JP4508670B2 - Method for producing high-purity adamantanetriols - Google Patents

Description

  The present invention relates to a production method in the case where high purity is particularly required for adamantanetriols used as intermediates for organic drugs such as high-functional polymers, electronic materials, and medical and agricultural chemicals.

  As a method for producing adamantanetriols, there is a method in which adamantane is halogenated and then substituted with a hydroxyl group. For example, there is a method by hydrolysis of tribromoadamantane (see Patent Document 1). However, in this method, it is difficult to produce tribromoadamantane, and adamantanetriol cannot be efficiently obtained from adamantane. In addition, adamantanetriol has been described as a method of separating by distillation from the residue obtained by distilling off water with ethanol after hydrolysis, but a purification method for removing bromide as a by-product is described. Absent.

  In addition, adamantane monools, adamantane polyols (adamantanediol, adamantanetriol, adamantanetetraol, etc.) have been obtained by a method in which adamantanes are oxidized with oxygen in acetic acid using an imide compound as a catalyst (Patent Documents 2 and 3). 4). Separation of the adamantanetriol produced by this method is carried out by concentrating the reaction solution, adding water and adding acetone to the aqueous phase after extracting adamantanediol from the filtrate obtained by filtering the resulting slurry and cooling. Adamantanetriol is crystallized (see Patent Document 5). However, the purification method is not clear.

  Further, there are a production method and a separation method in which adamantanes are oxidized using chromic anhydride (see Patent Documents 6 and 7). This method is obtained by oxidizing adamantane in acetic acid and then concentrating the reaction solution. The resulting residue is extracted with ethyl acetate, and high-purity adamantanetriol is obtained. However, since a large amount of chromic anhydride as a reagent and ethyl acetate as an extraction solvent are used, it is a preferable production method from an industrial point of view. I can't say there is.

On the other hand, the present inventors have developed a method for producing adamantane polyols (see Patent Document 8). However, in order to use adamantanetriol produced by this method in a field where a higher purity product is required, further purification treatment is required.
Japanese Patent Laid-Open No. 2-196744 JP-A-8-38909 JP-A-9-327626 Japanese Patent Laid-Open No. 10-286467 JP 2001-131105 A JP 2003-321408 A JP 2003-335715 A JP 2001-335519 A

  The object of the present invention is to produce high-purity adamantanetriol.

  As a result of intensive studies on a method for producing high-purity adamantanetriols, the present inventors have reacted adamantanes with hypochlorous acid or a salt thereof in the presence of a ruthenium compound in an organic solvent / water two-phase system. By recrystallizing a crude product of adamantanetriols obtained by crystallization from an aqueous phase obtained from water or a mixture of an aqueous alkali solution and a water-soluble organic solvent, high purity and low halogen It was found that adamantanetriol was efficiently obtained, and the present invention was completed.

  That is, the present invention was extracted from a reaction solution in a method for producing adamantanetriol represented by the following formula (1) by reacting adamantane with hypochlorous acid or a salt thereof in the presence of a ruthenium compound. The present invention relates to a method for producing high-purity adamantanetriol, characterized in that crude adamantanetriol is crystallized from water or a mixed solution of an aqueous alkali solution and a water-soluble organic solvent and purified to an impurity of 2 wt% or less and a halogen concentration of 100 ppm or less. Is.

（式中、置換基Ｒは、それぞれ独立にアルキル基、アリール基、シクロアルキル基、アルコキシ基、アリールオキシ基、アシルオキシ基、ハロゲン基を示し、ｎは０〜１３の整数である。）

(In the formula, each substituent R independently represents an alkyl group, an aryl group, a cycloalkyl group, an alkoxy group, an aryloxy group, an acyloxy group, or a halogen group, and n is an integer of 0 to 13.)

  According to the present invention, low halogen, high purity adamantanetriols with few impurities can be efficiently produced.

  The adamantane used as a raw material in the present invention is represented by the following general formula.

（式中、置換基Ｒは、それぞれ独立にアルキル基、アリール基、シクロアルキル基、アルコキシ基、アリールオキシ基、アシルオキシ基、ハロゲン基を示し、ｎは０〜１３の整数である。

(In the formula, each of the substituents R independently represents an alkyl group, an aryl group, a cycloalkyl group, an alkoxy group, an aryloxy group, an acyloxy group, or a halogen group, and n is an integer of 0 to 13.)

  Here, the alkyl group includes an alkyl group having 1 to 10 carbon atoms such as methyl, ethyl, propyl, butyl and hexyl groups, preferably an alkyl group having 1 to 6 carbon atoms, particularly an alkyl group having 1 to 4 carbon atoms. The aryl group includes a phenyl group, a naphthyl group, and the like, and the cycloalkyl group includes a cyclohexyl, a cyclooctyl group, and the like. Alkoxy groups include C 1-10 alkoxy groups such as methoxy, ethoxy, propoxy, butoxy, hexyloxy groups. The aryloxy group includes, for example, a phenoxy group. The acyloxy group includes an acyloxy group having 2 to 6 carbon atoms such as acetyloxy, propionyloxy, and butyryloxy groups. The halogen group includes a fluoro group, a chloro group, a bromo group, an iodo group, and the like.

  When adamantanes are reacted with hypochlorous acid or a salt thereof in the presence of a ruthenium compound in a two-phase system of an organic solvent / water, adamantane monool and adamantane polyol (diol, triol, tetraol) are obtained. The target adamantanetriol is selected by adjusting the amount of chlorite to 2.0 to 10.0 mol, preferably 3.0 to 5.0 mol, per 1 mol of adamantanes. Can be obtained.

  After completion of the reaction, the aqueous phase and the organic solvent phase are separated. Among adamantanols, adamantane monool has higher solubility in organic solvents than water, whereas adamantane polyols such as adamantanediol, triol, and tetraol have higher solubility in water than organic solvents. high. Thereby, adamantane monool and adamantane polyol are separated. Moreover, the organic solvent containing a lot of ruthenium compounds can be used for the next reaction as it is, or the ruthenium compounds can be recovered and reused.

  Since the separated aqueous phase contains adamantane polyol, sodium chloride produced as a by-product in the reaction, and a small amount of ruthenium compound (mostly present in an organic solvent), an operation for purifying adamantane triol from them. I do. First, the separated aqueous phase is crystallized by removing water. The amount of water to be removed is 60 to 90% with respect to the weight of the aqueous phase before removal. When the water removal is lower than this range, a sufficient adamantanetriol recovery rate cannot be obtained. If it is higher than this range, the slurry concentration becomes high, causing a problem in workability. By this crystallization, crude crystals of adamantanetriol containing sodium chloride, a ruthenium compound and other coloring components are precipitated. For the crystallization, a known evaporation type crystallizer can be used. The obtained crude crystals may be dried by a known dryer.

  Next, sodium chloride and a ruthenium compound are removed from the crude crystals by stirring the obtained crude crystals in ion-exchanged water. The amount of ion-exchanged water used at this time is in the range of 0.1 to 10 times, preferably 1 to 3 times the weight of the crude crystals. If the amount of ion-exchanged water used for washing is less than this range, sodium chloride, ruthenium compounds, etc. remain, and if it exceeds this range, the recovery rate of adamantanetriols is lowered. The stirring time is about 10 to 30 minutes. After stirring, filtration is performed to obtain adamantanetriol wet crystals.

  Next, the wet crystals are dissolved in a water-soluble organic solvent to obtain a solution of adamantanetriols. As the water-soluble organic solvent, a solvent having a boiling point of 100 ° C. or lower and completely dissolved in water is used. Solvents that satisfy these conditions include water-soluble alcohols such as methanol, ethanol, propanol, isopropanol, and t-butanol, and acetonitrile, tetrahydrofuran, acetone, and the like. However, considering the solubility of adamantanetriols, methanol is preferred.

  The amount of the water-soluble polar organic solvent is 4 to 100 times by weight, preferably 5 to 10 times by weight with respect to the crystal. The wet crystals are completely dissolved using a water-soluble organic solvent in this range. The melting temperature is 0 to 80 ° C, preferably 10 to 60 ° C.

  Ion exchange water is added to the obtained solution of adamantanetriols, and water washing is performed. The ion-exchanged water to be added is adjusted to a ratio of about 10 to 50% of the water-soluble organic solvent in the range of 0.1 to 10 times by weight, preferably 0.5 to 3 times by weight with respect to the crystal. At this time, if alkali washing is performed by adding an alkali, the halogen content in the adamantanetriol crystal can be reduced.

  Examples of the alkali used include inorganic alkalis such as sodium hydroxide, potassium hydroxide, and aqueous ammonia, and organic alkalis such as amines such as triethylamine and alkylammoniums such as tetramethylammonium hydroxide. The amount to be used is 0.1 to 10 times by weight, preferably 1 to 5 times by weight with respect to the crystal. The temperature at the time of washing is 20 to 80 ° C, preferably 50 to 70 ° C. If the cleaning time is long, there is no problem, but if it is too short, the amount of halogen and coloring components in the triol crystal increase.

  Next, the solution after washing is concentrated and crystallized. By concentrating, the water-soluble organic solvent is first distilled off, and crystals of adamantanetriols are precipitated. At this time, it is carried out so that the concentration of the water-soluble organic solvent in the mixed solution after concentration is in the range of 1 to 10 mol%. If it is lower than this range, slightly mixed organic impurities such as adamantanediol cannot be removed. If it is higher than this range, the recovery rate of adamantanetriol is reduced. After concentrating the mixture to this range, the crystals are collected by filtration.

  The obtained crystal is washed once or more with ion-exchanged water in an amount of 0.1 to 10 times by weight, preferably 0.5 to 3 times by weight with respect to the crystal. Highly pure adamantriol is obtained by drying the wet crystal at a reduced pressure or at room temperature. Thereby, it is possible to purify the impurities to 2% or less and a halogen concentration of 100 ppm or less, preferably 30 ppm or less.

Synthesis Example 68.2 g (0.5 mol) of adamantane, 500 ml of ethyl acetate, 3.35 g of ruthenium chloride n hydrate in a 2 L capacity jacketed glass reactor equipped with a stirrer, thermometer, Dimroth condenser, pH electrode, 90 g of water was charged, and 1084 g (2.0 mol) of a 12 wt% sodium hypochlorite aqueous solution was added dropwise at 70 ° C. At this time, 5 wt% hydrochloric acid was added dropwise so that the pH was 4. As a result of analysis by gas chromatography after the reaction, the organic phase contains 5.7 g of diol, 0.8 g of triol, and 2.4 g of ketone, and the aqueous phase contains 14.5 g of diol, 44.8 g of triol, and other salts. It was included.

Example 1
The aqueous phase after the reaction (1400 g) was concentrated to 510 g. The concentrate was cooled to about 5 ° C. and filtered to obtain wet crystals. The wet crystals were washed with 180 g of ion exchange water, extracted with 450 g of methanol and filtered. To the obtained methanol solution, 1.5 g of sodium hydroxide and 150 g of ion-exchanged water were added and stirred at 60 ° C. for 6 hours. Thereafter, the solution was concentrated to 210 g mainly under conditions where methanol was distilled off (the liquid composition at this time was about 6 mol% of methanol). The precipitated crystals were suction filtered and rinsed with 120 g of ion exchange water. The obtained crystals were vacuum dried to obtain 21.5 g of white crystals. The purity of the crystals was 99.2% and the halogen content was 10 ppm.

Example 2
The aqueous phase after the reaction (1400 g) was concentrated to 510 g. The concentrate was cooled to about 5 ° C. and filtered to obtain wet crystals. The wet crystals were washed with 180 g of ion exchange water, extracted with 450 g of methanol and filtered. To the obtained methanol solution, 1.5 g of sodium hydroxide and 150 g of ion-exchanged water were added and stirred at 60 ° C. for 6 hours. Thereafter, the solution was concentrated to 220 g mainly under conditions where methanol was distilled off (the liquid composition at this time was about 7 mol% of methanol). The precipitated crystals were suction filtered and rinsed with 120 g of ion exchange water. The obtained crystals were vacuum-dried to obtain 22.8 g of white crystals. The purity of the crystals was 99.3% and the halogen content was 25 ppm.

Comparative Example 1
The aqueous phase after the reaction (1400 g) was concentrated to 510 g. The concentrate was cooled to about 5 ° C. and filtered to obtain wet crystals. The wet crystals were washed with 180 g of ion exchange water, and then a suspension obtained by adding 10 g of methanol and 400 g of ion exchange water was stirred at room temperature for 10 hours. Thereafter, suction filtration was performed, and rinsing was performed with 120 g of ion exchange water. The obtained crystals were vacuum dried to obtain 28.7 g of white crystals. The purity of the crystals was 98%, and the halogen content was 85 ppm.

Comparative Example 2
To the crystal obtained in Comparative Example 1, 10 g of methanol and 400 g of ion-exchanged water were added, and the same washing operation as in Comparative Example 1 was repeated twice. After vacuum drying, 12.2 g of white crystals were obtained. The purity of the crystals was 98.7% and the halogen content was 27 ppm.

Claims (3)

In the method for producing adamantanetriol represented by the following formula (1) by reacting adamantane with hypochlorous acid or a salt thereof in the presence of a ruthenium compound, the crude adamantanetriol extracted from the reaction solution is converted to an alkaline aqueous solution. And purified from a mixed solution of water, a water-soluble alcohol selected from methanol, ethanol, propanol, isopropanol and t-butanol, and purified to an impurity of 2 wt% or less and a halogen concentration of 100 ppm or less Manufacturing method.

(In the formula, each substituent R independently represents an alkyl group, an aryl group, a cycloalkyl group, an alkoxy group, an aryloxy group, an acyloxy group, or a halogen group, and n is an integer of 0 to 13.) The manufacturing method of Claim 1 which crystallizes by distilling aqueous alcohol first from the mixed solution of aqueous alkali solution and water-soluble alcohol.   The production method according to claim 1, wherein the concentration of the water-soluble alcohol in the mixed solution after crystallization is in the range of 1 to 10 mol%.