KR20100112858A - 2-(2-styrylpyridin-4(1h)-ylidene)malononitrile derivatives, their preparation and applications - Google Patents

Abstract

PURPOSE: A 2-[2-styryl pyridine-4(1H)-ylidene]malononitrile derivative of which fluorescence characteristic changes is provided to use in composition for an optical sensor and the optical sensor. CONSTITUTION: A 2-[2-styryl pyridine-4(1H)-ylidene]malononitrile derivative is denoted by chemical formula 1. The 2-[2-styryl pyridine-4(1H)-ylidene]malononitrile derivative is prepared by condensing benzaldehyde derivative of chemical formula 4 with 2-[2-methylpyridine-4(1H)-ylidene]malononitrile derivative. A 2-[2-methylpyridine-4(1H)-ylidene]malononitrile derivative of chemical formula 2 is prepared by reacting a primary amine derivative of chemical formula 5 with 2-[2-methyl-4H-pyrane-4-ylidene]malononitrile derivative of chemical formula 4. A composition for sensing pH concentration contains 2-[2-styrylpyridine-4(1H)-ylidene]malononitrile derivative as a fluorescent dye.

Description

2- [2-Styrylpyridin-4 (1H) -ylidene] malononitrile derivatives, preparation method and use thereof {2- (2-Styrylpyridin-4 (1H) -ylidene) malononitrile Derivatives, Their Preparation and Applications }

The present invention provides a novel 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative having the property of changing the fluorescence intensity according to the concentration (pH) of hydrogen ions present in an aqueous solution, the preparation thereof It relates to a method and its use.

[Formula 1]

[In Formula 1, R ¹ is hydrogen or a linear or branched (C 1 -C 4) alkyl group; R ² is hydrogen or a linear or branched (C 1 -C 4) alkyl group, and the alkyl group of R ² may include a double bond or a triple bond carbon bond; R ³ and R ⁴ are independently of each other hydrogen, a hydroxy group, a carboxyl group or NR ⁵ R ⁶ , except when both R ³ and R ⁴ are hydrogen; R ⁵ and R ⁶ independently of one another are hydrogen, (C1-C4) alkyl or (C6-C12) aryl.]

Hydrogen ion concentration (pH) is an important chemical analysis that is widely used not only in natural sciences including chemistry, biochemistry and medicine, but also in applied sciences such as biotechnology and environmental engineering.

Traditional pH measurement method is an electrochemical method using a glass electrode, which can measure the hydrogen ion concentration of sample solution quickly and accurately.However, the electrochemical method requires that the sample solution have high ionic strength above the appropriate level. If it is low, measurement is impossible or error is big. In addition, the conventional electrochemical method using the glass electrode has a limitation in miniaturization of the measuring instrument, requires a minimum sample solution of at least several mL and always has a reference electrode (reference electrode). In addition, the use of electrochemical methods in biological or medical applications may lead to electrical shock, requiring very careful handling.

As a means to solve this disadvantage, a spectroscopic measurement method has been developed, and an optical pH sensor that can measure pH using a property in which the absorbance or luminescence of the indicator changes with pH. The development of sensor materials is of great interest. In particular, the development of a pH sensor using a fluorescent dye has been made actively because of the excellent sensitivity to pH changes when using the fluorescent properties of the compound (for example, fluorescence intensity, emission time, wavelength change).

In order to manufacture an optical pH sensor, the development of fluorescent dyes sensitive to pH change has to be preceded, and various compounds have been developed for this purpose. For example, mainly fluorescein-based dyes ((a) Cajlakovic, M .; Lobnik, A .; Werner, T. Anal.Chim.Acta 2002, 455, 207. (b) Lobnik, A .; Oehme, I .; Murkovic, I .; Wolfbeis, OS Anal . Chim . Acta 1998 , 367 , 159. (c) Nivens, DA; Zhang, Y .; Angel, SM Anal. Chim. Acta 1998 , 376 , 235. (d) Sanchez-Barragan, I .; Costa-Fernandez, JM; Sanz-Medel, A. Sens . Actuators , B 2005 , 107, 69] ruthenium polypyridyl complex-based dyes [(a) Price, JM; Xu, W .; Demas, JN; De Graff, BA Anal . Chem . 1998 , 70 , 265. (b) Goncalves, HMR; Maule, CD; Jorge, PAS; Esteves da Silva, JCG Anal . Chim . Acta 2008 , 626 , 62], and other corrole derivatives [Li, C.-Y .; Zhang, X.-B .; Han, Z.-X .; Akermark, B .; Sun, L .; Shen, G.-L .; Yu, R.-Q. Analyst 2006 , 131 , 388] and coumarin derivatives [Vasylevska, AS; Karasyov, AA; Borisov, SM; Krause, C. Anal . Bioanal . Chem . 2007 , 387 , 2131].

However, these dyes have a problem of being difficult to synthesize or having a limited range of some sensitive pH since they go through several steps of the synthetic route. Thus, there is still a need for the development of new fluorescent dyes that are simple to synthesize and have a wide range of measurable pH.

Therefore, the present inventors have tried to develop a new fluorescent dye having a simple pH range and a wide range of pH that can be measured. As a result, 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivatives are The derivative is a novel material that is relatively easy to synthesize, photochemically stable, has a high molar absorptivity, and has a high Stokes shift, and thus is very useful as a fluorescent dye. Was completed.

It is an object of the present invention to provide a novel structure of 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative having a functional group capable of deprotonation and protonation according to pH. .

It is another object of the present invention to provide a fluorescent dye whose fluorescence intensity is varied in a wider pH range (pH 2-11).

Still another object of the present invention is to provide a pH sensor and a pH sensor composition comprising the 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative as a fluorescent dye.

The present invention provides a novel 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile (2- () having the property of changing the fluorescence intensity according to the concentration (pH) of hydrogen ions present in the aqueous solution. The present invention relates to a 2-styrylpyridin-4 (1H) -ylidene) malononitrile) derivative, a method for preparing the same, and a use thereof, and in particular, a functional group capable of deprotonation and protonation according to the pH of a solution (OH, CO ₂ H). , NR ₂ ) is synthesized at least one substituted 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative (Formula 1) to a fluorescent dye of varying fluorescence intensity over a wide pH range It is about.

[Formula 1]

[In Formula 1, R ¹ is hydrogen or a linear or branched (C 1 -C 4) alkyl group; R ² is hydrogen or a linear or branched (C 1 -C 4) alkyl group, and the alkyl group of R ² may include a double bond or a triple bond carbon bond; R ³ and R ⁴ are independently of each other hydrogen, a hydroxyl group, a carboxyl group or NR ⁵ R ⁶ , except that both R ³ and R ⁴ are hydrogen; R ⁵ and R ⁶ independently of one another are hydrogen, (C1-C4) alkyl or (C6-C12) aryl.]

2 of the formula (1) [2-styryl-pyridin -4 (1H) - ylidene] words, R ¹ is hydrogen, methyl, ethyl furnace nitrile derivatives, n- propyl, i- propyl, n- butyl, i- Butyl or t-butyl; R ² is hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, 2-propenyl, 3-butenyl, 2-propynyl, 2-butynyl or 3 -Butynyl; R ³ and R ⁴ are each independently selected from hydrogen, a hydroxy group, a carboxyl group, a dimethylamino group or a diethylamino group, more preferably R ¹ is methyl or t-butyl; R ² is n-propyl, i-propyl or 2-propenyl; R ³ and R ⁴ are independently of each other selected from hydrogen, a hydroxy group, a dimethylamino group, or a diethylamino group, except that both R ³ and R ⁴ are hydrogen.

2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative of formula 1 according to the present invention is 2- [2-methylpyridine-4 (1H) -yl represented by the following formula (2) It is prepared by condensation of a den] malononitrile (2- (2-methylpyridin-4 (1H) -ylidene) malononitrile) derivative with a benzaldehyde derivative represented by the following formula (3). At this time, the solvent used is acetonitrile, n-butanol or dimethylformamide, and piperidine is preferable as the base catalyst.

[Formula 2]

(3)

[Wherein R ¹ , R ² , R ³ and R ⁴ are the same as defined in Formula 1 above.]

In addition, 2- [2-methylpyridine-4 (1H) -ylidene] malononitrile derivative represented by the formula (2) is 2- [2-methyl-4H-pyran-4-ylidene represented by the following formula (4) ] The malononitrile derivative and the primary amine derivative represented by the following formula (5) are prepared by heating a reaction, and dimethylformamide is preferable as the solvent used. As for heating temperature, 80-120 degreeC is preferable.

[Formula 4]

[Chemical Formula 5]

H ₂ NR ²

[Wherein R ¹ and R ² are the same as defined in Formula 1]

2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative of the present invention is a substance whose fluorescence intensity is changed in the range of pH 2-11, and the concentration of hydrogen ions in solution (pH) Deprotonation or protonation occurs according to, and the fluorescence intensity is changed according to the fraction of each species produced according to it can be used as a fluorescent dye of the composition for the optical pH sensor and pH sensor.

2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative according to the present invention is a compound of a novel structure in which the fluorescence properties change depending on the concentration of hydrogen ions, It has a benzene compound having at least one functional group capable of deprotonation and protonation as a substituent. 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivatives of the present invention changes the fluorescence intensity from pH 2 to pH 11, biochemical as well as natural science, such as chemistry, biochemistry, medicine It can be used to manufacture optical sensor for pH measurement in applied science field such as environmental engineering.

Hereinafter, the manufacturing method and fluorescent properties of the fluorescent dye according to the present invention will be described in more detail through Preparation Examples, Examples and Experimental Examples. However, the present invention is not limited by the following Preparation Examples, Examples and Experimental Examples.

Preparation Example 1 2- (2,6-dimethyl-1-propylpyridine-4 (1H) -ylidene) malononitrile (2- (2,6-dimethyl-1-propylpyridin-4 (1H) -ylidene) malononitrile)

The preparation of 2- (2,6-dimethyl-1-propylpyridine-4 (1H) -ylidene) malononitrile is described in the following by referring to the Journal of Materials Chemistry, 2005, 16, 376-383 . It was prepared as.

To 1.00 g of 2- (2,6-dimethyl-4H-pyran-4-ylidene) malononitrile, 5 mL of propylamine was refluxed for 2 hours with a solvent and a reactant. The residue was concentrated under reduced pressure, the residual solvent was blown off, recrystallized with chloroform for 24 hours, and the resulting crystals were filtered while washing with methanol. The residual solvent was blown in vacuo to give 950 mg (77%) of a final colorless transparent solid crystal.

mp: 237-238 ° C.

¹ H-NMR (300 MHz, CDCl ₃ -d): d 6.63 (s, 2H), 3.87 (t, J = 8.4 Hz, 2H), 2.46 (s, 6H), 1.74 (m, J = 3.3, 2.1 Hz , 2H), 1.05 (t, J = 7.5 Hz, 3H).

Example 1 (E) -2- (2- (4-hydroxystyryl) -6-methyl-1-propylpyridine-4 (1H) -ylidene) Malononitrile [(E) -2- (2- (4- hydroxystyryl ) -6- methyl -One- propylpyridin -4 (1H) -ylidene) malononitrile]

400 mg of 2- (2,6-dimethyl-1-propylpyridine-4 (1H) -ylidene) malononitrile prepared in Preparation Example 1 was dissolved in 2.5 mL of dimethylformamide (DMF) and piperidine Stir while adding 0.5 mL. 280 mg of 4-hydroxybenzaldehyde was added thereto, and the mixture was refluxed for 8 hours under a nitrogen stream. The reaction solution was cooled to room temperature, DMF was distilled under reduced pressure to remove most of them, and the precipitate formed by adding methanol was filtered and purified by column chromatography (dichloromethane: acetone = 10: 1). 268 mg (45%) of a solid were obtained.

mp: 289-290 ° C.

¹ H-NMR (300 MHz, DMSO-d ₆ ): d 9.92 (s, 1 H), 7.60 (d, 2 H), 7.21 (dd, 1 H). 7.18 (dd, 1H), 6.80 (d, 2H), 6.80 (d, 1H), 6.69 (d, 1H), 4.11 (t, 2H), 2.52 (s, 3H), 1.66 (m, 2H), 0.90 (t, 3H).

[ Example  2] E-2- (2- (4- ( Dimethylamino ) Styryl ) -6- methyl -One- Propylpyridine -4 (1H) -ylidene) Malononitrile [E-2- (2- (4- ( dimethylamino ) styryl ) -6- methyl -1-propylpyridin-4 (1H) -ylidene) malononitrile]

400 mg of 2- (2,6-dimethyl-1-propylpyridine-4 (1H) -ylidene) malononitrile prepared in Preparation Example 1 was dissolved in 2.5 mL of dimethylformamide (DMF) and piperidine Stir while adding 0.5 mL. 229 mg of 4- (dimethylamino) benzaldehyde was added thereto, and the mixture was refluxed for 8 hours under a nitrogen stream. The reaction solution was cooled to room temperature, DMF was distilled under reduced pressure to remove most of the residue, and methanol was added to the resulting precipitate. The precipitate was filtered and purified by column chromatography (ethyl ether: ethyl acetate = 3: 1) to obtain an orange solid as the target compound. 284 mg (44%) was obtained.

mp: 224-226 ° C.

¹ H-NMR (300 MHz, DMSO-d ₆ ): d 7.39 (d, 2H), 7.14 (dd, 1H), 6.98 (s, 1H), 6.70 (d, 2H), 6.69 (s, 1H), 6.66 (dd, 1H), 3.94 (t, 2H), 3.04 (s, 6H), 2.45 (s, 3H), 1.76 (sextet, 2H), 1.03 (t, 3H).

Experimental Example 1 Measurement of Fluorescence Properties of 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile Derivative of the Present Invention

Ten types of buffer solutions having a pH of 2 to 11 were prepared by mixing the first potassium phosphate aqueous solution, the second potassium phosphate aqueous solution and the aqueous phosphate solution. (E) -2- (2- (4-hydroxyhydroxyl) -6-methyl-1-propylpyridine-4 (1H) -ylidene) malononitrile prepared in Example 1 was dissolved in methanol 500 μl of the solution was taken and dissolved in 1.5 mL of different buffer solutions, and the sample solution was prepared to have a concentration of 5.0 × 10 ^-5 M. Fluorescence spectrophotometer measured the fluorescence intensity according to pH from each sample solution. The results are shown in FIGS. 1, 2, 3 and 4, respectively.

1 and 2 are three-dimensional fluorescence spectra of a sample solution adjusted to pH 2 and pH 11, respectively, and when the 350 nm ultraviolet ray was irradiated, the fluorescence intensity was measured to be 481 AU and 4500 AU at 530 nm, respectively.

FIG. 3 shows the results of recording the intensity of fluorescence emitted in the range of 450 nm to 650 nm after irradiating UV light of 350 nm wavelength to each of the sample solutions having various pHs, and fluorescence emitted from the compound with increasing pH. It shows that the intensity of is gradually increased.

4 is a graph showing the fluorescence intensity at 530 nm at which the fluorescence intensity is emitted the most according to the pH of the sample solution. As shown in FIG. 4, the 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative of the present invention has a characteristic of continuously increasing fluorescence intensity in the range of pH 2 to pH 11. Using these characteristics, it is shown that the dye is very useful as a fluorescent dye of optical pH sensor that can spectroscopically measure the concentration of hydrogen ions in aqueous solution.

Figure 1-Three-dimensional fluorescence spectrum of sample solution adjusted to pH 2

Figure 2-Three-dimensional fluorescence spectrum of the sample solution adjusted to pH 11

3-Graph of recording the intensity of emitted fluorescence in the range of 450 nm to 650 nm after irradiating ultraviolet rays of 350 nm wavelength to sample solutions having various pHs, respectively

4-Graph showing the fluorescence intensity at 530 nm where the fluorescence intensity is emitted the most after excitation with ultraviolet light of 350 nm wavelength according to the pH of the sample solution

Claims (9)

2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative represented by the following formula (1). [Formula 1]

[In Formula 1, R ¹ is hydrogen or a linear or branched (C 1 -C 4) alkyl group; R ² is hydrogen or a linear or branched (C 1 -C 4) alkyl group, and the alkyl group of R ² may include a double bond or a triple bond carbon bond; R ³ and R ⁴ are independently of each other hydrogen, a hydroxyl group, a carboxyl group or NR ⁵ R ⁶ , except that both R ³ and R ⁴ are hydrogen; R ⁵ and R ⁶ independently of one another are hydrogen, (C1-C4) alkyl or (C6-C12) aryl.] The method of claim 1, R ¹ is hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl or t-butyl; R ² is hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, 2-propenyl, 3-butenyl, 2-propynyl, 2-butynyl or 3 -Butynyl; R ³ and R ⁴ are independently of each other hydrogen, hydroxy, carboxyl, dimethylamino or diethylamino group, characterized in that 2- [2-styrylpyridine-4 (1H) -ylidene] Nonnitrile derivatives. 3. The method of claim 2, R ¹ is methyl or t-butyl; R ² is n-propyl, i-propyl or 2-propenyl; R ³ and R ⁴ are each independently selected from hydrogen, a hydroxy group, or a dimethylamino group, except that when both R ³ and R ⁴ are hydrogen, 2- [2-styrylpyridine- 4 (1H) -ylidene] malononitrile derivatives. Condensation reaction of 2- [2-methylpyridine-4 (1H) -ylidene] malononitrile derivative represented by the following Chemical Formula 2 with benzaldehyde derivative represented by the following Chemical Formula 3 to 2- [ A process for preparing 2-styrylpyridine-4 (1H) -ylidene] malononitrile derivatives. [Formula 2]

(3)

[Wherein R ¹ , R ² , R ³ and R ⁴ are the same as defined in Formula 1 of claim 1] The method of claim 4, wherein The 2- [2-methyl-4H-pyran-4-ylidene] malononitrile derivative represented by the following formula (4) and the primary amine derivative represented by the following formula (5) are reacted to produce the 2- [ To prepare 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative, characterized by preparing 2-methylpyridine-4 (1H) -ylidene] malononitrile derivative Way. [Formula 4]

[Chemical Formula 5] H ₂ NR ² [Wherein R ¹ and R ² are the same as defined in Formula 1 of claim 1] A pH sensor comprising the 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative of any one of claims 1 to 3 as a fluorescent dye. The method of claim 6, pH sensor is measured from the fluorescence intensity. A composition for a pH sensor comprising the 2- [2-styrylpyridine-4 (1H) -ylidene] malononitrile derivative of any one of claims 1 to 3 as a fluorescent dye. The method of claim 8, pH value is a composition for pH sensors, characterized in that measured from the fluorescence intensity.

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