5-chloro-3-methyl-1-phenyl-4-pyrazole formaldehyde-2-amino-5-(4-pyridyl)-1, 3, 4-thiadiazole compound as well as preparation method and application thereof

Abstract

The invention provides a Schiff base compound formed by condensing 5-chloro-3-methyl-1-phenyl-4-pyrazolecarboxaldehyde and a 2-amino-5-(4-pyridyl)-1, 3, 4-thiadiazole compound as well as a preparation method and application of the Schiff base compound. The Schiff base compound disclosed by the invention has certain DPPH free radical resisting activity and fluorescence property, and has potential application value in the aspect of preparing antioxidants and fluorescent materials.

Description

Technical Field

[0001] This invention relates to the fields of chemical and pharmaceutical chemistry, specifically to a compound of pyrazolaldehyde thiazolidinedioic acid Schiff base, its preparation method, and its use in the chemical and pharmaceutical fields. Background Technology

[0002] Schiff bases are a class of organic compounds containing the -RC=N- structure, generally synthesized through the condensation reaction of amines with carbonyl-containing compounds such as aldehydes or ketones. Since the first Schiff base was synthesized in 1963, research on the synthesis and bioactivity of Schiff bases and their derivatives has shown a rapid growth trend. Due to their large π-conjugated systems, Schiff bases exhibit strong photoelectric properties and excellent photosensitivity, making them suitable for applications in nonlinear optical materials. In recent years, Schiff bases have once again become a focus of research due to the discovery of certain pharmacological activities. Because the synthesis of Schiff bases is relatively easy, various aldehydes and ketones with carbonyl groups can be flexibly selected to react with various amines, thus enabling the development of many Schiff base compounds with different properties.

[0003] Pyrazole compounds are a very important class of heterocyclic compounds with significant applications in various fields, particularly pesticides and chemicals. Due to their structural characteristics, the substituents on the pyrazole ring can be varied in multiple orientations to form different compounds, thus finding wide applications in pharmaceuticals, dyes, conductive reagents, and antioxidant activities. In the prior art, Chinese patent CN201810162556.9 discloses a series of pyrazole aldehyde acetal aniline Schiff base compounds and their preparation methods. The general structural formula of the series of compounds is... Applications in combating DPPH free radicals. Chinese patent CN201810053585.1 discloses a novel compound, pyrazolaldehyde pyridinium amine Schiff base, its preparation method, and its applications. The general structural formula is... R=H or OCH3, its applications in fluorescent materials and antioxidants. Chinese patent CN202110371181.9, authorized in 2022, describes heterocyclic compounds containing pyrazole and quinoline rings, their preparation methods, and applications; its general structural formula is... All the compounds exhibit good DPPH free radical scavenging activity. The above series of patents demonstrates that pyrazole compounds with specific structures possess excellent activity against DPPH free radicals. Thiadiazole compounds, containing both nitrogen and sulfur atoms in their structure, often exhibit excellent biological and pharmacological activities and are widely used in fine chemicals, pesticides, pharmaceuticals, and materials.

[0004] Based on the above theoretical and current status analysis, as an in-depth study, this invention employs the active substructure splicing method to splice the pyrazole ring and the thiadiazole ring into a single molecule through a simple condensation reaction, synthesizing a compound containing both a pyrazole ring and a thiadiazole ring. A search revealed no relevant literature reports on its structure, and its fluorescence properties and DPPH free radical scavenging properties were investigated. Summary of the Invention

[0005] This invention provides a Schiff base compound of general formula I, with the following structure:

[0006] (I)

[0007] Methods for preparing Schiff base compounds of general formula I include:

[0008]

[0009] (1) Dissolve the newly prepared compound of formula (III) 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole in a solvent;

[0010] (2) Add the solution of 5-chloro-3-methyl-1-phenyl-4-pyrazole carbaldehyde of formula (II) and the compound of formula (III) into the reaction apparatus, heat to reflux, and react for 7 h;

[0011] (3) Cooling, desolvation, filtration and washing to obtain the target compound.

[0012] Preferably, the solvent in step (1) is selected from: N,N-dimethylformamide, acetic acid, dichloromethane, methanol, ethanol, isopropanol, tert-butanol, acetonitrile or acetone; more preferably, the solvent is selected from: ethanol.

[0013] Preferably, in step (2), the molar mass ratio of 5-chloro-3-methyl-1-phenyl-4-pyrazole carbaldehyde of formula (II) to the compound of formula (III) is 1:1~1.5.

[0014] Preferably, step (2) further includes monitoring the reaction process using TLC.

[0015] Preferably, ethanol is used for washing in step (3).

[0016] In a specific embodiment of the present invention, the reflux time used is 7 hours.

[0017] The present invention provides a fluorescent probe comprising a Schiff base compound of general formula I.

[0018] This invention provides an application of a Schiff base compound of general formula I as a fluorescent probe for detecting metal ions in aqueous solutions.

[0019] The metal ions are selected from: Al 3+ Zn 2+ Cu 2+ Pb 2+ Ag + Co 3+ Fe 3+ Hg 2+ or Cd 2+ wait.

[0020] The present invention also provides a free radical scavenger, which includes Schiff base compounds of general formula I.

[0021] Preferably, the free radical scavenger further includes one or more pharmaceutically acceptable mediators, excipients, auxiliaries, or diluents;

[0022] Preferably, the dosage forms of the free radical scavenger include, but are not limited to: emulsions, microemulsions, submicroemulsions, nanoparticles, capsules, gels, powders, suppositories, suspensions, creams, gels, sprays, etc.

[0023] Preferably, the free radical scavenger can be administered via methods including but not limited to: subcutaneous injection, intramuscular injection, intravenous injection, oral administration, and transdermal administration.

[0024] According to another aspect of the present invention, the application of the Schiff base compound of general formula I described in the present invention in the preparation of a free radical scavenger, wherein the free radical scavenger is used for anti-aging and prevention and treatment of diseases, preferably, the diseases are selected from tumors, stroke, etc.

[0025] This invention provides a novel pyrazolaldehyde acetal 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole Schiff base compound, its preparation method, and its applications. The Schiff base described in this invention has high purity, a simple preparation method, and is easy to industrialize. Property analysis revealed that the novel pyrazolaldehyde acetal 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole Schiff base provided in this invention exhibits good fluorescence properties and certain free radical scavenging activity, showing potential application value in the preparation of fluorescent probes, optical recording materials, antibacterial agents, free radical scavengers, and anti-aging drugs. Attached Figure Description

[0026] Figure 1 It is a compound of 5-chloro-3-methyl-1-phenyl-4-pyrazole carbaldehyde condensed with 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole. 1 H NMR spectrum.

[0027] Figure 2It is a compound of 5-chloro-3-methyl-1-phenyl-4-pyrazole carbaldehyde condensed with 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole. 13 C10 NMR spectrum.

[0028] Figure 3 The HRMS spectrum of the compound 5-chloro-3-methyl-1-phenyl-4-pyrazole carbaldehyde condensate 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole.

[0029] Figure 4 The fluorescence spectrum of 5-chloro-3-methyl-1-phenyl-4-pyrazole carboxaldehyde condensate 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole compound.

[0030] Figure 5 The free radical scavenging rate curves of the compound 5-chloro-3-methyl-1-phenyl-4-pyrazole carbaldehyde condensate 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole are shown. Detailed Implementation

[0031] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0032] Example 1: Preparation of 5-chloro-3-methyl-1-phenyl-4-pyrazole carbaldehyde condensate 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole compound

[0033] 0.22 g (1 mmol) of 5-chloro-3-methyl-1-phenyl-4-pyrazolecarbaldehyde and 0.178 g (1 mmol) of 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole dissolved in 30 mL of anhydrous ethanol were added to a 100 mL three-necked flask. The mixture was heated and refluxed, and the reaction was monitored by TLC. The reaction was completed in 7 h. After cooling, the solvent was removed by rotary evaporation, and a solid precipitated. The solid was washed several times with anhydrous ethanol, filtered, and dried to give 0.27 g of a pale yellow solid, which was the target product. Yield: 71%; Melting point: 212-213 °C.

[0034] 1 H NMR (400Hz, DMSO, δ / ppm): 8.88 (s, 1H, CH=N), 8.79 (d, 2H, H on α-pyridine), 7.94 (d, 2H, H on β-pyridine), 7.57-7.67 (m, 5H, H on benzene), 2.50 (s, 3H, CH3); Test results attached. Figure 1 .

[0035] 13 C10 NMR (100Hz, CDCl3, δ / ppm): 175.60, 164.59, 158.49, 152.85, 150.85, 137.67, 137.19, 133.11, 129.30, 129.16, 125.02, 121.14, 115.13, 14.87. See attached table for test results. Figure 2 .

[0036] Mass spectrometry data: HRMS (ESI) C 18 H 13 ClN4S[M+H] + Theoretical value: 381.0689; Test value: 381.0684. See attached table for test values. Figure 3

[0037] Example 2: Determination of the fluorescence properties of 5-chloro-3-methyl-1-phenyl-4-pyrazole carbaldehyde condensate 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole compound.

[0038] In 10 -5 The fluorescence spectrum of the compound was tested at room temperature at a concentration of mol / L; with attached... Figure 4 It can be seen that it has a strong fluorescence spectrum at 394 nm.

[0039] Example 3: Determination of the antioxidant activity of 5-chloro-3-methyl-1-phenyl-4-pyrazole carbaldehyde condensate 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole compound.

[0040] Antioxidant activity was determined using the DPPH method.

[0041] DPPH method: DPPH is a very stable free radical centered on nitrogen. Its ethanol solution has a maximum absorption peak at 517 nm. If Schiff bases can scavenge it, it indicates that Schiff bases have the function of reducing free radicals such as hydroxyl groups and interrupting lipid peroxidation chain reactions. At present, the DPPH method has been widely used in the screening of free radical scavengers.

[0042] Experimental method: 0.2 mL of sample solutions of different concentrations were respectively mixed with 3.8 mL of 6.35 x 10⁻⁶ solution. -6A mol / L DPPH ethanol solution was mixed thoroughly and reacted in the dark for 30 min. Using anhydrous ethanol as a reference, the absorbance was measured at 517 nm, and the DPPH scavenging rate K was calculated.

[0043] K=[(A0-As) / A0] * 100%,

[0044] A0 represents the absorbance of the DPPH ethanol solution at 517 nm, and As represents the absorbance of samples of different concentrations reacting with DPPH solution for 30 min at 517 nm. A scavenging rate against solution concentration was plotted to obtain the DPPH free radical scavenging rate curve of the compound. The results are shown in the attached figure. Figure 5 From the appendix Figure 5 It is known that the compounds of the present invention have a certain degree of scavenging effect on hydroxyl radicals at different concentrations, exhibiting certain antioxidant activity; the scavenging effect on free radicals is best at a concentration of 0.06 g / L, and it has potential application value in the field of oxidants.

Claims

1. A Schiff base compound, having the structure I: （Ⅰ）。 2. A method for preparing the Schiff base compound of claim 1, comprising:

3. (1) dissolving the freshly prepared 2-amino-5-(4-pyridyl)-1,3,4-thiadiazole compound of formula (III) with a solvent; (2) adding the 5-chloro-3-methyl-1-phenyl-4-pyrazole carboxaldehyde of formula (II) and the compound of formula (III) solution into a reaction device, heating to reflux, and reacting for 7 h; (3) cooling, desolventizing, filtering, and washing to obtain the target compound.

4. The process for the preparation of Schiff base compound as claimed in claim 2, wherein, The solvent in step (1) is selected from the group consisting of anhydrous ethanol.

5. The method of claim 2, wherein the Schiff base compound is prepared by the reaction of an aldehyde or a ketone with an amine. The step (2) further comprises monitoring the reaction progress by TLC.

6. The process for the preparation of Schiff base compound as claimed in claim 2, wherein, The molar ratio of the raw material II to the raw material III is 1:1-1.

5.

7. The Schiff base of claim 1, for use in the preparation of fluorescent materials and free radical scavengers for the prevention and treatment of aging and diseases.

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