liquid in the container was heated and toluene was recovered by distillation. Then it was once cooled and the pressure in the distillation system was reduced to 2.7 kPa. The liquid in the vessel was heated and distilled to obtain methyl 2-hydroxybutanoate. The yield of methyl 2-hydroxybutanoate by the above process was 46.0%. The separated aqueous and organic layers were distilled to separate 2-hydroxybutanoic acid methyl compounds. The total yield was 73.4%.

[0067] (Example 3)

Stirrer, thermocouple thermometer, and a container of 1L having connected the pipe to a container for receiving vapor condenser heat exchanger and distillate, toluene 29.2 wt _^0/0, 2-hydroxy butanoic acid methylation 30.0 mass _^0/0, methanol 19.8 wt _^0/0, chloride ammonium - was placed Esuterui spoon reaction solution 514. 3 g containing © beam 16.1 mass _^0/0 or the like. The liquid in the container was heated and methanol was distilled off by simple distillation until the temperature in the container reached 90 ° C.

[0068] Thereafter, the liquid in the container was cooled to 40 ° C, and 237 g of water and 3.6 g of sodium hydroxide were added. As a result, the pH of the liquid aqueous layer in the container was adjusted to 5.3, and the salt ammonia was dissolved in water.

[0069] Subsequently to carry out a liquid separation operation, toluene 38.9 wt _^0/0, and the organic layer 180. Og containing 2-hydroxy-butanoate 55.4 mass _^0/0, methyl 2-hydroxybutanoate 13. 7 mass _^0/0 was obtained and the aqueous layer 388. 2 g containing (53. lg).

 [0070] A 300 mL container having a stirrer, a thermocouple thermometer, a heat exchanger for vapor condensing, a container for receiving a distillate, and a pipe connected to a vacuum pump was obtained in the above two-layer separation process. The entire layer was charged and the pressure in the distillation system was reduced to 26.7 kPa. The liquid in the container was heated and toluene was recovered by distillation. Then, it was once cooled and the pressure in the distillation system was reduced to 2.7 kPa. The liquid in the container was heated to 83.8 g of methyl 2-hydroxybutanoate by distillation. The yield of methyl 2-hydroxybutanoate by the above process was 47.8%.

[0071] The water obtained in the above two-layer separation step in a 500 mL container having a stirrer, a thermocouple thermometer, a heat exchanger for vapor condensation, a container for receiving a distillate, and a pipe connected to a vacuum pump All layers were charged. The pH of the prepared aqueous layer was confirmed to be pH 5.2. The distillation process proceeded without adjusting the pH. The pressure in the distillation system was reduced to 26.7 kPa. The liquid in the container was heated and water and methyl 2-hydroxybutanoate were recovered by distillation. In this process methyl 2-hydroxybutanoate 24.2 mass _^0/0 was obtained distillate 202. Og containing (48. 9 g). The recovery rate of methyl 2-hydroxybutanoate by the above process was 92.1%, and the yield of raw material was 27.9%. The remaining 7.9% is considered pyrolysis. The total yield of methyl 2-hydroxybutanoate obtained by distilling the separated aqueous layer and organic layer was 75.7%. [Example 4]

Stirrer, thermocouple thermometer, and toluene 29.3 wt _^0/0 in a container 1L having connected the pipe to a container for receiving vapor condenser heat exchanger and distillate, methyl 2-hydroxy butanoic acid 29. 5 mass _^0/0, methanol 19.0 wt _^0/0, chloride ammonium - was charged © beam 16. S. Terui spoon reaction solution 515. 8 g containing 2 mass _^0/0 or the like. The liquid in the container was heated, and methanol was distilled off by simple distillation until the temperature in the container reached 90 ° C.

 [0073] Thereafter, the liquid in the container was cooled to 40 ° C.

[0074] Distillation liquid containing methyl 2-hydroxybutanoate and water obtained by distillation of the aqueous layer after the two-layer separation in Example 3 was obtained. 10.5 g, water 130 g, toluene 74.5 g and Sodium (2.5 g) was charged into the container to dissolve the salt-molybdenum in water and the pH of the liquid water layer in the container was adjusted to 5.3. Subsequently, liquid separation do, toluene 48.1 wt _^0/0, the organic layer 306. 9 g, and 2-hydroxy butanoate 15 containing 2-hydroxy-butanoate 44.6 mass ⁰ / _0.2 Weight _^0/0 to obtain an aqueous layer 414. 4g comprising (63. lg). The recovery rate of methyl 2-hydroxybutanoate by the above process was 94.6%. The total yield of methyl 2-hydroxybutanoate obtained by the same method as in Example 3 was 76.1%.

 [0075] (Example 5)

Stirrer, thermocouple thermometer, and a container of 1L having connected the pipe to a container for receiving vapor condenser heat exchanger and distillate, toluene 29.5 wt _^0/0, 2-hydroxy butanoic acid methylation 26.1 mass _^0/0, methanol 20.2 wt _^0/0, chloride ammonium - was charged esterification reaction 727g containing © arm 16.5 mass _^0/0 or the like. The liquid in the container was heated, and methanol was distilled off by simple distillation until the temperature in the container reached 90 ° C.

 [0076] Thereafter, the liquid in the container was cooled to 40 ° C, 336 g of water was added, and the salt ammonia contained therein was dissolved in water.

[0077] Subsequently to carry out a liquid separation operation, toluene 57.3 wt _^0/0, 2-hydroxyethyl and the organic layer 321g comprising butanoate 32.5 wt%, methyl 2-hydroxybutanoate 9.6 wt%, etc. A water layer containing 574 g was obtained.

[0078] The water obtained in the above-mentioned two-layer separation process in a 1 L container having a stirrer, a thermocouple thermometer, a heat exchanger for steam condensation, a container for receiving a distillate, and a pipe connected to a vacuum pump All layers The amount was charged. It was pH 6.5 when pH of the prepared water layer was confirmed. The pressure in the distillation system was reduced to 26.7 kPa, and the liquid in the vessel was heated to recover water and methyl 2-hydroxybutanoate. In this step, 372 g of a distillate containing 13.6% by mass of methyl 2-hydroxybutanoate was obtained. The recovery rate of methyl 2-hydroxybutanoate by the above process was 55.0%, and the yield of raw material was 12.3%.

 [0079] A 600 mL container having a stirrer, a thermocouple thermometer, a heat exchanger for steam condensation, a container for receiving a distillate, and a pipe connected to a vacuum pump was obtained in the above two-layer separation process. All the layers were charged. The pressure in the distillation system was reduced to 26.7 kPa, and the liquid in the vessel was heated to collect toluene by distillation. Then, it was once cooled and the pressure in the distillation system was reduced to 2.7 kPa. The solution in the container was heated to distillation to obtain methyl 2-hydroxybutanoate by distillation. The yield of methyl 2-hydroxybutanoate by the above process was 25.7%. The total yield of methyl 2-hydroxybutanoate obtained by distilling the separated aqueous layer and organic layer was 38.0%.

 Industrial applicability

[0080] The present invention relates to a method for producing a 2-hydroxyester from a reaction solution containing an ammonium salt, and is a simple and excellent method for producing a 2-hydroxyester, which is useful.

Claims

Claims [1] A method for producing a 2-hydroxyester compound represented by the general formula (1), wherein the 2-hydroxyester compound, alcohol, organic solvent, and ammonia A mixed liquid power containing salt, a step of distilling off alcohols, a step of adding water to the residual liquid obtained in the step of distilling off alcohols and separating the organic solvent layer and the aqueous layer, and the step of separating The method for producing a 2-hydroxyester compound comprising the step of purifying the 2-hydroxyester compound by distilling the organic solvent layer obtained in step 1:  [Chemical 1] R ¹ —CH (OH) —COOR ² (1) In the formula, R ¹ is a hydrogen atom, a substituted or unsubstituted fat having 1 to 12 carbon atoms and may contain an oxygen atom, a sulfur atom, or a nitrogen atom. An aromatic hydrocarbon group, a substituted or unsubstituted alicyclic hydrocarbon group having 3 to 6 carbon atoms and optionally containing an oxygen atom, sulfur atom, or nitrogen atom, or an oxygen atom having 3 to 14 carbon atoms , A sulfur atom, or a substituted or unsubstituted aryl or aralkyl group which may contain a nitrogen atom, and R ² is an alkyl group which has 1 to 12 carbon atoms and may contain an oxygen atom, a sulfur atom or a nitrogen atom. is there.  [2] The method according to claim 1, comprising a step of distilling the aqueous layer obtained in the step of separating to obtain a distillate containing a 2-hydroxyester compound and water. A method for producing a 2-hydroxy ester compound.  [3] The method for producing a 2-hydroxyester compound according to claim 1 or 2, wherein the pH of the aqueous layer obtained in the separating step is adjusted to 3 to 8.  4. The method for producing a 2-hydroxyester compound according to claim 2 or 3, wherein the distillate is used instead of water added in the step of separating. [5] The organic solvent is a group hydrocarbon composed of aromatic hydrocarbons having 6 to 12 carbon atoms, aliphatic hydrocarbons having 6 to 18 carbon atoms, esters, ethers, and chlorinated hydrocarbons. The 2-hydroxy ester according to any one of claims 1 to 4, which is one or more selected from the group consisting of Compound production method.  The method for producing a 2-hydroxyester compound according to any one of 1 to 5, wherein the 2-hydroxyester compound strength is 2-hydroxybutanoic acid methyl.