JP6274023B2 - Method for producing dicarboxylic acid monoester - Google Patents

Description

  The present invention relates to a method for producing a dicarboxylic acid monoester.

In recent years, liquid crystal materials that can be applied to optical films such as polarizing plates and retardation plates used in flat panel display devices (FPD) have attracted attention. A dicarboxylic acid monoester is used as an intermediate for producing such a liquid crystal material.
Patent Document 1 describes a method for producing a dicarboxylic acid monoester by reacting a dicarboxylic acid chloride with a phenol compound, and then precipitating and filtering the produced dicarboxylic acid monoester.

Japanese Patent Laid-Open No. 62-289545

  Conventional production methods of dicarboxylic acid monoesters have a problem of low reaction selectivity and low yield.

［式中、ｍは、０〜３の整数を表す。
Ｚは、メチルスルファニルメチル基、メトキシメチル基、エトキシメチル基、ｔｅｒｔ−
ブトキシメチル基、４−ペンテニルオキシメチル基、２−メトキシエトキシメチル基、１
−エトキシエチル基、ベンジルオキシメチル基、４−メトキシベンジルオキシメチル基、
２−メトキシベンジルオキシメチル基、４−ニトロベンジルオキシメチル基、１−メチル
−１−ベンジルオキシ−２−フルオロエチル基、１−メチル−１−フェノキシエチル基、
１−メチル−１−メトキシエチル基、１−メチル−１−ベンジルオキシエチル基、２，２
，２−トリクロロエトキシメチル基、１−［２−（トリメチルシリル）エトキシ］エチル
基、テトラヒドロピラニル基、３−ブロモテトラヒドロピラニル基、テトラヒドロチオピ
ラニル基、テトラヒドロフラニル基、テトラヒドロチオフラニル基、ｔｅｒｔ−ブチル基
、トリチル基、ベンジル基、４−メトキシベンジル基、３，４−ジメトキシベンジル基、
４−ニトロベンジル基、１，３−ベンゾジチオラン−２−イル基、２，２，２−トリクロ
ロエチル基、２−フェニル−２−エタノン−１−イル、シクロプロピルメチル基、−ＣＨ
_２−Ｏ−ＳｉＲ^５Ｒ^６Ｒ^７又は−ＳｉＲ^５Ｒ^６Ｒ^７を表す。
Ｒ^５、Ｒ^６及びＲ^７は、それぞれ独立に、水素原子、炭素数１〜８のアルキル基、炭素
数１〜８のアルコキシ基、フェニル基又はベンジル基を表す。
ｐは、０又は１を表す。］ The present invention includes the following inventions.
[1] A method for producing a dicarboxylic acid monoester comprising the following steps (1) to (4):
Step (1): An acid in an amount less than the molar equivalent of the dicarboxylic acid diester is added to a solution in which the dicarboxylic acid diester is dissolved in a solvent, and the ester bond of the dicarboxylic acid diester is decomposed to convert the dicarboxylic acid monoester. Step (2) for obtaining a mixture comprising: Step (3) for obtaining a slurry by cooling the mixture obtained in step (1) and precipitating dicarboxylic acid monoester: Slurry obtained in step (2) Heating step (4): adding an acid to decompose the ester bond of the dicarboxylic acid diester
[2] The production method according to [1], wherein the solvent is a solvent that dissolves the dicarboxylic acid diester more easily than the dicarboxylic acid monoester.
[3] The production method according to [1] or [2], wherein the difference between the temperature of the mixture before cooling and the temperature of the slurry obtained after cooling is 10 ° C or higher and 100 ° C or lower.
[4] The production method according to any one of [1] to [3], wherein the temperature difference of the slurry before and after heating in the step (3) is 10 ° C. or higher and 100 ° C. or lower.
[5] The production method according to any one of [1] to [4], wherein the dicarboxylic acid monoester is in a supersaturated state in the mixture before cooling.
[6] The difference between the solubility of the dicarboxylic acid monoester in the mixture before cooling and the solubility of the dicarboxylic acid monoester in the solution after cooling is from 10 g / L to 200 g / L in [1] to [5] The manufacturing method in any one.
[7] The production method according to any one of [1] to [6], wherein the temperature of the slurry after cooling is -80 ° C or higher and lower than 30 ° C.
[8] The production method according to any one of [1] to [7], wherein the temperature at which the ester bond of the dicarboxylic acid diester in step (4) is decomposed is -80 ° C or higher and lower than 35 ° C.
[9] The production method according to any one of [1] to [8], wherein the dicarboxylic acid monoester is a compound represented by the formula (A), and the dicarboxylic acid diester is a compound represented by the formula (B). .

[Wherein, m represents an integer of 0 to 3.
Z represents a methylsulfanylmethyl group, a methoxymethyl group, an ethoxymethyl group, tert-
Butoxymethyl group, 4-pentenyloxymethyl group, 2-methoxyethoxymethyl group, 1
-Ethoxyethyl group, benzyloxymethyl group, 4-methoxybenzyloxymethyl group,
2-methoxybenzyloxymethyl group, 4-nitrobenzyloxymethyl group, 1-methyl-1-benzyloxy-2-fluoroethyl group, 1-methyl-1-phenoxyethyl group,
1-methyl-1-methoxyethyl group, 1-methyl-1-benzyloxyethyl group, 2,2
, 2-trichloroethoxymethyl group, 1- [2- (trimethylsilyl) ethoxy] ethyl group, tetrahydropyranyl group, 3-bromotetrahydropyranyl group, tetrahydrothiopyranyl group, tetrahydrofuranyl group, tetrahydrothiofuranyl group, tert-butyl group, trityl group, benzyl group, 4-methoxybenzyl group, 3,4-dimethoxybenzyl group,
4-nitrobenzyl group, 1,3-benzodithiolan-2-yl group, 2,2,2-trichloroethyl group, 2-phenyl-2-ethanon-1-yl, cyclopropylmethyl group, -CH
_{It represents 2-} O—SiR ⁵ R ⁶ R ⁷ or —SiR ⁵ R ⁶ R ⁷ .
R ⁵ , R ⁶ and R ⁷ each independently represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, a phenyl group or a benzyl group.
p represents 0 or 1. ]

  According to the method for producing a dicarboxylic acid monoester of the present invention, a dicarboxylic acid monoester can be obtained in a high yield.

［式中、Ｒは炭素数３〜１５の炭化水素基を表し、Ｒに含まれる炭素原子は、窒素原子、酸素原子及び硫黄原子からなる群から選ばれる少なくとも１つの原子で置換されてもよい。
ｍは、０〜３の整数を表す。
Ｚは、メチルスルファニルメチル基、メトキシメチル基、エトキシメチル基、ｔｅｒｔ−
ブトキシメチル基、４−ペンテニルオキシメチル基、２−メトキシエトキシメチル基、１
−エトキシエチル基、ベンジルオキシメチル基、４−メトキシベンジルオキシメチル基、
２−メトキシベンジルオキシメチル基、４−ニトロベンジルオキシメチル基、１−メチル
−１−ベンジルオキシ−２−フルオロエチル基、１−メチル−１−フェノキシエチル基、
１−メチル−１−メトキシエチル基、１−メチル−１−ベンジルオキシエチル基、２，２
，２−トリクロロエトキシメチル基、１−［２−（トリメチルシリル）エトキシ］エチル
基、テトラヒドロピラニル基、３−ブロモテトラヒドロピラニル基、テトラヒドロチオピ
ラニル基、テトラヒドロフラニル基、テトラヒドロチオフラニル基、ｔｅｒｔ−ブチル基
、トリチル基、ベンジル基、４−メトキシベンジル基、３，４−ジメトキシベンジル基、
４−ニトロベンジル基、１，３−ベンゾジチオラン−２−イル基、２，２，２−トリクロ
ロエチル基、２−フェニル−２−エタノン−１−イル、シクロプロピルメチル基、−ＣＨ
_２−Ｏ−ＳｉＲ^５Ｒ^６Ｒ^７又は−ＳｉＲ^５Ｒ^６Ｒ^７を表す。
Ｒ^５、Ｒ^６及びＲ^７は、それぞれ独立に、水素原子、炭素数１〜８のアルキル基、炭素
数１〜８のアルコキシ基、フェニル基又はベンジル基を表す。
ｐは、０又は１を表す。］ The dicarboxylic acid diester is a compound in which the two carboxy groups in the dicarboxylic acid compound having two carboxy groups together form an ester bond. Examples of the dicarboxylic acid diester include a compound represented by the formula (X). Preferred are compounds represented by formula (B), more preferred are compounds represented by formula (O), even more preferred are compounds represented by formula (P), and particularly preferred are formula (Q). ).

[Wherein, R represents a hydrocarbon group having 3 to 15 carbon atoms, and the carbon atom contained in R may be substituted with at least one atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom. .
m represents an integer of 0 to 3.
Z represents a methylsulfanylmethyl group, a methoxymethyl group, an ethoxymethyl group, tert-
Butoxymethyl group, 4-pentenyloxymethyl group, 2-methoxyethoxymethyl group, 1
-Ethoxyethyl group, benzyloxymethyl group, 4-methoxybenzyloxymethyl group,
2-methoxybenzyloxymethyl group, 4-nitrobenzyloxymethyl group, 1-methyl-1-benzyloxy-2-fluoroethyl group, 1-methyl-1-phenoxyethyl group,
1-methyl-1-methoxyethyl group, 1-methyl-1-benzyloxyethyl group, 2,2
, 2-trichloroethoxymethyl group, 1- [2- (trimethylsilyl) ethoxy] ethyl group, tetrahydropyranyl group, 3-bromotetrahydropyranyl group, tetrahydrothiopyranyl group, tetrahydrofuranyl group, tetrahydrothiofuranyl group, tert-butyl group, trityl group, benzyl group, 4-methoxybenzyl group, 3,4-dimethoxybenzyl group,
4-nitrobenzyl group, 1,3-benzodithiolan-2-yl group, 2,2,2-trichloroethyl group, 2-phenyl-2-ethanon-1-yl, cyclopropylmethyl group, -CH
_{It represents 2-} O—SiR ⁵ R ⁶ R ⁷ or —SiR ⁵ R ⁶ R ⁷ .
R ⁵ , R ⁶ and R ⁷ each independently represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, a phenyl group or a benzyl group.
p represents 0 or 1. ]

  R may be an aromatic hydrocarbon group or an aliphatic hydrocarbon group. R preferably has a rigid structure because the resulting dicarboxylic acid monoester precipitates in solution. Therefore, R is preferably an aromatic hydrocarbon group or a cyclic aliphatic hydrocarbon group, and more preferably a cyclic aliphatic hydrocarbon group. Moreover, the carbon atom contained in these aromatic hydrocarbon group and aliphatic hydrocarbon group may be substituted with an atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom.

m is preferably 0.
p is preferably 1.

R ⁵ , R ⁶ and R ⁷ in —CH ₂ —O—SiR ⁵ R ⁶ R ⁷ and —SiR ⁵ R ⁶ R ⁷ represented by Z are each independently a hydrogen atom or an alkyl having 1 to 8 carbon atoms. Group, a C1-C8 alkoxy group, a phenyl group, or a benzyl group.

  Examples of the alkyl group having 1 to 8 carbon atoms include a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a hexyl group, and an octyl group.

  Examples of the alkoxy group having 1 to 8 carbon atoms include a methoxy group, an ethoxy group, an isopropoxy group, a tert-butoxy group, a hexyloxy group, and an octyloxy group.

Specific examples of the group represented by —CH ₂ —O—SiR ⁵ R ⁶ R ⁷ include trimethylsilyloxymethyl group, isopropyldimethylsilyloxymethyl group, tert-butyldimethylsilyloxymethyl group, and tert-butyldiphenyl. Examples thereof include a silyloxymethyl group, a tribenzylsilyloxymethyl group, a triisopropylsilyloxymethyl group, and a di-tert-butylmethylsilyloxymethyl group.

Specific examples of the group represented by —SiR ⁵ R ⁶ R ⁷ include a trimethylsilyl group, an isopropyldimethylsilyl group, a tert-butyldimethylsilyl group, a tert-butyldiphenylsilyl group, a tribenzylsilyl group, and a triisopropylsilyl group. Group, di-tert-butylmethylsilyl group and the like.

  Z is preferably a methylsulfanylmethyl group, a methoxymethyl group, an ethoxymethyl group, a 2-methoxyethoxymethyl group, a 1-ethoxyethyl group, a tert-butyldimethylsilyl group, a tert-butyldiphenylsilyl group, a triisopropylsilyl group, It is a tetrahydropyranyl group or a tetrahydrothiopyranyl group. More preferably, it is a methylsulfanylmethyl group, a methoxymethyl group, an ethoxymethyl group, a 2-methoxyethoxymethyl group, a tert-butyldimethylsilyl group, a tert-butyldiphenylsilyl group, or a triisopropylsilyl group, and more preferably It is a methoxymethyl group or an ethoxymethyl group. Z is preferably such a group because the stability of the compound (A) is higher and the productivity of the compound (A) is higher.

As a method for producing a dicarboxylic acid diester, for example, a method in which a dicarboxylic acid compound is reacted with a compound represented by the formula (F) (hereinafter sometimes referred to as a compound (F)) in the presence of a base (first compound) Method), a method of reacting a dicarboxylic acid compound with a compound represented by formula (G) or a compound represented by formula (H) (second method), a dicarboxylic acid compound and formula (I) A third compound, a dicarboxylic acid compound and a base to obtain a dicarboxylate compound, and then the resulting dicarboxylate compound and the compound (F) are reacted. A method (4th method) is mentioned. The di-salt is preferably an alkali metal salt.
Since the reaction conditions are milder, the first method, the second method, and the fourth method are preferable.

Z-W ¹ (F)

[Wherein Z represents the same meaning as described above. W ¹ represents a halogen atom, a tosyl group, or a mesityl group. ]

［式中、ｑは、０又は１を表す。Ｑは−Ｏ−又は−Ｓ−を表す。］

[Wherein q represents 0 or 1; Q represents -O- or -S-. ]

［式中、Ｒ^Ｌ１は、メチル基、エチル基、フェニル基、ベンジル基又はトリメチルシリルエチル基を表す。Ｒ^Ｌ２は、水素原子、メチル基又はフッ素原子を表す。Ｑは−Ｏ−又は−Ｓ−を表す。］

[Wherein, R ^L1 represents a methyl group, an ethyl group, a phenyl group, a benzyl group, or a trimethylsilylethyl group. R ^L2 represents a hydrogen atom, a methyl group or a fluorine atom. Q represents -O- or -S-. ]

Z-OH (I)

[In formula (I), Z represents the same meaning as described above. ]

  The first method is preferably performed in an organic solvent. The reaction may be performed while removing a salt generated by the reaction between the dicarboxylic acid compound and the compound (F).

Examples of bases include organic bases such as triethylamine, diisopropylethylamine, pyridine, N-methylmorpholine, dimethylaminopyridine, and dimethylaniline; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, and cesium hydroxide, sodium carbonate And alkali metal carbonates such as potassium carbonate and cesium carbonate, sodium hydrogen carbonate, alkali metal hydrogen carbonates such as potassium hydrogen carbonate, and inorganic bases such as cesium fluoride. When the base is an organic base, triethylamine, diisopropylethylamine, pyridine, N-methylmorpholine and dimethylaminopyridine are preferred, and triethylamine, diisopropylethylamine and pyridine are more preferred. When the base is an inorganic base, sodium hydroxide, potassium hydroxide, potassium carbonate and cesium carbonate are preferred, and potassium hydroxide and potassium carbonate are more preferred. When an inorganic base is used, a phase transfer catalyst such as a crown ether such as 18-crown-6 or a quaternary ammonium salt such as tetrabutylammonium bromide may be used in combination.
The addition amount of the base is usually 2 to 5 mol with respect to 1 mol of the dicarboxylic acid compound.

W ¹ is preferably a halogen atom. As a halogen atom, a chlorine atom, a bromine atom, and an iodine atom are preferable, and a chlorine atom and a bromine atom are more preferable.

  Examples of the compound (F) include methylsulfanylchloromethane, methylsulfanylbromomethane, methoxychloromethane, methoxybromomethane, chloromethoxyethane, bromomethoxyethane, 2-methoxyethoxymethyl chloride, 2-methoxyethoxymethyl bromide, ethoxyethyl chloride. , Ethoxyethyl bromide, benzyloxymethyl chloride, benzyloxymethyl bromide, 4-methoxybenzyloxymethyl chloride, 4-nitrobenzyloxymethyl chloride, 2-methoxyphenyloxymethyl chloride, tert-butoxymethyl chloride, tert-butoxymethyl bromide 4-pentenyloxymethyl chloride, 1- [2- (trimethylsilyl) ethoxy] ethyl chloride, 1-chloromethoxy-2,2, -Trichloroethane, 1- [2- (trimethylsilyl) ethoxy] ethyl chloride, 1-methyl-1-methoxyethyl chloride, 1-methyl-1-benzyloxyethyl chloride, 1-methyl-1-benzyloxy-2-fluoroethyl Chloride, 1-methyl-1-phenoxyethyl chloride, tert-butyl chloride, tert-butyl bromide, trityl chloride, trityl bromide, 1,3-benzodithiolane-2-chloride, trimethylchlorosilane, trimethylbromosilane, isopropyldimethylchlorosilane, Isopropyldimethylbromosilane, tert-butyldimethylchlorosilane, tert-butyldimethylbromosilane, tert-butyldiphenylchlorosilane, tert-butyldiphenylbromosilane, Ribenzylchlorosilane, tribenzylbromosilane, triisopropylchlorosilane, triisopropylbromosilane, di-tert-butylmethylchlorosilane, di-tert-butylmethylbromosilane, trimethylsilyloxychloromethane, 2-phenyl-2-ethanone-1- Ilyl chloride, 1,1,1,2-tetrachloroethane, chloromethylcyclopropane and the like can be mentioned. Commercially available products can be used for these.

The organic solvent is preferably a hydrophilic solvent other than alcohol and a hydrophobic solvent.
Examples of hydrophilic solvents other than alcohol include nitrile solvents such as acetonitrile, hydrophilic ketone solvents such as acetone, hydrophilic ether solvents such as tetrahydrofuran, dioxane and ethylene glycol dimethyl ether, N, N-dimethylformamide, N, N- Examples thereof include hydrophilic amide solvents such as dimethylacetamide and N-methylpyrrolidone, and hydrophilic sulfoxide solvents such as dimethyl sulfoxide.
Examples of the hydrophobic solvent include aromatic hydrocarbon solvents such as toluene, benzene, xylene, and chlorobenzene, hydrophobic ketone solvents such as methyl ethyl ketone, cyclopentanone, cyclohexanone, methyl amyl ketone, and methyl isobutyl ketone, pentane, hexane, and Examples thereof include aliphatic hydrocarbon solvents such as heptane, ester solvents such as ethyl lactate and ethyl acetate, and halogen solvents such as chloroform, dichloromethane, carbon tetrachloride, tetrachloroethane, and trichloroethane.
The organic solvent used in the first method is preferably a hydrophilic ether solvent, a hydrophilic amide solvent, a hydrophilic sulfoxide solvent, an aromatic hydrocarbon solvent, a hydrophobic ketone solvent, and a halogen-based solvent, more preferably Halogen solvent. These organic solvents may be used alone or in combination.

  The amount of compound (F) to be used is preferably 1.8 to 3 mol, more preferably 1.97 to 2.7 mol, still more preferably 2 to 2. mol, per 1 mol of the dicarboxylic acid compound. 7 moles.

The second method is preferably performed in an organic solvent, and is preferably performed in the presence of an acid catalyst.
Examples of the acid catalyst include p-toluenesulfonic acid, pyridinium p-toluenesulfonic acid, aqueous hydrochloric acid, sulfuric acid, and trifluoroacetic acid. The addition amount of the acid catalyst is preferably 0.005 to 0.2 mol with respect to 1 mol of the dicarboxylic acid compound.

  The organic solvent used in the second method is preferably a ketone solvent such as acetone, methyl ethyl ketone, cyclopentanone, cyclohexanone, methyl amyl ketone and methyl isobutyl ketone; an aliphatic hydrocarbon solvent such as pentane, hexane and heptane; Aromatic hydrocarbon solvents such as toluene, xylene, benzene and chlorobenzene; nitrile solvents such as acetonitrile; ether solvents such as tetrahydrofuran and dimethoxyethane; ester solvents such as ethyl lactate; and halogen systems such as chloroform and dichloromethane It is a solvent. These may be used alone or in combination.

Specific examples of the compound (G) include dihydropyran, 3-bromodihydropyran, dihydrothiopyran, dihydrofuran, dihydrothiofuran and the like.
Specific examples of the compound (H) include vinyl methyl ether vinyl ethyl ether, vinyl phenyl ether, vinyl benzyl ether, trimethylsilylethyl vinyl ether, and the like.

  The amount of compound (G) or compound (H) to be used is preferably 1.9 to 5 mol, more preferably 1.9 to 4 mol, further preferably 2 with respect to 1 mol of the dicarboxylic acid compound. .2-4 moles.

  The third method is preferably performed in an organic solvent. Compound (B) can be obtained by subjecting the dicarboxylic acid compound and compound (I) to a dehydration condensation reaction, and a condensing agent is preferably used for the dehydration condensation reaction.

Examples of the condensing agent include 1-cyclohexyl-3- (2-morpholinoethyl) carbodiimide met-para-toluenesulfonate, dicyclohexylcarbodiimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide, 1-ethyl-3- ( 3-dimethylaminopropyl) carbodiimide hydrochloride (water-soluble carbodiimide: commercially available as WSC), carbodiimides such as bis (2,6-diisopropylphenyl) carbodiimide, bis (trimethylsilyl) carbodiimide, 2-methyl-6-nitrobenzoic anhydride 2,2′-carbonylbis-1H-imidazole, 1,1′-oxalyldiimidazole, diphenylphosphoryl azide, 1 (4-nitrobenzenesulfonyl) -1H-1,2,4-triazole, 1H-benzotria 1-yloxytripyrrolidinophosphonium hexafluorophosphate, 1H-benzotriazol-1-yloxytris (dimethylamino) phosphonium hexafluorophosphate, N, N, N ′, N′-tetramethyl-O— ( N-succinimidyl) uronium tetrafluoroborate, N- (1,2,2,2-tetrachloroethoxycarbonyloxy) succinimide, N-carbobenzoxysuccinimide, O- (6-chlorobenzotriazol-1-yl)- N, N, N ′, N′-tetramethyluronium tetrafluoroborate, O- (6-chlorobenzotriazol-1-yl) -N, N, N ′, N′-tetramethyluronium hexafluorophosphate, 2-Bromo-1-ethylpyridinium tetrafluoroborate 2-chloro-1,3-dimethylimidazolinium chloride, 2-chloro-1,3-dimethylimidazolinium hexafluorophosphate, 2-chloro-1-methylpyridinium iodide, 2-chloro-1-methylpyridinium Examples include para-toluenesulfonate, 2-fluoro-1-methylpyridinium, para-toluenesulfonate, and trichloroacetic acid pentachlorophenyl ester.
The amount of the condensing agent to be used is preferably 1.5 to 2.5 mol per 1 mol of compound (E).

  As a preferable organic solvent used in the third method, the same organic solvent as mentioned in the first method can be used.

  The amount of compound (I) to be used is preferably 1.8 to 3 mol, more preferably 1.97 to 2.7 mol, particularly preferably 2 to 2. mol, per 1 mol of the dicarboxylic acid compound. 7 moles.

  The reaction of the dicarboxylic acid compound and the base in the fourth method is preferably performed in a solvent. Examples of such a solvent include water, methanol, ethanol, and the like. Preferably, the solvent dissolves the base, and methanol and ethanol are particularly preferable.

The base is preferably an inorganic base. Examples of the inorganic base include the same ones as described above. Sodium hydroxide and potassium hydroxide are preferable, and potassium hydroxide is more preferable. The reaction with the base may be performed in the presence of a phase transfer catalyst. Examples of the phase transfer catalyst include the same ones as described above.
The amount of the base used is preferably 2 to 3.5 mol with respect to 1 mol of the dicarboxylic acid compound.

  The di-salt of the dicarboxylic acid compound is preferably an alkali metal salt. Examples of the alkali metal include sodium, potassium, cesium and the like, and potassium is preferable.

After completion of the reaction between the dicarboxylic acid compound and the base, the dicarboxylic acid compound di-salt can be obtained by concentrating or filtering the obtained reaction mixture. The method of mixing the poor solvent of the di salt of the dicarboxylic acid compound and the reaction mixture, and filtering the resulting mixture is preferred. Examples of the poor solvent for the di-salt of the dicarboxylic acid compound include toluene and aromatic hydrocarbon solvents such as xylene; halogen solvents such as chloroform and dichloromethane; and ether solvents such as tetrahydrofuran, dioxane and dimethoxyethane. Preferably, tetrahydrofuran, dioxane, and toluene are used.
You may dry the di-salt of the obtained dicarboxylic acid compound.

  The reaction between the dicarboxylate of the dicarboxylic acid compound and compound (F) is preferably carried out in an organic solvent. The amount of compound (F) to be used is preferably 1.8 to 3 mol, more preferably 1.97 to 2.7 mol, still more preferably 2 to 2 with respect to 1 mol of the dicarboxylic acid compound di-salt. .3 moles.

As a preferable organic solvent used in the reaction between the di-salt of the dicarboxylic acid compound and the compound (F), the same organic solvent as mentioned in the first method can be mentioned. More preferred are aromatic hydrocarbon solvents, hydrophobic ketone solvents, and hydrophobic solvents such as halogen solvents, and more preferred are toluene, xylene, dichloromethane and chloroform. If these hydrophobic solvents are used, the dicarboxylic acid diester can be obtained in a high yield even if water is present in the reaction system. An organic solvent may be used independently and may be used in combination of multiple.
The reaction may be performed in the presence of a phase transfer catalyst. Examples of the phase transfer catalyst include the same ones as described above.

（式中、Ｒ、ｍ、Ｚ及びｐは前記と同じ意味を表す。） The dicarboxylic acid diester is a compound in which only one of the two carboxy groups in the dicarboxylic acid compound having two carboxy groups forms an ester bond. Examples of the dicarboxylic acid monoester include a compound represented by the formula (Y). Preferred are compounds represented by formula (A), more preferred are compounds represented by formula (L), even more preferred are compounds represented by formula (M), and particularly preferred are formula (N). ).

(In the formula, R, m, Z and p represent the same meaning as described above.)

  Preferable examples of the dicarboxylic acid diester include compounds represented by formula (B-1) to formula (B-38). Preferred are compounds represented by formula (B-1) to formula (B-5), and more preferred are compounds represented by formula (B-2) or formula (B-3). Preferable examples of the dicarboxylic acid monoester include compounds in which only one of the two ester structures of the exemplified compound (B) is substituted with a carboxy group.

<Step (1)>
The solvent is not particularly limited as long as it can dissolve the dicarboxylic acid diester, but an organic solvent is preferable, a water-insoluble solvent is more preferable, and a nonpolar solvent is further preferable in that the decomposition of the ester bond is easily controlled. Moreover, the solvent which is easy to melt | dissolve dicarboxylic acid diester rather than dicarboxylic acid monoester is preferable at the point that a dicarboxylic acid monoester is easy to selectively precipitate in a process (2).

  Solvents include aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, and dichlorobenzene, aliphatic hydrocarbons such as pentane, hexane, heptane, octane, isooctane, cyclopentane, cyclohexane, cycloheptane, and methylcyclohexane, Examples include tetrahydrofuran, dioxane, ether solvents such as ethylene glycol dimethyl ether, and ester solvents such as ethyl lactate and ethyl acetate. Examples of the organic solvent include the aromatic hydrocarbon, the aliphatic hydrocarbon, the ether solvent, and the ester solvent. Examples of the water-insoluble solvent include the aromatic hydrocarbon, the aliphatic hydrocarbon, and the ester solvent. Examples of the nonpolar solvent include the aromatic hydrocarbon and the aliphatic hydrocarbon. The aliphatic hydrocarbon may be cyclic or chain-like, and the aliphatic hydrocarbon may be linear or branched. Aliphatic hydrocarbons are preferred because the solubility of the dicarboxylic acid monoester is low and the yield of the dicarboxylic acid monoester tends to be higher. A saturated aliphatic hydrocarbon is more preferable, pentane, hexane, heptane, octane or cyclohexane is more preferable, heptane, octane or cyclohexane is further preferable, and heptane is particularly preferable. These solvents may be used alone or in combination.

  For example, when an aliphatic hydrocarbon and another solvent are used in combination, the content of the aliphatic hydrocarbon with respect to 100 parts by mass of the total amount of the aliphatic hydrocarbon and the other solvent is preferably 90 parts by mass or more. More preferably, it is 95 mass parts or more, More preferably, it is 97 mass parts or more.

  The amount of the solvent used is preferably 100 to 1200 parts by mass, more preferably 100 to 1000 parts by mass, and particularly preferably 200 to 800 parts by mass with respect to 1 part by mass of the dicarboxylic acid diester.

  Examples of the acid include Bronsted acid and Lewis acid. A Bronsted acid is preferable, and among them, an organic Bronsted acid is more preferable because it has high solubility in an organic solvent and is uniformly mixed with the organic solvent.

Examples of Bronsted acids include inorganic Bronsted acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid and sulfuric acid, and formic acid, acetic acid, propionic acid, p-toluenesulfonic acid, pyridinium p-toluenesulfonic acid. , Organic Bronsted acids such as trifluoroacetic acid, trichloroacetic acid, methanesulfonic acid, and trifluoromethanesulfonic acid.
Preferred organic Bronsted acids are trifluoroacetic acid, trichloroacetic acid, methanesulfonic acid, and trifluoromethanesulfonic acid. From the viewpoint that they are easy to handle and can be easily removed from the reaction solution, Fluoroacetic acid, trichloroacetic acid and methanesulfonic acid.

  Examples of Lewis acids include phosphorus pentafluoride, boron trifluoride, boron tribromide, aluminum chloride, titanium chloride, tin chloride, antimony chloride, iron trichloride, zinc bromide, and boron trifluoride diethyl ether complex. Can be mentioned. Aluminum chloride, titanium chloride, tin chloride, and boron trifluoride diethyl ether complex are more preferable because of easy handling, and aluminum chloride and boron trifluoride diethyl ether complex are more preferable because of low cost.

  The amount of acid used is less than the molar equivalent of the dicarboxylic acid diester. Preferably it is 0.1-0.9 mol with respect to 1 mol of dicarboxylic acid diester, More preferably, it is 0.2-0.7 mol, More preferably, it is 0.3-0.5 mol.

  In step (1), when the acid and the dicarboxylic acid diester are mixed, only the dicarboxylic acid compound formed by the decomposition of the two ester bonds of the dicarboxylic acid diester and the single ester bond of the dicarboxylic acid diester are decomposed. A mixture containing the dicarboxylic acid monoester produced in this way, the unreacted dicarboxylic acid diester, the acid, and the solvent is obtained.

  The dicarboxylic acid compound and the dicarboxylic acid monoester usually precipitate from the mixture because of low solubility in a solvent. However, since the polarity of the mixture is changed by adding an acid, the solubility of the dicarboxylic acid monoester may be increased, and the dicarboxylic acid monoester may be supersaturated.

  By reducing the solubility of the dicarboxylic acid monoester in the mixture and precipitating the dicarboxylic acid monoester, side reactions of the dicarboxylic acid monoester can be suppressed, and the dicarboxylic acid monoester can be obtained in a high yield. In order to lower the solubility of the dicarboxylic acid monoester in the mixture, the rate at which the acid is added and the temperature of the mixture may be suitably controlled.

  The rate of addition of the acid is preferably 0.01 mol / hour or more and 0.4 mol / hour or less, more preferably 0.01 mol / hour or more and 0.2 mol / hour, with respect to 1 mol of the dicarboxylic acid diester. It is as follows. In particular, the rate at which half of the total amount of acid added is slower than the initial rate at which the acid is added is preferred, and the total amount of acid added is less than the rate at which half the amount is added. It is preferred that the rate of addition is slower.

  During addition of the acid, the temperature of the solution in which the dicarboxylic acid diester is dissolved in the solvent is preferably −80 ° C. or higher and 160 ° C. or lower, more preferably −15 ° C. or higher and 100 ° C. or lower, Preferably they are -15 degreeC or more and 60 degrees C or less, More preferably, they are 30 degreeC or more and 60 degrees C or less, Most preferably, they are 35 degreeC or more and 50 degrees C or less. In order to lower the solubility of the dicarboxylic acid monoester, it is preferable to lower the temperature later.

  The temperature of the mixture after the acid is added is usually -80 ° C or higher and 55 ° C or lower, preferably -15 ° C or higher and 45 ° C or lower, more preferably -15 ° C or higher and 35 ° C or lower.

  The ester bond of the dicarboxylic acid ester can be easily decomposed by mixing and stirring the mixture after adding the acid. The mixing and stirring time is usually 0.1 to 20 hours.

<Step (2)>
Dicarboxylic acid monoester can be precipitated by cooling. The dicarboxylic acid monoester once precipitated is difficult to be redissolved by heating again in the step (3), and therefore the dicarboxylic acid monoester produced in the step (4) is caused by the dicarboxylic acid monoester precipitated here. Can easily be precipitated, and therefore, the side reaction of the dicarboxylic acid monoester can be suppressed, and the dicarboxylic acid monoester can be obtained in a high yield.

  The temperature of the slurry obtained after cooling is preferably −80 ° C. or higher and lower than 30 ° C., more preferably −25 ° C. or higher and 25 ° C. or lower, and further preferably −25 ° C. or higher and 15 ° C. or lower. In order to precipitate a larger amount of dicarboxylic acid monoester, the temperature is preferably lower. However, in consideration of productivity, it may be set to a temperature at least equal to or lower than the saturation solubility of the dicarboxylic acid monoester.

  The difference between the temperature of the mixture before cooling and the temperature of the slurry obtained after cooling is preferably 10 ° C. or higher and 100 ° C. or lower, more preferably 10 ° C. or higher and 50 ° C. or lower. In order to precipitate more dicarboxylic acid monoesters, a larger temperature difference is preferable.

  The cooling is preferably performed so that the difference between the solubility of the dicarboxylic acid monoester in the mixture before cooling and the solubility of the dicarboxylic acid monoester in the slurry obtained after cooling is 10 g / L or more and 200 g / L or less. .

<Step (3)>
The temperature difference of the slurry before and after heating is preferably 10 ° C. or higher and 100 ° C. or lower, more preferably 10 ° C. or higher and 50 ° C. or lower. However, it is set to a temperature at which at least a part of the precipitated dicarboxylic acid monoester remains undissolved.

<Process (4)>
Examples of the acid include the same ones as exemplified in step (1), and it is preferable to use the same acid as that used in step (1).

  The amount of acid used may be an amount such that the sum of the amount of acid used in step (1) is usually equal to or greater than the molar equivalent of the dicarboxylic acid diester. The total amount of acid used is preferably 1 to 3 moles, more preferably 1 to 2 moles, and even more preferably 1 to 1.6 moles per mole of dicarboxylic acid diester.

The temperature of the slurry during the addition of the acid is preferably −80 ° C. or higher and lower than 30 ° C., more preferably −15 ° C. or higher and 30 ° C. or lower. In particular, to reduce the solubility of the dicarboxylic acid monoester,
It is preferable that the temperature when half of the total amount of acid added is lower than the initial temperature at which the acid is added, and the total amount of acid added is higher than the temperature when half of the acid is added. The temperature at the time is preferably lower.

  The temperature of the slurry after adding the acid is preferably −80 ° C. or higher and 60 ° C. or lower, more preferably −15 ° C. or higher and 20 ° C. or lower, and particularly preferably −15 ° C. or higher and 10 ° C. or lower.

  The ester bond of the dicarboxylic acid ester can be easily decomposed by mixing and stirring the slurry after adding the acid. The mixing and stirring time is usually 0.1 to 20 hours.

  The dicarboxylic acid monoester can be obtained by purifying the obtained slurry by a usual method. When an unreacted acid is present in the obtained slurry, it is preferable to purify after neutralizing the acid in order to suppress decomposition of the produced dicarboxylic acid monoester. Specifically, it may be purified by liquid separation, recrystallization or the like.

  Hereinafter, the present invention will be described in more detail with reference to examples. Unless otherwise specified, “%” and “parts” in the examples are% by mass and parts by mass.

From a compound represented by formula (B-3-1) (hereinafter sometimes referred to as compound (B-3-1)), a compound represented by formula (A-3-1) (hereinafter referred to as compound (A). -3-1) was produced according to the following scheme.

Reference example 1
80 g (0.28 mmol) of the compound (B-3-1) and 706 mL of n-heptane were mixed to obtain an n-heptane solution. The obtained solution was added dropwise with 35 g (0.34 mmol) of trifluoroacetic acid while being kept warm and stirred at 40 ° C., and then kept at 5 ° C. for 8 hours. LC measurement of the reaction mixture after heat insulation was performed, content of each of a compound (B-3-1), a compound (A-3-1), and a cyclohexane dicarboxylic acid was quantified, and also the compound (B-3-1) The reaction yield of the compound (A-3-1) based on the above was calculated. The results are shown in Table 2.

Reference example 2
80 g (0.28 mmol) of the compound (B-3-1) and 706 mL of n-heptane were mixed to obtain an n-heptane solution. The obtained solution was added dropwise with 35 g (0.34 mmol) of trifluoroacetic acid while being kept warm and stirred at 25 ° C., and then kept at 5 ° C. for 8 hours. LC measurement of the reaction mixture after heat insulation was performed, content of each of a compound (B-3-1), a compound (A-3-1), and a cyclohexane dicarboxylic acid was quantified, and also the compound (B-3-1) The reaction yield of the compound (A-3-1) based on the above was calculated. The results are shown in Table 2.

Example 1
<Step (1)>
80 g (0.28 mmol) of the compound (B-3-1) and 706 mL of n-heptane were mixed to obtain an n-heptane solution. The obtained solution was added dropwise with 15 g (0.13 mmol) of trifluoroacetic acid while being kept warm and stirred at 40 ° C., and then kept at 27 ° C. for 8 hours. A part of the mixture after the incubation was collected, filtered through a 0.2 μm filter, and LC measurement of the filtrate was performed to determine the solubility of the compound (A-3-1) in the mixture. The results are shown in Table 1.
<Step (2)>
By cooling the mixture obtained in the step (1) to 0 ° C. and keeping the temperature for 1 hour, the dissolved compound represented by the formula (A-3-1) was precipitated. A part of the mixture after the incubation was collected, filtered through a 0.2 μm filter, and LC measurement of the filtrate was performed to determine the solubility of the compound (A-3-1) in the mixture. The results are shown in Table 1.
<Step (3)>
The slurry in which the compound represented by the formula (A-3-1) was precipitated was heated to 15 ° C. A part of the slurry after the temperature increase was collected, filtered through a 0.2 μm filter, and the LC measurement of the filtrate was performed to quantify the solubility of the compound (A-3-1) in the slurry. The results are shown in Table 1.
<Process (4)>
21 g (0.21 mmol) of trifluoroacetic acid was added to the slurry kept at 15 ° C., and then kept at 5 ° C. for 8 hours. LC measurement of the reaction mixture after heat insulation was performed, content of each of a compound (B-3-1), a compound (A-3-1), and a cyclohexane dicarboxylic acid was quantified, and also the compound (B-3-1) The reaction yield of the compound (A-3-1) based on the above was calculated. The results are shown in Table 2.

冷却することによって溶解度が低下し、その後に昇温しても溶解度が大きくは上がらないことを確認した。

It was confirmed that the solubility was lowered by cooling, and the solubility did not increase greatly even when the temperature was raised thereafter.

  The production method of the present invention is useful as a method for producing a dicarboxylic acid monoester in a high yield.

Claims (6)

The manufacturing method of the dicarboxylic acid monoester containing the following processes (1)-(4).
Step (1): In a solution in which the dicarboxylic acid diester is dissolved in a solvent, a rate of 0.01 mol / hour to 0.4 mol / hour and a temperature of 30 ° C. to 60 ° C. with respect to 1 mol of the dicarboxylic acid diester Step (2): Step of obtaining a mixture containing a dicarboxylic acid monoester by adding an organic Bronsted acid in an amount less than the molar equivalent of the dicarboxylic acid diester at the temperature of and decomposing the ester bond of the dicarboxylic acid diester The mixture obtained in (1) is cooled so that the difference between the temperature of the mixture before cooling and the temperature of the slurry obtained after cooling is 10 ° C. or more and 100 ° C. or less, and the dicarboxylic acid monoester is precipitated. step to obtain a slurry (3): as the temperature difference of the slurry between before and after heating the slurry obtained in step (2) is 10 ° C. or higher 100 ° C. or less pressurized Step process of (4): -15 ℃ adding further acid at 30 ° C. less than, decomposing the ester bond of the dicarboxylic acid diester The method according to claim 1, wherein the difference between the temperature of the mixture before cooling and the temperature of the slurry obtained after cooling is 10 ° C or higher and 50 ° C or lower. The manufacturing method according to claim 1 or 2 , wherein the temperature difference of the slurry before and after heating in the step (3) is 10 ° C or higher and 50 ° C or lower. The production method according to any one of claims 1 to 3 , wherein the dicarboxylic acid monoester is in a supersaturated state in the mixture before cooling in the step (2) . And the solubility of the dicarboxylic acid monoester in the mixture prior to cooling, the difference between the solubility of the dicarboxylic acid monoester in solution after cooling, to any one of claims 1 to 4 or less 10 g / L or more 200 g / L The manufacturing method as described. The production method according to any one of claims 1 to 5 , wherein the dicarboxylic acid monoester is a compound represented by the formula (A), and the dicarboxylic acid diester is a compound represented by the formula (B).

[Wherein, m represents an integer of 0 to 3.
Z is methylsulfanylmethyl group, methoxymethyl group, ethoxymethyl group, tert-butoxymethyl group, 4-pentenyloxymethyl group, 2-methoxyethoxymethyl group, 1-ethoxyethyl group, benzyloxymethyl group, 4-methoxy Benzyloxymethyl group, 2-methoxybenzyloxymethyl group, 4-nitrobenzyloxymethyl group, 1-methyl-1-benzyloxy-2-fluoroethyl group, 1-methyl-1-phenoxyethyl group, 1-methyl- 1-methoxyethyl group, 1-methyl-1-benzyloxyethyl group, 2,2,2-trichloroethoxymethyl group, 1- [2- (trimethylsilyl) ethoxy] ethyl group, tetrahydropyranyl group, 3-bromotetrahydro Pyranyl group, tetrahydrothiopyranyl group, tetrahydrofuran Group, tetrahydrothiofuranyl group, tert-butyl group, trityl group, benzyl group, 4-methoxybenzyl group, 3,4-dimethoxybenzyl group, 4-nitrobenzyl group, 1,3-benzodithiolan-2-yl A group, 2,2,2-trichloroethyl group, 2-phenyl-2-ethanon-1-yl, cyclopropylmethyl group, —CH ₂ —O—SiR ⁵ R ⁶ R ⁷ or —SiR ⁵ R ⁶ R ⁷ . Represent.
R ⁵ , R ⁶ and R ⁷ each independently represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, a phenyl group or a benzyl group.
p represents 0 or 1. ]