KR20130077402A - Chemosensor having selectivity for hydrazine and method for monitoring hydrazine using the same - Google Patents

Abstract

PURPOSE: A chemosensor having selectivity for hydrazine is provided to be used as a selective turn on type fluorescence sensor as the fluorescence intensity is remarkably increased by deprotection reaction in which the lebulinyl group is cut by hydrazine, and to detect the hydrazine with the naked eye using color reaction. CONSTITUTION: A compound represented by the chemical formula 1 is provided. The compound of the chemical formula 1 is the compound represented by the below chemical formula 1a. A sensor for detecting hydrazine comprises a compound represented by the chemical formula 2. A composition for detecting hydrazine comprises: the compound represented by the below chemical formula 2; and a mixed solution containing acetate buffer solution and DMSO aqueous solution. A method for detecting hydrazine is to use the above sensor. Hydrazine is detected by reacting the sensor with the sample containing hydrazine under the solution mixing the acetate buffer solution having a pH of 3-6 and 1-99% of DMSO aqueous solution.

Description

Chemical sensor with hydrazine selectivity and hydrazine detection method using the same {Chemosensor having selectivity for hydrazine and method for monitoring hydrazine using the same}

The present invention relates to a chemical sensor having hydrazine selectivity for selectively detecting hydrazine through colorimetric and fluorescence changes due to deprotection of a levulinate protecting group by hydrazine and a hydrazine detection method using the same.

Hydrazine is widely used as a reactant for rockets, missile propellants, and fuel cells. It is also a highly active base and a strong reducing agent and is used as an important reactant in the manufacture of chemicals, pesticides in the various chemical industries, chemicals used in photography, emulsifiers and dyes. It is also used as a chemical blowing agent and corrosion inhibitor for use in general heating systems. However, hydrazine is very toxic and is gradually absorbed through the inhalation route by mouth, skin, or exposure. Long studies with experimental animals have demonstrated that hydrazine is a mutagen and a carcinogen.

Due to the widespread application of hydrazine and human toxicity, there is a need to develop reliable and sensitive analytical methods for selective detection of hydrazine. Hydrazine can usually be analyzed by various chromatographic techniques, such as gas chromatography, HPLC, and ion chromatography. Electrochemical detection with chemically modified electrodes is also often used. However, despite these convenient techniques, no optical analysis system has been reported. It has been reported that the oxidation of hydrazine with Tl (III) produces fluorescent Tl (I) ⁸ , and the fluorescent derivatives are produced by reaction with arenedicarboxaldehydes. Fluorescent signaling involving the disruption of internal hydrogen bonds by hydrazine in carbazopyridinophan has also been reported. Swager et al. Reported an interesting result of detecting trace amounts of hydrazine using turn-on type fluorescently coupled polymer films. Among many complex optical signaling systems, active chemical probes have received much attention because of their specificity and cumulative signaling effects. There are many smart active probe systems used for the analysis of heavy constituents using metal ions, anions and unique chemical modifications. In particular, flower-purpose signal is deprotection of the specific protecting group tool, for example, silyl for fluoride, ether, benzene sulfonyl group for boronate, superoxide to hydrogen peroxide, hydrazine for Cu ^{2 +} zone, and Hg for ^{2 +} Thiol acetal, has been used as. Leblinoyl ester, a versatile protecting group often used in synthetic organic chemistry, can be selectively removed by hydrazine treatment. Interestingly, triphenol reblate has been used as a hydrazine cleavage protecting agent for hydroxyl groups.

Recently, we have reported the use of resorphin levulinate as a selective chromogenic probe for the detection of sulfites. Using this background for Revlinate, we have devised a new hydrazine-selective signaling system.

1. US Patent No. 5,719,061, 1998.02.17

Timin Hadi, Thesis "Peptidoglycan-Modifying Enzymes: Mechanistic studies and substrate and inhibitor design", P. 58-59, July 2011. 2. Samuel W. et al. Advanced Materials, vol. 18, p. 1047-1050, 2006. 3.Myung Gil Choi et al., Organic Letters, vol. 12 (24), p.5624-5627, November 17, 2010.

It is an object of the present invention to provide a novel color development or fluorescence signaling detection probe for hydrazine based on the selective deprotection of protecting groups.

In order to achieve the above object, the present invention provides a compound represented by the following formula (1)

[Formula 1]

Where

R ₁ , R ₂ and R ₃ each independently represent hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,

R ₄ represents hydrogen or cyano,

를 나타내어 X 및 Z을 함유하는 고리와 융합환을 형성하고, 여기서, R₆, R₇ 및 R₈은 각각 독립적으로 수소, 할로겐, 카르복실, 시아노, 니트로, 탄소수 1 내지 4의 알콕시, 또는 탄소수 1 내지 4의 알킬을 나타내며,R ₅ represents carbonyl, or R ₄ and R ₅ together or

To form a fused ring with a ring containing X and Z, wherein R ₆ , R ₇ and R ₈ are each independently hydrogen, halogen, carboxyl, cyano, nitro, alkoxy having 1 to 4 carbon atoms, or Alkyl having 1 to 4 carbon atoms;

Z represents a nitrogen atom or CR ₉ , wherein R ₉ represents hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy of 1 to 4 carbon atoms, or alkyl of 1 to 4 carbon atoms,

X represents an oxygen atom or a sulfur atom,

를 나타내어 X 및 Z을 함유하는 고리와 융합환을 형성하고, R₁, R₂, R₃, R₆, R₇ 및 R₈이 수소인 화합물은 제외된다.
X is an oxygen atom, Z is a nitrogen atom, R ₄ and R ₅ together or

To form a fused ring with a ring containing X and Z and excludes compounds in which R ₁ , R ₂ , R ₃ , R ₆ , R ₇ and R ₈ are hydrogen.

The present invention also provides a sensor for detecting hydrazine comprising a compound represented by the following formula (2):

[Formula 2]

Where

R ₁ , R ₂ and R ₃ each independently represent hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,

R ₄ represents hydrogen or cyano,

를 나타내어 X 및 Z을 함유하는 고리와 융합환을 형성하고, 여기서, R₆, R₇ 및 R₈은 각각 독립적으로 수소, 할로겐, 카르복실, 시아노, 니트로, 탄소수 1 내지 4의 알콕시, 또는 탄소수 1 내지 4의 알킬을 나타내며,R ₅ represents carbonyl, or R ₄ and R ₅ together or

To form a fused ring with a ring containing X and Z, wherein R ₆ , R ₇ and R ₈ are each independently hydrogen, halogen, carboxyl, cyano, nitro, alkoxy having 1 to 4 carbon atoms, or Alkyl having 1 to 4 carbon atoms;

Z represents a nitrogen atom or CR ₉ , wherein R ₉ represents hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy of 1 to 4 carbon atoms, or alkyl of 1 to 4 carbon atoms,

X represents an oxygen atom or a sulfur atom.

The present invention also

A compound represented by Formula 2; And

Provided is a composition for detecting hydrazine, including a mixed solution containing an acetate buffer solution and an aqueous DMSO solution.

The invention also provides a method for detecting hydrazine using the sensor according to the invention.

The chemical sensor of the present invention can detect the hydrazine with the naked eye through the fact that the color in the aqueous solution is changed from colorless to greenish yellow while the levulinate group is released through the selective deprotection reaction by the hydrazine, hydrazine because the fluorescence intensity is significantly increased It can be used as a selective coloration and fluorescence signaling probe of the turn-on type for.

1 shows hydrazine (5.0 × 10 ⁻⁴ M), representative metal ions (5.0 × 10 ⁻⁴ M) in a mixed solution of acetate buffer (pH 4.5, 10 mM) and DMSO (3: 7, v / v) and Fluorescence spectra measured after reacting anion (5.0 × 10 ⁻⁴ M) with probe 1 (5.0 × 10 ⁻⁶ M) for 15 minutes (l _ex = 360 nm).
2 shows hydrazine (1.0 × 10 ⁻³ M) and various metal ions (1.0 × 10 ⁻³ M) in a mixed solution of acetate buffer (pH 4.5, 10 mM) and DMSO (3: 7, v / v). ) And the absorbance ratio ( A ₄₂₆ / A ₃₃₆ ) according to the reaction of probe 1 (1.0 × 10 ^-5 M).
3 shows hydrazine (1.0 × 10 ⁻³ M) and various anions (1.0 × 10 ⁻³ M) in a mixed solution of acetate buffer (pH 4.5, 10 mM) and DMSO (3: 7, v / v) The absorbance ratio ( A ₄₂₆ / A ₃₃₆ ) according to the reaction between and probe 1 (1.0 × 10 ⁻⁵ M) is shown.
4 acetate buffer solution (pH 4.5, 10 mM) and a mixed solution of DMSO (3: 7, v / v) of hydrazine in ^{- (1.0 × 10 -3 M)} , a typical metal ion (1.0 × 10 ^-3 M) And UV-vis spectrums measured after reacting anion (1.0 × 10 ⁻³ M) with probe 1 (1.0 × 10 ⁻⁵ M) for 15 minutes.
5 shows hydrazine (5.0 × 10 ⁻⁴ M) and various metal ions (5.0 × 10 ⁻⁴ M) in a mixed solution of acetate buffer (pH 4.5, 10 mM) and DMSO (3: 7, v / v) ) And the change in fluorescence intensity ratio ( I / I _o ) at 458 nm according to the reaction of probe 1 (5.0 × 10 ⁻⁶ M) (l _ex = 360 nm).
6 shows hydrazine (5.0 × 10 ⁻⁴ M) and various anions (5.0 × 10 ⁻⁴ M) in a mixed solution of acetate buffer (pH 4.5, 10 mM) and DMSO (3: 7, v / v) And fluorescence intensity ratio ( I / I _o ) at 458 nm according to the reaction of and probe 1 (5.0 × 10 ⁻⁶ M) (l _ex = 360 nm).
7 shows probe 1 (5.0 × 10 ⁻³ M), probe 1 and hydrazine (1.0 × 10 ⁻² M), probe 2 (5.0 × 10 ⁻ ) in deuterium / DMSO-d ₆ (3: 7, v / v). ³ M) and partial ¹ H NMR spectra according to the reaction of hydrazine.
FIG. 8 shows probe 1 (5.0 × 10 ⁻³ M), probe 1 and hydrazine (1.0 × 10 ⁻² M), probe 2 (5.0 in D ₂ O: DMSO-d ₆ (3: 7, v / v). × 10 ^-3 shows the ¹ H NMR spectrum of the reaction of M) and hydrazine.
9 shows probe 1 (1.0 × 10 ⁻⁵ M), probe 1 and hydrazine (1.0 × 10 ⁻³ ) in a mixed solution of acetate buffer (pH 4.5, 10 mM) and DMSO (3: 7, v / v). M), UV-vis spectra according to the reaction of probe 2 (1.0 × 10 ⁻⁵ M) and hydrazine.
10 shows various metal ions (1.0 × 10 ⁻³ M) and probe 1 (1.0 × 10 ⁻⁵ M) in a mixed solution of acetate buffer (pH 4.5, 10 mM) and DMSO (3: 7, v / v). M)-Shows the UV-vis spectrum according to the reaction of the hydrazine (2.0 × 10 ^-4 M) system.
FIG. 11 shows various anions (1.0 × 10 ⁻³ M) and probe 1 (1.0 × 10 ⁻⁵ M) in a mixed solution of acetate buffer (pH 4.5, 10 mM) and DMSO (3: 7, v / v). UV-vis spectra according to the reaction of the) -hydrazine (2.0 × 10 ^-4 M) system.
FIG. 12 shows probe 1 with Hg (II) and Cu (II) (1.0 × 10 ⁻³ M) in a mixed solution of acetate buffer (pH 4.5, 10 mM) and DMSO (3: 7, v / v). The effect of resin (Chelex-100 chelating resin) treatment on the signaling of (1.0 × 10 ⁻⁵ M) -hydrazine (2.0 × 10 ⁻⁴ M) systems is shown.
FIG. 13 shows probe 1 (1.0 × 10 ⁻⁵ M) and hydrazine (1.0 × 10 ⁻³ M) in a mixed solution of acetate buffer (pH 4.5, 10 mM) and DMSO (3: 7, v / v). Represents signaling over time.
FIG. 14 shows UV-vis titration curves of probe 1 (1.0 × 10 ⁻⁵ M) and hydrazine in acetate buffer (pH 4.5, 10 mM) and mixed solution of DMSO (3: 7, v / v).

EMBODIMENT OF THE INVENTION Hereinafter, the structure of this invention is demonstrated concretely.

The present invention relates to a compound represented by the following general formula (1):

[Formula 1]

Where

R ₁ , R ₂ and R ₃ each independently represent hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,

R ₄ represents hydrogen or cyano,

를 나타내어 X 및 Z을 함유하는 고리와 융합환을 형성하고, 여기서, R₆, R₇ 및 R₈은 각각 독립적으로 수소, 할로겐, 카르복실, 시아노, 니트로, 탄소수 1 내지 4의 알콕시, 또는 탄소수 1 내지 4의 알킬을 나타내며,R ₅ represents carbonyl, or R ₄ and R ₅ together or

To form a fused ring with a ring containing X and Z, wherein R ₆ , R ₇ and R ₈ are each independently hydrogen, halogen, carboxyl, cyano, nitro, alkoxy having 1 to 4 carbon atoms, or Alkyl having 1 to 4 carbon atoms;

Z represents a nitrogen atom or CR ₉ , wherein R ₉ represents hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy of 1 to 4 carbon atoms, or alkyl of 1 to 4 carbon atoms,

X represents an oxygen atom or a sulfur atom,

를 나타내어 X 및 Z을 함유하는 고리와 융합환을 형성하고, R₁, R₂, R₃, R₆, R₇ 및 R₈이 수소인 화합물은 제외된다. X is an oxygen atom, Z is a nitrogen atom, R ₄ and R ₅ together or

To form a fused ring with a ring containing X and Z and excludes compounds in which R ₁ , R ₂ , R ₃ , R ₆ , R ₇ and R ₈ are hydrogen.

The terms used in the substituent definitions of the compounds of the present invention are as follows.

"Halogen" is -F, -Cl, -Br or -I.

"Alkyl" refers to a straight, branched or cyclic saturated hydrocarbon having 1 to 4 carbon atoms, for example 1 to 4 carbon atoms, unless otherwise noted. Examples of C _{1 -4} alkyl groups include, but are such as methyl, ethyl, propyl, butyl, isobutyl, sec- butyl, or tert- butyl, and is not limited to these.

"Alkoxy" means an alkyl group having 1 to 4 carbon atoms, such as 1 to 4 carbon atoms, bonded to an oxygen atom unless otherwise specified. Examples of C _{1 -4} alkoxy groups, including, methoxy, ethoxy, propoxy, and butoxy, and is not limited to these.

Specific examples of the compound of Formula 1 include a compound represented by the following Formula 1a:

[Formula 1a]

Where

R ₁ , R ₂ , R ₃ and R ₉ each independently represent hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,

R ₄ represents hydrogen or cyano.

Specific examples of Formula 1a

R ₁ , R ₂ , R ₃ and R ₉ each independently represent hydrogen, halogen or alkyl having 1 to 4 carbon atoms,

R ₄ may represent hydrogen or cyano.

The compound of Formula 1 may be used as a fluorescence sensor for selectively detecting hydrazine since the fluorescence intensity increases through a deprotection reaction in which a levinyl group is released by hydrazine.

In addition, when the deprotection reaction occurs under an aqueous solution, since the color of the aqueous solution shows a color change from colorless to greenish yellow, the hydrazine may be visually identified.

The compound of Formula 1a may be prepared according to one embodiment shown in Scheme 1 below:

[Scheme 19]

The compound of Formula 1a may be prepared through a conventional levulinate protecting group addition reaction using the hydroxycyanocoumarin compound of Formula 3 as a starting material, but is not particularly limited thereto.

The present invention also relates to a sensor for detecting hydrazine comprising a compound represented by the following Chemical Formula 2:

[Formula 2]

Where

R ₁ , R ₂ and R ₃ each independently represent hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,

R ₄ represents hydrogen or cyano,

를 나타내어 X 및 Z을 함유하는 고리와 융합환을 형성하고, 여기서, R₆, R₇ 및 R₈은 각각 독립적으로 수소, 할로겐, 카르복실, 시아노, 니트로, 탄소수 1 내지 4의 알콕시, 또는 탄소수 1 내지 4의 알킬을 나타내며,R ₅ represents carbonyl, or R ₄ and R ₅ together or

To form a fused ring with a ring containing X and Z, wherein R ₆ , R ₇ and R ₈ are each independently hydrogen, halogen, carboxyl, cyano, nitro, alkoxy having 1 to 4 carbon atoms, or Alkyl having 1 to 4 carbon atoms;

Z represents a nitrogen atom or CR ₉ , wherein R ₉ represents hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy of 1 to 4 carbon atoms, or alkyl of 1 to 4 carbon atoms,

X represents an oxygen atom or a sulfur atom.

Specific examples of the compound of Formula 2 may include a compound represented by the following Chemical Formula 2a:

(2a)

Where

R ₁ , R ₂ , R ₃ and R ₉ each independently represent hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,

R ₄ represents hydrogen or cyano.

Examples of specific examples of the compound of Formula 2a above

R ₁ , R ₂ , R ₃ and R ₉ each independently represent hydrogen, halogen or alkyl having 1 to 4 carbon atoms,

R ₄ may represent hydrogen or cyano.

In addition, embodiments of the compound of Formula 2 may include a compound of Formula 2b:

[Formula 2b]

Where

R ₁ , R ₂ , R ₃ , R ₆ , R ₇ and R ₈ each independently represent hydrogen, halogen, carboxyl, cyano, nitro, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,

X is an oxygen atom or a sulfur atom,

Z represents a nitrogen atom.

Examples of specific examples of the compound of Formula 2b above

R ₁ , R ₂ , R ₃ , R ₆ , R ₇ and R ₈ are hydrogen,

X can represent an oxygen atom.

The compound of Formula 2 may be used as a fluorescence sensor for selectively detecting hydrazine since the fluorescence intensity increases through a deprotection reaction in which a levinyl group is released by hydrazine.

According to the mechanism of Scheme 2, color development and fluorescence signaling are due to the selective deprotection of coumarin levulinate by hydrazine. The cleavage of the levulinate group proceeds preferentially at the ¹¹ ribonyl group at the 4 position of the levulinate group, and then forms an amid ring to induce cleavage of the ester functional group. The resulting hydroxycoumarin® compound of formula 3 shows its characteristic color development and fluorescence signaling behavior.

Therefore, the compound of Formula 2 exhibits strong fluorescence as it is converted to coumarin through a deprotection reaction in which levulinate is released by hydrazine, and exhibits colorimetric and fluorescence signaling characteristics of turn-on type, which show color change from colorless to greenish yellow. Represents:

[Scheme 2]

The compound of formula 2 according to the present invention shows a selective increase in fluorescence at wavelengths of 415 nm and 458 nm depending on the concentration of hydrazine in the aqueous solution, thus the compound is referred to as a "turn-on" type fluorescent probe. It can be used as a probe to detect hydrazine.

According to one embodiment of the invention, the compound of formula (2) is ^{F -, Cl -, Br -} , I -, HPO 4 2-, P 2 O 7 4 -, SO 4 2 -, SO 3 2 -, NO 3 _{^{-, N 3 -, HCO 3}} -, AcO -, or ClO ₄ ^- does not represent a change in fluorescence for negative ions, such as, shows a change in fluorescence when the reaction of hydrazine and a concentration-dependent manner by a significant margin.

According to an embodiment of the present invention, the compound of formula 2 according to the present invention, in addition to hydrazine in the aqueous solution, alkali metal ions (Li ⁺ , Na ⁺ , K ⁺ ), alkaline earth metal ions (Mg ^{2 +} , Ca ²⁺ ), or In the presence of transition metal ions (Fe ^{3 +} , Ni ^{2 +} , Zn ^{2 +} , Ba ^{2 +} , Co ^{2 +} , Ag ⁺ , Pd ^{2 +} , Hg ^{2 +} , Cd ^{2 +} ) selectively reacts with hydrazine It shows a large change in fluorescence.

In addition, the compound of Formula 2 exhibits UV-vis absorption at 307 nm and 336 nm wavelengths, but shows a significantly increased absorbance at 336 nm and 426 nm depending on concentration through selective reaction with hydrazine. You can also measure the signal of hydrazine.

In addition, detection of hydrazine can also be measured visually through colorimetric change.

According to one embodiment, as the concentration of the hydrazine reacted with the compound of formula (2) according to the present invention in the aqueous solution shows a color change from colorless to green yellow.

The sensor for detecting hydrazine of the present invention may be provided as a conventional kit that can check the presence and concentration of hydrazine by mixing with a sample solution to detect hydrazine.

The present invention also provides a compound represented by the formula (2);

The present invention relates to a composition for detecting hydrazine, including a mixed solution containing an acetate buffer solution and a DMSO aqueous solution.

The composition for detecting hydrazine 의 of the present invention may include a mixed solution in addition to the compound represented by the formula (2).

The mixed solution may be a mixture of an acetate buffer solution of pH 3 to 6 and 1 to 99% DMSO aqueous solution. More specifically, the DMSO aqueous solution may use a 10 to 30% DMSO aqueous solution to observe the color change in the aqueous solution. In addition, 1-99% DMSO aqueous solution may be used for DMSO aqueous solution for fluorescence detection. If it is in the above range can exhibit excellent hydrazine selectivity and sensitivity.

The invention also relates to a method for detecting hydrazine using a sensor according to the invention.

The compound of Formula 2 of the present invention is a "turn-on" type sensor that can detect hydrazine in an aqueous solution state and detects the fact that the intensity of fluorescence is amplified when hydrazine is detected in a state that does not exhibit fluorescence. It is a sensor of the type made and can detect hydrazine quickly because of the fast reaction speed.

According to one embodiment of the present invention, the reaction is completed within about 15 minutes, so rapid detection of hydrazine is possible.

In addition, the detection of the hydrazine by the compound of the formula (2) by reacting the sample containing the sensor (formula 2) and the hydrazine under a solution of pH 3-6 acetate buffer solution and 1 to 99% DMSO aqueous solution Can be detected.

The detection of the hydrazine can be measured through the color change of the aqueous solution. The DMSO aqueous solution for this may be 10 to 30% DMSO aqueous solution.

According to one embodiment of the present invention, the compound of formula # 2 can be visually observed that the color in the aqueous solution changes from colorless to greenish yellow after reaction with hydrazine.

In addition, the detection of the hydrazine by the compound of Formula 2 is to measure the change in the fluorescence intensity, since the fluorescence intensity increases depending on the concentration of the hydrazine can be measured.

In addition, the detection of the hydrazine shows a UV-vis spectrum in which the compound of Formula 2 reacts with the hydrazine and gradually decreases as the strong absorption band at 336 nm red shifts, while the new band is increased at 406 nm to 336 nm and 426. By measuring the absorbance ratio at nm (A ₄₂₆ / A ₃₃₆ ), the signaling of hydrazine can be measured ratiometrically.

According to one embodiment of the present invention, the "absorbance" ratio is increased by at least 500 times after the compound of formula (VII) is reacted with hydrazine.

Hereinafter, the present invention will be described in more detail with reference to Examples of the present invention, but the scope of the present invention is not limited by the following Examples.

Example 1 Preparation of Coumarinpyrebulinate

3-cyano-7-hydroxycoumarin reblate (hereinafter referred to as probe 1) for detecting hydrazine is referred to as 3-cyano-7-hydroxycoumarin (hereinafter referred to as probe 2). Naming) and levinyl chloride (65%, CH ₂ Cl ₂ ) (Scheme 1).

[Scheme 1]

3-Cyano-7-hydroxycoumarin and levulinic acid were purchased from Aldrich Chemical Corporation. All solvents were purchased from Aldrich Chemical Corporation in spectroscopic grade. ¹ H NMR (600 MHz) and ¹³ C NMR (150 MHz) spectra were obtained on a Varian VNS spectrometer and the residual solvent signal was applied. UV-Vis spectra were recorded using a Jasco V-550 spectrophotometer equipped with a Peltier temperature controller. Fluorescence spectra were measured on an Aminco-Bowman Series 2 spectrophotometer. Mass spectra were obtained on a Micromass Autospec mass spectrometer.

To prepare coumarin levulinate, oxalyl chloride (0.82 mL, 8.6 mmol) and DMF (15 μL) were added to a levulinic acid (500 mg, 4.3 mmol) dissolved in dichloromethane (50 mL). The reaction mixture was stirred at rt for 4 h, the volatiles were evaporated under reduced pressure and dried by vacuum pumping. The residue was dissolved in a small amount of dry dichloromethane. The solution was slowly added to a dispersed dichloromethane solution (50 mL) containing 3-cyano-7-hydroxycoumarin (243 mg, 1.3 mmol) and triethylamine (0.54 mL, 3.9 mmol). After stirring for 12 hours, the reaction mixture is filtered and treated with water on the solution. The organic phase was separated, washed with 1M sodium bicarbonate solution and evaporated to give a solid residue. The product was purified by crystallization from dichloromethane and hexanes (yield: 65%).

¹ H NMR (600 MHz, CDCl ₃ ): δ8.94 (s, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.35 (d, J = 2.2 Hz, 1H), 7.25 (dd, J = 8.5 and 2.2 Hz, 1H), 2.87 (t, J = 6.4 Hz, 2H), 2.78 (t, J = 6.4 Hz, 2H), 2.16 (s, 3H);

¹³ C NMR (150 MHz, CDCl ₃ ): δ 207.2, 171.2, 157.2, 155.9, 155.3, 153.3, 131.5, 120.0, 115.9, 115.0, 110.8, 101.9, 37.9, 29.9, 28.3;

HRMS (FAB); m / z calcd for C ₁₅ H ₁₂ NO ₅ [M + H] ⁺ : 286.0710, found 286.0716.

Experimental Example 1 Measurement of Coloring and Fluorescence Signaling Behavior of Coumarinpyrebulinate

Colorimetric signaling behavior of the coumarin sulfenulinate (Probe 1) prepared in Example 1 was investigated in 30% DMSO aqueous solution at pH 4.5 (acetate buffer, 10 mM).

Probe 1 showed adequate UV-vis absorbance at 307 and 336 nm. Upon interaction of probe 1 with hydrazine, a dominant absorption band developed at 426 nm (Figure 1). In addition, greenish yellow, which is a characteristic of hydroxycyanocoumarin (Probe 2), was developed to allow colorimetric detection of hydrazine with the naked eye. Changes in the absorbance band following the deprotection process induced by hydrazine were prominent and provided a ratiometric analysis for the modification from probe 1 to probe 2. Using 100 equivalents of hydrazine, the absorbance ratio A ₄₂₆ / A ₃₃₆ increased more than 500-fold (increase from 0.014 to 7.14) at two characteristic wavelengths, 426 and 336 nm.

Other common cations and anions were relatively unreacted. For example, in the case of metal ions, 0.019 (in the case of Pb ^{2 +)} to about 0.078 (in the case of Fe ^{3 +),} in the case of negative ion, 0.014 (Br ^- in the case) to 0.16 ^- A in the area defined by (N ₃ For) ₄₂₆ / A ₃₃₆ value was shown (FIGS. 2 and 3).

Next, the fluorescence signaling behavior of probe 1 for hydrazine was measured. Probe 1 showed very weak fluorescence emission at 415 nm and 458 nm (FIG. 4). Upon reaction with hydrazine, the fluorescence intensity increased 250-fold at 458 nm and the color of the solution changed from colorless to light blue when exposed to UV lamps.

Did not show any other metal ions and negative ions are almost no change in release behavior: For a variety of ions with or in the 458nm emission intensity ratio I / I _o is the case of metal ions, 1.01 (in the case of Zn ^{2 +)} to about 1.26 (Ca ^{2 +} ), And in the case of anions, a narrow range is shown from 1.07 (for HCO ₃ ⁻ ) to 2.37 (for N ₃ ⁻ ) (FIGS. 5 and 6).

Signaling occurs due to selective deprotection of the levazine group of probe 1 with hydrazine (Scheme 2). The cleavage of the reblinate group of probe 1 by reaction with hydrazine is known to proceed preferentially at the carbonyl group at position 4 of the reblinate group and then form an amid ring to induce cleavage of the ester functional group. Thus, the hydroxycoumarin generated exhibited its characteristic color development and fluorescence signaling behavior. Deprotection induced by the given hydrazine was demonstrated by ¹ H NMR and UV-vis measurements.

Resonance for the coumarin moiety of probe 1 was observed at 8.68, 7.79, 7.23, and 7.15 ppm by ¹ H NMR spectrometer. However, when treated with 2 equivalents of hydrazine, the ¹ H NMR spectrum of probe 1 was nearly identical to that of 7-hydroxycyanocoumarin (FIG. 7).

In addition, resonance of the reaction product 4,5-dihydro-6-methylpyridazine-3 (2H) -one (4,5-dihydro-6-methylpyridazin-3 (2H) -one) was observed (FIG. 8). ).

In the presence of hydrazine, the UV-vis spectrum of probe 1 was nearly identical to the deprotection product of hydroxycyanocoumarin itself (FIG. 9).

Experimental Example 2 Selective Detection of Hydrazine in the Presence of Other Metal Ions and Anions

The existence of competition experiments, common anions and metal ions, except for Cu ^{2 +} and Hg ^{+ 2} of UV-vis changes in the probe 1 is guided by the co-existence of hydrazine 100 equivalent to the signaling system of the probe 1-hydrazine Did not change significantly (FIGS. 10 and 11).

Cu ^{2 +,} and Hg ^{2 +} interference of the ions was successfully excluded using a chelating resin Chelex-100 (Fig. 12).

Signaling of hydrazine terminated within 15 minutes, while probe 1 did not respond at all under the measurement conditions (FIG. 13).

Experimental Example 3 Investigation of the Quantitative Analysis Behavior of Probe 1 for Hydrazine Analysis

The quantitative analysis behavior of probe 1 for the analysis of hydrazine according to UV-vis absorption titration was investigated.

In the spectrum obtained 15 minutes after adding hydrazine to probe 1, the absorbance ratio ( A ₄₂₆ / A ₃₃₆ ) gradually increased to a titration of about 14 equivalents in response to the increase of hydrazine (FIG. 14). From the concentration-dependent UV-vis absorption change, the detection limit of probe 1 for the measurement of hydrazine was estimated to be 2.46 mM (0.08 ppm) in 30% DMSO aqueous solution.

In conclusion, the present invention has been developed a new chemical signaling system for the selective sensing of hydrazine according to the deprotection of the levignate group. Probes of the invention exhibit selective color development and fluorescence signaling behavior in response to hydrazine in 30% aqueous DMSO solution. Selective signaling is based on effective deprotection of levazine groups by hydrazine. The developed system can be used as a convenient signaling tool for the optical measurement of hydrazine in aquatic environments.

Claims (15)

A compound represented by the following formula (1):
[Formula 1]

In this formula,
R ₁ , R ₂ and R ₃ each independently represent hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,
R ₄ represents hydrogen or cyano,
R ₅ represents carbonyl, or R ₄ and R ₅ together or

To form a fused ring with a ring containing X and Z, wherein R ₆ , R ₇ and R ₈ are each independently hydrogen, halogen, carboxyl, cyano, nitro, alkoxy having 1 to 4 carbon atoms, or Alkyl having 1 to 4 carbon atoms;
Z represents a nitrogen atom or CR ₉ , wherein R ₉ represents hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy of 1 to 4 carbon atoms, or alkyl of 1 to 4 carbon atoms,
X represents an oxygen atom or a sulfur atom,
X is an oxygen atom, Z is a nitrogen atom, R ₄ and R ₅ together or

To form a fused ring with a ring containing X and Z and excludes compounds in which R ₁ , R ₂ , R ₃ , R ₆ , R ₇ and R ₈ are hydrogen.
The method of claim 1,
Compound of Formula 1 is a compound represented by the following formula (1a):
[Formula 1a]

In this formula,
R ₁ , R ₂ , R ₃ and R ₉ each independently represent hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,
R ₄ represents hydrogen or cyano.
The method of claim 2,
R ₁ , R ₂ , R ₃ and R ₉ each independently represent hydrogen, halogen or alkyl having 1 to 4 carbon atoms,
R ₄ represents hydrogen or cyano.
Hydrazine detection sensor comprising a compound represented by the formula (2):
(2)

In this formula,
R ₁ , R ₂ and R ₃ each independently represent hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,
R ₄ represents hydrogen or cyano,
R ₅ represents carbonyl, or R ₄ and R ₅ together or

To form a fused ring with a ring containing X and Z, wherein R ₆ , R ₇ and R ₈ are each independently hydrogen, halogen, carboxyl, cyano, nitro, alkoxy having 1 to 4 carbon atoms, or Alkyl having 1 to 4 carbon atoms;
Z represents a nitrogen atom or CR ₉ , wherein R ₉ represents hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy of 1 to 4 carbon atoms, or alkyl of 1 to 4 carbon atoms,
X represents an oxygen atom or a sulfur atom.
5. The method of claim 4,
The compound of Formula 2 is a sensor for detecting hydrazine, a compound represented by the formula (2a):
(2a)

In this formula,
R ₁ , R ₂ , R ₃ and R ₉ each independently represent hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,
R ₄ represents hydrogen or cyano.
The method of claim 5,
R ₁ , R ₂ , R ₃ and R ₉ each independently represent hydrogen, halogen or alkyl having 1 to 4 carbon atoms,
R ₄ is a hydrazine detection sensor representing hydrogen or cyano.
5. The method of claim 4,
The compound of formula (2) is a sensor for detecting hydrazine is a compound represented by the formula (2b).
(2b)

In this formula,
R ₁ , R ₂ , R ₃ , R ₆ , R ₇ and R ₈ each independently represent hydrogen, halogen, carboxyl, cyano, nitro, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,
X is an oxygen atom or a sulfur atom,
Z represents a nitrogen atom.
The method of claim 7, wherein
R ₁ , R ₂ , R ₃ , R ₆ , R ₇ and R ₈ are hydrogen,
X is a hydrazine detection sensor representing an oxygen atom.
A compound represented by Formula 2; and
Hydrazine detection composition comprising a mixed solution containing an acetate buffer and DMSO aqueous solution:
(2)

In this formula,
R ₁ , R ₂ and R ₃ each independently represent hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy having 1 to 4 carbon atoms, or alkyl having 1 to 4 carbon atoms,
R ₄ represents hydrogen or cyano,
R ₅ represents carbonyl, or R ₄ and R ₅ together or

To form a fused ring with a ring containing X and Z, wherein R ₆ , R ₇ and R ₈ are each independently hydrogen, halogen, carboxyl, cyano, nitro, alkoxy having 1 to 4 carbon atoms, or Alkyl having 1 to 4 carbon atoms;
Z represents a nitrogen atom or CR ₉ , wherein R ₉ represents hydrogen, halogen, hydroxy, cyano, nitro, carboxy, alkoxy of 1 to 4 carbon atoms, or alkyl of 1 to 4 carbon atoms,
X represents an oxygen atom or a sulfur atom.
10. The method of claim 9,
The mixed solution is a composition for detecting hydrazine, which is a mixture of pH 3 to 6 acetate buffer solution and 1 to 99% DMSO aqueous solution.
A method for detecting hydrazine using a sensor according to any one of claims 4 to 8.
The method of claim 11,
The detection of hydrazine is detected by reacting the sensor and the sample containing hydrazine under a mixture of an acetate buffer solution of pH 3 to 6 and 1 to 99% DMSO aqueous solution.
The method of claim 12,
The detection of hydrazine is a measure of the change of the color of the solution from colorless to green yellow.
The method of claim 11,
The detection of hydrazine measures the increase in fluorescence intensity.
The method of claim 11,
The detection of hydrazine is a method of measuring the signaling of hydrazine in a ratiometric manner by measuring the absorbance ratio (A ₄₂₆ / A ₃₃₆ ) at 336 nm and 426 nm.

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