KR20010038527A - Pyridylbenzoxazol Derivatives and Their Copolymers, and Process of Forming Fluorescent Image Using the Same - Google Patents

Abstract

PURPOSE: The pyridyl benzoxazole derivatives, their copolymers, and a fluorescence image making method are provided, thereby the pyridyl benzoxazole copolymers have good sensor properties in solution, film and particle status, so that they can be used as recording materials or sensor materials. CONSTITUTION: The pyridyl benzoxazole derivative is represented by formula (1), in which A and B are independently CH and N; R1 is alkyl or phenyl; R2 is O or NH, R3 is vinyl, acryl, allyl, alpha-methylvinyl or 4-vinylphenyl; m is an integer from 0 to 20. The pyridyl benzoxazole copolymer represented by formula (2) is produced by radical polymerization of comonomer selected from the group consisting of pyridyl benzoxazole derivatives, styrene, maleimide and methacrylate, in which A and B are independently CH and N; R1 is alkyl or phenyl; R2 is O or NH, m is an integer from 0 to 20; R4 is hydrogen or methyl; R5 is methyloxycarbonyl or phenyl; and x and y are integer from 10 to 5000. The fluorescence image making method comprises the steps of: dissolving pyridyl benzoxazole copolymer of formula (2) wherein A is CH and B is N, AIBN, organic acid or inorganic acid in an organic solvent; coating the solution on board and drying to form a thin layer; prebaking the thin layer; and exposing the thin layer to light using photomask and post-exposure baking it.

Description

Pyridylbenzoxazole derivatives and copolymers thereof, and fluorescent imaging methods using the same {Pyridylbenzoxazol Derivatives and Their Copolymers, and Process of Forming Fluorescent Image Using the Same}

The present invention relates to a pyridylbenzoxazole derivative useful as a precursor of a fluorescent image forming material and a copolymer thereof, and a fine fluorescent image forming method using the copolymer. More particularly, the present invention relates to pyridylbenzoxazole derivatives and copolymers thereof in which the intensity of fluorescence decreases upon reaction with acid or metal ions, and a method for forming a microfluorescence image using the copolymer.

Fluorescence generally refers to the ground state when the electrons in the ground state are excited and excited by the light, and then move from the singlet state to the ground state without the transfer of energy from the singlet state to other chemical reactions or solvents or the transition to the triplet state. The light emitted in turn. Representative fluorescent materials include polyaromatic compounds of rigid structure.

The development of sensors that selectively respond to special molecules, metal ions, or acids is widely studied because of its potential for a variety of applications, including diagnostic reagents and environmental pollutant measurements. In general, several methods are used to detect trace substances. The detection method varies depending on the type of material to be analyzed, but usually uses a redox potential difference, a change in absorption spectrum, or a change in fluorescence spectrum. Among other methods, many analyzes using comparatively simple measurements and changes in fluorescence that can detect trace concentrations have been studied (Chem. Rev. vol. 97, page 1515 (1997); J. Org. Chem). Vol. 62, p. 6203 (1997); Angew. Chem. Int. Ed. Engl. Vol. 33, p. 1044 (1994); Top. Current Chem. Vol. 168, p. 223 (1993); Angew Chem. Int. Ed. Engl. Vol. 35, p. 202 (1996); J. Am. Chem. Soc. Vol. 119, p. 5551 (1997)). Compounds for fluorescent sensors known to date have usually been small molecules having a molecular weight of 1000 or less. The disadvantage of small molecule fluorescent sensors is that they only appear when the sensor function is in solution and difficult to recycle. Until now, no research on the formation of fluorescence images using the polymer fluorescence sensor function has been reported.

The present inventors have intensively studied to solve the above problems, and as a result, a copolymer containing pyridylbenzoxazole which exhibits strong fluorescence due to an amine group that pushes electrons at one end and an electron-rich pyridyl group at the other end Based on the fact that when the amine element of pyridyl in ions is ion-bonded by acid, it will attract electrons and decrease the intensity of fluorescence, thereby obtaining a pyridylbenzoxazole derivative and using the copolymer prepared therefrom. The fine fluorescent image can be formed, and these copolymers have been found to be excellent in sensor function in solution, film and particle states, and thus can be applied as recording materials and sensor materials.

It is therefore an object of the present invention to provide pyridylbenzoxazole derivatives, which are useful as precursors for microfluorescence image forming materials.

Another object of the present invention is to provide a pyridylbenzoxazole-containing copolymer prepared from the pyridylbenzoxazole derivatives.

Still another object of the present invention is to provide a method for producing the pyridylbenzoxazole-containing copolymer.

It is still another object of the present invention to provide a method for forming a fine fluorescent image using the pyridylbenzoxazole-containing copolymer.

According to the present invention, there is provided a pyridylbenzoxazole derivative of the general formula (1) in which the intensity of fluorescence is reduced by hydrogen bonds, ionic bonds, and coordinating bonds, which are useful as precursors for the microfluorescence image forming material.

Where

One of A and B is CH, the other is N,

R ₁ is an alkyl or phenyl group,

R ₂ is O or NH,

R ₃ is vinyl, acrylic, allyl, α-methylvinyl or 4-vinylphenyl,

m is an integer of 0-20.

R ₁ is an alkyl group such as methyl, ethyl, and propyl, or a phenyl group.

R ₃ is a polymerization functional group, and is vinyl, acrylic, allyl, α-methylvinyl or 4-vinylphenyl, which are generally styrene and acrylate-based polymers, which are commonly used for polymerization.

m is an integer of 0 to 20, and an alkyl group having 0 to 20 carbon atoms serves as a ring connecting the pyridylbenzoxazole and the polymerization functional group.

In addition, according to the present invention, the pyridylbenzoxazole of formula (1) prepared by radical polymerization with conventional comonomers such as styrene, maleimide and methacrylate using the pyridylbenzoxazole derivative of formula (1) as a monomer Copolymers are provided.

Where

A, B, R ₁ , R ₂ and m are as defined in Formula 1,

C is or ego,

R ₄ is hydrogen or a methyl group,

R ₅ is methyloxycarbonyl or phenyl,

x and y are integers from 10 to 5000.

The pyridylbenzoxazole-containing copolymer of Formula 2 is prepared by radical polymerization of a pyridylbenzoxazole derivative of Formula 1 and a comonomer selected from the group consisting of styrene, maleimide and methacrylate in the presence of a polymerization initiator.

At this time, the polymerization reaction is preferably carried out at a temperature of about 60 to 75 ℃.

According to another aspect of the invention,

A pyridylbenzoxazole-containing copolymer of Formula 2, a photoacid generator, and an organic or inorganic acid, wherein A is CH and B is N, are dissolved in an organic solvent to prepare a solution.

The solution is applied to a substrate and dried to form a thin film,

Prebaking the thin film coated substrate,

A method of forming a microfluorescence image is provided which is characterized by exposing using a photomask and then post-exposure baking to change the fluorescence.

According to another aspect of the invention,

A solution is prepared by dissolving a pyridylbenzoxazole-containing copolymer of formula (2), a photoacid generator and a metal ion according to item 4, wherein A is N and B is CH.

The solution is applied to a substrate and dried to form a thin film,

Prebaking the thin film coated substrate,

A method of forming a microfluorescence image is provided which is characterized by exposing using a photomask and then post-exposure baking to change the fluorescence.

Examples of the organic solvent used in the preparation of the solution containing the copolymer of Formula 2 include cyclohexanone, chloroform, dichloromethane, and dimethylformamide (DMF). The copolymer of the above formula (2) is easily dissolved in these solvents, and exhibits good film forming ability upon rotation coating on a silicon wafer, a glass substrate, or a quartz substrate. In addition, the polymer was easily polymerized using a large amount of crosslinking agent and then easily processed into a particle form when using a grinder.

In the case of the pyridylbenzoxazole-containing copolymer of Formula 2 wherein A is CH and B is N, the fluorescence changes by dissolving the organic acid or the inorganic acid together in the organic solvent to reduce the fluorescence. In the case of the pyridylbenzoxazole-containing copolymer of the formula (2) wherein A is N and B is CH, the fluorescence is changed by dissolving the metal ions together in the organic solvent to reduce the fluorescence by the action of the metal.

In order to confirm the change in fluorescence caused by acid, a pyridylbenzoxazole-containing copolymer of formula (2) in which A is CH and B is N is dissolved in chloroform, and various organic acids such as acetic acid, benzoic acid, trifluoroacetic acid and camphorsulfonic acid are dissolved. It was put at a constant concentration and the change in fluorescence properties was observed. The pyridylbenzoxazole-containing copolymer of formula (2), wherein A is CH and B is N, exhibits strong fluorescence around 550 nm due to the fluorescence properties of pyridylbenzoxazole. When a strong acid acts on the amine of the pyridyl benzoxazole chromophore and an ion pair is formed, the electron distribution of the pyridyl benzoxazole chromophore changes, accompanied by a change in fluorescence. In general, aromatic compounds have strong fluorescence when there are substituents such as amine groups or hydroxyl groups that push electrons at both ends. However, the intensity of fluorescence decreases when there are substituents that attract electrons on both sides, or when one end pushes electrons and the other end turns off electrons. In the case of the pyridylbenzoxazole-containing copolymer represented by Chemical Formula 2 wherein A is CH and B is N, the pyridylbenzoxazole-containing copolymer has an amine group for boosting electrons at one end thereof and a pyridyl group rich in electrons at one end thereof. Strong fluorescence. However, when the amine element of pyridyl is ion-bonded by an acid, it attracts electrons and decreases the intensity of fluorescence. The degree of decrease in fluorescence intensity is proportional to the acid intensity. Therefore, the use of weak acid, acetic acid or benzoic acid, showed little change in fluorescence. However, the use of strong acid, trifluoroacetic acid or sulfonic acid, greatly decreased the intensity of fluorescence.

On the other hand, the pyridyl benzoxazole-containing copolymer of formula (2) wherein A is N and B is CH synthesized in the present invention has a structure of bipyridyl (pypyridyl) in which the structure of the pyridyl benzoxazole bonds well with the metal ion Therefore, a decrease in fluorescence is expected when reacting with metal ions. For example, in a chloroform solution in which a pyridylbenzoxazole-containing copolymer represented by Chemical Formula 2 in which A is N and B is CH, various metal ions such as iron, copper, nickel, and cobalt are added to observe the change in fluorescence. Although there is a difference in the intensity of the fluorescence was shown to decrease. In particular, the use of copper and iron as metal ions was more than 100 times higher than the concentration of the pyridylbenzoxazole-containing copolymer of Formula 2 where A is N and B is CH.

The microfluorescence image formation according to the present invention comprises, for example, dissolving the copolymer of the present invention mixed with a photoacid generator such as triphenylsulfonium triflate in an organic solvent and spin coating on a silicon wafer to about 1 μm. It is carried out by rotating the coating to a thickness to make a thin film and then ultraviolet exposure through a photomask. When ultraviolet exposure is performed using a photomask, an acid is generated in the exposed portion and ionic bonds with pyridylbenzoxazole, so that the fluorescence is reduced, and the fluorescence remains in the unexposed portion, thereby forming a fine fluorescence pattern.

Hereinafter, examples of the pyridylbenzoxazole derivatives of the present invention, the preparation of copolymers therefrom, the fluorescence increase experiments with acids and metals of the copolymers, and the method for forming a microfluorescence image using the copolymers will be given. It demonstrates concretely.

<Example 1>

Preparation of Monomer 4-PBZMA:

(a) Synthesis of Intermediate 2:

20.72 g of potassium carbonate (0.15) in a 200 mL solution of DMF completely dissolved 37.04 g (0.15 mmol) of known 2- (benzyloxy) -4-fluoronitrobenzene and 22.34 g (0.30 mmol) of 2- (methylamino) ethanol mmol) was added and stirred at 100 ° C. for 3 hours. The mixture obtained after stirring was precipitated in 1 L water, filtered and dried to recover a yellow precipitate. The precipitate was dissolved in tetrahydrofuran (THF) again, and added dropwise to hexane to obtain 43.1 g of a reaction product (yield: 95%), which was then recrystallized from ethyl acetate to obtain an intermediate 2 of yellow crystals. mp 104-106 ° C. ¹ H-NMR (DMSO-d6): d 3.04 (s, 3H, NCH ₃ ), 3.52 (s, 4H, CH ₂ ), 4.79 (s, 1H, OH), 5.28 (s, 2H, OCH ₂ ), 6.35-6.41 (m, 2H, ArH), 7.31-7.52 (m, 5H, ArH), and 7.89 ppm (d, 1H, ArH);

Analysis for C1 ₆ H ₁₈ N ₂ 0 ₄ (302.33):

Calc .: C, 63.57%; H, 6.00%; N, 9.27%.

Found: C, 63.5%; H, 6.09%; N, 9.21%.

(b) Synthesis of Intermediate 5:

Dissolve Intermediate 2 (9.07 g, 0.03 mol) synthesized in (a) above in 150 mL of THF, and carefully add 1.0 g of palladium on 10% carbon. The mixed solution was stirred for 12 hours while adding hydrogen under normal pressure and ambient temperature. The unreacted solid was filtered through a filter to obtain a filtrate containing intermediate 3. To this solution, 6.43 g (0.06 mol) of 4-pyridine carboxaldehyde was added and reacted for 2 hours under a stream of nitrogen, which was then dissolved in 1 L hexane. Precipitation gave intermediate 4. The precipitated intermediate 4 was dissolved in THF without separation, and then 17.7 g (0.04 mol) of lead (IV) acetate was added thereto, followed by stirring for 2 hours. After the reaction, the solid was filtered off, and the silica column was purified using THF as the eluent to obtain 5.1 g of yellow crystal intermediate 5. mp 176-178 ° C; ¹ H-NMR (DMSO-d ₆ ): δ 2.98 (s, 3H, NCH ₃ ), 3.46-3.58 (m, 4H, CH ₂ ), 4.70 (t, 1H, OH), 6.84 (d, 1H, ArH ), 6.96 (s, 1H, ArH), 7.94 (d, 2H, ArH), and 8.73 (d, 2H, ArH)

(c) Synthesis of Monomer 4-PBZMA:

Intermediate 5 (4.04 g, 15 mmol) synthesized in (b) was dissolved in 200 mL of dichloromethane, and 2.09 g (0.02 mol) of methacryloyl chloride was slowly added dropwise thereto. 5 mL of triethylamine was added to the mixed solution, followed by stirring at room temperature for 12 hours. Then, the mixture was extracted using a separating funnel in water and dichloromethane solvent, and the organic layers were collected and dried over anhydrous magnesium sulfate, and then the solvent was evaporated to obtain a red crystalline powder. Purification gave 4.77 g of monomer 4-PBZMA. ¹ H-NMR (CDCl ₃ ): δ 1.91 (s, 3H, CH ₃ ), 3.09 (s, 3H, NCH ₃ ), 3.75 (t, 2H, CH ₂ ), 4.38 (t, 2H, CH ₂ ) , 5.55 (s, 1H, = CH ₂ ), 6.07 (s, 1H, = CH ₂ ), 6.84-6.89 (m, 2H, ArH), 7.62 (d, 1H, ArH), 7.99 (d, 2H, ArH ), And 8.76 (d, 4H, ArH).

<Example 2>

Preparation method of copolymer P (4PBZMA / MMA) using the monomer of Example 1:

149 mg (1.49 mmol) of methyl methacrylate was added to a solution of monomer 4-PBZMA (500 mg, 1.48 mmol) synthesized in Example 1 and dissolved in 1.0 ml of N-methylpyrrolidinone (NMP) in a glass tube polymerization vessel. After that, 9.7 mg (2 mol%) of initiator azoisobutyronitrile (AIBN) was added thereto, and the resultant was washed with 1.5 ml of solvent N-methylpyrrolidone (NMP). The mixed solution was sealed in vacuo through three freeze-thaw cycles, and the polymer tube was allowed to react for 12 hours in a 65 DEG C oil bath. After confirming that the viscosity increased to some extent, the polymerization vessel was broken and the copolymer was slowly dropped into about 100 ml of methanol to precipitate. The obtained copolymer was filtered, dissolved in a minimum amount of DMF, and then reprecipitated in 100 mL of methanol to obtain 385 mg of a yellow copolymer. The molecular weight of the obtained copolymer was about 61,000. The structure of the copolymer was confirmed by ¹ H NMR and FTIR spectroscopy, and the composition ratio of pyridylbenzoxazole and MMA repeating unit was 4: 6.

<Example 3>

Preparation of Copolymer P (4PBZMA / St) Using Monomer of Example 1:

According to Scheme 3 below, using the monomer 4-PBZMA (1.0 g), styrene (0.8 g) and initiator AIBN (30 mg) synthesized in Example 1, radical polymerization was carried out under the same conditions as in Example 2 to obtain copolymer P ( 1.2 g of 4PBZMA / St) was obtained.

<Example 4>

Preparation method of copolymer P (4PBZMA / MA) using the monomer of Example 1:

According to Scheme 4 below, the copolymer P was subjected to radical polymerization under the same conditions as in Example 2 using the monomer 4-PBZMA (0.9 g), maleic anhydride (0.7 g) and initiator AIBN (23 mg) synthesized in Example 1 0.6 g (4PBZMA / MA) was obtained.

<Example 5>

Synthesis of Monomer 2-PBZMA:

Synthesis of monomer 2-PBZMA was carried out according to the method used for synthesis of monomer 4-PBZMA of Example 1.

(a) Synthesis of Intermediate 7:

Example 1 Intermediate 2 (4.05 g, 13.41 mmol) synthesized in (a) was dissolved in 150 mL of THF, and then intermediate 3 was obtained in the same manner as in Example 1 (b), where 2-pyridine was used under similar conditions. Carboxaldehyde 1.6g (13.94 mmol) was added, and intermediate 6 was obtained in the same manner, followed by 2.48 g of intermediate 7 using lead (IV) acetate. mp: 105-111 ° C .; ¹ H NMR (DMSO-d ₆ ): δ 2.94 (s, 3H, NCH ₃ ), 3.39 (m, 4H, CH ₂ ), 4.72 (t, 1H, OH), 6.19-6.29 (m, 2H, ArH) , 7.26-8.10 (m, 3H, ArH), 8.95 (s, 1H, = CH), and 9.23 ppm (s, 1H, ArOH).

(b) Synthesis of Monomer 2-PBZMA:

Synthesis of monomer 2-PBZMA was prepared from intermediate 7 using a method similar to (c) of Example 1. mp: 72-74 ° C .; UV-vis: λ _max (CHCl ₃ ): 369.5 nm; ¹ H NMR (CDCl ₃ ): δ 1.88 (s, 3H, CH ₃ ), 3.05 (s, 3H, NCH ₃ ), 3.71 (t, 2H, NCH ₂ ), 4.35 (t, 2H, OCH ₂ ), 5.51 (s, 1H, = CH ₂ ), 6.03 (s, 1H, = CH ₂ ), 6.82-6.93 (m, 2H, ArH), 7.33-7.39 (m, 1H, ArH), 7.51 (d, 1H, ArH ), 7.83 (m, 1H, ArH), 8.24 (d, 1H, ArH) and 8.76 (d, 1H, ArH).

<Example 6>

Preparation of Copolymer P (2-PBZMA / MMA) Using Monomer of Example 5:

According to Scheme 6 below, copolymer P (2-PBZMA / MMA) was obtained in a similar manner to Example 2 using the monomer 2-PBZMA synthesized in Example 5. The molecular weight of the obtained copolymer was about 24,000. The structure of the copolymer was confirmed by ¹ H NMR, FTIR and the like, the ratio of pyridyl benzoxazole and MMA showed a 4: 6 ratio as in the copolymer obtained in Example 2.

<Example 7>

Experiment for Fluorescence Reduction of Copolymer P (4-PBZMA / MMA) with Acid:

Copolymer P (4-PBZAMA / MMA) prepared in Example 2 was dissolved in chloroform to give a solution having a concentration of 1 x 10 ^-7 M of pyridylbenzoxazole chromophore, in which acetic acid, benzoic acid, trifluoroacetic acid, And camphorsulfonic acid was added to measure the decrease in fluorescence. In the case of acetic acid and benzoic acid, the fluorescence was reduced by less than 5% even when 100 times the chromophore concentration was added, but the same concentration of trifluoroacetic acid showed a decrease in fluorescence of 60% or more. In addition, it was observed that fluorescence completely disappeared in the case of sulfonic acid, which is the strongest acid among the measured acids. Accordingly, the copolymer P (4-PBZMA / MMA) was shown to function well as a sensor because the intensity of fluorescence decreased proportionally with increasing acid intensity.

<Example 8>

Experiment for Fluorescence Reduction of Copolymer P (2-PBZMA / MMA) by Metal Ion:

Copolymer P (2-PBZMA / MMA) prepared in Example 6 was dissolved in chloroform to prepare a solution having a chromophore concentration of 1 × 10 ⁻⁷ M, and various metal ions were added thereto to measure the decrease in fluorescence. When the concentration of the metal ions was 100 times the chromophore, about 60% of fluorescence was reduced in cobalt and nickel, about 90% was decreased in copper, and fluorescence was completely eliminated in iron. The above experiments demonstrate that the copolymer shows selectivity for specific metal ions.

<Example 9>

Fluorescence Image Formation Using Copolymer P (4-PBZMA / MMA):

Copolymer P (4-PBZMA / MMA) prepared in Example 2 was dissolved in 1,4-dioxane in an amount of 70% by weight, and triphenylsulfonium triflate, a known photoacid generator, was added to 30 The solution dissolved in the amount by weight was filtered through a 0.2 μm pore size membrane filter. This solution was spun on a silicon wafer to produce a thin film having a thickness of about 1.0 mu m. This sample wafer was predbaked for 1 minute on a 100 degreeC hotplate, and exposed for 60 second with the 250-nm UV exposure apparatus using the photomask. The exposed sample was post-exposure baked for 60 seconds on a 120 ° C. hotplate and fine fluorescence pattern formation was observed using a fluorescence microscope. The generated fluorescence pattern showed good resolution at 1 μm level and yellow pattern. The resulting fluorescent pattern was stable for at least 6 months at room temperature and did not involve a change in resolution.

The pyridylbenzoxazole-containing copolymer of the present invention is fluorescence is changed by the organic acid or inorganic acid, or metal ions, and can be easily mixed with a photoacid generator to form a micro-fluorescence image of the micrometer unit when exposed in a thin film state, Its excellent sensor function in solution, film and particle conditions makes it applicable to recording materials and sensor materials.

Claims (6)

A pyridylbenzoxazole derivative of the formula <Formula 1> Where One of A and B is CH, the other is N, R ₁ is an alkyl or phenyl group, R ₂ is O or NH, R ₃ is vinyl, acrylic, allyl, α-methylvinyl or 4-vinylphenyl, m is an integer of 0-20. In the presence of a polymerization initiator, pyridylbenzoxazole of formula (2) characterized by radically polymerizing a pyridylbenzoxazole derivative according to claim 1 and a comonomer selected from the group consisting of styrene, maleimide and methacrylate. Method of Making Copolymers. <Formula 2> Where One of A and B is CH, the other is N, R ₁ is an alkyl or phenyl group, R ₂ is O or NH, m is an integer of 0-20. C is or ego, R ₄ is hydrogen or a methyl group, R ₅ is methyloxycarbonyl or phenyl, x and y are integers from 10 to 5000. The method according to claim 2, wherein the polymerization temperature is 60 to 75 ° C. A pyridyl benzoxazole-containing copolymer represented by the following formula (2). <Formula 2> Where One of A and B is CH, the other is N, R ₁ is an alkyl or phenyl group, R ₂ is O or NH, m is an integer of 0-20. C is or ego, R ₄ is hydrogen or a methyl group, R ₅ is methyloxycarbonyl or phenyl, x and y are integers from 10 to 5000. A solution is prepared by dissolving a pyridylbenzoxazole-containing copolymer of formula (2), a photoacid generator and an organic or inorganic acid according to claim 4, wherein A is CH and B is N in an organic solvent, The solution is applied to a substrate and dried to form a thin film, Prebaking the thin film coated substrate, And exposing using a photomask and then post-exposure baking to change the fluorescence. A solution is prepared by dissolving a pyridylbenzoxazole-containing copolymer of formula (2), a photoacid generator and a metal ion according to item 4, wherein A is N and B is CH. The solution is applied to a substrate and dried to form a thin film, Prebaking the thin film coated substrate, And exposing using a photomask and then post-exposure baking to change the fluorescence.