An organic small-molecule compound capable of differentiating detection of hydrazine and hypochlorite and a preparation method thereof

Abstract

The application discloses a kind of distinguishable detection hydrazine and hypochlorite organic small molecule compound and its preparation method and application.By diketopyrrolopyrazole and nitrogen-containing aromatic primary amine condensation reaction, coordination with BF3.Et2O obtains the PzDP-PPAB compound with electronic push-pull effect, and its maximum absorption peak and emission peak are located in near infrared region.PzDP-PPAB and hydrazine and hypochlorite carry out irreversible chemical reaction in organic solvent, and the distinguishable detection of two kinds of substances can be realized, the detection limit of hydrazine is 0.04 μmol / L, and the detection limit of hypochlorite is 0.059 μmol / L, with simple operation, reaction sensitivity, naked eye detection and the like.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic small molecule fluorescent probes, and relates to an organic small molecule compound capable of distinguishing detection of hydrazine and hypochlorite and a preparation method thereof. BACKGROUND

[0002] Hydrazine (N2H4) is widely used in chemical synthesis, fuel and pharmaceutical fields as a key reducing agent, developing agent and fuel component. However, its high toxicity poses a significant risk to the skin, mucous membranes and central nervous system, and may even have carcinogenic effects. Therefore, strict safety procedures must be followed during its production, storage and use. Hypochlorite (ClO-) is commonly found in hypochlorous acid and hypochlorite salts, and is a strong oxidizing agent that plays an important role in disinfection, bleaching and water treatment, but 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 detection methods for N2H4 and ClO-.

[0003] Small molecule fluorescent probes have high efficiency, rapidness, good sensitivity, high selectivity, good biocompatibility and other advantages, and have broad application prospects in various fields such as biology, chemistry, medicine and environmental protection. Based on the nucleophilicity and reducing property of hydrazine, fluorescent probes for detecting hydrazine through deprotection, cyclization and ring-opening reaction have been reported. In addition, based on the oxidizing property of ClO-, some fluorescent probes through carbon-carbon double bond cleavage, oxidation of sulfur / selenium compounds, oxidative hydrolysis of oxime or hydrazide 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 detection; more importantly, at present, single fluorescent probes are used to detect single compounds, and there is no report on the simultaneous detection of N2H4 and ClO- by a single fluorescent probe. SUMMARY

[0004] The purpose of the present application is to provide a fluorescent probe with high sensitivity for distinguishing detection of N2H4 and ClO-, solving the problem that there is no single fluorescent probe for simultaneous detection of N2H4 and ClO- at present. The present application provides a novel pyrazine-fused diaza BODIPY compound, which improves the reaction rate of the diaza BODIPY ring to N2H4 and ClO- by the strong electron-withdrawing pyrazine ring, and modifies the trimethylsilyl group to extend the conjugation length of the compound, making the absorption and emission wavelength red-shifted. The addition of N2H4 and ClO - causes a significant color change and significant ratio fluorescence behavior of the compound, which is beneficial for naked-eye detection. The structural formula of the pyrazine-fused diaza BODIPY compound is:

[0005]

[0006] The present application also provides a preparation method of the pyrazine-fused diazabodipy compound, and a preparation flow thereof is as follows:

[0007]

[0008] The preparation method comprises the following steps:

[0009] (1) Ethyl 4-bromophenylglyoxylate and 1,4-diacetyl piperazine-2,5-dione are dissolved in an organic base in a molar ratio of 2-4:1, and the mixed system is stirred at 55-60°C for 7-9 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 an intermediate 1.

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

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

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

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

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

[0015] Figure 1 The hydrogen spectrum of the example PzDP-PPAB.

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

[0017] Figure 3 UV-Vis spectra of PzDP-PPAB with hydrazine hydrate, hypochlorite and other substances.

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

[0019] Figure 5 Fluorescence spectra of PzDP-PPAB with different concentrations of hypochlorite.

[0020] Figure 6 Absorbance changes of PzDP-PPAB at 627 nm after adding different concentrations of hypochlorite.

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

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

[0023] Figure 9 Absorbance changes of PzDP-PPAB at 627 nm after adding different concentrations of hydrazine hydrate. DETAILED DESCRIPTION

[0024] The specific implementation of the present application will be further described below in combination with examples, but the scope of protection claimed by the present application is not limited to the scope expressed by the examples. The percentages in brackets below are all yields without special instructions.

[0025] Example

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

[0027]

[0028] (1) In a 100 mL round-bottom flask, compound 1 (34.0 g, 132 mmol) and compound 2 (11.38 g, 57.5 mmol) and triethylamine (34 mL) were added, and the mixed system was stirred at 55-60°C for 8.5 hours. After the raw material was completely consumed, the triethylamine was removed by distillation under reduced pressure to obtain a 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 (400 MHz, CDC13): 11.75 (s, 2H), 7.50-7.47 (m, 4H), 7.02-6.98 (m, 4H), 4.17 (q, J = 7.17 Hz, 4H), 1.15 (t, J = 7.17 Hz, 6H).

[0029]

[0030] (2) In a 100 mL round bottom flask, compound 3 (20.0 g, 33 mmol) and formamide (100 mL) were added, 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, and a solid was precipitated, 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 reaction due to poor solubility.

[0031]

[0032] (5) In a 100 mL round bottom flask, compound 4 (100 mg, 0.2 mmol) and heavy toluene (20 mL) were added, 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, and 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 etherate (440 mg, 3.1 mmol) was added to the mixture, and stirring was continued at this temperature for 1.5 hours, and the reaction was monitored using thin layer chromatography. After the reaction was completed, the reaction was quenched with water, and extraction was performed with a water-dichloromethane system, the combined organic extract was dried with anhydrous Na2SO4, filtered, concentrated in vacuo, and purified using column chromatography (eluent: petroleum ether:dichloromethane = 2:1) to obtain a blue solid PzDP-PPAB (yield: 39 mg, 21%)1H NMR, mass spectrum were shown in Figure 1 and Figure 2 1 H NMR (400 MHz, CDC13) δ 8.66 (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] + calcd 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, n-butylamine solution, UV-visible spectrum 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 - (0-1.2mM), 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 blue shift of 257nm 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 the concentration, a new peak appeared at 525 nm and the intensity gradually increased, leading to "turning on" of fluorescence, as shown in Fig. 3. Figure 5

[0036] (3) The lowest detection limit (LOD) of ClO - : The absorbance of PzDP-PPAB at 627 nm corresponding to the concentration of N2H4 in the range of 0-50 μM was linearly fitted, and the linear fitting equation Y = 2030.87X + 0.527 was obtained, with the fitting constant R 2 = 0.995. The calculated lowest detection limit of PzDP-PPAB for ClO - was 0.059 μM, as shown in Fig. 3. Figure 6

[0037] (4) Detection of hydrazine: After different concentrations of N2H4 (0-1.2 mM) were added to the dioxane solution of PzDP-PPAB, the UV-Vis absorption spectrum and the fluorescence emission spectrum of PzDP-PPAB molecule changed obviously. In terms of the UV-Vis absorption spectrum, with the gradual increase of the concentration of added N2H4 to 1.2 mM, the absorption peaks of PzDP-PPAB at 627 nm, 597 nm and 471 nm gradually decreased and disappeared, while a new absorption peak appeared at 389 nm and gradually increased, and a blue shift of 238 nm occurred between the maximum absorption peak and the new absorption peak, which was conducive to naked-eye detection, as shown in Fig. 4. Figure 7 In terms of the fluorescence emission spectrum, PzDP-PPAB did not emit fluorescence, but with the increase of the concentration of added ClO - , a new peak appeared at 560 nm and the intensity gradually increased, leading to "turning on" of fluorescence, as shown in Fig. 5. Figure 8 Figure 4 5 Figure 7 8 It can be seen that PzDP-PPAB probe molecule produced different UV and fluorescence changes in the presence of hydrazine and ClO - , and the two can be distinguished and detected.

[0038] (5) The lowest detection limit (LOD) of N2H4: the emission value of PzDP-PPAB at 627 nm corresponding to the concentration of N2H4 in the range of 0-50 μM was linearly fitted, and the linear fitting equation Y = 4809.5X + 0.5115 was obtained, with the fitting constant R 2 = 0.9927. The calculated lowest detection limit of PzDP-PPAB for N2H4 was 0.04 μM, as shown in Fig. 6. Figure 9 In summary, any modification, equivalent replacement and improvement within the spirit and principles of the present application shall be included in the protection scope of the present application.​​​​​​

Claims

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

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

3. The method for preparing the compound according to claim 2, wherein The steps include: (1) Ethyl 4-bromophenylglyoxylate and 1,4-diacetylpiperazine-2,5-dione are dissolved in an organic base at a molar ratio of 2 to 4:

1. The mixture 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. The resulting 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. After the solid is precipitated, it is filtered and the filter cake is washed with cold methanol 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, rotary evaporated, and the solvent was removed. 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.

5. The organic base according to claim 4, preferably triethylamine.

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

7. The organic base according to claim 6, preferably triethylamine.

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

9. The use of the compound according to claim 8, 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.

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

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