Preparation method of BODIPY fluorescent probe containing triazole ring and ion monitoring application

Abstract

The present application relates to a kind of synthesis method of BODIPY fluorescent probe containing triazole ring BODIPY, the present application synthesizes a kind of ionic probe, select the better probe body BODIPY, triazole ring is constructed in the meso position of BODIPY by click reaction.The synthesis method is recognized by anion through triazole structure, and the self-aggregation phenomenon of BODIPY molecule is improved by the introduction of meso position fat chain, since spectral shift is not conducive to observation, the defect of small stoke shift is effectively made up by click reaction, wavelength shift is in near infrared region, form a kind of triazole ring fluorescent probe that can sensitively identify CN ‑ ion. Triazole ring has good chemical activity and biological activity, since lone pair of electrons can form conjugated system with ion, chelation occurs, and chelate is formed.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and mainly to a method for synthesizing a triazole ring-containing BODIPY fluorescent probe and its application in the field of ion monitoring. Background Technology

[0002] Due to the excellent bio and chemical activity of nitrogen-containing heterocycles, they can rapidly bind with ions in solution via lone pairs, inducing a conjugation effect to form chelates, thus serving as important functional groups for ion probes. BODIPY-type compounds possess high fluorescence quantum yields and molar absorptivity, exhibiting strong resistance to external environmental interference, and show promising applications in medicine, pesticides, dyes, and other fields; therefore, this type of probe molecule was chosen as the fluorophore. Since cyanide ions are highly toxic and readily soluble in water, they can be absorbed by the human body through the mouth, respiratory tract, and even skin. After being acted upon by gastric acid, they produce cyanogenic acid, which, once absorbed, combines with Fe in the blood... 3+ Cyanide ions bind to and lose their ability to transport cells, hindering cellular respiration and promoting apoptosis. Water resources that humans are frequently exposed to are highly susceptible to cyanide contamination; therefore, industrial monitoring of cyanide ions is of paramount importance.

[0003] Since industrial emissions are unavoidable and pose numerous problems, it is of great practical significance to find a way to quickly monitor whether cyanide ions in water exceed the standard in order to meet national environmental protection requirements and protect water resources. Summary of the Invention

[0004] The technical problem to be solved by this invention is to synthesize a BODIPY-type fluorescent probe containing a triazole ring for cyanide ion monitoring. The synthesis method identifies anions through the triazole structure, and the introduction of the fatty chain at the meso position improves the self-aggregation phenomenon of BODIPY molecules. Since the spectral shift is not conducive to observation, the small Stocker shift is effectively compensated by the Knaussen reaction.

[0005] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows:

[0006] A novel method for synthesizing a triazole ring-containing BODIPY-type fluorescent probe, characterized by the following reaction:

[0007]

[0008] The DDQ is 2,3-dichloro-5,6-dicyanobenzoquinone.

[0009] Furthermore, since the catalyst is not readily soluble in organic reagents, care should be taken to prevent the reaction system from being in a heterogeneous state to avoid incomplete reaction. The optimal reaction temperature is 30°C. The reaction time is 1.5 hours.

[0010] Moreover, compounds The specific preparation method is as follows:

[0011] (1) 2,4-Dimethylpyrrole and 4-ethynylbenzaldehyde were added to a solvent and reacted for 8-9 h. Then, an organic acid was added to the reaction system, and the mixture was heated and stirred. The reaction progress was monitored by TLC. The mixture was then cooled to 0 °C, and boron trifluoride diethyl ether and a weak organic base were added. After the reaction was complete, the compound was separated by silica gel chromatography.

[0012] (2) The compound in (1) The compound was added to a solvent, along with cuprous iodide and ethyl azide. The reaction was allowed to proceed for 1.5 hours. After the reaction was complete, the mixture was extracted, rotary evaporated, and then subjected to silica gel column chromatography to obtain the compound.

[0013] Moreover, the solvent in step (1) is one or more of dichloromethane, N,N-dimethylformamide, dimethyl sulfoxide, and tetrahydrofuran;

[0014] The organic acid should be trifluoroacetic acid;

[0015] The organic weak base may be at least one of diethylamine, triethylamine, and ethylamine;

[0016] The reaction temperature is 25-80℃, preferably 30-60℃;

[0017] The molar ratio of 4-ethynylbenzaldehyde, 2,4-dimethylpyrrole, organic acid, boron trifluoride ether, and organic weak base can be 1:(2-6):(0-2):(2-8):(2-8).

[0018] Moreover, the reaction solvent mixture used in step (2) is one of three aqueous solutions: tetrahydrofuran and water, methanol and water, or dimethyl sulfoxide and water.

[0019] Application of the novel triazole ring-containing BODIPY fluorescent probe in ion detection.

[0020] Moreover, the compound (Ⅲ) in CN - The fluorescence in the solution was significantly reduced, decreasing to around 1000, and a new emission peak appeared at 520 nm.

[0021] The advantages and positive effects of this invention are as follows:

[0022] 1. The compound (Ⅲ) prepared in this invention is in CN -The fluorescence in solution was significantly reduced, decreasing to around 1000 nm, and a new emission peak appeared at 520 nm. Due to the lone pair of electrons in the triazole ring, it readily combines with ions in solution to form a complex, hindering the PET phenomenon. Therefore, this compound exhibits good sensitivity to CN- ions. First, based on its structural characteristics, the conjugation effect of this compound was verified by ultraviolet fluorescence testing, and the change in fluorescence spectral shift was used for judgment.

[0023] 2. The method for synthesizing the triazole ring-containing BODIPY-type fluorescent probe of this invention introduces a triazole ring through a click reaction to improve the self-aggregation of probe molecules, and achieves the recognition of cyanide ions through chelation. This effectively enables the detection of trace concentrations of cyanide ions in drinking water.

[0024] 3. This invention synthesizes an ion-type probe, using the high-performance probe body BODIPY. A triazole ring is constructed at the meso site of BODIPY via a click reaction. The synthesis method recognizes anions through the triazole structure, and the introduction of the aliphatic chain at the meso site improves the self-aggregation phenomenon of the BODIPY molecule. Since the spectral shift is unfavorable for observation, the Kreutz-Nauvilla reaction effectively compensates for the small Stokes shift, placing the wavelength shift in the near-infrared region, thus forming a probe capable of sensitively recognizing CN. - Triazole ring fluorescent probes for ions. Triazole rings have good chemical and biological activity. Due to the lone pair of electrons, ions can form a conjugated system, resulting in chelation and the formation of chelates. Attached Figure Description

[0025] Figure 1 UV-Vis absorption spectra of compounds (Ⅰ)(Ⅱ)(Ⅲ) in chloroform.

[0026] Figure 2 NMR spectrum of compound (II).

[0027] Figure 3 Fluorescence spectra of compounds (Ⅰ)(Ⅱ)(Ⅲ) in CN- ion solution.

[0028] Figure 1 As can be seen from the UV-Vis spectra, the UV emission wavelength of compound (Ⅰ) is 498 nm, that of compound (Ⅱ) is 497.5 nm, and that of compound (Ⅲ) is 623 nm. Compound (Ⅱ) exhibits UV enhancement after the click reaction, increasing from position 1.26 to 3.27, indicating that the introduction of aliphatic chains improves the weak fluorescence caused by self-aggregation. The Knovengel reaction significantly red-shifts the UV spectrum of compound (Ⅲ), increasing the Stokes shift, enhancing the conjugation effect, and reducing background light interference.

[0029] Figure 2 It is known that the fluorescence emission wavelength of compound (Ⅰ) is 531 nm, that of compound (Ⅱ) is 518 nm, and that of compound (Ⅲ) is 641 nm. Compared with compound (Ⅰ), compound (Ⅱ) exhibits enhanced fluorescence, increasing by 5000 nm, which improves the self-aggregation phenomenon by introducing aliphatic chains. Compound (Ⅲ) introduces conjugated groups, increasing the spectral shift by 123 nm, while the fluorescence intensity remains within the observable range, reducing the influence of background light.

[0030] Next, experimental studies were conducted on ion detection, and common anions Cl- were prepared. - , Br - ClO4 - NO3 - CN - HSO4 - The solution was tested at room temperature using UV-Vis absorption and fluorescence spectra. The results showed that compound (III) was only effective against CN. - Ions respond.

[0031] Figure 3 Figure a), b), and c) show the fluorescence spectra of compounds (Ⅰ), (Ⅱ), and (Ⅲ) in CN- solution, respectively; d) is a magnified view of a portion of figure c.

[0032] according to Figure 3 It can be seen that compound (Ⅰ) in CN - No significant changes were observed in the ionic solution. Compound (II) showed a marked decrease in fluorescence, indicating that the triazole ring of this compound has a strong electron-withdrawing ability and readily combines with solution ions to form a complex, thus hindering the PET phenomenon. Compound (III) showed a significant decrease in fluorescence, decreasing to around 1000, and a new emission peak appeared at 520 nm, proving that a complex had been formed. This compound is effective against CN. - The ions have good sensitivity. Detailed Implementation

[0033] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be further described in detail below with reference to specific embodiments.

[0034] A novel method for synthesizing a triazole ring-containing BODIPY-type fluorescent probe, characterized by the following reaction:

[0035]

[0036] The DDQ is 2,3-dichloro-5,6-dicyanobenzoquinone.

[0037] The catalyst is not readily soluble in organic reagents, so care should be taken to prevent the reaction system from being in a heterogeneous state to avoid incomplete reaction. The optimal reaction temperature is 30°C. The reaction time is 1.5 hours.

[0038] Furthermore, the specific preparation method of compound (II) is as follows:

[0039] (1) 2,4-Dimethylpyrrole and 4-ethynylbenzaldehyde were added to a solvent and reacted for 8-9 h. Then, an organic acid was added to the reaction system, and the mixture was heated and stirred. The reaction progress was monitored by TLC. The mixture was then cooled to 0 °C, and boron trifluoride diethyl ether and a weak organic base were added. After the reaction was complete, the compound was separated by silica gel chromatography.

[0040] (2) The compound in (1) The compound was added to a solvent, along with cuprous iodide and ethyl azide. The reaction was allowed to proceed for 1.5 hours. After the reaction was complete, the mixture was extracted, rotary evaporated, and then subjected to silica gel column chromatography to obtain the compound.

[0041] In step (1), the solvent is one or more of dichloromethane, N,N-dimethylformamide, dimethyl sulfoxide, and tetrahydrofuran; the organic acid should be trifluoroacetic acid; the organic weak base can be at least one of diethylamine, triethylamine, and ethylamine; the reaction temperature is 25-80℃, preferably 30-60℃; and the molar ratio of 4-ethynylbenzaldehyde, 2,4-dimethylpyrrole, organic acid, boron trifluoride ether, and organic weak base can be 1:(2-6):(0-2):(2-8):(2-8).

[0042] The reaction solvent mixture used in step (2) is one of three aqueous solutions: tetrahydrofuran and water, methanol and water, or dimethyl sulfoxide and water.

[0043] Application of the novel triazole ring-containing BODIPY fluorescent probe in ion detection. Compound (III) in CN... - The fluorescence in the solution was significantly reduced, decreasing to around 1000, and a new emission peak appeared at 520 nm.

[0044] Example 1

[0045] Synthesis of compound (I)

[0046] In a 100 mL three-necked round-bottom flask, add 0.5 g of 4-ethynylbenzaldehyde, 10 mL of THF, and 0.4 mL of 2,4-dimethylpyrrole, and stir at room temperature for 15 min. Add 0.1 mL of trifluoroacetic acid and allow the reaction to proceed until the starting material disappears. Dissolve 0.4 g of 2,3-dichloro-5,6-dicyanobenzoquinone in 10 mL of THF and continue the reaction. Add 8 mL of triethylamine and dropwise add 7 mL of boron trifluoride diethyl ether, and react overnight. Wash with water, extract with dichloromethane, and precipitate by silica gel column chromatography to give 260 mg of an orange-red solid, yield 59%, purity 87%.

[0047]

[0048] The product was tested and found to be:

[0049] Melting point: 25-253℃

[0050] 1 H NMR (400MHz, CDCl3-d1) δ7.66-7.61(m,2H,PhH),7.27 (s,2H,PhH),6.00(s,2H),3.19(s,1H,CH≡C),2.56(s,6H, CH3),1.41(s,6H,CH3).

[0051] 13 C NMR (100MHz, CDCl3-d1) δ155.84,142.99,140.57, 135.58,132.89,131.14,128.22,122.96,121.43,82.89,78.63, 29.72,14.62,14.59.

[0052] High-resolution mass spectrometry (HRMS): Calculated value: [M+1]+ = 348.2041, Measured value: 348.2046.

[0053] Example 2

[0054] Synthesis of compound (II)

[0055] In a 100 mL single-necked round-bottom flask, 0.2 g of an orange solid, 11 mg of cuprous iodide, and 80 mL of ethyl azide were added. The mixture was reacted at room temperature in a system of tetrahydrofuran and water until complete. After washing with water, silica gel column chromatography was performed to give 185 mg of an orange-red solid, with a yield of 82% and a purity of 85%.

[0056]

[0057] The product was tested and found to be:

[0058] Melting point: 259-260℃

[0059] 1 H NMR (400MHz, CDCl3-d1) δ8.00(d,J=7.7Hz,3H,PhH), 7.37(d,J=8.3Hz,2H,PhH),5.99(s,2H),4.32(q,J=7.1 Hz,2H),2.56(s,6H,CH3),1.45(s,6H,CH3),1.35(t,J=7.1 Hz,3H,CH3).

[0060] 13 C NMR(100MHz,Acetone-d6)δ166.25,155.63,147.53, 143.12,141.20,134.95,131.40,131.17,128.66,126.47,121.29,62.61,51.01,29.71,29.32,14.61,14.11.

[0061] High-resolution mass spectrometry (HRMS): Calculated value: [M+1]+ = 477.2159, Measured value: 477.2155.

[0062] Example 3

[0063] Synthesis of compound (III)

[0064] Compound (II) 0.15 g, p-bromobenzaldehyde 0.3 g, and p-toluenesulfonic acid 0.12 g were added to a 100 mL single-necked round-bottom flask, along with an appropriate amount of piperidine. The mixture was heated to react. After washing with water, the mixture was subjected to silica gel column chromatography to give 188.5 mg of a purplish-black solid, with a yield of 55% and a purity of 89%.

[0065]

[0066] The product was tested and found to be:

[0067] Melting point: 358-359℃

[0068] 1 H NMR (400MHz, CDCl3) δ8.08 (d, J = 8.2Hz, 2H), 8.03 (s, 1H), 7.97 (s, 1H), 7.74 (d, J = 16.4Hz, 2H), 7.54-7.47 (d, J=2.6Hz,12HPhH),6.88(d,J=8.6Hz,2H),5.37(t,J=4.6Hz,1H),4.41(q,J=7.1Hz,2H,CH2),1.58(s,6H,CH3),1.46 (m,3H,CH3).

[0069] 13 C NMR(100MHz,DMSO-d6)δ162.84,152.48,147.45,142.42, 139.25,135.46,135.03,132.49,132.00,131.70,129.11,128.94,126.59,125.56,123.02,121.76,119.78,118.08,62.76,37.11, 31.94,29.71,29.38,27.10,22.70,19.74,15.07,14.25,14.13

[0070] High-resolution mass spectrometry (HRMS): Calculated value: [M+1]+ = 811.0961, Measured value: 811.0963.

[0071] Example 4

[0072] To determine the ion recognition characteristics of the probe, common anions Cl- were prepared using deionization. - , Br - ClO4 - NO3 - CN - HSO4 - A probe solution (10 μM) was prepared in chloroform. The UV-Vis absorption and fluorescence spectra were detected at room temperature by reacting acetonitrile and deionized water (V / V = 5 / 1). The results showed that compound (III) showed no response to other ions and no significant change. The probe was detected in CN... - Changes occurred in the ionic solution.

[0073] The above detailed description of the synthesis method of a triazole ring-containing BODIPY fluorescent probe with reference to specific embodiments is illustrative rather than limiting. Several embodiments can be listed within the defined scope. Therefore, changes and modifications without departing from the overall concept of the present invention should be within the protection scope of the present invention.

Claims

1. A method for synthesizing a novel triazole ring-containing BODIPY-type fluorescent probe, characterized in that, The reaction is as follows: The DDQ is 2,3-dichloro-5,6-dicyanobenzoquinone.

2. The novel triazole ring-containing BODIPY-type fluorescent probe synthesized according to claim 1 in CN - Applications in ion detection, but not for the diagnosis and treatment of diseases in living human or animal bodies.

3. The novel triazole ring-containing BODIPY-type fluorescent probe according to claim 2 in CN - Its application in ion detection is characterized by: The compound (Ⅲ) in CN - The fluorescence in the solution was significantly weakened, and a new emission peak appeared at 520 nm.

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