JP5790430B2 - Process for producing and purifying hydroxyadamantanecarboxylic acids - Google Patents

Description

  The present invention has an adamantane skeleton and is excellent in optical properties, heat resistance, acid dissociation properties, etc., and optical materials such as cross-linked resins, optical fibers, optical waveguides, optical disk substrates, and photoresists, raw materials thereof, pharmaceutical and agricultural chemical intermediates The present invention relates to a novel method for producing hydroxyadamantanecarboxylic acids useful as a body and other various industrial products.

  A compound having an adamantane skeleton has a rigid structure and exhibits high heat resistance and optical properties, so that it is known to be useful for highly functional resin materials, pharmaceutical intermediates, optical materials, photoresist materials, and the like. (For example, refer patent documents 1-4). Among them, hydroxyadamantanecarboxylic acids having a hydroxyl group and a carboxyl group in the same molecule are excellent in heat resistance and can be used as a unique resin material and pharmaceutical intermediate by utilizing the difference in reactivity between the hydroxyl group and the carboxyl group. Because it is useful.

Hydroxyadamantanecarboxylic acids are known to be produced from adamantanediols as by-products when producing adamantanedicarboxylic acids by the Koch reaction (see Patent Document 5), but they are produced using hydroxyadamantanecarboxylic acids as the target product. No method has been shown so far.
In addition, hydroxyadamantanecarboxylic acids and adamantanedicarboxylic acids have a problem that their polarities are very close to each other, so that they are difficult to separate by ordinary purification methods.

JP-A-6-0305044 Japanese Patent Publication No. 1-53333 Japanese Patent Laid-Open No. 4-39665 JP 2006-016379 A JP 2010-150220 A

  The present invention provides a method for obtaining hydroxyadamantanecarboxylic acids as main products from adamantanediols, and further provides a specific purification method for a mixture containing hydroxyadamantanecarboxylic acids and adamantanedicarboxylic acids obtained by the reaction or the like. It is an object to obtain high purity hydroxyadamantane dicarboxylic acids by using them.

  As a result of intensive studies on the above problems, the present inventors have obtained a target hydroxyadamantanecarboxylic acid by using a specific amount of carbon monoxide source when converting the hydroxyl group of adamantanediol into a carboxyl group by the Koch reaction. Obtaining as a main product and finding a method for precipitating and removing adamantane dicarboxylic acids using a polar solvent and water with respect to a mixture of hydroxyadamantane carboxylic acids and adamantane dicarboxylic acids as obtained by the reaction, The present invention has been reached.

  According to the present invention, an optical material such as a crosslinkable resin, an optical fiber, an optical waveguide, an optical disk substrate, a photoresist, etc. having an adamantane skeleton and excellent in optical properties, heat resistance, acid dissociation properties, etc. Provided are a method for producing hydroxyadamantanecarboxylic acids which can efficiently produce hydroxyadamantanecarboxylic acids useful as an agrochemical intermediate and other various industrial products, and a method for purifying hydroxyadamantane containing adamantanedicarboxylic acids as impurities.

  Hereinafter, embodiments of the present invention will be described in detail.

The present invention is as follows.
1.
The adamantanediol represented by the general formula (1) is reacted in a liquid protonic acid solvent with a carbon monoxide source of 2 equivalents or less per 1 equivalent of the hydroxyl group of the adamantanediol, and then represented by the general formula (2). A method for producing hydroxyadamantanecarboxylic acids, wherein the crystals of hydroxyadamantanecarboxylic acid are filtered off.
(1)
(In the formula, X is the same or different and represents a hydrogen atom, an alkyl group or an alkoxy group, and n represents an integer of 14.)
(2)
(In the formula, X is the same or different and represents a hydrogen atom, an alkyl group or an alkoxy group, and n represents an integer of 14.)
2.
The method for filtering the crystals is the following (i) to (iii):
(I) adding water to the reaction solution and filtering the precipitated crystals;
(Ii) Crystals deposited by adding water to the reaction solution are filtered out, an alkaline aqueous solution and an organic solvent are added to the obtained crystal, the alkaline aqueous solution and the organic solvent are separated, and an acidic aqueous solution is added to the alkaline aqueous solution. In addition, the precipitated crystals are filtered out.
(Iii) An alkaline aqueous solution and an organic solvent are added to the reaction solution, the alkaline aqueous solution and the organic solvent are separated, an acidic aqueous solution is added to the alkaline aqueous solution, and the precipitated crystals are separated by filtration.
Which is one of the following methods: The manufacturing method as described in.
3.
The carbon monoxide source is at least one selected from the group consisting of carbon monoxide, formic acid, and alkyl formate. Or 2. The manufacturing method as described in.
4).
A method for purifying a mixture containing at least an adamantanedicarboxylic acid represented by the general formula (3) as an impurity, the main component being a hydroxyadamantanecarboxylic acid represented by the general formula (2), the purification method comprising: A method for purifying hydroxyadamantanecarboxylic acids, wherein the adamantanedicarboxylic acid is precipitated and removed by crystallization using a polar organic solvent and water.
(3)
(In the formula, X is the same or different and represents a hydrogen atom, an alkyl group or an alkoxy group, and n represents an integer of 14.)
5.
3. The mixture further contains an adamantane monocarboxylic acid represented by the general formula (4). The purification method according to 1.
(4)
(Wherein X is the same or different and represents a hydrogen atom, an alkyl group or an alkoxy group, and n represents an integer of 15)
6).
In the crystallization method, the mixture is dissolved in a polar organic solvent, and then water is added to precipitate and remove the adamantane dicarboxylic acid. Or 5. The purification method according to 1.
7).
3. The polar organic solvent is at least one selected from the group selected from methanol, ethanol, propanol, 2-propanol, tetrahydrofuran, 1,4-dioxane, dimethylformamide, and dimethyl sulfoxide. ~ 6. The purification method according to any one of the above.
8).
The usage-amount of the said polar organic solvent is 4-40 mass times with respect to the said mixture. ~ 7. The purification method according to any one of the above.
9.
3. The amount of water used is 3 to 5 times by mass with respect to the polar organic solvent. ~ 8. The purification method according to any one of the above.
10.
The mixture is 1. ~ 3. 3. It is obtained by the method for producing a hydroxyadamantanecarboxylic acid according to any one of 4). ~ 9. The purification method according to any one of the above.

The adamantanediols used in the present invention are represented by the general formula (1). Specifically, 1,3-adamantanediol, 5-methyl-1,3-adamantanediol, 5,7-dimethyl-1,3-adamantanediol, 5,7-diethyl-1,3-adamantanediol, 5 -Methoxy-1,3-adamantanediol, 5-ethoxy-1,3-adamantanediol, 5-propoxy-1,3-adamantanediol, 5-butoxy-1,3-adamantanediol and the like.
In particular, 1,3-adamantanediol is preferable because it is easy to procure raw materials.

As the solvent in the present invention, liquid protonic acid is used because the reaction can be carried out smoothly. For example, organic acids (organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, citric acid, tartaric acid, organic sulfonic acids such as ethanesulfonic acid, propanesulfonic acid, trifluoromethylsulfonic acid, etc.), inorganic acids (for example, Hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, etc.), and sulfuric acid is preferred from the viewpoint of selectivity in the reaction of the hydroxyadamantanecarboxylic acid obtained therein.
In particular, when sulfuric acid is used, the concentration of concentrated sulfuric acid used is preferably an aqueous solution of 90% by mass or more, more preferably an aqueous solution of 96% by mass or more from the viewpoint of the conversion rate of hydroxyl groups.

  The amount of the liquid protic acid solvent used is 2 to 20 times by mass, preferably 4 to 16 times by mass, more preferably 4 to 6 times by mass with respect to the adamantanediol. Within this range, the carboxylation reaction of the hydroxyl group proceeds sufficiently, and the separation step can be performed with a small amount of organic solvent or water.

In this reaction, a carbon monoxide source is used to convert a hydroxyl group into a carboxyl group. As the carbon monoxide source, carbon monoxide, formic acid, and alkyl formate are used.
Carbon monoxide may be pure carbon monoxide or may be used after diluted with an inert gas. Carbon monoxide may be used under normal pressure or under pressure using an autoclave.
Formic acid and formic acid alkyl ester can be used reagents or industrial chemicals.

Specific examples of the alkyl formate include methyl formate, ethyl formate, propyl formate, butyl formate, pentyl formate, hexyl formate, heptyl formate, octyl formate, nonyl formate, decanyl formate, cyclohexyl formate and the like.
Among these, methyl formate is preferable because it is inexpensive and easy to handle.

  As for the usage-amount of a carbon monoxide source, 2 equivalent or less is used with respect to 1 equivalent of hydroxyl groups of adamantanediol. When the amount is more than 2 equivalents, adamantane dicarboxylic acids are produced as main products, and the desired hydroxyadamantane carboxylic acids are hardly obtained. Moreover, it is preferable to use 0.9-2 equivalent in order to manufacture the target hydroxyadamantanecarboxylic acid with sufficient yield. Furthermore, it is particularly preferable to use it at 0.9 to 1.2 equivalents.

Next, the reaction conditions of the present invention will be described in detail.
The reaction temperature is, for example, −78 to 200 ° C., preferably −20 to 100 ° C., more preferably about 0 to 80 ° C. Within this range, the carboxylation reaction of the hydroxyl group proceeds sufficiently and the side reaction proceeds little.
In addition, the reaction pressure is not particularly limited, and the reaction can be performed at normal pressure or under pressure.

  The reaction time is not particularly limited as long as the carbon monoxide source is sufficiently converted, but it is preferably 1 to 100 hours, more preferably 1 to 10 hours. This is because by carrying out the reaction within this range, the carboxylation can be sufficiently advanced and the production efficiency can be made compatible.

After completion of the carboxylation reaction, the target dihydroxyadamantanecarboxylic acid is filtered off to obtain the target dihydroxyadamantanecarboxylic acid. The filtering method is not particularly limited, but the following three methods are particularly effective in precipitating the hydroxyadamantanecarboxylic acids and having few impurities.
(I) Water is added to the reaction solution to precipitate crystals, which are filtered off.
(Ii) Crystals deposited by adding water to the reaction solution are filtered out, an alkaline aqueous solution and an organic solvent are added to the obtained crystal, the alkaline aqueous solution and the organic solvent are separated, and an acidic aqueous solution is added to the alkaline aqueous solution. In addition, the precipitated crystals are filtered off.
(Iii) An alkaline aqueous solution and an organic solvent are added to the reaction solution, and the alkaline aqueous solution and the organic solvent are separated, and an acidic aqueous solution is added to the alkaline aqueous solution and the precipitated crystals are separated by filtration.

  The amount of water added for precipitating crystals by the operations of (i) and (ii) is 1 to 20 times, preferably 1 to 10 times, more preferably 2 to the proton acid solvent used in the reaction. It carries out by 5 mass times. Within this range, the sulfuric acid is sufficiently diluted, and the residue of the hydroxyadamantanecarboxylic acid in the solution is reduced.

Examples of the alkali in the alkaline aqueous solution added in the operations (ii) and (iii) include tetraalkyls such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, ammonium hydroxide, and tetramethylammonium hydroxide. Examples thereof include ammonium hydroxides, and sodium hydroxide is particularly preferable because it is inexpensive and easy to handle.
The concentration of the alkaline aqueous solution is preferably 1 to 30% by mass, and more preferably 10 to 20% by mass.
The amount of the alkaline aqueous solution to be added is 1 to 10 times by mass with respect to the raw material adamantane diol in the operation (ii), and 10 with respect to the raw material adamantane diol in the operation (iii). Use a mass to 40 mass times and add until the pH is on the alkaline side.

In addition, the organic solvent added in the operations of (ii) and (iii) is not particularly limited as long as hydroxyadamantanecarboxylic acids can be dissolved. For example, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, pentyl acetate, Esters such as hexyl acetate, methyl formate, ethyl formate, propyl formate, butyl formate, pentyl formate, hexyl formate, methyl propionate, ethyl propionate, propyl propionate, butyl propionate, pentyl propionate, hexyl propionate, butanol , Alcohol compounds such as pentanol, hexanol, heptanol, octanol, methyl ethyl ketone, methyl isobutyl ketone, 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone, cyclopentanone, cyclohexanone Ketone compounds such as non thereof. Of these, ethyl acetate is preferred from the viewpoint of dissolution efficiency.
Moreover, the quantity of the organic solvent to add uses 1-100 mass times with respect to raw material adamantanediol, Preferably it is 1-20 mass times, More preferably, 2-20 mass times is used. There is no particular limitation on the number of extractions.

Furthermore, examples of the acid of the acidic aqueous solution added in the operations (ii) and (iii) include aqueous solutions of inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and sulfuric acid is particularly preferable because it is inexpensive and easy to handle.
As for the density | concentration of acidic aqueous solution, 1-30 mass% is preferable, More preferably, the aqueous solution of a density | concentration of 10-20 mass% is used.
The amount of the acidic aqueous solution to be added is 1 to 20 times by mass and is added until the pH becomes acidic.

  As a filtration method, a general filtration method such as natural filtration using a filter, vacuum filtration, pressure filtration, and centrifugal filtration can be used.

  Specifically, the above operation is exemplified by adding 4.0 mass times concentrated sulfuric acid to 1.0 mol of 1,3-adamantanediol represented by the formula (5), and stirring formic acid as a carbon monoxide source while stirring 1.0 mol (0.5 equivalent with respect to the hydroxyl group of adamantanediol) was added dropwise, and the mixture was allowed to react at 35 ° C. with stirring at normal pressure for 3 hours. Then, ethyl acetate and sodium hydroxide aqueous solution were added to the reaction solution. In addition, liquid separation is performed, and an aqueous solution of sulfuric acid is added to the resulting aqueous layer to precipitate hydroxyadamantanecarboxylic acids, and crystals are obtained by filtration to produce hydroxyadamantanecarboxylic acids.

(5)

Next, a method for purifying a mixture containing at least an adamantanedicarboxylic acid represented by the general formula (3) as an impurity and containing a hydroxyadamantanecarboxylic acid as a main component will be described in detail.
In the present invention, a polar organic solvent and water are added to the mixture to precipitate crystals of adamantanedicarboxylic acids as impurities, and the crystals are removed by filtration or the like to purify the hydroxyadamantanes.
In the mixture, a compound having an adamantane skeleton may be present. For example, adamantanecarboxylic acids represented by the general formula (4) can be efficiently removed by the present invention.

A polar organic solvent is used as one of the solvents used in the present invention. By using a polar organic solvent with water, it is possible to adjust so that hydroxyadamantanecarboxylic acids are dissolved and adamantanedicarboxylic acids are not dissolved.
Examples of the polar organic solvent include alcohol compounds such as methanol, ethanol, propanol and 2-propanol, ether compounds such as tetrahydrofuran and 1,4-dioxane, dimethylformamide and dimethyl sulfoxide, and particularly methanol, ethanol, propanol, 2 Alcohol compounds such as -propanol are preferred because the difference in solubility between hydroxyadamantanecarboxylic acids and adamantanedicarboxylic acids is large and the adamantanedicarboxylic acids can be easily separated.
These polar organic solvents can use 1 type (s) or 2 or more types.
Although there is no restriction | limiting in particular as the usage-amount of the organic solvent to be used, 4-40 mass times is preferable with respect to the said mixture from a viewpoint of fully melt | dissolving hydroxyadamantanecarboxylic acids, and it is 4-10 mass times especially. preferable.

Water used in the present invention has an effect of reducing the solubility of adamantane dicarboxylic acids in a solvent and facilitating precipitation of crystals of adamantane dicarboxylic acids.
The amount of water to be used is not particularly limited as long as it can be separated by precipitation of adamantane dicarboxylic acids, but in order to obtain hydroxyadamantane carboxylic acids with good yield, use 3 to 5 times by mass with respect to the polar organic solvent. It is preferable to do.

  In the present invention, the order in which the polar organic solvent and water are added is not particularly limited, but the method of dissolving the mixture in the polar organic solvent and then adding water to precipitate the crystals is particularly effective for removing adamantanecarboxylic acids. Is preferable.

  In the present invention, adamantanedicarboxylic acids and the like are removed by filtration, and the target hydroxyadamantanecarboxylic acids are present in a state of being dissolved in the filtrate. Therefore, the polar organic solvent in the filtrate is distilled off to obtain hydroxyadamantanecarboxylic acids. Obtained by precipitation. At that time, it may be dried, but by concentrating the filtrate 2 to 20 times, other trace impurities can also be efficiently removed, and the purity of hydroxyadamantanecarboxylic acid can be improved.

  Hereinafter, the contents of the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples.

Example 1
(1) Carboxylation step 50 g of 1,3-adamantanediol (purity 96%) was charged into a flask equipped with a stirrer, a thermometer, a dropping funnel, and a Dim funnel, and 200.7 g of concentrated sulfuric acid was added. The flask was heated in a 35 ° C. water bath and stirred for 30 minutes, and then 13.7 g of formic acid was added dropwise over 1 hour while maintaining the reaction temperature at 35 ° C. to 40 ° C. After completion of the dropwise addition, the mixture was stirred for 2 hours at room temperature, and then the flask was ice-cooled, and over time, 775.2 g of ion-exchanged water was added so as to stay in the liquid temperature range of 10 to 40 ° C. Thereafter, the mixture was sufficiently stirred, and the precipitated crystals were subjected to suction filtration to obtain No. Filtered off using 5C filter paper. To the crystal, 120 g of a 15% by mass aqueous sodium hydroxide solution and 200 mL of ethyl acetate were added, and the mixture was sufficiently stirred and separated. After liquid separation, 180 g of a 10% by mass sulfuric acid aqueous solution was added to an aqueous sodium hydroxide solution, and the precipitated crystals were separated by filtration to obtain 39.2 g (purity 74%) of a mixture containing 3-hydroxy-1-adamantanecarboxylic acid. Components other than 3-hydroxy-1-adamantanecarboxylic acid were as shown in Table 1.

Example 2
(2) Purification step After adding 200 g of methanol to the mixture obtained in Example 1 and stirring for 30 minutes, 770 g of ion-exchanged water was added and stirred for 2 hours while cooling with ice. Thereafter, the crystals were filtered off, and the filtrate was concentrated to 579 g. Crystals precipitated and were filtered off to obtain 21.7 g of 3-hydroxy-1-adamantanecarboxylic acid (removal yield 38%, purity 96%).

Example 3
(1) Carboxylation process In a flask equipped with a stirrer, a thermometer, a dropping funnel and a Dim funnel, 50.6 g of 1,3-adamantanediol (purity 96%) was charged and 201.6 g of concentrated sulfuric acid was added. The flask was heated in a 35 ° C. water bath and stirred for 30 minutes, and then 13.7 g of formic acid was added dropwise over 1 hour while maintaining the reaction temperature at 35 ° C. to 40 ° C. After completion of the dropwise addition, the mixture was stirred for 2 hours at room temperature. Thereafter, the flask was ice-cooled, and 1100 g of a 15% by mass aqueous sodium hydroxide solution was added over a period of time so as to remain in the liquid temperature range of 10 to 40 ° C. Thereafter, 200 mL of ethyl acetate was added, and the mixture was sufficiently stirred and separated. After separation, 230 g of a 10% by mass sulfuric acid aqueous solution was added to an aqueous sodium hydroxide solution, and the precipitated crystals were filtered by suction filtration. The mixture was filtered using 5C filter paper to obtain 36.4 g (purity 67%) of a mixture containing 3-hydroxy-1-adamantanecarboxylic acid. Components other than 3-hydroxy-1-adamantanecarboxylic acid were as shown in Table 1.

Example 4
(2) Purification Step After adding 120 g of methanol to the mixture obtained in Example 3 and stirring for 30 minutes, 360 g of ion-exchanged water was added and stirred for 2 hours while cooling with ice. Thereafter, the crystals were filtered off, and the filtrate was concentrated to 340 g. Crystals precipitated and were filtered off to obtain 16.8 g of 3-hydroxy-1-adamantanecarboxylic acid (removal yield 31%, purity 96%).

Comparative Example 1
In the purification step of Example 2, the same operation as in Example 2 was performed except that 1000 g of acetonitrile was added instead of the methanol / ion exchange water mixed solvent, and 9 g of 3-hydroxy-1-adamantanecarboxylic acid was obtained ( Extraction yield 10%, purity 78%). The yield was greatly reduced and the purity was hardly improved.

Claims (10)

The adamantanediol represented by the general formula (1) is reacted in a liquid protonic acid solvent with a carbon monoxide source of 2 equivalents or less per 1 equivalent of the hydroxyl group of the adamantanediol, and then represented by the general formula (2). A method for producing hydroxyadamantanecarboxylic acids, wherein the crystals of hydroxyadamantanecarboxylic acid are filtered off.
(1)
(In the formula, X is the same or different and represents a hydrogen atom, an alkyl group or an alkoxy group, and n represents an integer of 14.)
(2)
(In the formula, X is the same or different and represents a hydrogen atom, an alkyl group or an alkoxy group, and n represents an integer of 14.) The method for filtering the crystals is the following (i) to (iii):
(I) adding water to the reaction solution and filtering the precipitated crystals;
(Ii) Crystals deposited by adding water to the reaction solution are filtered out, an alkaline aqueous solution and an organic solvent are added to the obtained crystal, the alkaline aqueous solution and the organic solvent are separated, and an acidic aqueous solution is added to the alkaline aqueous solution. In addition, the precipitated crystals are filtered out.
(Iii) An alkaline aqueous solution and an organic solvent are added to the reaction solution, the alkaline aqueous solution and the organic solvent are separated, an acidic aqueous solution is added to the alkaline aqueous solution, and the precipitated crystals are separated by filtration.
The manufacturing method of Claim 1 which is any one method of these.   The manufacturing method according to claim 1 or 2, wherein the carbon monoxide source is at least one selected from the group consisting of carbon monoxide, formic acid, and alkyl formate. A method for purifying a mixture containing at least an adamantanedicarboxylic acid represented by the general formula (3) as an impurity, the main component being a hydroxyadamantanecarboxylic acid represented by the general formula (2), the purification method comprising: A method for purifying hydroxyadamantanecarboxylic acids, wherein the adamantanedicarboxylic acid is precipitated and removed by crystallization using a polar organic solvent and water.
(3)
(In the formula, X is the same or different and represents a hydrogen atom, an alkyl group or an alkoxy group, and n represents an integer of 14.) The purification method according to claim 4, wherein the mixture further contains an adamantane monocarboxylic acid represented by the general formula (4).
(4)
(Wherein X is the same or different and represents a hydrogen atom, an alkyl group or an alkoxy group, and n represents an integer of 15)   The purification method according to claim 4 or 5, wherein the crystallization method comprises dissolving the mixture in a polar organic solvent and then adding water to precipitate the adamantane dicarboxylic acid.   The polar organic solvent is any one or more selected from the group consisting of methanol, ethanol, propanol, 2-propanol, tetrahydrofuran, 1,4-dioxane, dimethylformamide, and dimethyl sulfoxide. The purification method according to claim 1.   The purification method according to any one of claims 4 to 7, wherein an amount of the polar organic solvent used is 4 to 40 times by mass with respect to the mixture.   The purification method according to any one of claims 4 to 8, wherein the amount of water used is 3 to 5 times by mass with respect to the polar organic solvent.   The purification method according to any one of claims 4 to 9, wherein the mixture is obtained by the method for producing a hydroxyadamantanecarboxylic acid according to any one of claims 1 to 3.