WO1992018459A1

WO1992018459A1 - Benzoic ester compound and production thereof

Info

Publication number: WO1992018459A1
Application number: PCT/JP1992/000481
Authority: WO
Inventors: Naoki Hanayama; Kenji Sakanashi; Shuuichi Wakamatsu
Original assignee: Yoshitomi Pharmaceutical Industries, Ltd.
Priority date: 1991-04-18
Filing date: 1992-04-15
Publication date: 1992-10-29

Abstract

A process for producing a mono- or dibenzoate of a glycol compound by the transesterification between a benzoic ester and a glycol in the presence of monobutyltin oxide, dibutyltin oxide, zinc oxide and zinc acetate; and a novel halogenated benzoic ester. The obtained compound is useful as the starting material of industrial chemicals and polymers. This process can provide an objective compound readily in a high yield.

Description

Specification

Benzoic acid ester compound and method for producing the same

"Technical field"

The present invention relates to a method for producing a benzoic acid ester useful as a raw material for industrial chemicals and polymers, and to certain novel benzoic acid ester compounds.

`` Background technology J

JP-A-52-29826 discloses that an acrylic polymer is mixed with an ester of p-hydroxybenzoic acid such as p-hydroxybenzoic acid 6-hydroxyhexyl ester and glycol. No. 4,487,917 discloses an improved processability containing a hydroxyalkyl p-hydroxybenzoate. Polyester-carbonate copolymers are disclosed.

In producing these esters of p-hydroxybenzoic acid and glycol, direct esterification, i.e., reaction of the hydroxybenzoic acids and glycols in the absence of a catalyst or in the presence of an acid catalyst, to form a monoester or diester However, it is difficult to implement them industrially because by-products other than monoesters and diesters are generated to a degree that cannot be ignored. In addition, a transesterification reaction, that is, a method of reacting a hydroxybenzoic acid ester with a glycol in the presence of a catalyst to obtain a monoester or a diester can be naturally considered. However, when a transesterification reaction is performed using protonic acid or metal acetyl acetate as a catalyst, monoesters and diesters still remain. Outside by-products produce significant quantities. In addition, catalysts such as metal alcohols which do not exhibit transesterification ability do not show any transesterification ability. In addition, in order to selectively obtain a monoester of glycol by transesterification, it is desirable to charge an excess of glycol to the benzoate, balance the monoester side, and suppress the formation of diester . At this time, as a method for removing the excessively charged glycol, a method may be considered in which the glycol is dissolved in water to separate the glycol from the monoester, but the reaction product obtained after the completion of the reaction is directly subjected to a distillation operation. It is simple to distill off the excess glycol and economical with no waste water. However, since a catalyst having transesterification activity remains as it is in the reaction product, there is a problem that the equilibrium shifts and the diester content increases as glycol recovery by distillation proceeds. Accordingly, an object of the present invention is to solve the above-mentioned problems, that is, to provide a method for obtaining a monoester or diester of a hydroxybenzoic acid and a glycol with a low conversion of by-products and a high conversion. It is another object of the present invention to provide a novel benzoate compound.

"Disclosure of Invention J

In the ester exchange reaction of benzoic esters and glycols, the use of organotin compounds, zinc oxide or zinc carboxylate in the ester exchange reaction of benzoic acid esters and glycols resulted in fewer by-products and higher conversion. At the same time as the reaction progresses, a new industrially useful compound was found, and the present invention was achieved. That is, the present invention relates to a general formula

[In the formula, X represents hydrogen, a lower alkyl group, a lower alkoxy group, or halogen (when m represents 2, may be the same or different), m represents 1 or 2, and R ¹ represents a lower alkyl group. A benzoic acid ester represented by the following general formula (I):

^{H 0 - R 2 - 0 H} (I)

(Wherein, R ² represents a residue other than the hydroxyl group of glycol.) (Hereinafter referred to as the compound of the general formula (H)). General formula characterized by reacting in the presence of zinc carboxylate

(Wherein n represents 0 or 1, and the other symbols have the same meanings as described above.) A method for producing a benzoate compound [hereinafter, referred to as a compound of the general formula (I)], and a general formula

(Wherein, Y represents halogen, and R ² and m have the same meanings as described above.) A novel benzoic acid ester compound represented by

(The compound of ()).

In the present specification, a lower alkyl group means a linear or branched alkyl having 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, and tertiary butyl. The lower alkoxy group means a straight-chain or branched-chain alkoxy having 1 to 4 carbon atoms such as methoxy, ethoxy, propoquine, isobroboxy, butoxy and tertiary butoxy. Halogen is chlorine, bromine, iodine or fluorine. Residues other than the hydroxyl group of glycol include ethylene glycol, 1,3-brobandiol, 1,6-hexanediol, 1,8-octanediol, 1,12-dodecanediol, diethylene glycol, and It represents a residue obtained by removing a hydroxyl group from glycols having preferably 2 to 12 carbon atoms, such as ethylene glycol, tetraethylene glycol, and 1,4-hexanedimethanol.

—Specific examples of the compound of formula (I) include methyl 4-hydroxybenzoate, methyl 3-hydroxybenzoate, methyl 2-hydroxybenzoate, and 3-chloro-4-hydroxy. Methyl hydroxybenzoate, 3,5-dichloro-4-methyl hydroxybenzoate, 3-hydroxymethyl 4-methylbenzoate, 4-hydroxy-3-methyl benzoate, and the like.

Specific examples of the compound represented by the general formula (II) include ethylene glycol, 1,3-propanediol, 6-hexanediol, 1,8-octanediol, 1,12-dodecanediol, Examples include ethylene glycol, triethylene glycol, tetraethylene glycol, and 1,4-hexanedimethanol.Organic tin compounds include monobutyl tin oxide, dibutyl methoxide, tributyl tin oxide and monobutyl tin oxide Chloride, dibutyltin chloride, tributyltin chloride, dibutyltin dilaurate, dioctyltin oxide, diphenyltin oxide, or a mixture thereof, particularly monobutyltin oxide, dibutyltin oxide. Is preferred. Examples of the carboxylic acid zinc salt include zinc acetate, zinc octylate, zinc stearate, zinc naphthenate, and zinc terephthalate.

One of the features of the present invention is that when the transesterification reaction is carried out in the presence of zinc oxide or a zinc carboxylate, after adding a specific chelating agent, the unreacted glycol compound is distilled off to obtain the reactant. When the solvent is distilled off, the equilibrium transfer of the reaction is suppressed, and the monoester in the compound of the general formula (I) is obtained in high yield. Such a chelating agent is a compound which shares at least a nitrogen atom and a plurality of carboxyl groups or carboxylate groups in one molecule, and specifically includes ethylenediaminetetraacetic acid and methylentriamine. Pentaacetic acid, triethylenetriaminehexanoic acid, N-hydroxyshethylethylenediamin triacetic acid, nitric triacetate and their alkali metal salts (such as sodium salt and potassium salt)ミ amine salt.

— The number of moles of the compound of the general formula (Π) per mole of the compound of the general formula (I) is determined based on whether the target compound is a monoester Depending on whether the compound is an ester, the compound of the general formula (m) is used in an amount of about 1 to 10 mol when the monoester is the target compound, and the compound of the general formula (m) is used when the ester is the target product. 0.4 to o.

It is desirable to charge about 6 mol. The catalyst selected from the organotin compound, zinc oxide and zinc carboxylate may be used in a catalytic amount, and is used in an amount of about 0.1 to 5% based on the weight of the compound of the general formula (I). Anti応温degree 1 0 0 to 2 0 0 ^e C, preferably 1 3 0-1 7 0 Dedea Ru o

Lower alcohols such as methanol produced by the transesterification reaction may be removed from the system at normal pressure or reduced pressure, or the solvent may be added to the reaction system while adding a solvent such as toluene or xylene to the reaction system. May be removed from the system by azeotropy. The reaction time varies depending on the amount of the etchant used and the reaction temperature, but is usually about 5 to 20 o

After the transesterification reaction using the organotin compound, if there is excess glycol, distill the glycol out of the system by distillation, or add water to the reaction product to convert the glycol to an aqueous layer. It may be removed by a method such as transfer. The obtained crude product can be further purified by an ordinary method such as recrystallization or column chromatography.

After completion of the ester exchange reaction in the presence of zinc oxide or zinc carboxylate, if the residual glycol is very small, for example, when the target product is a diester, a solvent is added to the reaction product, and water is added. After removing the glycol by washing with a solvent, the solvent is distilled off to obtain a crude product of the desired diester. Also, if the target is a monoester When excess glycol is present as in the case of (1), water can be added to the reaction product and removed by a method such as transfer of the glycol to an aqueous layer. It is more preferable to add a chelating agent to the mixture and deactivate the catalyst, and then distill off glycol by distillation. It is better to add the chelating agent in the form of an aqueous solution. Next, when the distillation residue is diluted with an organic solvent, the chelate compound precipitates as a solid, and can be separated by filtration. In addition, since the chelate compound is water-soluble, it may be removed by washing with water. After removing the chelate compound, the solvent is distilled off to obtain a crude ester. The obtained crude product of monoester or diester can be further purified by a usual method such as recrystallization, column chromatography and the like.

Next, the present invention will be described with reference to examples, but the present invention is not limited thereto.

Example 1

4-Methyl hydroxybenzoate 30.4 g, 1,3-Brono. 7.6 g of didiol and 0.05 g of dibutyltin oxide were placed in a flask and heated and stirred. From the point when the temperature of the reaction product reached 150, the dropwise addition of toluene was started, and from 150 to 155. (: In a period of 12 hours, 200 ml of toluene was added dropwise, and the distillate was removed outside the system. After the reaction was completed, ethyl acetate was added, the organic layer was washed with water, and unreacted 1,3-propanediol was added. After removal of the solvent, the solvent was distilled off to obtain 29 g of a residual residue, which was found to have a content of 92 area% according to HPLC analysis, and a part thereof was purified by silica gel chromatography. , 3 — bis (4-hydroxybenzoyloxy) propane A white powder was obtained. With melting point 1998-200

Example 2

74.6 g of methyl 3-chloro-4-hydroxybenzoate, 23.6 g of 1.6-hexanediol, and 0.1 g of monobutyltin oxide were placed in a flask, and the reaction temperature was 150 to 160. The reaction was continued while removing the distillate out of the system at a decompression pressure of 200 to 60 mmHg for 12 hours. After completion of the reaction, the mixture was treated in the same manner as in Example 1 to obtain 84 g of a concentrated residue. According to the HPLC analysis, the content of the target substance was 89 area. White powder of 1,6-bis (3-chloro-4-hydroxybenzoyloxy) hexane was obtained by silica gel column chromatography. Melting point 1 3 4 to 1 3 7

Example 3

Methyl 3-chloro-4-hydroxybenzoate (37.3 g), 1,3-propanediol (7.6 g) and monobutyltin oxide (0.1 g) were placed in a flask, and stirring with heating was started. When the temperature of the reaction product reached 150 ° C, the dropwise addition of toluene was started, and the amount of toluene was dropped from 100 to 150 mL over a period of 8 hours from 1450 to 1555. Removed. After the completion of the reaction, toluene and excess 1,3-propanediol were distilled off under reduced pressure, ethyl ether was added, and the organic layer was washed with water to remove the remaining 3-propanediol and the solvent was removed. Evaporation gave 45 g of crude crystals. According to HP LC analysis, the contents of monoester and diester were 95 area and 4 area%, respectively. An aliquot was taken and purified by silica gel column chromatography to obtain white crystals of 3-chloro-4-hydroxybenzoic acid 3-hydroxybutyrate pill ester. Melting point 109-1 Example 4

Methyl 4-hydroxybenzoate (30.4 g), triethylene glycol (15. Og), and monobutyltin oxide (0.1 g) were placed in a flask, and heating stirring was started. From the time the internal temperature reached 150, the dropwise addition of toluene was started, and from 150 to 160, 25 O ml of toluene was added dropwise in 14 hours, and the distillate was removed from the system. Removed. After the completion of the reaction, ethyl diethyl phosphate was added, the organic layer was washed with water, and unreacted triethylene glycol was removed. Then, the solvent was distilled off to obtain an oily target product.

Example 5

30.4 g of methyl 4-hydroxybenzoate, 7.6 g of 1,3-brono, ethylene glycol and 0.2 g of zinc oxide were placed in a flask, and heating and stirring were started. When the temperature of the reactant reached 140, the dropwise addition of toluene was started, and between 140 and 150, 200 ml of toluene was added dropwise in 12 hours, and the distillate was out of the system. Removed. After completion of the reaction, ethyl acetate was added, the organic layer was washed with water, and unreacted 1,3-propanediol was removed. Then, the solvent was distilled off to obtain 33 g of a concentrated residue.

According to the HPLC analysis, the content of the target substance was 90 areas. A part thereof was purified by silica gel column chromatography to obtain a white powder of 1,3-bis (4-hydroxybenzoyloxy) propane. With melting point 1998-200

Example 6

3 —Methyl chloro-4-hydroxyhydroxybenzoate 74.6 g, 1, '3 —Propanediol 15.2 ^, 0.2 g of zinc acetate are placed in a flask, and the reaction temperature is 150 to 1555. ^e C, Decompression degree 200 to 60 m The reaction was continued for 7 hours at mHg while distillate was removed from the system. After the completion of the reaction, the same treatment as in Example 5 was performed to obtain 74 g of a concentrated residue.

According to HPLC analysis, the content of the target substance was 89 area%. A white powder of 1,3-bis (3-chloro-4-hydroxybenzoyloxy) propane was obtained by silica gel column chromatography. With a melting point of 16 0 to 16 3

Example 7

30.4 g of methyl 4-hydroxybenzoate, 76 lg of 1,3-propanediol and 0.1 lg of zinc oxide were placed in a flask, and ripening and stirring was started. From the time when the temperature of the reaction product reached 150, toluene dripping was started, and from 150 to 155, 100 ml of toluene was dropped in 8 hours, and the distillate was removed outside the system. . After the reaction was completed, ethyl acetate was added to the reaction product, the organic layer was sufficiently washed with water to remove the remaining 1,3-propanediol, and the solvent was distilled off to obtain 32 g of crude crystals. According to HPLC analysis, the monoester and the ester content were 95 area and 4 area%, respectively. An aliquot was taken and purified by silica gel column chromatography to obtain white crystals of 4-hydroxybenzoic acid 3-hydroxypropyl ester. Melting point 100 ~ 103

Example 8

30.4 g of methyl 4-hydroxybenzoate, 94.5 g of 1,6-hexanediol and 0.3 g of zinc acetate were placed in a flask, and heating and stirring were started. The reaction was continued at an internal temperature of 160, at normal pressure for 1 hour, and under reduced pressure of 500 to 20 mmHg for 7 hours. After the completion of the reaction, the reaction mixture was treated with sodium ethylenediaminetetraacid salt (hereinafter referred to as EDT). (Abbreviated as A4Na) 0.8 g dissolved in 5 ml of water was added, and the mixture was stirred for 0.5 hour, and then under reduced pressure of 2 to 5 mmHg, excess 1,6-monohexanediol was added. Was distilled off. Ethyl acetate and toluene were added to the residue, and the precipitated solid was removed by filtration. The solution was cooled and the precipitated crystals were filtered to obtain white powder of 4-hydroxybenzoic acid 6-hydroxyhexyl ester. Melting point 97-98 ° C Example 9

37.3 g of methyl 3-chloro-4-hydroxybenzoate, 94.5 g of 1,6-hexanediol, and 0.3 g of zinc oxide were placed in a flask and reacted in the same manner as in Example 8. . After completion of the reaction, the same treatment as in Example 8 was carried out except that the amount of EDTA 4 Na was changed to 1.8 g, to obtain a white powder of 3-chloro-4-hydroxybenzoic acid 6-hydroxyhexyl ester. Was. Mp 78-80 'C

Example 10

3—Methyl 3-chloro-4-hydroxybenzoate 37.3 g, 1,3-propanediol 76.12, and zinc nitrate 0.2 g were placed in a flask, and heating and stirring were started. The reaction was carried out at 140 at normal pressure for 2 hours and at 500 to 200 mmHg for 8 hours. According to gas chromatography, the composition at the end of the reaction was 3-methyl-3-chloro-4-hydroxybenzoate 3.6 areas, 3-chloro-4-hydroxybenzoic acid 3-hydroxypropyl ester 9 4. 5 area%, 1,3-bis (3-chloro-4-hydroxybenbuyloxy) propane 3 planes 穑%. A solution prepared by dissolving 0.5 g of EDTA4Na in 3 ml of water was added to the reaction mixture, and the mixture was stirred at 80 for 0.5 hour, and then the excess 1 was reduced under reduced pressure of 30 to 15 mmHg. , 3 — propane The diol was distilled off. The composition of the enriched residue is 3-chloro-methyl 4-hydroxymethyl benzoate 2.2 area%, 3-chloro-4-hydroxybenzoic acid 3-hydroxypyrucyl ester 95.4 area%, 1 , 3-bis (3-chloro-4-hydroxybenzoyloxy) propane was 1.8 area%. Thereafter, the same treatment as in Example 8 was carried out to obtain a white powder of 3-chloro-4-hydroxybenzoic acid 3-hydroxypropyl pill ester. Example 11 with a melting point of 109 to 110

The charging and the reaction were carried out exactly as in Example 10. According to gas chromatography, the composition at the end of the reaction was 3-methyl-3-chloro-4-hydroxybenzoate 3.5 area%, 3-chloro-4-hydroxybenzoic acid 3-hydroxybutyryl ester 9 3. 6 areas, 1,3-bis (3-chloro-4-hydroxybenzoyloxy) propane 2.0 areas. Without addition of EDTA 4Na to the reaction product, excess 1,3-propanediol was distilled off under a reduced pressure of 30 to 15 mmHg. The composition of the concentrated residue is 0.1 area% methyl 3-chloro-4-hydroxybenzoate, 3-chloro-4-hydroxybenzoic acid 3-hydroxypropyl pill ester 75.7 area%, 1, 3 —Bis (3-chloro-4-hydroxybenzoyloxy) propane 23.9 Area 7

Example 1 2

Methyl 3-chloro-4-hydroxyhydroxybenzoate 152.2 g, 1,5—pentanediol 5.20.7 g and zinc nitrate 1.5 g were placed in a flask and placed at 160 ^e C for 8 hours. , 200 ~ 50 mmH The mixture was stirred and reacted under reduced pressure of g. After completion of the reaction, 2.7 g of EDTA-4Na and 5 O ml of water were added to the reaction mixture, and after stirring for 0.5 hour, water was distilled off under reduced pressure, and then under reduced pressure of l to 5 mmHg. The excess 1,5-pentanediol was distilled off. Acetonitrile was added to the residue, and solids were removed by filtration. The filtrate was cooled, and the precipitated crystals were collected to give 3-chloro-4-hydroxybenzoic acid 5-hydroxypentyl ester. A white powder was obtained. 95-97. C

Example 13

The reaction and treatment were carried out in the same manner as in Example 12 except that 1,5-pentanediol was changed to 80,1.3 g of 1,9-nonanediol in Example 12, to give 3-chloro-4-hydroxy. A white powder of benzoic acid 91-hydroxyxynonyl ester was obtained. As shown in melting point 8 2~ 8 4 ^e C Example, commercially useful benzoate compound obtained by the present invention, and easily and in high yield benzoic acids and glycol ethers by the method of the present invention Thus, a monoester or diester of the above is obtained.

Although the present invention has been adequately and fully described in the foregoing specification and the examples contained therein, they can be changed or modified without departing from the spirit and scope of the invention.

Claims

Claims General formula

[In the formula, X represents hydrogen, a lower alkyl group, a lower alkoxy group or halogen (when m represents 2, may be the same or different), m represents 1 or 2, and R ¹ represents a lower alkyl group. The hydroxybenzoic acid ester represented by the general formula

HO - R ² - 0 H

(In the formula, R ² represents a residue other than the hydroxyl group of glycol.) At least one kind selected from organotin compounds, zinc oxide and zinc carboxylate General formula characterized by reacting in the presence of a catalyst

(I)

(In the formula, n represents 0 or 1, and the other symbols have the same meanings as described above.)

2. The method according to claim 1, wherein the organotin compound is monobutyltin oxide or dibutyltin oxide.

3. The reaction product obtained by the reaction in the presence of zinc oxide or zinc carboxylate contains at least a nitrogen atom and multiple 2. The method according to claim 1, wherein, after adding a carboxyl group or a chelating agent sharing a carboxylate group, unreacted products of the glycol compound are removed from the reaction product by distillation.

4. General formula

(Wherein, Y represents a halogen, m represents 1 or 2, and R ² represents a residue other than a hydroxyl group of glycol.).