JP2016023165A - Method for producing trimethyladamantylammonium hydroxide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To solve a problem in the conventional method for synthesizing trimethyladamantylammonium hydroxide that an equipment cost and a production cost become high.SOLUTION: The problem can be solved by a production method comprising: reacting N,N-dimethyladamantylamine with a quarternarizing agent in a nonpolar solvent having a solubility parameter of less than 10 to obtain N,N,N-trimethyladamantylammonium salt; and, at that time, adding a protic polar solvent to the reaction system before the reaction is started, while the reaction is proceeding, or after the reaction is complete, to selectively obtain N,N,N-trimethyladamantylammonium hydroxide from the reaction system.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a method for producing trimethyladamantyl ammonium hydroxide.

  Since adamantane derivatives have various characteristics depending on their structures, they are widely used in various industries as pharmaceutical raw materials, optical disk substrates, optical fibers, resin materials for photoresists, and the like.

  Among them, trimethyladamantyl ammonium hydroxide is an industrially important compound used as a template agent (structure-directing agent) for zeolite.

Patent Document 1 below discloses a method for synthesizing trimethyladamantyl ammonium hydroxide.
First, amantadine hydrochloride (1-aminoadamantane hydrochloride) is prepared as a starting material, and dehydrochlorination is performed by reacting with a base such as an alkali metal hydroxide to obtain 1-aminoadamantane (dehydrochlorination). Next, 1-aminoadamantane, formic acid, and formaldehyde or paraformaldehyde are reacted in an alcohol solvent to obtain N, N-dimethyladamantylamine (dimethylation). Subsequently, N, N-dimethyladamantylamine is reacted with methyl halide to obtain 1-adamantanetrimethylammonium halogen salt (quaternization). Finally, 1-adamantane trimethylammonium halogen salt is anion-exchanged using an OH type ion exchanger to obtain trimethyladamantyl ammonium hydroxide (ion exchange).

Patent Document 2 below discloses a method of synthesizing trimethyladamantyl ammonium hydroxide by a quaternization method different from the above.
First, similarly to the method described in Patent Document 1, amantadine hydrochloride is prepared as a starting material, and the steps of dehydrochlorination and dimethylation are sequentially performed. Subsequently, dimethyl sulfate and N, N-dimethyladamantylamine are reacted using water or an alcohol miscible with water as a reaction solvent to obtain 1-adamantyltrimethylammonium sulfate (quaternization). Finally, anion exchange is performed using an OH type ion exchanger to obtain trimethyladamantyl ammonium hydroxide (ion exchange).
Conventional synthesis methods represented by Patent Document 1 and Patent Document 2 can be represented by, for example, the scheme shown in FIG.

JP 2011-246429 A JP 2012-520263 A

  However, in the method for synthesizing trimethyladamantyl ammonium hydroxide described in Patent Document 1, it is necessary to use expensive methyl halide for quaternization, and there is a problem in that the production cost increases.

  In addition, in the method for synthesizing trimethyladamantyl ammonium hydroxide described in Patent Document 2, quaternization is performed because a protic polar solvent such as water or water-miscible lower alcohol is used as a quaternization reaction solvent. In order to advance efficiently, it was necessary to carry out under the high temperature of 120-200 degreeC and the pressurization of 5-300 bar, and there existed a problem that an installation cost and a manufacturing cost became high.

  Accordingly, an object of the present invention is to provide a method capable of producing trimethyladamantyl ammonium hydroxide at low cost and high yield.

As a result of extensive studies, the present inventor conducted a quaternization reaction in a nonpolar solvent having a solubility parameter in a specific range, and before the quaternization reaction started, during the reaction proceeding, and after the reaction ended. At this point, it was found that the conventional problems as described above can be solved by adding a protic polar solvent to the reaction system, and the present invention has been completed.
That is, the present invention is as follows.

The method for producing N, N, N-trimethyladamantyl ammonium hydroxide of the present invention comprises:
(B) a step of reacting N, N-dimethyladamantylamine with a quaternizing agent in a nonpolar solvent having a solubility parameter of less than 10 to obtain an N, N, N-trimethyladamantyl ammonium salt, and (C) Obtaining N, N, N-trimethyladamantyl ammonium hydroxide from the N, N, N-trimethyladamantyl ammonium salt,
A protic polar solvent is added to the reaction system at any time before the start of the reaction in the step (B), during the progress of the reaction, and after the end of the reaction.

In the present invention, the quaternization reaction is constituted by a two-phase reaction system of a nonpolar solvent (hereinafter also referred to as nonpolar solvent) having a solubility parameter of less than 10 and a protic polar solvent. The nonpolar solvent acts as a reaction phase between N, N-dimethyladamantylamine (hereinafter also referred to as DMAA) and a quaternizing agent, and the protic polar solvent is N, N, N-trimethyl which is a quaternized product. It has a relationship of acting as an extraction phase for adamantyl ammonium salt. For example, when dimethyl sulfate is used as the quaternizing agent, the quaternized product is N, N, N-trimethyladamantyl ammonium methyl sulfate (hereinafter also referred to as TMAA-MeSO ₄ ). Since the produced N, N, N-trimethyladamantyl ammonium salt is hydrophilic, it moves to a protic polar solvent, and the quaternization equilibrium reaction is greatly biased toward the reaction product. As a result, at normal pressure In addition, a quantitative quaternization reaction is possible.
Moreover, since only the N, N, N-trimethyladamantyl ammonium salt obtained in the step (B) is dissolved in the protic polar solvent, the process proceeds to the step (C) continuously without isolation. Can do. Therefore, processes can be reduced and manufacturing costs can be suppressed. The N, N, N-trimethyladamantyl ammonium salt also includes N, N, N-trimethyladamantyl ammonium hydroxide, but in this case, step (C) is not necessary.
The solubility parameter (SP value) is a value defined by the regular solution theory introduced by Hildebrand, and is a measure of the solubility of the binary solution.

  In the production method of the present invention, before the step (B), (A) the N, N-dimethyladamantylamine is obtained by dimethylating 1-aminoadamantane, the nonpolar solvent is added, It is desirable to further include a step of extracting the N, N-dimethyladamantylamine into the nonpolar solvent.

  Thereby, since it can transfer to a process (B), without isolating N, N- dimethyladamantylamine obtained at a process (A), a process can be reduced and manufacturing cost can be suppressed.

  In the production method of the present invention, the quaternizing agent is preferably at least one of dimethyl sulfate and dimethyl carbonate.

  It is not necessary to use an expensive quaternization reagent such as methyl halide in the technique described in Patent Document 1, and it does not require reaction conditions under high temperature and high pressure in the technique described in Patent Document 2. It becomes possible to remarkably suppress the facility cost and the manufacturing cost.

  In the production method of the present invention, the nonpolar solvent is preferably at least one of toluene and xylene.

  Since toluene and xylene are relatively inexpensive and have a boiling point of 100 ° C. or higher, the amount of evaporation when heated can be suppressed. Therefore, N, N, N-trimethyladamantyl ammonium salt can be obtained with high yield by heating so that the reaction can proceed easily.

  In the production method of the present invention, the protic polar solvent is preferably at least one of water and methanol.

  Since water and methanol are relatively inexpensive and the solubility of N, N, N-trimethyladamantyl ammonium salt is high, it is possible to dissolve almost the entire amount of N, N, N-trimethyladamantyl ammonium salt in a protic polar solvent. it can. In particular, in the case of water, N, N, N-trimethyladamantyl ammonium hydroxide is preferable because it does not require solvent substitution when used as a zeolitic template agent (structure-directing agent).

  In the production method of the present invention, it is desirable to obtain the 1-aminoadamantane by reacting 1-aminoadamantane hydrochloride with a base.

  Since 1-aminoadamantane hydrochloride is structurally stable and has high storage stability, it is easier to obtain than N, N-dimethyladamantylamine and facilitates N, N, N-trimethyladamantylammonium hydroxide. Can be manufactured.

  In the production method of the present invention, in step (A), it is desirable to react 1-aminoadamantane, formic acid, formaldehyde or paraformaldehyde in an alcohol solvent to obtain N, N-dimethyladamantylamine. This is because N, N-dimethyladamantylamine can be obtained quantitatively.

  In the production method of the present invention, it is desirable that the N, N, N-trimethyladamantyl ammonium salt obtained in step (B) is contained at least 95% with respect to the total mass of the product. By increasing the yield of N, N, N-trimethyladamantyl ammonium salt in the step (B), N, N, N-trimethyladamantyl ammonium hydroxide can be obtained with good yield.

  In the production method of the present invention, it is desirable to use a strongly basic anion exchanger in the step (C). By using a strongly basic anion exchanger, ion exchange can be easily performed.

  In the production method of the present invention, it is preferable that the step (C) further includes a step of removing the solvent from the obtained N, N, N-trimethyladamantyl ammonium hydroxide solution and concentrating to 15% by mass or more. Concentration makes it easy to use as a zeolitic template agent (structure-directing agent).

According to the production method of the present invention, a quantitative quaternization reaction is possible even at normal pressure, so that the equipment cost and production cost can be remarkably suppressed.
Furthermore, since the solubility of N, N, N-trimethyladamantyl ammonium salt in the protic polar solvent depends on the temperature and amount of the protic polar solvent, recrystallization purification can be performed by cooling after the reaction or removing the solvent. It becomes.

FIG. 1 is a diagram for explaining a method for synthesizing trimethyladamantyl ammonium hydroxide of the present invention. FIG. 2 is a diagram for explaining a conventional method for synthesizing trimethyladamantyl ammonium hydroxide.

Hereinafter, the present invention will be described in more detail.
The production method of the present invention is a method for synthesizing trimethyladamantylammonium hydroxide by reacting N, N-dimethyladamantylamine with a quaternizing agent in a specific nonpolar solvent and starting the quaternization reaction. It is characterized in that a protic polar solvent is added to the reaction system at any time before, during the reaction, or after the completion of the reaction.

Hereinafter, each process suitable for implementing the production method of the present invention will be described.
It is preferable to use amantadine hydrochloride which is easily available as a starting material in the production method of the present invention. In this case, as shown in FIG. 1, the production method of the present invention can be carried out through the steps of dehydrochlorination, dimethylation, quaternization and ion exchange of amantadine hydrochloride.

(Dehydrochlorination process)
The dehydrochlorination step is preferably a step in which 1-aminoadamantane hydrochloride as a starting material is dissolved in an alcohol having a relative dielectric constant of 10.0 to 20.0 and reacted with a base to obtain 1-aminoadamantane. Examples of the alcohol include 1-propanol, 2-propanol, 1-butanol, isobutanol, sec-butanol, t-butanol, 1-pentanol, sec-pentanol, 3-pentanol, and 2-methyl-1. -Butanol, 3-methyl-1-butanol, 2-methyl-2-butanol, 3-methyl-2-butanol, 2,2-dimethyl-1-propanol, 1-hexanol, 2-hexanol, 3-hexanol, 1 -Heptanol, 2-heptanol, 3-heptanol, etc. are mentioned. Moreover, as this base, an alkali metal hydroxide etc. are preferable, for example, sodium hydroxide is preferable. Sodium hydroxide is usually added to the reaction system as an aqueous solution, and the concentration of the aqueous sodium hydroxide solution is usually about 25 to 50% by mass. The reaction is performed for several hours, for example, at a temperature of about 50 ° C.

After reacting 1-aminoadamantane hydrochloride with a base, there is no need for separation or purification of the reactant, and the subsequent dimethylation step can be carried out in the reaction system as it is.
In addition, if 1-aminoadamantane is directly available, it is not necessary to perform the dehydrochlorination step, and 1-aminoadamantane can be dissolved in the alcohol and the subsequent dimethylation step can be performed.

(Dimethylation process)
Next, 1-aminoadamantane obtained in the dehydrochlorination step, formic acid, and formaldehyde or paraformaldehyde are reacted in an alcohol solvent to obtain N, N-dimethyladamantylamine (DMAA). This dimethylation step corresponds to the step (A) in the present invention together with the above-described dehydrochlorination step.
The dimethylation step is an Eschweiler-Clark methylation reaction, which is a reductive amination reaction that introduces a methyl group into a primary amine. The Eschweiler-Clark reaction is an excess of formic acid in the primary amine. , And excess formaldehyde or paraformaldehyde is added and heated to reduce to a secondary amine. Thereby, a methyl group is introduced into the primary amine, and a methyl group is introduced into the secondary amine by the same reaction mechanism, so that the tertiary amine can be obtained efficiently and with high purity and high yield. Can do. The formic acid to be used is preferably added to the reaction system as a formic acid aqueous solution of about 75 to 97% by mass. The amount of formic acid used is usually preferably 0.3 to 0.7 molar times, more preferably 0.4 to 0.5 molar times with respect to formaldehyde or paraformaldehyde. Formaldehyde or paraformaldehyde is preferably added to the reaction system as an aqueous solution of about 30 to 50% by mass. The amount of formaldehyde or paraformaldehyde used is usually preferably 2 to 20 moles, more preferably 3 to 8 moles, with respect to 1-aminoadamantane. The temperature in the reaction system after adding formic acid and formaldehyde or paraformaldehyde is preferably about 50 to 90 ° C.
As the alcohol solvent, it is sufficient if 1-aminoadamantane can be dissolved, and secondary alcohols such as 2-propanol, sec-butanol, sec-pentanol, and 3-pentanol can be preferably used.

  The obtained DMAA is extracted using an organic solvent. Here, as the organic solvent, it is preferable to use a nonpolar solvent which is a reaction solvent in the quaternization step described later. As a result, the quaternization reaction can be carried out continuously from the extraction operation, so that the DMAA isolation operation after the dimethylation reaction can be omitted. That is, since it can move to a process (B), without isolating N, N- dimethyladamantylamine obtained at a process (A), a process can be reduced and manufacturing cost can be suppressed.

(Quaternization process)
The quaternization step in the present invention is a step of reacting the DMAA obtained in the dimethylation step with a quaternizing agent in a nonpolar solvent to obtain N, N, N-trimethyladamantyl ammonium salt, A protic polar solvent is added to the reaction system at any time before the start of the reaction, during the progress of the reaction, and after the end of the reaction. This quaternization step corresponds to step (B) in the present invention.
Hereinafter, the case where dimethyl sulfate is used as the quaternizing agent will be described as an example. In this case, the quaternized product is N, N, N-trimethyladamantyl ammonium methyl sulfate (hereinafter also referred to as TMAA-MeSO ₄ ).

DMAA and quaternizing agent (dimethyl sulfate) are lipophilic substances and are miscible with nonpolar solvents, but hardly dissolve in protic polar solvents. On the other hand, TMAA-MeSO _4, which is a quaternization reaction product, is an organic salt and is therefore a hydrophilic substance and exhibits high solubility in a protic polar solvent, but hardly dissolves in a nonpolar solvent. For this reason, the raw material (DMAA) exists in a nonpolar solvent, and the quaternization reaction itself proceeds in the nonpolar solvent. Thereafter, the generated TMAA-MeSO ₄ moves to the protic polar solvent side. Therefore, the reaction product TMAA-MeSO ₄ is hardly present in the nonpolar solvent that is the reaction, and the quaternization equilibrium reaction can be largely biased toward the reaction product. As a result, quantitative quaternization reaction is possible even at normal pressure. Therefore, the production cost of trimethyladamantyl ammonium hydroxide can be greatly reduced.

  The solubility parameter (SP value) in the nonpolar solvent needs to be 10 or less (nonpolar solvent) as described above. It is particularly preferable that the SP value is 9 or less.

Examples of the nonpolar solvents that can be used in the present invention include aromatic hydrocarbon solvents such as toluene, xylene, mesitylene, naphthalene, ethylbenzene, methylbenzene, methylethylbenzene, diethylbenzene, triethylbenzene, dimethylethylbenzene, methyldiethylbenzene, and tetralin. Examples include hydrocarbon solvents such as decalin, ethers such as diethyl ether, and nonpolar solvents such as ethyl acetate, and one or more of these can be used in combination.
Among these, at least one selected from toluene and xylene is particularly preferable because it can be suitably used as a DMAA extraction solvent and a quaternization reaction solvent after the dimethylation reaction.

  Examples of the quaternizing agent include at least one selected from dimethyl sulfate, dimethyl carbonate, and the like. Among them, dimethyl sulfate is preferable from the viewpoint of reactivity.

Examples of the protic polar solvent include protic polar solvents having a solubility of TMAA-MeSO ₄ at 25 ° C. of 5 g / dL or more, such as alcohols such as water, methanol, ethanol, propanol, butanol, benzyl alcohol, diethylene glycol monomethyl ether, Examples include alcohol solvents such as polyhydric alcohols such as ethylene glycol and glycerin, and one or more of these can be used in combination. By using these protic polar solvents, it is possible to continuously carry out the quaternization step and the ion exchange step while omitting the isolation and purification operations of TMAA-MeSO ₄ . Therefore, the production cost of trimethyladamantyl ammonium hydroxide can be greatly reduced.
Especially, the ion exchange process which is a post process can be advanced efficiently by using at least 1 sort (s) chosen from water and methanol.

  The reaction of N, N-dimethyladamantylamine and the quaternizing agent can be carried out under normal pressure. In addition, the quaternization process can also be performed under pressure in a range that does not adversely affect the effects of the present invention as necessary. Moreover, the reaction temperature in quaternization reaction is 50 to 120 degreeC, for example, Preferably it is 80 to 100 degreeC.

  The timing of the addition of the protic polar solvent can be any time before the start of the reaction in the quaternization step, during the progress of the reaction, or after the end of the reaction (95 mol% or more, the reaction has progressed). In particular, when water is used as the protic polar solvent and dimethyl sulfate is used as the quaternizing agent, it is preferable to add the water after the reaction in order to avoid side reactions between water and dimethyl sulfate. .

Moreover, the ratio of dimethyl sulfate to DMAA is, for example, 0.90 to 1.30, preferably 0.90 to 1.10.
Moreover, the usage-amount of a nonpolar solvent is 1.0-12.0 times, for example with respect to the total capacity | capacitance of DMAA and a quaternizing agent, Preferably it is 2.0-8.0 times.
Moreover, the usage-amount of a protic polar solvent is 1.0-12.0 times with respect to the total capacity | capacitance of N, N-dimethyladamantylamine and a quaternizing agent, Preferably it is 2.0-8. 0 times.

By the quaternization process as described above, TMAA-MeSO _{4 as} a product is obtained. After completion of the quaternization step, purification can be performed by recrystallization by reducing the solubility of the product by cooling the protic polar solvent or by removing the solvent.

  According to the quaternization step as described above, N, N, N-trimethyladamantyl ammonium methyl sulfate is contained, for example, at least 95% with respect to the total mass (the total mass of the quaternary ammonium salt). Is 99.5%. By increasing the yield of N, N, N-trimethyladamantyl ammonium methyl sulfate in the step (B), N, N, N-trimethyladamantyl ammonium hydroxide can be obtained with good yield.

(Ion exchange process)
The ion exchange step is a step of obtaining TMAA-OH from TMAA-MeSO ₄ obtained in the quaternization step, and corresponds to the step (C) of the present invention.
Specifically, in the ion exchange step, an anion exchange is performed on the TMAA-MeSO ₄ obtained in the quaternization step using a strongly basic anion exchanger, for example, an OH type ion exchanger. To obtain TMAA-OH. That is, after adding an OH type ion exchanger, for example, an OH type ion exchange resin, to the solution containing TMAA-MeSO ₄ obtained in the quaternization step, the resin is removed by filtration or the like. A method in which a solution containing TMAA-MeSO ₄ obtained in the quaternization step is charged into a column packed with a type of ion exchange resin, and water or alcohol is used as a developing solvent and the solution is allowed to flow out from the column outlet. . By using a strongly basic anion exchanger, ion exchange can be easily performed.
As the OH type ion exchange resin, any strongly basic one can be used. For example, Amberlite IRA400J (organo), Diaion SA10A (Mitsubishi Chemical), SANUPB (Mitsubishi Resin), DOWEX MONOSSPHERE 550A (manufactured by DOW Chemical), Muromac A2004 (manufactured by Muromachi Technos), and the like are typical examples.

The amount of TMAA-MeSO ₄ contained in the N, N, N-trimethyladamantyl ammonium hydroxide solution after the ion exchange step is 0.5% by mass or less, preferably 0.1% by mass or less, alkali metal Is 0.1% by mass or less, preferably 0.01% by mass or less.

From the above, the production method of the present invention preferably has the following embodiments.
(A) 1-aminoadamantane hydrochloride is dehydrochlorinated to obtain 1-aminoadamantane, and the resulting 1-aminoadamantane is dimethylated to obtain N, N-dimethyladamantylamine with a solubility parameter of 10 Adding a less than nonpolar solvent to extract N, N-dimethyladamantylamine into the nonpolar solvent;
(B) reacting N, N-dimethyladamantylamine and dimethyl sulfate in a nonpolar solvent having a solubility parameter of less than 10 to obtain N, N, N-trimethyladamantyl ammonium methyl sulfate;
A protic polar solvent is added to the reaction system at any time before the start of the quaternization reaction in step (B), during the progress of the reaction, or after the end of the reaction, and the N, N, N-trimethyladamantyl ammonium salt is protonated. (C) N, N, N-trimethyladamantylammonium hydroxide by performing anion exchange using a protic polar solvent solution of (C) N, N, N-trimethyladamantylammonium methylsulfate Trimethyladamantyl ammonium hydroxide is produced by including a step of obtaining a product.

After the ion exchange step, water as a solvent is removed from the obtained N, N, N-trimethyladamantyl ammonium hydroxide solution, and the concentration of N, N, N-trimethyladamantyl ammonium hydroxide is adjusted. A step of concentrating to 15% by mass or more can be further provided. By passing through such a concentration step, it can be used as a template agent (structure-directing agent) for zeolite. Further, it is advantageous in that the volume during transportation / storage can be reduced.
Examples of means for removing water include simple distillation, evaporator, flash distillation, and thin film evaporator.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further, this invention is not restrict | limited to the following example.

<Example 1>
(Dehydrochlorination process)
To a 500 ml three-necked flask equipped with a reflux condenser, a thermometer, and a stirrer, 30 g of 2-propanol was added, and 30.0 g (0.16 mol) of 1-aminoadamantane hydrochloride (molecular weight: 187.1) was added with stirring. . After raising the temperature of the reaction system to 50 ° C., 14.0 g (0.17 mol) of a 48 mass% sodium hydroxide aqueous solution was slowly added dropwise and stirred for 1 hour to carry out dehydrochlorination reaction.

(Dimethylation process)
Next, 29.1 g (0.48 mol) of a 76% by mass aqueous formic acid solution (molecular weight 46.0) was added over 15 minutes with stirring, and further 65.1 g (0) of a 37% by mass aqueous formaldehyde solution (molecular weight: 30.0). .81 mol) was added over 15 minutes. After completion of the dropwise addition, the temperature was raised to the reflux temperature of 2-propanol and the reaction was performed for 5 hours. After cooling, the excess formic acid and formaldehyde were deactivated using a 48 mass% aqueous sodium hydroxide solution, and the pH of the reaction solution water layer was adjusted to 10 or more.
Subsequently, 200 ml of toluene was added, and the organic phase was extracted to obtain a solution (1) corresponding to 27.8 g of N, N-dimethyladamantylamine (pale yellow liquid) (yield 96.8%). According to gas chromatography (apparatus: GC-2010 manufactured by Shimadzu Corporation, column: DB-1 (0.25 mm × 30 m, 0.25 um), carrier gas: He, vaporization temperature: 270 ° C., detector: FID (300 ° C.)) When the purity was determined from the peak area, it was 99.8% or more.

(Quaternization process)
All of the solution (1) obtained in the dimethylation step was added to a 500 ml three-necked flask equipped with a reflux condenser, a thermometer, and a stirrer, and the temperature was raised to 50 ° C. Next, 19.8 g (0.16 mol) of dimethyl sulfate (molecular weight: 126.1) was slowly added dropwise with stirring, and then the reaction system was heated to 100 ° C. and reacted at normal pressure for 3 hours. Thereafter, 150 g of ion-exchanged water was added to the reaction system, and the produced N, N, N-trimethyladamantyl ammonium methyl sulfate was isolated by extraction into an ion-exchanged water phase. The amount of N, N, N-trimethyladamantyl ammonium methyl sulfate contained in the ion-exchanged water phase was 45.8 g (yield 97%). Liquid-liquid chromatography (Apparatus: Waters Alliance 2795 Column: Xbridge C18 Film thickness: 3.5 μm Size: 4.6 × 150 mm Temperature: 40 ° C. Eluent: 0.1% formic acid / CH ₃ CN = 9/1 detector : Purity was determined from the peak area by MS), and the purity was 99.5% or more.

(Ion exchange process)
The column was packed with 400 ml of strongly basic ion exchange resin (SANUPB (Mitsubishi Chemical)). Next, an aqueous solution equivalent to 45.0 g (0.15 mol) of N, N, N-trimethyladamantyl ammonium methyl sulfate (molecular weight: 305.4) obtained in the quaternization step was poured into the column. Next, ion-exchanged water was added as a developing solvent to obtain an aqueous solution of N, N, N-trimethyladamantyl ammonium hydroxide (yield 98%). Furthermore, it concentrated by heating at 40 degreeC so that the density | concentration of the N, N, N-trimethyladamantyl ammonium hydroxide in the collect | recovered aqueous solution might be 25 mass%.
Liquid chromatography (Apparatus: Waters Alliance 2795 Column: Xbridge C18 Film thickness: 3.5 μm Size: 4.6 × 150 mm Temperature: 40 ° C. Eluent: 0.1% formic acid / CH ₃ CN = 9/1 detector : Purity was determined from the peak area by MS) and found to be 99.5% or more.
Containing alkali metal by ICP (apparatus: 710 ICP-OES sample (TMAA-OH) manufactured by Agilent Technologies, Inc., 2.7 mL of H ₂ O and 30.3 mL of 69% HNO are added, measuring temperature: 20 ° C.) When the amount was measured, it was less than 0.5%.
When spectrum data was measured by nuclear magnetic resonance spectrum (apparatus: JOEL 300 MHz solvent: d6-DMSO integration number: 16 times), 1H-NMR (300 MHz): 1.6 ppm (b ′, 6H), 2.0 ppm (d ', 6H), 2.2 ppm (c', 3H), 2.9 ppm (a ', 9H), and it was confirmed that the structure was represented by the following formula (1). By titration using a 0.1N aqueous HCl solution as the neutralizing agent and a phenolphthalein solution as the indicator, it was confirmed that the methyl sulfate ion was ion-exchanged 99.5% or more to the hydroxy ion.

<Example 2>
Through the same dehydrochlorination step as in Example 1 and further through the dimethylation step as in Example 1 except that xylene was used instead of toluene as the extraction solvent, a solution of N, N-dimethyladamantylamine (2) (N, N-dimethyladamantylamine corresponding to 27.8 g (0.16 mol)) was obtained.

(Quaternization process)
Solution (2) and 150 g of ion-exchanged water were added to a 500 ml three-necked flask equipped with a reflux condenser, a thermometer, and a stirrer, and the temperature was raised to 50 ° C. Subsequently, 21.7 g (0.17 mol) of dimethyl sulfate was slowly added dropwise with stirring, and then the reaction system was heated to 100 ° C. and reacted at normal pressure for 3 hours. Thereafter, the aqueous phase was isolated to obtain an aqueous solution corresponding to 45.0 g of N, N, N-trimethyladamantyl ammonium methyl sulfate (yield 90%). When the purity was measured by liquid chromatography in the same manner as in Example 1, it was> 99.5% or more.

(Ion exchange process)
An aqueous solution of N, N, N-trimethyladamantyl ammonium hydroxide was obtained through an ion exchange step in the same manner as in Example 1 (yield 98%). The recovered aqueous solution was concentrated by heating at 40 ° C. so that the concentration of N, N, N-trimethyladamantyl ammonium hydroxide was 25% by mass.
As in Example 1, when the purity was measured by liquid chromatography, it was 99.5% or more, and when the alkali metal content was measured by ICP, it was less than 0.5%. Spectral data was obtained by nuclear magnetic resonance spectrum. When measured, 1H-NMR (300 MHz): 1.6 ppm (b ′, 6H), 2.0 ppm (d ′, 6H), 2.2 ppm (c ′, 3H), 2.9 ppm (a ′, 9H) It was confirmed that the structure is represented by the above formula (1). By titration using a 0.1N aqueous HCl solution as the neutralizing agent and a phenolphthalein solution as the indicator, it was confirmed that the methyl sulfate ion was ion-exchanged 99.5% or more to the hydroxy ion.

(Examples 3 to 8)
TMAA-OH was synthesized in the same manner as in Example 1 except that the addition amount of solvent, dimethyl sulfate, synthesis temperature, synthesis time, and synthesis pressure in the quaternization step were changed as shown in Table 1. As a result, the yield, purity, alkali metal content, structure, and hydroxy ion exchange rate were as shown in Table 1.

Claims (10)

(B) a step of reacting N, N-dimethyladamantylamine with a quaternizing agent in a nonpolar solvent having a solubility parameter of less than 10 to obtain an N, N, N-trimethyladamantyl ammonium salt, and (C) Obtaining N, N, N-trimethyladamantyl ammonium hydroxide from the N, N, N-trimethyladamantyl ammonium salt,
Production of N, N, N-trimethyladamantylammonium hydroxide in which a protic polar solvent is added to the reaction system at any point before the start of the reaction in the step (B), during the progress of the reaction, and after the end of the reaction. Method.   Before the step (B), (A) the N, N-dimethyladamantylamine is obtained by dimethylating 1-aminoadamantane, the nonpolar solvent is added, and N, N-dimethyladamantylamine is obtained. The manufacturing method of Claim 1 which further includes the process of extracting this in the said nonpolar solvent.   The production method according to claim 1 or 2, wherein the quaternizing agent is at least one of dimethyl sulfate and dimethyl carbonate.   The production method according to claim 1, wherein the nonpolar solvent is at least one of toluene and xylene.   The manufacturing method of any one of Claims 1-4 whose said protic polar solvent is at least one among water and methanol.   The production method according to any one of claims 2 to 5, wherein the 1-aminoadamantane is obtained by a reaction of 1-aminoadamantane hydrochloride and a base.   In the step (A), 1-aminoadamantane, formic acid and formaldehyde or paraformaldehyde are reacted in an alcohol solvent to obtain N, N-dimethyladamantylamine. The manufacturing method as described in.   The production method according to any one of claims 1 to 7, wherein the N, N, N-trimethyladamantyl ammonium salt obtained in the step (B) is contained at least 95% with respect to the total mass of the product.   The production method according to claim 1, wherein a strong basic anion exchanger is used in the step (C).   10. The method according to claim 1, further comprising a step of removing the solvent from the obtained N, N, N-trimethyladamantyl ammonium hydroxide solution and concentrating to 15% by mass or more in the step (C). The manufacturing method as described in.

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