JP6249210B2 - Organic fluorescent material - Google Patents

Description

  The present invention relates to an organic fluorescent material having a sulfonylaniline skeleton.

  Organic fluorescent materials have attracted attention in recent years because they can be applied to bioimaging, organic EL light-emitting dyes, and dye lasers. In order to exhibit the high performance of this organic fluorescent material, a high molar extinction coefficient and emission quantum efficiency are required.

For this reason, molecular design of organic fluorescent materials has been conventionally performed by extending a rigid π-electron system that suppresses molecular motion.
However, such organic fluorescent materials have problems such as a decrease in solubility due to strong intermolecular interaction, concentration quenching due to intermolecular energy transfer, and low material stability. In particular, concentration quenching significantly reduces the contrast of bioimaging and becomes a problem in the case of organic EL light-emitting dyes that use solid-state light emission. Furthermore, the decrease in solubility is extremely disadvantageous in bioimaging applications performed mainly in aqueous media, and is represented by processes that make the most of the characteristics of organic electronic materials, that is, inkjet methods. It becomes a big obstacle in the wet process.
Bioimaging as used herein is a technology that captures the distribution / localization of proteins and the like at the cell / tissue or individual level and analyzes their dynamics as an image, specifically, a fluorescence emission imaging system, This refers to a technique (fluorescence imaging method) for visualizing biomolecules using fluorescence.

  Therefore, new molecular design guidelines are required. As one of them, introduction of bulky substituents that are not directly related to the fluorescence properties has been studied. In this case, it is often essential to introduce a functional group that adds solubility.

  On the other hand, the inventors of the present application allow a single benzene skeleton to coexist with a plurality of amino groups and sulfonyl groups without introducing other functional groups. (2) Improved solubility and solid fluorescence resulting from the bent structure of the sulfonyl group, (3) Fluorescence quantum efficiency resulting from suppression of free rotation of the amino group due to hydrogen bonding between the amino group and the sulfonyl group The present inventors have found an organic fluorescent material capable of obtaining characteristics superior to those of the prior art, such as improved stability. Specifically, "Synthesis and fluorescence characteristics of 2,6-bis (arylsulfonyl) aniline analog" shown below (Chemical Formula 1) has already been reported (see Non-Patent Document 1).

Teruo Betsube, Yoshihiro Oba, Hiroshi Katagiri, “Proceedings of the 93rd Annual Meeting of the Chemical Society of Japan (2013)”, Program No. 2A2-05

  However, the above 2,6-bis (arylsulfonyl) aniline analog has a fluorescence wavelength of 432 nm at the longest and does not dissolve in water, and thus has low adaptability to bioimaging. In addition, the quantum efficiency is low, making it difficult to use as a coating-type organic EL material. Furthermore, in the synthesis, a nitrobenzene derivative is used as a substrate, but such a substrate available at the present time is limited to a material having one nitro group, and there are many restrictions from the viewpoint of synthesis.

  Therefore, it has higher solubility, can emit fluorescence in any state of solution and solid, can further improve fluorescence quantum efficiency and stability, and can be synthesized simply and efficiently. Fluorescent materials that can be used are required.

  The present invention is excellent as a light emitting material in bioimaging and organic EL in order to improve the above technical problems in the organic fluorescent material in which the amino group and the sulfonyl group introduced into the benzene skeleton are reported. An object of the present invention is to provide an organic fluorescent material capable of exhibiting excellent performance.

  According to the present invention, an organic fluorescent material having a sulfonylaniline skeleton represented by the following general formulas (1) to (9) is provided.

Here, in the formulas (1) to (9), the substituents R ^{1 to} R ³ are each independently a phenyl group substituted with an alkyl group, a fluoroalkyl group, a phenyl group, a halogen atom, an amino group or an alkoxy group. , A naphthyl group, a thienyl group, a thienyl group substituted with a halogen atom, a thiazolyl group, a thiazolyl group substituted with a halogen atom, a pyridyl group, and a pyridyl group substituted with a halogen atom.

  The organic fluorescent material having a sulfonylaniline skeleton as described above is a novel fluorescent material that can emit fluorescence in either a solution or a solid state and is excellent in fluorescence quantum efficiency and stability.

According to the present invention, it has higher solubility than conventional ones, and can emit fluorescent light in either a solution or a solid state. Further improvement in fluorescence quantum efficiency and stability can be achieved, and efficiency can be improved. A fluorescent material that can be synthesized in a labile manner is obtained.
Therefore, the fluorescent material according to the present invention can exhibit excellent performance as a light emitting material in bioimaging and organic EL.

It is the graph which showed the relationship between the irradiation time of the organic fluorescent material in an Example, and an absorbance decreasing rate.

Hereinafter, the present invention will be described in more detail.
The organic fluorescent material according to the present invention is a compound having a sulfonylaniline skeleton represented by the general formulas (1) to (9). That is, the compound is a novel organic fluorescent material having a structure in which an amino group and 2 or 3 sulfonyl groups are introduced into a benzene skeleton.
A compound having such a sulfonylaniline skeleton has a simple structure, a low molecular weight, excellent solubility, water solubility, and a large Stokes shift compared to conventional fluorescent dyes. It is very useful in bioimaging and can also be suitably applied as a coating-type organic EL material.

In addition, the organic fluorescent material is less susceptible to concentration quenching, emits fluorescence with high quantum efficiency, even in a solution state or in a solid state, and has a characteristic that it is more stable than conventional fluorescent dyes. ing.
Furthermore, these organic fluorescent materials have an advantage that they can be synthesized by a simple and highly efficient method via the Ullmann reaction.

In the general formulas (1) to (9), various substituents can be introduced into the substituents R ^{1 to} R ³ , except that an electron donating group or an electron accepting group is introduced. In addition, it is possible to design a molecule with a high degree of freedom, such as introducing aniline to form a twisted intramolecular charge transfer (TICT) structure, or introducing a small molecule for water-soluble expression. it can.

Specifically, the substituents R ^{1 to} R ³ are each independently an alkyl group, a fluoroalkyl group, a phenyl group, a halogen atom, a phenyl group substituted with an amino group or an alkoxy group, a naphthyl group, a thienyl group, Any of a thienyl group substituted with a halogen atom, a thiazolyl group, a thiazolyl group substituted with a halogen atom, a pyridyl group, and a pyridyl group substituted with a halogen atom.

  Specific examples of the organic fluorescent material represented by the general formula (1) are shown below.

  The method for synthesizing the organic fluorescent material according to the present invention as described above is not particularly limited, but the organic fluorescent material has a simple skeleton in which an amino group and a sulfonyl group are introduced into a benzene skeleton, And since it is a compound with a comparatively small molecular weight, it can obtain efficiently using simple synthesis methods, such as an Ullmann reaction. Specific synthesis methods are shown in the following examples.

As described above, the organic fluorescent material according to the present invention has a larger Stokes shift, suppresses autofluorescence, and is more stable than conventional organic fluorescent dyes. Can do.
Compared to conventional organic fluorescent materials, solubility and quantum efficiency are improved, and the synthesis process is simple, so it is possible to fabricate organic electronic devices such as organic EL elements at low cost by a wet process. It is a material that can be applied to a dye laser.

EXAMPLES Hereinafter, although this invention is demonstrated further more concretely based on an Example, this invention is not limited to the following Example.
Of the organic fluorescent materials according to the present invention, four representative examples were synthesized by a method using the Ullmann reaction.

(Synthesis Example 1) Synthesis of BPS-p-A BPS-p-A was synthesized through the steps shown below.

  First, in a nitrogen atmosphere, 50 ml of water, 130 mg of sodium hydroxide, and 300 mg of Compound 1 were placed in a 100 ml two-necked flask and stirred at room temperature for 30 minutes. Subsequently, 60 mg of copper (I) chloride, 2.10 g of trans-1,2-cyclohexanediamine and 900 mg of iodobenzene (Compound 2) were added, and the mixture was refluxed and stirred for 1 day. After allowing to cool, extraction was performed 3 times with 100 ml of dichloromethane, and the organic layer was washed twice with 100 ml of water and 100 ml of saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was distilled off with a rotary evaporator and the residue was purified by silica gel column chromatography (NH silica gel, dichloromethane: hexane = 2: 3) to obtain colorless scaly crystals of compound 3 (303 mg, yield 76%).

  Next, under a nitrogen atmosphere, 50 mg of Compound 3, 10 ml of dichloromethane, 78 mg of triethylamine and 79 mg of acetic anhydride were placed in a 30 ml two-necked flask and stirred at room temperature for 1 day. After adding 10 ml of water and stirring for 30 minutes, extraction was performed three times with 30 ml of dichloromethane. The organic layer was washed 5 times with 30 ml of water and 100 ml of saturated brine and dried over anhydrous sodium sulfate. Then, the solvent was distilled off with a rotary evaporator to obtain a colorless powder of Compound 4 (61 mg, yield 97%).

  Then, under a nitrogen atmosphere, 68 mg of compound 4, 20 ml of dichloromethane, and 212 mg of m-CPBA 75% were placed in a 50 ml two-necked flask and stirred at room temperature for 1 day. Thereafter, 10 ml of saturated aqueous sodium sulfite solution and 10 ml of 1N aqueous sodium hydroxide solution were added to inactivate the reaction solution. The reaction solution was transferred to a separatory funnel, and 50 ml of dichloromethane and 50 ml of water were added to separate the organic layer and the aqueous layer. The aqueous layer was extracted 10 times with 40 ml of dichloromethane, combined with the organic layer, washed with 200 ml of saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was distilled off with a rotary evaporator to obtain a colorless powder of Compound 5 (73 mg, quantitative).

  A 50 ml two-necked flask was charged with 55 mg of compound 5, 6 ml of 6N hydrochloric acid, and 8 ml of tetrahydrofuran, and stirred under reflux for 3 hours. This was added little by little to 400 ml of 4N aqueous sodium hydroxide solution, stirred vigorously at room temperature for 1 day, suction filtered, washed with 50 ml of water, and the filtrate was dried under reduced pressure to give compound 6 (BPS-p-A). A yellowish green powder was obtained (44.3 mg, 98% yield).

(Synthesis Example 2) Synthesis of BAS-p-A BAS-p-A was synthesized through the steps shown below.

  First, under a nitrogen atmosphere, 75 ml of water, 10 ml of ethanol, 190 mg of sodium hydroxide, and 500 mg of compound 1 were placed in a 100 ml two-necked flask and stirred at room temperature for 30 minutes. Subsequently, 100 mg of copper (I) chloride, 3.5 g of trans-1,2-cyclohexanediamine, and 1.42 g of 2-iodoaniline (Compound 7) were added, and reflux stirring was performed for 1 day. After allowing to cool, extraction was performed 5 times with 100 ml of dichloromethane, and the organic layer was washed twice with 100 ml of water and 100 ml of saturated brine, and dried over anhydrous sodium sulfate. Thereafter, the solvent was removed by a rotary evaporator, and the residue was purified by silica gel column chromatography (NH silica gel, dichloromethane). Next, recrystallization was performed with a mixed solvent of dichloromethane-hexane to obtain colorless scaly crystals of compound 8 (554 mg, yield 77%).

  Next, under a nitrogen atmosphere, 300 mg of Compound 8, 60 ml of dichloromethane, 1.29 g of triethylamine and 1.30 g of acetic anhydride were placed in a 100 ml two-necked flask and stirred at room temperature for 1 day. 30 ml of water was added and stirred for 30 minutes. The reaction solution was transferred to a separating funnel, 50 ml of dichloromethane and 50 ml of water were added, and the aqueous layer and the organic layer were separated. The aqueous layer was extracted 4 times with 80 ml of dichloromethane, combined with the organic layer, washed twice with 100 ml of water and 100 ml of saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was distilled off with a rotary evaporator to obtain a colorless powder of Compound 9 (440 mg, quantitative).

  Then, under a nitrogen atmosphere, 150 mg of compound 9 and 100 ml of dichloromethane were added to a 200 ml two-necked flask, and 660 mg of m-CPBA 75% was added and stirred at room temperature for 1 day. Thereafter, 30 ml of saturated aqueous sodium sulfite solution and 30 ml of 1N aqueous sodium hydroxide solution were added to inactivate the reaction solution. The reaction solution was transferred to a separatory funnel, and 50 ml of dichloromethane and 50 ml of water were added to separate the aqueous layer and the organic layer. The aqueous layer was extracted 5 times with 80 ml of dichloromethane, combined with the organic layer, washed with 200 ml of saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was distilled off with a rotary evaporator to obtain a colorless powder of Compound 10 (165 mg, quantitative).

  Then, 70 mg of compound 10, 30 ml of 6N hydrochloric acid and 30 ml of tetrahydrofuran were added to a 100 ml two-necked flask, and the mixture was refluxed and stirred for 3 hours. This was added little by little to 600 ml of 4N aqueous sodium hydroxide solution, stirred vigorously at room temperature for 1 day, suction filtered, washed with 50 ml of water, and the filtrate was dried under reduced pressure to obtain a yellowish green powder. This was coated with 30 ml of 1,2-dichloroethane and purified by silica gel column chromatography (NH silica gel, dichloromethane: methanol = 30: 1) to obtain a yellowish green powder of compound 10 (BAS-p-A) (34 mg). Yield 69%).

(Synthesis Example 3) BThS-p-A
BThS-p-A was synthesized through the steps as shown below.

  First, under a nitrogen atmosphere, 140 ml of water, 270 mg of sodium hydroxide, and 800 mg of Compound 1 were placed in a 200 ml three-necked flask and stirred at room temperature for 30 minutes. Subsequently, 30 mg of copper (I) chloride, 5.3 g of trans-1,2-cyclohexanediamine, and 3.1 g of 2-iodothiophene (Compound 12) were added, and the mixture was refluxed for 1 day. After allowing to cool, extraction was performed 3 times with 150 ml of dichloromethane, and the organic layer was washed 3 times with 100 ml of water and 100 ml of saturated brine and dried over anhydrous sodium sulfate. Thereafter, the solvent was distilled off with a rotary evaporator, and the residue was purified by silica gel column chromatography (neutral silica gel, dichloromethane) and (NH silica gel, dichloromethane) to obtain yellow flake crystals of compound 3 (704 mg, yield 65%). .

  Next, in a nitrogen atmosphere, 500 mg of Compound 13, 100 ml of dichloromethane, 1.63 g of triethylamine, and 1.52 g of acetic anhydride were placed in a 200 ml three-necked flask and stirred at room temperature for 6 days. 100 ml of water was added and stirred for 30 minutes. The reaction solution was transferred to a separatory funnel, and the organic layer and the aqueous layer were separated. Subsequently, the organic layer was washed twice with 100 ml of water and 100 ml of saturated saline, and dried using anhydrous sodium sulfate. Thereafter, the solvent was distilled off with a rotary evaporator, and the mixture was washed with 50 ml of ethyl acetate and then with 10 ml of dichloromethane to obtain a colorless powder of Compound 14 (602 mg, yield 96%).

  Then, under a nitrogen atmosphere, 100 mg of Compound 14, 100 ml of chloroform, and 280 mg of m-CPBA 75% were placed in a 200 ml three-necked flask and stirred at room temperature for 5 days. Thereafter, 10 ml of a saturated aqueous sodium sulfite solution and 50 ml of a 1N aqueous sodium hydroxide solution were added to inactivate the reaction solution. The aqueous layer was extracted 5 times with 50 ml of chloroform, combined with the organic layer, washed with 200 ml of saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was distilled off with a rotary evaporator and the residue was purified by silica gel column chromatography (NH silica gel, dichloromethane) to obtain a colorless powder of Compound 15 (115 mg, quantitative).

  A 200 ml three-necked flask was charged with 100 mg of compound 15, 60 ml of 6N hydrochloric acid, and 60 ml of tetrahydrofuran, and refluxed and stirred for 7 days. At this time, 10 ml of concentrated hydrochloric acid was added every 24 hours. This was added little by little to 1200 ml of 4N aqueous sodium hydroxide solution, stirred vigorously at room temperature for 1 day, filtered with suction, and washed with 50 ml of water. The residue was dried under reduced pressure to obtain yellowish green powder of compound 16 (BThS-p-A) (82 mg, quantitative).

(Synthesis Example 4) BMeS-p-A
BMeS-p-A was synthesized through the steps shown below.

  First, 10 ml of methanol and 190 mg of sodium metal were placed in a 25 ml two-necked flask under a nitrogen atmosphere and stirred at room temperature for 5 minutes. Compound 1 (520 mg) was added, and the mixture was stirred at room temperature for 5 minutes. Then, iodomethane (620 mg) was added, and the mixture was stirred at room temperature for 4 hours. The reaction solution was transferred to a separatory funnel and added with 50 ml of dichloromethane and 50 ml of water, and separated into an organic layer and an aqueous layer. The aqueous layer was extracted four times with 50 ml of dichloromethane, combined with the organic layer, washed with 150 ml of saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was distilled off with a rotary evaporator to obtain dark green scaly crystals of compound 17 (400 mg, yield 95%).

  Next, under a nitrogen atmosphere, 300 mg of Compound 17, 40 ml of dichloromethane, 1.52 g of triethylamine and 1.53 g of acetic anhydride were placed in a 100 ml two-necked flask and stirred at room temperature for 1 day. The reaction solution was suction filtered, and the residue was dried under reduced pressure (260 mg). The filtrate was transferred to a separatory funnel, and 100 ml of dichloromethane and 100 ml of water were added to separate the organic layer and the aqueous layer. The aqueous layer was extracted 5 times with 50 ml of dichloromethane, combined with the organic layer, washed twice with 150 ml of water and 150 ml of saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was distilled off with a rotary evaporator and combined with the filtrate to obtain a colorless powder of compound 18 (385 mg, yield 90%).

  In a nitrogen atmosphere, 135 mg of compound 18, 50 ml of dichloromethane, and 1090 mg of m-CPBA 75% were placed in a 100 ml two-necked flask and stirred at room temperature for 2 days. Subsequently, 10 ml of saturated aqueous sodium sulfite solution and 20 ml of 6N aqueous sodium hydroxide solution were added, and the mixture was stirred at room temperature for 18 hours. The reaction solution was transferred to a separatory funnel, 20 ml of water was added, and the organic layer and the aqueous layer were separated. The aqueous layer was extracted 5 times with 50 ml of dichloromethane, combined with the organic layer, washed with 150 ml of water and 150 ml of saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was distilled off with a rotary evaporator, suspended in 30 ml of dichloromethane, suction filtered, and the filtrate was dried under reduced pressure (30 mg). The filtrate was purified by silica gel column chromatography (NH silica gel, dichloromethane) and combined with the filtrate to obtain a yellow green powder of compound 19 (BMeS-p-A) (40 mg, yield 32%).

(Optical property evaluation)
For the BPS-p-A, BAS-p-A, BThS-p-A, and BMeS-p-A synthesized above, the absorption spectrum and fluorescence spectrum in the THF solution were measured, respectively.
BMeS-p-A was also measured in an aqueous solution, and for comparison, fluorescein (0.1N aqueous sodium hydroxide solution), which is a general-purpose water-soluble fluorescent dye, was similarly measured. The structural formula of fluorescein is shown below.

These results are summarized in Table 1.
In addition, quantum efficiency (PHI) in Table 1 is a value corresponding to the case where 9,10-diphenylanthracene (cyclohexane solution) is 0.95.

As can be seen from the results shown in Table 1, all of BPS-p-A, BAS-p-A, BThS-p-A, and BMeS-p-A, which are organic fluorescent materials according to the present invention, have high fluorescence quantum. It was observed to show efficiency and a large Stokes shift.
In addition, BMeS-p-A exhibits water solubility, exhibits higher fluorescence quantum efficiency and larger Stokes shift in water, and is superior to Stokes shift in comparison with fluorescein , which is a general-purpose water-soluble fluorescent dye. Was recognized.

(Stability evaluation)
BMeS-p-A and fluorescein were evaluated for stability in water.
BMeS-p-A is a 2.5 × 10 ⁻⁵ M aqueous solution, and fluorescein is a 1.0 × 10 ⁻⁵ M 0.1N sodium hydroxide aqueous solution, which emits white light from a 150 W xenon lamp. Irradiation was performed, and the change in absorbance with the passage of the irradiation time was measured to evaluate stability.
FIG. 1 is a graph showing the relationship between each irradiation time and the absorbance decrease rate.

  From the graph shown in FIG. 1, it was recognized that BMeS-p-A exhibits higher stability than fluorescein, which is a general-purpose fluorescent dye.

Claims (1)

An organic fluorescent material having a sulfonylaniline skeleton represented by the following general formula (1).

(In the formula (1), the substituents R ¹ and R ² are each independently a phenyl group, a naphthyl group, or a thienyl group substituted with an alkyl group, a fluoroalkyl group, a phenyl group, a halogen atom, an amino group, or an alkoxy group. Any one of a thienyl group substituted with a halogen atom, a thiazolyl group, a thiazolyl group substituted with a halogen atom, a pyridyl group, and a pyridyl group substituted with a halogen atom.)

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