A carbazole derivative, its preparation method and application

Abstract

The present application relates to a kind of carbazole derivatives and its preparation method and application.The structure formula of carbazole derivative provided by the present application is as shown in (I), which is prepared by the reaction of 2-furan boronic acid and chloroisoquinoline after halogenation, then the halogenated product is reacted with N-phenyl-3-carbazole boronic acid.The carbazole derivative can be used as organic small molecule probe, for testing deuterated reagent, can be very simple and convenient for the rapid qualitative and quantitative analysis of deuterated acetone in acetone, and has higher detection sensitivity and accuracy.

Description

Technical Field

[0001] This invention belongs to the field of organic chemistry and analytical detection technology, specifically relating to a carbazole derivative, its preparation method, and its application. Background Technology

[0002] Currently, the conventional method for qualitative and quantitative analysis of deuterated acetone in acetone is to use specialized analytical instruments (such as nuclear magnetic resonance (NMR) and mass spectrometry). In NMR spectra, deuterium signals typically appear at positions different from those of ordinary hydrogen. By analyzing the chemical shift, intensity, and pattern of these signals, the presence of deuterium in the sample can be identified. The deuterium content in the sample can be quantitatively calculated by comparing the intensity of the deuterium signal with internal or external standards. Mass spectrometry can distinguish different isotopes within a molecule, making it highly suitable for detecting the presence and content of deuterium in acetone. Therefore, mass spectrometry (MS) is an effective method for detecting deuterated acetone in acetone. The sample is ionized in a mass spectrometer, and the ionized molecules are guided into the mass analyzer, which separates the ions based on their mass-to-charge ratio (m / z). Deuterated acetone molecules or fragments will have a different mass-to-charge ratio than acetone (because deuterium is heavier than ordinary hydrogen), causing a slight shift in the peak position of deuterated acetone in the mass spectrum compared to non-deuterated acetone. By comparing the peak positions and intensities of deuterated and non-deuterated acetone, the presence and content of deuterated acetone can be qualitatively and quantitatively analyzed.

[0003] These instrumental analysis methods require professional, trained testing personnel to operate, are cumbersome and complex to perform, and are limited by testing instruments and venues, making them unsuitable for portable testing. Summary of the Invention

[0004] Therefore, the purpose of this invention is to provide a simple, convenient, and rapid detection method for the qualitative and quantitative analysis of deuterated acetone in acetone.

[0005] To achieve the above-mentioned objectives, the present invention includes the following technical solutions.

[0006] On the one hand, the present invention provides a carbazole derivative having the structure shown in formula (I) below.

[0007]

[0008] Secondly, the present invention provides a method for preparing the carbazole derivative, comprising the following steps:

[0009] (1) 2-Furanboronic acid reacts with compound A to give compound 1;

[0010] (2) Compound 1 reacts with a halogenated reagent to give compound 2;

[0011] (3) Compound 2 reacts with N-phenyl-3-carbazole boric acid to obtain a carbazole derivative with the structure shown in formula (I);

[0012] The reaction formula is as follows:

[0013]

[0014] Where R is a halogen.

[0015] Thirdly, this invention provides the application of the carbazole derivative as a probe for a deuterated reagent in the detection of deuterated reagents. The deuterated reagent can be deuterated acetone.

[0016] Fourthly, the present invention provides a method for detecting deuterated acetone in acetone, comprising: adding the carbazole derivative described in the present invention to the test solution, and testing the ultraviolet absorption intensity and / or fluorescence intensity of the resulting mixed solution.

[0017] When testing ultraviolet absorption intensity, the concentration of carbazole derivative in the mixed solution is preferably 45 μmol / L to 55 μmol / L; when testing fluorescence intensity, the concentration of carbazole derivative in the mixed solution is preferably 0.10 μmol / L to 0.15 μmol / L.

[0018] This invention designs and synthesizes a novel carbazole derivative. The carbazole derivative is prepared by reacting 2-furanboronic acid with chloroisoquinoline followed by halogenation, and then reacting the halogenated product with N-phenyl-3-carbazoleboronic acid. This compound can be used as a small organic molecule probe for testing deuterated reagents. Adding the carbazole derivative of this invention to an acetone solution and measuring its UV absorption intensity using a simple device can determine whether deuterated acetone is present in the acetone. Further testing its fluorescence spectrum and determining the fluorescence intensity allows for the identification of deuterated acetone and its concentration in the acetone solution, thus enabling a simple and rapid detection of deuterated reagents in acetone solutions. The carbazole derivative provided by this invention can be used very simply and conveniently for rapid qualitative and quantitative analysis of deuterated acetone in acetone, and it exhibits high detection sensitivity and accuracy. Attached Figure Description

[0019] Figure 1 This is the 1H NMR spectrum of compound 1.

[0020] Figure 2 This is the 1H NMR spectrum of compound 2.

[0021] Figure 3 This is the 1H NMR spectrum of the carbazole derivative probe.

[0022] Figure 4 This is the carbon NMR spectrum of the carbazole derivative probe.

[0023] Figure 5 The image shows the UV spectrum of an acetone solution containing a carbazole derivative probe.

[0024] Figure 6 The graph shows the fluorescence response of the carbazole derivative probe to the percentage concentration of deuterated acetone in the acetone solution.

[0025] Figure 7 The graph shows the linear relationship between fluorescence intensity and deuterated acetone concentration. Detailed Implementation

[0026] To facilitate understanding of the present invention, a more complete description will be provided below. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of the present invention.

[0027] Unless otherwise specified, experimental methods in the following examples are generally performed under standard conditions or as recommended by the manufacturer. All commonly used chemical reagents used in the examples are commercially available products.

[0028] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to limit the invention. The term "and / or" as used in this invention includes any and all combinations of one or more of the associated listed items.

[0029] Furthermore, as used herein, the term "or" is an inclusive "or" sign and is equivalent to the term "and / or" unless the context clearly specifies otherwise. The term "based on" is not exclusive and allows for basing on other factors not described unless the context clearly specifies otherwise. Additionally, throughout the specification, the meanings of "an," "a," and "the" include plural indicators. The meaning of "in" includes both "in" and "on."

[0030] To provide a simple, convenient, and rapid detection method for the qualitative and quantitative analysis of deuterated acetone in acetone, the inventors of this invention designed and synthesized a novel carbazole derivative. This compound can be used as an organic small molecule probe to test deuterated reagents, and can be used very simply and conveniently for rapid qualitative and quantitative analysis of deuterated acetone in acetone, with high detection sensitivity and accuracy.

[0031] In one embodiment of the present invention, a carbazole derivative having the structure shown in formula (I) is provided:

[0032]

[0033] In another embodiment of the present invention, a method for preparing the carbazole derivative is provided, comprising the following steps:

[0034] (1) 2-Furanboronic acid reacts with compound A to give compound 1;

[0035] (2) Compound 1 reacts with a halogenated reagent to give compound 2;

[0036] (3) Compound 2 reacts with N-phenyl-3-carbazole boric acid to obtain a carbazole derivative with the structure shown in formula (I);

[0037] The reaction formula is as follows:

[0038]

[0039] Where R is a halogen.

[0040] In the synthetic route of the present invention, R in compound A is a halogen, such as chlorine, bromine, etc.; that is, compound A can be 1-chloroisoquinoline or 1-bromoisoquinoline.

[0041] In the synthetic route of this invention, the halogenating agent can be a brominating agent or a chlorinating agent; the brominating agent can be N-bromosuccinimide, etc., and the chlorinating agent can be N-chlorosuccinimide, etc.

[0042] In some embodiments, the 2-furanboronic acid described in step (1) reacts with compound A in the presence of tetra(triphenylphosphine)palladium and a base.

[0043] The alkali can be an organic or inorganic alkali, preferably potassium carbonate or sodium carbonate; the alkali is preferably added to the reaction system as an alkaline solution (water as solvent), therefore, the solvent of the reaction may contain water. Preferably, the concentration of the alkali in the alkaline solution is 1.8 mol / L to 2.5 mol / L.

[0044] In some embodiments, the molar ratio of compound A to tetra(triphenylphosphine)palladium is 1:0.05 to 0.1, preferably 1:0.05 to 0.07.

[0045] In some embodiments, the solvent for the reaction in step (1) is tetrahydrofuran and water, and the volume ratio of the tetrahydrofuran to the alkaline solution is preferably 2 to 6:1, more preferably 2 to 3:1.

[0046] In some embodiments, the molar ratio of 2-furanboronic acid to compound A in step (1) is 1.2 to 1.8:1, more preferably 1.4 to 1.6.

[0047] In some embodiments, the temperature of the reaction in step (1) is 80°C to 90°C, and the time is 40 hours to 56 hours, more preferably 45 hours to 50 hours.

[0048] In some embodiments, the molar ratio of compound 1 to the halogenated reagent in step (2) is 1:1.1 to 1.5, preferably 1:1.1 to 1.3.

[0049] In some of these embodiments, the solvent for the reaction in step (2) is dichloromethane.

[0050] In some embodiments, the reaction in step (2) is carried out at a temperature of 20°C to 30°C for 12 hours to 24 hours, preferably 15 hours to 20 hours.

[0051] In some embodiments, compound 2 in step (3) reacts with N-phenyl-3-carbazoleboronic acid in the presence of tetra(triphenylphosphine)palladium and a base.

[0052] The alkali can be an organic or inorganic alkali, preferably potassium carbonate or sodium carbonate; the alkali is preferably added to the reaction system as an alkaline solution (water as solvent), therefore, the solvent of the reaction may contain water. Preferably, the concentration of the alkali in the alkaline solution is 1.8 mol / L to 2.5 mol / L.

[0053] In some embodiments, the molar ratio of compound A to tetra(triphenylphosphine)palladium is 1:0.06 to 0.12, preferably 1:0.09 to 0.11.

[0054] In some embodiments, the solvent for the reaction in step (3) is tetrahydrofuran and water, and the volume ratio of the tetrahydrofuran to the alkaline solution is preferably 2 to 6:1, more preferably 5 to 6:1.

[0055] In some embodiments, the molar ratio of compound 2 in step (3) to N-phenyl-3-carbazoleboronic acid is 1:1.2 to 1.8, more preferably 1:1.4 to 1.6.

[0056] In some embodiments, the reaction temperature in step (3) is 80°C to 90°C and the time is 40 hours to 56 hours, more preferably 45 hours to 50 hours.

[0057] In another embodiment of the present invention, the application of the carbazole derivative as a probe for a deuterated reagent in the detection of the deuterated reagent, which may be deuterated acetone, etc. The inventors have found that the carbazole derivative of the present invention can be used very simply and conveniently for rapid qualitative and quantitative analysis of deuterated acetone in acetone, and has high detection sensitivity and accuracy.

[0058] In another embodiment of the present invention, a method for detecting deuterated acetone in acetone is provided, comprising: adding the carbazole derivative of the present invention to the test solution, and testing the ultraviolet absorption intensity and / or fluorescence intensity of the resulting mixed solution.

[0059] When testing ultraviolet absorption intensity, the concentration of carbazole derivative in the mixed solution is preferably 45 μmol / L to 55 μmol / L; when testing fluorescence intensity, the concentration of carbazole derivative in the mixed solution is preferably 0.10 μmol / L to 0.15 μmol / L.

[0060] By adding the carbazole derivative described in this invention to an acetone solution, the presence of deuterated acetone in the acetone can be determined by testing its ultraviolet absorption intensity (e.g., at 380 nm) using a simple device. Further testing its fluorescence spectrum, based on the fluorescence intensity (e.g., at 480 nm), reveals the presence and content of deuterated acetone in the acetone, thus enabling a simple and rapid detection of deuterated reagents in acetone solutions. This detection method is simple to operate and requires minimal equipment, allowing for portable and rapid detection of deuterated acetone.

[0061] The present invention will be further described in detail below with reference to specific embodiments.

[0062] Example 1: Synthesis of the probe (carbazole derivative)

[0063] The synthesis route is as follows:

[0064]

[0065] Its synthesis method is as follows:

[0066] Step 1: Preparation of Compound 1

[0067] 2-Furanboric acid (4.22 g, 37.68 mmol) and 1-chloroisoquinoline (4.11 g, 25.12 mmol) were added to 200 mL of tetrahydrofuran, followed by tetratetraphenylphosphine palladium (1.45 g, 1.26 mmol) and 76 mL of 2 M potassium carbonate solution (water). The mixture was heated at 85°C for 48 hours. After cooling to room temperature, the mixture was extracted with ethyl acetate and purified water. The organic phase was evaporated to dryness using a rotary evaporator and then purified by silica gel column chromatography with dichloromethane and n-hexane to give compound 1 (4.1 g, 83.67% yield).

[0068] 1 H NMR (600MHz, CDCl3) δ8.74(d,J=8.5Hz,1H),8.61–8.49(m,1H),7.85–7.75(m,1H),7.72–7.51(m,4H),7.18(d,J=2.7Hz,1H),6.62(d,J=1.6Hz,1H).

[0069] Step 2: Preparation of Compound 2

[0070] Compound 1 (2.47 g, 12.63 mmol) and N-bromosuccinimide (NBS) (2.70 g, 15.16 mmol) were added to 20 mL of dichloromethane and reacted at room temperature for 18 hours. The reaction mixture was evaporated to dryness and then purified by silica gel column chromatography with dichloromethane and n-hexane to give compound 2 (3.12 g, 90.17% yield).

[0071] 1 H NMR (600MHz, CDCl3) δ8.68(d,J=8.5Hz,1H),8.53(d,J=5.5Hz,1H),7.81(d,J=8.1H z,1H),7.63(ddd,J=34.9,21.2,6.4Hz,3H),7.17–7.10(m,1H),6.57–6.49(m,1H).

[0072] Step 3: Preparation of Compound 3

[0073] Compound 2 (1.50 g, 5.47 mmol) and N-phenyl-3-carbazoleboronic acid (2.36 g, 8.21 mmol) were added to 100 mL of tetrahydrofuran, followed by tetratetraphenylphosphine palladium (0.63 g, 0.55 mmol) and 17 mL of 2 M potassium carbonate solution (water). The mixture was heated at 85°C for 48 hours. After cooling to room temperature, the mixture was extracted with ethyl acetate and purified water. The organic phase was evaporated to dryness and then purified by silica gel column chromatography with dichloromethane and n-hexane to obtain the target product probe (2.18 g, 91.40% yield).

[0074] 1 H NMR (600MHz, DMSO) δ9.05–8.96(m,1H),8.79(d,J=1.8Hz,1H),8.60(d,J=5.5Hz,1H),8.41(d,J=7.7Hz,1H),8.12–7.98(m,2H),7.93–7.79( m,3H),7.76–7.64(m,4H),7.59(tt,J=7.1,1.4Hz,1H),7.54–7.45(m,3H),7.42(d,J=8.2Hz,1H),7.39–7.34(m,1H),7.28(d,J=3.5Hz,1H).

[0075] 13 C NMR (151MHz, DMSO) δ156.22,153.05,148.20,142.71,141.20,140.35,137.28,137.03,130.85,130.76,128.99,128.41,127.95,12 7.31,127.22,126.53,124.87,123.71,123.23,123.11,122.91,121.45,120.95,120.45,116.65,115.95,110.87,110.38,107.24.

[0076] Example 2: Ultraviolet Spectroscopy Detection

[0077] The testing method is as follows:

[0078] The carbazole derivative probe prepared in Example 1 was prepared into a 50 μM solution using acetone and deuterated acetone as solvents, respectively, and these solutions were denoted as acetone solution and acetone-d solution.

[0079] Take 4 mL of acetone solution and 4 mL of acetone-d solution respectively and add them to the measuring dish. Perform the test at room temperature using a UV spectrometer (gilent Technologies Cary 8454UV–Vis spectrometer).

[0080] Test results are as follows Figure 5As shown, the carbazole derivative probe exhibits strong absorption in the ultraviolet region at approximately 380 nm, which is caused by the charge transfer transition within the carbazole derivative. In acetone-D solution, the absorption peak at 380 nm of the carbazole derivative probe decreases significantly. This demonstrates that deuterated acetone affects the charge transfer state within the carbazole derivative, thus leading to changes in its spectral properties. This indicates that the carbazole derivative probe prepared in this invention can be used to detect the presence of deuterated acetone in acetone, and can be used very simply and conveniently for rapid qualitative analysis of deuterated acetone in acetone.

[0081] Example 3: Fluorescence Spectroscopy Detection

[0082] The detection method is as follows:

[0083] The carbazole derivative probe was prepared into a 0.125 μM solution using acetone and deuterated acetone (acetone-d) as solvents, or a mixture of acetone and deuterated acetone (acetone-d) in different ratios as solvents. The percentage of acetone-d in the solution was adjusted (e.g., ...). Figure 6 (As shown).

[0084] Take 4 mL of each solution and add it to a measuring dish. Perform fluorescence spectroscopy at room temperature with a wavelength of 400 to 800 nm. The instrument used is an Agilent Technologies Cary Eclipse Fluorescence spectrometer.

[0085] Test results are as follows Figure 6 As shown: In undeuterated acetone solution, the carbazole derivative probe exhibited the highest fluorescence intensity at 480 nm; upon the addition of deuterated acetone, the fluorescence intensity at 480 nm decreased significantly, and the decrease was more pronounced with increasing deuterated acetone content. Within the deuterated acetone concentration range of 0% to 100%, a good linear relationship was observed between the fluorescence intensity at 480 nm and the deuterated acetone concentration (e.g., ...). Figure 7 (As shown).

[0086] These results demonstrate that the carbazole derivative probe synthesized in this invention can be used for the quantitative analysis of deuterated acetone in acetone and has sufficient sensitivity to quantitatively detect the content of deuterated acetone in acetone.

[0087] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A carbazole derivative having a structure shown in formula (I) as follows: 。 2. A method for producing a carbazole derivative, characterized by, comprising the following steps: (1) reacting 2-furanboronic acid with compound A to obtain compound 1; (2) reacting compound 1 with a halogenating agent to obtain compound 2; (3) reacting compound 2 with N-phenyl-3-carbazoleboronic acid to obtain the carbazole derivative having a structure shown in formula (I); a reaction formula of which is as follows: ； wherein R is halogen.

3. The method for producing a carbazole derivative according to claim 2, characterized by, Compound A is 1-chloroisoquinoline or 1-bromoisoquinoline; and / or, the halogenating agent is N-bromosuccinimide or N-chlorosuccinimide.

4. The method for producing a carbazole derivative according to claim 2 or 3, characterized by, In step (1), the 2-furanboronic acid reacts with compound A in the presence of tetrakis(triphenylphosphine)palladium and a base; and / or, In step (1), the solvent of the reaction is tetrahydrofuran and water; and / or, In step (1), the molar ratio of the 2-furanboronic acid to compound A is 1.2-1.8:1; and / or, In step (1), the reaction temperature is 80-90°C, and the reaction time is 40-56 hours.

5. The method of producing a carbazole derivative according to claim 4, wherein In step (1), the base is potassium carbonate or sodium carbonate.

6. The method of claim 4, wherein the method is characterized by, In step (1), the base is added to the reaction system in the form of a base solution, and the volume ratio of tetrahydrofuran to the base solution is 2-6:

1.

7. The method of producing a carbazole derivative according to claim 6, wherein In step (1), the concentration of the base in the base solution is 1.8-2.5 mol / L.

8. The method of claim 4, wherein the method is characterized by, In step (1), the molar ratio of compound A to tetrakis(triphenylphosphine)palladium is 1:0.05-0.

1.

9. The method of producing a carbazole derivative according to claim 2 or 3, wherein In step (2), the molar ratio of compound 1 to the halogenating agent is 1:1.1-1.5; and / or, In step (2), the solvent of the reaction is dichloromethane; and / or, In step (2), the reaction temperature is 20-30°C, and the reaction time is 12-24 hours.

10. The method of producing a carbazole derivative according to claim 2 or 3, characterized by, In step (3), compound 2 reacts with N-phenyl-3-carbazoleboronic acid in the presence of tetrakis(triphenylphosphine)palladium and a base; and / or, In step (3), the solvent of the reaction is tetrahydrofuran and water; and / or, In step (3), the molar ratio of compound 2 to N-phenyl-3-carbazoleboronic acid is 1:1.2-1.8; and / or, In step (3), the reaction temperature is 80-90°C, and the reaction time is 40-56 hours.

11. The method of claim 10, wherein the method is characterized by, In step (3), the base is potassium carbonate or sodium carbonate.

12. The method for preparing the carbazole derivative according to claim 10, characterized in that, In step (3), the base is added to the reaction system in the form of a base solution, and the volume ratio of tetrahydrofuran to the base solution is 2-6:

1.

13. The method of claim 12, wherein the method is characterized by: In step (3), the concentration of the base in the base solution is 1.8-2.5 mol / L.

14. The method for preparing the carbazole derivative according to claim 10, characterized in that, In step (3), the molar ratio of compound 2 to tetrakis(triphenylphosphine)palladium is 1:0.06-0.

12.

15. Use of the carbazole derivative of claim 1 as a probe of deuterium reagent in detecting deuterated acetone in acetone.

16. A method of detecting deuterated acetone in acetone, characterized by, comprising: adding the carbazole derivative of claim 1 to a solution to be tested, and testing the ultraviolet absorption intensity and / or the fluorescence intensity of the obtained mixed solution.

17. The method of claim 16, wherein the deuterated acetone is detected in acetone. The concentration of the carbazole derivative in the mixed solution is 45-55 umol / L, and the ultraviolet absorption intensity of the mixed solution is tested; and / or, The concentration of the carbazole derivative in the mixed solution is 0.10 umol / L to 0.15 umol / L, and the fluorescence intensity of the mixed solution is tested.

18. The method of detecting deuterated acetone in acetone according to claim 16 or 17, wherein, The ultraviolet absorption intensity of the mixed solution at 380 nm is tested; and / or, The fluorescence intensity of the mixed solution at 480 nm is tested.

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