KR20110134713A - Novel alkanoic 2-(oxazol-2-yl)phenyl ester compounds and a preparation method of the same - Google Patents

Abstract

PURPOSE: A novel alkanoic 2-(oxazole-2-yl)phenyl ester compound and a method for preparing the same are provided to be used as a precursor compound for a fluorescence expression marker. CONSTITUTION: An alkanoic 2-(oxazole-2-yl)phenyl ester compound is denoted by chemical formula 1. In chemical formula 1, X is CH or N; R1, R2, R3, and R4 are same or different hydrogen atom, halogen atom, or C1-C6 alkyl group; and R5 is C1-C20 alkyl group. A precursor for a fluorescence expression marker is the compound of chemical formula 1. A method for preparing the compound of chemical formula 1 comprises a step of reacting an oxazolyl phenol compound of chemical formula 2 with alkanoyl chloride compound of chemical formula 3 under the presence of a base.

Description

Alkanoic 2- (oxazol-2-yl) phenyl ester compound and preparation method thereof {Novel alkanoic 2- (oxazol-2-yl) phenyl ester compounds and a preparation method of the same}

The present invention relates to novel alkanoic 2- (oxazol-2-yl) phenyl ester compounds and methods for their preparation.

Since the alkannoic 2- (oxazol-2-yl) phenyl ester compound of the present invention is hydrolyzed under acidic or alkaline conditions to express fluorescent properties, it is useful as a precursor compound for fluorescent expression markers (makers).

Recently, in the field of biochemistry or cytology, analytical methods in cells of living organisms or blood plasma of the human body have been applied. In other words, organisms harmonize with the body through numerous microbiological chemical reactions, and enzymes are involved in such chemical reactions. Enzymes act as reaction catalysts that affect the choice of specific reactants and their reaction rates, and proteins mainly act as enzymes. Recently, a method has been known in which fluorescent dyes that form specific covalent bonds with these enzymes have been developed, and fluorescent dyes are bound to enzymes to measure and investigate the reaction catalyst action of enzymes in vivo. These pigments are called 'enzyme substrate pigments' or 'enzyme directed pigments'.

Enzyme substrates can mainly observe the catalytic action of enzymes, or can measure and search the concentration of substrates contained in fermentation broths or culture fluids. Moreover, if the enzyme-based pigments have fluorescence properties, their useful value can be even greater. Thus, enzyme substrate pigments can be widely used in the biochemical or cytology field.

Enzyme-based pigments developed to date include benzoxazole-based fluorescent dyes, coumarin-based fluorescent dyes, oxazine-based fluorescent dyes, and rhodamine-based fluorescent dyes.

US Pat. No. 5,587,112 as benzoxazole-based fluorescent dyes discloses benzazole, dibenzothiazole and benzoimidazole compounds. Also disclosed are techniques for applying benzoxazole compounds as herbicides [US Pat. No. 6,844,295], fungicides [US Pat. No. 5,491,156], and UV-blocking agents [US Pat. No. 260,144]. And, J. of Photochemistry and Photobiology A, Chemistry Vol 179, p320-323, 2006, discloses benzoxazole compounds and their fluorescence expression through the combination of carbon and oxygen by UV light irradiation. In addition, a paper on biochemical analysis and evaluation using 6-nitro or amino-substituted phenylbenzoxazole-based compounds as fluorescent dyes [European Journal of Medicinal Chemistry, Vol 44, p501-510, 2009], and diphenyl-substituted benzoxazoles A Study on the Luminescence Characteristics of Fluorescent Pigments for OLEDs Using Chemical Compounds [Current Applied Physics, Vol 5, 75-78, 2005] [Med Chem Res, Vol 17, p 412-424, 2008] has been published.

As described above, since the fluorescent dye compound can be widely used in the field of biochemistry or cytology, it is urgently needed to develop a fluorescent dye having a new structure.

The alkannoic 2- (oxazol-2-yl) phenyl ester compound characterized by the present invention is a benzoxazole-based compound, which is hydrolyzed under acidic or alkaline conditions to express fluorescent properties. Therefore, the alkanoic 2- (oxazol-2-yl) phenyl ester compounds of the present invention are useful as precursor compounds for fluorescence markers.

It is an object of the present invention to provide alkanenoic 2- (oxazol-2-yl) phenyl ester compounds of novel structure.

Another object of the present invention is to provide a use of the alkanoic 2- (oxazol-2-yl) phenyl ester compound as a precursor compound for a fluorescent marker maker.

Another object of the present invention is to provide a method for preparing the alkanoic 2- (oxazol-2-yl) phenyl ester compound.

The present invention is characterized by an alkanonoic 2- (oxazol-2-yl) phenyl ester compound represented by the following Chemical Formula 1 useful as a precursor compound for a fluorescent marker and a method for preparing the same.

In Formula 1, X represents CH or N; R ¹ , R ² , R ³ , and R ⁴ , which are the same as or different from each other, represent a hydrogen atom, a halogen atom, or a C ₁ -C ₆ alkyl group; R ⁵ represents a C ₁ to C ₂₀ alkyl group.

The alkanoic 2- (oxazol-2-yl) phenyl ester compound represented by Chemical Formula 1 has a maximum absorption wavelength of 300 nm to 320 nm, a molar extinction coefficient of 20,000 to 40,700 L / mol · cm, and initial pyrolysis. Temperature is 45-87 degreeC.

Since the alkannoic 2- (oxazol-2-yl) phenyl ester compound represented by the formula (1) is hydrolyzed under acidic or alkaline conditions and expresses fluorescence properties, the alkanoic 2- (oxazol-2-yl) Phenyl ester compounds are useful as precursor compounds for fluorescent expression markers.

The present invention relates to alkanonoic 2- (oxazol-2-yl) phenyl ester compounds represented by the formula (1) useful as precursor compounds for fluorescent markers.

When an alkanoic 2- (oxazol-2-yl) phenyl ester compound represented by the said Formula (1) is illustrated more concretely, it is as follows.

Butanoic 2- (benz [ d ] oxazol-2-yl) phenyl ester,

Octanoic 2- (benz [ d ] oxazol-2-yl) phenyl ester,

Decannoic 2- (benz [ d ] oxazol-2-yl) phenyl ester,

Palmitoic 2- (benz [ d ] oxazol-2-yl) phenyl ester,

Butanoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester,

Octanoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester,

Decannoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester,

Palmitoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester,

Butanoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester,

Octanoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester,

Decannoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester,

Palmitoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester.

On the other hand, the present invention is characterized by a method for producing an alkanonoic 2- (oxazol-2-yl) phenyl ester compound represented by the formula (1).

According to the preparation method according to the present invention, as shown in Scheme 1, the oxazolyl phenol compound represented by the following formula (2) and the alkanonoyl chloride compound represented by the following formula (3) are reacted in the presence of a base to be represented by the following formula (1) It comprises a process for preparing an alkanoic 2- (oxazol-2-yl) phenyl ester compound.

Scheme 1

In Scheme 1, X, R ¹ , R ² , R ³ , R ⁴ , and R ⁵ are the same as defined in Chemical Formula 1, respectively.

The preparation method according to Scheme 1 will be described in more detail as follows.

First, after installing a thermometer, a stirrer, and a condenser in a three-necked reactor, an oxazolyl phenol compound represented by the formula (2), a base, and a solvent are added and mixed. Then, after slowly dropwise adding the alkanoyl chloride represented by Formula 3, the reaction solution is heated to reflux. After the reaction is completed, the reaction solution is cooled to room temperature, and then neutralized with dilute hydrochloric acid or the like. Then, water is added to the reaction solution to separate the layers, and the organic layer is separated and dried under reduced pressure to obtain an alkanenoic 2- (oxazol-2-yl) phenyl ester compound represented by Chemical Formula 1.

The base used in the reaction may be an organic or inorganic base commonly used in the art. The organic base is a primary, secondary or tertiary amine compound having 1 to 10 carbon atoms, specifically, may include methylamine, ethylamine, diethylamine, triethylamine and the like. The inorganic base is selected from hydroxides, carbonates, hydrogen carbonates of alkali or earth metals, and specifically, may include sodium hydroxide, sodium carbonate, sodium hydrogen carbonate, calcium carbonate and the like. The base may be used in the range of 1 to 3 molar ratios based on 1 mole of the oxazolyl phenol compound represented by Chemical Formula 2.

As the solvent used in the reaction, hydrocarbons, alcohols, esters, ethers, and the like may be used as an inert organic solvent that does not affect the reaction, and specifically, hexane, benzene, toluene, or the like may be included.

The reaction temperature is in the range of room temperature to the reflux temperature of the solvent, preferably by reacting under reflux conditions the reaction temperature is maintained at about 70 ℃ to 130 ℃.

In addition, the oxazolyl-based phenol compound represented by Formula 2 used in the present invention as a starting material may be prepared by the method shown in Scheme 2 below.

Scheme 2

In Scheme 2, X, R ¹ , R ² , R ³ , R ⁴ , and R ⁵ are the same as defined in Chemical Formula 1, respectively.

According to the production method according to Scheme 2, first, a thermometer, a stirrer, and a condenser are installed in a three-neck reactor, and then the 1-amino-2-hydroxyaromatic compound represented by Chemical Formula 4 and 2 represented by Chemical Formula 5 The hydroxybenzoic acid compound was dissolved in o -dichlorobenzene and the reaction solution was heated to reflux for 2 to 3 hours and then cooled to room temperature. After the solvent is removed and concentrated, water is added to the reaction solution and stirred. When the pH of the reaction solution is adjusted to 11 with an aqueous alkali solution, for example, ammonia water, various oxazolyl phenol compounds represented by Chemical Formula 2 are precipitated as crystals.

The present invention as described above will be described in more detail through the following Preparation Examples, Examples and Experimental Examples, the present invention is not limited by the following Preparation Examples, Examples and Experimental Examples.

Preparation Example Synthesis of Oxazolyl Phenol Compound (Formula 2)

Preparation Example 1 Synthesis of 2- (benz [ d ] oxazol-2-yl) phenol

1-amino-2-hydroxybenzene (10.9 g 0.1 mole), 2-hydroxybenzoic acid (18 g, 0.13 mole) and 40 ml of o -dichlorobenzene were dissolved in a three-necked reactor. The reaction solution was heated to reflux for 2 hours and then cooled to room temperature. After o -dichlorobenzene was removed from the reaction solution, 100 mL of water was added to the reaction solution, and the reaction solution was adjusted with alkali (pH 11) with ammonia water while stirring the reaction product. The precipitated crystals were filtered and dried to obtain 18 g of the target compound as a solid.

Yield 85%; Molecular weight (C ₁₃ H ₉ NO ₂ ) Theoretical M = 211, Experimental M = 211; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 7.08 (t, H, J = 6.20 Hz), 7.13 (d, H, J = 7.81 Hz), 7.26 (dd, 2H, J = 3.20 Hz) , 7.55 (t, H, J = 2.82 Hz), 8.03 (dd, H, J = 2.97 Hz), 8.27 (dd, H, J = 2.50 Hz), 8.55 (dd, H, J = 2.67 Hz), 10.96 (s, H)

Preparation Example 2 Synthesis of 4-chloro-2- (oxazolo [4,5- b ] pyridin-2-yl) phenol

1-amino-2-hydroxypyridine (11.0 g 0.1 mole), 2-hydroxy-5-chlorobenzoic acid (22.3 g, 0.13 mole) and 40 ml of o -dichlorobenzene were dissolved in a three-necked reactor. The reaction solution was heated to reflux for 2 hours and then cooled to room temperature. After o -dichlorobenzene was removed from the reaction solution, 100 mL of water was added to the reaction solution, and the reaction solution was adjusted with alkali (pH 11) with ammonia water while stirring the reaction product. Precipitated crystals were filtered and dried to obtain 19.5 g of a solid.

Yield 80%; Molecular weight (C ₁₂ H ₇ ClN ₂ O ₂ ) Theoretical M = 246, Experimental M = 246; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 7.16 (d, H, J = 7.21 Hz), 7.51 (dd, H, J = 6.87 Hz), 7.57 (dd, H, J = 2.53 Hz) , 7.99 (d, H, J = 3.12 Hz), 8.28 (dd, H, J = 2.45 Hz), 8.57 (dd, H, J = 3.50 Hz), 11.03 (s, H).

Preparation Example 3 Synthesis of 5-methyl-2- (oxazolo [4,5- b ] pyridin-2-yl) phenol

1-amino-2-hydroxypyridine (11.0 g 0.1 mole), 2-hydroxy-5-methylbenzoic acid (15.2 g, 0.1 mole) and 40 ml of o -dichlorobenzene were dissolved in a three-necked reactor. The reaction solution was heated to reflux for 40 hours and then cooled to room temperature. After o -dichlorobenzene was removed from the reaction solution, 300 mL of water was added to the reaction solution, and the reaction solution was adjusted with alkali (pH 11) with ammonia water while stirring the reaction product. Precipitated crystals were filtered and dried to obtain 19 g of a solid.

Yield 84%; Molecular weight (C ₁₃ H ₁₀ N ₂ O ₂ ) Theoretical M = 226, Experimental M = 226; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 2.34 (s, 3H), 6.90 (d, H, J = 7.18 Hz), 6.95 (s, H), 7.46 (dd, H, J = 2.62 Hz), 7.91 (d, H, J = 2.42 Hz), 8.25 (dd, H, J = 3.01 Hz), 8.53 (dd, H, J = 2.50 Hz), 10.90 (s, H).

Example Synthesis of Alkannoic 2- (oxazol-2-yl) phenyl Ester Compound (Formula 1)

Example 1 Synthesis of Butannoic 2- (Benz [ d ] oxazol-2-yl) phenyl Ester

After installing a thermometer, a stirrer and a condenser in a three-necked reactor, 0.29 g (0.0014 mol) of 2- (benz [ d ] oxazol-2-yl) phenol, 0.28 g (0.0028 mol) of triethylamine, and 5 ml of benzene Put in order to dissolve. 0.164 g (0.00154 mol) of butyryl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 85%; Molecular weight theory M = 282, experimental value M-1 = 281; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 1.08 (t, 3H, J = 7.4 Hz), 1.86 (t, 2H, J = 7.4 Hz), 2.74 (t, 2H, J = 7.4 Hz), 7.18 (t, H, J = 1.10 Hz), 7.33 (t, H, J = 3.60 Hz), 7.34 (t, 2H, J = 1.9 Hz), 7.52 (t, H, J = 1.7 Hz), 8.26 (t, H, J = 1.99 Hz); Elemental Analysis: Theoretical C ₁₇ H ₁₅ NO ₃ , C 72.58, H 5.37, N 4.98: Experimental Value C 72.65, H 5.45, N 4.67.

Example 2. Synthesis of Octanenoic 2- (Benz [ d ] oxazol-2-yl) phenyl Ester

After installing a thermometer, a stirrer and a condenser in a three-necked reactor, 0.29 g (0.0014 mol) of 2- (benz [ d ] oxazol-2-yl) phenol, 0.28 g (0.0028 mol) of triethylamine, and 5 ml of benzene Put in order to dissolve. 0.25 g (0.00154 mol) of octanoyl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 86%; Molecular weight theory M = 338, experimental value M-1 = 337;^OneH NMR (300 MHz, CDCl₃-d, ppm) δ 0.877 (t, 3H,J= 6.9 Hz), 1.30 (q, 4H,J= 7.55 Hz), 1.45 (q, 4H,J= 7.65 Hz), 1.82 (t, 2H,J= 7.6 Hz), 2.75 (t, 2H,J= 7.7 Hz), 7.18 (t, H,J= 7.0 Hz), 7.24 (t, 2H,J= 7.2 Hz), 7.33 (t, H,J= 3.6 Hz), 7.40 (t, 2H,J= 2.8 Hz), 7.53 (t, H,J= 1.75 Hz), 8.26 (t, H,J= 2.9 Hz); Elemental Analysis: Theory C₂₁H₂₃NO₃, C 74.75, H 6.87, N 4.15. Experimental C 74.71, H 7.01, N 3.83.

Example 3 Synthesis of Decanoic 2- (Benz [ d ] oxazol-2-yl) phenyl Ester

After installing a thermometer, a stirrer and a condenser in a three-necked reactor, 0.29 g (0.0014 mol) of 2- (benz [ d ] oxazol-2-yl) phenol, 0.28 g (0.0028 mol) of triethylamine, and 5 ml of benzene Put in order to dissolve. 0.29 g (0.00154 mol) of decanoyl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 90%; Theoretical value M = 366, experimental value M-1 = 365; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 0.88 (t, 3H, J = 7.0 Hz), 1.27 (m, 4H), 1.35 (q, 4H, J = 7.05 Hz), 1.43 (q, 4H, J = 7.6 Hz), 1.82 (t, 2H, J = 7.6 Hz), 2.75 (t, 2H, J = 7.65 Hz), 7.20 (t, H, J = 7.0 Hz), 7.23 (t, 2H, J = 7.1 Hz), 7.33 (t, H, J = 3.6 Hz), 7.39 (t, 2H, J = 2.1 Hz), 7.53 (t, H, J = 7.65 Hz), 8.26 (t, H, J = 7.2 Hz); Elemental Analysis: Theoretical C ₂₃ H ₂₇ NO ₃ , C 75.59, H 7.45, N 3.83: Experimental C 75.56, H 7.40, N 3.75

Example 4 Synthesis of Palmitoic 2- (Benz [ d ] oxazol-2-yl) phenyl Ester

After installing a thermometer, a stirrer and a condenser in a three-necked reactor, 0.29 g (0.0014 mol) of 2- (benz [ d ] oxazol-2-yl) phenol, 0.28 g (0.0028 mol) of triethylamine, and 5 ml of benzene Put in order to dissolve. 0.42 g (0.00154 mol) of palmitoyl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 96%; Molecular weight theory M = 450, experimental value M-1 = 449; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 0.86 (m, 5H), 1.24 (m, 14H), 1.33 (q, 4H, J = 7.25 Hz), 1.44 (q, 4H, J = 7.75 Hz), 1.83 (t, 2H, J = 7.5 Hz), 2.75 (t, 2H, J = 7.65 Hz), 7.20 (t, H, J = 6.95 Hz), 7.24 (t, 2H, J = 7.1 Hz), 7.34 (t, H, J = 1.95 Hz), 7.39 (t, 2H, J = 2.0 Hz), 7.52 (t, H, J = 7.2 Hz), 8.25 (t, H, J = 7.4 Hz); Elemental Analysis: Theoretical C ₂₉ H ₃₉ NO ₃ , C 77.47, H 8.74, N 3.12: Experimental Value C 77.53, H 8.68, N 2.54

Example 5 Synthesis of Butannoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester

After installing the thermometer, stirrer and condenser in the three-necked reactor, 0.34 g (0.0014 mol) of 4-chloro-2- (oxazolo [4,5- b ] pyridin-2-yl) phenol and 0.28 g of triethylamine ( 0.0028 mol) and 5 ml of benzene were added sequentially to dissolve. 0.164 g (0.00154 mol) of butyryl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 91%; Molecular weight theory M = 316, experimental value M = 316; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 1.07 (t, 3H, J = 7.4 Hz), 1.84 (q, 2H, J = 7.4 Hz), 2.79 (t, 2H, J = 7.4 Hz), 7.16 (d, H, J = 8.6 Hz), 7.32 (dd, H, J = 4.85 Hz), 7.54 (dd, H, J = 2.6 Hz), 7.85 (dd, H, J = 1.45 Hz), 8.29 (d, H, J = 2.55 Hz), 8.59 (dd, H, J = 3.45 Hz); Elemental Analysis: Theoretical C ₁₆ H ₁₃ ClN ₂ O ₃ , C 60.67, H 4.14, N 8.84. Experimental C 59.95, H 4.16, N 8.79.

Example 6 Synthesis of Octanenoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester

After installing the thermometer, stirrer and condenser in the three-necked reactor, 0.34 g (0.0014 mol) of 4-chloro-2- (oxazolo [4,5- b ] pyridin-2-yl) phenol and 0.28 g of triethylamine ( 0.0028 mol) and 5 ml of benzene were added sequentially to dissolve. 0.25 g (0.00154 mol) of octanoyl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 92%; Molecular weight theory M = 372, experimental value M = 372; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 0.86 (t, 3H, J = 3.35 Hz), 1.25 (m, 4H), 1.34 (m, 4H), 1.80 (q, 2H, J = 7.6 Hz), 2.80 (t, 2H, J = 7.5 Hz), 7.15 (d, H, J = 8.6 Hz), 7.31 (dd, H, J = 3.25 Hz), 7.52 (dd, H, J = 2.6 Hz), 7.84 (dd, H, J = 1.4 Hz), 8.29 (d, H, J = 2.55 Hz), 8.59 (dd, H, J = 1.4 Hz); Elemental Analysis: Theoretical C ₂₀ H ₂₁ ClN ₂ O ₃ , C 64.43, H 5.68, N 7.51: Experimental C 64.42, H 6.20, N 6.98.

Example 7.Synthesis of decannoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester

After installing the thermometer, stirrer and condenser in the three-necked reactor, 0.34 g (0.0014 mol) of 4-chloro-2- (oxazolo [4,5- b ] pyridin-2-yl) phenol and 0.28 g of triethylamine ( 0.0028 mol) and 5 ml of benzene were added sequentially to dissolve. 0.29 g (0.00154 mol) of decanoyl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 95%; Molecular weight theory M = 400, experimental value M = 400; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 0.86 (t, 3H, J = 6.8 Hz), 1.26 (m, 8H), 1.33 (m, 4H), 1.81 (q, 2H, J = 7.65 Hz), 2.81 (t, 2H, J = 7.5 Hz), 7.15 (d, H, J = 8.6 Hz), 7.31 (dd, H, J = 4.85 Hz), 7.54 (dd, H, J = 2.55 Hz), 7.83 (dd, H, J = 1.45 Hz), 8.29 (d, H, J = 2.55 Hz), 8.59 (dd, H, J = 1.40 Hz); Elemental Analysis: Theoretical C ₂₂ H ₂₅ ClN ₂ O ₃ , C 65.91, H 6.29, N 6.99: Experimental C 66.34, H 6.52, N 6.80.

Example 8. Synthesis of Palmitoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester

After installing the thermometer, stirrer and condenser in the three-necked reactor, 0.34 g (0.0014 mol) of 4-chloro-2- (oxazolo [4,5- b ] pyridin-2-yl) phenol and 0.28 g of triethylamine ( 0.0028 mol) and 5 ml of benzene were added sequentially to dissolve. 0.42 g (0.00154 mol) of palmitoyl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 90%; Molecular weight theory M = 484, experimental value M = 484;^OneH NMR (300 MHz, CDCl₃-d, ppm) δ 0.85 (t, 3H,J= 7.1 Hz), 1.27 (m, 8H), 1.33 (m, 4H), 1.43 (q, 2H,J= 7.34 Hz), 1.80 (q, 2H,J= 7.55 Hz), 2.80 (t, 2H,J= 7.55 Hz), 7.17 (d, H,J= 8.6 Hz), 7.31 (dd, H,J= 4.85 Hz), 7.54 (dd, H,J= 2.71 Hz), 7.85 (dd, H,J= 1.4 Hz), 8.29 (d, H,J= 2.55 Hz), 8.59 (dd, H,J= 1.4 Hz); Elemental Analysis: Theory C₂₈H₃₇ClN₂O₃, C 69.33, H 7.69, N 5.78: Experimental C 71.06, H 8.77, N 4.66

Example 9 Synthesis of Butannoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester

After installing a thermometer, a stirrer and a condenser in a three-necked reactor, 0.31 g (0.0014 mol) of 5-methyl-2- (oxazolo [4,5- b ] pyridin-2-yl) phenol and 0.28 g of triethylamine ( 0.0028 mol) and 5 ml of benzene were added sequentially to dissolve. 0.164 g (0.00154 mol) of butyryl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 83%; Molecular weight theory M = 296, experimental value M = 296; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 1.10 (t, 3H, J = 7.44 Hz), 1.89 (q, 2H, J = 7.47 Hz), 2.45 (s, 3H), 2.82 (t, 2H, J = 7.38 Hz), 7.04 (s, H), 7.25 (m, 2H), 7.82 (dd, H, J = 1.47 Hz), 8.20 (dd, H, J = 8.04 Hz), 8.57 (dd, H, J = 1.44 Hz); Elemental Analysis: Theoretical C ₁₇ H ₁₆ N ₂ O ₃ , C 68.91, H 5.44, N 9.45: Experimental C 68.61.78, H 5.50, N 9.35.

Example 10. Synthesis of Octanenoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester

After installing a thermometer, a stirrer and a condenser in a three-necked reactor, 0.31 g (0.0014 mol) of 5-methyl-2- (oxazolo [4,5- b ] pyridin-2-yl) phenol and 0.28 g of triethylamine ( 0.0028 mol) and 5 ml of benzene were added sequentially to dissolve. 0.25 g (0.00154 mol) of octanoyl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 87%; Molecular weight theory M = 352, experimental value M = 352; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 0.87 (t, 3H, J = 4.71 Hz), 1.32 (m, 6H), 1.35 (q, 2H, J = 5.28 Hz), 1.43 (q, 2H, J = 3.39 Hz), 2.31 (s, 3H), 2.81 (t, 2H, J = 7.56 Hz), 7.0 (s, H), 7.20 (m, 2H), 7.79 (dd, H, J = 1.32 Hz), 8.17 (dd, H, J = 8.04 Hz), 8.55 (dd, H, J = 1.29 Hz); Elemental Analysis: Theoretical C ₂₁ H ₂₄ N ₂ O ₃ , C 71.57, H 6.86, N 7.95: Experimental C 71.42, H 6.36, N 7.46.

Example 11.Synthesis of decannoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester

After installing a thermometer, a stirrer and a condenser in a three-necked reactor, 0.31 g (0.0014 mol) of 5-methyl-2- (oxazolo [4,5- b ] pyridin-2-yl) phenol and 0.28 g of triethylamine ( 0.0028 mol) and 5 ml of benzene were added sequentially to dissolve. 0.29 g (0.00154 mol) of decanoyl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 81%; Molecular weight theory M = 380, experimental value M = 380; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 0.87 (m, 6H), 1.26 (m, 9H), 1.47 (q, 2H, J = 7.22 Hz), 1.83 (q, 2H, J = 7.38 Hz), 2.32 (q, 2H, J = 7.68 Hz), 2.37 (s, 3H), 2.83 (t, 2H, J = 7.32 Hz), 7.04 (s, H), 7.27 (m, 2H), 7.84 (dd, H, J = 1.44 Hz), 8.22 (dd, H, J = 8.04 Hz), 8.57 (dd, H, J = 3.48 Hz); Elemental Analysis: Theoretical C ₂₃ H ₂₈ N ₂ O ₃ , C 72.60, H 7.42, N 7.36: Experimental C 72.89, H 7.55, N 7.03.

Example 12 Synthesis of Palmitoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester

After installing a thermometer, a stirrer and a condenser in a three-necked reactor, 0.31 g (0.0014 mol) of 5-methyl-2- (oxazolo [4,5- b ] pyridin-2-yl) phenol and 0.28 g of triethylamine ( 0.0028 mol) and 5 ml of benzene were added sequentially to dissolve. 0.42 g (0.00154 mol) of palmitoyl chloride was added to the reaction mixture with benzene. The mixture was diluted in a weight ratio of 1: 1 and slowly added dropwise over 1 hour and 30 minutes, and the reaction solution was further reacted for 4 hours while heating to reflux. After the reaction solution was cooled to room temperature, the reaction solution was neutralized with diluted hydrochloric acid. Water was added to the reaction solution to separate the layers, and then the organic layer of benzene was separated, and benzene was distilled off under reduced pressure to obtain the target compound as a solid.

Yield 85%; Molecular weight theory M = 464, experimental value M = 464; ¹ H NMR (300 MHz, CDCl ₃ - d , ppm) δ 0.85 (m, 6H), 1.25 (m, 10H), 1.41 (m, 4H), 1.62 (q, 4H, J = 3.69 Hz), 1.80 (q, 4H, J = 7.59 Hz), 2.35 (s, 3H), 2.82 (t, 3H, J = 7.56 Hz), 7.04 (s, H), 7.25 (m, 2H), 7.82 (dd, H, J = 1.35 Hz), 8.20 (dd, H, J = 8.04 Hz), 8.56 (dd, H, J = 1.29 Hz); Elemental Analysis: Theoretical C ₂₉ H ₄₀ N ₂ O ₃ , C 74.96, H 8.68, N 6.03: Experimental C 75.15, H 8.68, N 6.42.

Experimental Example

Experimental Example 1. Spectroscopic and thermal characteristics experiment

The spectroscopic and thermal properties of the compound represented by Chemical Formula 1 synthesized in Examples 1 to 12 were confirmed by the following method, and the results are shown in Table 1 below.

(1) Spectroscopic characteristics: The maximum absorption wavelength (λ _max ) and the molar extinction coefficient (ε _max ) were measured by the infrared absorption measurement method using a near infrared spectrometer.

(2) Thermal Properties: In order to confirm thermal stability, the initial decomposition temperature was measured using thermogravimetric analysis.

division Spectroscopic Properties (in CH ₂ Cl ₂ ) Initial pyrolysis temperature
(℃) Absorption wavelength
(nm) Molar absorption coefficient
(Lmol ^-1 cm ^-1 ) Example 1 300 37,200 77-78 Example 2 300 35,600 50 to 51 Example 3 300 40,700 46-49 Example 4 300 36,000 55-57 Example 5 310 23,400 72-74 Example 6 310 23.000 76-78 Example 7 310 23,600 66-68 Example 8 310 20,900 85-87 Example 9 311 37,200 83-85 Example 10 311 35,600 54 to 55 Example 11 311 40,700 45 to 47 Example 12 311 36,000 64 to 66

As shown in Table 1, the alkanonoic 2- (oxazol-2-yl) phenyl ester compound has a maximum absorption wavelength range of 300 to 320 nm, a molar extinction coefficient of 20,000 to 40,700 L / mol · cm, Initial pyrolysis temperature has spectroscopic and thermal properties ranging from 45 to 87 ° C.

Experimental Example 2. Experiment for confirming fluorescence properties of hydrolyzate

The alkanoic 2- (oxazol-2-yl) phenyl ester compound of Examples 1 to 12 was hydrolyzed with a mixed solution of sodium methoxide and methanol, and an oxazolyl phenol compound as shown in Table 2 below. Switched. The results of confirming the fluorescence characteristics of the prepared oxazolyl phenolic compounds are shown in Table 2 below.

Oxazolyl Phenolic Compounds Fluorescence ^* (in CH ₂ Cl ₂ ) 2- (benz [ d ] oxazol-2-yl) phenol 427 nm 4-chloro 2- (oxazolo [4,5- b ] pyridin-2-yl) phenol 438nm 5-methyl 2- (oxazolo [4,5- b ] pyridin-2-yl) phenol 440 nm ^* Fluorescence characteristics were measured by LS 50 (Perkin Elmer) fluorescence measuring instrument.

As described above, in the present invention, the alkanonoic 2- (oxazol-2-yl) phenyl ester compound has a maximum absorption wavelength range of 300 to 320 nm and a molar extinction coefficient of 20,000 to 40,700 L / mol · cm And a novel compound having an initial pyrolysis temperature in the range of 45-87 ° C.

In addition, alkannoic 2- (oxazol-2-yl) phenyl ester compounds characterized by the present invention are useful as precursor compounds for fluorescent markers.

Claims (5)

Alkanoic 2- (oxazol-2-yl) phenyl ester compounds represented by Formula 1 below:
[Formula 1]

In Chemical Formula 1,
X represents CH or N; R ¹ , R ² , R ³ , and R ⁴ , which are the same as or different from each other, represent a hydrogen atom, a halogen atom, or a C ₁ -C ₆ alkyl group; R ⁵ represents a C ₁ to C ₂₀ alkyl group.
The method according to claim 1,
Butanoic 2- (benz [ d ] oxazol-2-yl) phenyl ester,
Octanoic 2- (benz [ d ] oxazol-2-yl) phenyl ester,
Decannoic 2- (benz [ d ] oxazol-2-yl) phenyl ester,
Palmitoic 2- (benz [ d ] oxazol-2-yl) phenyl ester,
Butanoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester,
Octanoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester,
Decannoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester,
Palmitoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -4-chlorophenyl ester,
Butanoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester,
Octanoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester,
Decannoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester, and
Palmitoic 2- (oxazolo [4,5- b ] pyridin-2-yl) -5-methylphenyl ester
Alkanoic 2- (oxazol-2-yl) phenyl ester compound, characterized in that it is selected from the group consisting of:
The method according to claim 1,
Alkannoic 2- (oxazole-2), characterized in that the maximum absorption wavelength ranges from 300 to 320 nm, the molar extinction coefficient is from 20,000 to 40,700 L / mol · cm, or the initial pyrolysis temperature is from 45 to 87 ° C. -Yl) phenyl ester compound.
Precursor compound for a fluorescence marker (maker), characterized in that the compound of any one of claims 1 to 3.
An alkanoyl 2- (oxazole-2) represented by Chemical Formula 1, which is prepared by reacting an oxazolyl phenol compound represented by the following Chemical Formula 2 with an alkanoyl chloride compound represented by the following Chemical Formula 3 in the presence of a base: -Yl) phenyl ester compound preparation method:
(2)

(3)

[Formula 1]

In Chemical Formula 1, 2, or 3,
X represents CH or N; R ¹ , R ² , R ³ , and R ⁴ , which are the same as or different from each other, represent a hydrogen atom, a halogen atom, or a C ₁ -C ₆ alkyl group; R ⁵ represents a C ₁ to C ₂₀ alkyl group.