Organic small molecule compound capable of distinguishing and detecting hydrazine and hypochlorite and preparation method of organic small molecule compound

Abstract

The invention discloses an organic small molecule compound capable of distinguishing and detecting hydrazine and hypochlorite as well as a preparation method and application of the organic small molecule compound. Diketopyrrolopyrazine and nitrogen-containing aromatic primary amine are subjected to a condensation reaction and coordinated with BF3. Et2O to obtain a PzDP-PPAB compound with an electron push-pull effect, and the maximum absorption peak and emission peak of the compound are located in a near-infrared region. In an organic solvent, PzDP-PPAB is subjected to an irreversible chemical reaction with hydrazine and hypochlorite so as to realize different detection of two substances, the detection limit of hydrazine is 0.04 [mu] mol / L, the detection limit of hypochlorite is 0.059 [mu] mol / L, and the method has the advantages of simple operation, sensitive reaction, naked eye detection and the like.

Description

Technical Field

[0001] The invention belongs to the field of organic small molecule fluorescent probes and relates to an organic small molecule compound capable of distinguishing and detecting hydrazine and hypochlorite and a preparation method thereof. Background Art

[0002] Hydrazine (N2H4) is widely used in chemical synthesis, fuel and pharmaceutical fields as a key reducing agent, developer and fuel component. However, its high toxicity poses a significant risk to the skin, mucous membranes and central nervous system, and may even be carcinogenic. Therefore, safety regulations must be strictly followed during its production, storage and use. Hypochlorite (ClO-), commonly found in hypochlorous acid and hypochlorites, is a strong oxidant that plays an important role in disinfection, bleaching and water treatment, but its excessive intake can irritate the skin and respiratory tract and even cause toxic reactions. Therefore, the concentration and application of hypochlorite-based products must be strictly controlled to ensure their safety and effectiveness. Based on this, it is crucial to develop sensitive methods for detecting N2H4 and ClO-.

[0003] Small molecule fluorescent probes have the advantages of high efficiency, rapidity, good sensitivity, high selectivity, and good biocompatibility. They have broad application prospects in various fields such as biology, chemistry, medicine, and environmental protection. Based on the nucleophilicity and reducibility of hydrazine, fluorescent probes for detecting hydrazine through sensing mechanisms such as deprotection, cyclization, and ring-opening reactions have been reported. In addition, based on the oxidizing property of ClO-, some fluorescent probes through sensing mechanisms such as carbon-carbon double bond cleavage, oxidation of sulfur / selenium compounds, and oxidative hydrolysis of oximes or hydrazides have also been reported. However, they all have problems such as slow reaction rate, long response time, and single detection signal, which greatly affects the real-time nature of the detection; more importantly, at present, a single compound is detected by a single fluorescent probe, and the use of a fluorescent probe to simultaneously achieve the differentiated detection of N2H4 and ClO- has not been reported. Summary of the invention

[0004] The purpose of the present invention is to provide a fluorescent probe with high sensitivity and the ability to distinguish and detect N2H4 and ClO-, so as to solve the problem that there is no single fluorescent probe that can detect N2H4 and ClO- at the same time. The present invention provides a novel pyrazine-fused diaza BODIPY compound, which increases the reaction rate of the aza BODIPY ring to N2H4 and ClO- by means of the pyrazine ring that strongly pulls electrons, and modifies the trimethylsilylene group to extend the conjugation length of the compound, so that the absorption and emission wavelengths are red-shifted, and N2H4 and ClO- are detected. - The addition of causes a significant color change and significant ratio fluorescence behavior of the compound, which is conducive to naked eye detection. The structural formula of the pyrazine-fused diaza BODIPY compound is:

[0005]

[0006] The present invention also provides a method for preparing the pyrazine-fused diaza BODIPY compound, and the preparation process is as follows:

[0007]

[0008] The preparation method thereof comprises the following steps:

[0009] (1) Ethyl 4-bromophenylglyoxylate and 1,4-diacetylpiperazine-2,5-dione are dissolved in an organic base in a molar ratio of 2 to 4:1, and the mixed system is stirred at 55-60° C. for 7 to 9 hours. After the raw materials are completely consumed, the organic base is removed under reduced pressure, and the obtained residue is stirred in methanol for 12 hours, filtered, and the residue is washed with cold methanol to obtain intermediate 1.

[0010] (2) Under nitrogen protection, the intermediate 1 is dissolved in formamide, the temperature is raised to 130-150°C, and the reaction is carried out for 4-6 hours. After the reaction is completed, methanol is added after cooling to room temperature, and the solid is precipitated and filtered. The filter cake is washed with cold methanol 3-5 times to obtain the intermediate 2.

[0011] (3) Under nitrogen protection, the intermediate 2 and the compound 5-((trimethylsilyl)ethynyl)pyridin-2-amine were dissolved in toluene in a mass ratio of 1:4-6, and stirred at 90°C for 1-2 hours. At this temperature, 5-10 times the molar equivalent of TiCl4 and 10-15 times the molar equivalent of an organic base were added in sequence. After reacting for 2-3 hours, 15-30 times the molar equivalent of BF3·Et2O was added. After the reaction was completed, the temperature was cooled to room temperature. Water was added to quench the reaction, and dichloromethane was used for extraction. The organic phases were combined. The solvent was removed by rotary evaporation, and the crude product was separated and purified by column chromatography to obtain PzDP-PPAB.

[0012] Compared with the prior art, the present invention has the following advantages:

[0013] (1) The organic small molecule probe PzDP-PPAB of the present invention has the characteristics of near-infrared absorption and near-infrared emission, a wide absorption range and a high molar extinction coefficient.

[0014] (2) The organic small molecule fluorescent probe of the present invention can realize the differential detection of N2H4 and ClO - , with the advantages of different colorimetric and fluorescent dual signals, naked eye detection, high sensitivity and low detection limit. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 This is the hydrogen spectrum of Example PzDP-PPAB.

[0016] Figure 2 The mass spectrum of Example PzDP-PPAB.

[0017] Figure 3 This is the UV-visible spectrum of PzDP-PPAB with hydrazine hydrate, hypochlorite and other substances added.

[0018] Figure 4 UV-visible spectra of PzDP-PPAB with different concentrations of hypochlorite added.

[0019] Figure 5 The fluorescence spectra of PzDP-PPAB with different concentrations of hypochlorite added.

[0020] Figure 6 The absorbance change of PzDP-PPAB at 627 nm after adding different concentrations of hypochlorite.

[0021] Figure 7 UV-visible spectra of PzDP-PPAB after adding different concentrations of hydrazine hydrate.

[0022] Figure 8 The fluorescence spectra of PzDP-PPAB after adding different concentrations of hydrazine hydrate.

[0023] Fig. 9 The absorbance change of PzDP-PPAB at 627nm after adding different concentrations of hydrazine hydrate. DETAILED DESCRIPTION

[0024] The specific implementation of the present invention is further described below in conjunction with the examples, but the scope of the present invention is not limited to the scope described in the examples. The percentages in brackets below are all yields unless otherwise specified.

[0025] Example

[0026] Compound 1 and Compound 2 were synthesized according to the literature (Synth Met. 2016, 220, 236-246). 5-((Trimethylsilyl)ethynyl)pyridine-2-amine was synthesized according to the literature (J. Mater. Chem. B, 2018, 6, 5570-5581).

[0027]

[0028] (1) Compound 1 (34.0 g, 132 mmol), compound 2 (11.38 g, 57.5 mmol) and triethylamine (34 mL) were added to a 100 mL round-bottom flask, and the mixture was stirred at 55-60° C. for 8.5 hours. After the raw materials were completely consumed, triethylamine was removed by distillation under reduced pressure to obtain the residue, which was stirred in methanol for 12 hours, filtered, and the residue was washed with cold methanol to obtain compound 3 as an orange solid (yield: 24 g, 71%). 1H NMR (400MHz, CDCl3): 11.75 (s, 2H), 7.50-7.47 (m, 4H), 7.02-6.98 (m, 4H), 4.17 (q, J = 7.17Hz, 4H), 1.15 (t, J = 7.17Hz, 6H).

[0029]

[0030] (2) Compound 3 (20.0 g, 33 mmol) and formamide (100 mL) were added to a 100 mL round-bottom flask, and the mixture was heated to 140-150° C. and stirred at this temperature for 4-5 hours. After the reaction was completed and cooled to room temperature, methanol was added to the reaction mixture to precipitate a solid, which was filtered and the filter cake was washed with methanol to obtain a dark brown solid 4 (yield: 3.8 g, 23%), which was directly used in the next step due to its poor solubility.

[0031]

[0032] (5) Compound 4 (100 mg, 0.2 mmol) and redistilled toluene (20 mL) were added to a 100 mL round-bottom flask, and the mixture was heated to 90°C and stirred for 1.5 hours. Then, 5-((trimethylsilyl)ethynyl)pyridin-2-amine (172 mg, 0.9 mmol) and TiCl4 (207.9 mg, 1.0 mmol) were added. After stirring for 2 hours, triethylamine (293 mg, 2.9 mmol) was added to the mixture, and stirring was continued for 2.5 hours. Then, boron trifluoride ether complex (440 mg, 3.1 mmol) was added to the mixture, and stirred at this temperature for 1.5 hours. The reaction was monitored by thin layer chromatography. After the reaction was completed, water was added to quench the reaction, and the mixture was extracted with a water-dichloromethane system. The combined organic extracts were dried over anhydrous Na2SO4, filtered, concentrated in vacuo, and purified by column chromatography (eluent: petroleum ether: dichloromethane = 2:1) to obtain a blue solid PzDP-PPAB (yield: 39 mg, 21%). The hydrogen spectrum and mass spectrum were as follows Figure 1 and Figure 2 shown. 1 H NMR(400MHz, CDCl3)δ8.66(s,2H),8.61–8.51(d,4H),8.25–7.95(m,2H),7.75–7.50(m,6H),1.71–1.55(s,18H).HRMS(ESI):m / z[M+H] + Calculate for C 40 H 32 B2Br2F4N8Si2:939.0835,found:939.6942.

[0033] Detection performance test

[0034] (1) Selectivity test: 1,4-dioxane was used as solvent and the concentration was 10 -5 M PzDP-PPAB mother solution. At the same time, the concentration of Na + , K + , Li + , Ca 2+ 、Co 2+ Mg 2+ , Mn 2+ NH4 + 、Al 3+ , Fe 2+ , Fe 3+ 、Zn 2+ , Ba 2+ ,OAc － Br － 、CO3 2－ 、HCO3 - 、F － 、NO2 － 、NO3 － 、SO3 2－ 、SO4 2－ 、SCN - , Cl - , ClO - , H2O2, GSH, N2H4, dimethylamine, triethylamine, aniline, and n-butylamine solutions showed that only when hydrazine hydrate and ClO were added - When the UV absorption peak of PzDP-PPAB changes significantly, it indicates that the PzDP-PPAB probe molecule has a strong affinity for hydrazine hydrate and ClO - The test has good selectivity, such as Figure 3 shown.

[0035] (2) ClO - Detection: Add different concentrations of ClO to the dioxane solution of PzDP-PPAB. - After the addition of ClO (0-1.2 mM), the UV-visible absorption spectrum and fluorescence emission spectrum of PzDP-PPAB molecules changed significantly. - With the increase of concentration, the absorption peaks of PzDP-PPAB at 627nm, 597nm, and 471nm gradually decreased and disappeared, and a new absorption peak was generated at 350nm and the absorbance gradually increased. A 257nm blue shift occurred between the maximum absorption peak wavelength and the new absorption peak, which is conducive to naked eye detection. Figure 4 In addition, PzDP-PPAB itself does not emit fluorescence, but with the addition of ClO -With the increase of concentration, a new peak appears at 525 nm and the intensity gradually increases, resulting in “fluorescence on”, e.g. Figure 5 shown.

[0036] (3)ClO - The minimum detection limit (LOD) was obtained by linear fitting the absorbance of PzDP-PPAB at 627 nm in the range of 0-50 μM N2H4 concentration, and the linear fitting equation Y=2030.87X+0.527 was obtained. The fitting constant R 2 =0.995. After calculation, PzDP-PPAB has a - The minimum detection limit is 0.059 μM. Figure 6 shown.

[0037] (4) Detection of hydrazine hydrate: After adding different concentrations of N2H4 (0-1.2mM) to the dioxane solution of PzDP-PPAB, the UV-visible absorption spectrum and fluorescence emission spectrum of the PzDP-PPAB molecule changed significantly. In terms of the UV-visible absorption spectrum, as the concentration of the added N2H4 gradually increased to 1.2mM, the absorption peaks of PzDP-PPAB at 627nm, 597nm, and 471nm gradually decreased and disappeared, while a new absorption peak was generated at 389nm and gradually increased. A 238nm blue shift occurred between the maximum absorption peak wavelength and the new absorption peak, which is conducive to naked eye detection. Figure 7 As shown in the fluorescence emission spectrum, PzDP-PPAB does not emit fluorescence, but with the ClO - As the concentration of added increases, new and gradually increasing intensity appears at 560 nm, resulting in “fluorescence on”, e.g. Figure 8 Compare Figure 4 , 5 and Figure 7 , 8 It can be seen that the PzDP-PPAB probe molecule is - In the presence of , different ultraviolet and fluorescence changes occur, which can realize the distinguishing detection of the two.

[0038] (5) Limit of detection (LOD) of N2H4: The emission values ​​of PzDP-PPAB at 627 nm corresponding to the concentration range of 0 to 50 μM N2H4 were linearly fitted to obtain the linear fitting equation Y=4809.5X+0.5115, and the fitting constant R 2 =0.9927. After calculation, the minimum detection limit of PzDP-PPAB for N2H4 is 0.04μM. Fig. 9 In summary, any modification, equivalent substitution and improvement made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. An organic small molecule compound that can distinguish and detect hydrazine and hypochlorite, and its structural formula is:

2. The method for preparing the compound according to claim 1, characterized in that The reaction process is as follows:

3. The method for preparing the compound according to claim 2, characterized in that: The steps include: (1) Ethyl 4-bromophenylglyoxylate and 1,4-diacetylpiperazine-2,5-dione are dissolved in an organic base in a molar ratio of 2 to 4:1, and the mixed system is stirred at 55-60° C. for 7 to 9 hours. After the raw materials are completely consumed, the organic base is removed under reduced pressure, and the obtained residue is stirred in methanol for 12 hours, filtered, and the residue is washed with cold methanol to obtain intermediate 1. (2) Under nitrogen protection, the intermediate 1 is dissolved in formamide, the temperature is raised to 130-150°C, and the reaction is carried out for 4-6 hours. After the reaction is completed, methanol is added after cooling to room temperature, and the solid is precipitated and filtered, and the filter cake is washed with cold methanol for 3-5 times to obtain the intermediate 2. (3) Under nitrogen protection, the intermediate 2 and the compound 5-((trimethylsilyl)ethynyl)pyridin-2-amine were dissolved in toluene in a mass ratio of 1:4-6, and stirred at 90°C for 1-2 hours. At this temperature, 5-10 times the molar equivalent of TiCl4 and 10-15 times the molar equivalent of an organic base were added in sequence. After reacting for 2-3 hours, 15-30 times the molar equivalent of BF3·Et2O was added. After the reaction was completed, the temperature was cooled to room temperature. Water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic phases were combined. The solvent was removed by rotary evaporation, and the crude product was separated and purified by column chromatography to obtain PzDP-PPAB.

4. The method for preparing the compound according to claim 3, wherein the organic base in step (1) is triethylamine, dimethylamine, or diethylamine, preferably triethylamine.

5. The method for preparing the compound according to claim 3, wherein the organic base in step (3) is triethylamine, dimethylamine, trimethylamine, or diethylamine, preferably triethylamine.

6. The use of the compound according to claim 1, characterized in that: Hydrazine and hypochlorite can be detected and differentiated in organic solvents.

7. The use of the compound according to claim 6, characterized in that: The concentration of the compound was 10 μmol / L, the detection limit of hydrazine was 0.04 μmol / L, and the detection limit of hypochlorite was 0.059 μmol / L.

8. The use of the compound according to claim 6, characterized in that: The solvent is 1,4-dioxane.

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