CN118373839A - Preparation of a seven-membered bopyin heterocyclic compound and its application in detecting viscosity in organic solutions - Google Patents

Abstract

The present invention discloses the preparation of a seven-membered bopyin heterocyclic compound and its application in detecting the viscosity of an organic solution. The structure of the heterocyclic compound is as follows: . Wherein, the substituent _R1 is any one selected from hydrogen, methoxy, bromine, and cyano. The dye is obtained by using a para-substituted derivative of a seven-membered fluoroboron dipyrrole and p-dimethylaminocinnamaldehyde as raw materials, and is catalyzed and condensed by piperidine, acetic acid, and phosphorus oxychloride. The synthesis method is simple, the separation and purification are convenient, and the yield is high. The introduction of different substituents causes the absorption and emission spectra of the molecule to red shift, and its structure can be used to monitor the change of viscosity in a mixed solution.

Description

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

Technical Field

The invention relates to a seven-membered bopyin heterocyclic compound, and more specifically to a seven-membered bopyin heterocyclic compound and viscosity application thereof.

Background technique

As a key parameter of the microenvironment, viscosity plays an important role in organisms. However, high viscosity values are often associated with major diseases such as cardiovascular disease, diabetes, and tumors. Therefore, accurate viscosity detection is of great significance for a better understanding of the pathology of related diseases.

The methods and instruments for detecting viscosity that have been developed and used so far include capillary viscometer, falling ball viscometer, rotational viscometer, etc. Among them, the capillary viscometer has a simple principle, but low working efficiency and large detection error. The rotational viscometer is fast, convenient and accurate, but this method requires a lot of hardware equipment, complex structure and high price, which limits its practical application. In short, the above methods are not suitable for real-time detection of small samples or local viscosity, but the method of applying fluorescent probes can effectively avoid these defects, because of its high spatial resolution and time resolution, it can perform tissue or cell imaging. Therefore, it is of great value to develop new and efficient viscosity detection methods for the diagnosis and pathological screening of related diseases.

In view of the above problems, the present invention discloses a seven-membered bopyin heterocyclic compound fluorescent probe, which can be used for viscosity detection in mixed solutions, monitoring viscosity changes during polymerization, and viscosity measurement in cells or mitochondria, etc., due to its long-wavelength emission in the near-infrared range. It has the advantages of easy detection, sensitive reaction, and wide detection range.

Summary of the invention

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:

A seven-membered bopyin heterocyclic compound and viscosity application thereof, wherein the chemical structural formula of the compound is:

;

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

Any one of .

A method for synthesizing the seven-membered bopyin heterocyclic compound, the method comprising the following synthesis path:

;

The method comprises the following steps:

(1) Add compound 1, compound 2, and toluene to a reaction bottle at room temperature, dissolve them by ultrasonication, then add piperidine, and heat to obtain a reaction solution;

(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.

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

The heating temperature of step (1) is 20-100° C. and the heating time is 2-5 hours.

The beneficial effects of the present invention are as follows:

(1) The compounds of the present invention have a certain response to viscosity. The fluorescence of the compounds themselves 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.

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

(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 820nm.

(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

FIG1 is a hydrogen spectrum of compound Y-1 obtained in Example 1.

FIG2 is a hydrogen spectrum of compound Y-2 obtained in Example 3.

FIG3 is a hydrogen spectrum of compound Y-3 obtained in Example 4.

FIG4 is a hydrogen spectrum of compound Y-4 obtained in Example 5.

Figure 5 is a graph of the fluorescence spectrum of compound Y-1 obtained in Example 1 in DMF-glycerol mixtures of different proportions.

FIG6 is a linear relationship between the fluorescence intensity logI _807nm and logη of compound Y-1 obtained in Example 1.

Figure 7 is a graph of the fluorescence spectrum of compound Y-2 obtained in Example 2 in DMF-glycerol mixtures of different proportions.

FIG8 is a linear relationship between the fluorescence intensity logI _800nm and logη of compound Y-2 obtained in Example 2.

Figure 9 is a graph of the fluorescence spectrum of compound Y-3 obtained in Example 3 in DMF-glycerol mixtures of different proportions.

FIG. 10 is a linear relationship between the fluorescence intensity logI _815nm and logη of compound Y-3 obtained in Example 3.

Figure 11 is a graph of the fluorescence spectrum of compound Y-4 obtained in Example 4 in DMF-glycerol mixtures of different proportions.

FIG. 12 is a linear relationship between the fluorescence intensity logI _820nm and logη of compound Y-4 obtained in Example 4.

Detailed ways

The present invention is further described below with reference to embodiments, but the scope of protection claimed by the present invention is not limited to the scope described in the embodiments.

Example 1

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 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%.

Y1

Example 2

Compound 1 heptafluoroboranedipyrrole (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. and stirred 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 increased by 1 times compared with Example 1, and the yield was increased by 12%.

Y-1

Example 3

Compound 1 heptafluoroboranedipyrrole (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%.

Y-2

Example 4

Compound 1 heptafluoroboranedipyrrole (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%.

Y-3

Example 5

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 reactants were rotary evaporated and purified by column chromatography to obtain a purple-black solid Y-1 (190 mg) with a yield of 40%.

Y-4

Example 6 - Response of Compound Y-1 to Viscosity

Weigh compound Y-1 (4.55 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 with different viscosities to prepare a 33.3 μmol/L test solution, including (DMF: glycerol = 7:3 = 2.1 ml: 0.9 ml, viscosity is 4.22 mPa·s), (DMF: glycerol = 6:4 = 1.8 ml: 1.2 ml, viscosity is 7.36 mPa·s) (DMF: glycerol = 5:5 = 1.5 ml: 1.5 ml, viscosity is 14.2 mPa·s) 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) respectively detect their fluorescence spectra, get Figure 5, and fit the linear relationship between fluorescence intensity logI _807nm and logη, get Figure 6. Y-1 itself has weak fluorescence, but with the increase of viscosity, the fluorescence intensity gradually increases. The viscosity coefficient is 4.73, and the maximum fluorescence enhancement to viscosity is 1.2 times.

Example 7 - Response of Compound Y-2 to Viscosity

Weigh compound Y-2 (4.85 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 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 = 1.2ml: 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) respectively detect their fluorescence spectra, get Figure 7, and fit the linear relationship between fluorescence intensity logI _807nm and logη, get Figure 8. Y-1 itself has weak fluorescence, but with the increase of viscosity, the fluorescence intensity gradually increases. The viscosity coefficient is 3.83, and the maximum fluorescence enhancement for viscosity is 2.4 times.

Example 8 - Response of Compound Y-3 to Viscosity

Weigh compound Y-3 (5.33 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 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 were detected respectively to obtain Figure 9, and the linear relationship between the fluorescence intensity logI _807nm and logη was fitted to obtain Figure 10. The viscosity coefficient is 4.70, and the maximum fluorescence enhancement for viscosity is 1.4 times.

Example 9 - Response of Compound Y-4 to Viscosity

Weigh compound Y-4 (5.05 mg, 0.01 mmol) and dissolve it in 1 mL DMF to prepare a 0.01 mol/L mother solution. Then take 10 μL of the mother solution and dissolve it 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 is 4.22 mPa·s), (DMF: glycerol = 6:4 = 1.8 ml: 1.2 ml, viscosity is 7.36 mPa·s) (DMF: glycerol = 5:5 = 1.5 ml: 1.5 ml, viscosity is 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 were detected respectively to obtain Figure 11, and the linear relationship between the fluorescence intensity logI _807nm and logη was fitted to obtain Figure 12. The viscosity coefficient is 4.20, and the maximum fluorescence enhancement for viscosity is 2.3 times.

The above-mentioned embodiments are only preferred technical solutions of the present invention and should not be regarded as limitations of the present invention. The embodiments and features in the embodiments of the present application can be arbitrarily combined with each other without conflict. The protection scope of the present invention shall be the technical solutions recorded in the claims, including the equivalent replacement solutions of the technical features in the technical solutions recorded in the claims. That is, equivalent replacement improvements within this scope are also within the protection scope of the present invention.

Claims (8)

1. A seven-membered bopyin heterocyclic compound, characterized in that the chemical structural formula of the compound is: ; The substituent R is any one selected from hydrogen, methoxy, bromine and cyano. 2. The method for synthesizing the heterocyclic compound according to claim 1, characterized in that the method comprises the following synthesis path: ; Wherein, the substituent R is any one selected from hydrogen, methoxy, bromine, cyano (1) Add compound 1, compound 2, and toluene to a reaction bottle at room temperature, dissolve them by ultrasonication, then add piperidine, and heat to obtain a reaction solution; (2) The reaction solution in step (1) is subjected to rotary evaporation, and then separated by silica gel column chromatography to obtain product Y. 3. The method according to claim 2, characterized in that in the step (1), the molar ratio of compound 1, compound 2 and piperidine is 1:1~2:0.3~1. 4. The method according to claim 2, characterized in that the heating temperature in step (1) is 20-100°C and the heating time is 2-5 hours. 5. The method according to claim 2, characterized in that the compound 1 in step (1) is a para-derivative of the seven-membered heterocyclic bopyin. 6. Use of the seven-membered bopyin heterocyclic compound according to claim 1 in detecting the viscosity in an organic solution. 7. The use according to claim 6, characterized in that the organic solution comprises DMF and glycerol. 8. The use according to claim 6, characterized in that the viscosity detection range is 0.3-300 mPa·s.