Preparation of a seven-membered bopyin heterocyclic compound and its application in detecting viscosity in organic solutions

Abstract

The present invention discloses the preparation of a seven-membered bopyrin heterocyclic compound and its application in viscosity detection in organic solutions. The heterocyclic compound has the following structure: #imgabs0#. The substituent R1 is selected from any one of hydrogen, methoxy, bromine, and cyano. The dye is derived from a para-substituted derivative of a seven-membered fluoroboron dipyrrole and p-dimethylaminocinnamaldehyde via catalytic condensation with piperidine, acetic acid, and phosphorus oxychloride. The synthesis method is simple, separation and purification are convenient, and the yield is high. The introduction of different substituents red-shifts the absorption and emission spectra of the molecule, making its structure useful for monitoring viscosity changes in mixed solutions.

Description

Technical Field

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

[0002] Viscosity, as a key parameter of the microenvironment, plays an important role in living organisms. However, high viscosity values ​​are often associated with major diseases such as cardiovascular disease, diabetes, and cancer. Therefore, accurate viscosity measurement is important for better understanding the pathology of these diseases.

[0003] Currently developed and utilized methods and instruments for measuring viscosity include capillary viscometers, falling ball viscometers, and rotational viscometers. While capillary viscometers have a simple principle, they suffer from low efficiency and large detection errors. Rotational viscometers offer rapid, convenient, and highly accurate measurements, but they require extensive hardware, are complex, and are expensive, limiting their practical application. In summary, these methods are unsuitable for real-time viscosity measurement of small samples or localized areas. However, the use of fluorescent probes can effectively avoid these limitations, enabling imaging within tissues or cells due to their high spatial and temporal resolution. Therefore, developing novel, efficient viscosity measurement methods for diagnosis and pathological screening of related diseases is of great value.

[0004] To address these issues, the present invention describes a fluorescent probe based on a seven-membered bopyin heterocyclic compound. Due to its long-wavelength emission in the near-infrared range, this probe can be used to detect viscosity in mixed solutions, monitor viscosity changes during polymerization, and measure viscosity in cells or mitochondria. It also offers advantages such as ease of detection, high sensitivity, and a wide detection range. Summary of the Invention

[0005] The main purpose of the present invention is to provide a seven-membered bopyin heterocyclic compound and its viscosity application. The technical solution of the present invention is as follows:

[0006] A seven-membered bopyin heterocyclic compound and its viscosity application, wherein the chemical structural formula of the compound is:

[0007] ;

[0008] The substituent R is any one selected from hydrogen, methoxy, bromine, and cyano. The chemical structural formula of the compound is:

[0009]

[0010] Any one of .

[0011] The synthesis method of the seven-membered bopyin heterocyclic compound comprises the following synthesis path:

[0012] ;

[0013] The method comprises the following steps:

[0014] (1) Compound 1, compound 2, and toluene were added to a reaction flask at room temperature, dissolved by ultrasonication, and then piperidine was added and heated to obtain a reaction solution;

[0015] (2) The reaction solution in step (1) is subjected to rotary evaporation and then separated by silica gel column chromatography to obtain product Y. Compound 1 is a seven-membered fluoroborane dipyrrole derivative, and compound 2 is p-dimethylaminocinnamaldehyde; the molar ratio of compound 1 to compound 2 is 1:1~2.

[0016] (3) The order of feeding the materials in step (1) is compound 1, compound 2, toluene, and piperidine; the feeding ratio of compound 1 to piperidine is 1:0.3~1.

[0017] The heating temperature of step (1) is 20-100° C., and the heating time is 2-5 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 0.2 to 2.5 times, which improves the imaging contrast of viscosity monitoring.

[0020] (2) The preparation method of the seven-membered bopyin heterocyclic compound viscosity probe described in the present invention is simple, and the synthesized viscosity probe responds sensitively to viscosity in a mixed solution of DMF and glycerol.

[0021] (3) Compared with other viscosity probes, the maximum fluorescence emission of one of the compounds in the viscosity probe described in this patent can reach about 820 nm.

[0022] (4) The synthesis steps of the present invention are simpler, the reaction temperature is milder, the operation difficulty is small, the reaction time is fast, not exceeding 5 hours at most, the yield is relatively high, and the post-processing and purification are simple. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is the hydrogen spectrum of compound Y-1 obtained in Example 1.

[0024] Figure 2 This is the hydrogen spectrum of compound Y-2 obtained in Example 3.

[0025] Figure 3This is the hydrogen spectrum of compound Y-3 obtained in Example 4.

[0026] Figure 4 This is the hydrogen spectrum of compound Y-4 obtained in Example 5.

[0027] Figure 5 Graph showing the fluorescence spectra of compound Y-1 obtained in Example 1 in DMF-glycerol mixtures of different proportions.

[0028] Figure 6 is the fluorescence intensity logI of compound Y-1 obtained in Example 1 807nm Linear relationship with logη.

[0029] Figure 7 Graph showing the fluorescence spectra of compound Y-2 obtained in Example 2 in DMF-glycerol mixtures of different proportions.

[0030] Figure 8 is the fluorescence intensity logI of compound Y-2 obtained in Example 2 800nm Linear relationship with logη.

[0031] Figure 9 3 is a graph showing the fluorescence spectra of compound Y-3 obtained in Example 3 in DMF-glycerol mixtures of different proportions.

[0032] Figure 10 is the fluorescence intensity logI of compound Y-3 obtained in Example 3 815nm Linear relationship with logη.

[0033] Figure 11 Graph showing the fluorescence spectra of compound Y-4 obtained in Example 4 in DMF-glycerol mixtures of different proportions.

[0034] Figure 12 is the fluorescence intensity logI of compound Y-4 obtained in Example 4 820nm Linear relationship with logη. DETAILED DESCRIPTION

[0035] 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.

[0036] Example 1

[0037] Compound 1 (298 mg, 1 mmol) and 4-dimethylaminocinnamaldehyde (175 mg, 1 mmol) were weighed and dissolved in 20 mL of toluene. Piperidine (59 μL, 0.3 mmol) was then added and heated at 100 °C with stirring for 5 hours until the reaction was complete. The reactant was rotary evaporated and purified by column chromatography to obtain a purple-black solid Y-1 (218.4 mg) with a yield of 48%.

[0038]

[0039] Y1

[0040] Example 2

[0041] Compound 1 heptafluoroborane dipyrrole (298 mg, 1 mmol) and 4-dimethylaminocinnamaldehyde (175 mg, 1 mmol) were weighed and dissolved in 20 mL of toluene. Piperidine (59 μL, 0.6 mmol) was added and heated at 100 ° C with stirring for 5 hours until the reaction was complete. The reactants were rotary evaporated and purified by column chromatography to obtain a purple-black solid Y-1 (273.1 mg) with a yield of 60%. The amount of piperidine was doubled compared to Example 1, and the yield was increased by 12%.

[0042]

[0043] Y-1

[0044] Example 3

[0045] Compound 1 (328 mg, 1 mmol), 4-dimethylaminocinnamaldehyde (210 mg, 1.2 mmol), and piperidine (99 μL, 1 mmol) were weighed and heated at 100°C with stirring for 3 hours until the reaction was complete. The reactants were rotary evaporated and purified by column chromatography to obtain a purple-black solid Y-1 (203.7 mg) with a yield of 42%.

[0046]

[0047] Y-2

[0048] Example 4

[0049] Compound 1 (377 mg, 1 mmol), 4-dimethylaminocinnamaldehyde (210 mg, 1.2 mmol), and piperidine (59 μL, 0.6 mmol) were weighed and heated at 100°C with stirring for 3 hours until the reaction was complete. The reactants were rotary evaporated and purified by column chromatography to obtain a purple-black solid Y-1 (224.3 mg) with a yield of 42%.

[0050]

[0051] Y-3

[0052] Example 5

[0053] Compound 1 (323 mg, 1 mmol), 4-dimethylaminocinnamaldehyde (210 mg, 1.2 mmol), and piperidine (99 μL, 1 mmol) were weighed and heated at 100°C with stirring for 3 hours until the reaction was complete. The reactant was rotary evaporated and purified by column chromatography to obtain a purple-black solid Y-1 (190 mg) with a yield of 40%.

[0054]

[0055] Y-4

[0056] Example 6 - Response of Compound Y-1 to Viscosity

[0057] Compound Y-1 (4.55 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 = 7:3 = 2.1 ml: 0.9 ml, viscosity of 4.22 mPa·s), (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). s), (DMF: glycerol = 4: 6 = 1.2 ml: 1.8 ml, viscosity is 19.9 mPa·s), (DMF: glycerol = 3: 7 = 0.9 ml: 2.1 ml, viscosity is 64.6 mPa·s), (DMF: glycerol = 2: 8 = 0.6 ml: 2.4 ml, viscosity is 127.5 mPa·s), (DMF: glycerol = 1: 9 = 0.3 ml: 2.7 ml, viscosity is 258.7 mPa·s) and their fluorescence spectra are detected respectively. Figure 5 , and fitting the fluorescence intensity logI 807nm The linear relationship with logη gives Figure 6 The fluorescence of Y-1 itself is weak, but the fluorescence intensity gradually increases with increasing viscosity. The viscosity coefficient is 4.73, and the maximum fluorescence enhancement with viscosity is 1.2 times.

[0058] Example 7 - Response of Compound Y-2 to Viscosity

[0059] Compound Y-2 (4.85 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 with different viscosities to prepare a 33.3 μmol / L test solution, including (DMF: glycerol = 7:3 = 2.1 ml: 0.9 ml, viscosity of 4.22 mPa·s), (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). s), (DMF: glycerol = 4: 6 = 1.2 ml: 1.8 ml, viscosity is 19.9 mPa·s), (DMF: glycerol = 3: 7 = 0.9 ml: 2.1 ml, viscosity is 64.6 mPa·s), (DMF: glycerol = 2: 8 = 0.6 ml: 2.4 ml, viscosity is 127.5 mPa·s), (DMF: glycerol = 1: 9 = 0.3 ml: 2.7 ml, viscosity is 258.7 mPa·s) and their fluorescence spectra are detected respectively. Figure 7 , and fitting the fluorescence intensity logI 807nm The linear relationship with logη gives Figure 8 The fluorescence of Y-1 itself is weak, but as the viscosity increases, the fluorescence intensity gradually increases. The viscosity coefficient is 3.83, and the maximum fluorescence enhancement with viscosity is 2.4 times.

[0060] Example 8 - Response of Compound Y-3 to Viscosity

[0061] Compound Y-3 (5.33 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 with different viscosities to prepare a 33.3 μmol / L test solution, including (DMF: glycerol = 7:3 = 2.1 ml: 0.9 ml, viscosity of 4.22 mPa·s), (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). s), (DMF: glycerol = 4: 6 = 1.2 ml: 1.8 ml, viscosity is 19.9 mPa·s), (DMF: glycerol = 3: 7 = 0.9 ml: 2.1 ml, viscosity is 64.6 mPa·s), (DMF: glycerol = 2: 8 = 0.6 ml: 2.4 ml, viscosity is 127.5 mPa·s), (DMF: glycerol = 1: 9 = 0.3 ml: 2.7 ml, viscosity is 258.7 mPa·s) and their fluorescence spectra are detected respectively. Figure 9 , and fitting the fluorescence intensity logI 807nmThe linear relationship with logη gives Figure 10 , the viscosity coefficient is 4.70, and the maximum fluorescence enhancement to viscosity is 1.4 times.

[0062] Example 9 - Response of Compound Y-4 to Viscosity

[0063] Compound Y-4 (5.05 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 with different viscosities to prepare a 33.3 μmol / L test solution, including (DMF: glycerol = 7:3 = 2.1 ml: 0.9 ml, viscosity of 4.22 mPa·s), (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). s), (DMF: glycerol = 4: 6 = 1.2 ml: 1.8 ml, viscosity is 19.9 mPa·s), (DMF: glycerol = 3: 7 = 0.9 ml: 2.1 ml, viscosity is 64.6 mPa·s), (DMF: glycerol = 2: 8 = 0.6 ml: 2.4 ml, viscosity is 127.5 mPa·s), (DMF: glycerol = 1: 9 = 0.3 ml: 2.7 ml, viscosity is 258.7 mPa·s) and their fluorescence spectra are detected respectively. Figure 11 , and fitting the fluorescence intensity logI 807nm The linear relationship with logη gives Figure 12 , the viscosity coefficient is 4.20, and the maximum fluorescence enhancement to viscosity is 2.3 times.

[0064] 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. Application of a seven-membered bopyin heterocyclic compound in detecting the viscosity of an organic solution, wherein the organic solution is DMF or glycerol; The structural formula of the seven-membered bopyin heterocyclic compound is: 。 2. The use according to claim 1, characterized in that The viscosity detection range is 0.3-300mPa·s.

3. The use according to claim 1, characterized in that The preparation method of the seven-membered bopyin heterocyclic compound includes the following synthetic route: ； Wherein, the substituent R is any one selected from hydrogen, methoxy, bromine, and cyano; (1) Compound 1, compound 2, and toluene were added to a reaction flask at room temperature, dissolved by ultrasonication, and then piperidine was added and heated 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 Y.

4. The use according to claim 3, characterized in that In the step (1), the molar ratio of compound 1, compound 2 and piperidine is 1:1~2:0.3~1.

5. The use according to claim 4, characterized in that The heating temperature of step (1) is 20-100° C., and the heating time is 2-5 hours.

Images