Salicylaldehyde acylhydrazone grafted DASA molecular switch as well as synthesis method and application thereof
By designing a DASA molecular switch for salicylylhydrazone graft, the lack of photochromic compounds and coordination chemical combination is solved, the specific identification and response to zinc ions is achieved, and the ability to respond to multiple stimulations is provided, and it is suitable for optical information storage and metal ion detection.
Patent Information
- Application Number
- CN202311762815.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-19
- Publication Date
- 2025-06-20
AI Technical Summary
In the prior art, the combination of photochromic compounds and coordination chemistry has not been fully explored, especially in terms of direct coordination and coordination, and many photochromic molecules lack inherent coordination sites and are difficult to directly connect to metal ions.
A DASA molecular switch grafted with salicylyoylhydrazone was designed to provide new active sites by introducing salicylyoylhydrazone bond structure, so that DASA molecules have the coordination ability and photochromic ability of acylhydrazone, which can specifically recognize zinc ions and achieve dual switching of fluorescence and color under coordination drive.
DASA molecules have been able to introduce new coordination sites in their structure, enhance their recognition and response capabilities to zinc ions, and have multiple stimulus response capabilities, including photo stimulation and chemical stimulation, which are suitable for optical information storage and metal ion detection.
Smart Images
Figure CN120172950A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of organic photochromic compounds, and relates to a salicylaldehyde hydrazone-grafted DASA molecular switch, a synthesis method thereof, and an application thereof. Background Art
[0002] Donor-acceptor Stenhouse adducts (DASAs) are a new type of organic photochromic compounds, which are composed of a donor, an acceptor, and a triene enol bridge. They have very excellent visible light photoisomerization properties, adjustable absorption wavelengths in a wide range, excellent solvent adaptability, and unique light response characteristics, and have received extensive attention. The combination of organic photochromic molecules and coordination chemistry has always been an important research direction for optical switches. Coordination chemistry can precisely control the photochemical properties of these systems through ligand and metal ion modification to meet specific requirements. In addition to photochromism, many coordination compounds also exhibit other satisfactory properties, including luminescence, magnetism, redox activity, or catalytic behavior. These complementary properties can interact synergistically with the photochromic behavior of the ligand, further expanding the potential applications and capabilities of these integrated systems.
[0003] In recent years, various methods have been used to integrate photo-responsive units into coordination systems, including direct binding to metal ions, grafting photo-chromic units onto ligand skeletons or side chains, and inclusion as guests / anions. Many compounds have been developed, including photo-responsive liquid crystal materials, catalyst materials for polymerization reactions, drug carrier materials, and chemical sensing detector materials, etc. [Controlling Dark Equilibria and Enhancing DASAPhotoswitching Proper-ties Through Carbon Acid Design, 2018, 140(33), 10425-10429]. Although significant progress has been made in this field, compared with other methods, the exploration of direct coordination and integration is still relatively insufficient. This limitation stems from the lack of inherent coordination sites in many photochromic molecules, and they can only be connected to metals by using linkers.
[0004] Organic fluorescent probes can detect various metal ions by showing obvious changes in physical and chemical properties. Due to its easy-to-read-by-naked-eye, energy-free detection method combined with a simple optical system and low cost, zinc ion fluorescent probes have received great attention and have been widely used in various fields. Summary of the Invention
[0005] The object of the present invention is to provide a salicylaldehyde hydrazone-grafted DASA molecular switch and a synthesis method thereof.
[0006] The technical solution for achieving the object of the present invention is as follows:
[0007] The salicylaldehyde acylhydrazone-grafted DASA molecular switch is (4-((benzyl((1E,3Z)-5-(2,2-dimethyl-4,6-dioxo-1,3-dioxolan-5-ylidene)-4-hydroxypent-1,3-dien-1-yl)amino)methyl)-N'-((E)-2-hydroxybenzylidene)benzohydrazide (Compound (III)), and its structural formula is shown as follows:
[0008]
[0009] The synthesis method of the above salicylaldehyde acylhydrazone-grafted DASA molecular switch includes the following steps:
[0010] (1) Using hydrazine hydrate as a reducing agent and reaction solvent, reacting methyl 4-((benzylamino)methyl)benzoate with hydrazine hydrate at 120 ± 5 °C. After the reaction is completed, water is added, allowed to stand, and the insoluble product is separated by filtration. After drying, 4-((benzylamino)methyl)benzohydrazide (Compound (I)) is obtained. The synthesis route is as follows:
[0011]
[0012] (2) Using absolute ethanol as a reaction solvent, refluxing 4-((benzylamino)methyl)benzohydrazide and salicylaldehyde at 80 ± 5 °C. After the reaction is completed, the organic solvent is removed by rotary evaporation, washed, and dried to obtain (E)-4-((benzylamino)methyl)-N'-(2-hydroxybenzylidene)benzohydrazide (Compound (II)). The synthesis route is as follows:
[0013]
[0014] (3) Using methanol as a reaction solvent, reacting (E)-4-((benzylamino)methyl)-N'-(2-hydroxybenzylidene)benzohydrazide and 5-(furan-2-ylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (MAF) at room temperature. After the reaction is completed, the precipitate is collected by filtration, washed, dried, and purified to obtain 4-((benzyl((1E,3Z)-5-(2,2-dimethyl-4,6-dioxo-1,3-dioxolan-5-ylidene)-4-hydroxypent-1,3-dien-1-yl)amino)methyl)-N'-((E)-2-hydroxybenzylidene)benzohydrazide. The synthesis route is as follows:
[0015]
[0016] In step (3), the structural formula of MAF is
[0017] Further, in step (1), the reaction time is more than 12 h, and the standing time is more than 12 h.
[0018] Further, in step (2), the reaction time is more than 8 h.
[0019] Further, in step (2), the washing method is washing with ethyl acetate three or more times.
[0020] Further, in step (3), the molar ratio of (E)-4-((benzylamino)methyl)-N'-(2-hydroxybenzylidene)benzohydrazide to MAF is 1:1.1 - 1.2.
[0021] Further, in step (3), the reaction time is 40 - 60 min.
[0022] The present invention also provides the application of the above salicylaldehyde acylhydrazone-grafted DASA molecular switch in the detection of zinc ions.
[0023] Specifically, the application method is as follows: Dissolve 4-((benzyl((1E,3Z)-5-(2,2-dimethyl-4,6-dioxo-1,3-dioxolan-5-ylidene)-4-hydroxypent-1,3-dien-1-yl)amino)methyl)-N'-((E)-2-hydroxybenzylidene)benzohydrazide in tetrahydrofuran (THF), add the compound to be tested at room temperature, stir and then let stand. If blue-green fluorescence is observed under ultraviolet light after standing, it indicates that zinc ions are coordinated with it, and the compound to be tested is a compound containing zinc ions.
[0024] Further, in the above application, the compound to be tested is fully dissolved in methanol or tetrahydrofuran and then added to the tetrahydrofuran solution of 4-((benzyl((1E,3Z)-5-(2,2-dimethyl-4,6-dioxo-1,3-dioxolan-5-ylidene)-4-hydroxypent-1,3-dien-1-yl)amino)methyl)-N'-((E)-2-hydroxybenzylidene)benzohydrazide.
[0025] Compared with the prior art, the present invention has the following advantages:
[0026] (1) 4-((Benzyl((1E,3Z)-5-(2,2-dimethyl-4,6-dioxo-1,3-dioxolan-5-ylidene)-4-hydroxypent-1,3-dien-1-yl)amino)methyl)-N'-((E)-2-hydroxybenzylidene)benzohydrazide of the present invention firstly introduces a salicylaldehyde acylhydrazone bond structure in the structure. The new active site endows the DASA molecule with both the coordination ability of acylhydrazone and the photochromic ability of the DASA molecule. In particular, the DASA molecule can specifically recognize zinc ions to produce fluorescence, and at the same time, under the drive of coordination, dual switching of fluorescence and color is achieved. And different from the characteristics of other types of DASA molecules that only show excellent anti-fatigue ability in toluene solvent, the salicylaldehyde acylhydrazone-grafted DASA molecular switch of the present invention also has strong anti-fatigue ability in chloroform and tetrahydrofuran.
[0027] (2) The synthesis method of the present invention is simple, time-consuming is short, the raw materials are environmentally friendly and pollution-free, the yield is high, and the solution synthesis method is adopted, which improves the production efficiency and reduces the synthesis energy consumption, and is suitable for industrial application.
[0028] (3) The salicylaldehyde acylhydrazone-grafted DASA molecular switch of the present invention has multiple stimulus responses, including light stimulus, chemical stimulus, etc., and has the advantages of rapid reaction and no side reactions, and has great application potential in the fields of optical information storage, metal ion detectors, etc. Description of the Drawings
[0029] Figure 1 1H NMR spectrum of compound (I).
[0030] Figure 2 1H NMR spectrum of compound (II).
[0031] Figure 3 1H NMR spectrum of compound (III).
[0032] Figure 4 13C NMR spectrum of compound (III).
[0033] Figure 5 2D COSY spectrum of compound (III).
[0034] Figure 6 2D HSQC spectrum of compound (III).
[0035] Figure 7 IR spectrum of compound (III).
[0036] Figure 8 XRD pattern of compound (III).
[0037] Figure 9Crystal structure diagram of compound (III), where N: blue, O: red, C: gray, H: white.
[0038] Figure 10 Is the ultraviolet response spectrum of the metal ions of compound (III).
[0039] Figure 11 Is the fluorescence response spectrum of the metal ions of compound (III).
[0040] Figure 12 Is the dual ultraviolet and fluorescence switching diagram of compound (III) in THF.
[0041] Figure 13 Is the absorbance change with time and cyclic UV diagram of compound (III) in tetrahydrofuran, dichloromethane, and toluene solutions. Detailed implementation mode
[0042] The present invention will be further described below in conjunction with specific embodiments and the accompanying drawings.
[0043] In the following examples, the preparation of methyl 4-((benzylamino)methyl)benzoate refers to the reference [Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis, 2020, 63, 8, 3868 - 3880], and the specific steps are as follows:
[0044] Using methanol as the solvent, methyl p-toluate and benzylamine are reacted at room temperature. After the reaction is completed, extraction, washing, drying, and rotary evaporation are used to remove the organic solvent, obtaining methyl 4-((benzylamino)methyl)benzoate. The synthesis route is as follows:
[0045]
[0046] The preparation of 5-(furan-2-ylmethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (MAF) refers to the reference [Photoswitching Using Visible Light: A New Class of Organic Photochromic Molecules, 2014, 136, 8169 - 817], and the specific steps are as follows:
[0047] Using water as the solvent, 2-furaldehyde and isopropylidene malonate are reacted at room temperature. After the reaction is completed, extraction, washing, drying, and rotary evaporation are used to remove the organic solvent, obtaining 5-(furan-2-ylmethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione. The synthesis route is as follows:
[0048]
[0049] Example 1
[0050] (1) Compound (I), which is 4-((benzylamino)methyl)benzohydrazide, has the molecular structure shown below:
[0051]
[0052] It is prepared through the following steps:
[0053] In a single-neck flask, dissolve methyl 4-((benzylamino)methyl)benzoate (2.55 g, 0.01 mol) in 20 mL of 85% hydrazine hydrate solution, and reflux at 120 °C for 12 h with stirring. Monitor the reaction by TLC method (V 乙酸乙酯 : V 甲醇 = 2:1). After the reaction is completed, cool the reaction mixture to room temperature. Add 150 mL of deionized water, let it stand for 12 h, filter to separate the insoluble product, wash the obtained solid with ice-cold ethanol, and dry the mixture in air to obtain the white solid compound (I). Conduct NMR characterization on it, and the results are as Figure 1 shown.
[0054] (2) The target compound (II), which is (E)-4-((benzylamino)methyl)-N'-(2-hydroxybenzylidene)benzohydrazide, has the molecular structure shown below:
[0055]
[0056] It is prepared through the following steps:
[0057] In a single-neck flask, according to the molar ratio of compound (I) salicylaldehyde = 1:1, add it to anhydrous ethanol, and heat under reflux at 80 °C for 8 h with stirring. Then evaporate the solvent to dryness by rotary evaporation to obtain a yellow solid. Wash the obtained solid three times with ice-cold ethyl acetate, and dry the solid in air to obtain the pale yellow solid compound (II). Conduct NMR characterization on it, and the results are as Figure 2 shown.
[0058] (3) The target compound (III), which is 4-((benzyl((1E,3Z)-5-(2,2-dimethyl-4,6-dioxo-1,3-dioxolan-5-ylidene)-4-hydroxypent-1,3-dien-1-yl)amino)methyl)-N'-((E)-2-hydroxybenzylidene)benzohydrazide, has the molecular structure shown below:
[0059]
[0060] Prepared by the following steps:
[0061] In a single-necked flask, according to the molar ratio of compound (II) MAF was added to methanol. After the mixture was stirred at 25 °C for 1 h, it was filtered to obtain a precipitate. The solid was washed with cold ethyl acetate and dried to obtain a dark purple compound (III), which was characterized by NMR and IR, and the results are as Figures 3 - 7 shown.
[0062] Compound (III) was recrystallized from methanol and left for 1 - 2 days to obtain crystalline compound (III). It was characterized by XRD, as Figure 8 shown.
[0063] The data of the crystals obtained after recrystallization of compound (III) are shown in Table 1, and the crystal structure is as Figure 9 shown.
[0064] Table 1 Crystal data of compound (III)
[0065]
[0066] Example 2
[0067] UV test of the metal ions of compound (III):
[0068] Compound (III) was prepared into a tetrahydrofuran solution with a concentration of 1.0×10 -5 mol / L. Different metal ions were selected: Zn 2+ , Ni 2+ , Na + , Mn 2+ , Mg 2+ , K + , Fe 3+ , Fe 2+ , Cu 2+ , Co 2+ , Ca 2+ , Be 2+ , Al 3+ , Ag + were prepared into tetrahydrofuran solutions with a concentration of 10 - 3 mol / L. Compound (III) and the metal ions were mixed at a molar ratio of 1:1. By observing the absorption peak near λ = 400 nm, it was found that there were many metal ions that could make the salicylaldehyde acylhydrazone part participate in coordination. The results of the UV absorption spectrum determination are as Figure 10 shown.
[0069] Example 3
[0070] Fluorescence test of metal ions of compound (III):
[0071] Compound (III) was prepared into a tetrahydrofuran solution with a concentration of 1.0×10 -5 mol / L, and the above metal ions were configured into a tetrahydrofuran solution with a concentration of 10 -3 mol / L. Compound (III) and metal ions were mixed at a molar ratio of 1:1. It was found that only zinc ions could produce fluorescence, indicating that it has a special recognition effect only on zinc ions. The results of fluorescence spectrum measurement are as Figure 11 shown.
[0072] Example 4
[0073] Test on the dual fluorescence color switching property of compound (III) after adding zinc ions in THF:
[0074] Compound (III) was prepared into a THF solution with a concentration of 1.0×10 -5 mol / L, and 1 equivalent of zinc ions was added. After reaching equilibrium, its fatigue resistance was tested. The test results are as Figure 12 shown. The solution realizes color switching under visible light irradiation, accompanied by fluorescence switching. The anti-fatigue test shows that it can maintain more than 5 cycles.
[0075] Example 5
[0076] Test on the photochromic behavior properties of compound (III) in different solvents:
[0077] Under the irradiation of visible light with a wavelength of 550 nm, compound (III) was dissolved in toluene, dichloromethane and tetrahydrofuran respectively to prepare a concentration of c = 10 -5 mol / L. The results of its performance characterization are as Figure 13 shown.
[0078] From Figure 13It can be seen that the cuvette containing the solution of compound (III) is stored in the dark, and the ultraviolet absorption spectrum is measured at regular intervals. The structural change of compound (III) is judged by the change of ultraviolet absorbance in the cuvette over time to test its stability. After compound (III) reaches the dark equilibrium (the absorbance at the maximum absorption wavelength no longer changes), light with a wavelength of 550 nm is applied to reduce its maximum absorbance to nearly 0, and then it is placed in the dark to recover, and the cycle is repeated for testing its fatigue resistance. It can be seen from the figure that the absorbance at λ = 546 nm in tetrahydrofuran drops to the lowest point, indicating that the isomerization process of compound (III) has been basically completed in tetrahydrofuran at this time. Subsequently, light with a wavelength of 550 nm is applied to reduce its absorbance to nearly 0, and then it is placed in the dark to recover. It can be seen that only the maximum absorbance in the first cycle will decay. Therefore, it can be concluded that compound (III) partially undergoes a ring-opening to ring-closing transformation when reaching the dark equilibrium in tetrahydrofuran, and the anti-fatigue test shows that compound (III) can perform a good switching cycle in tetrahydrofuran. Similarly, similar properties are also observed in dichloromethane and toluene, indicating that compound (III) has relatively good reversible anti-fatigue properties in these three solvents.
[0079] Comparative Example 1
[0080] This comparative example is substantially the same as Example 1, except that the reaction solvent in the synthesis of the target compound (III) is THF. When THF is used as the reaction solvent, the initial phenomenon is the same as that in Example 1. The reaction solution changes from light yellow to purple-red, and as time prolongs and the reaction progresses, the color will gradually deepen. After the reaction ends, a purple-black oily mixture is obtained, and the pure solid compound (III) cannot be obtained.
Claims
1. The salicylaldehyde acylhydrazone-grafted DASA molecular switch, characterized in that, is (4-((benzyl((1 E ,3 Z -5-(2,2-dimethyl-4,6-dioxo-1,3-dioxolan-5-ylidene)-4-hydroxypent-1,3-dien-1-yl)amino)methyl)-N'-(( E )-2-hydroxybenzylidene)benzohydrazide, and its structural formula is shown as follows: 。 2. The synthesis method of the salicylaldehyde acylhydrazone-grafted DASA molecular switch according to claim 1, characterized in that, It includes the following steps: (1) Using hydrazine hydrate as a reducing agent and reaction solvent, reacting methyl 4-((benzylamino)methyl)benzoate with hydrazine hydrate at 120 ± 5 °C. After the reaction is completed, water is added, allowed to stand, and the insoluble product is separated by filtration. After drying, 4-((benzylamino)methyl)benzohydrazide is obtained; (2) Using absolute ethanol as the reaction solvent, 4-((benzylamino)methyl)benzohydrazide and salicylaldehyde were refluxed at 80 ± 5 °C. After the reaction was completed, the organic solvent was removed by rotary evaporation, washed, and dried to obtain ( E )-4-((benzylamino)methyl)-N'-(2-hydroxybenzylidene)benzohydrazide; (3) Using methanol as the reaction solvent, react ( E )-4-((benzylamino)methyl)-N'-(2-hydroxybenzylidene)benzohydrazide and 5-(furan-2-ylmethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione at room temperature. After the reaction is completed, filter to collect the precipitate, wash, dry, and purify to obtain 4-((benzyl((1 E ,3 Z )-5-(2,2-dimethyl-4,6-dioxo-1,3-dioxolan-5-ylidene)-4-hydroxypent-1,3-dien-1-yl)amino)methyl)-N'-(( E )-2-hydroxybenzylidene)benzohydrazide.
3. The synthesis method according to claim 2, characterized in that, In step (1), the reaction time is more than 12 h, and the standing time is more than 12 h.
4. The synthesis method according to claim 2, characterized in that, In step (2), the reaction time is more than 8 h.
5. The synthesis method according to claim 2, characterized in that, In step (2), the washing method is to wash with ethyl acetate more than three times.
6. The synthesis method according to claim 2, characterized in that, In step (3), ( E ) the molar ratio of -4-((benzylamino)methyl)-N'-(2-hydroxybenzylidene)benzohydrazide to 5-(furan-2-ylmethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione is 1:1.1 to 1.
2.
7. The synthesis method according to claim 2, characterized in that, In step (3), the reaction time is 40 - 60 min.
8. The application of the salicylaldehyde acylhydrazone-grafted DASA molecular switch according to claim 1 in zinc ion detection.
9. The application according to claim 8, characterized in that, The specific application method is as follows: Dissolve 4-((benzyl((1 E ,3 Z -)-5-(2,2-dimethyl-4,6-dioxo-1,3-dioxolan-5-ylidene)-4-hydroxypent-1,3-dien-1-yl)amino)methyl)-N'-(( E )-2-hydroxybenzylidene)benzohydrazide in tetrahydrofuran, add the compound to be tested at room temperature, stir and then let it stand. If blue-green fluorescence is observed under ultraviolet light after standing, it indicates that zinc ions are coordinated with it, and the compound to be tested is a compound containing zinc ions.
10. The application according to claim 9, characterized in that, Dissolve the compound to be tested thoroughly with methanol or tetrahydrofuran and then add it to a tetrahydrofuran solution of 4-((benzyl((1 E ,3 Z ))-5-(2,2-dimethyl-4,6-dioxo-1,3-dioxolan-5-ylidene)-4-hydroxypent-1,3-dien-1-yl)amino)methyl)-N'-(( E ))-2-hydroxybenzylidene)benzohydrazide.