Process for producing 3-hydroxy-γ-butyrolactone

Abstract

To provide a method for producing 3-hydroxy-γ-butyrolactone that suppresses the formation of impurities more effectively.SOLUTION: The present invention discloses a method for producing 3-hydroxy-γ-butyrolactone represented by formula (2) by subjecting 4-halogeno-3-hydroxybutyric acid ester represented by formula (1) to a cyclization reaction in the presence of a weak acid compound and water. In the formula, X is a halogen atom, and R is an ester-based protecting group.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for producing 3-hydroxy-γ-butyrolactone.

Background Art

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

[0003] Patent Document 1 describes a method for producing 3-hydroxy-γ-butyrolactone by subjecting ethyl 4-chloro-3-hydroxybutyrate to a cyclization reaction. In the examples of Patent Document 1, an aqueous hydrochloric acid solution or an aqueous sulfuric acid solution was added to ethyl 4-chloro-3-hydroxybutyrate, heated under reflux, neutralized with a caustic soda solution, water was distilled off under reduced pressure, ethyl acetate was added to the remaining mixture of crystals and an oily substance and stirred, the crystals were filtered off, and the filtrate was concentrated under reduced pressure to produce 3-hydroxy-γ-butyrolactone. Patent Document 2 describes an example in which ethyl 4-chloro-3-hydroxybutyrate was subjected to a cyclization reaction without adding an acid in a water-containing solvent to produce 3-hydroxy-γ-butyrolactone.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] According to the findings of the present inventors, the methods described in Patent Documents 1 and 2 cannot sufficiently suppress the generation of impurities in the cyclization reaction. The present invention provides a method for producing 3-hydroxy-γ-butyrolactone capable of further suppressing the generation of impurities.

Means for Solving the Problems

[0006] The present invention has the following aspects. [1] A method for producing 3-hydroxy-γ-butyrolactone represented by the following formula (2), characterized by subjecting a 4-halogeno-3-hydroxybutyric acid ester represented by the following formula (1) to a cyclization reaction in the presence of a weakly acidic compound and water. In formula (1), X represents a halogen atom, and R represents an ester-type protecting group.

[0007]

Chemical Formula

Effects of the Invention

[0008] According to the method for producing 3-hydroxy-γ-butyrolactone of the present invention, the generation of impurities in the cyclization reaction can be further suppressed.

Modes for Carrying Out the Invention

[0009] The production method of the present embodiment (hereinafter, also simply referred to as "the present production method") is a method for producing 3-hydroxy-γ-butyrolactone (hereinafter, also referred to as "the target compound") represented by the following formula (2) by cyclizing a 4-halogeno-3-hydroxybutyric acid ester (hereinafter, also referred to as "the raw material compound") represented by the following formula (1).

[0010] [Chemical formula]

[0011] 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. The ester-type protecting group in this specification means a group that can protect a carboxylic acid as an ester. Examples of the ester-type protecting group include an alkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 20 carbon atoms, an aralkyl group having 7 to 20 carbon atoms, a silyl-based protecting group, and the like. Specific examples include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a tert-butyl group, a phenyl group, a benzyl group, an α-methylbenzyl group, a phenylpropyl group, a trimethylsilyl group, a tert-butyldimethylsilyl group, or a group in which a part of these groups is substituted by a substituent. Examples of the substituent include a halogen atom, a nitro group, a hydroxyl group, an ether group, an amide group, and the like. R is preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a tert-butyl group, or a benzyl group, and more preferably an ethyl group. The 4-halogeno-3-hydroxybutyric acid ester used in this production method may be either the (R)-form or the (S)-form, which are optical isomers, and these may be used in combination.

[0012] In this production method, the 4-halogeno-3-hydroxybutyric acid ester is subjected to a cyclization reaction in the presence of a weakly acidic compound and water. The weakly acidic compound in this specification means a compound having a pH of 2.1 to 6.0 at 20 °C in a 0.5 M aqueous solution. Specific examples include weak acids such as acetic acid, propionic acid, butyric acid, isobutyric acid, crotonic acid, acrylic acid, methacrylic acid, potassium hydrogen oxalate, potassium hydrogen tartrate, potassium hydrogen phthalate; and weakly acidic salts such as ammonium chloride, trimethylamine hydrochloride.

[0013] In this production method, it is preferable to carry out the cyclization reaction in an aqueous solution of the weakly acidic compound in which the weakly acidic compound is dissolved in a medium containing water. Specifically, a raw material composition is prepared by adding 4-halogeno-3-hydroxybutyric acid ester to the aqueous solution of the weakly acidic compound, and the raw material composition is heated to carry out the cyclization reaction. The content of the medium containing water in the raw material composition is preferably 1 to 10 times by weight, more preferably 2 to 6 times by weight, relative to the 4-halogeno-3-hydroxybutyric acid ester. The content of the weakly acidic compound in the raw material composition is preferably 0.05 to 2.0 molar equivalents, more preferably 0.1 to 1.0 molar equivalents, relative to the 4-halogeno-3-hydroxybutyric acid ester.

[0014] The medium may contain a water-soluble organic solvent in addition to water. Examples of the water-soluble organic solvent 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 proportion of water in the medium is preferably 30% by mass or more, more preferably 60% by mass or more, and particularly preferably 100% by mass.

[0015] The pH of the aqueous solution of the weakly acidic compound at 20 ° C (hereinafter also referred to as "initial pH") is preferably higher than 2.0, more preferably 2.1 to 5.0.

[0016] The reaction temperature of the cyclization reaction 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 is not particularly limited, but for example, 0.5 to 24 hours is preferable, and 1 to 10 hours is more preferable.

[0017] The reaction solution obtained by heating the raw material composition and carrying out the cyclization reaction may contain one or more selected from impurities, unreacted raw material compounds, and intermediates in addition to the target compound. In the cyclization reaction of 4-halo-3-hydroxybutyric acid ester, γ-crotonolactone represented by the following formula (3) may be generated as an impurity.

[0018]

Chemical formula

[0019] According to this production method, as shown in the examples described later, the amount of γ-crotonolactone generated in the cyclization reaction can be reduced. For example, the impurity generation ratio obtained by the measurement method described later can be reduced to 4.3% or less, preferably 4.2% or less, more preferably 4.0% or less, and even more preferably 3.0% or less.

[0020] As a method for isolating and purifying the target compound from the reaction solution obtained by carrying out the cyclization reaction, a known method can be used. For example, after adding an alkali such as caustic soda or sodium carbonate to the reaction solution for neutralization, the medium is distilled off under reduced pressure to obtain a neutralized solution containing the target compound and a salt. One or more organic solvents capable of dissolving the target compound are added to this neutralized solution to precipitate the salt, the precipitate is filtered off, and the filtrate is concentrated under reduced pressure to obtain a crude form of the target compound. Further, this operation can be repeated a plurality of times for purification to obtain a purified product of the target compound.

Examples

[0021] The present invention will be described in more detail below using examples, but the present invention is not limited to these examples. Reaction tracking was carried out by gas chromatography, and the yield and impurity generation ratio were calculated from the peak area ratio by the following formulas. Yield (%) = Target compound / (Unreacted raw material compound + Intermediate + Target compound + Impurity) × 100 Impurity generation ratio (%) = Impurity / Target compound × 100

[0022] In Examples 1 to 4 below, ethyl (S)-4-chloro-3-hydroxybutyrate (where X in formula (1) is a chlorine atom and R is an ethyl group) was used as the starting compound. In Examples 1 to 4, the yield and the impurity formation ratio were calculated from the following peak areas. Starting compound: Peak area of ethyl (S)-4-chloro-3-hydroxybutyrate Target compound: Peak area of (S)-3-hydroxy-γ-butyrolactone Impurity: Peak area of γ-crotonolactone Intermediate: Peak area of (S)-4-chloro-3-hydroxybutyric acid

[0023] Examples 1 and 2 are examples, and Examples 3 and 4 are comparative examples. <Example 1> To a glass flask, 15 mL of water and 456 mg (7.5 mmol) of acetic acid were added to prepare an aqueous solution of a weak acid compound, and further 5.00 g (30 mmol) of ethyl (S)-4-chloro-3-hydroxybutyrate was added to prepare a starting composition. The starting composition was heated under reflux for 2 hours to obtain a reaction solution. The initial pH of the aqueous solution of the weak acid compound is shown in Table 1 (the same applies hereinafter). The obtained reaction solution was analyzed by gas chromatography, and the yield and the impurity formation ratio were determined by the above method. The results are shown in Table 1 (the same applies hereinafter).

[0024] <Example 2> Example 1 was carried out in the same manner as in Example 1, except that 7.5 mmol of acetic acid was changed to 7.5 mmol of ammonium chloride. <Example 3> Example 1 was carried out in the same manner as in Example 1, except that 7.5 mmol of acetic acid was changed to 7.5 mmol of hydrochloric acid. <Example 4> Example 1 was carried out in the same manner as in Example 1, except that acetic acid was not added.

[0025]

Table 1

[0026] As shown in the results of Table 1, in Examples 1 and 2 where the cyclization reaction was carried out in the presence of a weakly acidic compound, the generation of impurities was suppressed. In Example 3 where the cyclization reaction was carried out in the presence of hydrochloric acid, which is a strong acid, and in Example 4 where no weakly acidic compound was added, the impurity generation ratio was larger than that in Examples 1 and 2.

Claims

1. A method for producing 3-hydroxy-γ-butyrolactone represented by the following formula (2), characterized in that a 4-halogeno-3-hydroxybutyric acid ester represented by the following formula (1) is subjected to a cyclization reaction in an aqueous solution of a weakly acidic compound in which the weakly acidic compound is dissolved in a medium containing water, and the initial pH of the aqueous solution of the weakly acidic compound at 20 ° C is higher than 2.

0. 【Chemical 1】 (In the formula, X represents a halogen atom, and R represents an ester-type protecting group.) [Chemical 2]

2. The production method according to claim 1, wherein the weakly acidic compound is a weak acid or a weakly acidic salt.

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