Trimethylene carbonate derivatives and polymers

Abstract

To provide a novel trimethylene carbonate derivative which has biodegradability and biocompatibility and further has functions such as hydrophobicity and adhesiveness.SOLUTION: The trimethylene carbonate derivative is represented by the general formula (1) in the figure. (In the formula, R1 represents a hydrogen atom or C1-C6 alkyl group; and R2 represents a C2-C30 alkyl group, C2-C30 alkenyl group, or C2-C30 alkynyl group.)SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to trimethylene carbonate derivatives and polymers thereof. [Background technology]

[0002] Plastics are an indispensable material in modern social life, but environmental pollution, such as marine pollution by microplastics, is becoming widespread. In addition to approaches such as recycling plastics and preventing them from leaking into the ocean, new biodegradable polymeric materials are attracting attention.

[0003] Biodegradable polymers include, for example, ester-based polymers such as polyhydroxyalkanoates and polylactic acids. However, since ester-based polymers generate acidic organic molecules by hydrolysis, there are concerns about the environmental impact. Under such circumstances, Patent Document 1 and Non-Patent Documents 1-3 disclose polymers obtained from non-ester trimethylene carbonate derivatives. Since the polymers use non-ester compounds as monomers, they do not generate acidic organic molecules after hydrolysis of the polymer, and are therefore expected to be novel biodegradable polymers. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2012-232909 A [Non-patent literature]

[0005] [Non-Patent Document 1] Hiroaki Nobuoka, Hiroharu Ajiro, “Development of Ester Free Type Poly(trimethylene carbonate) Derivatives with Pendant Fluoroaromatic Groups”, Macromol. Chem. Phys. 2019 , 220, 1900051(1-5). [Non-Patent Document 2] Hiroaki Nobuoka, Hiroharu Ajiro, “Novel synthesis method of ester free trimethylene carbonate derivatives”, Tetrahedron Lett. 2019, 60(2), 164-170. [Non-Patent Document 3] Hiroharu Ajiro, Yoshikazu Takahashi, Mitsuru Akashi, “Thermosensitive Biodegradable Homopolymer of Trimethylene Carbonate Derivative at Body Temperature”, Macromolecules 2012, 45(6), 2668-2674. Summary of the Invention [Problem to be solved by the invention]

[0006] Since polymers obtained from non-ester trimethylene carbonate derivatives are expected to be novel biodegradable polymers, there is a demand for the development of polymers having additional properties. An object of the present invention is to provide a novel trimethylene carbonate derivative and a polymer thereof which can impart additional properties. [Means for solving the problem]

[0007] In order to solve the above problems, the trimethylene carbonate derivative according to the present invention is represented by the following general formula (1).

[0008] [ka] (In the formula, R1 represents a hydrogen atom or a C1 to C6 alkyl group, and R2 represents a C2 to C30 alkyl group, a C2 to C30 alkenyl group, or a C2 to C30 alkynyl group.) Effect of the Invention

[0009] The present invention can provide novel trimethylene carbonate derivatives that can impart additional properties, such as hydrophobicity, to polymers. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Hereinafter, an embodiment for carrying out the present invention (hereinafter, simply referred to as "the present embodiment") will be described in detail. The present embodiment is an example for explaining the present invention, and is not intended to limit the present invention to the following content. The present invention can be carried out by appropriately modifying it within the scope of its purpose.

[0011] [Trimethylene carbonate derivatives] The trimethylene carbonate derivative according to the present embodiment is a novel trimethylene carbonate derivative represented by the following general formula (1), in which the side chain represented by R2 is an aliphatic hydrocarbon group.

[0012] [ka] In the trimethylene carbonate derivative represented by the general formula (1), R1 is a hydrogen atom or a C1-C6 alkyl group. Examples of the C1-C6 alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a cyclobutyl group, an n-pentyl group, a neopentyl group, an isopentyl group, a 1-methylbutyl group, a 1-ethylpropyl group, a cyclopentyl group, an n-hexyl group, a 1-methylpentyl group, a 4-methylpentyl group, a 1-ethylbutyl group, a 2-ethylbutyl group, and a cyclohexyl group. In terms of the ease of synthesis of the trimethylene carbonate derivative and high polymerization reactivity, R1 is preferably a hydrogen atom, a methyl group, or an ethyl group.

[0013] R2 is an aliphatic hydrocarbon group, specifically, a C2 to C30 alkyl group, a C2 to C30 alkenyl group, or a C2 to C30 alkynyl group.

[0014] The C2 to C30 alkyl group is not particularly limited as long as it is a linear alkyl group, a branched alkyl group, or a cycloalkyl group having 2 to 30 carbon atoms. Examples of the C2 to C30 alkyl group include an ethyl group, an n-propyl group, an isopropyl group, a cyclopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a cyclobutyl group, an n-pentyl group, a neopentyl group, an isopentyl group, a 1-methylbutyl group, a 1-ethylpropyl group, a cyclopentyl group, an n-hexyl group, a 1-methylpentyl group, a 4-methylpentyl group, a 1,1-dimethylpropyl group, a 2,2-dimethylpropyl group, a 1-ethylbutyl group, a 2-ethylbutyl group, a cyclohexyl group, an n-heptyl group, an n-octyl group, an n-nonyl group, an n-decyl group, an n-undecyl group, an n-dodecyl group, an n-tridecyl group, an n-tetradecyl group, an n-pentadecyl group, an n-hexadecyl group, an n-heptadecyl group, an n-octadecyl group, an n-nonadecyl group, and an n-icosyl group. From the viewpoint of ease of handling of the polymer formed from the trimethylene carbonate derivative, an alkyl group having from C8 to C30 is preferred, and an alkyl group having from C8 to C20 is more preferred.

[0015] The C2-C30 alkenyl group is not particularly limited as long as it is a linear alkenyl group, a branched alkenyl group, or a cycloalkenyl group having a carbon number of 2 to 30. Examples of the C2-C30 alkenyl group include an ethenyl group, a 2-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propenyl group, a 1-butenyl group, a 2-butenyl group, a 3-methyl-2-butenyl group, a 1-methyl-2-butenyl group, a 3-butenyl group, a 1-pentenyl group, a 2-pentenyl group, a 1-hexenyl group, and a 5-hexenyl group.

[0016] The C2 to C30 alkynyl group is not particularly limited as long as it is a linear alkynyl group, a branched alkynyl group, or a cycloalkynyl group having a carbon number of 2 to 30. Examples of the C2 to C30 alkynyl group include an ethynyl group, a 1-propynyl group, a 2-propynyl group, a 1-butynyl group, a 2-butynyl group, a 3-butynyl group, a pentynyl group, and a 1-hexynyl group.

[0017] The above-mentioned trimethylene carbonate derivative is a novel trimethylene carbonate derivative having an alkyl group, an alkenyl group, or an alkynyl group in the side chain, and by making it into such a trimethylene carbonate derivative, it is possible to impart properties such as substrate adhesion and hydrophobicity to a polymer obtained from the trimethylene carbonate derivative in addition to biodegradability and biocompatibility.

[0018] In this specification, "substrate adhesion" refers to the property of a polymer adhering to a substrate. The method for judging the improvement of substrate adhesion is not particularly limited, but for example, if a coating film is uniformly formed on the substrate, it can be judged that the adhesion of the substrate to which the polymer is applied is improved.

[0019] In this specification, "biocompatibility" means that it is unlikely to cause a large pH change during treatment that may cause inflammation, etc. The polymer of the present invention is decomposed by biodegradation into alcohols such as ethylene glycol and oligoethylene glycol, which have low toxicity, and carbon dioxide, and therefore has good biocompatibility even after decomposition.

[0020] In this specification, the term "biodegradable" refers to a property in which a substance (polymer) disappears due to hydrolysis, enzymatic degradation, or microbial decomposition. The polymer obtained from the trimethylene carbonate derivative of this embodiment is decomposed into ethylene glycol, carbon dioxide, or oligoethylene glycol by these decompositions.

[0021] Furthermore, from the viewpoint of the thermal properties of a polymer made of a trimethylene carbonate derivative, a trimethylene carbonate derivative in which the substituent R2 in the general formula (1) has an alkyl group of C8 to C30 is preferred.

[0022] Here, the preferred thermal properties of the trimethylene carbonate derivative may be those evaluated by the 10% thermal weight loss temperature or the melting point, or both, of the polymer. For example, the 10% thermal weight loss temperature is preferably 250°C or higher, more preferably 275°C or higher. The melting point is preferably 0°C or higher, more preferably 4°C or higher.

[0023] Further, from the viewpoint of ease of handling, a trimethylene carbonate derivative in which the substituent R2 in the general formula (1) has an alkyl group of C16 to C30 is more preferable. When the substituent R2 is within this range, the melting point of the polymer becomes higher than room temperature, so that the polymer is in a solid state and is easy to handle.

[0024] Examples of the trimethylene carbonate derivative represented by the general formula (1) include 5-ethoxymethyl-5-methyl-1,3-dioxan-2-one, 5-(n-propoxymethyl)-5-methyl-1,3-dioxan-2-one, 5-isopropoxymethyl-5-methyl-1,3-dioxan-2-one, 5-cyclopropoxymethyl-5-methyl-1,3-dioxan-2-one, 5-(n-butoxymethyl)-5-methyl-1,3-dioxan-2-one, 5-isobutoxymethyl-5-methyl-1,3-dioxan-2-one, 5-(s ec-Butoxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(tert-butoxymethyl)-5-methyl-1,3-dioxan-2-one, 5-cyclobutoxymethyl-5-methyl-1,3-dioxan-2-one, 5-(n-pentyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-neopentyloxymethyl-5-methyl-1,3-dioxan-2-one, 5-isopentyloxymethyl-5-methyl-1,3-dioxan-2-one, 5-(1-methylbutoxymethyl)-5-methyl-1,3-dioxan-2-one San-2-one, 5-(1-ethylpropoxymethyl)-5-methyl-1,3-dioxan-2-one, 5-cyclopentyloxymethyl-5-methyl-1,3-dioxan-2-one, 5-(n-hexyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(1-methylpentyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(4-methylpentyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(1-ethylbutoxymethyl)-5-methyl-1,3-dioxan-2-one, 5-( 2-ethylbutoxymethyl)-5-methyl-1,3-dioxan-2-one, 5-cyclohexyloxymethyl-5-methyl-1,3-dioxan-2-one, 5-(n-heptyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(n-octyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(n-nonyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(n-decyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(n-undecyloxymethyl)-5-methyl-1,3-Dioxan-2-one, 5-(n-dodecyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(n-tridecyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(n-tetradecyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(n-pentadecyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(n-hexadecyloxymethyl)- Examples of such compounds include 5-methyl-1,3-dioxan-2-one, 5-(n-heptadecyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(n-octadecyloxymethyl)-5-methyl-1,3-dioxan-2-one, 5-(n-nonadecyloxymethyl)-5-methyl-1,3-dioxan-2-one, and 5-(n-icosyloxymethyl)-5-methyl-1,3-dioxan-2-one.

[0025] [Manufacturing method] The method for producing the trimethylene carbonate derivative represented by the general formula (1) is not particularly limited, and the derivative can be produced by combining known reactions. For example, the derivative can be produced by the reaction shown in the following synthesis scheme (1).

[0026] After all the reactions shown in the following synthesis scheme (1) are completed, the reaction solution may be purified as necessary to obtain the target product. The purification method is not particularly limited, and may be solvent extraction, silica gel column chromatography, preparative liquid chromatography, recrystallization, or the like.

[0027] [ka]

[0028] Hereinafter, the synthetic scheme (1) will be described. In addition, in the synthetic scheme (1), R1 and R2 are the same as R1 and R2 in the general formula (1), respectively.

[0029] In the first step, the starting triol compound is ring-closed and benzylated to obtain a diol protected compound in which two hydroxy groups are simultaneously protected. The starting triol compound is not particularly limited as long as R1 is a hydrogen atom or a C1-C6 alkyl group. Some specific examples of the starting triol compound are trimethylolmethane, trimethylolethane, and trimethylolpropane.

[0030] The benzylation of a triol compound can be carried out, for example, by reacting it with benzaldehyde in the presence of p-toluenesulfonic acid in an organic solvent such as tetrahydrofuran.

[0031] In the second step, the hydrogen atom of the unreacted hydroxy group of the diol protected product obtained in the first step is substituted with a side chain represented by R2. The type of R2 to be introduced may be within the range of R2 in the above-mentioned general formula (1), and the method of introducing R2 is not particularly limited. For example, when R2 is an alkyl group, R2 can be introduced by reacting with an alkyl bromide represented by R2-Br in an organic solvent in the presence of a base.

[0032] Examples of the organic solvent used in the second step include tetrahydrofuran, N,N-dimethylformamide, and dimethylsulfoxide. Examples of the base used in the second step include sodium hydride, butyllithium, sodium hydroxide, and potassium hydroxide. Examples of the alkyl bromide represented by R2-Br used in the second step include bromoethane, bromopropane, bromobutane, bromopentane, bromohexane, bromoheptane, bromooctane, bromononane, bromoundecane, bromododecane, bromotridecane, bromotetradecane, bromopentadecane, bromohexadecane, bromooctadecane, bromononadecane, and bromoicosane.

[0033] In the third step, the benzyl group of the diol-protected product obtained in the second step is deprotected to obtain a diol compound. A known reaction may be carried out to deprotect the benzyl group as long as it does not affect R1 and R2. For example, the benzyl group can be deprotected by adding an acid such as hydrochloric acid or methanesulfonic acid in an organic solvent such as tetrahydrofuran and carrying out the reaction.

[0034] In the fourth step, the diol compound obtained in the third step is carbonated. A known reaction for carbonation may be carried out as long as it does not affect R1 and R2. For example, carbonation can be carried out by reacting with ethyl chloroformate in an organic solvent such as tetrahydrofuran in the presence of a base such as triethyleneamine, to obtain a trimethylene carbonate derivative represented by general formula (1).

[0035] [polymer] The polymer according to the present embodiment is a polymer obtained by polymerizing the trimethylene carbonate derivative described above. Since the trimethylene carbonate derivative according to the present embodiment is used as a monomer, the polymer has biocompatibility and biodegradability. Furthermore, since the polymer has an aliphatic hydrocarbon group in its side chain, the polymer has substrate adhesion and hydrophobic properties. Therefore, when the polymer is applied to a substrate, the substrate surface can be made hydrophobic.

[0036] The polymer of the present embodiment can be used as a material for bioplastics such as containers and films, a material for medical devices such as catheters and surgical sutures, and a material for drug delivery system (DDS) carriers.

[0037] [Polymer manufacturing method] The trimethylene carbonate derivative represented by the general formula (1) can be polymerized, for example, by the reaction shown in the following synthesis scheme (2). In detail, a polymer can be obtained from the trimethylene carbonate derivative by a polymerization reaction by ring-opening reaction using diazabicycloundecene as a catalyst and an alcohol compound such as benzyl alcohol as an initiator. In addition, in the synthesis scheme (2), R1 and R2 are the same as R1 and R2 in the general formula (1), respectively.

[0038] [ka]

[0039] There is no particular limit to the molecular weight of the polymer obtained by the polymerization reaction, and the weight average molecular weight (Mw), number average molecular weight (Mn), viscosity average molecular weight, etc. can be used as the molecular weight of the polymer depending on the measurement method. The polymer according to this embodiment preferably has a weight average molecular weight (Mw) of 1,000 to 100,000, and more preferably 2,000 to 50,000 from the viewpoint of strength and processability of the polymer. There is no particular limit to the molecular weight distribution (Mw / Mn) of the polymer according to this embodiment, but it is preferably about 1 to 2 from the viewpoint of polymerization control. The method of calculating the molecular weight and molecular weight distribution can include known methods such as gel permeation chromatography (GPC) method, light scattering method, and viscosity method, which are converted based on standard samples such as polystyrene and polyethylene glycol.

[0040] (summary) The present invention can also be expressed as follows.

[0041] The trimethylene carbonate derivative according to the present embodiment 1 is represented by the following general formula (1).

[0042] [ka] (In the formula, R1 represents a hydrogen atom or a C1 to C6 alkyl group, R2 represents a C2 to C30 alkyl group, a C2 to C30 alkenyl group, or a C2 to C30 alkynyl group.

[0043] The configuration of this embodiment 1 makes it possible to impart properties such as substrate adhesion and hydrophobicity in addition to biodegradability and biocompatibility to the polymer obtained from the trimethylene carbonate derivative.

[0044] The trimethylene carbonate derivative according to Aspect 2 has the structure of Aspect 1, where R2 in the above formula (1) is a C8 to C30 alkyl group. The configuration of Aspect 2 makes it possible to improve the thermal properties of a polymer made of the trimethylene carbonate derivative.

[0045] The polymer according to the present embodiment 3 is a polymer obtained by polymerizing the trimethylene carbonate derivative according to the above embodiment 1 or 2. The polymer according to the present embodiment 3 has properties of substrate adhesion and hydrophobicity in addition to biocompatibility and biodegradability. EXAMPLES

[0046] The following examples are provided to further explain the embodiments of the present invention, but they are merely illustrative and are not intended to limit the scope of the present invention. The present invention can be modified as appropriate within the scope of the present invention. Unless otherwise specified, commercially available reagents were used.

[0047] [Example 1] Synthesis of 5-(n-octyloxymethyl)-5-methyl-1,3-dioxan-2-one The above compound was synthesized by the following reactions (1) to (3).

[0048] (1) Synthesis of 5-(n-octyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane In a 500mL one-neck flask, 3.46g (144mmol) of sodium hydride was added under a nitrogen atmosphere and washed with tetrahydrofuran (THF), then 20g (96.5mmol) of (5-methyl-2-phenyl-1,3-dioxane-5-yl)methanol and 100mL of THF were added, cooled to 0°C, 36mL (207mmol) of 1-bromooctane was added dropwise, and the mixture was stirred at room temperature for 23.5 hours. The solvent was then removed, and a separation operation was performed using ion-exchanged water and dichloromethane to recover the organic layer. Magnesium sulfate was added to the recovered organic layer, and the solvent was removed after filtration. The mixture was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate=10:1→8:1) to obtain 13g (40mmol) of a white solid compound. 1H-NMR and FT-IR measurements confirmed that the compound obtained was 5-(n-octyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane.

[0049] (2) Synthesis of 2-(n-octyloxymethyl)-2-methylpropane-1,3-diol In a 100mL one-neck flask, 10g (31mmol) of 5-(n-octyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane, 8mL (124mmol) of methanesulfonic acid, and 10mL (93.3mmol) of anisole were added, and the mixture was stirred at 0°C for 3 hours, and then at room temperature for 15 hours. Next, a separation operation was performed using an aqueous sodium bicarbonate solution and dichloromethane, and the organic layer was recovered. The recovered organic layer was then washed three times with a sodium bicarbonate solution, and the organic layer was recovered. Magnesium sulfate was added to the recovered organic layer, and the solvent was removed after filtration. The product was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate=10:1→1:1), and 4.5g of a white solid compound was obtained. 1H-NMR and FT-IR measurements confirmed that the obtained compound was 2-(n-octyloxymethyl)-2-methylpropane-1,3-diol.

[0050] (3) Synthesis of 5-(n-octyloxymethyl)-5-methyl-1,3-dioxan-2-one In a 100mL two-neck flask, 2.04g (8.78mmol) of 2-(n-octyloxymethyl)-2-methylpropane-1,3-diol and a small amount of THF were added under a nitrogen atmosphere, and the resulting mixture was anhydrous using MS4A and added to a 100mL two-neck flask under a nitrogen atmosphere. 1.80mL (18.9mol) of ethyl chloroformate was added to the two-neck flask and cooled to 0°C in an ice bath. 2.40mL (17.4mmol) of triethylamine was then slowly added dropwise and stirred for 17 hours. 1.0mol / L of hydrochloric acid was added to stop the reaction, and separation was performed using ion-exchanged water and dichloromethane to recover the organic layer.

[0051] Magnesium sulfate was added to the collected organic layer, and the solvent was removed after filtration. The product was purified by silica gel column chromatography (eluent hexane:ethyl acetate=10:1→1:1) and recrystallized in a mixed solvent of isopropanol:hexane=1:9 to obtain a white solid compound (1.4g, 5.4mmol, 63%). 1H-NMR and FT-IR measurements confirmed that the compound obtained was 5-(n-octyloxymethyl)-5-methyl-1,3-dioxane-2-one.

[0052] [Example 2] Synthesis of 5-(n-decyloxymethyl)-5-methyl-1,3-dioxan-2-one The above compound was synthesized by the following reactions (1) to (3).

[0053] (1) Synthesis of 5-(n-decyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane In a 500mL two-neck flask, 2.0g (83.3mmol) of sodium hydride was added under a nitrogen atmosphere and washed with tetrahydrofuran (THF), then 11g (83.5mmol) of (5-methyl-2-phenyl-1,3-dioxane-5-yl)methanol and 50mL of THF were added, cooled to 0°C, 20mL (83.5mmol) of 1-bromododecane was added dropwise, and stirred at room temperature for 16 hours. Then, THF was removed, and separation was performed with ion-exchanged water and dichloromethane to recover the organic layer. Magnesium sulfate was added to the recovered organic layer to remove moisture, and the magnesium sulfate was filtered and the dichloromethane was distilled off to recover the product. The product was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate = 10:1 to 8:1) to obtain 31g of a white solid compound. 1H-NMR and FT-IR measurements confirmed that the compound obtained was 5-(n-decyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane.

[0054] (2) Synthesis of 2-(n-decyloxymethyl)-2-methylpropane-1,3-diol In a 100 mL one-neck flask, 5.09 g (13.5 mmol) of 5-(n-decyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane, 2.7 mL of 5 mol / L hydrochloric acid, and 11.4 mL of THF were added and stirred at 90°C for 15 hours. Next, a separation operation was performed with an aqueous sodium bicarbonate solution and dichloromethane, and the organic layer was recovered. Magnesium sulfate was added to the recovered organic layer to remove moisture, and then the magnesium sulfate was filtered and the dichloromethane was distilled off to recover the product. The product was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate = 10:1 to 10:6), and 0.662 g of a white solid compound was obtained. 1H-NMR and FT-IR measurements confirmed that the obtained compound was 2-(n-decyloxymethyl)-2-methylpropane-1,3-diol.

[0055] (3) Synthesis of 5-(n-decyloxymethyl)-5-methyl-1,3-dioxan-2-one In a 100mL two-neck flask, 2.2g (7.7mmol) of 2-(n-decyloxymethyl)-2-methylpropane-1,3-diol and a small amount of THF were added under a nitrogen atmosphere, and the mixture was added to a 100mL two-neck flask under a nitrogen atmosphere. 1.50mL (16mmol) of ethyl chloroformate was added to the two-neck flask and cooled to 0°C in an ice bath. Then, 2.2mL (16.0mmol) of triethylamine was slowly added dropwise and stirred for 17 hours. 1.0mol / L hydrochloric acid was added to stop the reaction, and a separation operation was performed using ion-exchanged water and dichloromethane to recover the organic layer. Magnesium sulfate was added to the recovered organic layer, and the solvent was removed after filtration. The product was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate = 10:1 → 1:1) and recrystallized in a mixed solvent of ethyl acetate:hexane = 4:15, and 0.7g of a white solid compound was obtained. 1H-NMR and FT-IR measurements confirmed that the compound obtained was 5-(n-decyloxymethyl)-5-methyl-1,3-dioxan-2-one.

[0056] [Example 3] Synthesis of 5-(n-hexadecyloxymethyl)-5-methyl-1,3-dioxan-2-one The above compound was synthesized by the following reactions (1) to (3).

[0057] (1) Synthesis of 5-(n-hexadecyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane In a 300mL two-neck flask, 3.5g (145mmol) of sodium hydride was added under a nitrogen atmosphere and washed with tetrahydrofuran (THF), then 21g (100mmol) of (5-methyl-2-phenyl-1,3-dioxane-5-yl)methanol and 100mL of THF were added, cooled to 0°C, 46mL (232mmol) of 1-bromohexadecane was added dropwise, and stirred at room temperature for 16.5 hours. Then, THF was removed, and the organic layer was separated with ion-exchanged water and dichloromethane to recover the organic layer. Magnesium sulfate was added to the recovered organic layer to remove moisture, and the magnesium sulfate was filtered and the dichloromethane was distilled off to recover the product. The product was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate=20:1-16:1) to obtain 14g of a white solid compound. 1H-NMR and FT-IR measurements confirmed that the compound obtained was 5-(n-hexadecyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane.

[0058] (2) Synthesis of 2-(n-hexadecyloxymethyl)-2-methylpropane-1,3-diol In a 100mL one-neck flask, 5g (12mmol) of 5-(n-hexadecyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane, 3mL (46mmol) of methanesulfonic acid, and 3.8mL (35mmol) of anisole were added, and the mixture was stirred at 0°C for 2 hours, and then stirred at room temperature for 15.5 hours. Next, a separation operation was performed with an aqueous sodium hydrogen carbonate solution and dichloromethane, and the organic layer was recovered. Magnesium sulfate was added to the recovered organic layer to remove moisture, and then the magnesium sulfate was filtered and the dichloromethane was distilled off to recover the product. The product was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate = 10:1 to 1:3), and 2.9g of a white solid compound was obtained. 1H-NMR and FT-IR measurements confirmed that the obtained compound was 2-(n-hexadecyloxymethyl)-2-methylpropane-1,3-diol.

[0059] (3) Synthesis of 5-(n-hexadecyloxymethyl)-5-methyl-1,3-dioxan-2-one In a 100mL two-neck flask, 1.6g (4.6mmol) of 2-(n-hexadecyloxymethyl)-2-methylpropane-1,3-diol and 6.5mL of THF were added under a nitrogen atmosphere, cooled to 0°C, and 1.2mL (8.7mmol) of triethylamine was added dropwise and stirred for 16.5 hours. 1mol / L hydrochloric acid was added to stop the reaction, and the organic layer was collected by liquid separation using ion-exchanged water and dichloromethane. Magnesium sulfate was added to the collected organic layer to remove moisture, and then the magnesium sulfate was filtered and the dichloromethane was distilled off to collect the product. The product was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate = 10:1 to 1:1) to obtain 0.8g of a white solid compound. 1H-NMR and FT-IR measurements confirmed that the obtained compound was 5-(n-hexadecyloxymethyl)-5-methyl-1,3-dioxan-2-one.

[0060] [Example 4] Synthesis of 5-(n-octadecyloxymethyl)-5-methyl-1,3-dioxan-2-one The above compound was synthesized by the following reactions (1) to (3).

[0061] (1) Synthesis of 5-(n-octadecyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane In a 300mL two-neck flask, 3.6g (151mmol) of sodium hydride was added under a nitrogen atmosphere and washed with tetrahydrofuran (THF), then 20g (97mmol) of (5-methyl-2-phenyl-1,3-dioxane-5-yl)methanol and 100mL of THF were added, cooled to 0°C, 51mL (236mmol) of 1-bromooctadecane was added dropwise, and stirred at room temperature for 16.5 hours. Then, THF was removed, and separation was performed with ion-exchanged water and dichloromethane to recover the organic layer. Magnesium sulfate was added to the recovered organic layer to remove moisture, and the magnesium sulfate was filtered and the dichloromethane was distilled off to recover the product. The product was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate=20:1-16:1) to obtain 20g of a white solid compound. 1H-NMR and FT-IR measurements confirmed that the compound obtained was 5-(n-octadecyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane.

[0062] (2) Synthesis of 2-(n-octadecyloxymethyl)-2-methylpropane-1,3-diol In a 100mL one-neck flask, 10g (22mmol) of 5-(n-octadecyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane, 5.7mL (87mmol) of methanesulfonic acid, and 7.2mL (66mmol) of anisole were added, and the mixture was stirred at 0°C for 1 hour, and then stirred at room temperature for 17 hours. Next, a separation operation was performed with an aqueous sodium bicarbonate solution and dichloromethane, and the organic layer was recovered. Magnesium sulfate was added to the recovered organic layer to remove moisture, and then the magnesium sulfate was filtered and the dichloromethane was distilled off to recover the product. The product was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate = 10:1 to 1:1), and 6g of a white solid compound was obtained. 1H-NMR and FT-IR measurements confirmed that the obtained compound was 2-(n-octadecyloxymethyl)-2-methylpropane-1,3-diol.

[0063] (3) Synthesis of 5-(n-octadecyloxymethyl)-5-methyl-1,3-dioxan-2-one In a 100mL two-neck flask, 3g (8.2mmol) of 2-(n-octadecyloxymethyl)-2-methylpropane-1,3-diol and 12mL of THF were added under a nitrogen atmosphere, cooled to 0°C, and 2.3mL (16mmol) of triethylamine was added dropwise and stirred for 16.5 hours. 1mol / L hydrochloric acid was added to stop the reaction, and separation was performed with ion-exchanged water and dichloromethane to recover the organic layer. Magnesium sulfate was added to the recovered organic layer to remove moisture, and then the magnesium sulfate was filtered and the dichloromethane was distilled off to recover the product. After purification by silica gel column chromatography (developing solvent hexane:ethyl acetate = 10:1 to 1:1), recrystallization was performed in a mixed solvent of dichloromethane:diethyl ether = 1:18 to obtain 2.3g of a white solid compound. 1H-NMR and FT-IR measurements confirmed that the compound obtained was 5-(n-octadecyloxymethyl)-5-methyl-1,3-dioxan-2-one.

[0064] [Example 5] Synthesis of 5-(n-isoxyloxymethyl)-5-methyl-1,3-dioxan-2-one The above compound was synthesized by the following reactions (1) to (3).

[0065] (1) Synthesis of 5-(n-isopropyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane In a 100mL two-neck flask, 0.9g (38mmol) of sodium hydride was added under a nitrogen atmosphere and washed with tetrahydrofuran (THF), then 5g (24mmol) of (5-methyl-2-phenyl-1,3-dioxane-5-yl)methanol and 25mL of THF were added, cooled to 0°C, 13.5mL (37mmol) of 1-bromoicosane was added dropwise, and stirred at room temperature for 24 hours. Then, THF was removed, and separation was performed with ion-exchanged water and dichloromethane to recover the organic layer. Magnesium sulfate was added to the recovered organic layer to remove moisture, and the magnesium sulfate was filtered and the dichloromethane was distilled off to recover the product. The product was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate = 10:1 to 6:1) to obtain 2.6g of a white solid compound. 1H-NMR and FT-IR measurements confirmed that the compound obtained was 5-(n-icosyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane.

[0066] (2) Synthesis of 2-(n-methyloxymethyl)-2-methylpropane-1,3-diol In a 100mL one-neck flask, 1.3g (2.6mmol) of 5-(n-icosyloxymethyl)-5-methyl-2-phenyl-1,3-dioxane, 0.7mL (10mmol) of methanesulfonic acid, and 0.9mL (7.9mmol) of anisole were added, and the mixture was stirred at 0°C for 1 hour, and then at room temperature for 17 hours. Next, a separation operation was performed with an aqueous sodium bicarbonate solution and dichloromethane, and the organic layer was recovered. Magnesium sulfate was added to the recovered organic layer to remove water, and then the magnesium sulfate was filtered and the dichloromethane was distilled off to recover the product. The product was purified by silica gel column chromatography (developing solvent hexane:ethyl acetate = 10:1 to 1:1), and 0.8g of a white solid compound was obtained. 1H-NMR and FT-IR measurements confirmed that the obtained compound was 2-(n-icosyloxymethyl)-2-methylpropane-1,3-diol.

[0067] (3) Synthesis of 5-(n-isocyanyloxymethyl)-5-methyl-1,3-dioxane-2-one In a 100mL two-neck flask, 0.4g (1mmol) of 2-(n-icosyloxymethyl)-2-methylpropane-1,3-diol and 2mL of THF were added under a nitrogen atmosphere, cooled to 0°C, 0.2mL (2mmol) of ethyl chloroformate was added dropwise, and the mixture was stirred for 16.5 hours. 1mol / L hydrochloric acid was added to stop the reaction, and the organic layer was separated with ion-exchanged water and dichloromethane to recover the organic layer. Magnesium sulfate was added to the recovered organic layer to remove moisture, and the magnesium sulfate was filtered and the dichloromethane was distilled off to recover the product. After purification by silica gel column chromatography (developing solvent hexane:ethyl acetate = 10:1 to 1:1), recrystallization was performed in a mixed solvent of dichloromethane:diethyl ether = 1:22.5 to obtain 15g of a white solid compound. 1H-NMR and FT-IR measurements confirmed that the compound obtained was 5-(n-icosyloxymethyl)-5-methyl-1,3-dioxane-2-one.

[0068] [Example 6] Polymerization of 5-(n-octyloxymethyl)-5-methyl-1,3-dioxan-2-one A 2 mol / L dichloromethane solution of 5-(n-octyloxymethyl)-5-methyl-1,3-dioxane-2-one synthesized in Example 1 was prepared in a 10 mL one-mouth test tube under a nitrogen atmosphere, and diazabicycloundecene (DBU) and benzyl alcohol were added to carry out a polymerization reaction at room temperature for 16.5 hours. Reprecipitation was carried out with methanol, the precipitate was collected by centrifugation, and the methanol was distilled off to collect a polymer of 5-(n-octyloxymethyl)-5-methyl-1,3-dioxane-2-one.

[0069] GPC measurement of the polymer showed that the weight average molecular weight Mw was 11,000 and the molecular weight distribution was 1.2. Thermogravimetric analysis (TGA) showed that the 10% weight loss temperature was 304°C, which was a sufficiently high value.

[0070] [Example 7] Polymerization of 5-(n-decyloxymethyl)-5-methyl-1,3-dioxan-2-one In a 10 mL one-mouth test tube, a 2 mol / L dichloromethane solution of 5-(n-decyloxymethyl)-5-methyl-1,3-dioxane-2-one synthesized in Example 2 was prepared under a nitrogen atmosphere, and diazabicycloundecene (DBU) and benzyl alcohol were added to carry out a polymerization reaction at room temperature for 23 hours. Reprecipitation was carried out with methanol, the precipitate was collected by centrifugation, and the methanol was distilled off to collect a polymer of 5-(n-decyloxymethyl)-5-methyl-1,3-dioxane-2-one.

[0071] The polymer was measured by GPC and found to have a weight average molecular weight (Mw) of 9,000 and a molecular weight distribution of 1.2. Thermogravimetry (TGA) showed that the 10% weight loss temperature was 312°C, which was sufficiently high. Differential scanning calorimetry (DSC) confirmed that the polymer had a melting point of 8°C.

[0072] [Example 8] Polymerization of 5-(n-hexadecyloxymethyl)-5-methyl-1,3-dioxan-2-one In a 10 mL one-mouth test tube, a 2 mol / L dichloromethane solution of 5-(n-hexadecyloxymethyl)-5-methyl-1,3-dioxane-2-one synthesized in Example 3 was prepared under a nitrogen atmosphere, and diazabicycloundecene (DBU) and benzyl alcohol were added to carry out a polymerization reaction at room temperature for 21 hours. Reprecipitation was carried out with methanol, the precipitate was collected by centrifugation, and the methanol was distilled off to collect a polymer of 5-(n-hexadecyloxymethyl)-5-methyl-1,3-dioxane-2-one.

[0073] The polymer was measured by GPC and found to have a weight average molecular weight (Mw) of 11,000 and a molecular weight distribution of 1.3. Thermogravimetry (TGA) showed that the 10% weight loss temperature was 305°C, which was sufficiently high. Differential scanning calorimetry (DSC) confirmed that the polymer had a melting point of 34°C.

[0074] [Example 9] Polymerization of 5-(n-octadecyloxymethyl)-5-methyl-1,3-dioxan-2-one A 2 mol / L dichloromethane solution of 5-(n-octadecyloxymethyl)-5-methyl-1,3-dioxane-2-one synthesized in Example 4 was prepared in a 10 mL single-mouth test tube under a nitrogen atmosphere, and diazabicycloundecene (DBU) and benzyl alcohol were added to carry out a polymerization reaction at room temperature for 21 hours. Reprecipitation was carried out with methanol, the precipitate was collected by centrifugation, and the methanol was distilled off to collect a polymer of 5-(n-octadecyloxymethyl)-5-methyl-1,3-dioxane-2-one.

[0075] The polymer was measured by GPC and found to have a weight average molecular weight (Mw) of 9,000 and a molecular weight distribution of 1.2. Thermogravimetry (TGA) showed that the 10% weight loss temperature was 296°C, which was a sufficiently high value. Differential scanning calorimetry (DSC) confirmed that the polymer had a melting point of 44°C.

[0076] [Example 10] Polymerization of 5-(n-isoxyloxymethyl)-5-methyl-1,3-dioxan-2-one A 2 mol / L dichloromethane solution of 5-(n-icosyloxymethyl)-5-methyl-1,3-dioxane-2-one synthesized in Example 5 was prepared in a 10 mL single-mouth test tube under a nitrogen atmosphere, and diazabicycloundecene (DBU) and benzyl alcohol were added to carry out a polymerization reaction at room temperature for 23 hours. Reprecipitation was carried out with methanol, the precipitate was collected by centrifugation, and the methanol was distilled off to collect a polymer of 5-(n-icosyloxymethyl)-5-methyl-1,3-dioxane-2-one.

[0077] The polymer was measured by GPC and found to have a weight average molecular weight (Mw) of 3,000 and a molecular weight distribution of 1.2. Thermogravimetry (TGA) showed that the 10% weight loss temperature was 281°C, which was a sufficiently high value. Differential scanning calorimetry (DSC) confirmed that the polymer had a melting point of 60°C.

[0078] [Evaluation of Surface Properties of Polymer Coating Film] The polymers of Examples 6 to 10 were prepared as solutions with a polymer concentration of 10 mg / mL (solvent: dichloromethane). A polyethylene terephthalate (PET) substrate was immersed in the polymer solution and dried to form a polymer coating. At this time, the polymer coatings of Examples 6 to 10 were formed uniformly. After a water droplet was applied to the substrate with the polymer coating, the contact angle of the water droplet was calculated from the radius and height of the water droplet. The calculated contact angle values ​​are shown in Table 1 below.

[0079] [Table 1]

[0080] The contact angle value of the polymer-coated substrate is larger than that of the uncoated substrate, indicating that the polymer coating makes the substrate surface hydrophobic.

[0081] Furthermore, in all of the Examples, the coating film was formed uniformly on the substrate, which indicates that the adhesion of the polymer to the substrate is excellent. [Industrial Applicability]

[0082] The present invention can be applied to biodegradable and biocompatible polymeric materials.

Claims

1. A trimethylene carbonate derivative represented by the following general formula (1): 【Chemistry 1】 (In the formula, R １ represents a hydrogen atom or a C1-C6 alkyl group, R ２ represents an alkyl group having C8 to C30.

2. A polymer obtained by polymerizing the trimethylene carbonate derivative according to claim 1.

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