Carbazole derivative as well as preparation method and application thereof

Abstract

The invention relates to a carbazole derivative as well as a preparation method and application thereof. The structural formula of the carbazole derivative provided by the invention is as shown in (I), and the carbazole derivative is prepared by reacting 2-furanboronic acid with chloroisoquinoline, then halogenating, and then reacting the halogenated product with N-phenyl-3-carbazole boronic acid. The carbazole derivative can be used as an organic small molecule probe for testing a deuterated reagent, can be very simply and conveniently used for rapid qualitative and quantitative analysis of deuterated acetone in acetone, and has relatively high detection sensitivity and accuracy. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemistry and analytical detection, and specifically relates to a carbazole derivative and a preparation method and application thereof. Background Art

[0002] The conventional detection method commonly used in the qualitative and quantitative analysis of deuterated acetone in acetone at present is to use professional analytical instruments (such as nuclear magnetic resonance instrument, mass spectrometer, etc.) to detect. In the NMR spectrogram, the signal of deuterium usually appears in the position different from ordinary hydrogen. By analyzing the chemical shift (chemical shift), intensity and pattern of these signals, the presence of deuterium in the sample can be identified, and the content of deuterium in the sample can be quantitatively calculated by comparing the intensity of the deuterium signal with the internal or external standard. Mass spectrum can distinguish different isotopes in molecules, and is very suitable for detecting the presence and content of deuterium in acetone. Therefore, it is an effective method to use mass spectrometry (Mass Spectrometry, MS for short) to detect the deuterated acetone in acetone. The test sample is ionized in the mass spectrometer, and the ionized molecules are guided into the mass analyzer, which separates the ions according to the mass-to-charge ratio (m / z); the molecules or fragment ions of deuterated acetone will have a different mass-to-charge ratio from acetone (because deuterium is heavier than ordinary hydrogen), which causes the peak of deuterated acetone in the mass spectrum to be slightly shifted from that of non-deuterated acetone; by comparing the peak position and intensity 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 and trained testing personnel to operate, are cumbersome and complicated, and are limited by the testing instruments and sites, making them impossible to carry out portable testing. Summary of the invention

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

[0005] In order to achieve the above-mentioned object of the invention, the present invention includes the following technical solutions.

[0006] In one aspect, the present invention provides a carbazole derivative having a structure as shown in the following formula (I):

[0007]

[0008] In a second aspect, 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 obtain compound 1;

[0010] (2) Compound 1 reacts with a halogenating agent to obtain compound 2;

[0011] (3) Compound 2 reacts with N-phenyl-3-carbazole boronic acid to obtain a carbazole derivative having a structure represented by formula (I);

[0012] The reaction formula is as follows:

[0013]

[0014] Wherein, R is a halogen.

[0015] In a third aspect, the present invention provides the use of the carbazole derivative as a probe of a deuterated reagent in detecting a deuterated reagent, wherein the deuterated reagent may be deuterated acetone.

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

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

[0018] The present invention designs and synthesizes a novel carbazole derivative. 2-furanboronic acid reacts with chloroisoquinoline and then undergoes halogenation. The halogenated product is then reacted with N-phenyl-3-carbazoleboronic acid to prepare the carbazole derivative. The compound can be used as an organic small molecule probe for testing deuterated reagents. The carbazole derivative of the present invention is added to an acetone solution, and its ultraviolet absorption intensity is tested by simple equipment to determine whether the acetone contains deuterated acetone; further, its fluorescence spectrum is tested, and according to the fluorescence intensity, it can be determined whether the acetone contains deuterated acetone and the content of the deuterated acetone, thereby achieving simple and rapid detection of whether the acetone solution contains deuterated reagents. The carbazole derivative provided by 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. BRIEF DESCRIPTION OF THE DRAWINGS

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

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

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

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

[0023] Figure 5 This is the UV spectrum of an acetone solution containing a carbazole derivative probe.

[0024] Figure 6 This is a graph showing the concentration percentage of deuterated acetone in acetone solution and the fluorescence response of the carbazole derivative probe.

[0025] Figure 7 The linear relationship between fluorescence intensity and deuterated acetone concentration. DETAILED DESCRIPTION

[0026] In order to facilitate the understanding of the present invention, the present invention will be described more fully below. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0027] The experimental methods in the following examples without specifying specific conditions are usually carried out under conventional conditions or conditions recommended by the manufacturers. The various commonly used chemical reagents used in the examples are all commercially available products.

[0028] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used in the present invention includes any and all combinations of one or more of the related listed items.

[0029] In addition, as used in the present invention, the term "or" is an inclusive "or" symbol and is equivalent to the term "and / or", unless the context clearly dictates otherwise. The term "based on" is not exclusive and allows for being based on other factors not described, unless the context clearly dictates otherwise. In addition, throughout the specification, the meanings of "a", "an", and "the" include plural referents. The meaning of "in..." includes "in..." and "on...".

[0030] In order to provide a simple, convenient and rapid detection method for the qualitative and quantitative analysis of deuterated acetone in acetone, the inventors of the present invention designed and synthesized a novel carbazole derivative, which can be used as an organic small molecule probe for testing deuterated reagents, can be very simple and conveniently used for the rapid qualitative and quantitative analysis of deuterated acetone in acetone, and has high detection sensitivity and accuracy.

[0031] In one embodiment of the present invention, a carbazole derivative having a structure shown in the following 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 obtain compound 1;

[0035] (2) Compound 1 reacts with a halogenating agent to obtain compound 2;

[0036] (3) Compound 2 reacts with N-phenyl-3-carbazole boronic acid to obtain a carbazole derivative having a structure represented by formula (I);

[0037] The reaction formula is as follows:

[0038]

[0039] Wherein, R is a halogen.

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

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

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

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

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

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

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

[0047] In some embodiments, the reaction temperature of step (1) is 80° C. to 90° C., and the reaction 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 halogenating agent in step (2) is 1:1.1-1.5, preferably 1:1.1-1.3.

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

[0050] In some embodiments, the reaction temperature of step (2) is 20° C. to 30° C., and the reaction time is 12 hours to 24 hours, preferably 15 hours to 20 hours.

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

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

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

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

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

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

[0057] In another embodiment of the present invention, the use of the carbazole derivative as a probe of a deuterated reagent in detecting a deuterated reagent is provided, and the deuterated reagent may be deuterated acetone, etc. The inventors have found that the carbazole derivative of the present invention can be very simple and conveniently used 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, which comprises: adding the carbazole derivative of the present invention to a solution to be tested, and testing the ultraviolet absorption intensity and / or fluorescence intensity of the resulting mixed solution.

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

[0060] The carbazole derivative of the present invention is added to an acetone solution, and its ultraviolet absorption intensity (for example, ultraviolet absorption intensity at 380nm) is tested by simple equipment to determine whether the acetone contains deuterated acetone; further, its fluorescence spectrum is tested, and according to the fluorescence intensity (for example, fluorescence intensity at 480nm), it can be determined whether the acetone contains deuterated acetone and the content of deuterated acetone, thereby realizing a simple and rapid detection of whether the acetone solution contains a deuterated reagent. The detection method is simple to operate and simple to use, and can realize portable and rapid detection of deuterated acetone.

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

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

[0063] The synthetic route is as follows:

[0064]

[0065] The 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, and then tetrakistriphenylphosphine palladium (1.45 g, 1.26 mmol) and 2M potassium carbonate solution (76 mL, the solvent is water) were added, and heated at 85 degrees Celsius for 48 hours. After cooling to room temperature, it was extracted with ethyl acetate and purified water, and the organic phase was dried with a rotary evaporator, and then purified with dichloromethane and n-hexane using silica gel column chromatography to obtain compound 1 (4.1 g, yield 83.67%).

[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 solution was dried by rotary evaporation, and then purified by silica gel column chromatography with dichloromethane and n-hexane to obtain compound 2 (3.12 g, yield 90.17%).

[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-carbazole boronic acid (2.36 g, 8.21 mmol) were added to 100 mL of tetrahydrofuran, and then tetrakistriphenylphosphine palladium (0.63 g, 0.55 mmol) and 2M potassium carbonate solution (17 mL, the solvent is water) were added, and heated at 85 degrees Celsius for 48 hours. After cooling to room temperature, it was extracted with ethyl acetate and purified water, the organic phase was dried by rotary evaporation, and then purified by silica gel column chromatography with dichloromethane and n-hexane to obtain the target product probe (2.18 g, yield 91.40%).

[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 UV spectrum detection

[0077] The test method is as follows:

[0078] The carbazole derivative probe prepared in Example 1 was prepared into solutions with a concentration of 50 uM using acetone and deuterated acetone (acetone-d) as solvents, respectively, and were recorded as acetone solution and acetone-d solution, respectively.

[0079] 4 mL of acetone solution and 4 mL of acetone-d solution were added to measuring dishes respectively, and tested at room temperature using an ultraviolet spectrometer (gilent Technologies Cary 8454 UV–Vis spectrometer).

[0080] Test results such as Figure 5As shown: the carbazole derivative probe exhibits strong absorption in the ultraviolet region of about 380nm, which is caused by the charge transfer transformation inside the carbazole derivative. The absorption peak at 380nm of the carbazole derivative probe in the acetone-d solution decreases significantly. It can be seen that deuterated acetone will affect the charge transfer state inside the carbazole derivative, thereby causing changes in the spectral performance. This shows that the carbazole derivative probe prepared by the present invention can be used to detect whether acetone contains deuterated acetone, and can be used very simply and conveniently for the rapid qualitative analysis of deuterated acetone in acetone.

[0081] Example 3 Fluorescence spectroscopy detection

[0082] The detection method is as follows:

[0083] Acetone and acetone-d were used as solvents, or acetone and acetone-d were used as mixed solvents in different ratios to prepare a solution of the carbazole derivative probe with a concentration of 0.125 uM, and the content percentage of acetone-d in the solution was adjusted (e.g. Figure 6 shown).

[0084] 4 mL of each solution was added to a measuring dish, and fluorescence spectrum test was performed at room temperature with a test wavelength of 400 to 800 nm using an Agilent Technologies Cary Eclipse Fluorescence spectrometer.

[0085] Test results such as Figure 6 As shown in the figure: In the undeuterated acetone solution, the fluorescence intensity of the carbazole derivative probe at 480nm is the highest; after adding deuterated acetone, the fluorescence intensity at 480nm decreases significantly, and as the content of deuterated acetone increases, the fluorescence intensity at 480nm decreases more. In the deuterated acetone concentration range of 0% to 100%, there is a good linear relationship between the fluorescence intensity at 480nm and the deuterated acetone concentration (such as Figure 7 shown).

[0086] These results indicate that the carbazole derivative probe synthesized in the present 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 above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A carbazole derivative having a structure represented by the following formula (I):

2. A method for preparing a carbazole derivative, characterized in that: The steps include: (1) 2-Furanboronic acid reacts with compound A to obtain compound 1; (2) Compound 1 reacts with a halogenating agent to obtain compound 2; (3) Compound 2 reacts with N-phenyl-3-carbazole boronic acid to obtain a carbazole derivative having a structure represented by formula (I); The reaction formula is as follows: Wherein, R is a halogen.

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

4. The method for preparing a carbazole derivative according to claim 2 or 3, characterized in that: The 2-furanboric acid in step (1) reacts with compound A under the action of tetrakis(triphenylphosphine)palladium and a base; and / or, The solvent for the reaction in step (1) is tetrahydrofuran and water; and / or, The molar ratio of 2-furanboronic acid to compound A in step (1) is 1.2 to 1.8:1; and / or, The reaction temperature of step (1) is 80°C to 90°C and the reaction time is 40 hours to 56 hours; Preferably, the base is potassium carbonate or sodium carbonate; Preferably, the base is added to the reaction system in the form of an alkaline solution, and the volume ratio of the tetrahydrofuran to the alkaline solution is 2 to 6:1; Preferably, the concentration of the alkali in the alkali solution is 1.8 mol / L to 2.5 mol / L; Preferably, the molar ratio of the compound A to the tetrakis(triphenylphosphine)palladium is 1:0.05-0.

1.

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

6. The method for preparing a carbazole derivative according to claim 2 or 3, characterized in that: Step (3) the compound 2 is reacted with N-phenyl-3-carbazole boronic acid in the presence of tetrakis(triphenylphosphine)palladium and a base; and / or, The solvent for the reaction in step (3) is tetrahydrofuran and water; and / or, In step (3), the molar ratio of the compound 2 to N-phenyl-3-carbazole boronic acid is 1:1.2-1.8; and / or, The reaction temperature in step (3) is 80°C to 90°C and the reaction time is 40 hours to 56 hours; Preferably, the base is potassium carbonate or sodium carbonate; Preferably, the base is added to the reaction system in the form of an alkaline solution, and the volume ratio of the tetrahydrofuran to the alkaline solution is 2 to 6:1; Preferably, the concentration of the alkali in the alkali solution is 1.8 mol / L to 2.5 mol / L; Preferably, the molar ratio of the compound A to the tetrakis(triphenylphosphine)palladium is 1:0.06-0.

12.

7. Use of the carbazole derivative according to claim 1 as a probe of a deuterated reagent in detecting a deuterated reagent, preferably, the deuterated reagent is deuterated acetone.

8. A method for detecting deuterated acetone in acetone, characterized in that: include: The carbazole derivative according to claim 1 is added to the solution to be tested, and the ultraviolet absorption intensity and / or fluorescence intensity of the obtained mixed solution is tested.

9. The method for detecting deuterated acetone in acetone according to claim 8, characterized in that: The concentration of the carbazole derivative in the mixed solution is 45umol / L to 55umol / 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.

10. The method for detecting deuterated acetone in acetone according to claim 8 or 9, characterized in that: Testing the ultraviolet absorption intensity of the mixed solution at 380 nm; and / or, The fluorescence intensity of the mixed solution was tested at 480 nm.

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