JP5286604B2 - Method for producing calixarene - Google Patents

Description

  The present invention relates to a method for producing calix [4] arene, which becomes a fine chemical material such as a molecular recognition material and a functional material, by detertiary butylation of p-tert-butylcalix [4] arene.

  In general, calixarene is a cyclic compound in which a plurality of phenols are cross-linked with methylene, that is, cyclic tetrameric calix [4] arene, cyclic hexamer calix [6] arene, cyclic octamer calix [8]. It is known as a useful substance for creating molecular recognition substances and functional materials, such as arene. Such calixarene can introduce a functional group at the removed position by removing the tertiary butyl group from p-tert-butylcalixarene, enabling synthesis of compounds having the expected properties. Become.

  Regarding the method of synthesizing calixarene by deterbutylation as described above, C. D. Gutsche et al. Of the United States use anhydrous aluminum chloride as an acid catalyst and toluene as a reaction solvent (Non-patent Document 1).

  In such a production method using anhydrous aluminum chloride which is a Lewis acid catalyst, the catalyst cannot be recovered after the reaction. Therefore, water must be added to aluminum chloride and discarded as aluminum hydroxide. Another problem is that a large amount of waste liquid containing hydrochloric acid and aluminum chloride is generated in the separation / purification process.

  On the other hand, in recent years, in the manufacture of chemical substances, so-called environmentally friendly chemistry (green chemistry) that reduces the burden on the environment from raw materials to products has been demanded. Energy saving, solvent saving, higher yield, and shorter production time are desired.

  On the other hand, a method for producing calixarene by a detertiary butylated reaction using a strongly acidic type ion exchange resin is known (Patent Document 1). Such a production method using an ion exchange resin has an advantage that no waste liquid is produced. However, the synthetic ion exchange resin is expensive and has a problem that its heat resistance is low, so that it deteriorates quickly due to heat during the reaction.

  By the way, the solubility of calixarene in a hydrophobic solvent differs depending on the number of phenols constituting the arene ring. For example, p-tert-butylcalix [6] is the most soluble in toluene and xylene, followed by p-tert-butylcalix [4] arene, but p-tert-butylcalix [8] arene is insoluble. It is. These are considered to be related to formation by intramolecular hydrogen bonding of calixarene. In addition, p-tert-butylcalix [4] arene has a higher density between phenols than p-tert-butylcalix [6] arene and p-tert-butylcalix [8] arene. Due to the steric hindrance involving butyl groups, the methylene group between phenols is less likely to be separated and a detertiary butylation reaction is likely to occur.

JP 2001-172215 A C. D. Gutsche, et al., Org. Chem., 50, 5802 (1985).

  The present invention has been made paying attention to the above points, and an object of the present invention is to provide an inexpensive and environmentally friendly manufacturing method that can simplify the manufacturing process.

  In order to achieve the above object, the present inventors focused on a solid superacid catalyst having zirconia as a support as a reaction catalyst and a benzene derivative having an electron-donating group as a reaction solvent, and as a result of intensive studies, The present invention has been completed.

で示されるp-tert-ブチルカリックス［４］アレーン１重量部を、２重量部以上８重量部以下の硫酸化ジルコニアおよび８．６６重量部以上３４．６４重量部以下のトルエンの存在下で８０℃以上１１０℃以下の温度に加熱して、下記の一般式（ＩＩ）；

で示されるカリックス［４］アレーンを得ることを特徴とするものである。 That is, the method for producing calixarene according to claim 1 of the present invention comprises the following general formula (I):

The p-tert-butyl-calix [4] arene 1 part by weight shown in, 80 in the presence of 8 parts by weight or more than 2 parts by weight of sulfated zirconia and 8.66 parts by weight or more 34.64 parts by weight of toluene By heating to a temperature not lower than 110 ° C. and not higher than 110 ° C., the following general formula (II):

The calix [4] arene represented by the above is obtained.

The reaction formula of the present invention is shown in the following formula (III). In this case, toluene having an electron-donating group dissolves p-tert-butylcalix [4] arene and uses it for the detertiary butylation reaction, and reacts with the tertiary butyl group released by the reaction. Has the property of capturing.

In addition, the present invention provides 2 to 4 parts by weight of sulfated zirconia and 8.66 parts by weight with respect to 1 part by weight of p-tert-butylcalix [4] arene represented by the above general formula (I). those above 17.32 by heating to a temperature of 100 ° C. or higher 110 ° C. or less in the presence of parts by weight of toluene, and wherein the Rukoto give calix [4] arene represented by the above general formula (II) It is.

The present invention is characterized in that sulfated zirconia is a regenerated catalyst obtained the step of heating dried after washing the solid were used superacid catalyst in the reaction 5 times repeat following multiple It is what.

Although sulfated zirconia used in the present invention is a solid super acid catalyst, it can become a catalyst for removing tertiary butyl reaction, easily available at cheaper. Furthermore, when sulfated zirconia is used, there is an advantage that it can be easily regenerated.

Toluene having an electron donating group used in the reaction of the present invention reacts with a function of a reaction solvent for dissolving p-tert-butylcalix [4] arene and a tertiary butyl group released by the reaction to form a molecule. that it has a function to capture.

In the present invention, the amount of sulfated zirconia used per 1 part by weight of p-tert-butylcalix [4] arene is not particularly limited as long as it does not inhibit the detertiary butylated reaction, but preferably 2 parts by weight or more. 8 parts by weight or less. Thus, when sulfated zirconia is used in the range of 2 parts by weight or more and 8 parts by weight or less, a detertiary butylated reaction can be practically and efficiently performed to produce calix [4] arene with high yield. Can do.

The reaction temperature of the present invention is not particularly limited as long as it does not cleave the basic skeleton (arene ring) of the calix [4] arene during the detertiary butylated reaction. Although it is related to the amount of sulfated zirconia used relative to the starting material p-tert-butylcalix [4] arene, the reaction temperature is preferably 70 ° C. or higher and 110 ° C. or lower under normal pressure. When the reaction temperature is lower than 70 ° C., it takes a very long time to complete the reaction when the amount of sulfated zirconia is small. When the reaction temperature exceeds 110 ° C., the arene ring of p-tert-butylcalix [4] arene is cleaved and the desired product cannot be obtained. The means for heating the reaction system is not particularly limited, and electric resistance, steam, microwave energy and the like can be used. The reaction vessel may be a batch type or a continuous flow type. Moreover, although reaction of this invention advances under a normal pressure, it is also possible to make it react under pressure.

After completion of the reaction, sulfated zirconia is filtered off, filtered, and methanol or the like is added to the reaction solution to precipitate the target product. This precipitate is filtered, washed, and dried, which is close to 100%. A calix [4] arene is obtained in purity. That is, high-purity calix [4] arene can be obtained with high yield only by heating, filtration, and concentration.

The sulfated zirconia used in the reaction of the present invention can be reused in the next reaction by regeneration. Regeneration of sulfated zirconia, washing liquid active sites on the catalyst surface (e.g., sulfuric acid) is washed and activated with, after washing away the cleaning liquid such as water, is achieved by heating and drying at about 500 ° C. .

In the production method according to the present invention, as described above, the detertiary butylated reaction is carried out at a predetermined heating temperature in the presence of a predetermined amount of sulfated zirconia and toluene , so that toluene is p-tert-butylcalix [4] arene. The sulfated zirconia allows the detertiary butylated reaction to proceed with high efficiency. In addition, a portion of the toluene binds to and traps the tertiary butyl group released during the reaction. Due to these reasons, the production method of the present invention can produce calix [4] arene with high yield.

  Further, the production method according to the present invention does not generate toxic gas compared to the conventional reaction using anhydrous aluminum chloride, and does not require a water washing step for the catalyst after the reaction. Can be obtained. Accordingly, water is not required for separation and purification of the target product after the reaction, that is, almost no waste liquid is generated, so that an environmentally friendly production method can be provided.

On the other hand, sulfated zirconia, which is a solid superacid catalyst , is more expensive than anhydrous aluminum chloride and less expensive than strongly acidic ion exchange resins. However, anhydrous aluminum chloride can only be used for one reaction. In addition, the ion exchange resin can be regenerated. However, since the heat deterioration during reaction use is fast, the catalyst activity decreases every time it is regenerated, so that it cannot be used many times. In contrast, sulfated zirconia can be regenerated by washing and heat drying after use of the reaction, and the target product can be obtained in a high yield without reducing the catalytic activity even after a large number of regenerations. That is, when sulfated zirconia is repeatedly used many times, the overall price is reduced.
As described above, according to the present invention, there is provided a method for producing calix [4] arene that can simplify the production process while achieving high-yield production of calix [4] arene, and is inexpensive and environmentally friendly. It can be provided.

Hereinafter, embodiments of the present invention will be specifically described with reference to examples. However, the technical scope of the present invention is not limited to these examples.
First, optimum reaction conditions were sought in Examples 1 to 10.

  Put 0.5 g of p-tert-butylcalix [4] arene, 1 g of sulfated zirconia (S04 / ZrO2; manufactured by Wako Pure Chemical Industries, Ltd .; product code 268-01762) formed into pellets and 5 ml of toluene into an eggplant flask. , And reacted at 110 ° C. under reflux for 5 hours. Next, after cooling the reaction solution, pelletized sulfated zirconia was filtered off, the reaction solution obtained by filtration was placed in a rotary evaporator maintained at 60 ° C., and toluene was distilled off and concentrated to 1 to 3 ml. Subsequently, methanol was added to the concentrated solution to precipitate insoluble components, and then the insoluble components were collected by filtration and dried to obtain a white powder as a product. When the obtained product was analyzed by NMR, only detertially butylated calix [4] arene (yield 214 mg, yield 65%) was detected, and no other product was observed.

  For reference, the 1H NMR spectrum obtained in Example 1 is shown in FIG. FIG. 1A shows the NMR spectrum of the starting material p-tert-butylcalix [4] arene, and FIG. 1B shows the NMR spectrum of the target product calix [4] arene. In addition, the gas chromatogram and mass spectrum of the reaction liquid after 30 minutes from the start of the detertiary butylated reaction are shown in FIG. 2, and the gas chromatogram and mass spectrum of the reaction liquid after 180 minutes from the start of the reaction are shown in FIG. Show.

The reaction of such an example is shown in the following reaction formula (IV). As shown in this reaction formula (IV), the tertiary butyl group released from the p-tert-butylcalix [4] arene is combined with a part of toluene to form tert-butylmethylbenzene.

  The same operation as in Example 1 was performed except that 5 ml of toluene used in Example 1 was changed to 10 ml, and 230 mg of white powder was obtained as a product. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 70%) was detected, and no other products were observed.

  The same operation as in Example 1 was carried out except that 5 ml of toluene used in Example 1 was changed to 20 ml and the reaction time was changed to 6 hours to obtain 250 mg of white powder as a product. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 76%) was detected, and no other products were observed.

  The same operation as in Example 1 was carried out except that 1 g of sulfated zirconia used in Example 1 was 2 g, 5 ml of toluene was 20 ml, and the reaction time was 5 hours, and 150 mg of white powder was obtained as a product. Got as. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 46%) was detected, and no other product was observed.

  The same operation as in Example 4 was carried out except that the reaction time of 2 hours in Example 4 was changed to 5 hours to obtain 131 mg of white powder as a product. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 40%) was detected, and no other products were observed.

  The same operation as in Example 4 was carried out except that 2 g of sulfated zirconia used in Example 4 was changed to 4 g and the reaction time was set to 1 hour to obtain 147 mg of white powder as a product. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 45%) was detected, and no other products were observed.

  The same operation as in Example 6 was carried out except that the reaction time in Example 6 was changed to 4 hours to obtain 46 mg of white powder as a product. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 14%) was detected, and no other products were observed.

  The same operation as in Example 7 was performed except that the reaction temperature of 110 ° C. in Example 7 was changed to 100 ° C., and 122 mg of white powder was obtained as a product. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 37%) was detected, and no other product was observed.

  The same operation as in Example 7 was performed except that the reaction temperature 110 ° C. in Example 7 was changed to 90 ° C., and 184 mg of white powder was obtained as a product. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 56%) was detected, and no other products were observed.

  The same operation as in Example 7 was carried out except that the reaction temperature of 110 ° C. in Example 7 was changed to 80 ° C., and 194 mg of white powder was obtained as a product. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 59%) was detected, and no other products were observed.

The reaction conditions from Example 1 to Example 10, the yield of calix [4] arene and the yield are summarized in Table 1 below. The results of Examples 1-10 are also shown in FIGS. FIG. 4 is a graph showing changes in yield depending on the amount of sulfated zirconia used and the reaction time, FIG. 5 is a graph showing changes in yield depending on the reaction temperature and reaction time, and FIG. 6 is based on the amount of solvent used and reaction time. It is the graph which showed the change of the yield. The amount of sulfated zirconia shown in FIG. 4 is expressed as a percentage (% w / w) of the weight of sulfated zirconia with respect to the total weight of p-tert-butylcalix [4] arene, sulfated zirconia, and toluene. It represents.

  According to Table 1, among Examples 1 to 10, Example 3 had the best yield. Further, as apparent from Table 1 and FIGS. 4 to 6, 1 g to 4 g of sulfated zirconia and 10 to 20 ml of toluene as a reaction solvent are reacted with 0.5 g of p-tert-butylcalix [4] arene. It can be seen that the reaction can be carried out efficiently when the temperature is in the range of 110 to 80 ° C. If the amount of sulfated zirconia is increased beyond this range or the amount of toluene is decreased, the basic skeleton of calix [4] arene is decomposed, leading to a decrease in yield. On the other hand, when the amount of sulfated zirconia is reduced, the reaction temperature is lowered, or the amount of toluene is increased, the reaction time becomes much longer than 6 hours, and much labor and energy cost are required.

The following Examples 11 and 12 show examples in which used sulfated zirconia is regenerated and reused in a detertiary butylated reaction.
In Example 11, 1 g of pelletized sulfated zirconia that had been used once was washed with 2N H ₂ SO ₄ , water, and acetone, and heated and dried in an electric furnace at 500 ° C. for 1 hour, and p-tert-butyl Calix [4] arene 0.5 g and toluene 10 ml were placed in an eggplant flask and the same operation as in Example 2 was performed. As a result, 230 mg of white powder was obtained as a product. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 70%) was detected, and no other products were observed.

  1 g of pelletized sulfated zirconia used in Example 11 (used twice) was regenerated and used in the reaction in the same manner as in Example 11. Such a reaction and regeneration operation was repeated to obtain sulfated zirconia after 5 times of used regeneration. The reaction operation was performed in the same manner as in Example 11 using the pelletized sulfated zirconia that had been used five times. As a result, 230 mg of white powder was obtained as a product in the sixth reaction. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 70%) was detected, and no other products were observed.

[Comparative Example 1]
The same operation as in Example 2 was performed except that 1 g of Nafion SAC13 (strongly acidic ion exchange resin) was used instead of 1 g of sulfated zirconia used in Example 2, and 240 mg of white powder was used as a product. Obtained. When the obtained product was analyzed by NMR, only detertiary butylated calix [4] arene (yield 73%) was detected, and no other product was observed.

[Comparative Example 2]
Nafion SAC13 (1 g) used once in Comparative Example 1 was washed with 2N H ₂ SO ₄ , water and acetone and dried at 110 ° C. for 2 hours, p-tert-butylcalix [4] arene 0 .5 g and 10 ml of toluene were placed in an eggplant flask and the same operation as in Example 4 was performed. As a result, 190 mg of white powder was obtained as a product. When the obtained product was analyzed by NMR, only de-tert-butylated calix [4] arene (yield 58%) was detected, and no other products were observed.

[Comparative Example 3]
For Nafion SAC13, the same operation as in Comparative Example 2 was performed, and the reaction and regeneration were repeated 5 times. In each case, the amount of the target product (white powder) obtained was 150 mg (when using Nafion SAC13 after used regeneration twice), 120 mg (when using Nafion SAC13 after used regeneration three times) , 98 mg (when Nafion SAC13 after 4 times used regeneration was used) and 80 mg (when Nafion SAC13 after 5 times used regeneration was used; yield 24%) were successively decreased.

As described above, the reaction yield of Nafion SAC13 decreased each time the reaction and regeneration were repeated, and the yield of the target product was as low as 24% after the sixth use. On the other hand, in Example 12, in which sulfated zirconia, which had been repeated and regenerated five times, was used for the sixth reaction, the yield of the target product was as shown in Table 2 below when the first reaction was used. It was as high as (Example 2, 70%). That is, the sulfated zirconia used in the examples of the present invention can be obtained in a high yield even if it is a regenerated product that has undergone a considerable number of regenerations.

[Comparative Example 4 ]
0.5 g of p-tert-butylcalix [8] arene, 1 g of pelleted sulfated zirconia and 20 ml of toluene were refluxed at 110 ° C. for 6 hours, but p-tert-butylcalix [8] arene was almost dissolved in toluene. The detertiary butylation reaction could not be performed.

  The calix [4] arene obtained by the production method according to the present invention can introduce various substituents at the 4-position of each phenol unit. Since such modifications can change the inclusion ability, calix [4] arene can be an important host molecule in supramolecular chemistry.

The NMR spectrum obtained in the Examples is shown, (a) is a diagram showing the NMR spectrum of the starting p-tert-butylcalix [4] arene, and (b) is the target product calix [4] arene. It is a figure which shows a NMR spectrum. It is a figure which shows the gas chromatogram and mass spectrum of a reaction liquid at the time of 30-minute progress after a detertiary butylated reaction start. It is a figure which shows the gas chromatogram and mass spectrum of a reaction liquid at the time of 180-minute progress after the start of detertiary butylation reaction. It is the graph which showed the change of the yield of calix [4] arene by the usage-amount of sulfated zirconia and reaction time. It is the graph which showed the change of the yield of calix [4] arene by reaction temperature and reaction time. It is the graph which showed the change of the yield of calix [4] arene by solvent usage-amount and reaction time.

Claims (3)

The following general formula (I);

The p-tert-butyl-calix [4] arene 1 part by weight shown in, 80 in the presence of 8 parts by weight or more than 2 parts by weight of sulfated zirconia and 8.66 parts by weight or more 34.64 parts by weight of toluene By heating to a temperature not lower than 110 ° C. and not higher than 110 ° C., the following general formula (II):

A method for producing calixarene, which comprises obtaining a calix [4] arene represented by the formula:
The following general formula (I);

In the presence of 2 to 4 parts by weight of sulfated zirconia and 8.66 to 17.32 parts by weight of toluene with respect to 1 part by weight of p-tert-butylcalix [4] arene represented by Heat to a temperature of 100 ° C. or higher and 110 ° C. or lower, and the following general formula (II):

In indicated the calix [4] arene and the resulting manufacturing process characteristics and to Luke calixarene the Rukoto. Sulfated zirconia, claim 1 or, wherein the reaction is several times repeatedly regenerated catalyst obtained in the following steps five times for heating and drying the After washing the used solid superacid catalysts The manufacturing method of the calixarene of Claim 2.

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