A benzothiadiazine-1,1-dione-quinoline derivative and its preparation method and application

Abstract

The present invention discloses a benzothiadiazine-1,1-diketo-quinoline derivative, a preparation method, and an application thereof, belonging to the technical field of chemical optical materials. A benzothiadiazine-1,1-diketo-quinoline derivative is provided. The structural formula of the benzothiadiazine-1,1-diketo-quinoline derivative is: wherein R is -N(CH2CH3)2 or -OCH3. The present invention introduces a benzothiadiazine-1,1-diketo heterocycle at the 2-aldehyde position of quinoline to prepare the benzothiadiazine-1,1-diketo-quinoline derivative. The preparation cost is low, the operation is simple, and the method is simple. The obtained benzothiadiazine-1,1-diketo-quinoline derivative exhibits fluorescent properties and can be used as a probe for the detection of heavy metal copper and / or mercury ions. At the same time, the synthesis method can be used for synthesis in fine organic chemical fields such as printing and dyeing technology and analytical detection.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical optical materials, and in particular relates to a benzothiadiazine-1,1-diketo-quinoline derivative, a preparation method thereof, and an application thereof. Background Art

[0002] Quinoline and its derivatives are an important class of heterocyclic compounds, first used in the medical field and possessing significant medicinal value. Antibacterial drugs such as quinolone antibiotics and antimalarial drugs such as chloroquine can achieve therapeutic effects by inhibiting the expression of genetic material of pathogenic microorganisms. Subsequent studies have confirmed the application of quinoline derivatives in optical materials, especially the preparation of fluorescent probes. Quinoline derivatives are important active intermediates in the synthesis of optical materials, textile dyes, and cosmetics. For example, patent application number CN20231176670.1, entitled “A Synthesis Method for a Disperse Dye Coupling Component Containing a Tetrahydroquinoline Structure and Its Application,” discloses disperse dyes containing quinoline derivatives. Therefore, the synthesis of quinoline and its derivatives and their products have been widely used in the field of fine chemicals.

[0003] Mercury is highly toxic, volatile, and accumulates harmfully. Direct exposure to the human body can cause significant harm, including body aches, dizziness, insomnia, various skin diseases, and even cancer. Long-term exposure can also damage internal organs and the nervous system. Excessive copper accumulation in the body not only adversely affects the skin and internal organs but can also lead to neurological diseases such as Alzheimer's and Parkinson's diseases. Current techniques for detecting mercury and copper, such as atomic absorption spectrometry (AAS) and inductively coupled plasma mass spectrometry (ICP-MS), are plagued by expensive equipment, complex operation, and tedious sample preparation. For example, AAS may encounter interference from other heavy metal ions or organic matter, which can compete with mercury or copper for binding sites or form complexes that affect the detection results, thereby reducing accuracy. Although various mercury and copper detection technologies have been developed, practical application still faces numerous challenges, including but not limited to the aforementioned operational complexity, cost-effectiveness, interference resistance, and standardization. Future research should focus on simplifying the operational process, reducing costs, and improving portability and field applicability. Summary of the Invention

[0004] To solve the above technical problems, the present invention provides a benzothiadiazine-1,1-dione-quinoline derivative, a preparation method and application thereof. The present invention introduces a benzothiadiazine-1,1-dione heterocycle at the 2-aldehyde position of quinoline to prepare a benzothiadiazine-1,1-dione-quinoline derivative. The preparation method is low-cost, easy to operate and simple. The obtained benzothiadiazine-1,1-dione-quinoline derivative exhibits fluorescence properties and can be used as a probe for the detection of heavy metal copper and / or mercury ions. At the same time, the synthesis method can be used for synthesis in fine organic chemical fields such as printing and dyeing technology and analytical detection.

[0005] To achieve the above object, the present invention provides a benzothiadiazine-1,1-dione-quinoline derivative, the structural formula of the benzothiadiazine-1,1-dione-quinoline derivative is:

[0006]

[0007] Wherein R is -N(CH2CH3)2 or -OCH3.

[0008] The present invention also provides a method for preparing the benzothiadiazine-1,1-dione-quinoline derivative, comprising the following steps: dissolving 6-R-2-quinolinecarboxaldehyde and o-aminobenzenesulfonamide in a solvent, and heating the mixture to react under the action of a catalyst to obtain the benzothiadiazine-1,1-dione-quinoline derivative;

[0009] The specific synthesis process of the benzothiadiazine-1,1-dione-quinoline derivative is as follows:

[0010]

[0011] Wherein R is -N(CH2CH3)2 or -OCH3.

[0012] Preferably, the 6-R-2-quinolinecarboxaldehyde is 6-diethylamino-2-quinolinecarboxaldehyde or 6-methoxy-2-quinolinecarboxaldehyde.

[0013] Preferably, the solvent is N,N-dimethylformamide (DMF).

[0014] Preferably, the catalyst is sodium bisulfite.

[0015] Preferably, the molar ratio of 6-R-2-quinolinecarboxaldehyde, o-aminobenzenesulfonamide, solvent and catalyst is 1:1:25:4.

[0016] Preferably, the heating reaction temperature is 80-150° C., and the heating reaction time is 1 hour.

[0017] The present invention also provides the use of the benzothiadiazine-1,1-dionone-quinoline derivative in detecting metallic copper and / or mercury ions.

[0018] Preferably, the application is specifically as follows: the benzothiadiazine-1,1-dione-quinoline derivative, N,N-dimethylformamide and water are mixed to obtain an aqueous dispersion of the fluorescent compound, the test object is added, and after shaking for 3 seconds, the fluorescence intensity is measured at a wavelength of 440nm or 559nm. The visible strong fluorescence turns into colorless quenching, thereby realizing fluorescence spectrophotometric detection of copper and / or mercury ions.

[0019] Preferably, the concentration of the benzothiadiazine-1,1-dione-quinoline derivative in the aqueous dispersion solution of the fluorescent compound is 1 μM, the volume ratio of N,N-dimethylformamide and water in the aqueous dispersion solution of the fluorescent compound is 2:8, and the volume ratio of the aqueous dispersion solution of the fluorescent compound to the object to be tested is 3 mL:10~30 μL.

[0020] Compared with the prior art, the present invention has the following advantages and technical effects:

[0021] The present invention provides a new method for synthesizing a previously unreported benzothiadiazine-1,1-dione-quinoline derivative. The method comprises placing 6-R-2-quinolinecarboxaldehyde and o-aminobenzenesulfonamide in DMF, using sodium bisulfite as a catalyst, and reacting at elevated temperature to produce the benzothiadiazine-1,1-dione-quinoline derivative. When the 6-R-2-quinolinecarboxaldehyde is 6-diethylamino-2-quinolinecarboxaldehyde, the resulting benzothiadiazine-1,1-dione-quinoline derivative is named compound GN; when the 6-R-2-quinolinecarboxaldehyde is 6-methoxy-2-quinolinecarboxaldehyde, the resulting benzothiadiazine-1,1-dione-quinoline derivative is named compound GO. The resulting compounds GN and GO exhibit fluorescent properties, with compound GO emitting a shorter wavelength of 440 nm and compound GN emitting a longer wavelength of 559 nm. The preparation method of the present invention has significant advantages, including readily available raw materials, low cost, and simple operation. The prepared compound GN has obvious fluorescence properties and can be used for the detection of heavy metal copper and mercury ions. When compounds GN and GO encounter copper and mercury ions, coordination reactions will occur, causing the fluorescence of the generated GN or GO to change. The solution changes from visible strong fluorescence to colorless and quenching, thereby realizing sensitive, accurate, long-lasting, fast and non-destructive detection of copper and mercury ions. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0023] Figure 1 The NMR of the compound GN synthesized in Example 1 of the present invention is 1 HNMR spectrum;

[0024] Figure 2 The NMR of the compound GN synthesized in Example 1 of the present invention is 13 C NM map;

[0025] Figure 3 This is a high-resolution mass spectrum of compound GN synthesized in Example 1 of the present invention;

[0026] Figure 4 This is a single crystal structure diagram of compound GN synthesized in Example 1 of the present invention;

[0027] Figure 5 The nuclear magnetic resonance of the compound GO synthesized in Example 2 of the present invention 1 HNMR spectrum;

[0028] Figure 6 The nuclear magnetic resonance of the compound GO synthesized in Example 2 of the present invention 13 C NM map;

[0029] Figure 7 This is a high-resolution mass spectrum of the compound GO synthesized in Example 2 of the present invention;

[0030] Figure 8 This is a single crystal structure diagram of the compound GO synthesized in Example 2 of the present invention;

[0031] Figure 9 The compound GO synthesized in Example 2 of the present invention is used for the detection of copper and mercury ions, wherein A is the fluorescence spectrum response of compound GO to different concentrations of copper and mercury ions, and B is the fluorescence spectrum response of compound GO, GO+Cu 2+ and GO+Hg 2+ Effect diagram under 365nm ultraviolet light;

[0032] Figure 10 The compound GN synthesized in Example 1 of the present invention is used for copper ion detection, wherein A is the fluorescence spectrum response of compound GN to different concentrations of copper ions, and B is the fluorescence spectrum response of compound GN and GN+Cu 2+ Effect diagram under 365nm ultraviolet light;

[0033] Figure 11 The compound GN synthesized in Example 1 of the present invention is used for mercury ion detection, wherein A is the fluorescence spectrum response of compound GN to different concentrations of mercury ions, and B is the fluorescence spectrum response of compound GN and GN+Hg 2+ Effect diagram under 365nm ultraviolet light;

[0034] Figure 12 This is a graph showing the fluorescence intensity of the compound GN synthesized in Example 1 of the present invention as a function of copper ion concentration;

[0035] Figure 13 This is a graph showing the fluorescence intensity of the compound GN synthesized in Example 1 of the present invention as a function of mercury ion concentration;

[0036] Figure 14 This is a graph showing the selectivity of compound GN synthesized in Example 1 of the present invention for different metal ions. DETAILED DESCRIPTION

[0037] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0038] It should be understood that the terms described herein are intended only to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges herein, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between any intermediate value within a stated value or stated range and any other stated value or intermediate value within the stated range is also encompassed by the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0039] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0040] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the description of the invention. The description and examples are intended to be exemplary only.

[0041] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0042] Sources of the materials used in the present invention: 6-diethylamino-2-quinolinecarboxaldehyde was purchased from Zheng Kaibo's group at the School of Materials and Chemical Engineering of China Three Gorges University, 6-methoxy-2-quinolinecarboxaldehyde was purchased from Zheng Kaibo's group at the School of Materials and Chemical Engineering of China Three Gorges University, o-aminobenzenesulfonamide was purchased from Sane Chemical Technology (Shanghai) Co., Ltd., N,N-dimethylformamide (DMF) was purchased from Tianjin Hengxing Chemical Reagent Manufacturing Co., Ltd., and sodium bisulfite was purchased from Changde Beekman Biotechnology Co., Ltd.

[0043] Example 1

[0044] 6-Diethylamino-2-quinolinecarboxaldehyde and o-aminobenzenesulfonamide were dissolved in DMF and heated at 150°C for 1 hour in the presence of sodium bisulfite. The mixture was cooled to 20-30°C, 0.2 mL of water was added, and extraction was performed with ethyl acetate. The organic layer was collected and the solvent was removed by vacuum distillation at 50°C for 5 minutes under a vacuum pressure of 0.098 MPa. The crude product was dissolved in 2 mL of dichloromethane and separated on a silica gel column. Eluent ethyl acetate was used as the eluent to purify the product. Compound GN was obtained as a yellow solid with a yield of 63%.

[0045] The molar ratio of 6-diethylamino-2-quinolinecarboxaldehyde, o-aminobenzenesulfonamide, DMF and sodium bisulfite added during the preparation process is 1:1:25:4.

[0046] The compound GN obtained in this example is a new compound. 1 H NMR, 13 C NMR), high resolution mass spectrometry (HRMS) and single crystal characterization. 1 H NMR Figure 1 As shown, the compound GN NMR 13 CNMR Figure 2 As shown, the high-resolution mass spectrum of compound GN is as follows Figure 3 As shown, the single crystal structure of compound GN is as follows Figure 4 shown. 1H NMR (400MHz, DMSO-d6) δ12.26(s,1H),8.25(d,J=8.7Hz,1H),8.11(dd,J=14.5,9.1Hz,2H),7.99(d,J=8.3Hz,1H),7.89 (d,J=7.9Hz,1H),7.75(t,J=7.7Hz,1H),7.64-7.46(m,2H),6.99(d,J=2.1Hz,1H),3.53(q,4H),1.19(t,J=6.9Hz,6H). 13 C NMR(100MHz,DMSO-d6)δ152.60,147.81,142.11,140.17,135.62,135.22,133.59,132.23,130.94 ,126.99,123.79,122.05,120.62,119.57,119.50,103.22,44.50,12.95.HRMS:m / z:Calcd.for(C 20 H 21 N4O2S)[M+H] + :381.1385;found,381.1386.

[0047] Example 2

[0048] 6-Methoxy-2-quinolinecarboxaldehyde and o-aminobenzenesulfonamide were dissolved in DMF and heated at 150°C for 1 hour in the presence of sodium bisulfite. The mixture was cooled to 20-30°C, 0.2 mL of water was added, and extraction was performed with ethyl acetate. The organic layer was collected and the solvent was removed by vacuum distillation at 50°C for 5 minutes under a vacuum pressure of 0.098 MPa. The crude product was dissolved in 2 mL of dichloromethane and separated on a silica gel column. Eluent ethyl acetate was used as the eluent to purify the product, yielding GO as a light pink solid in 94% yield.

[0049] The molar ratio of 6-methoxy-2-quinolinecarboxaldehyde, o-aminobenzenesulfonamide, DMF and sodium bisulfite added during the preparation process is 1:1:25:4.

[0050] The compound GO obtained in this example is a new compound. 1 H NMR, 13 C NMR), high resolution mass spectrometry (HRMS) and single crystal characterization. 1 H NMR Figure 5 As shown, the NMR of compound GO 13 CNMR Figure 6 As shown, the high-resolution mass spectrum of compound GO is as follows Figure 7As shown, the single crystal structure of compound GO is as follows Figure 8 shown. 1 H NMR (400MHz, DMSO-d6) δ12.43(s,1H),8.55(d,J=8.7Hz,1H),8.32(d,J=8.6Hz,1H),8.23(d,J=9.2Hz,1H ),8.00(d,J=8.2Hz,1H),7.91(dd,J=7.9,1.1Hz,1H),7.82-7.74(m,1H),7.52-7.61(m,3H),3.97(s,3H). 13 C NMR(100MHz,DMSO-d6)δ159.59,152.34,145.67,142.80,137.41,135.53,133.71,131.31 ,127.28,124.33,123.85,122.05,119.85,119.62,106.33,56.31.HRMS:m / z:Calcd.for(C 17 H 14 N3O3S)[M+H] + :340.0756;found,340.0758.

[0051] like Figure 9 China A and Figure 9 As shown in Figure B, the compound GO obtained in this example has fluorescent properties, but the emission wavelength of GO is relatively short (440 nm), and the fluorescent effect is not obvious.

[0052] Experimental Example 1

[0053] 1. Determination of the relationship between the fluorescence emission spectrum of compound GN and the concentrations of copper ions and mercury ions:

[0054] 1. Relationship between the fluorescence emission spectrum of compound GN and the concentration of copper ions:

[0055] Compound GN was dissolved in a mixed solution of DMF and water to obtain an aqueous dispersion of the fluorescent compound. 3 mL of the prepared aqueous dispersion of the fluorescent compound was added with 20 μL of aqueous copper chloride solutions of different concentrations (0, 1, 2, 3, 5, 20, 40, 60, 100 μM). The solution was shaken for 3 seconds and allowed to stand. The changes in fluorescence intensity at 559 nm were recorded by a fluorescence spectrometer.

[0056] The concentration of the compound GN in the aqueous dispersion of the fluorescent compound was 1 μM, and the mixed solution of DMF and water was prepared by mixing DMF and water in a volume ratio of 2:8.

[0057] The fluorescence intensity is plotted as the ordinate and the excitation wavelength as the abscissa to obtain a curve showing the relationship between the fluorescent compound GN and the copper ion concentration, as shown in FIG. Figure 10 As shown in A. Figure 10 Where B is compound GN and GN+Cu 2+ The effect diagram under 365nm ultraviolet light. The determination of the copper ion concentration of compound GN, the relationship between the fluorescence intensity and the copper ion concentration under 380nm excitation light, as shown in the figure Figure 12 shown.

[0058] 2. Relationship between GN fluorescence emission spectrum and mercury ion concentration:

[0059] Compound GN was dissolved in a mixed solution of DMF and water to obtain an aqueous dispersion of the fluorescent compound. 3 mL of the prepared aqueous dispersion of the fluorescent compound was added with 20 μL of aqueous mercuric perchlorate trihydrate solution of different concentrations (0, 1, 5, 10, 20, 40, 60, 80, 100 μM). The mixture was shaken for 3 seconds and allowed to stand. The changes in fluorescence intensity at 559 nm were recorded using a fluorescence spectrometer.

[0060] The concentration of the compound GN in the aqueous dispersion of the fluorescent compound was 1 μM, and the mixed solution of DMF and water was prepared by mixing DMF and water in a volume ratio of 2:8.

[0061] The fluorescence intensity is plotted as the ordinate and the excitation wavelength as the abscissa to obtain a curve showing the relationship between compound GN and mercury ion concentration, as shown in FIG. Figure 11 As shown in A. Figure 11 Where B is compound GN and GN+Hg 2+ The effect diagram under 365nm ultraviolet light. The determination of mercury ion concentration of compound GN, the relationship between the fluorescence intensity and mercury ion concentration under 380nm excitation light, as shown in the figure Figure 13 shown.

[0062] 2. Selective determination of fluorescent compound GN cation:

[0063] Dissolve compound GN in a mixed solution of DMF and water, take 3 mL of the prepared aqueous dispersion of the fluorescent compound, and add 20 μL of a 5×10 -3 M's Cd 2+ 、Fe 2+ 、Fe 3+ , Ca 2+ , K + Mg 2+ 、Na + 、Pd 2+ 、Zn 2+ The aqueous solution was shaken for 3 seconds and then allowed to stand. The changes in fluorescence intensity at 559 nm were recorded by fluorescence spectrometer.

[0064] The concentration of the compound GN in the aqueous dispersion of the fluorescent compound was 1 μM, and the mixed solution of DMF and water was prepared by mixing DMF and water in a volume ratio of 2:8.

[0065] The experimental results are as follows Figure 14 The results show that, except for copper and mercury ions, other ions do not cause obvious changes in fluorescence at 559 nm. Copper and mercury ions directly quench the fluorescence at 559 nm, indicating that the fluorescent compound of the present invention has good selectivity.

[0066] The embodiments described above are merely descriptions of preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by persons skilled in the art should fall within the scope of protection defined by the claims of the present invention.

Claims

1. A benzothiadiazine-1,1-dione-quinoline derivative, characterized in that: The structural formula of the benzothiadiazine-1,1-dione-quinoline derivative is: Wherein R is -N(CH2CH3)2 or -OCH3.

2. The method for preparing the benzothiadiazine-1,1-dione-quinoline derivative according to claim 1, wherein: The following steps are involved: 6-R-2-quinolinecarboxaldehyde and o-aminobenzenesulfonamide are dissolved in a solvent and heated to react in the presence of a catalyst to obtain a benzothiadiazine-1,1-dione-quinoline derivative.

3. The preparation method according to claim 2, characterized in that: The 6-R-2-quinolinecarboxaldehyde is 6-diethylamino-2-quinolinecarboxaldehyde or 6-methoxy-2-quinolinecarboxaldehyde.

4. The preparation method according to claim 2, characterized in that The solvent is N,N-dimethylformamide.

5. The preparation method according to claim 2, characterized in that: The catalyst is sodium bisulfite.

6. The preparation method according to claim 2, characterized in that: The molar ratio of the 6-R-2-quinolinecarboxaldehyde, o-aminobenzenesulfonamide, solvent and catalyst is 1:1:25:

4.

7. The preparation method according to claim 2, characterized in that: The temperature of the heating reaction is 80-150° C., and the heating reaction time is 1 hour.

8. Use of the benzothiadiazine-1,1-dione-quinoline derivative according to claim 1 in detecting metallic copper and / or mercury ions.

9. The application according to claim 8, characterized in that: The specific application is: mixing the benzothiadiazine-1,1-dionato-quinoline derivative, N,N-dimethylformamide and water to obtain an aqueous dispersion of the fluorescent compound, adding the object to be tested, shaking for 3 seconds, and measuring the fluorescence intensity at a wavelength of 440nm or 559nm. Quenching occurs when the visible strong fluorescence turns into colorless fluorescence, thereby realizing fluorescence spectrophotometric detection of copper and / or mercury ions.

10. The use according to claim 9, characterized in that: The concentration of the benzothiadiazine-1,1-dione-quinoline derivative in the aqueous dispersion of the fluorescent compound is 1 μM, the volume ratio of N,N-dimethylformamide and water in the aqueous dispersion of the fluorescent compound is 2:8, and the volume ratio of the aqueous dispersion of the fluorescent compound to the object to be tested is 3 mL:10-30 μL.

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