A tanshinone benzimidazole-type fluorescent probe and its preparation method and its application in detecting BF3

Abstract

The present invention discloses a tanshinone benzimidazole fluorescent probe, a preparation method thereof, and an application thereof in detecting BF3. Tanshinone IIa is directly subjected to a condensation reaction with 2-hydroxy-5-methylbenzaldehyde and ammonium acetate to prepare 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol. The compound can selectively react with BF3. After the reaction, green fluorescence is weakened and blue fluorescence is enhanced. The compound can be used as a fluorescent probe for detecting BF3.

Description

Technical Field

[0001] The present invention belongs to the field of fine organic synthesis, and in particular relates to a tanshinone benzimidazole type fluorescent probe, a preparation method thereof, and an application thereof in detecting BF3. Background Art

[0002] Boron trifluoride (BF3) is an important inorganic compound and an important raw material for the synthesis of a variety of organic and inorganic borides. At the same time, it is also widely used in organic synthesis as a Lewis acid. However, boron trifluoride is highly toxic and reactive. Boron trifluoride reacts extremely strongly with metals and organic matter. The upper limit of the safety threshold of BF3 is 1ppm. Inhalation toxicity studies have shown that exposure to 17mg / m 3 The presence of BF3 in an atmosphere of high concentrations can cause kidney toxicity in rats. As can be seen from the above data, even a small amount of BF3 leakage can lead to serious environmental pollution and biological toxicity. Therefore, developing an effective method for detecting BF3 is of great significance.

[0003] Traditional methods for detecting boron trifluoride, such as chromatography, titration, electrochemistry, and high-performance liquid chromatography, suffer from expensive instrumentation, complex operation, and high costs, making them incapable of rapid on-site detection. Fluorescent probes, however, offer advantages such as rapid detection, wide scope, and high sensitivity, and have been widely used in the detection of boron trifluoride and other substances.

[0004] Tanshinone, one of the active ingredients in Danshen (Salvia miltiorrhiza), is widely used in clinical practice in my country for anti-tumor treatment. Tanshinone primarily consists of tanshinone I, tanshinone IIa, and cryptotanshinone. Tanshinone IIa is a key pharmacological component of tanshinone and is present in relatively high concentrations.

[0005] Up to now, many organic fluorescent probes have been studied for detecting ions, such as NIR iridium (III)-based fluorescent probes, coumarin-based fluorescent probes, and triarylborane fluorescent probes for detecting boron trifluoride. However, there are currently no reports on the synthesis of tanshinone benzimidazole-based fluorescent probes for detecting boron trifluoride. Summary of the Invention

[0006] The purpose of this section is to summarize some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of this application to avoid obscuring the purpose of this section, the abstract and the title of the invention, and such simplifications or omissions should not be used to limit the scope of the present invention.

[0007] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.

[0008] Therefore, the purpose of the present invention is to overcome the deficiencies in the prior art and provide a tanshinone benzimidazole-type fluorescent probe.

[0009] To solve the above technical problems, the present invention provides the following technical solution: a tanshinone benzimidazole-type fluorescent probe, the fluorescent probe is named: 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furano[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol, with the structural formula:

[0010]

[0011] Another object of the present invention is to overcome the deficiencies in the prior art and provide a method for preparing a tanshinone benzimidazole-type fluorescent probe.

[0012] In order to solve the above technical problems, the present invention provides the following technical solutions: a method for preparing a tanshinone benzimidazole-type fluorescent probe, comprising:

[0013] Tanshinone IIa, 2-hydroxy-5-methylbenzaldehyde and ammonium acetate are condensed to prepare 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol.

[0014] As a preferred embodiment of the preparation method of the present invention, the method comprises:

[0015] p-2-Hydroxy-5-methylbenzaldehyde and ammonium acetate were dissolved in acetic acid, and then the acetic acid solution of Tanshinone IIa was slowly added. After the reaction was completed, the precipitated solid was neutralized with a saturated sodium bicarbonate aqueous solution, filtered, and purified by column chromatography using petroleum ether:ethyl acetate in a volume ratio of 500:1 to 100:1 to obtain a white solid 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol.

[0016] As a preferred embodiment of the preparation method of the present invention, the molar ratio of tanshinone IIa, 2-hydroxy-5-methylbenzaldehyde and ammonium acetate is 1:3:7.

[0017] As a preferred embodiment of the preparation method of the present invention, the reaction reflux temperature is 110-125° C., and the reaction time is 40-60 min.

[0018] As a preferred embodiment of the preparation method of the present invention, the reaction reflux temperature is 125° C. and the reaction time is 60 min.

[0019] Another object of the present invention is to overcome the deficiencies in the prior art and provide a tanshinone benzimidazole-based fluorescent probe for use in detecting boron trifluoride, wherein the concentration of the boron trifluoride is 0 to 80 μM.

[0020] Beneficial effects of the present invention:

[0021] The present invention uses tanshinone IIa, a natural product with abundant resources and excellent fluorescent activity, as a raw material to prepare 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthrene[3,4-d]imidazol-11-yl)phenol (TBS). Compared with the previous tanshinone IIa, the ketone carbonyl group is modified and a phenol group is introduced, which can effectively improve the water solubility of the compound. The o-hydroxybenzimidazole portion has an excited state intramolecular proton transfer (ESIPT) effect and can selectively complex with boron trifluoride to form a boron difluoride complex, effectively inhibiting the ESIPT effect, weakening green fluorescence and enhancing blue fluorescence. The compound can be used as a fluorescent probe for detecting boron trifluoride. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive effort. Among them:

[0023] Figure 1 This is a fluorescence emission spectrum effect diagram of the interaction of 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol with different analytes in the examples of the present invention.

[0024] Figure 2 This is a fluorescence emission spectrum effect diagram of 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol and different concentrations of boron trifluoride in an embodiment of the present invention.

[0025] Figure 3 This is a fluorescence effect diagram of 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol under 365nm ultraviolet light with boron trifluoride and different interfering analytes in an embodiment of the present invention.

[0026] Figure 4This is a fluorescence emission spectrum effect diagram of 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol in Example 4 of the present invention after complexing with boron trifluoride and interacting with different analytes.

[0027] Figure 5 Figures 1 and 2 show the experimental conditions and results in Example 7 of the present invention, wherein (a) shows a method for preparing test paper for detecting gaseous boron trifluoride; (b) shows the fluorescence effect of test paper loaded with 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthrene[3,4-d]imidazol-11-yl)phenol when exposed to gaseous boron trifluoride in a boron trifluoride solution (0-30%) under 365nm ultraviolet light; and (c) shows the fluorescence effect of test paper loaded with 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthrene[3,4-d]imidazol-11-yl)phenol when exposed to different volatile organic compounds (VOCs) under 365nm ultraviolet light. DETAILED DESCRIPTION

[0028] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0029] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0030] Secondly, the term "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in various places throughout this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive of other embodiments.

[0031] Example 1

[0032] The synthesis method of tanshinone benzimidazole compounds comprises the following steps:

[0033]

[0034] The specific steps are as follows:

[0035] Preparation of 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol:

[0036] Accurately weigh 0.4 g of 2-hydroxy-5-methylbenzaldehyde and 0.6 g of ammonium acetate were added to a three-necked flask, and 8 ml of acetic acid was added and stirred to dissolve. Accurately weigh 0.29 g of tanshinone IIa was added 4 mL of acetic acid to dissolve it and then added to a dropping funnel. The acetic acid solution of tanshinone IIa was slowly added dropwise to the three-necked flask using a dropping funnel. The reaction was carried out at 125° C. for 60 minutes, and the precipitated solid was neutralized with saturated sodium bicarbonate aqueous solution. The solid was filtered and purified by column chromatography with petroleum ether: ethyl acetate = 500:1 to 100:1 to obtain a white solid compound 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furano[2',3':1,2]phenanthro[3,4-d]imidazol-11-yl)phenol with a yield of 80.2%.

[0037] Product characterization data are: 1 H NMR (600MHz, CDCl3): δ11.6(brs,1H),8.17(d,J=8.6Hz,1H),7.80(dd,J=4.6,1.6Hz,1H),7.64(d d,J=8.7,2.5Hz,1H),7.57(dd,J=3.6,1.6Hz,1H),7.23(ddd,J=10.8,8.3,2.2Hz,1H),7.04(dd,J= 8.4,3.3Hz,1H),3.76(t,J=6.4Hz,1H),3.62(t,J=6.4Hz,1H),2.58(dd,J=13.1,1.4Hz,3H),2.41 (d,J=12.4Hz,3H),2.09(m,1H),2.02(m,1H),1.84(m,1H),1.80(m,1H),1.43(s,3H),1.42(s,3H). 13 C NMR (151MHz, CDCl3): δ155.92,151.10,149.84,144.06,141.29,133.69,133.34,132.42,131.34,130.27,128.66,125.99,125.2 4,121.82,118.51,117.15,116.89,116.33,114.76,38.53,34.56,31.90,30.21,20.58,19.72,9.31.ESI-MS: m / zcalculatedforC 27 H 27 N2O2[M+H]+ 411.2073,found411.2083.

[0038] Example 2

[0039] Accurately weigh 4.1 mg of fluorescent probe TBS and dissolve it in acetonitrile to prepare 1×10 -3 M solution, take 100 μM stock solution and dilute it with acetonitrile to 10 mL with a concentration of 1×10 -5 M solution, and then added equimolar amounts of BF3, NaF, NaHF, NaBH4, B2O3, KF, HF, H2BO3, benzoic acid, phenylboric acid, acetic acid, acetyl chloride, oxalyl chloride and other analytes, and recorded the fluorescence changes of the solution.

[0040] like Figure 1 As shown, when other analytes are added, the fluorescence spectrum does not change significantly, with a higher fluorescence intensity at 496 nm. After adding boron trifluoride, the wavelength blue-shifts to 427 nm with a higher fluorescence emission intensity.

[0041] This indicates that the compound has excellent selectivity as a fluorescence ratio probe for detecting boron trifluoride.

[0042] Example 3

[0043] The fluorescent probe TBS was dissolved in acetonitrile (1×10 -5 M), add (0~70)×10 -5 The fluorescence emission spectra of 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furano[2',3':1,2]phenanthro[3,4-d]imidazol-11-yl)phenol with different concentrations of boron trifluoride were measured. Figure 2 As shown in the figure, the fluorescence emission spectra of boron trifluoride with different concentrations are added. With the addition of boron trifluoride, the fluorescence intensity of the compound at 496 nm gradually decreases and the fluorescence intensity at 427 nm gradually increases, indicating that the compound can be complexed with boron trifluoride.

[0044] In the concentration range of 0 to 80 μM, the fluorescence intensity ratio of the fluorescent probe TBS showed a good linear relationship with the concentration of boron trifluoride, and the linear regression equation was y = 0.012x + 0.229, R 2 =0.9964.

[0045] According to the formula LOD = 3δ / K, the detection limit (LOD) was calculated to be as low as 98 nM.

[0046] Example 4

[0047] Accurately weigh 4.1 mg of fluorescent probe TBS and dissolve it in acetonitrile to prepare 1×10-3 M solution, take 70 μM stock solution and dilute it with acetonitrile to 10 mL with a concentration of 1×10 -5 M solution, add 80 μL of boron trifluoride (1×10 -2 M), observed under 365nm ultraviolet light, as Figure 3 As shown, after adding boron trifluoride, the solution fluorescence changes from green to blue, indicating that the compound can complex with BF3.

[0048] However, by adding equimolar amounts of NaF, NaHF, NaBH4, B2O3, KF, HF, H2BO3, benzoic acid, phenylboric acid, acetic acid, acetyl chloride, oxalyl chloride and other test substances, no obvious change in fluorescence color was found.

[0049] This indicates that the compound can be used as a fluorescent probe to effectively identify boron trifluoride.

[0050] Example 5

[0051] In the fluorescent probe TBS (1×10 -5 M) and boron trifluoride (1×10 -4 Interference experiments were conducted by adding equimolar amounts of other analytes, including NaF, NaHF, NaBH₄, B₂O₃, KF, HF, H₂BO₃, benzoic acid, phenylboric acid, acetic acid, acetyl chloride, and oxalyl chloride, to the fluorescence system (M). Changes in fluorescence intensity were recorded using a fluorescence spectrophotometer.

[0052] like Figure 4 As shown, after adding other analytes, the ratio of the fluorescence intensity at 427 nm to the fluorescence intensity at 496 nm did not change significantly, so the compound has good anti-interference ability when detecting boron trifluoride, indicating that the compound is a highly specific fluorescent probe for detecting boron trifluoride.

[0053] Example 6

[0054] Optimization of the preparation method of 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol:

[0055] Experiment 1: Accurately weigh 200 mg of 2-hydroxy-5-methylbenzaldehyde and 228 mg of ammonium acetate, add them to a three-necked flask, then add 5 mL of dichloromethane and stir to dissolve, accurately weigh 216 mg of tanshinone IIa, add 10 mL of dichloromethane to dissolve it, and then add it to a dropping funnel. Use a dropping funnel to slowly add the dichloromethane solution of tanshinone IIa to the three-necked flask, add a few drops of acetic acid, reflux at 50°C, stir overnight, neutralize with saturated sodium bicarbonate aqueous solution to precipitate the solid, filter, and purify by column chromatography with petroleum ether: ethyl acetate = 300:1~5:1 to obtain 102 mg of yellow solid compound 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furano[2',3':1,2]phenanthro[3,4-d]imidazol-11-yl)phenol, with a yield of 50%.

[0056] Experiment 2: Accurately weigh 100 mg of 2-hydroxy-5-methylbenzaldehyde and 114 mg of ammonium acetate, add them to a three-necked flask, then add 5 mL of acetic acid and stir to dissolve, accurately weigh 142 mg of tanshinone IIa, add 5 mL of acetic acid to dissolve it and then add it to a dropping funnel, and use a dropping funnel to slowly add the acetic acid solution of tanshinone IIa dropwise into the three-necked flask. Under N2 protection, reflux at 125 ° C for 5 hours. The reaction mixture is cooled to room temperature, neutralized with saturated sodium bicarbonate aqueous solution to precipitate the solid, filtered, and purified by column chromatography with petroleum ether: ethyl acetate = 500: 1-100: 1 to obtain 126 mg of a white solid compound 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furano[2',3':1,2]phenanthro[3,4-d]imidazol-11-yl)phenol, with a yield of 62%.

[0057] Experiment 3: Accurately weigh 400 mg of 2-hydroxy-5-methylbenzaldehyde and 600 mg of ammonium acetate, add them to a three-necked flask, then add 8 ml of acetic acid and stir to dissolve, accurately weigh 290 mg of tanshinone IIa, add 4 mL of acetic acid to dissolve it, and then add it to a dropping funnel. Use a dropping funnel to slowly add the acetic acid solution of tanshinone IIa to the three-necked flask, react at 125°C for 60 minutes, neutralize with saturated sodium bicarbonate aqueous solution to precipitate the solid, filter it, and purify it by column chromatography with petroleum ether: ethyl acetate = 500:1~100:1 to obtain 232 mg of a white solid compound 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furano[2',3':1,2]phenanthro[3,4-d]imidazol-11-yl)phenol, with a yield of 80.2%.

[0058] Table 1

[0059]

[0060] As can be seen from Table 1, the reaction time of the conditions of Experiment 3 is the fastest and the yield is the highest compared with other reaction conditions, so this condition is selected for the reaction.

[0061] Example 7

[0062] Boron trifluoride often exists in the atmosphere in gaseous form, so it is necessary to develop an effective method to detect boron trifluoride. In recent years, based on its many advantages such as rapid on-site detection, low cost, and simple operation, the method of detecting various analytes with probe-loaded solid materials has received widespread attention and development. Figure 5 (a) The method shown in Figure 2 detects gaseous boron trifluoride. We fabricated a test paper loaded with the fluorescent probe TBS to utilize the high sensing ability of the fluorescent probe TBS for boron trifluoride.

[0063] The results showed that after exposure to acetonitrile solution containing different concentrations of boron trifluoride (0, 2%, 5%, 10%, 20%, 30%, v / v) for 15 minutes, the fluorescence of the test paper changed from dark green to bright blue (such as Figure 5 It is worth noting that the fluorescent probe TBS can effectively detect gaseous boron trifluoride at a concentration below 5%.

[0064] In addition, the selectivity of the test paper for other volatile organic compounds (VOCs) ((1) ether, (2) acetone, (3) chloroform, (4) ethyl acetate, (5) toluene, (6) benzene, (7) ethylene glycol, (8) ammonia, (9) formaldehyde, (10) tetrahydrofuran, (11) boron trifluoride) was also studied. Figure 5 As shown in (c), the test paper showed no fluorescence changes after being exposed to these volatile organic compounds. These results indicate that the test paper containing the fluorescent probe TBS can be used as a portable, highly sensitive boron trifluoride gas detection kit.

[0065] The invention provides a tanshinone benzimidazole type fluorescent probe for detecting boron trifluoride, which reacts with boron trifluoride and enhances blue fluorescence under irradiation of ultraviolet light with a wavelength of 365nm, and is used for detecting the concentration of boron trifluoride.

[0066] The present invention provides a method for preparing the aforementioned tanshinone benzimidazole-based fluorescent probe for detecting boron trifluoride. The method utilizes tanshinone IIa, a natural product with abundant resources and excellent fluorescent activity, as a raw material. The probe is prepared through a simple and easy-to-operate chemical reaction. The raw material is widely available, laying the foundation for large-scale production. The present invention also provides an application of the aforementioned tanshinone benzimidazole-based fluorescent probe for detecting boron trifluoride. The compound selectively reacts with boron trifluoride, enhancing blue fluorescence, and can be used as a fluorescent probe for detecting boron trifluoride.

[0067] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, and all of these should be included in the scope of the present invention.

Claims

1. Application of a tanshinone benzimidazole-based fluorescent probe in the detection of boron trifluoride, characterized in that: The fluorescent probe is named: 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol, and its structural formula is: Among them, the tanshinone benzimidazole-type fluorescent probe reacts with boron trifluoride and enhances its blue fluorescence under irradiation with ultraviolet light at a wavelength of 365 nm, which is used to detect the concentration of boron trifluoride.

2. The use according to claim 1, characterized in that: The method for preparing the tanshinone benzimidazole fluorescent probe comprises: Tanshinone IIa, 2-hydroxy-5-methylbenzaldehyde and ammonium acetate were condensed to prepare 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol.

3. The use according to claim 2, characterized in that: The method for preparing the tanshinone benzimidazole fluorescent probe comprises: p-2-Hydroxy-5-methylbenzaldehyde and ammonium acetate were dissolved in acetic acid, and then the acetic acid solution of Tanshinone IIa was slowly added. After the reaction was completed, the precipitated solid was neutralized with a saturated sodium bicarbonate aqueous solution, filtered, and purified by column chromatography using petroleum ether:ethyl acetate in a volume ratio of 500:1 to 100:1 to obtain 4-methyl-2-(1,6,6-trimethyl-7,8,9,12-tetrahydro-6H-furo[2',3':1,2]phenanthren[3,4-d]imidazol-11-yl)phenol as a white solid.

4. The use according to claim 3, characterized in that: The molar ratio of tanshinone IIa, 2-hydroxy-5-methylbenzaldehyde and ammonium acetate is 1:3:

7.

5. The use according to claim 4, characterized in that: The reaction reflux temperature is 110~125℃, and the reaction time is 40~60min.

6. The use according to claim 5, characterized in that: The reaction reflux temperature was 125°C and the reaction time was 60 min.

7. The use according to claim 1, characterized in that: The concentration of the boron trifluoride is 0-80 μM.

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