JP2009040872A - Acylated rotaxane and method for producing it - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide rotaxane and a method for producing it wherein hydroxy groups of cyclodextrin as a ring component are modified at a high modification ratio. <P>SOLUTION: When rotaxane, wherein a straight chain molecule penetrates an opening part of cyclodextrin while both terminal ends of the straight chain molecule have blocking groups, and vinyl esters as a solvent are brought into reaction with each other in the presence of an acid catalyst, some or all of the hydroxy groups of the cyclodextrin are acylated with acyl groups of the vinyl esters. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an acylated rotaxane containing an acyl derivative of cyclodextrin as a ring component and a method for producing the same.

  As a kind of rotaxane, a rotaxane in which a linear molecule penetrates through an opening of a cyclodextrin and both ends of the linear molecule are blocked is known. This rotaxane has a low solubility in organic solvents, and therefore its use is limited for that reason.

Patent Document 1 includes nitrogen-containing organic solvents such as dimethylacetamide containing lithium chloride and the like, and ionic liquids containing dialkylimidazolium and the like as good solvents for rotaxane. In Patent Document 1, various solubilized rotaxanes are obtained by modifying rotaxanes using these good solvents.
JP 2007-63517 A

  Even if the hydroxyl group of cyclodextrin, which is a ring component of rotaxane, is modified by various conventional methods and solubilized, the reaction does not proceed easily due to the low solubility of rotaxane, and as a result, the rotaxane has a low modification rate. I could only get it. Moreover, if the special solution described in Patent Document 1 is used, the modification rate is improved as compared with the conventional method, but it is not sufficient.

  The present invention has been made in view of such a situation, and an object thereof is to provide a rotaxane in which the hydroxyl group of cyclodextrin as a ring component is modified at a high modification rate, and a method for producing the rotaxane.

  In order to achieve the above object, first, the present invention provides an acylated rotaxane comprising an acyl derivative of cyclodextrin as a ring component, wherein the acyl derivative of cyclodextrin is modified with a hydroxyl group of cyclodextrin of 80% or more. The present invention provides an acylated rotaxane characterized by being acylated at a high rate (claim 1).

  In the above invention (Invention 1), the acyl derivative of cyclodextrin may be one in which all hydroxyl groups of cyclodextrin are acylated (Invention 2).

  In the above invention (Invention 1), the cyclodextrin acyl derivative may be one in which the hydroxyl group of cyclodextrin is acetylated at a modification rate of 80% or more (Invention 3).

  In the above invention (Invention 1), the cyclodextrin acyl derivative may be one in which all hydroxyl groups of cyclodextrin are acetylated (Invention 4).

  Secondly, in the present invention, a rotaxane having a linear molecule penetrating through an opening of a cyclodextrin and having a blocking group at both ends of the linear molecule, and a vinyl ester are produced under an acid catalyst. Provided is a method for producing an acylated rotaxane, characterized by reacting and acylating a part or all of the hydroxyl groups of the cyclodextrin with the acyl groups of the vinyl esters (Claim 5).

  According to the said invention (invention 5), the acylated rotaxane acylated with the high modification rate of the cyclodextrin which is a ring | wheel component with the high modification rate, specifically, the modification rate of 80% or more can be manufactured.

  In the said invention (invention 5), it is preferable to use the said vinyl ester as a solvent (invention 6).

  According to the present invention, an acylated rotaxane obtained by acylating a hydroxyl group of cyclodextrin as a ring component with a high modification rate can be obtained. This acylated rotaxane has high solubility in organic solvents and can be used for various applications.

Hereinafter, embodiments of the present invention will be described.
In this embodiment, an acylated rotaxane is produced using a cyclodextrin acyl derivative in which the hydroxyl group of cyclodextrin is acylated at a modification rate of 80% or more as a ring component.

  In this embodiment, as a first step, a rotaxane having a linear molecule penetrating through an opening of a cyclodextrin molecule and having blocking groups at both ends of the linear molecule is produced. This rotaxane can be produced by a conventional method. Usually, a pseudo rotaxane is produced, and then a rotaxane is produced from the obtained pseudo rotaxane.

  The pseudo-rotaxane produced in this embodiment is one in which a linear molecule (axial molecule) having a functional group at the terminal penetrates through an opening of a cyclodextrin molecule that is a ring component. In this embodiment, first, a linear molecule having a functional group at the terminal is prepared.

  In the present specification, “linear” of “linear molecule” means substantially “linear”. That is, as long as the cyclic molecule (ring component) can move on the linear molecule, the linear molecule may have a branched chain.

  Examples of the linear molecule include linear alkanes having 8 or more carbon atoms having a functional group at the end, such as diaminooctane, diaminodecane, diaminododecane, diaminopentadecane, diaminooctadecane, diaminoeicosane; polytetrahydrofuran, Examples include polyethylene glycol, polypropylene glycol, polyisoprene, polyisobutylene, polybutadiene, polydimethylsiloxane, and the like. In view of the modification rate of cyclodextrin, the number of carbon atoms having a functional group at the terminal is 8 to 20, particularly 10 to 15 carbon atoms. The linear alkane is preferable.

  The number average molecular weight (Mn) of the linear molecule is preferably 200 to 1,000,000, and more preferably 1,000 to 100,000. When the number average molecular weight is less than 200, it is difficult to penetrate the cyclodextrin, and when the number average molecular weight exceeds 1,000,000, the modification rate of the cyclodextrin may be lowered.

  The terminal functional group of the linear molecule is not particularly limited as long as it can react with a block group described later to block the end of the linear molecule, but preferably a hydroxyl group, an amino group, an isocyanate group, At least one selected from the group consisting of a carboxyl group, a vinyl group and an epoxy group is used.

  When the linear molecule has the functional group at the end, the functional group may be used, but it is necessary even when the linear molecule does not have the functional group at the end or has the functional group. Accordingly, the functional group is added to the end of the linear molecule. The addition of the functional group to the end of the linear molecule can be carried out by a conventionally known method such as the method described in Nature, 356, 325-327 (1992).

  As described above, a linear molecule having a functional group at the terminal is prepared, and the linear molecule is included with cyclodextrin (cyclodextrin is skewered with the linear molecule) to obtain a pseudorotaxane.

  The cyclodextrin may be any of α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin, but it is particularly preferable to use α-cyclodextrin. Because α-cyclodextrin has the smallest ring, it is easy to block the linear molecular terminal of the pseudorotaxane with a blocking group.

  Pseudorotaxane is produced by placing a linear molecule having a functional group at the end and a cyclodextrin in a solvent, usually in water (for example, adding the linear molecule to an aqueous solution of cyclodextrin. ), By stirring the solution. In addition, it is preferable to stand the solution after stirring because the yield can be improved. A preferable stationary period is about 1 to 7 days.

  There is no restriction | limiting in particular about the stirring method, It can stir by methods, such as a mechanical stirring process and an ultrasonic treatment, at normal temperature or the temperature controlled appropriately. In particular, stirring by ultrasonic treatment is preferable because the number of penetrations can be easily controlled. The stirring time is preferably performed under conditions of several minutes to 1 hour. Although there is no restriction | limiting in particular about the irradiation conditions of an ultrasonic wave, It is preferable to carry out with a frequency of 20-40 kHz.

  After the pseudorotaxane is produced as described above, a blocking group that can react with the terminal functional group of the linear molecule of the pseudorotaxane is reacted with the terminal functional group, and the blocking group is added to the terminal of the linear molecule. As a result, rotaxane is obtained.

  The blocking group is not particularly limited as long as the cyclodextrin as a ring component can maintain a form skewered by a linear molecule, but preferably a dialkylphenyl group, a dinitrophenyl group, a cyclo group. Dextrins, adamantane groups, trityl groups, fluoresceins, pyrenes, anthracenes and the like are appropriately selected. Specifically, dimethylphenyl isocyanate, tritylphenyl isocyanate and the like are suitably used as the reaction reagent for the blocking group.

  The reaction of the blocking group on the linear molecule can be carried out by a conventionally known method, for example, the method described in Nature, 356, 325-327 (1992).

  Once the rotaxane is produced as described above, as a second step, the obtained rotaxane and the vinyl ester are reacted in the presence of an acid catalyst to acylate the hydroxyl group of cyclodextrin with the acyl group of the vinyl ester. To do. At this time, vinyl esters are preferably used as a solvent. Specifically, it is preferable to react by adding a rotaxane and an acid catalyst to vinyl esters.

  In the present invention, vinyl esters refer to a compound group having a structure in which a carboxylic acid and a compound having a double bond are ester-bonded via a carbon atom constituting the double bond. It can have a functional group of Examples of such vinyl esters include isopropenyl acetate, vinyl acetate, isopropenyl benzoate, 2-benzoxypentafluoropropene, etc. Among them, the reactivity is good, and purification of the obtained acylated rotaxane is possible. From an easy viewpoint, isopropenyl acetate and isopropenyl benzoate are preferred. In addition, when acetate is used as vinyl ester, the hydroxyl group of cyclodextrin will be acetylated.

The usage-amount of vinylesters is not specifically limited, It can select suitably in the range which can be used as a solvent.

  The acid catalyst is not particularly limited as long as it is generally used in acylation of a hydroxyl group. For example, p-toluenesulfonic acid, pyridinium p-toluenesulfonate, sulfuric acid, hydrochloric acid, benzenesulfonic acid, methanesulfone An acid or the like can be used. However, p-toluenesulfonic acid is more preferred because it is solid and easy to handle and has fewer side reactions than high reactivity.

  Although the usage-amount of an acid catalyst changes also with the kind of catalyst, generally it is preferable that it is 1-20 mass parts with respect to 100 mass parts of cyclodextrins, and it is especially preferable that it is 2-10 mass parts. .

  Since the reaction between the rotaxane and the vinyl ester proceeds efficiently under heating, the vinyl ester, the rotaxane, and the acid catalyst are usually mixed and then heated. The heating temperature is preferably 40 to 150 ° C, and particularly preferably 60 to 90 ° C.

  The reaction time is preferably 3 to 15 hours. In particular, when acylating the hydroxyl group of cyclodextrin by 90% or more, it is preferably 5 to 12 hours, and the hydroxyl group of cyclodextrin is 100% acylated. When it does, it is preferable that it is 7 to 12 hours.

  Further, by performing the above reaction step twice or more, the hydroxyl group of cyclodextrin can be acylated by 90% or more, and in some cases 100%. For example, when the above reaction step is performed twice, the reaction time per reaction step is preferably 2 to 6 hours, and more preferably 3 to 5 hours. When the second and subsequent reactions are performed, the acylated rotaxane obtained in the previous reaction may be mixed with the newly prepared vinyl ester and the acid catalyst, and the reaction may be performed. The acylated rotaxane may be introduced into the reaction vessel in which the vinyl esters and acid catalyst used in the previous reaction remain and reacted.

  According to the above method, an acylated rotaxane having a cyclodextrin acyl derivative acylated with a cyclodextrin having a hydroxyl group of 80% or more and, in some cases, 100%, can be obtained. In particular, when acetic acid esters are used as vinyl esters, it is possible to obtain an acetylated rotaxane containing a cyclodextrin acetylated derivative in which the hydroxyl group of cyclodextrin is 80% or more, and in some cases 100% acetylated, as a ring component. it can. Thus, the acylated rotaxane with a high modification rate of the hydroxyl group of cyclodextrin is a novel rotaxane that has not existed before. The purification may be performed by a conventional method.

  The obtained acylated rotaxane has high solubility in organic solvents such as alcohols, ketones, ethers, esters and halogenated alkyls. Specifically, it exhibits high solubility in tetrahydrofuran (THF), methanol, ethanol, isopropanol, chloroform, methylene chloride, ethyl acetate, dimethylformamide (DMF) and the like. On the other hand, since normal rotaxane is soluble only in dimethyl sulfoxide (DMSO) or sodium hydroxide solution, the acylated rotaxane obtained in this embodiment can be used for various applications.

  As described above, in this embodiment, a rotaxane can be obtained as a first step, and a hydroxyl group of a cyclodextrin of the rotaxane can be acylated as a second step to obtain a rotaxane with a high modification rate.

  In order to obtain an acylated rotaxane, a method of previously acylating the hydroxyl group of cyclodextrin and then skewing the acylated cyclodextrin with a linear molecule is also conceivable. However, with this method, the acylated cyclodextrin does not dissolve in water, and the acyl group blocks the cyclodextrin opening, making it difficult to skew the acylated cyclodextrin with linear molecules. There is no rotaxane.

  On the other hand, cyclodextrin dissolves in vinyl esters, but rotaxane does not dissolve in vinyl esters, and multiple cyclodextrins that include linear molecules are close to each other by hydrogen bonds. Since it seems difficult to acylate the hydroxyl group, the method according to this embodiment is not usually selected, but when actually performed, the hydroxyl group of cyclodextrin was acylated at a high modification rate.

  EXAMPLES Hereinafter, although an Example etc. demonstrate this invention further more concretely, the scope of the present invention is not limited to these Examples etc.

[Example 1]
65 mg of 1,10-diaminodecane was added to 5 ml of a saturated aqueous solution of α-cyclodextrin (manufactured by Nacalai Tesque), subjected to ultrasonic treatment (frequency: 25 kHz) for 60 minutes, and then allowed to stand at room temperature for 1 day. Thereafter, while stirring in an ice bath, 550 mg of 3,5-dimethylphenyl isocyanate (manufactured by Aldrich) was added dropwise and stirred as it was for 1 hour. Next, the reaction solution was poured into tetrahydrofuran, and the precipitated solid was collected, washed with water, and dried to obtain 900 mg of a white solid rotaxane.

900 mg of the obtained rotaxane and 20 mg of p-toluenesulfonic acid as a catalyst were added to 10 ml of isopropenyl acetate as a solvent, and reacted at 70 ° C. for 4 hours. The reaction solution was distilled off under reduced pressure, and the resulting solid was washed with a 10% by mass aqueous sodium carbonate solution. Subsequently, a peak having a molecular weight of about 3000 was collected by preparative gel permeation chromatography (developing solvent: chloroform) to obtain 400 mg of a white solid acetylated rotaxane. ¹ H-NMR (manufactured by JEOL Ltd., using nuclear magnetic resonance apparatus JNM-LA400 / WB) and MALDI-TOF mass spectrometry (manufactured by SHIMAZU, using Mass AXIMA-CFR-S, matrix during measurement) of the obtained acetylated rotaxane 1 and FIG. 2 show the analysis results by using 2,5-dihydroquinbenzoic acid as

As a result of ¹ H-NMR measurement, it was obtained from the integration ratio of 3 to 6 ppm peak derived from cyclodextrin and 6.7 ppm and 7.0 ppm peaks derived from 3,5-dimethylphenyl group which is a blocking group. The acylated rotaxane was found to contain two cyclodextrins. Further, the modification rate is determined from the integration ratio of the peak near 6.7 ppm derived from the aromatic ring of the 3,5-dimethylphenyl group which is a blocking group and the three peaks near 2 ppm derived from the acetyl group of the acetylated cyclodextrin. Was found to be 92%.

  In addition, as a result of MALDI-TOF mass spectrometry, a molecule corresponding to an acylated rotaxane (hereinafter referred to as “[3] rotaxane”) in which two cyclodextrins are included as a ring component and all the hydroxyl groups thereof are acetylated. An ion peak (3947) could be confirmed.

[Example 2]
The acylated rotaxane obtained in Example 1 was added to the reaction solution distilled under reduced pressure in Example 1, and reacted again at 70 ° C. for 4 hours. And the reaction solution was depressurizingly distilled and the obtained solid was wash | cleaned with 10 mass% sodium carbonate aqueous solution. Subsequently, a peak having a molecular weight of about 3000 was collected by preparative gel permeation chromatography (developing solvent: chloroform) to obtain 350 mg of a white solid acetylated rotaxane. ¹ H-NMR (manufactured by JEOL, using nuclear magnetic resonance apparatus JNM-LA400 / WB) and MALDI-TOF mass spectrometry (manufactured by SHIMAZU, using Mass AXIMA-CFR-S, matrix for measurement) of the obtained acetylated rotaxane 3 and 4 show the results of analysis by using 2,5-dihydroquinbenzoic acid as

As a result of ¹ H-NMR measurement, a peak around 6.7 ppm derived from the aromatic ring of the 3,5-dimethylphenyl group, which is a blocking group, and three peaks around 2 ppm derived from the acetyl group of acetylated cyclodextrin From the integration ratio, it was found that the modification rate was 100%.

  Further, as a result of MALDI-TOF mass spectrometry, a single peak of the molecular ion peak (3947) corresponding to [3] rotaxane could be confirmed. Also from this result, it became clear that the modification rate of acylation was 100%.

[Comparative Example 1]
65 mg of 1,10-diaminodecane was added to 5 ml of a saturated aqueous solution of α-cyclodextrin (manufactured by Nacalai Tesque), irradiated with ultrasonic waves for 60 minutes, and allowed to stand at room temperature for 1 day. Next, 550 mg of 3,5-dimethylphenyl isocyanate (manufactured by Aldrich) was added dropwise with stirring in an ice bath, and the mixture was stirred as it was for 1 hour. Thereafter, the reaction solution was poured into tetrahydrofuran, and the precipitated solid was collected, washed with water, and then dried to obtain 900 mg of a white solid rotaxane.

900 mg of the obtained white solid was added to a solution in which 3.5 g of lithium chloride was dissolved in 40 ml of dimethylacetamide, and the mixture was stirred at 60 ° C. for 2 hours. Next, the solution was cooled to room temperature, 2.3 g of pyridine, 8.5 g of acetic anhydride and 90 mg of dimethylaminopyridine were added, and the mixture was stirred at room temperature for 24 hours. Then, water and chloroform were added to the reaction solution, liquid separation operation was performed, and the chloroform layer was collect | recovered. And after drying under reduced pressure, it wash | cleaned with hexane and 350 mg of acetylated rotaxane of white solid was obtained. ¹ H-NMR (manufactured by JEOL Ltd., using nuclear magnetic resonance apparatus JNM-LA400 / WB) and MALDI-TOF mass spectrometry (manufactured by SHIMAZU, using Mass AXIMA-CFR-S, matrix during measurement) of the obtained acetylated rotaxane The analysis results by using 2,5-dihydroquinbenzoic acid as are shown in FIGS. 5 and 6, respectively.

As a result of ¹ H-NMR measurement, it was obtained from the integration ratio of 3 to 6 ppm peak derived from cyclodextrin and 6.7 ppm and 7.0 ppm peaks derived from 3,5-dimethylphenyl group which is a blocking group. The acylated rotaxane was found to contain two cyclodextrins. Further, the modification rate is determined from the integration ratio of the peak near 6.7 ppm derived from the aromatic ring of the 3,5-dimethylphenyl group which is a blocking group and the three peaks near 2 ppm derived from the acetyl group of acetylated cyclodextrin Was found to be 63%.

  In addition, as a result of MALDI-TOF mass spectrometry, a molecular ion peak (3947) corresponding to [3] rotaxane could not be confirmed.

[Test example] (Solubility test)
For 1 g of various solvents shown in Table 1 (tetrahydrofuran (THF), methanol, ethanol, isopropanol, chloroform (CHCl ₃ ), methylene chloride (CH ₂ Cl ₂ ), ethyl acetate, toluene, dimethylformamide (DMF)) 50 mg of the acylated rotaxane obtained in Example 1, 2 or Comparative Example 1 was added, and the mixture was stirred with a magnetic stirrer for 5 minutes at room temperature to evaluate the solubility of the acylated rotaxane. The solubility was visually confirmed and evaluated according to the following criteria.
○: Dissolved ×: Insoluble matter remained Table 1 shows the results.

  From Example 1 and Example 2, according to the production method of the present invention, it is possible to obtain an acylated rotaxane in which all hydroxyl groups of cyclodextrin, which has been impossible so far, are acylated, and the modification rate is also obtained. It became clear that 80% or more, and in some cases 100% acylated rotaxanes can be obtained.

  Further, from Table 1, the acylated rotaxane having a modification rate of 80% or more obtained in Example 1 and Example 2 is superior in solubility in various solvents compared to the conventional acylated rotaxane of Comparative Example 1. It became clear that.

  Unlike the conventional rotaxane, the acylated rotaxane according to the present invention has high solubility in an organic solvent, and thus can be used for various applications. For example, since the compatibility with the polymer matrix is good, it can be used as one component of the polymer composition. For example, it can be used as a switching element sensor in the electronics field.

2 is a ¹ H-NMR chart of rotaxane produced in Example 1. FIG. 2 is a MALDI-TOF mass spectrometry chart of rotaxane produced in Example 1. FIG. 2 is a ¹ H-NMR chart of rotaxane produced in Example 2. FIG. 2 is a MALDI-TOF mass spectrometry chart of rotaxane produced in Example 2. 2 is a ¹ H-NMR chart of a rotaxane produced in Comparative Example 1. 2 is a MALDI-TOF mass spectrometry chart of rotaxane produced in Comparative Example 1.

Claims (6)

An acylated rotaxane comprising an acyl derivative of cyclodextrin as a ring component,
The acyl derivative of cyclodextrin is characterized in that the hydroxyl group of cyclodextrin is acylated with a modification rate of 80% or more.   The acylated rotaxane according to claim 1, wherein the acyl derivative of cyclodextrin is one in which all hydroxyl groups of cyclodextrin are acylated.   2. The acylated rotaxane according to claim 1, wherein the acyl derivative of cyclodextrin is one in which a hydroxyl group of cyclodextrin is acetylated at a modification rate of 80% or more.   2. The acylated rotaxane according to claim 1, wherein the acyl derivative of cyclodextrin is one in which all hydroxyl groups of cyclodextrin are acetylated.   A cyclodextrin is formed by allowing a linear molecule to pass through the opening of the cyclodextrin and reacting a rotaxane having a blocking group at both ends of the linear molecule with vinyl esters in the presence of an acid catalyst. A method for producing an acylated rotaxane, wherein a part or all of the hydroxyl groups are acylated with an acyl group of the vinyl ester.   The method for producing an acylated rotaxane according to claim 5, wherein the vinyl ester is used as a solvent.

Images