JP2005120263A - Method for producing organic polymer compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing an organic polymer compound capable of reducing adverse effects against natural environment. <P>SOLUTION: A heterocyclic compound and a cyclodextrin are mixed and heated. An empty cyclodextrin may be used. However, the use of a clathrate compound leads to better polymer yields and the like. A further reduction in production cost is possible by collecting and repeatedly using the clathrate compound. Further improvement in polymer yields, the physical properties thereof, and the like can be expected by appropriately selecting guest molecules and the like that are suitable for the type and the cavity size of cyclodextrin depending on the type of a heterocyclic compound to be used as a raw material for the polymer. The organic polymer compound can be produced without using any toxic metal element or the like, so that adverse effects against natural environment can be reduced. In particular, the organic polymer compound can be effectively used for producing a biodegradable polymer such as biodegradable polyester. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a method for producing an organic polymer compound.

  Organic polymer compounds are indispensable materials for various industrial materials in modern society. In particular, in recent years, biodegradable polymers have attracted attention from the viewpoint of consideration for the natural environment. There are a wide variety of biodegradable polymers, for example, polyesters such as polylactic acid, and polyesters obtained by ring-opening polymerization of γ-butyrolactone, δ-valerolactone, ε-caprolactone, etc. Can be mentioned.

  In the production of the organic polymer compound, a metal-containing substance such as a heavy metal catalyst or an inorganic salt machine is often used, and the biodegradable polymer is no exception. However, it is difficult to completely remove the metal element contained in the metal-containing substance from the produced polymer, and this metal element may adversely affect the natural environment. If the polymer is biodegradable, there is an advantage that it does not pollute the natural environment even if it is discarded. However, since the polymer contains a metal element derived from its production process, it is biodegradable. In some cases, the advantages of being a polymer have been impaired. In particular, ring-opening polymerization of γ-butyrolactone, δ-valerolactone, ε-caprolactone and the like has a problem that the reaction does not proceed unless a metal-containing substance is used as a polymerization initiator or the like.

  It is considered that adverse effects on the natural environment can be reduced by eliminating or reducing toxic substances derived from the manufacturing process from all organic polymer compounds as well as the biodegradable polymer.

  Therefore, an object of the present invention is to provide a method for producing an organic polymer compound that can reduce adverse effects on the natural environment.

  In order to solve the above problems, the production method of the present invention is a method for producing an organic polymer compound, comprising cyclodextrin, a derivative thereof, and an inclusion compound having at least one of the both as a host. The method includes a step of heating a composition containing at least one selected compound and a heterocyclic compound.

  Since the production method of the present invention can produce an organic polymer compound without using a toxic metal element or the like, adverse effects on the natural environment can be reduced. It can be used effectively for the production of degradable polymers.

  Hereinafter, although embodiment of this invention is described, this invention is not limited to these embodiment.

  As described above, the production method of the present invention comprises cyclodextrin, a derivative thereof, and at least one compound selected from the group consisting of an inclusion compound having at least one of the two as a host and a heterocyclic compound. Heating the composition comprising. In the present invention, only an empty cyclodextrin or a derivative thereof not containing a guest may be used, or only an inclusion compound including a guest may be used, and an inclusion compound and an empty compound may be mixed. It may be used. The guest of the inclusion compound is not particularly limited and may be any substance, but is preferably a guest that does not contain a toxic heavy metal or the like. The composition of the composition is not particularly limited. For example, the heterocyclic compound may also serve as a guest of the clathrate compound, and the composition may be composed of only the clathrate compound. A composition in which a heterocyclic compound is further added to the compound may be used. Moreover, the said composition may contain suitably substances other than a cyclodextrin, a cyclodextrin derivative, a heterocyclic compound, and the said guest, and a guest may or may not exist as above-mentioned.

  The structure of the organic polymer compound is not particularly limited, but preferably includes a structure obtained by ring-opening polymerization of the heterocyclic compound. In this case, it may contain only a structure derived from the heterocyclic compound, but may contain a structure derived from another substance. For example, it has a structure in which the cyclodextrin or a derivative thereof is bonded to the terminal. You may do it. Since cyclodextrin is a biodegradable substance that does not harm the natural environment, it has the advantage of not imparting undesirable physical properties such as toxicity even if it is bound to the organic polymer compound.

  The cyclodextrin is not particularly limited, and a cyclodextrin having an appropriate size may be used according to the purpose. For example, it includes at least one of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. Is preferred. In particular, a mixture of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin is very inexpensive, and if an organic polymer compound is produced using the mixture, compared with a conventional method using a metal catalyst or the like. Very low cost production is possible. Furthermore, as described above, cyclodextrin has the advantage of being non-toxic unlike metal catalysts.

The cyclodextrin derivative is, for example, a derivative in which at least one hydrogen atom of a hydroxyl group of cyclodextrin is substituted with a substituent, and the substituent is an alkyl group, a hydroxyalkyl group, a dihydroxyalkyl group, a hydroxyaryl group, From the group consisting of a carboxyalkyl group, a carboxyaryl group, an acyl group, a glycosyl group, a maltosyl group, a sulfo group (—SO ₃ H), a phosphono group (—PO ₃ H ₂ ), a group containing an imidazole ring, and a hydroxyamino group It is preferable that at least one selected. Examples of the group containing an imidazole ring include groups derived from imidazole, methylimidazole, histamine and the like. The substituent is more preferably a linear or branched alkyl group having 1 to 18 carbon atoms, a linear or branched hydroxyalkyl group having 1 to 18 carbon atoms, or a linear or branched dihydroxy group having 1 to 18 carbon atoms. An alkyl group, a hydroxyaryl group having 6 to 18 carbon atoms, a linear or branched carboxyalkyl group having 2 to 18 carbon atoms, a carboxyaryl group having 7 to 18 carbon atoms, and an acyl group having 1 to 18 carbon atoms (however, Chain, branched or cyclic structure, which may be saturated or unsaturated), glycosyl groups, maltosyl groups, sulfo groups (—SO ₃ H), phosphono groups (—PO ₃ H ₂ ), and 1-imidazolyl group, 2-imidazolyl group, 4-imidazolyl group, (1-imidazolyl) methyl group, (2-imidazolyl) methyl group, (4-imidazolyl) methyl group, [2- (4-imidazolyl) Chill] amino group, and at least one selected from the group consisting of hydroxy amino group. In the present invention, examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, an isobutyl group, a tert-butyl group, and the like, and a hydroxyalkyl group As, for example, hydroxymethyl group, 2-hydroxyethyl group, 2-hydroxypropyl group, 3-hydroxypropyl group, 2-hydroxybutyl group, 3-hydroxybutyl group, 4-hydroxybutyl group, 2-hydroxypentyl group 3-hydroxypentyl group, 4-hydroxypentyl group, 5-hydroxypentyl group, 2-hydroxyhexyl group, 3-hydroxyhexyl group, 4-hydroxyhexyl group, 5-hydroxyhexyl group, 6-hydroxyhexyl group, etc. Examples of the dihydroxyalkyl group include 2,3-dihydro Cypropyl group, 2,3-dihydroxybutyl group, 3,4-dihydroxybutyl group, 2,4-dihydroxybutyl group, 2,3-dihydroxypentyl group, 3,4-dihydroxypentyl group, 4,5-dihydroxypentyl group 3,5-dihydroxypentyl group, 2,5-dihydroxypentyl group, 2,3-dihydroxyhexyl group, 2,4-dihydroxyhexyl group, 2,5-dihydroxyhexyl group, 3,4-dihydroxyhexyl group, 3 , 5-dihydroxyhexyl group, 4,5-dihydroxyhexyl group, 3,6-dihydroxyhexyl group, 5,6-dihydroxyhexyl group and the like, and examples of the hydroxyaryl group include hydroxyphenyl group and the like, Examples of the carboxyalkyl group include a carboxymethyl group and a carboalkyl group. Examples include a xyethyl group, a carboxypropyl group, a carboxybutyl group, a carboxypentyl group, and a carboxyhexyl group. Examples of the carboxyaryl group include a carboxyphenyl group. Examples of the acyl group include an acetyl group and an ethanoyl group. , Propanoyl group, butanoyl group, pentanoyl group, hexanoyl group, benzoyl group and the like.

  Examples of the heterocyclic compound include lactone, α-hydroxy acid dehydrate, lactam, cyclic carbonate, cyclic acid anhydride, N-carboxy-α-amino acid anhydride (NCA), N-substituted NCA, oxirane, thiirane, It is preferable to include at least one selected from the group consisting of cyclic siloxane, cyclic disilane, cyclic carbonate, oxazole and derivatives thereof, oxazoline and derivatives thereof, thiolactone, cyclic ether, and cyclic thioether. For example, polylactic acid can be produced by using lactide, and various biodegradable polyesters can be produced by using β-propiolactone, β-butyrolactone, γ-butyrolactone, δ-valerolactone, and the like. . “Lactide” may be a generic term for α-hydroxy acid bimolecular dehydrated product or a lactic acid bimolecular dehydrated product, which is the latter in the present invention. Moreover, although the said heterocyclic compound may be used independently, for example, the organic polymer compound manufactured by using together 2 or more types of heterocyclic compounds may be those copolymers.

  More preferably, the heterocyclic compound includes at least one of the compounds represented by any of the following formulas.

式中、Ｒは、水素原子または炭素数１〜１８の直鎖もしくは分枝アルキル基であり、複数の場合は互いに同一でも異なっていても良い。また、前記ヘテロ環式化合物は、β−プロピオラクトン、β−ブチロラクトン、γ−ブチロラクトン、δ−バレロラクトン、ε−カプロラクトン、β−プロピオラクタム、γ−ブチロラクタム、δ−バレロラクタム、ε−カプロラクタム、Ｌ−ラクチド、Ｄ，Ｌ−ラクチド、Ｎ−カルボキシサルコシン無水物、オキサゾール、オキサゾリン、エチレンカーボネート、プロピレンカーボネート、ネオペンチレンカーボネート、５−メチル−１，３−ジオキサン−２−オン、ピバロラクトン、およびγ−ノナノイック−ラクトンからなる群から選択される少なくとも一種類を含むことが特に好ましい。

In the formula, R is a hydrogen atom or a linear or branched alkyl group having 1 to 18 carbon atoms, and when there are a plurality of R groups, they may be the same or different. The heterocyclic compound includes β-propiolactone, β-butyrolactone, γ-butyrolactone, δ-valerolactone, ε-caprolactone, β-propiolactam, γ-butyrolactam, δ-valerolactam, and ε-caprolactam. , L-lactide, D, L-lactide, N-carboxysarcosine anhydride, oxazole, oxazoline, ethylene carbonate, propylene carbonate, neopentylene carbonate, 5-methyl-1,3-dioxan-2-one, pivalolactone, and It is particularly preferable to include at least one selected from the group consisting of γ-nonanoic-lactone.

  The guest of the clathrate compound is not particularly limited as described above and may be any substance. For example, γ-butyrolactone, δ-valerolactone, ε-caprolactone, oxazole, oxazoline, ethylene carbonate, propylene carbonate, neopent It is preferable to include at least one selected from the group consisting of lencarbonate, 5-methyl-1,3-dioxane-2-one, pivalolactone, and γ-nonanoic-lactone. By using such an inclusion compound containing a guest, it is possible to further improve the reaction rate and yield as compared with the case of using empty cyclodextrin. For example, when the inclusion compound contains an inclusion compound formed from β-cyclodextrin and ε-caprolactone, the reaction rate and yield of ring-opening polymerization using various lactones are particularly preferable.

  In the production method of the present invention, the heating temperature is not particularly limited, and may be appropriately determined in consideration of the reaction rate, the yield of the organic polymer compound, and the like, but for example, 20 to 150 ° C., preferably 80 to 150 ° C. More preferably, it is 100-120 degreeC. The heating time is not particularly limited. In order to obtain a high molecular weight organic polymer compound in a high yield, the heating time is preferably as long as possible. From the viewpoint of balance with production efficiency, for example, 24 to 168 hours. , Preferably 48 to 144 hours, more preferably 48 to 72 hours. The heating is preferably performed in an atmosphere of an inert gas such as argon or nitrogen from the viewpoint of improving the yield and suppressing side reactions, but may be performed in the atmosphere depending on circumstances.

  In a conventional method for producing an organic polymer compound, for example, polymerization using a metal catalyst, it is common to perform the reaction at a high temperature of several hundred degrees C or higher, but in the present invention, the reaction is performed at a temperature much lower than that. It is also possible. When the reaction is performed at a low temperature, there are advantages such as high safety, cost reduction associated with heating to a high temperature, and stabilization of quality because deterioration of the organic polymer compound due to high heat can be prevented.

  The composition of the composition is not particularly limited, and may be appropriately determined in consideration of the reaction rate, the yield of the organic polymer compound, and the like. For example, the total amount of the heterocyclic compound is cyclodextrin and its derivatives. The total number is preferably in the range of 1 to 1000 times in terms of moles. The total amount of the heterocyclic compound is more preferably 5 to 100 times by mole, and particularly preferably 5 to 10 times by mole, relative to the total amount of cyclodextrin and its derivatives.

  In the production method of the present invention, as described above, substances other than cyclodextrin, cyclodextrin derivatives, heterocyclic compounds and guests may be used. For example, various organic solvents may be appropriately added. However, according to the production method of the present invention, for example, it is possible to carry out the reaction without using any substance other than cyclodextrin or a derivative thereof and a heterocyclic compound. A polymer compound can be produced. If a toxic organic solvent is not used, adverse effects on the natural environment can be further reduced. If an organic solvent is not required for the reaction, the cost can be reduced and the manufacturing process can be simplified.

  The organic polymer compound of the present invention is produced by the production method of the present invention, and thus has advantages derived from the advantages of the production method of the present invention. The advantages of the production method of the present invention are various as described above. For example, according to the production method that does not use a metal-containing substance, the produced organic polymer compound does not contain a metal element, so that the natural environment caused by the metal element can be obtained. There is no risk of adverse effects.

  Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are only illustrative of the present invention, and the scope of the present invention is not limited to the following examples.

(Measurement conditions, etc.)
The nuclear magnetic resonance (NMR) spectrum was measured using JNM-GSX400 (400 MHz at ¹ H measurement) or JNM-LA500 (500 MHz at ¹ H measurement) manufactured by JEOL Ltd. (JEOL). JNM-GSX400 and JNM-LA500 are trade names of JEOL Ltd. Chemical shifts are expressed in parts per million (ppm). As a standard peak, the peak of water in heavy water was used as an internal standard, or acetonitrile was used as an external standard. Coupling constants (J) are in hertz, and the abbreviations s, d, t, q, m, and br are singlet, doublet, triplet, quadruple, respectively. Represents a quartet, a multiplet, and a broad line. Mass spectrometry (MS) is performed by MALDI-TOF-MS method using AXIMA (trade name) manufactured by Shimadzu / KRATOS, or ESI- using API III plus (trade name) manufactured by Perkin Elmer / Sciex. Performed by MS method. Gel permeation chromatography (GPC) was performed using an instrument manufactured by Tosoh Corporation. All chemicals are reagent grade and purchased from Nacalai Tesque, Tokyo Kasei, Kanto Chemical, Wako Pure Chemicals, or Aldrich.

(Polymer synthesis using δ-valerolactone and γ-cyclodextrin)
In this example, a polymer (organic polymer compound) was synthesized using a composition comprising δ-valerolactone (δ-VL) and γ-cyclodextrin (γ-CD). That is, first, about 270 μmol of γ-cyclodextrin was prepared, enclosed in a simple Schlenk, and dried while heating to 70 ° C. in an oil bath under reduced pressure. Next, 5 times molar amount of δ-valerolactone with respect to γ-cyclodextrin was added to the Schlenk, mixed well with the γ-cyclodextrin, purged with argon, and heated at 100 ° C. for a certain time. After heating, the Schlenk was cooled to room temperature, 10 ml of DMF was added to the composition therein, and the mixture was thoroughly stirred to dissolve it completely. Thereto was added 100 ml of THF to cause precipitation of insoluble matter, which was removed by centrifugation, the solvent was distilled off under reduced pressure, and the precipitated solid was dried at 50 ° C. under reduced pressure to obtain the desired polymer. When ¹ HNMR and MALDI-TOF-MS of this polymer were measured, it was found that poly (δ-valerolactone) and a polymer having a structure in which γ-cyclodextrin was covalently bonded to the end of the poly (δ-valerolactone) chain. It was confirmed to be a mixture of On the other hand, the insoluble material was dried at 50 ° C. under reduced pressure, and its weight was measured. The same experiment was performed several times with different reaction times, and the yield and yield of polymer and the recovered amount of insoluble matter were measured for each. The results are shown in Table 1 below.

表１から分かる通り、本実施例ではきわめて優れた収率でポリ（δ−バレロラクトン）が得られた。しかも、反応に有機溶媒や金属触媒等を必要とせず、δ−バレロラクトンとγ−シクロデキストリンとを混合して不活性ガス置換し、１００℃という低温で加熱するのみで反応が進行した。なお、表１では、ポリマーの収率を算出するにあたり、末端に結合したシクロデキストリンの分子量は考慮していない。

As can be seen from Table 1, poly (δ-valerolactone) was obtained in a very good yield in this example. In addition, an organic solvent or a metal catalyst was not required for the reaction, and the reaction proceeded only by mixing δ-valerolactone and γ-cyclodextrin, substituting with inert gas, and heating at a low temperature of 100 ° C. In Table 1, the molecular weight of the cyclodextrin bonded to the terminal is not considered in calculating the yield of the polymer.

FIG. 1 shows a ¹ HNMR spectrum of each polymer in Table 1. The upper part of FIG. 1 is a ¹ HNMR spectrum diagram of each polymer, and the numbers on the left side show the reaction time. Note that DMSO-d ₆ was used as a measurement solvent. The lower part of FIG. 1 is a ¹ HNMR spectrum of γ-cyclodextrin. As shown in the figure, each polymer showed a signal derived from poly (δ-valerolactone). Further, a signal derived from γ-cyclodextrin bound to the terminal also appeared slightly. As shown in the chemical structural formula of poly (δ-valerolactone) in the figure, a carbon atom sandwiched between carbonyl carbon and ether oxygen in the main chain of poly (δ-valerolactone) is ether from the carbonyl carbon side. The a-position, b-position, c-position and d-position are arranged in order toward the oxygen side. The symbols “a” and “d” in the ¹ HNMR spectrum diagram indicate the signals of protons bonded to the a-position and d-position of poly (δ-valerolactone), respectively.

When ¹ HNMR of the insoluble material was measured, signals indicating the presence of γ-cyclodextrin and δ-valerolactone were confirmed. In Table 1, there is an example in which the weight of the insoluble matter is larger than the weight of the used γ-cyclodextrin, but this is because δ-valerolactone is mixed in the insoluble matter. It was. Presumably, δ-valerolactone is included in γ-cyclodextrin to form a complex (inclusion compound).

Furthermore, when the number average molecular weight Mn (polystyrene conversion) of the polymers shown in Table 1 was measured by GPC, the Mn value increased with an increase in the reaction time, and after reacting for 144 hours or more, Mn = 6.0 × A large value of 10 ⁴ was obtained. This indicates that the polymer obtained in this example has a sufficiently large molecular weight and can have high physical strength and heat resistance that can withstand practical use.

Further, Table 1 except that the amount of γ-cyclodextrin used is twice that described above, the amount of δ-valerolactone used is four times that described above, and the molar amount of δ-valerolactone is 10 times that of γ-cyclodextrin. The reaction was carried out in the same manner as the example shown in. As a result, it was found that although the yield of the polymer was lower than that in Table 1, a larger value of Mn = 1.3 × 10 ⁵ was obtained for the molecular weight.

(Polymer synthesis using D, L-lactide and γ-cyclodextrin)
In this example, a polymer was synthesized using a composition comprising D, L-lactide and γ-cyclodextrin (γ-CD). That is, first, about 400 μmol of γ-cyclodextrin was prepared, sealed in a simple Schlenk, and dried while heating to 70 ° C. in an oil bath under reduced pressure. Next, about 3 times or 5 times the molar amount of D, L-lactide with respect to γ-cyclodextrin is added to this Schlenk, mixed well with the γ-cyclodextrin, then purged with argon, and constant at 100 ° C. Heated for hours. During heating, a part of D, L-lactide sublimated and came out of the reaction system at the lower part of the Schlenk and adhered to the upper part of the Schlenk. The reaction was allowed to return. After heating, the Schlenk was cooled to room temperature, 10 ml of DMF was added to the composition therein, and the mixture was thoroughly stirred to dissolve it completely. Thereto was added 100 ml of THF to cause precipitation of insoluble matter, which was removed by centrifugation, the solvent was distilled off under reduced pressure, and the precipitated solid was dried at 50 ° C. under reduced pressure to obtain the desired polymer. As a result of measuring ¹ HNMR and MALDI-TOF-MS of this polymer, a polymer having a structure in which D, L-lactide is polymerized and a structure in which γ-cyclodextrin is covalently bonded to the end of the polylactic acid chain It was confirmed that this was a mixture. On the other hand, the insoluble material was dried at 50 ° C. under reduced pressure, and its weight was measured. The same experiment was performed several times with different reaction times, and the yield and yield of polymer and the recovered amount of insoluble matter were measured for each. The results are shown in Table 2 below.

本実施例では、ポリ乳酸がきわめて簡単に得られた。また、実施例１と同様、反応に有機溶媒や金属触媒等を必要とせず、しかも低温で反応が進行した。ポリ乳酸は現在生分解性ポリマーとしてもっとも普遍的なポリマーの一つであり、本発明の製造方法で製造することにより、従来品よりもきわめて毒性が低くしかも低コストなポリ乳酸の製造が可能となる。なお、表２では、ポリマーの収率を算出するにあたり、末端に結合したシクロデキストリンの分子量は考慮していない。

In this example, polylactic acid was obtained very easily. Further, as in Example 1, the reaction did not require an organic solvent or a metal catalyst, and the reaction proceeded at a low temperature. Polylactic acid is currently one of the most universal polymers as a biodegradable polymer, and it is possible to produce polylactic acid that is much less toxic and less costly than conventional products by using the production method of the present invention. Become. In Table 2, the molecular weight of the cyclodextrin bonded to the terminal is not considered in calculating the polymer yield.

FIG. 2 shows the polymer of Run 2 in Table 2, that is, the ¹ HNMR spectrum after 48 hours of reaction. Note that DMSO-d ₆ was used as a measurement solvent. A ¹ HNMR spectrum diagram of FIG lower said polymer, middle commercially available polylactic acid, that is, ¹ HNMR spectrum diagram of poly (L- lactide), the upper part is ¹ HNMR spectrum of γ- cyclodextrin. Comparing the illustrated spectrum diagrams, it can be seen that the polymer of this example showed a signal derived from polylactic acid. In addition, a signal derived from γ-cyclodextrin bound to the terminal also appeared slightly. The polymer of this example has a broader peak compared to commercially available poly (L-lactide). This is because the structure of D, L-lactide was used as a raw material for the polymer in this example. It seems to be derived from irregularities compared to poly (L-lactide). It can be expected that poly (L-lactide) can be obtained by using L-lactide as a raw material instead of D, L-lactide. Further, when ¹ HNMR was measured in the same manner for the other polymers in Table 2, a spectrum diagram similar to FIG. 2 was obtained except that the peak intensity ratio was different.

Further, when ¹ HNMR of the insoluble matter was measured, a signal indicating the presence of γ-cyclodextrin and D, L-lactide was confirmed in the same manner as in Example 1, and the presence of D, L-lactide and γ-cyclodextrin was confirmed. It was found that an inclusion compound seems to be formed.

  In addition, since D, L-lactide is easily sublimated, in this example, as described above, a part of the D, L-lactide sublimated during the heating, and it came out of the reaction system at the lower part of Schlenk and adhered to the upper part of Schlenk. D, L-lactide adhering to the upper part of Schlenk was reacted while irradiating the ultrasonic wave as much as possible, dropping it from the vessel wall, and returning it to the reaction system. The substantial amount of D, L-lactide in the system increases, and further improvement in yield can be expected.

(Polymer synthesis using ε-caprolactone and γ-cyclodextrin)
In this example, a polymer was synthesized using a composition comprising ε-caprolactone (ε-CL) and γ-cyclodextrin (γ-CD). That is, first, about 400 μmol of γ-cyclodextrin was prepared, sealed in a simple Schlenk, and dried while heating to 70 ° C. in an oil bath under reduced pressure. Next, about 5-fold molar amount of ε-caprolactone was added to the schlenk, and mixed well with the γ-cyclodextrin, followed by argon substitution and heating at 100 ° C. for a certain time. After heating, the Schlenk was cooled to room temperature, 10 ml of DMF was added to the composition therein, and the mixture was thoroughly stirred to dissolve it completely. Thereto was added 100 ml of THF to cause precipitation of insoluble matter, which was removed by centrifugation, the solvent was distilled off under reduced pressure, and the precipitated solid was dried at 50 ° C. under reduced pressure to obtain the desired polymer. As a result of measuring ¹ HNMR and MALDI-TOF-MS of this polymer, a mixture of poly (ε-caprolactone) and a polymer having a structure in which γ-cyclodextrin is covalently bonded to a chain end of poly (ε-caprolactone). It was confirmed that. In addition, DMSO-d ₆ was used as a measurement solvent for ¹ HNMR. On the other hand, the insoluble material was dried at 50 ° C. under reduced pressure, and its weight was measured. The same experiment was performed several times with different reaction times, and the yield and yield of polymer and the recovered amount of insoluble matter were measured for each. The results are shown in Table 3 below.

表３から分かる通り、本実施例では良い収率でポリ（ε−カプロラクトン）が得られた。また、実施例１および２と同様、反応に有機溶媒や金属触媒等を必要とせず、しかも低温で反応が進行した。なお、表３では、ポリマーの収率を算出するにあたり、末端に結合したシクロデキストリンの分子量は考慮していない。

As can be seen from Table 3, poly (ε-caprolactone) was obtained in a good yield in this example. Moreover, like Example 1 and 2, an organic solvent, a metal catalyst, etc. were not required for reaction, and reaction advanced at low temperature. In Table 3, the molecular weight of the cyclodextrin bonded to the terminal is not considered in calculating the polymer yield.

Further, when ¹ HNMR of the insoluble matter was measured, signals indicating the presence of γ-cyclodextrin and ε-caprolactone were confirmed as in Example 1, and the inclusion compound of ε-caprolactone and γ-cyclodextrin was found to be I found out that it was formed.

(Polymer synthesis using β-butyrolactone and γ-cyclodextrin)
In this example, a polymer was synthesized using a composition comprising β-butyrolactone (β-BL) and γ-cyclodextrin (γ-CD). That is, first, 613 μmol of γ-cyclodextrin was prepared, sealed in a simple Schlenk, and dried while heating to 70 ° C. in an oil bath under reduced pressure. Next, 3070 μmol of β-butyrolactone (about 5 times the molar amount of γ-cyclodextrin) is added to this Schlenk, mixed well with the γ-cyclodextrin, purged with argon, and heated at 100 ° C. for a certain time. did. After heating, the Schlenk was cooled to room temperature, 8 ml of DMF was added to the composition therein, and the mixture was thoroughly stirred to dissolve it completely. Thereto was added 20 ml of THF to cause precipitation of insoluble matter, which was removed by centrifugation, the solvent was distilled off under reduced pressure, and the precipitated solid was dried at 50 ° C. under reduced pressure to obtain the desired polymer. When ¹ HNMR and MALDI-TOF-MS of this polymer were measured, a mixture of poly (β-butyrolactone) and a polymer having a structure in which γ-cyclodextrin was covalently bonded to the end of the chain of poly (β-butyrolactone) It was confirmed that. In addition, DMSO-d ₆ was used as a measurement solvent for ¹ HNMR. On the other hand, the insoluble material was dried at 50 ° C. under reduced pressure, and its weight was measured. The same experiment was performed several times with different reaction times, and the yield and yield of polymer and the recovered amount of insoluble matter were measured for each. The results are shown in Table 4 below.

表４から分かる通り、β−ブチロラクトンを用いても、δ−バレロラクトンやε−カプロラクトンと同様、反応に有機溶媒や金属触媒等を必要とせず、しかも低温で重合させることができた。

As can be seen from Table 4, even when β-butyrolactone was used, the reaction did not require an organic solvent, a metal catalyst, or the like as in the case of δ-valerolactone or ε-caprolactone, and polymerization could be performed at a low temperature.

The yields in Table 4 were calculated by subtracting the weight of γ-cyclodextrin bound to the terminal from the weight of the obtained polymer. This is because the results of ¹ HNMR measurement show that in this example, the effect of γ-cyclodextrin bonded to the polymer terminal is not negligible on the yield calculation. Specifically, it is as follows.

The polymer is composed of a β-butyrolactone residue and a γ-cyclodextrin residue. When the proportion of _β- butyrolactone residues in the polymer is X _β-BL , X _β-BL is represented by the following formula (1 ). In formula (1), N _β-BL is an average value of the number of β-butyrolactone residues bonded to the terminal γ-cyclodextrin residues in the polymer. In this example, Nβ _-BL was calculated from the peak intensity ratio of ¹ HNMR. In formula (1), 86.09 is the molecular weight of β-butyrolactone, and 1297.15 is the molecular weight of γ-cyclodextrin.

Xβ _-BL = (86.09 × Nβ _-BL ) / (1297.15+ (86.09 × Nβ _-BL )) (1)

The value of X _β-BL thus calculated was substituted into the following formula (2) to calculate the yield Y (%) of the polymer. In formula (2), w is the weight of the polymer, and w _i is the weight of β-butyrolactone used in the reaction.

Y = ((w × X _β-BL ) / w _i ) × 100 (2)

When the N _β-BL value was calculated for each polymer in Table 4, the reaction time increased and the N _β-BL value increased. That is, it was found that the longer the reaction time, the higher the molecular weight polymer was obtained.

Further, when ¹ HNMR of the insoluble matter was measured, signals indicating the presence of γ-cyclodextrin and ε-caprolactone were confirmed as in Example 1, and the inclusion compound of ε-caprolactone and γ-cyclodextrin was found to be I found out that it was formed.

(Polymer synthesis using ε-caprolactone and β-cyclodextrin / ε-caprolactone inclusion compound)
In this example, a polymer was synthesized using a composition composed of ε-caprolactone (ε-CL) and β-cyclodextrin / ε-caprolactone inclusion compound (β-CD / ε-CL inclusion compound).

First, a β-CD / ε-CL inclusion compound was prepared. That is, first, a saturated aqueous solution of β-cyclodextrin and a saturated aqueous solution of ε-caprolactone were prepared, and then they were mixed. At this time, the mixing ratio was adjusted so that the molar amount of ε-caprolactone was twice that of β-cyclodextrin. When this mixed aqueous solution was allowed to stand overnight, a white precipitate was formed. The precipitate was collected by filtration and dried at 50 ° C. under reduced pressure for 12 hours to obtain the target β-CD / ε-CL inclusion compound in a yield of 73%. When ¹ HNMR (solvent DMSO-d ₆ or D ₂ O) of this clathrate was measured, it was found that the clathrate was β-CD: ε-CL = 1: 1.

Next, 229 mg (181 μmol) of the β-CD / ε-CL inclusion compound was sealed in a simple Schlenk, and dried while heating to 70 ° C. in an oil bath under reduced pressure. Then, in this Schlenk, 5 times molar amount of ε-caprolactone is added to the β-CD / ε-CL inclusion compound, mixed well with the β-CD / ε-CL inclusion compound, and then purged with argon. And heated at 100 ° C. for a certain time. After heating, the Schlenk was cooled to room temperature, 10 ml of DMF was added to the composition therein, and the mixture was thoroughly stirred to dissolve it completely. Thereto was added 100 ml of THF to cause precipitation of insoluble matter, which was removed by centrifugation, the solvent was distilled off under reduced pressure, and the precipitated solid was dried at 50 ° C. under reduced pressure to obtain the desired polymer. When ¹ HNMR and MALDI-TOF-MS of this polymer were measured, most were poly (ε-caprolactone) and had a structure in which γ-cyclodextrin was covalently bonded to the end of the poly (ε-caprolactone) chain. It was confirmed that the polymer was slightly mixed. In addition, DMSO-d ₆ was used as a measurement solvent for ¹ HNMR. On the other hand, the insoluble material was dried at 50 ° C. under reduced pressure, and its weight was measured. When ¹ HNMR (solvent D ₂ O) of this insoluble material was measured, it was found to be the recovered β-CD / ε-CL inclusion compound. The same experiment was performed several times with different reaction times, and the yield and yield of the polymer and the β-CD / ε-CL clathrate recovery rate were measured for each. The results are shown in Table 5 below.

表５から分かる通り、本実施例では良い収率でポリ（ε−カプロラクトン）が得られた。また、実施例１〜４と同様、反応に有機溶媒や金属触媒等を必要とせず、しかも低温で反応が進行した。なお、表５では、ポリマーの収率を算出するにあたり、末端に結合したシクロデキストリンの分子量は考慮していない。

As can be seen from Table 5, poly (ε-caprolactone) was obtained in good yield in this example. Further, as in Examples 1 to 4, the reaction did not require an organic solvent or a metal catalyst, and the reaction proceeded at a low temperature. In Table 5, the molecular weight of the cyclodextrin bonded to the terminal is not considered in calculating the polymer yield.

Furthermore, when the number average molecular weight Mn (polystyrene conversion) of the polymers shown in Table 1 was measured by GPC, the Mn value increased with an increase in the reaction time. After reacting for 120 hours or more, Mn = 2.8 × After reacting for 10 ⁴ or 144 hours or more, a large value of Mn = 3.2 × 10 ⁴ was obtained. This indicates that the polymer obtained in this example has a sufficiently large molecular weight and can have high physical strength and heat resistance that can withstand practical use.

  In this example, a cyclodextrin inclusion compound and ε-caprolactone were used, but the yield was further improved as compared with Example 3 using empty cyclodextrin and ε-caprolactone. And as can be seen from Table 5, the recovery rate of the β-CD / ε-CL inclusion compound used in this example was 90% or more in all Runs 1 to 5. Therefore, if the production method of this example is applied industrially, poly (ε-caprolactone) can be produced at a very low cost by recovering and reusing the β-CD / ε-CL inclusion compound. Can also be expected.

  In addition, it was when it was made to react by heating at 100 degreeC similarly to a present Example using only a β-CD / ε-CL inclusion compound instead of using a β-CD / ε-CL inclusion compound and ε-caprolactone. The production of polymer was confirmed. However, this example using β-CD / ε-CL inclusion compound and ε-caprolactone had a better yield and the like.

(Polymer synthesis using δ-valerolactone and β-cyclodextrin / ε-caprolactone inclusion compound)
In this example, a polymer was synthesized using a composition comprising δ-valerolactone (δ-VL) and β-cyclodextrin / ε-caprolactone inclusion compound (β-CD / ε-CL inclusion compound). That is, first, a β-CD / ε-CL inclusion compound was prepared in the same manner as in Example 5. Next, 229 mg (181 μmol) of this β-CD / ε-CL inclusion compound was enclosed in a simple Schlenk, and dried while heating to 70 ° C. in an oil bath under reduced pressure. And in this Schlenk, 5-fold molar amount of δ-valerolactone is added to the β-CD / ε-CL clathrate compound and mixed well with the β-CD / ε-CL clathrate compound. And heated at 100 ° C. for a fixed time. After heating, the Schlenk was cooled to room temperature, 10 ml of DMF was added to the composition therein, and the mixture was thoroughly stirred to dissolve it completely. Thereto was added 100 ml of THF to cause precipitation of insoluble matter, which was removed by centrifugation, the solvent was distilled off under reduced pressure, and the precipitated solid was dried at 50 ° C. under reduced pressure to obtain the desired polymer. When ¹ HNMR and MALDI-TOF-MS of this polymer were measured, most of them were poly (δ-valerolactone), and β-cyclodextrin and ε-hydroxycapron at both ends of the poly (δ-valerolactone) chain. It was confirmed that the polymer having a structure in which an acid is covalently bonded is slightly mixed. In addition, DMSO-d ₆ was used as a measurement solvent for ¹ HNMR. On the other hand, the insoluble material was dried at 50 ° C. under reduced pressure, and its weight was measured. When ¹ HNMR (solvent D ₂ O) of this insoluble material was measured, it was found to be the recovered β-CD / ε-CL inclusion compound. The same experiment was performed several times with different reaction times, and the yield and yield of the polymer and the β-CD / ε-CL clathrate recovery rate were measured for each. The results are shown in Table 6 below.

表６から分かる通り、本実施例では非常に優れた収率でポリ（δ−バレロラクトン）が得られた。また、実施例１〜５と同様、反応に有機溶媒や金属触媒等を必要とせず、しかも低温で反応が進行した。なお、表６では、ポリマーの収率を算出するにあたり、末端に結合したシクロデキストリンの分子量は考慮していない。

As can be seen from Table 6, poly (δ-valerolactone) was obtained in a very good yield in this example. Moreover, like Example 1-5, the reaction did not require an organic solvent, a metal catalyst, etc., and reaction advanced at low temperature. In Table 6, the molecular weight of the cyclodextrin bonded to the terminal is not considered in calculating the polymer yield.

Furthermore, when the number average molecular weight Mn (polystyrene conversion) of the polymers shown in Table 1 was measured by GPC, the numerical value of Mn increased as the reaction time increased, and after reacting for 72 hours or more, Mn = 3.0 × A large value of 10 ⁴ was obtained. This indicates that the polymer obtained in this example has a sufficiently large molecular weight and can have high physical strength and heat resistance that can withstand practical use.

A polymer having a structure in which β-cyclodextrin and ε-hydroxycaproic acid are covalently bonded to both ends of a poly (δ-valerolactone) chain is separated from the polymer reacted for 72 hours or longer by GPC, and ¹ HNMR (solvent DMSO -d ₆ ) was measured. FIG. 3 shows the spectrum thereof. The lower part of the figure is a ¹ HNMR spectrum of the polymer, the middle part is a ¹ HNMR spectrum of β-cyclodextrin, and the upper part is a ¹ HNMR spectrum of δ-valerolactone. In the lower spectrum diagram, the chemical structural formula of the polymer is shown, and the half cone in the chemical structural formula is a symbol schematically showing the β-cyclodextrin structure. In the chemical structural formula, the carbon atoms in the polymer chain are labeled α, β, γ, δ, α ′, β ′, γ ′, δ ′, and ε ′, and in the lower spectrum diagram, Each peak with the same symbol corresponds to hydrogen bonded to carbon in the chemical structural formula. In the upper spectrum diagram, the chemical structural formula of δ-valerolactone is shown. In this chemical structural formula, α, β, γ, and δ are attached to carbon atoms, and the peaks with the same reference in the upper spectrum diagram are respectively hydrogen bonded to carbon in the chemical structural formula. Corresponding to The peak indicated by * in each spectrum diagram is a solvent peak. As shown in the spectrum diagram of FIG. 3, the polymer shows a peak derived from a poly (δ-valerolactone) structure, and a peak derived from a β-cyclodextrin structure and an ε-hydroxycaproic acid structure bonded to the terminal. It showed a little. As described above, the polymer having such a structure was a small part of the product of this example, and most of the polymer was poly (δ-valerolactone).

  Since the polymer having the structure shown in FIG. 3 was produced in this example, the mechanism of polymer chain growth in Example 5 and this example was presumed. This is shown in FIG. The figure shows the case where β-CD / ε-CL inclusion compound and ε-caprolactone were used (Example 5), but β-CD / ε-CL inclusion compound and δ-valerolactone were used. The same applies to the case. Moreover, the half cone in the same figure is the symbol which shows a beta-cyclodextrin structure typically like FIG. As shown in FIG. 4, first, ε-caprolactone included in the β-CD / ε-CL inclusion compound binds to the hydroxyl group at the 2-position of β-cyclodextrin and opens the ring. Next, ε-caprolactone (δ-valerolactone in this example) added simultaneously with the inclusion compound is inserted between the opened ε-caprolactone and β-cyclodextrin and opened. To do. In the same manner, polymer chains grow sequentially.

  In addition, FIG. 4 only shows an example of the estimated reaction mechanism typically, and does not limit this invention at all. Moreover, it is unclear whether the polymers of Example 5 and this Example are actually produced by the mechanism of FIG. As described above, the polymer having the structure shown in FIGS. 3 and 4 is only a part of the product of Example 5 and this example. For example, there is another reaction mechanism in addition to the reaction mechanism of FIG. It can also be involved.

  Furthermore, as can be seen from Table 6, the recovery rate of the β-CD / ε-CL inclusion compound used in this example was 90% or more in all of Run 1 to 9 as in Example 5. Therefore, if the production method of this example is applied industrially, poly (δ-valerolactone) is produced at a very low cost by recovering and reusing the β-CD / ε-CL inclusion compound. I can also expect that.

  Further, when the reaction was carried out in the same manner except that the amount of δ-valerolactone used was doubled as described above (10 times the molar amount of β-CD / ε-CL inclusion compound), a polymer having the same structure Was obtained in a very high yield. The results are shown in Table 7 below. This was a better result from the viewpoint of yield and the like than Example 1 using empty cyclodextrin and δ-valerolactone.

以上の通り、実施例１〜６では、反応に有機溶媒や金属触媒等を必要とせず、ヘテロ環式化合物とシクロデキストリンとを混合して不活性ガス置換し、１００℃という低温で加熱するのみで反応が進行した。実施例１〜６では前記不活性ガスとしてアルゴンを使用したが、本発明はこれに限定されず、安価で入手容易な窒素を用いても良いし、場合により不活性ガス置換せずに加熱しても良い。また、シクロデキストリンは空のものを用いても良いが、包接化合物を用いることによりポリマーの収率等がさらに良好になることも分かった。ポリマーの原料となるヘテロ環式化合物の種類に合わせて、シクロデキストリンの種類およびその空孔サイズに合うゲスト分子等を適宜選択することにより、ポリマーの収率および物性等のさらなる向上が見込める。

As mentioned above, in Examples 1-6, an organic solvent, a metal catalyst, etc. are not required for reaction, a heterocyclic compound and cyclodextrin are mixed, inert gas substitution is performed, and it heats only at the low temperature of 100 degreeC. The reaction proceeded. In Examples 1 to 6, argon was used as the inert gas. However, the present invention is not limited to this, and cheap and easily available nitrogen may be used, and in some cases, heating is performed without replacing the inert gas. May be. Moreover, although an empty thing may be used for cyclodextrin, it turned out that the yield of a polymer, etc. become still better by using an inclusion compound. Further improvement in the yield and physical properties of the polymer can be expected by appropriately selecting the type of cyclodextrin and the guest molecule suitable for the pore size according to the type of the heterocyclic compound used as the raw material of the polymer.

  As described above, the production method of the present invention can produce an organic polymer compound without using a toxic metal element or the like, and thus can reduce adverse effects on the natural environment, particularly biodegradation. It can be effectively used for the production of biodegradable polymers such as reactive polyesters. According to the present invention, it is possible to produce a polymer simply by mixing a heterocyclic compound and cyclodextrin without using an organic solvent or a metal catalyst for the reaction and heating at a low temperature. Manufacturing is possible. Moreover, although an empty thing may be used for cyclodextrin, the yield of a polymer, etc. become still better by using an inclusion compound. And if the said inclusion compound is collect | recovered and used repeatedly, the further reduction of manufacturing cost is also possible. Furthermore, the yield and physical properties of the polymer can be further improved by appropriately selecting the type of cyclodextrin and the guest molecule suitable for the pore size according to the type of heterocyclic compound used as the raw material of the polymer. .

1 is a ¹ HNMR spectrum diagram of the product of Example 1. FIG. 2 is a ¹ HNMR spectrum diagram of the product of Example 2. FIG. 2 is a ¹ HNMR spectrum diagram of a part of the product of Example 6. FIG. It is a schematic diagram which shows an example of the reaction mechanism estimated in this invention.

Claims (16)

A method for producing an organic polymer compound, comprising at least one compound selected from the group consisting of cyclodextrin, a derivative thereof, and an inclusion compound having at least one of the two as a host, and a heterocyclic compound The manufacturing method characterized by including the process of heating the composition containing. The production method according to claim 1, wherein the organic polymer compound includes a structure obtained by ring-opening polymerization of the heterocyclic compound. The production method according to claim 1 or 2, wherein the cyclodextrin contains at least one of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. The cyclodextrin derivative is a derivative in which at least one hydrogen atom of a hydroxyl group of cyclodextrin is substituted with a substituent, and the substituent is an alkyl group, a hydroxyalkyl group, a dihydroxyalkyl group, a hydroxyaryl group, a carboxyalkyl group. Selected from the group consisting of a group, a carboxyaryl group, an acyl group, a glycosyl group, a maltosyl group, a sulfo group (—SO ₃ H), a phosphono group (—PO ₃ H ₂ ), a group containing an imidazole ring, and a hydroxyamino group The production method according to claim 1, wherein the production method is at least one. The cyclodextrin derivative is a derivative in which at least one hydrogen atom of a hydroxyl group of cyclodextrin is substituted with a substituent, and the substituent is a linear or branched alkyl group having 1 to 18 carbon atoms, 1 carbon atom -18 linear or branched hydroxyalkyl group, straight chain or branched dihydroxyalkyl group having 1 to 18 carbon atoms, hydroxyaryl group having 6 to 18 carbon atoms, straight chain or branched carboxyalkyl having 2 to 18 carbon atoms Group, a carboxyaryl group having 7 to 18 carbon atoms, an acyl group having 1 to 18 carbon atoms (however, it may contain a linear, branched or cyclic structure and may be saturated or unsaturated), a glycosyl group , maltosyl group, a sulfo group (-SO ₃ H), a phosphono group (-PO ₃ H _2), 1-imidazolyl group, 2-imidazolyl group, 4-imidazolyl group, (1-imidazol And at least one selected from the group consisting of a methyl group, a (2-imidazolyl) methyl group, a (4-imidazolyl) methyl group, a [2- (4-imidazolyl) ethyl] amino group, and a hydroxyamino group. Item 4. The production method according to any one of Items 1 to 3. The heterocyclic compound is lactone, α-hydroxy acid dehydrate, lactam, cyclic ester carbonate, cyclic acid anhydride, N-carboxy-α-amino acid anhydride (NCA), N-substituted NCA, oxirane, thiirane, cyclic siloxane. The manufacturing method in any one of Claims 1-5 containing at least 1 sort (s) selected from the group which consists of a cyclic disilane, cyclic carbonate, oxazole and its derivative (s), oxazoline and its derivative (s), thiolactone, cyclic ether, and cyclic thioether. . The manufacturing method according to any one of claims 1 to 5, wherein the heterocyclic compound contains at least one kind of compounds represented by any of the following formulas.

In the formula, R is a hydrogen atom or a linear or branched alkyl group having 1 to 18 carbon atoms, and when there are a plurality of R groups, they may be the same or different. The heterocyclic compound is β-propiolactone, β-butyrolactone, γ-butyrolactone, δ-valerolactone, ε-caprolactone, β-propiolactam, γ-butyrolactam, δ-valerolactam, ε-caprolactam, L -Lactide, D, L-lactide, N-carboxysarcosine anhydride, oxazole, oxazoline, ethylene carbonate, propylene carbonate, neopentylene carbonate, 5-methyl-1,3-dioxane-2-one, pivalolactone, and γ- The production method according to claim 1, comprising at least one selected from the group consisting of nonanoic lactones. The inclusion compound guest is γ-butyrolactone, δ-valerolactone, ε-caprolactone, oxazole, oxazoline, ethylene carbonate, propylene carbonate, neopentylene carbonate, 5-methyl-1,3-dioxane-2-one, The production method according to any one of claims 1 to 8, comprising at least one selected from the group consisting of pivalolactone and γ-nonanoic-lactone. The manufacturing method in any one of Claims 1-9 in which the said inclusion compound contains the inclusion compound formed from (beta) -cyclodextrin and (epsilon) -caprolactone. The said heating temperature is the range of 20-150 degreeC, The manufacturing method in any one of Claims 1-10. The manufacturing method according to claim 1, wherein the heating time is in the range of 24 to 168 hours. The manufacturing method according to any one of claims 1 to 12, wherein the total amount of the heterocyclic compound in the composition is in a range of 1 to 1000 times in terms of moles with respect to the total amount of cyclodextrin and a derivative thereof. The production method according to claim 1, wherein two or more kinds of the heterocyclic compounds are used in combination, and the organic polymer compound is a copolymer of the two or more kinds of heterocyclic compounds. The organic polymer compound manufactured by the manufacturing method in any one of Claims 1-14. The organic polymer compound according to claim 15, which has a structure in which the cyclodextrin or a derivative thereof is bonded to a terminal.

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