A red-light bopyin heterocyclic compound and its application

Abstract

This invention discloses a red-emitting bopyin heterocyclic compound and its application. The dye is prepared from a seven-membered fluoroborane dipyrrole derivative and a para-derivative of benzaldehyde via a piperidine- and acetic acid-catalyzed condensation reaction. The synthesis method is simple, separation and purification are convenient, and the yield is high. The introduction of aromatic ring substituents increases molecular conjugation, red-shifting the absorption and emission spectra, enabling monitoring of viscosity changes in mixed solutions.

Description

Technical Field

[0001] The present invention relates to a bopyin heterocyclic compound, and more specifically to a red-light bopyin heterocyclic compound and application thereof. Background Art

[0002] To date, the methods and instruments for measuring viscosity that have been developed and utilized include capillary viscometers, falling ball viscometers, and rotational viscometers. Capillary viscometers, with their simple principle and high measurement accuracy, are widely used in industries such as textiles, chemicals, and defense. Traditional capillary viscometers suffer from low efficiency and large detection errors. Rotational viscometers are suitable for all fluids, including Newtonian and non-Newtonian fluids, and offer fast, convenient, and highly accurate measurements. However, these methods require extensive hardware, are complex in structure, and are expensive, limiting their practical application. In summary, these methods have significant limitations when applied to small samples or for real-time detection of local viscosity. However, methods using fluorescent probes can effectively avoid these drawbacks, offer high spatial and temporal resolution, and can also perform tissue or cell imaging.

[0003] To address these issues, the present invention describes a red-emitting bopyin heterocyclic compound fluorescent probe, which can be used to detect viscosity in mixed solutions, determine glucose concentration, monitor viscosity changes during polymerization, and measure viscosity in cells or mitochondria. It offers advantages such as ease of detection, high sensitivity, and a wide detection range. Summary of the Invention

[0004] The main purpose of the present invention is to provide a red-light bopyin heterocyclic compound and its application. The technical solution of the present invention is as follows:

[0005] A red-light bopyin heterocyclic compound and its application, the chemical structural formula of the compound is:

[0006]

[0007] Wherein, the substituent R1 is any one selected from fluorine, chlorine, and bromine, and the substituent R2 is any one selected from diphenylamino and cyano. As a preferred embodiment, the chemical structure of the compound is:

[0008]

[0009] Any one of .

[0010] The synthesis method of the red-light bopyin heterocyclic compound comprises the following synthesis path:

[0011]

[0012] The method comprises the following steps:

[0013] (1) Add compound 1 and toluene to a reaction flask at room temperature, stir to dissolve, then add compound 2, piperidine, and acetic acid, and heat under reflux to obtain a reaction solution;

[0014] (2) The reaction solution in step (1) was subjected to rotary evaporation and then separated by silica gel column chromatography to obtain product I.

[0015] The compound 1 is a seven-membered fluoroborane dipyrrole compound, and the compound 2 is a para-derivative of benzaldehyde; the feeding molar ratio of the compound 1 to the compound 2 is 1:1-10.

[0016] The order of adding the materials in step (1) is compound 1, toluene, compound 2, piperidine, and acetic acid. Piperidine and acetic acid both act as activating reactants and need to be added last. The feeding ratio of compound 1 to piperidine is 1:1-10; the feeding ratio of compound 1 to acetic acid is 1:1-10.

[0017] The heating temperature of step (1) is 30 to 150° C., and the heating time is 2 to 18 hours.

[0018] The beneficial effects of the present invention are as follows:

[0019] (1) The compound of the present invention has a certain response to viscosity. The fluorescence of the compound itself is weak, but as the viscosity increases, the fluorescence gradually increases, and the maximum fluorescence enhancement to viscosity is 3.8 to 17.5 times, which improves the imaging contrast of viscosity monitoring.

[0020] (2) The preparation method of the red-light bopyin heterocyclic compound viscosity probe of the present invention is simple, the synthesized viscosity probe has good water solubility, and is sensitive to viscosity in a mixed solution of DMF and glycerol.

[0021] (3) The synthesis reaction conditions of the present invention are easy to control, the product purification is simple, and it has universal applicability. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is the hydrogen spectrum of compound I-1 obtained in Example 1.

[0023] Figure 2 This is the hydrogen spectrum of compound I-2 obtained in Example 8.

[0024] Figure 3 Graph showing the fluorescence spectra of compound I-1 obtained in Example 1 in DMF-glycerol mixtures of different proportions.

[0025] Figure 4 is the fluorescence intensity logI of compound I-1 obtained in Example 1 737nm Linear relationship with logη.

[0026] Figure 5 Graph showing the fluorescence spectra of compound I-2 obtained in Example 8 in DMF-glycerol mixtures of different proportions.

[0027] Figure 6 is the fluorescence intensity logI of compound I-2 obtained in Example 8 636nm Linear relationship with logη. DETAILED DESCRIPTION

[0028] The present invention is further described below with reference to the following examples. However, the scope of protection claimed in the present invention is not limited to the scope described in the examples.

[0029] Example 1

[0030] Weigh compound 1 (376 mg, 1 mmol) of heptafluoroborane dipyrrole and dissolve it in 30.00 mL of toluene. Then add 4-diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) in sequence. Heat and stir at 90 ° C for 8 hours until the reaction is complete. The reactant is rotary evaporated and purified by column chromatography to obtain a purple-red solid I-1 (198.8 mg) with a yield of 31.5%.

[0031]

[0032] Example 2

[0033] Compound 1 (376 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-Diphenylaminobenzaldehyde (546 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was stirred at 90°C for 8 hours until complete. The reaction mixture was rotary evaporated and purified by column chromatography to obtain a purple-red solid I-1 (361.6 mg) with a yield of 57.3%. When the amount of 4-cyanobenzaldehyde was doubled compared to Example 1, the yield increased by 25.8%.

[0034]

[0035] Example 3

[0036] Compound 1 (7-membered fluoroborane dipyrrole) (376 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-Diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.18 mL, 2 mmol), and acetic acid (0.12 mL, 2 mmol) were then added sequentially. The mixture was heated and stirred at 90°C for 8 hours until complete reaction. The reactants were rotary evaporated and purified by column chromatography to obtain a purple-red solid I-1 (213.9 mg) with a yield of 33.9%. When the amounts of piperidine and acetic acid were doubled relative to Example 1, the yield did not change significantly.

[0037]

[0038] Example 4

[0039] Compound 1 (376 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-Diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was heated and stirred at 120°C for 6 hours until the reaction was complete. The reactants were rotary evaporated and purified by column chromatography to obtain a purple-red solid I-1 (417.1 mg) with a yield of 66.1%. When the reaction temperature was increased by 30°C relative to Example 1, the reaction time was reduced by 2 hours, and the yield increased by 34.6%.

[0040]

[0041] Example 5

[0042] Compound 1 (376 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-Diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was stirred at 140°C for 6 hours until complete. The product was then rotary evaporated and purified by column chromatography to afford a purple-red solid I-1 (174.8 mg) with a yield of 27.7%. When the reaction temperature was increased by 50°C relative to Example 1, the reaction time was reduced by 2 hours, resulting in a 3.8% decrease in yield.

[0043]

[0044] Example 6

[0045] Compound 1 (376 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-Diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was stirred at 60°C for 12 hours until complete. The reaction mixture was rotary evaporated and purified by column chromatography to obtain a purple-red solid I-1 (102.2 mg) with a yield of 16.2%. When the reaction temperature was reduced by 30°C and the reaction time was increased by 4 hours compared to Example 1, the yield decreased by 15.3%.

[0046]

[0047] Example 7

[0048] Compound 1 (376 mg, 1 mmol) was weighed and dissolved in 60.00 mL of toluene. 4-Diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was stirred at 90°C for 8 hours until complete. The reaction mixture was rotary evaporated and purified by column chromatography to obtain a purple-red solid I-1 (183.0 mg) with a yield of 29.0%. When the volume of toluene was doubled relative to Example 1, the yield decreased by 2.5%.

[0049]

[0050] Example 8

[0051] Weigh compound 1 (376 mg, 1 mmol) of heptafluoroborane dipyrrole and dissolve it in 30.00 mL of toluene. Then add 4-cyanobenzaldehyde (131 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) in sequence. Heat and stir at 90 ° C for 8 hours until the reaction is complete. The reactant is rotary evaporated and purified by column chromatography to obtain a purple solid I-1 (116.9 mg) with a yield of 23.9%.

[0052]

[0053] Example 9 - Response of Compounds I-1 and I-2 to Viscosity

[0054] Compound I-1 (6.31 mg, 0.01 mmol) was weighed and dissolved in 1 mL of DMF to prepare a 0.01 mol / L mother solution. Then, 10 μL of the mother solution was dissolved in 3 ml of a mixture of DMF and glycerol of different viscosities to prepare a 33.3 μmol / L test solution, including (DMF: glycerol = 10:0 = 3 ml:0 ml, viscosity of 0.77 mPa·s), (DMF: glycerol = 9:1 = 2.7 ml:0.3 ml, viscosity of 1.5 mPa·s), (DMF: glycerol = 8:2 = 2.4 ml:0.6 ml, viscosity of 2.41 mPa·s), (DMF: glycerol = 7:3 = 2.1 ml:0.9 ml, viscosity of 4.22 mPa·s), (DMF: glycerol = 6:1 = 2.7 ml:0.3 ml, viscosity of 1.5 mPa·s), 4=1.8ml:1.2ml, viscosity is 7.36mPa·s)(DMF:glycerol=5:5=1.5ml:1.5ml, viscosity is 14.2mPa·s), (DMF:glycerol=4:6=1.2ml:1.8ml, viscosity is 19.9mPa·s), (DMF:glycerol=3:7=0.9ml:2.1ml, viscosity is 64.6mPa·s), (DMF:glycerol=2:8=0.6ml:2.4ml, viscosity is 127.5mPa·s), (DMF:glycerol=1:9=0.3ml:2.7ml, viscosity is 258.7mPa·s) and their fluorescence spectra are detected respectively, and the results are shown in FIG. Figure 3 , and fitting the fluorescence intensity logI 737nm The linear relationship with logη gives Figure 4 The fluorescence of I-1 itself is weak, but with the increase of viscosity, the fluorescence gradually increases. The viscosity coefficient is 4.58, and the maximum fluorescence enhancement with viscosity is 3.8 times.

[0055] Compound I-1 (6.31 mg, 0.01 mmol) was weighed and dissolved in 1 mL of ethylene glycol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of a mixture of ethylene glycol and glycerol of varying viscosities to prepare a 33.3 μmol / L test solution. Fluorescence spectra of the following solutions were measured: (ethylene glycol:glycerol = 10:0), (ethylene glycol:glycerol = 9:1), (ethylene glycol:glycerol = 8:2), (ethylene glycol:glycerol = 7:3), (ethylene glycol:glycerol = 6:4), (ethylene glycol:glycerol = 5:5), and (ethylene glycol:glycerol = 4:6). Fluorescence gradually increased with increasing viscosity. The detectable viscosity range was 0.1-182 mPa·s.

[0056] Compound I-1 (6.31 mg, 0.01 mmol) was weighed and dissolved in 1 mL of ethanol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of ethanol and glycerol mixtures of varying viscosities to prepare 33.3 μmol / L test solutions. Fluorescence spectra of the solutions were measured at (ethanol:glycerol = 10:0), (ethanol:glycerol = 9:1), (ethanol:glycerol = 8:2), (ethanol:glycerol = 7:3), (ethanol:glycerol = 6:4), (ethanol:glycerol = 5:5), and (ethanol:glycerol = 4:6). Fluorescence gradually increased with increasing viscosity. The detectable viscosity range was 0.1-180 mPa·s.

[0057] Weigh compound I-2 (4.89 mg, 0.01 mmol) and dissolve it in 1 mL of DMF to prepare a 0.01 mol / L mother solution. Then, 10 μL of the mother solution was dissolved in 3 ml of a mixture of DMF and glycerol of different viscosities to prepare a 33.3 μmol / L test solution, wherein (DMF: glycerol = 9:1 = 2.7 ml: 0.3 ml, viscosity of 1.5 mPa·s), (DMF: glycerol = 8:2 = 2.4 ml: 0.6 ml, viscosity of 2.41 mPa·s), (DMF: glycerol = 7:3 = 2.1 ml: 0.9 ml, viscosity of The fluorescence spectra of the two samples were detected respectively, and the results were as follows: (DMF: glycerol = 6: 4 = 1.8 ml: 1.2 ml, viscosity of 7.36 mPa s) (DMF: glycerol = 5: 5 = 1.5 ml: 1.5 ml, viscosity of 14.2 mPa s) (DMF: glycerol = 4: 6 = 1.2 ml: 1.8 ml, viscosity of 19.9 mPa s) and (DMF: glycerol = 3: 7 = 0.9 ml: 2.1 ml, viscosity of 64.6 mPa s). Figure 5 , and fitting the fluorescence intensity logI 636nm The linear relationship with logη gives Figure 6 The fluorescence of I-2 itself is weak, but as the viscosity increases, the fluorescence gradually increases. The viscosity coefficient is 2.99, and the maximum fluorescence enhancement with viscosity is 17.5 times.

[0058] Compound I-2 (4.89 mg, 0.01 mmol) was weighed and dissolved in 1 mL of ethylene glycol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of a mixture of ethylene glycol and glycerol of varying viscosities to prepare a 33.3 μmol / L test solution. Fluorescence spectra of the following solutions were measured: (ethylene glycol:glycerol = 10:0), (ethylene glycol:glycerol = 9:1), (ethylene glycol:glycerol = 8:2), (ethylene glycol:glycerol = 7:3), (ethylene glycol:glycerol = 6:4), (ethylene glycol:glycerol = 5:5), (ethylene glycol:glycerol = 4:6), and (ethylene glycol:glycerol = 3:7). Fluorescence gradually increased with increasing viscosity. The detectable viscosity range was 0.1-200 mPa·s.

[0059] Compound I-2 (4.89 mg, 0.01 mmol) was weighed and dissolved in 1 mL of ethanol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of ethanol and glycerol mixtures of varying viscosities to prepare 33.3 μmol / L test solutions. Fluorescence spectra of the following solutions were measured: (ethanol:glycerol = 10:0), (ethanol:glycerol = 9:1), (ethanol:glycerol = 8:2), (ethanol:glycerol = 7:3), (ethanol:glycerol = 6:4), (ethanol:glycerol = 5:5), (ethanol:glycerol = 4:6), and (ethanol:glycerol = 3:7). Fluorescence gradually increased with increasing viscosity. The detectable viscosity range was 0.1-200 mPa·s.

[0060] The above embodiments are merely preferred technical solutions of the present invention and should not be construed as limiting the present invention. The embodiments and features in the embodiments of this application may be arbitrarily combined with each other unless they conflict. The scope of protection of the present invention shall be the technical solutions described in the claims, including equivalent alternatives to the technical features of the technical solutions described in the claims. Equivalent alternatives and improvements within this scope are also within the scope of protection of the present invention.

Claims

1. An application of a red-light bopyin heterocyclic compound in detecting the viscosity of an organic solution, characterized in that: The chemical structure of the red-light bopyin heterocyclic compound is: 。 2. The use according to claim 1, characterized in that The synthesis method of the red-light bopyin heterocyclic compound includes the following synthesis path: wherein the substituent R1 is selected from bromine, and the substituent R2 is selected from cyano; (1) Add compound 1 and toluene to a reaction flask at room temperature, stir to dissolve, then add compound 2, piperidine, and acetic acid, heat under reflux to obtain a reaction solution; (2) The reaction solution in step (1) was subjected to rotary evaporation and then separated by silica gel column chromatography to obtain product I.

3. The use according to claim 2, characterized in that In the step (1), the molar ratio of compound 1 to compound 2 is 1:1-10.

4. The use according to claim 2, characterized in that The order of feeding in step (1) is compound 1, toluene, compound 2, piperidine, and acetic acid; the feeding ratio of compound 1, piperidine, and acetic acid is 1:1-10:1-10.

5. The use according to claim 1, characterized in that The organic solution includes one or more of DMF, glycerol, ethylene glycol and ethanol.

6. The use according to claim 1, characterized in that The viscosity detection range is 0.1-300mPa·s.

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