JP2019147743A - Bisamino benzylpiperazine dione, amide acid polymer and polyimide, and hollow polyimide particle and manufacturing method therefor - Google Patents

Abstract

To provide polyimide which is rigid, easily powdered, and excellent in chemical resistance, heat resistance, or the like, an amide acid polymer useful as a manufacturing intermediate of the polyimide, an amide acid polymer useful as a manufacturing intermediate of the amide acid polymer, and bisamino benzylpiperazine dione useful as a manufacturing intermediate of the amide acid polymer.SOLUTION: There are provided a bisamino benzylpiperazine dione of the formula (I), an amide acid polymer using the bisamino benzylpiperazine dione as a raw material, and polyimide using the amide acid polymer as a raw material.SELECTED DRAWING: None

Description

  The present invention relates to bisaminobenzylpiperazinedione, amic acid polymer and polyimide, and hollow polyimide particles and a method for producing the same. More specifically, the present invention relates to a polyimide, an amic acid polymer useful as a production intermediate of the polyimide, a bisaminobenzylpiperazinedione useful as a production intermediate of the amidic acid polymer, and a hollow polyimide using the polyimide The present invention relates to particles and a method for producing the same.

  The polyimide of the present invention is rigid and easy to be powdered, and is excellent in chemical resistance, heat resistance, etc., so it should be used for applications requiring these properties, such as heat resistant fillers. There is expected.

  Moreover, since the said polyimide is used, the hollow polyimide particle of this invention not only is excellent in chemical resistance, heat resistance, etc., but also has a hollow and can be micronized. By filling the inside thereof with a drug, it is expected to be used for biomaterials such as microcapsules filled with a drug used in a drug delivery system.

  Polyimide has been spotlighted as a super engineering plastic because of its excellent heat resistance and high mechanical strength. In general, a polyimide is obtained by reacting an aromatic diamine and an aromatic tetracarboxylic acid in an organic solvent, mixing the resulting reaction mixture containing an amic acid polymer, an imidization catalyst, and a dehydrating agent, and then obtaining the resulting amic acid. The polymer solution is produced by drying and heating (for example, see Patent Document 1).

  However, since polyimide has a rigid skeleton, and exhibits poor solubility in water and various organic solvents, a polyimide molded body is conventionally formed by molding an amic acid polymer that is a raw material of the polyimide into a predetermined shape, It is produced by imidizing an amic acid polymer. However, when a polyimide molded body is produced by the above method, the molecular weight of the polyimide is reduced by water produced as a by-product when the amic acid polymer is imidized, or voids are generated in the molded body by the water. There is.

  Therefore, in recent years, it has been studied to use polyimide by dissolving it in an organic solvent so that a molded product can be produced directly from polyimide. As a polyimide that can be dissolved in an organic solvent, a polyimide obtained by copolymerizing 3,3 ′, 4,4′-biphenyltetracarboxylic dianhydride, diamine and / or diisocyanate has been proposed ( For example, see Patent Document 2). Since the polyimide can be dissolved in an organic solvent, a molded body can be produced using an organic solvent solution of the polyimide.

  However, when molding using the organic solvent solution of polyimide, the organic solvent contained in the organic solvent solution is volatilized during molding, so the working environment during molding deteriorates and adversely affects the operator's body. Is concerned.

  In recent years, a polyimide aqueous solution in which a water-soluble polyimide resin is dissolved in water has been proposed as an alternative to the conventional organic solution of polyimide (see, for example, Patent Document 3). The water-soluble polyimide resin is suitable for development because it has water solubility by introducing a siloxane skeleton into its basic skeleton.

  However, since the siloxane skeleton of the water-soluble polyimide resin is inferior in heat resistance, the water-soluble polyimide resin has a defect that the heat resistance inherent in polyimide is necessarily inferior.

JP 2004-223787 A JP2015-000939A JP 2011-144374 A

  The present invention has been made in view of the above prior art, and is a rigid, easily powdered polyimide excellent in chemical resistance, heat resistance, etc., an amic acid polymer useful as a production intermediate of the polyimide, and the amide It is an object of the present invention to provide bisaminobenzylpiperazinedione useful as an intermediate for producing an acid polymer, hollow polyimide particles using the polyimide, and a method for producing the same.

The present invention
(1) Formula (I):

Bisaminobenzylpiperazinedione represented by:
(2) Formula (III):

(Where A is the formula:

Indicate)
An amic acid polymer having a repeating unit represented by:
(3) Formula (IV):

(Where A is the formula:

Indicate)
A polyimide having a repeating unit represented by:
(4) A hollow polyimide particle characterized by having a surface layer made of the polyimide described in (3) and having an inside thereof hollow, and (5) consisting of an amic acid polymer described in (2). After the particles are imidized with an imidizing agent to form a surface layer made of polyimide as described in (3) above, the particles are treated with alkali to dissolve the amic acid polymer inside the particles and The present invention relates to a method for producing hollow polyimide particles, wherein the inside of the particles is hollowed out.

  According to the present invention, a polyimide that is rigid and easily pulverized, has excellent chemical resistance, heat resistance, and the like, an amic acid polymer useful as a production intermediate of the polyimide, and a bis acid useful as a production intermediate of the amidic acid polymer Provided are aminobenzylpiperazinedione, hollow polyimide particles using the polyimide, and a method for producing the same.

2 is a graph showing a ¹ H-NMR spectrum of 3,6-bis (4-aminobenzyl) piperazine-2,5-dione obtained in Example 6. FIG. 2 is a graph showing a ¹³ C-NMR spectrum of 3,6-bis (4-aminobenzyl) piperazine-2,5-dione obtained in Example 6. FIG. 4 is a graph showing measurement results of infrared spectroscopic analysis of 3,6-bis (4-aminobenzyl) piperazine-2,5-dione obtained in Example 6. FIG. 4 is a graph showing the ESI-MS measurement results of 3,6-bis (4-aminobenzyl) piperazine-2,5-dione obtained in Example 6. 6 is a graph showing an infrared absorption (IR) spectrum of amic acid polymer A obtained in Example 7. FIG. 6 is a graph showing an infrared absorption (IR) spectrum of polyimide A obtained in Example 8. FIG. 6 is a graph showing measurement results of gel permeation chromatography (GPC) of amic acid polymer D obtained in Example 13. 2 is a scanning electron micrograph of fine particles of amic acid polymer obtained in Example 19. FIG. 6 is a graph showing measurement results of average particle diameter of polyimide D fine particles obtained in Example 20. FIG. 2 is a scanning electron micrograph of polyimide fine particles obtained in Example 21. FIG. 2 is a graph showing the particle size distribution of polyimide fine particles obtained in Example 19 and Example 21. FIG.

(Preparation of bisaminobenzylpiperazinedione)
As described above, the bisaminobenzylpiperazinedione of the present invention has the formula (I):

It is a compound represented by these.

  The formal name of bisaminobenzylpiperazinedione represented by formula (I) is 3,6-bis (4-aminobenzyl) piperazine-2,5-dione. 4-Aminophenylalanine can be used as a raw material for the bisaminobenzylpiperazinedione represented by the formula (I). 4-Aminophenylalanine can be easily prepared by fermenting glucose. Therefore, the bisaminobenzylpiperazinedione of the present invention can be prepared using a biomass compound that is friendly to the global environment as a raw material.

  Hereinafter, a method for preparing bisaminobenzylpiperazinedione represented by the formula (I) using 4-aminophenylalanine as a raw material will be described, but the present invention is not limited only to the method.

(A) Protection of aromatic amine group of 4-aminophenylalanine 4-aminophenylalanine is dissolved in a solvent such as an acetic acid aqueous solution, and an aromatic amine group protecting agent such as 4-aminophenylalanine and benzyl chloroformate in the solution. For example, the formula:

As shown in (4), a 4-aminophenylalanine derivative (A) in which the aromatic amine group of 4-aminophenylalanine is protected by an aromatic amine group protecting agent such as benzyl chloroformate can be prepared.

  In the above example, benzyl chloroformate is used as a protecting agent for the aromatic amine group, but the present invention is not limited by the type of the protecting agent.

(B1) Protection of aliphatic amine group of 4-aminophenylalanine derivative (A) Protecting agent for aliphatic amine group such as 4-aminophenylalanine derivative (A) obtained in (A) above and di-tert-dicarbonate By reacting with the formula:

As shown in (4), a 4-aminophenylalanine derivative (B1) in which an aliphatic amine group of 4-aminophenylalanine is protected by a protecting agent for an aliphatic amine group such as ditert-dicarbonate can be prepared.

  In the above example, ditert-dicarbonate is used as a protecting agent for an aliphatic amine group, but the present invention is not limited by the type of the protecting agent.

(B2) Esterification of carboxyl group of 4-aminophenylalanine derivative (A) reacting 4-aminophenylalanine derivative (A) obtained in (A) with an esterifying agent such as ditert-butyldicarbonate. By the formula:

As shown in FIG. 4, a 4-aminophenylalanine derivative (B2) in which the carboxyl group of the 4-aminophenylalanine derivative (A) is esterified can be prepared.

  In the above example, di-tert-butyl dicarbonate is used as the esterifying agent, but the present invention is not limited by the type of the esterifying agent.

(C) Preparation of chain peptide (C) By reacting 4-aminophenylalanine derivative (B1) obtained in (B1) and 4-aminophenylalanine derivative (B2) obtained in (B2) above. ,formula:

As shown in Fig. 2, a chain peptide (C) can be prepared.

(D) Deprotection of the protecting group of the chain peptide (C) and cyclization thereof The deprotection of the protecting group of the chain peptide (C) obtained above and the cyclization thereof have the formula:

It can be carried out by the reaction shown in More specifically, the protecting group of the chain peptide (C) can be deprotected and cyclized by the following method.

[Deprotection of protecting group of chain peptide (C)]
Deprotection of the protecting group of the chain peptide (C) obtained above can be performed using a deprotecting agent such as formic acid. In the above example, formic acid is used as a deprotecting agent for the protecting group of the chain peptide (C), but the present invention is not limited by the type of the deprotecting agent.

[Cyclization of chain peptide (C)]
The cyclization of the chain peptide (C) from which the protecting group has been deprotected is performed, for example, by refluxing in a mixed solvent of an aliphatic alcohol such as butanol and an aromatic organic solvent such as toluene. Can do.

  The cyclic peptide (D) can be prepared by deprotecting and cyclizing the protecting group of the chain peptide (C) as described above.

(E) Deprotection of the protecting group of the cyclic peptide (D) The protecting group of the cyclic peptide (D) obtained above has the formula:

Can be deprotected by a deprotecting agent such as hydrogen bromide, for example. In the above example, hydrogen bromide is used as the deprotecting agent, but the present invention is not limited by the type of the deprotecting agent.

  As described above, the bisaminobenzylpiperazinedione represented by the formula (I) of the present invention can be obtained.

  The bisaminobenzylpiperazinedione of the present invention is useful as a raw material for an amic acid polymer that is an intermediate for producing the polyimide of the present invention.

(Preparation of amic acid polymer)
The amic acid polymer of the present invention can be prepared by reacting bisaminobenzylpiperazinedione represented by the formula (I) with tetracarboxylic dianhydride.

  As tetracarboxylic dianhydride, for example, formula (II):

(Where A is the formula:

Indicate)
And a group derived from tetracarboxylic dianhydride represented by:

  The tetracarboxylic dianhydride can be easily obtained commercially. Examples of the tetracarboxylic dianhydride include oxydiphthalic dianhydride (OPDA), 3,3 ′, 4,4′-diphenylsulfone tetracarboxylic dianhydride (DSDA), 1,2,3,4 -Tetracarboxycyclobutane dianhydride (CBDA), 3,3 ', 4,4'-benzophenone tetracarboxylic dianhydride (BTDA), 5- (2,5-dioxotetrahydrofuryl) -3-methyl-3 -Cyclohexene-1,2-dicarboxylic anhydride (DHCDA), 3,3 ', 4,4'-biphenyltetracarboxylic dianhydride (BPDA) and the like are included, but the present invention is limited to such examples only Is not to be done.

  Since the reaction between bisaminobenzylpiperazinedione and tetracarboxylic dianhydride theoretically proceeds stoichiometrically, the amount of tetracarboxylic dianhydride per mole of bisaminobenzylpiperazinedione is: Preferably it is about 0.5-1.5 mol, More preferably, it is about 0.8-1.2 mol.

  When reacting bisaminobenzylpiperazinedione with tetracarboxylic dianhydride, an organic solvent can be used.

  Examples of the organic solvent include amide organic solvents such as N-methyl-2-pyrrolidone (NMP), N, N-dimethylacetamide (DMAc), and N, N-dimethylformamide; methanol, ethanol, isopropanol, butanol, octanol Alcohol organic solvents such as acetone; ketone organic solvents such as acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ester organic solvents such as ethyl acetate, butyl acetate and ethyl lactate; ethers such as ethylene glycol monomethyl ether and diethylene glycol monobutyl ether Organic solvents; aromatic hydrocarbon compound organic solvents such as benzene, toluene, xylene and the like can be mentioned, but the present invention is not limited to such examples. Among these organic solvents, amides such as N-methyl-2-pyrrolidone (NMP), N, N-dimethylacetamide (DMAc), N, N-dimethylformamide and the like from the viewpoint of efficiently producing an amic acid polymer Organic solvents are preferred.

  The amount of the organic solvent is not particularly limited, but from the viewpoint of efficiently reacting bisaminobenzylpiperazinedione and tetracarboxylic dianhydride, the total amount of bisaminobenzylpiperazinedione and tetracarboxylic dianhydride is 100 volumes. It is preferably about 50 to 500 parts by volume per part.

  The reaction temperature at the time of reacting bisaminobenzylpiperazinedione and tetracarboxylic dianhydride is not particularly limited, but it is usually preferably about 5 to 60 ° C. from the viewpoint of efficiently reacting both.

  The atmosphere for reacting bisaminobenzylpiperazinedione and tetracarboxylic dianhydride is, for example, an inert gas such as nitrogen gas or argon gas from the viewpoint of eliminating the influence of oxygen contained in the air. Preferably there is.

  The reaction time for reacting bisaminobenzylpiperazinedione and tetracarboxylic dianhydride varies depending on the reaction conditions such as the reaction temperature and cannot be determined unconditionally, but is usually about 10 to 60 hours. is there.

  By reacting bisaminobenzylpiperazinedione with tetracarboxylic dianhydride as described above, the formula:

(In the formula, A is the same as described above, and n represents the degree of polymerization)
The reaction proceeds as shown in Formula (III):

(Wherein A is the same as above)
An amic acid polymer having a repeating unit represented by the following formula is obtained.

  In addition, you may use the reaction solution containing the produced | generated amic acid polymer as it is after completion | finish of reaction with bisamino benzyl piperazine dione and tetracarboxylic dianhydride. Alternatively, the amic acid polymer may be precipitated by mixing the produced reaction solution containing the amic acid polymer with a poor solvent such as water or acetone, and the precipitated amic acid polymer may be used. If necessary, the amic acid polymer may be used after drying.

The generated amic acid polymer has a repeating unit represented by the formula (III), for example, ¹ H-nuclear magnetic resonance (NMR) spectrum, ¹³ C-nuclear magnetic resonance (NMR) spectrum, infrared absorption (IR) It can be easily confirmed by analyzing the produced amic acid polymer by spectrum or the like.

  The number average molecular weight of the amic acid polymer is preferably 5000 to 300,000, more preferably 6000 to 100,000, and still more preferably 7000 to 50,000, from the viewpoint of improving mechanical strength and processability. The number average molecular weight of the amic acid polymer can be easily measured by, for example, gel permeation chromatography (GPC).

  The amic acid polymer may contain a polymer other than the amic acid polymer as long as the object of the present invention is not impaired.

[Preparation of polyimide]
Next, a polyimide can be obtained by heating the amic acid polymer or imidizing with an imidizing agent.

(1) Preparation of polyimide by heating of amic acid polymer When preparing a polyimide by heating the amic acid polymer, the heating temperature of the amic acid polymer is preferably 50 ° C or higher from the viewpoint of efficiently producing polyimide. More preferably, it is 80 degreeC or more, From a viewpoint of suppressing the thermal deterioration of a polyimide, Preferably it is 400 degrees C or less, More preferably, it is 350 degrees C or less, More preferably, it is 300 degrees C or less. The amic acid polymer may be heated while the heating temperature is increased stepwise. For example, for example, the amic acid polymer may be 0.5 to 3 hours at 100 ° C., 0.5 to 3 hours at 150 ° C., 0.5 to 3 hours at 200 ° C., and 0.5 to 4 at 250 ° C. A polyimide can be manufactured by raising the temperature stepwise at each temperature for a predetermined time and heating.

  The atmosphere for heating the amic acid polymer is not particularly limited, and may be an atmosphere such as air or an inert gas, and may be normal pressure, reduced pressure or increased pressure as necessary.

  The heating time of the amic acid polymer varies depending on the heating temperature of the amic acid polymer and cannot be determined unconditionally, but is usually about 2 to 10 hours.

  The imidization of the amic acid polymer may be performed until the polyimide is completely formed. When the amidic acid polymer particles are imidized, only the surface layer may be imidized. You may carry out until the whole is polyimide-ized.

  By heating the amic acid polymer as described above, the formula (IV):

(Wherein A is the same as above)
The polyimide which has a repeating unit represented by this can be obtained.

(2) Preparation of polyimide by imidizing an amic acid polymer with an imidizing agent When preparing a polyimide by imidizing an amic acid polymer with an imidizing agent, contacting the amic acid polymer with an imidizing agent Thus, a polyimide having a repeating unit represented by the formula (IV) can be obtained.

  As the imidizing agent, a ring closure agent and an organic acid anhydride can be used. Examples of the ring-closing agent include bases such as pyridine, triethylamine, quinoline, N, N-dimethylaniline, diazabicycloundecene, potassium carbonate, sodium hydroxide, etc., but the present invention is limited only to such examples. Is not to be done. Among these ring-closing agents, pyridine is preferable because it is easy to separate. Examples of the organic acid anhydride include lactones such as acetic anhydride, propionic anhydride, and γ-butyrolactone, but the present invention is not limited to such examples. Among these organic acid anhydrides, acetic anhydride is preferable because it can be easily separated. The ratio of the ring-closing agent to the organic acid anhydride varies depending on the type of the ring-closing agent and the organic acid anhydride and cannot be determined unconditionally. The agent / organic acid anhydride) is preferably 30/70 to 70/30, more preferably 40/60 to 60/40. Moreover, it is preferable that the quantity of the imidizing agent is about 1 to 10 moles per mole of the carboxyl group of the amic acid polymer.

  The temperature at which the amic acid polymer is brought into contact with the imidizing agent is not particularly limited, and is usually preferably about 5 to 80 ° C. The contact between the amic acid polymer and the imidizing agent can be performed until the amic acid polymer is imidized at a predetermined ratio.

  By imidizing the amic acid polymer with an imidizing agent as described above, a polyimide having a repeating unit represented by the formula (IV) can be obtained.

  The polyimide of the present invention can be used in the form of particles. As the raw material for the polyimide particles, amic acid polymer particles can be used. The amic acid polymer particles are prepared, for example, by dissolving the amic acid polymer in an organic solvent such as dimethylacetamide, and adding the obtained amic acid polymer solution to an aqueous solvent such as an aqueous surfactant solution. For example, the dispersion can be prepared by applying an external stress such as an ultrasonic wave or a shearing force.

  The particle diameter of the amic acid polymer particles can be easily adjusted by selecting an external stress applied to the dispersion of the amic acid polymer. The particle diameter of the amic acid polymer particles is not particularly limited, and is preferably determined as appropriate according to the intended use of the resulting polyimide particles. Examples of the particle diameter of the amic acid polymer particles include about 20 to 1000 nm. Moreover, as an average particle diameter of the particle | grains of an amic acid polymer, about 100-400 nm is mentioned, for example.

  Next, by contacting the amic acid polymer particles obtained above with an imidizing agent, the amic acid polymer can be imidized to obtain polyimide particles.

  By controlling the temperature at which the amidic acid polymer particles are imidized with an imidizing agent, the imidization time, etc., only the surface of the amic acid polymer particles is imidized, and the amidic acid polymer remains inside. Alternatively, the entire amic acid polymer particles may be imidized.

  According to the present invention, only the surface of the amic acid polymer particles can be imidized, and the amidic acid polymer can be left in the inside thereof, so that only the surface is imidized and the hollow polyimide particles whose inside is the amic acid polymer Can be obtained.

  The thickness of the surface layer of the hollow polyimide particles can be easily adjusted by adjusting the degree of imidization on the surface of the particles. The thickness of the surface layer of the hollow polyimide particles is not particularly limited, and is preferably determined as appropriate according to the application. As thickness of the surface layer of hollow polyimide particle, about 10-800 nm is mentioned, for example. The mechanical strength of the hollow polyimide particles can be adjusted by adjusting the thickness of the surface layer of the hollow polyimide particles.

  For example, the hollow polyimide particles are formed by imidizing particles made of an amic acid polymer with an imidizing agent to form a surface layer made of polyimide, and then treating the particles with an alkali to thereby treat the amidic acid polymer inside the particles. Can be prepared by dissolving the particles to hollow out the interior of the particles.

  Examples of a method for forming a surface layer made of polyimide by imidizing the surface of particles made of an amic acid polymer are described in the above-mentioned section “Preparation of polyimide by imidizing an amic acid polymer with an imidizing agent”. In this method, only the surface of the amic acid polymer particles is imidized, and the amidic acid polymer is left in the inside.

  Next, an alkali treatment is performed on the particles whose surfaces are imidized and the inside is an amic acid polymer, whereby the amidic acid polymer inside the particles can be dissolved to hollow the inside of the particles.

  When the surface is imidized only and the inside is an amic acid polymer, the amidic acid polymer in the particle dissolves when the alkali treatment is applied to the particles, but the polyimide constituting the surface layer has chemical resistance. It is difficult to dissolve because it is excellent. Therefore, by subjecting the particles to an alkali treatment, hollow polyimide particles having a surface layer made of polyimide and hollow inside can be obtained.

  The alkali treatment of the particles can be performed, for example, by immersing the particles in an alkaline aqueous solution. Examples of the aqueous alkali solution include an aqueous sodium hydroxide solution, but the present invention is not limited to such examples. Moreover, there is no limitation in particular also about the liquid temperature of aqueous alkali solution, and it is preferable that it is normal temperature normally. The alkali treatment of the particles can be performed until the amic acid polymer in the particles is dissolved.

  The particle diameter of the hollow polyimide particles obtained as described above can be easily adjusted by adjusting the production conditions for producing a dispersion of the amic acid polymer that is a raw material of the hollow polyimide particles. The particle diameter of the hollow polyimide particles is not particularly limited, and is preferably determined as appropriate according to the application. Examples of the particle size of the hollow polyimide particles include about 20 to 1000 nm. Moreover, as an average particle diameter of a hollow polyimide particle, about 100-400 nm is mentioned, for example.

  The hollow polyimide particles can be used as a capsule filled with a medicine by filling the hollow portion inside the medicine because the polyimide constituting the surface layer is excellent in chemical resistance. . The capsule filled with the drug can be obtained, for example, by mixing hollow polyimide particles and a chemical solution, pressurizing the obtained mixture, and pressing the drug into the hollow portion of the hollow polyimide particles. Capsules filled with the drug are expected to be used as biomaterials used in drug delivery systems.

The polyimide of the present invention has a repeating unit represented by the formula (IV), for example, ¹ H-nuclear magnetic resonance (NMR) spectrum, ¹³ C-nuclear magnetic resonance (NMR) spectrum, infrared absorption (IR ) It can be easily confirmed by analyzing the produced polyimide by spectrum or the like.

  The polyimide having the repeating unit represented by the formula (IV) is insoluble in, for example, alcohol solvents such as water and ethanol, aromatic solvents such as benzene, toluene and xylene, and ester solvents such as ethyl acetate. Therefore, it is difficult to measure the average molecular weight of the polyimide by gel permeation chromatography (GPC) or the like.

  The polyimide of the present invention obtained as described above is rigid and easy to be powdered, and is excellent in chemical resistance, heat resistance, and the like. It is expected to be used for such applications.

  Moreover, since the said polyimide is used, the hollow polyimide particle of this invention not only is excellent in chemical resistance, heat resistance, etc., but also has a hollow and can be micronized. By filling the inside thereof with a drug, it is expected to be used for biomaterials such as microcapsules filled with a drug used in a drug delivery system.

  Next, the present invention will be described in more detail based on examples. However, the present invention is not limited to such examples.

The physical properties of the compounds obtained in the following examples and comparative examples were investigated based on the following methods.
[ ¹ H-NMR and ¹³ C-NMR]
Measurement device: Nuclear magnetic resonance spectrometer (Bruker, product name: AVANCE III)

[ESI-MS]
-Measuring device: Mass spectrometer (Bruker, trade name: SolariX-JA)

[Infrared spectroscopy (IR)]
・ Measuring device: manufactured by Perkin Elmer, trade name: Spectrum 100
Measurement method: ATR method Measurement range: 380-4000 cm ^-1
-Number of scans: 4 times-Resolution: 4.00 cm ^-1
・ Top plate: Diamond / KRS-5

Example 1
formula:

Was dissolved in 340 mL of 10% aqueous acetic acid solution, and 5 M aqueous sodium hydroxide solution was added dropwise to the resulting solution to adjust the pH of the solution to 3. A solution obtained by dissolving 6 mL of benzyl chloroformate in 340 mL of 1,4-dioxane was slowly added to the solution obtained above, and the resulting mixture was stirred at room temperature for about 10 hours.

  The pH of the mixture obtained above was adjusted to 7 with 5M aqueous sodium hydroxide solution, and the mixture was filtered through a filter. By washing the resulting product with water, the formula:

[Wherein Cbz represents a (phenylmethoxy) carbonyl group]
A white powder of 4- (phenylmethoxy) carbonylaminophenylalanine (4APhe-z) represented by the formula:

Example 2
While mixing 5 g of 4- (phenylmethoxy) carbonylaminophenylalanine (4APhe-z) obtained in Example 1 and 80 mL of methanol, 8.5 mL of chlorotrimethylsilane was stirred at room temperature while stirring the resulting milky white mixture. Added. The resulting mixture became clear after the addition of chlorotrimethylsilane was complete.

  The mixture obtained above was stirred at room temperature for about 10 hours, then methanol was evaporated, and the resulting crude product was dried under reduced pressure. The crude product obtained above is further recrystallized from methanol and diethyl ether to give the formula:

(Where Cbz is the same as above)
4- (phenylmethoxy) carbonylaminophenylalanine methyl ester hydrochloride represented by the formula (methyl-4APhe-z) was obtained in a yield of 90%.

Example 3
4.5 g of 4- (phenylmethoxy) carbonylaminophenylalanine (4APhe-z) obtained in Example 1 was added to 62 mL of a mixed solvent of tetrahydrofuran and water [tetrahydrofuran: water (volume ratio) = 1: 1], To the obtained solution, 1.3 g of 5M aqueous sodium hydroxide solution was added at room temperature with stirring, followed by 3.5 g of ditert-butyl dicarbonate (Bo ₂ O), and the resulting reaction mixture was stirred at room temperature. Under stirring for about 10 hours.

  Next, the tetrahydrofuran was volatilized and removed from the reaction mixture obtained above, the pH of the reaction mixture was adjusted to 4 with 1M hydrochloric acid, and then filtered through a filter to obtain the formula:

(Where Cbz and Boc are the same as above)
In represented 4- (phenylmethoxy) carbonyl aminophenyl -N ^alpha - a (tert- butylcarbonyl) alanine (Boc-4APhe-z) was obtained in 98% yield.

Example 4
Obtained in Example 3 4- (phenylmethoxy) carbonyl aminophenyl -N ^alpha - (tert-butylcarbonyl) dissolved alanine (Boc-4APhe-z) 8.5g in dichloromethane 120 mL, the resulting solution 0 At a solution temperature of ° C., 3.05 g of 1-hydroxybenzotriazole was added, followed by 5.08 g of dicyclohexylcarbodiimide. The obtained reaction mixture was stirred at room temperature for 1 hour, and 8.25 g of 4- (phenylmethoxy) carbonylaminophenylalanine methyl ester hydrochloride (methyl-4APhe-z) obtained in Example 2 was dissolved in 23 mL of dimethylformamide. The resulting solution was added to the reaction mixture followed by the addition of 3.4 mL of trimethylamine.

  The reaction mixture obtained above was stirred at room temperature for about 10 hours, and then precipitated dicyclohexylurea was filtered through a filter and washed with a small amount of dichloromethane. The filtrate was evaporated under reduced pressure to recover the crude product, and the pH of the recovered crude product was adjusted to 2-3 with 1N hydrochloric acid. The crude product is then washed with a saturated aqueous sodium bicarbonate solution and filtered through a filter to obtain the formula:

(Where Cbz and Boc are the same as above)
N ^α- {4- (phenylmethoxy) carbonylaminophenyl-N ^α '(tert-butylcarbonyl) alaninoyl} -4- (phenylmethoxy) carbonylaminophenylalanine methyl ester (Boc-4APhe-z-methyl-4APhe) -Z) was obtained as a yellow powder in a yield of 70%.

Example 5
N ^α- {4- (phenylmethoxy) carbonylaminophenyl-N ^α ′ (tert-butylcarbonyl) alaninoyl} -4- (phenylmethoxy) carbonylaminophenylalanine methyl ester (Boc-4APhe-z) obtained in Example 4 -Methyl-4APhe-z) To 7.7 g, 466 mL of 98% formic acid was added and stirred at room temperature for about 10 hours.

  Next, excess formic acid was removed from the reaction mixture obtained above under reduced pressure, and the liquid temperature was adjusted to 30 ° C. or lower. The obtained crude product was refluxed in a mixed solvent of 310 mL of 2-butanol and 155 mL of toluene at a temperature of 110 ° C. for 5 hours, filtered through a filter, and dried under reduced pressure to obtain the formula:

(Where Cbz is the same as above)
3,6-bis {4- (phenylmethoxy) carbonylaminobenzyl} piperazine-2,5-dione (4APhe-z-4APhe-z) represented by the formula: was obtained in a yield of 58%.

Example 6
3,6-bis {4- (phenylmethoxy) carbonylaminobenzyl} piperazine-2,5-dione (4APhe-z-4APhe-z) obtained above with 38.5 mL of 33% hydrobromic acetic acid solution3. The resulting mixture was stirred at room temperature for 3 hours 30 minutes.

  Diethyl ether was added to the mixture obtained above, and decantation was repeated several times to remove excess acid to obtain a crude product. After drying the obtained crude product under reduced pressure, the crude product was dissolved in water, and aqueous ammonia was added dropwise with stirring until the pH of the resulting aqueous solution reached 12. The resulting mixture is heated at a temperature of 60 ° C. for 1 hour, cooled and filtered through a filter to give formula (I):

3,6-bis (4-aminobenzyl) piperazine-2,5-dione (BAPD) represented by the formula: was obtained in a yield of 98%.

That the 3,6-bis (4-aminobenzyl) piperazine-2,5-dione obtained above is a compound represented by the formula (I) indicates that it is a ¹ H-NMR (nuclear magnetic resonance) spectrum, ¹³ C It could be confirmed from the results of -NMR (nuclear magnetic resonance) spectrum, infrared spectroscopic analysis and ESI-MS. The ¹ H-NMR (nuclear magnetic resonance) spectrum of 3,6-bis (4-aminobenzyl) piperazine-2,5-dione obtained above is shown in FIG. 1, and the measurement result of ¹³ C-NMR is shown in FIG. FIG. 3 shows the results of infrared spectroscopic analysis, and FIG. 4 shows the results of ESI-MS measurement.

Example 7
3,6-bis (4-aminobenzyl) piperazine-2,5-dione (BAPD) 0.20 g (0.62 mmol) and oxydiphthalic dianhydride (OPDA) 0.19 g (0.62 mmol) were mixed with N, N-dimethylacetamide was added to 1.0 mL and reacted at room temperature (about 25 ° C.) in a nitrogen gas atmosphere for 48 hours to obtain an amic acid polymer. The reaction solution containing the amic acid polymer obtained above was reprecipitated using a poor solvent of about 50 mL of water and about 50 mL of acetone, and the obtained amic acid polymer was vacuum dried. The yield of the obtained amic acid polymer A was 0.35 g, and the yield was 90%.

  The infrared absorption (IR) spectrum of the amic acid polymer A obtained above was examined. The result is shown in FIG. From the infrared absorption (IR) spectrum of the amic acid polymer A, the amic acid polymer A has the formula:

It was confirmed that the polymer is an amic acid polymer having a repeating unit represented by:

  The number average molecular weight of the amic acid polymer A obtained above was measured by gel permeation chromatography (GPC) under the following measurement conditions. As a result, it was confirmed that the number average molecular weight of the amic acid polymer A was in the range of 7300 to 21000. Since the amic acid polymer A could not be completely dissolved in the solvent, the number average molecular weight of the amic acid polymer A may not be an accurate value.

〔Measurement condition〕
・ Device: Showa Denko Co., Ltd., trade name: Shodex-101
・ Concentration at injection: 0.01% by mass
・ Injection volume: 100 μL
・ Flow rate: 1 mL / min
Solvent: N, N-dimethylformamide Column: Showa Denko K.K., trade name: Shodex KD-803 and trade name: Shodex KD-804
Column temperature: 40 ° C
・ Standard: Polymethylmethacrylate

Example 8
The amic acid polymer A was cast on a glass plate, placed in a vacuum oven, heated stepwise at 100 ° C. for 1 hour, 150 ° C. for 1 hour, 200 ° C. for 1 hour and 250 ° C. for 3 hours, and then to room temperature. By allowing to cool, the formula:

A film having a thickness of about 30 μm made of polyimide A having a repeating unit represented by

  The infrared absorption (IR) spectrum of the polyimide A obtained above was examined. The result is shown in FIG. From the infrared absorption (IR) spectrum of polyimide A, it was confirmed that polyimide A had the repeating unit.

Example 9
0.20 g (0.62 mmol) of 3,6-bis (4-aminobenzyl) piperazine-2,5-dione (BAPD) and 3,3 ′, 4,4′-diphenylsulfone tetracarboxylic dianhydride Amidic acid polymer B was obtained by adding 22 g (0.62 mmol) to 4.8 mL of N, N-dimethylacetamide and reacting at room temperature (about 25 ° C.) for 48 hours in a nitrogen gas atmosphere.

  The reaction solution containing the amic acid polymer B obtained above was reprecipitated using a poor solvent of about 50 mL of water and about 50 mL of acetone, and the obtained amic acid polymer B was vacuum dried. The yield of the obtained amic acid polymer B was 0.39 g, and the yield was 93%.

As a result of examining the ¹ H-NMR (nuclear magnetic resonance) spectrum of the amic acid polymer B, the amic acid polymer B was found to have a repeating unit in which A is a group represented by the formula (b) in the formula (III). It was confirmed to be a polymer. When the number average molecular weight of the amic acid polymer B was examined in the same manner as in Example 7, the number average molecular weight of the amic acid polymer B was 22,000.

Example 10
The amic acid polymer B was cast on a glass plate, placed in a vacuum oven, heated stepwise at 100 ° C. for 1 hour, 150 ° C. for 1 hour, 200 ° C. for 1 hour and 250 ° C. for 3 hours. By allowing to cool, a film having a thickness of about 30 μm made of polyimide B having a repeating unit of formula (IV) in which A is a group represented by formula (b) was obtained.

It was confirmed by examining the ¹ H-NMR (nuclear magnetic resonance) spectrum and infrared absorption (IR) spectrum of polyimide B that polyimide B obtained above had the repeating unit.

Example 11
3,6-bis (4-aminobenzyl) piperazine-2,5-dione (BAPD) 0.20 g (0.62 mmol) and cyclobutane-1,2,3,4-tetracarboxylic dianhydride (CBDA) 0 .12 g (0.62 mmol) was added to 4.8 mL of N, N-dimethylacetamide and reacted at room temperature (about 25 ° C.) for 48 hours in a nitrogen gas atmosphere to obtain amic acid polymer C. The reaction solution containing the amic acid polymer C obtained above was reprecipitated using a poor solvent of about 50 mL of water and about 50 mL of acetone, and the obtained amic acid polymer C was vacuum dried. The yield of the obtained amic acid polymer C was 0.29 g, and the yield was 91%.

As a result of examining the ¹ H-NMR (nuclear magnetic resonance) spectrum of the amic acid polymer C, the amic acid polymer C was found to have a repeating unit in which A is a group represented by the formula (c) in formula (III). It was confirmed to be a polymer. When the number average molecular weight of the amic acid polymer C was examined in the same manner as in Example 7, the number average molecular weight of the amic acid polymer C was 20,000.

Example 12
The amic acid polymer C was cast on a glass plate, placed in a vacuum oven, heated stepwise at 100 ° C. for 1 hour, 150 ° C. for 1 hour, 200 ° C. for 1 hour and 250 ° C. for 3 hours, and then to room temperature. By allowing to cool, a film having a thickness of about 30 μm made of polyimide C having a repeating unit of formula (IV) in which A is a group represented by formula (c) was obtained.

It was confirmed by examining the ¹ H-NMR (nuclear magnetic resonance) spectrum and infrared absorption (IR) spectrum of polyimide C that polyimide C obtained above had the repeating unit.

Example 13
3,6-bis (4-aminobenzyl) piperazine-2,5-dione (BAPD) 0.2 g (0.62 mmol) and 3,3 ′, 4,4′-benzophenone tetracarboxylic dianhydride (BTDA) Amidic acid polymer D was obtained by adding 0.20 g (0.62 mmol) to 4.8 mL of N, N-dimethylacetamide and reacting at room temperature (about 25 ° C.) for 48 hours in a nitrogen gas atmosphere. . The reaction solution containing the amic acid polymer D obtained above was reprecipitated using a poor solvent of about 50 mL of water and about 50 mL of acetone, and the obtained amic acid polymer D was vacuum dried. The yield of the obtained amic acid polymer D was 0.37 g, and the yield was 93%.

As a result of examining the ¹ H-NMR (nuclear magnetic resonance) spectrum of the amic acid polymer D, it was found that the amic acid polymer D had a repeating unit in which A is a group represented by the formula (d) in the formula (III). It was confirmed to be a polymer. The number average molecular weight of the amic acid polymer D was examined in the same manner as in Example 7. The measurement result of the gel permeation chromatography (GPC) of the amic acid polymer D is shown in FIG. From the results shown in FIG. 7, it was confirmed that the number average molecular weight of the amic acid polymer D was 21,000.

Example 14
The amic acid polymer D was cast on a glass plate, placed in a vacuum oven, heated stepwise at 100 ° C. for 1 hour, 150 ° C. for 1 hour, 200 ° C. for 1 hour and 250 ° C. for 3 hours. By allowing to cool, a film having a thickness of about 30 μm made of polyimide D having a repeating unit of formula (IV) in which A is a group represented by formula (d) was obtained.

It was confirmed by examining the ¹ H-NMR (nuclear magnetic resonance) spectrum and infrared absorption (IR) spectrum of polyimide D that polyimide D obtained above had the repeating unit.

Example 15
3,6-Bis (4-aminobenzyl) piperazine-2,5-dione (BAPD) 0.20 g (0.62 mmol) and 5- (2,5-dioxotetrahydrofuryl) -3-methyl-3-cyclohexene -1,2-dicarboxylic anhydride (DHCDA) 0.16 g (0.62 mmol) was added to 4.8 mL of N, N-dimethylacetamide, and at room temperature (about 25 ° C.) for 48 hours in a nitrogen gas atmosphere. By reacting, amic acid polymer E was obtained. The reaction solution containing the amic acid polymer E obtained above was reprecipitated using a poor solvent of about 50 mL of water and about 50 mL of acetone, and the obtained amic acid polymer E was vacuum dried. The yield of the obtained amic acid polymer E was 0.32 g, and the yield was 89%.

As a result of investigating the ¹ H-NMR (nuclear magnetic resonance) spectrum of the amic acid polymer E, the amic acid polymer E has an amic acid having a repeating unit in which A is a group represented by the formula (e) in the formula (III). It was confirmed to be a polymer. When the number average molecular weight of the amic acid polymer E was examined in the same manner as in Example 7, the number average molecular weight of the amic acid polymer E was 21,000.

Example 16
The amic acid polymer E was cast on a glass plate, placed in a vacuum oven, heated stepwise at 100 ° C. for 1 hour, 150 ° C. for 1 hour, 200 ° C. for 1 hour and 250 ° C. for 3 hours. By allowing to cool, a film having a thickness of about 30 μm made of polyimide E having a repeating unit in which formula (IV) is a group represented by formula (e) in formula (IV) was obtained.

It was confirmed by examining the ¹ H-NMR (nuclear magnetic resonance) spectrum and the infrared absorption (IR) spectrum of polyimide E that polyimide E obtained above had the repeating unit.

Example 17
2,6-bis (4-aminobenzyl) piperazine-2,5-dione (BAPD) 0.20 g (0.62 mmol) and 3,3 ′, 4,4′-biphenyltetracarboxylic dianhydride (BPDA) 0.18 g (0.62 mmol) was added to 4.8 mL of N, N-dimethylacetamide and reacted at room temperature (about 25 ° C.) for 48 hours in a nitrogen gas atmosphere to obtain amic acid polymer E. . The reaction solution containing the amic acid polymer E obtained above was reprecipitated using a poor solvent of about 50 mL of water and about 50 mL of acetone, and the obtained amic acid polymer E was vacuum dried. The yield of the obtained amic acid polymer F was 0.35 g, and the yield was 92%.

As a result of examining the ¹ H-NMR (nuclear magnetic resonance) spectrum of the amic acid polymer F, the amic acid polymer F was found to have a repeating unit in which A is a group represented by the formula (f) in the formula (III). It was confirmed to be a polymer. When the number average molecular weight of the amic acid polymer F was examined in the same manner as in Example 7, the number average molecular weight of the amic acid polymer F was 19000.

Example 18
The amic acid polymer F was cast on a glass plate, placed in a vacuum oven, heated stepwise at 100 ° C. for 1 hour, 150 ° C. for 1 hour, 200 ° C. for 1 hour and 250 ° C. for 3 hours, then to room temperature By allowing to cool, a film having a thickness of about 30 μm composed of polyimide F having a repeating unit in which formula (IV) is a group represented by formula (f) in formula (IV) was obtained.

It was confirmed by examining the ¹ H-NMR (nuclear magnetic resonance) spectrum and infrared absorption (IR) spectrum of polyimide F that the polyimide F obtained above had the repeating unit.

Experimental example 1
5% weight reduction temperature of the film made of polyimide A, the film made of polyimide B, the film made of amic acid polymer C, the film made of polyimide C, the film made of amidic acid polymer D and the film made of polyimide D obtained above. (T _d5 ) and 10 weight loss temperature (T _d10 ) were examined by thermogravimetric analysis. The results are shown in Table 1. The method of thermogravimetric analysis is as follows.

[Thermogravimetric analysis]
・ Measurement device: Thermogravimetric-differential heat simultaneous measurement device [manufactured by Hitachi High-Technologies Corporation, trade name: STA7200]
The film was heated to 800 ° C. at a temperature rising rate of 10 ° C./min in an atmosphere of nitrogen gas, and the weight reduction degree was measured.

  From the results shown in Table 1, it can be seen that the polyimide film obtained above has excellent heat resistance since it has a heat resistant temperature of about 390 ° C. or higher.

Example 19
The amic acid polymer D obtained above was dissolved in dimethylacetamide to prepare a 4 w / v% amic acid polymer solution. As a surfactant solution, 30 mL of a mixed solution of 50% by mass of 1% sodium lauryl sulfate aqueous solution and 50% by mass of 1% nonionic surfactant [manufactured by Nacalai Tesque, Inc., trade name: TRITON X-100] was used. The mixed solution is put into a 100 mL reagent bottle, and the amic acid polymer solution obtained above is dropped into the mixed solution at room temperature with vigorous stirring. Then, ultrasonic waves are applied to the amic acid polymer solution for 30 minutes. A dispersion was prepared by irradiation. The obtained dispersion was centrifuged at a rotational speed of 2000 rpm for 20 minutes at room temperature, thereby removing the mixed solution and collecting fine particles of the amic acid polymer.

  The fine particles of the amic acid polymer obtained above were observed with a scanning electron microscope (SEM). The result is shown in FIG. FIG. 8 is a scanning electron micrograph of the amic acid polymer fine particles obtained above. From the results shown in FIG. 8, the fine particles of the amic acid polymer obtained above include spherical fine particles having a diameter of 383 ± 153 nm and spherical fine particles having a diameter of 7.9 ± 1.3 nm. Recognize.

  When the average particle size of the fine particles of the amic acid polymer obtained above was examined by light scattering, the average particle size of the main fine particles (about 97%) was 270 nm, and the average particle size of the remaining fine particles (about 3%) The diameter was 5 μm.

  Next, the fine particles of the amic acid polymer obtained above were put in a vacuum oven, and the temperature was raised stepwise at 100 ° C. for 1 hour, 150 ° C. for 1 hour, 200 ° C. for 1 hour and 250 ° C. for 3 hours. The mixture was allowed to cool to room temperature to obtain polyimide D fine particles having a repeating unit in which A is a group represented by formula (d) in formula (IV).

It was confirmed by examining the ¹ H-NMR (nuclear magnetic resonance) spectrum and infrared absorption (IR) spectrum of polyimide D that the fine particles of polyimide D obtained above had the repeating unit.

The 5% weight reduction temperature (T _d5 ) and 10% weight reduction temperature (T _d10 ) of the polyimide D fine particles obtained above were examined in the same manner as in Experimental Example 1. As a result, it was confirmed that the 5% weight reduction temperature (T _d5 ) of the fine particles of polyimide D was 383 ° C., and the 10 weight reduction temperature (T _d10 ) was 414 ° C. From these results, it can be seen that the fine particles of polyimide D are excellent in heat resistance.

The 5% weight reduction temperature (T _d5 ) and 10% weight reduction temperature (T _d10 ) of the fine particles of polyimide D are the 5% weight reduction temperature (T _d5 ) and 10% weight reduction temperature ( The reason why it is lower than T _d10 ) is considered to be that its surface is oxidized because the surface area of the fine particles of polyimide D is large.

Example 20
In Example 19, 1% sodium lauryl sulfate aqueous solution, 1% nonionic surfactant [trade name: TRITON X-100], or 1% sodium lauryl sulfate aqueous solution as a surfactant solution Use a mixed solvent of 50% by mass and 1% nonionic surfactant (trade name: TRITON X-100, manufactured by Nacalai Tesque Co., Ltd.), 50% by volume, or use water instead of the surfactant solution. Except that was used, polyimide D fine particles were prepared in the same manner as in Example 19.

  The average particle diameter of the fine particles of polyimide D obtained above was measured. The result is shown in FIG. The average particle size of the fine particles of polyimide D is a value of D50 obtained from a cumulative particle size distribution curve measured by a laser diffraction method.

  In FIG. 9, A is the measurement result of the fine particles of polyimide D prepared using water instead of the surfactant solution, B is the measurement result of the fine particles of polyimide D prepared using a 1% aqueous sodium lauryl sulfate solution, C is a measurement result of fine particles of polyimide D prepared using an aqueous solution of 1% nonionic surfactant [manufactured by Nacalai Tesque, Inc., trade name: TRITON X-100], D is an aqueous solution of 1% sodium lauryl sulfate 50 Measurement results of fine particles of polyimide D prepared using a mixed solvent consisting of 50% by volume of an aqueous solution containing 50% by mass of 1% non-ionic surfactant [Nacalai Tesque, Inc., trade name: TRITON X-100] Show.

  From the results shown in FIG. 9, it can be seen that the particle diameter of the polyimide fine particles can be appropriately adjusted by changing the type of the surfactant solution used in preparing the polyimide.

Experimental example 2
After the polyimide A fine particles, polyimide B fine particles, polyimide fine particles C or polyimide D fine particles are freeze-dried, 0.001 g of each fine particle is uniformly dispersed in 1.0 mL of water, and polyimide is obtained by a dynamic light diffusion method. The redispersibility of the fine particles was investigated.

  As a result, the polyimide fine particles C can be easily dispersed in water, the polyimide D fine particles can be easily dispersed in water by ultrasonic irradiation, and the polyimide A fine particles and the polyimide B fine particles are Although it could be dispersed in water by ultrasonic irradiation, aggregates were observed. From these results, it can be seen that the redispersibility of the fine particles of each polyimide in water is good.

Experimental example 3
When negative charges were charged on the surface of the fine particles of amic acid polymer A, fine particles of amic acid polymer B, fine particles C of amic acid polymer, or amic acid polymer D, a negative zeta potential was observed in each fine particle. From these results, it is considered that the fine particles of each amic acid polymer can be prevented from agglomerating and the resulting polyimide fine particles can be agglomerated.

Example 21
0.04 g of amidic acid polymer D is uniformly dissolved in 1.0 mL of dimethylacetamide, and 100 μL of the resulting solution is 1% nonionic surfactant [Nacalai Tesque, trade name: TRITON X-100] aqueous solution It added to 1 mL, and the amic acid polymer D was disperse | distributed uniformly by irradiating an ultrasonic wave to the obtained mixed solution for 1 hour. After removing the supernatant liquid of the obtained dispersion liquid and ultrasonically washing the dispersion liquid several times, 3 mL of a mixed liquid in which acetic anhydride and pyridine are mixed in an equal mass as an imidizing agent to the dispersion liquid at room temperature. The amic acid polymer D was imidized by adding and leaving the resulting mixture for 10 minutes.

  Next, the pH of the dispersion was adjusted to 12 with an aqueous sodium hydroxide solution, and the produced polyimide fine particles were collected. The polyimide fine particles obtained above were observed with a scanning electron microscope (SEM). The result is shown in FIG.

  FIG. 10 is a scanning electron micrograph of the polyimide fine particles obtained above. From the results shown in FIG. 10, it was confirmed that the obtained polyimide fine particles were fine particles having a particle diameter of about 10 to 1000 nm. From this, it can be seen that by using the polyimide, fine particles having a particle size of the order of nanometers can be easily prepared.

  Further, when the cross section of the polyimide fine particles obtained above was observed, the fine particles were formed of polyimide, and the amic acid polymer present in the fine particles was obtained by using an aqueous sodium hydroxide solution (alkali). It melt | dissolved and it was confirmed that the inside is hollowed.

  From this, the polyimide fine particles obtained above are not only excellent in heat resistance, but also difficult to dissolve by alkali, excellent in chemical resistance, and hollow because the polyimide is used. Therefore, it is expected to be used for applications such as biomaterials such as microcapsules filled with a drug used in a drug delivery system by filling the drug inside thereof. I understand that.

  Next, the imidization time of the mixture was changed from 10 minutes to about 10 hours to produce polyimide fine particles. When the cross section of the obtained polyimide fine particles was observed, it was confirmed that the entire fine particles were formed of polyimide.

  From the above results, it can be seen that the thickness of the polyimide surface layer formed on the surface of the polyimide fine particles can be appropriately adjusted by appropriately adjusting the imidization time of the amic acid polymer fine particles.

Experimental Example 4
The particle size distribution of the polyimide fine particles obtained in Example 19 and Example 21 was measured using a product name: Zeta Sizer Nano ZS manufactured by Malvern. The result is shown in FIG.

  In FIG. 11, A is the particle size distribution of the capsule-shaped polyimide fine particles obtained in Example 21, B is the particle size distribution of the polyimide fine particles obtained in Example 19, and C is the capsule shape obtained in Example 21. The particle size distribution of the polyimide fine particles, D shows the particle size distribution of the polyimide fine particles obtained in Example 21.

  From the results shown in FIG. 11, it can be seen that the hollow polyimide fine particles obtained in Example 21 have a remarkably narrow particle size distribution compared to the other polyimide fine particles.

  The polyimide of the present invention is rigid and easy to be powdered, and is excellent in chemical resistance, heat resistance, etc., so it should be used for applications requiring these properties, such as heat resistant fillers. There is expected.

The hollow polyimide particles of the present invention are not only excellent in chemical resistance and heat resistance because the polyimide is used, but also have a hollow and can be made into fine particles. By filling the drug inside, it is expected to be used for biomaterials such as microcapsules filled with the drug used in the drug delivery system.

Claims (5)

Formula (I):
Bisaminobenzylpiperazinedione represented by Formula (III):
(Where A is the formula:
Indicate)
An amic acid polymer having a repeating unit represented by: Formula (IV):
(Where A is the formula:
Indicate)
A polyimide having a repeating unit represented by:   A hollow polyimide particle comprising a surface layer made of the polyimide according to claim 3 and having a hollow inside.   The particles comprising the amic acid polymer according to claim 2 are imidized with an imidizing agent to form a surface layer made of the polyimide according to claim 3, and then the particles are treated with an alkali to treat the particles. A method for producing hollow polyimide particles, wherein the inside amidic acid polymer is dissolved to hollow out the inside of the particles.