A camphor-based benzothiazole ratiometric fluorescent probe for the detection of hydrazine, its preparation method and application

Abstract

This invention discloses a camphor-based benzothiazole ratiometric fluorescent probe for detecting hydrazine, its preparation method, and its application. The fluorescent probe is 3-(benzothiazole-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate. Starting with camphor, it first undergoes an aldol condensation reaction with 5-bromosalicylic acid; subsequently, a hexamethylenetetramine formylation reaction yields the corresponding benzaldehyde derivative; then, a coupling reaction with 4-morpholinophenylboronic acid forms a biphenyl structure; next, a coupling cyclization reaction with 2-aminothiophenol constructs a benzothiazole structure; finally, an acetyl chloride substitution reaction yields the target fluorescent probe. This compound exhibits a specific reaction with hydrazine, causing a redshift in fluorescence emission wavelength from 506 nm to 613 nm, thereby achieving sensitive detection of hydrazine in solution. This probe has advantages such as good selectivity, low detection limit, and strong anti-interference ability, and has good application prospects in the fields of environmental monitoring and chemical analysis.

Description

Technical Field

[0001] This invention belongs to the field of fine organic synthesis technology, and relates to a camphor-based benzothiazole ratiometric fluorescent probe for detecting hydrazine, its preparation method and application. Background Technology

[0002] Hydrazine is a toxic, teratogenic, and carcinogenic substance that threatens not only human health but also ecosystems and wildlife. Improper disposal of hydrazine waste can lead to its entry into waterways, seeping into soil and ecosystems, causing environmental pollution. Excessive hydrazine in the environment can cause crop leaves to wither, inhibit seedling growth, and harm agricultural production. It can also enter the animal body through the food chain, increasing oxidative stress, leading to lipid peroxidation and the formation of reactive oxygen species, ultimately damaging proteins. For humans, hydrazine can enter the body through the mouth and skin. Short-term exposure can cause skin irritation, while long-term exposure can cause metabolic disorders, liver damage, and other organ dysfunctions, and even increase the risk of cancer. Therefore, developing a simple and effective method for detecting hydrazine in the environment is of great significance.

[0003] Currently, methods for detecting hydrazine mainly include chromatography, Raman spectroscopy, colorimetry, mass spectrometry, and electrochemical methods. Compared with these traditional detection methods, fluorescent probes are favored due to their simple synthesis, good selectivity, and high sensitivity. Using camphor as a raw material, a camphor-based benzothiazole ratiometric fluorescent probe for hydrazine, 3-(benzothiazole-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester, was synthesized through aldol condensation, formylation, coupling, coupling cyclization, and substitution reactions. No relevant reports have been published yet. Summary of the Invention

[0004] To address the shortcomings of existing technologies, another technical problem this invention aims to solve is to provide a method for preparing 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester. A further technical problem this invention aims to solve is to provide an application of the above-mentioned 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester.

[0005] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows:

[0006] A camphor-based benzothiazole ratiometric fluorescent probe for the detection of hydrazine is 3-(benzothiazole-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate, with the following structural formula:

[0007]

[0008] The method for preparing a camphor-based benzothiazole ratiometric fluorescent probe for detecting hydrazine includes the following steps:

[0009] 1) Camphor undergoes an aldol condensation reaction with 5-bromosalicylaldehyde to give 3-(5-bromo-2-hydroxybenzylmethyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one;

[0010] 2) 3-(5-bromo-2-hydroxybenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was formylated with hexamethylenetetramine to give 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde;

[0011] 3) 5-Bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde was coupled with 4-morpholinophenylboronic acid to give 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde;

[0012] 4) 4-Hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,11-biphenyl]-3-carboxaldehyde undergoes a coupled cyclization reaction with 2-aminobenzylthiophenol to yield 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one;

[0013] 5) 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was substituted with acetyl chloride to give 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester.

[0014] In step 1), camphor undergoes an aldol condensation reaction with 5-bromosalicylic acid to obtain 3-(5-bromo-2-hydroxybenzylmethyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one. The specific preparation steps are as follows:

[0015] 1) Add 0.10-0.15 mol camphor, 0.12-0.14 mol 5-bromosalicylic acid aldehyde, 0.30-0.35 mol potassium tert-butoxide, and 20-25 mL tert-butanol sequentially into a round-bottom flask and react at 80-90℃ for 2-5 h.

[0016] 2) After distillation to recover the solvent from the reaction solution, the crude product 3-(5-bromo-2-hydroxybenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was obtained;

[0017] 3) The crude product of 3-(5-bromo-2-hydroxybenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was extracted with ethyl acetate and recrystallized with methanol to obtain a white powder of 3-(5-bromo-2-hydroxybenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one.

[0018] In step 2), 3-(5-bromo-2-hydroxybenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one undergoes a formylation reaction with hexamethylenetetramine to obtain 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde. The specific preparation steps are as follows:

[0019] 1) Add 0.10–0.15 mol of 3-(5-bromo-2-hydroxybenzylmethyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one, 0.20–0.30 mol of hexamethylenetetramine, and 10–15 mL of trifluoroacetic acid sequentially to a round-bottom flask and react at 88–92 °C for 10–14 h.

[0020] 2) After distillation to recover the solvent from the reaction solution, crude product 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde was obtained;

[0021] 3) The crude product of 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 30:1) to obtain a yellow powder of 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde.

[0022] In step 3), 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde undergoes a coupling reaction with 4-morpholinophenylboronic acid to obtain 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde. The specific preparation steps are as follows:

[0023] 1) Add 0.10–0.15 mol of 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde, 0.12–0.25 mol of 4-morpholinophenylboronic acid, 0.25–0.30 mol of potassium carbonate, 0.01–0.02 mol of tetrakis(triphenylphosphine)palladium, and 20–25 mL of mixed solvent (1,4-dioxane / water = 5:1) sequentially to a round-bottom flask and react at 88–92 °C for 8–12 h;

[0024] 2) After distillation to recover the solvent from the reaction solution, crude product 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde was obtained;

[0025] 3) The crude product of 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 20:1) to obtain a yellow powder of 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde.

[0026] In step 4), 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde undergoes a coupled cyclization reaction with 2-aminobenzylthiophenol to obtain 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one. The specific preparation steps are as follows:

[0027] 1) Add 0.10–0.15 mol of 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde, 0.15–0.20 mol of 2-aminobenzylthiophenol, 0.15–0.20 mol of sodium metabisulfite, and 5–6 mL of N,N-dimethylformamide sequentially to a round-bottom flask and react at 108–112 °C for 2–4 h.

[0028] 2) After distillation to recover the solvent from the reaction solution, the crude product 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was obtained;

[0029] 3) The crude product of 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 20:1) to obtain a yellow powder 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one.

[0030] In step 5), 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one undergoes a substitution reaction with acetyl chloride to obtain 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester. The specific preparation steps are as follows:

[0031] 1) Add 0.10–0.15 mol of 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one, 0.15–0.20 mol of acetyl chloride, 0.15–0.20 mol of pyridine, and 20–25 mL of anhydrous dichloromethane sequentially to a round-bottom flask, and react at 20–30 °C for 0.5–1.5 h;

[0032] 2) After distillation to recover the solvent from the reaction solution, the crude product of 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester was obtained.

[0033] 3) 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1 ′ Biphenyl-4-acetic acid ester was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 20:1) to obtain a yellow powder 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester.

[0034] The compound 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate specifically recognizes hydrazine, with its fluorescence emission wavelength red-shifted from 506 nm to 613 nm. This compound can sensitively detect the concentration of hydrazine in solution within a detection range of 0–100 μM, with a detection limit as low as 3.3 × 10⁻⁶ μM. -8 mol / L.

[0035] Beneficial effects: Compared with the prior art, the present invention uses camphor as a raw material, reacts with 5-bromosalicylaldehyde in an aldol condensation reaction to obtain 3-(5-bromo-2-hydroxybenzylmethyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one, then reacts with hexamethylenetetramine in a formylation reaction to obtain 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde, and then reacts with 4-morpholinophenylboronic acid in a coupling reaction to obtain 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde. [1]Heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde, followed by a coupled cyclization reaction with 2-aminothiophenol to yield 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one, which is then substituted with acetyl chloride to give 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester. This compound can specifically recognize hydrazine and sensitively detect the concentration of hydrazine in solution. It can be used as a ratiometric fluorescent probe for the detection of hydrazine, with advantages such as low detection limit, good selectivity, and strong anti-interference ability, showing good application prospects. Attached Figure Description

[0036] Figure 1The fluorescence spectra of 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate reacting with hydrazine of different concentrations are shown.

[0037] Figure 2 The fluorescence intensity ratio (IL) of 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate after reaction with different analytes is shown in Figure 1. 613nm / I 506nm )picture. Detailed Implementation

[0038] The present invention will be further described below with reference to specific embodiments.

[0039] Example 1

[0040] The preparation of compound 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate is shown in the following reaction formula:

[0041]

[0042] The specific steps are as follows:

[0043] (1) Preparation of 3-(5-bromo-2-hydroxybenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one:

[0044] 0.10 mol camphor, 0.12 mol 5-bromosalicylic acid, 0.30 mol potassium tert-butoxide, and 20 mL tert-butanol were added sequentially to a round-bottom flask and reacted at 88 °C for 3 h. After distillation to recover the solvent, crude product 3-(5-bromo-2-hydroxybenzylmethyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was obtained. After extraction with ethyl acetate, the product was recrystallized with methanol to obtain white powder 3-(5-bromo-2-hydroxybenzylmethyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one. 1H NMR (600MHz, CDCl3) δ: 7.79 (s, 1H), 7.60 (d, J=2.4Hz, 1H), 7.45 (dd, J=8.6, 2.4Hz, 1H), 7.39 (s, 1H), 6.99 (d, J=8.6Hz, 1H), 3.1 7 (d, J=4.2Hz, 1H), 2.32 (tt, J=10.6, 4.1Hz, 1H), 2.00-1.91 (m, 1H), 1.74-1.60 (m, 2H), 1.18 (s, 3H), 1.15 (s, 3H), 0.95 (s, 3H).

[0045] (2) Preparation of 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde:

[0046] 0.10 mol of 3-(5-bromo-2-hydroxybenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one, 0.20 mol of hexamethylenetetramine, and 10 mL of trifluoroacetic acid were added sequentially to a round-bottom flask and reacted at 90 °C for 12 h. After distillation to recover the solvent, crude product 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde was obtained. After chromatography on a silica gel column (petroleum ether: ethyl acetate = 30:1), yellow powder 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde was obtained. 1 H NMR (600MHz, DMSO-d6) δ: 11.47 (s, 1H), 10.29 (s, 1H), 8.17 (d, J=2.5Hz, 1H), 7 .91 (d, J=2.5Hz, 1H), 7.48 (s, 1H), 3.21 (d, J=4.2Hz, 1H), 2.39 (tt, J=11.9, 4.6 Hz, 1H), 2.02 (ddd, J=13.2, 11.5, 3.9Hz, 1H), 1.73 (ddd, J=12.6, 9.2, 3.9Hz, 1 H), 1.61 (ddd, J=13.7, 9.2, 4.7Hz, 1H), 1.20 (s, 3H), 1.16 (s, 3H), 0.95 (s, 3H).

[0047] (3) Preparation of 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde:

[0048] 0.10 mol of 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde, 0.12 mol 4-Morpholinylbenzeneboronic acid, 0.25 mol potassium carbonate, 0.01 mol tetra(triphenylphosphine)palladium, and 24 mL of mixed solvent (1,4-dioxane / water = 5:1) were sequentially added to a round-bottom flask and reacted at 90 °C for 8 h. After distillation to recover the solvent, crude product 4-hydroxy-4′-morpholinyl-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde was obtained. After chromatography on a silica gel column (petroleum ether: ethyl acetate = 20:1), yellow powder 4-hydroxy-4′-morpholinyl-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde was obtained. 1 H NMR (600MHz, DMSO-d6) δ: 11.43 (s, 1H), 10.35 (s, 1H), 8.29-8.24 (m, 1H), 8.04 (d, J=2.3Hz, 1H), 7.76 (d, J=8.3Hz, 2H), 7.59 (s, 1H), 7.28 (d, J=8.4Hz, 2H), 3.97 (t, J=4.8Hz, 4H), 3.38 (t, J=4.9 Hz, 4H), 3.25 (d, J=4.2Hz, 1H), 2.40 (tt, J=11.3, 4.5Hz, 1H), 2.07-1.98 (m, 1H), 1.81 (ddd, J=12 .6, 9.4, 3.9Hz, 1H), 1.62 (ddd, J=13.7, 9.2, 4.6Hz, 1H), 1.19 (s, 3H), 1.15 (s, 3H), 0.95 (s, 3H).

[0049] (4) Preparation of 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one:

[0050] 0.10 mol of 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde, 0.15 mol 2-Aminothiophenol, 0.15 mol sodium metabisulfite, and 5 mL N,N-dimethylformamide were added sequentially to a round-bottom flask and reacted at 110 °C for 3 h. After distillation to recover the solvent, the crude product 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was obtained. After chromatography on a silica gel column (petroleum ether: ethyl acetate = 20:1), a yellow powder 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was obtained. 1 H NMR (600MHz, DMSO-d6) δ: 12.78 (s, 1H), 8.22 (d, J=8.0Hz, 1H), 8.14 (d, J=8.2Hz, 1H), 8.03 (s, 1H), 7.7 1 (d, J=2.2Hz, 1H), 7.65-7.49 (m, 5H), 7.09 (d, J=8.4Hz, 2H), 3.77 (t, J=4.8Hz, 4H), 3.18 (dd, J=6.0, 3 .6Hz, 4H), 3.09 (d, J=4.2Hz, 1H), 2.20 (td, J=11.6, 5.9Hz, 1H), 1.83 (td, J=13.2, 12.5, 3.8Hz, 1H), 1. 63 (ddd, J=12.5, 9.2, 3.9Hz, 1H), 1.43 (td, J=9.2, 4.9Hz, 1H), 0.99 (s, 3H), 0.96 (s, 3H), 0.77 (s, 3H).

[0051] (5) Preparation of 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester:

[0052] 0.10 mol of 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one, 0.15 mol of acetyl chloride, 0.15 mol of pyridine, and 20 mL of anhydrous dichloromethane were sequentially added to a round-bottom flask and reacted at 25 °C for 1 h. After distillation to recover the solvent, 3-(benzothiazol-2-yl)-4′- The crude product of methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate was further subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 20:1) to obtain a yellow powder of 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate. 1 H NMR (600MHz, DMSO-d6) δ: 8.41 (d, J=2.2Hz, 1H), 8.20 (dd, J=7.8, 1.1Hz, 1H), 8.16 (dt, J=8.2, 0.9Hz, 1H), 7.75 (d, J=2.3 Hz, 1H), 7.66 (d, J=8.8Hz, 2H), 7.61 (ddd, J=8.3, 7.1, 1.3Hz, 1H), 7.53 (ddd, J=8.2, 7.1, 1.2Hz, 1H), 7.12 (dd, J=9.3, 2.3 Hz, 3H), 3.80-3.76 (m, 4H), 3.21 (dd, J=5.8, 4.0Hz, 4H), 3.02 (d, J=4.2Hz, 1H), 2.48 (s, 3H), 2.19 (dq, J=11.1, 6.0, 4.6H z, 1H), 1.84 (ddd, J=15.0, 11.8, 4.1Hz, 1H), 1.64 (d, J=11.1Hz, 1H), 1.40 (s, 1H), 0.98 (s, 3H), 0.96 (s, 3H), 0.73 (s, 3H).

[0053] Example 2

[0054] 3-(benzothiazo-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate was formulated into a 2×10 -5 A solution of M (pH = 7.4, THF / PBS = 6 / 4) was prepared by dissolving 10M hydrazine in distilled water to obtain concentrations of 0.1×10⁻⁶. -5 2×10 -5 3×10 -5 4×10 -5 5×10-5 6×10 -5 7×10 -5 8×10 -5 9×10 -5 10×10 -5 The solution of M. Fluorescence emission spectra of 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate were measured on a fluorescence spectrophotometer at different concentrations using fluorescence spectrophotometric titration. Figure 1 As shown, the results indicate that with increasing hydrazine concentration in the solution, the fluorescence intensity of 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate at 506 nm gradually decreases, while the fluorescence intensity at 613 nm continuously increases. This suggests that this compound can serve as a ratiometric fluorescent probe for sensitive detection of hydrazine concentration.

[0055] Example 3

[0056] The compound 3-(benzothiazo-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate was formulated into a 2×10 -5 A solution of M (pH = 7.4, DMSO / PBS = 6 / 4) was prepared, and different metal ions, anions, amino acids, and other analytes were dissolved in PBS buffer to prepare a solution with a concentration of 2.0 × 10⁻⁶. -4 The solution of M was analyzed by fluorescence spectrophotometry using a fluorescence spectrophotometer. The fluorescence intensity ratio (IL) of different analytes present in 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate was measured. 613nm / I 506nm ),like Figure 2 As shown. Only the addition of hydrazine resulted in the fluorescence intensity of 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate being higher than that of (I0.05). 613nm / I 506nm The concentration of ) increased significantly, while the addition of metal ions (Ca) significantly increased the concentration of ) and the concentration of ) increased significantly. 2+ Hg 2+ Na + Cu 2+ Zn 2+ K + Al 2+ Mn2+ ), anions (CO3) 2- HS - SO4 2- NO3 - H3PO4 2- HSO3 - ,ClO - , Br - The fluorescence intensity of this compound was compared with that of different analytes such as amino acids (Trp, Gly, Val, Leu, Thr, Lea) to determine the fluorescence intensity ratio (I0.05). 613nm / I 506nm No significant changes were observed. This indicates that the compound can serve as a ratiometric fluorescent probe for the specific detection of hydrazine.

Claims

1. A camphor-based benzothiazole ratiometric fluorescent probe for detecting hydrazine, characterized in that, Its structural formula is:

2. The method for preparing the camphor-based benzothiazole ratiometric fluorescent probe for detecting hydrazine according to claim 1, comprising the following steps: 1) Camphor undergoes an aldol condensation reaction with 5-bromosalicylaldehyde to give 3-(5-bromo-2-hydroxybenzylmethyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one; 2) 3-(5-bromo-2-hydroxybenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one undergoes formylation with hexamethylenetetramine to give 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[ 2.2.1] Heptane-2-ethylene)methyl)benzaldehyde; 3) 5-Bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[ 2.2.1] Heptane-2-yl)methyl)benzaldehyde undergoes a coupling reaction with 4-morpholinophenylboronic acid to give 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[ 2.2.1]Heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde; 4) 4-Hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[ 2.2.1]Heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde undergoes a coupled cyclization reaction with 2-aminothiophenol to give 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one; 5) 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was substituted with acetyl chloride to give 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester.

3. The method for preparing a camphor-based benzothiazole ratiometric fluorescent probe for detecting hydrazine according to claim 2, characterized in that, Step 1), under potassium tert-butoxide catalysis, camphor undergoes an aldol condensation reaction with 5-bromosalicylaldehyde to obtain 3-(5-bromo-2-hydroxybenzylmethyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one. The specific preparation method includes: 1) Add 0.10-0.15 mol camphor, 0.12-0.14 mol 5-bromosalicylic acid aldehyde, 0.30-0.35 mol potassium tert-butoxide, and 20-25 mL tert-butanol sequentially into a round-bottom flask and react at 80-90℃ for 2-5 h; 2) After distillation to recover the solvent from the reaction solution, the crude product 3-(5-bromo-2-hydroxybenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was obtained; 3) The crude product of 3-(5-bromo-2-hydroxybenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was extracted with ethyl acetate and recrystallized with methanol to obtain a white powder of 3-(5-bromo-2-hydroxybenzyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one.

4. The method for preparing a camphor-based benzothiazole ratiometric fluorescent probe for detecting hydrazine according to claim 2, characterized in that, Step 2), under the catalysis of trifluoroacetic acid, 3-(5-bromo-2-hydroxybenzylmethyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one undergoes a formylation reaction with hexamethylenetetramine to give 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[ 2.2.1] Heptane-2-yl)methyl)benzaldehyde, the specific preparation method includes: 1) Add 0.10–0.15 mol of 3-(5-bromo-2-hydroxybenzylmethyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one, 0.20–0.30 mol of hexamethylenetetramine, and 10–15 mL of trifluoroacetic acid sequentially to a round-bottom flask and react at 88–92 °C for 10–14 h. 2) After distillation to recover the solvent from the reaction solution, 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[ 2.2.1] Crude product of heptane-2-yl)methyl)benzaldehyde; 3) 5-Bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[ 2.2.1] The crude product of heptane-2-yl)methyl)benzaldehyde was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 30:1) to obtain a yellow powder, 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[ 2.2.1] Heptane-2-yl)methyl)benzaldehyde.

5. The method for preparing a camphor-based benzothiazole ratiometric fluorescent probe for detecting hydrazine according to claim 2, characterized in that, in step 3), under tetrakis(triphenylphosphine)palladium catalysis, 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)benzaldehyde undergoes a coupling reaction with 4-morpholinophenylboronic acid to obtain 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde, the specific preparation method including: 1) Add 0.10–0.15 mol of 5-bromo-2-hydroxy-3-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-yl)methyl)benzaldehyde, 0.12–0.25 mol of 4-morpholinophenylboronic acid, 0.25–0.30 mol of potassium carbonate, 0.01–0.02 mol of tetrakis(triphenylphosphine)palladium, and 20–25 mL of mixed solvent (1,4-dioxane / water = 5:1) sequentially to a round-bottom flask and react at 88–92 °C for 8–12 h; 2) After distillation to recover the solvent from the reaction solution, crude product 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde was obtained; 3) The crude product of 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 20:1) to obtain a yellow powder of 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde.

6. The method for preparing a camphor-based benzothiazole ratiometric fluorescent probe for detecting hydrazine according to claim 2, characterized in that, in step 4), under the catalysis of sodium metabisulfite, 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde undergoes a coupled cyclization reaction with 2-aminobenzylthiophenol to obtain 3-((5-(benzothiazole-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one, the specific preparation method including: 1) Add 0.10–0.15 mol of 4-hydroxy-4′-morpholino-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2-ylidene)methyl)-[1,1′-biphenyl]-3-carboxaldehyde, 0.15–0.20 mol of 2-aminobenzylthiophenol, 0.15–0.20 mol of sodium metabisulfite, and 5–6 mL of N,N-dimethylformamide sequentially to a round-bottom flask and react at 108–112 °C for 2–4 h. 2) After distillation to recover the solvent from the reaction solution, the crude product 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was obtained; 3) The crude product of 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 20:1) to obtain a yellow powder 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one.

7. The method for preparing a camphor-based benzothiazole ratiometric fluorescent probe for detecting hydrazine according to claim 2, characterized in that, Step 5): Under pyridine catalysis, 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one undergoes a substitution reaction with acetyl chloride to give 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester. Specific preparation methods include: 1) Add 0.10–0.15 mol of 3-((5-(benzothiazol-2-yl)-4-hydroxy-4′-morpholino-[1,1′-biphenyl]-3-yl)methylene)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-one, 0.15–0.20 mol of acetyl chloride, 0.15–0.20 mol of pyridine, and 20–25 mL of anhydrous dichloromethane sequentially to a round-bottom flask, and react at 20–30 °C for 0.5–1.5 h; 2) After distillation to recover the solvent from the reaction solution, the crude product of 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester was obtained. 3) After chromatography on a silica gel column (petroleum ether: ethyl acetate = 20:1), 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetic acid ester was obtained as a yellow powder.

8. The application of the camphor-based benzothiazole ratiometric fluorescent probe 3-(benzothiazole-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate as described in claim 1 in the detection of hydrazine.

9. The application according to claim 8, characterized in that, 3-(benzothiazol-2-yl)-4′-methoxy-5-((4,7,7-trimethyl-3-oxo-3-cyclohexylcyclopentenyl)methyl)-1,1′-biphenyl-4-acetate specifically reacts with hydrazine, red-shifting the fluorescence emission wavelength from 506 nm to 613 nm. It can also detect the concentration of hydrazine in solution within a range of 0–100 μM, with a detection limit as low as 3.3 × 10⁻⁶ μM. -8 mol / L.

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