Method for producing 3-hydroxy-γ-butyrolactone

Abstract

To provide a 3-hydroxy-γ-butyrolactone purifying method that can efficiently improve the purity.SOLUTION: A 3-hydroxy-γ-butyrolactone purifying method includes the step of adding, to a crude composition containing 3-hydroxy-γ-butyrolactone, at least one solvent selected from the group consisting of a C2-6 alcohol, a C4-8 ketone, a C2-6 nitrile and a C4-8 ether for the precipitation of salts.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for purifying 3-hydroxy-γ-butyrolactone, and a method for producing 3-hydroxy-γ-butyrolactone using the purification method. [Background technology]

[0002] 3-Hydroxy-γ-butyrolactone is useful, for example, as a raw material for monomers of resist polymers used in the semiconductor manufacturing field. In addition, optically active 3-hydroxy-γ-butyrolactone is useful as an intermediate for pharmaceuticals, agricultural chemicals, etc.

[0003] Patent Document 1 describes a method for producing 3-hydroxy-γ-butyrolactone by subjecting ethyl 4-chloro-3-hydroxybutyrate to a cyclization reaction. The examples in Patent Document 1 describe a purification example in which an aqueous hydrochloric acid solution or an aqueous sulfuric acid solution is added to ethyl 4-chloro-3-hydroxybutyrate, the mixture is heated to reflux to produce 3-hydroxy-γ-butyrolactone, the mixture is neutralized with caustic soda solution, water is distilled off under reduced pressure, ethyl acetate is added to the mixture of remaining crystals and oil and the mixture is stirred, the crystals are separated by filtration, and the filtrate is concentrated under reduced pressure. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 3855033 Summary of the Invention [Problem to be solved by the invention]

[0005] In purifying 3-hydroxy-γ-butyrolactone, it is desirable to efficiently increase the purity. The present invention provides a method for purifying 3-hydroxy-γ-butyrolactone, which can efficiently increase the purity, and a method for producing 3-hydroxy-γ-butyrolactone using the same. [Means for solving the problem]

[0006] The present invention has the following aspects. [1] A method for purifying 3-hydroxy-γ-butyrolactone, comprising the step of adding one or more solvents selected from the group consisting of alcohols having 2 to 6 carbon atoms, ketones having 4 to 8 carbon atoms, nitriles having 2 to 6 carbon atoms, and ethers having 4 to 8 carbon atoms to a crude composition containing 3-hydroxy-γ-butyrolactone to precipitate a salt. [2] The purification method according to [1], wherein the salt comprises sodium chloride. [3] A reaction step of subjecting a 4-halogeno-3-hydroxybutyric acid ester represented by the following formula (1) to a cyclization reaction in a medium containing water to obtain a reaction liquid containing 3-hydroxy-γ-butyrolactone represented by the following formula (2); a neutralization step of neutralizing the reaction solution obtained in the reaction step to obtain a crude composition containing the 3-hydroxy-γ-butyrolactone and a salt; A method for producing 3-hydroxy-γ-butyrolactone, comprising a step of adding one or more solvents selected from the group consisting of alcohols having 2 to 6 carbon atoms, ketones having 4 to 8 carbon atoms, nitriles having 2 to 6 carbon atoms, and ethers having 4 to 8 carbon atoms to the crude composition to precipitate the salt. In formula (1), X represents a halogen atom, and R represents an ester-type protecting group.

[0007] [ka]

[0008] [4] The method according to [3], further comprising a pH adjustment step of adjusting the pH of the reaction solution after the initiation and before the completion of the cyclization reaction. [5] The method according to [4], further comprising an alcohol removing step of removing an alcohol by-produced in the cyclization reaction after the initiation of the cyclization reaction and before the pH adjustment step. [6] The method according to any one of [3] to [5], wherein X in the formula (1) is a chlorine atom, and an alkaline compound containing sodium hydroxide is added to the reaction liquid in the neutralization step. Effect of the Invention

[0009] According to the present invention, high-purity 3-hydroxy-γ-butyrolactone can be obtained efficiently. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The purification method of the present embodiment (hereinafter also simply referred to as "the purification method") includes a step of adding a specific solvent to a crude composition containing 3-hydroxy-γ-butyrolactone (hereinafter also referred to as "target compound") represented by the following formula (2) to precipitate a salt (salt precipitation step). Furthermore, a step of removing the precipitate and isolating and purifying the target compound may be included.

[0011] The crude composition to be purified is, for example, a neutralized liquid obtained by subjecting a 4-halogeno-3-hydroxybutyric acid ester represented by the following formula (1) (hereinafter also referred to as a "raw material compound") to a cyclization reaction in a medium containing water (reaction step), and neutralizing the reaction liquid obtained in the reaction step (neutralization step). The neutralized liquid contains the target compound and a salt (neutralized salt).

[0012] [ka]

[0013] In formula (1), X represents a halogen atom. Examples of the halogen atom include a chlorine atom, a bromine atom, and an iodine atom. A chlorine atom is preferred. In formula (1), R represents an ester-type protecting group. In this specification, the term "ester-type protecting group" refers to a group capable of protecting a carboxylic acid as an ester. Examples of ester-type protecting groups include alkyl groups having 1 to 10 carbon atoms, aryl groups having 6 to 20 carbon atoms, aralkyl groups having 7 to 20 carbon atoms, and silyl-based protecting groups. Specific examples include methyl groups, ethyl groups, n-propyl groups, isopropyl groups, n-butyl groups, isobutyl groups, tert-butyl groups, phenyl groups, benzyl groups, α-methylbenzyl groups, phenylpropyl groups, trimethylsilyl groups, tert-butyldimethylsilyl groups, and groups in which these groups are partially substituted with a substituent. Examples of the substituent include halogen atoms, nitro groups, hydroxyl groups, ether groups, and amide groups. R is preferably a hydrocarbon group, more preferably an alkyl group, and is preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, or a tert-butyl group, more preferably an ethyl group. The 4-halogeno-3-hydroxybutyric acid ester used in the reaction step may be either the (R)- or (S)-optical isomer, and these may be used in combination.

[0014] Hereinafter, an embodiment of a method for producing 3-hydroxy-γ-butyrolactone through the reaction step, the neutralization step, and a step using the present purification method will be described. In this embodiment, the cyclization reaction of the 4-halogeno-3-hydroxybutyric acid ester is carried out in a medium containing water. Specifically, a raw material composition is prepared by adding raw material compounds to the medium, and the raw material composition is heated to start the cyclization reaction. After the initiation of the cyclization reaction and before its completion, it is preferable to adjust the pH of the reaction solution (pH adjustment step). When an alcohol is produced as a by-product in the cyclization reaction, it is preferable to remove the by-product alcohol before the pH adjustment step (alcohol removal step). When the alcohol removing step is carried out, the period from the start of the cyclization reaction to before the alcohol removing step is defined as the first reaction step, and the period from after the pH adjustment step to before the end of the cyclization reaction is defined as the second reaction step. When the alcohol removal step is not performed, the first reaction step is from the start of the cyclization reaction to before the pH adjustment step, and the second reaction step is from after the pH adjustment step to before the end of the cyclization reaction.

[0015] The medium may contain a water-soluble organic solvent in addition to water. Examples of water-soluble organic solvents include ketone solvents such as acetone and methyl ethyl ketone, ether solvents such as dioxane and tetrahydrofuran, alcohol solvents such as methanol, ethanol and isopropanol, and nitrile solvents such as acetonitrile. The ratio of water to the medium is preferably 30% by mass or more, more preferably 60% by mass or more, and particularly preferably 100% by mass. The content of the medium in the raw material composition is preferably 1 to 10 times by weight, and more preferably 2 to 6 times by weight, the amount of the 4-halogeno-3-hydroxybutyric acid ester.

[0016] It is preferable to add the acidic compound to the raw material composition before the initiation of the cyclization reaction. For example, it is preferable to prepare a raw material composition by adding the raw material compound to an aqueous solution of an acidic compound in which the acidic compound is dissolved in a medium containing water, and to heat the raw material composition to initiate the cyclization reaction. In this specification, an acidic compound refers to a compound whose 0.5 M aqueous solution has a pH of 6.0 or less at 20° C. Specific examples include hydrochloric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, perchloric acid, phosphoric acid, acetic acid, propionic acid, butyric acid, isobutyric acid, crotonic acid, acrylic acid, methacrylic acid, oxalic acid, succinic acid, phthalic acid, benzoic acid, tartaric acid, lactic acid, glycolic acid, potassium hydrogen oxalate, potassium hydrogen tartrate, potassium hydrogen phthalate, ammonium chloride, trimethylamine hydrochloride, and the like. From the viewpoint of easiness in shortening the reaction time, compounds having a pH of 2.0 or less are preferred, and examples of suitable compounds include hydrochloric acid and sulfuric acid. From the viewpoint of ease of suppressing impurities, compounds having a pH of more than 2.0 and not more than 5.0 are preferred, and examples of suitable compounds include acetic acid and ammonium chloride. The content of the acidic compound in the raw material composition is preferably 0.05 to 2.0 molar equivalents, and more preferably 0.1 to 1.0 molar equivalents, relative to the 4-halogeno-3-hydroxybutyric acid ester. The pH of the aqueous acidic compound solution at 20° C. (hereinafter also referred to as “initial pH”) is preferably 0 to 6.0, more preferably 0 to 5.0.

[0017] (First reaction step) The reaction temperature in the first reaction step is preferably 40 to 150° C., more preferably 70 to 120° C. The cyclization reaction may be carried out while heating up to the boiling point of the medium and refluxing. In the first reaction step, the target compound is produced, and an acid component (HX) is also produced as a by-product, and when R is a hydrocarbon group, an alcohol (ROH) is also produced as a by-product. In addition, the reaction solution after the start of the cyclization reaction may contain, in addition to the target compound, one or more selected from impurities, unreacted raw material compounds, and intermediates. In the cyclization reaction of 4-halogeno-3-hydroxybutyric acid ester, γ-crotonolactone represented by the following formula (3) may be generated as an impurity.

[0018] [ka]

[0019] In the first reaction step, it is preferable to carry out the cyclization reaction until the yield (intermediate yield) of the target compound obtained by the measurement method described below is 10% or more. The yield (intermediate yield) at the end of the first reaction step is preferably 10 to 60%, more preferably 20 to 50%. If the intermediate yield is equal to or greater than the lower limit of the above range, it is easy to shorten the reaction time in the second reaction step, and if it is equal to or less than the upper limit, it is easy to suppress the generation of impurities.

[0020] (Alcohol removal process) When the ester-type protecting group R in the starting compound is a hydrocarbon group, it is preferable to remove the alcohol (ROH) by-produced in the cyclization step during the cyclization step. In the alcohol removal step, at least a portion of the alcohol contained in the reaction solution is removed. It is preferable to remove a larger amount of alcohol, and it is also possible to remove all of the alcohol in the reaction solution. For example, the alcohol in the reaction solution is removed by concentrating the reaction solution under reduced pressure to remove a portion of the reaction solution. The amount of the reaction solution removed by concentrating the reaction solution under reduced pressure is, for example, preferably 1 to 10 times by weight, more preferably 2 to 8 times by weight, the amount of the alcohol in the reaction solution. In this process, the reaction time can be shortened by removing the alcohol during the cyclization step. In particular, by carrying out the alcohol removal step before the pH adjustment step, the production of the intermediate is promoted and the yield is improved.

[0021] (pH adjustment process) The pH adjustment step is a step for varying the pH of the reaction solution in addition to the change in pH that accompanies an increase in the acid components produced as by-products in the cyclization reaction. The pH is preferably adjusted by adding an alkaline compound to the reaction solution. In this specification, an alkaline compound refers to a compound whose 5% by mass aqueous solution has a pH of 8.0 or higher at 20° C. Specific examples include alkali metal hydroxides (sodium hydroxide, etc.), carbonates (sodium carbonate, potassium carbonate, etc.), and bicarbonates (sodium bicarbonate, etc.).

[0022] In the pH adjustment step, the pH is preferably adjusted to 0.5 to 5.5 at 20° C. The pH is more preferably 1.0 to 4.5, and even more preferably 1.5 to 4.5. When the pH is equal to or higher than the lower limit of the above range, the yield is improved and the impurity formation is inhibited. When the pH is equal to or lower than the upper limit, the impurity formation is inhibited.

[0023] (Second reaction step) In the second reaction step, the reaction solution whose pH has been adjusted in the pH adjustment step is heated to cause a cyclization reaction, which produces an acid as a by-product. The reaction temperature in the second reaction step is preferably 40 to 150° C., more preferably 70 to 120° C. The cyclization reaction may be carried out while heating to the boiling point of the medium and refluxing. The reaction time in the second reaction step is not particularly limited, and is preferably 0.5 to 24 hours, more preferably 1 to 10 hours. When the desired yield is reached, the reaction is terminated by lowering the temperature of the reaction solution, for example by allowing the reaction solution to cool to room temperature. The yield of the target compound at the end of the second reaction step, as determined by the measurement method described below, is, for example, preferably 50 to 100%, more preferably 60 to 100%.

[0024] (neutralization process) Next, the resulting reaction solution is neutralized to obtain a neutralized solution containing the target compound and a neutralized salt. Specifically, an alkaline compound is added to the reaction liquid containing an acid to neutralize it. Examples of alkaline compounds used for neutralization include alkali metal hydroxides (sodium hydroxide, etc.), carbonates (sodium carbonate, potassium carbonate, etc.), and bicarbonates (sodium bicarbonate, etc.). The pH of the neutralization solution at 20° C. is preferably 2 to 7. The obtained neutralized liquid may be used as it is as a crude composition in the subsequent salt precipitation step, but it is preferable in terms of efficiency to use a concentrate obtained by distilling off a part of the medium under reduced pressure as the crude composition.

[0025] In this embodiment, the neutralizing salt preferably comprises sodium chloride. For this purpose, it is preferable that X in formula (1) is a chlorine atom, and the alkaline compound added in the neutralization step contains sodium hydroxide. When an acidic compound is added to the raw material composition, it is preferable that the acidic compound contains hydrochloric acid. When a pH adjustment step is performed, it is preferable that the alkaline compound added contains sodium hydroxide.

[0026] (purification process) In this purification method, a solvent is added to the crude composition to precipitate a salt (salt precipitation step). As the solvent to be added to the crude composition, at least one selected from the group consisting of alcohols having 2 to 6 carbon atoms, ketones having 4 to 8 carbon atoms, nitriles having 2 to 6 carbon atoms, and ethers having 4 to 8 carbon atoms is used. As the alcohol having 2 to 6 carbon atoms, ethanol, propanol, isopropanol, butanol, and 2-butanol are preferred. As the ketone having 4 to 8 carbon atoms, methyl ethyl ketone, 2-pentanone, 3-pentanone, cyclohexanone, and methyl isobutyl ketone are preferred. As the nitrile having 2 to 6 carbon atoms, acetonitrile, propionitrile and butyronitrile are preferred. As the ether having 4 to 8 carbon atoms, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, diisopropyl ether, and dioxane are preferred.

[0027] The amount of the solvent added is preferably 1 to 10 times by weight, more preferably 1 to 5 times by weight, relative to the raw material compound. When the amount is equal to or more than the lower limit of the above range, the salt is sufficiently precipitated, and the effect of improving the purity of the crude product is excellent. When the amount is equal to or less than the upper limit, the load during the reduced pressure concentration of the filtrate obtained in the subsequent filtration step can be reduced.

[0028] After the solvent is added to the crude composition, it is preferable to cool the crude composition to promote precipitation of the salt. The cooling temperature is, for example, preferably -40 to 15°C, more preferably -30 to 10°C. The salt precipitated in the salt precipitation step preferably contains sodium chloride. The salt content of the precipitate in the salt precipitation step is preferably 50% by mass or more, more preferably 70% by mass or more, and even more preferably 80% by mass or more. It may be 100% by mass.

[0029] After the salt precipitation step, it is preferable to filter off the precipitate by a known method (filtration step). The filtrate obtained in the filtration step contains the target compound, and the filtrate can be concentrated under reduced pressure to obtain the target compound in crude form. Furthermore, the procedure of adding the above-mentioned solvent to the obtained crude product to precipitate a salt, filtering off the precipitate, and concentrating the filtrate under reduced pressure may be repeated one or more times.

[0030] According to this embodiment, as shown in the examples described later, the purity of the crude product obtained by filtering the precipitate is improved by using the specific solvent in the salt precipitation step. Therefore, the purity of the purified product can be efficiently increased by using this purification method.

[0031] The crude composition to be purified is not limited to that prepared by the method of the present embodiment, and may be a crude composition containing 3-hydroxy-γ-butyrolactone and a neutralization salt prepared by a known method. In particular, preparing the crude composition by a method having the above-mentioned pH adjustment step is preferable in that the yield of the target compound in the crude composition is likely to be high and the production of impurities is likely to be suppressed. EXAMPLES

[0032] The present invention will be described in more detail below using examples, but the present invention is not limited to these examples. The reaction was monitored by gas chromatography, and the yield was calculated from the peak area ratio according to the following formula. Yield (%) = target compound / (unreacted raw material compound + intermediate + target compound + impurities) x 100

[0033] In the following example, (S)-ethyl 4-chloro-3-hydroxybutyrate (X in formula (1) is a chlorine atom and R is an ethyl group) was used as the raw material. The yield was calculated from the following peak areas. Raw material compound: Peak area of ​​(S)-ethyl 4-chloro-3-hydroxybutyrate Target compound: (S)-3-hydroxy-γ-butyrolactone peak area Impurity: γ-crotonolactone peak area Intermediate: (S)-4-chloro-3-hydroxybutyric acid peak area

[0034] Examples 1 to 4 are working examples, and Examples 5 and 6 are comparative examples. <Example 1> A raw material composition was prepared by adding 15.59 g (150 mmol) of 35% hydrochloric acid, 131 mL of water, and 30.0 g (180 mmol) of ethyl (S)-4-chloro-3-hydroxybutyrate to a glass flask equipped with a thermometer, a condenser, and a stirrer. The raw material composition was stirred for 20 minutes at 90° C. (first reaction step). The resulting reaction liquid was analyzed by gas chromatography, and the intermediate yield was determined by the above-mentioned method to be 32%. Thereafter, the pressure was reduced and 40 g of the reaction liquid was distilled off (alcohol removal step). A 40% aqueous solution of sodium hydroxide was added to the remaining reaction liquid to adjust the pH to 1.4 at 33° C. (pH adjustment step). The mixture was then heated under reflux for 4 hours (second reaction step), and cooled to room temperature to terminate the reaction. The reaction solution obtained was analyzed by gas chromatography, and the yield was determined by the above method to be 82%.

[0035] The reaction solution was neutralized by adding 40% aqueous sodium hydroxide (neutralization step), and a part of the medium of the neutralized solution was distilled off under reduced pressure to obtain 42 g of a crude composition. The crude composition contained the target compound, water, and sodium chloride as a neutralization salt. Next, 75 g of 2-propanol was added to the obtained crude composition, and the mixture was cooled to 0° C. to precipitate a salt (salt precipitation step). The precipitate was filtered off, and the resulting filtrate was concentrated under reduced pressure to obtain a crude product of the desired compound. The purity of the obtained crude product was determined by gas chromatography analysis. The appearance of the obtained crude product was also visually observed to evaluate the presence or absence of insoluble matter. The results are shown in Table 1 (hereinafter the same).

[0036] <Examples 2 to 6> In Example 1, the solvent added to the crude composition was changed as shown in Table 1. The amount of the solvent added was 75 g in each case. The rest was the same as in Example 1.

[0037] [Table 1]

[0038] As shown by the results in Table 1, in Examples 1 to 4, the inclusion of precipitates in the crude product was suppressed, and a crude product containing the target compound at a high purity could be obtained. In Example 5, a relatively large amount of precipitate was present in the crude product, and therefore the purity was not measured. In Example 6, the precipitate dissolved in the crude product, and the purity of the crude product decreased.

Claims

1. a reaction step of subjecting a 4-chloro-3-hydroxybutyric acid ester represented by the following formula (1) to a cyclization reaction in a medium containing water to obtain a reaction liquid containing 3-hydroxy-γ-butyrolactone represented by the following formula (2); a neutralization step of neutralizing the reaction solution obtained in the reaction step to obtain a crude composition containing the 3-hydroxy-γ-butyrolactone and sodium chloride; A method for producing 3-hydroxy-γ-butyrolactone, comprising a step of adding one or more solvents selected from the group consisting of alcohols having 2 to 6 carbon atoms, ketones having 4 to 8 carbon atoms, nitriles having 2 to 6 carbon atoms, and ethers having 4 to 8 carbon atoms to the crude composition to precipitate the sodium chloride. 【Chemistry 1】 (In the formula, X represents a chlorine atom, and R represents an ester-type protecting group.) 【Chemistry 2】

2. The method according to claim 1, further comprising a pH adjustment step of adjusting the pH of the reaction solution at 20° C. to 0.5 or more by adding an alkaline compound at a point in time when the intermediate yield is 10 to 60% after the initiation and before the completion of the cyclization reaction.

3. The method according to claim 2 , further comprising an alcohol removing step of removing an alcohol by-produced by the cyclization reaction after the initiation of the cyclization reaction and before the pH adjustment step.

4. A manufacturing method described in any one of claims 1 to 3, wherein an alkaline compound containing sodium hydroxide is added to the reaction solution in the neutralization step.

Images