CN114644625A - 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole and preparation method and application thereof - Google Patents
2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole and preparation method and application thereof Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
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- A23L3/34—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by treatment with chemicals
- A23L3/3454—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by treatment with chemicals in the form of liquids or solids
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- A23L3/3544—Organic compounds containing hetero rings
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
Abstract
The invention relates to the technical field of antioxidant reagents, and particularly relates to 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole and a preparation method and application thereof. The 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole comprises three aromatic ring structures including an indole ring, a thiazole ring and a benzene ring, wherein the aromatic ring structures are connected by alternate single double bonds to form a large conjugated structure, so that the orbital energy level difference between the highest occupied orbit and the lowest vacant molecular orbit in the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole is reduced, the reaction activity is increased, and the free radical scavenging capacity is enhanced. Thus, the DPPH radical scavenging rate is higher at lower concentrations.
Description
Technical Field
The invention relates to the technical field of antioxidant reagents, and particularly relates to 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole and a preparation method and application thereof.
Background
In 1864, the German chemist Hugo Schiff (Schiff, H.Mitteilungen au des univariate slabstodorferi um in Pisa: Einene reihe organischer basen. (in German). Justus LiebigsAnnalen der Chemie.1864,131, 118-119.) described for the first time the formation of Schiffbase by condensation of two equal amounts of aldehyde and amine by the reaction mechanism: aldehyde and ketone compounds containing carbonyl and primary amine compounds are subjected to nucleophilic addition reaction, the nucleophilic reagent is an amine compound, single atoms with lone electron pairs in the structure of the amine compound attack carbon atoms with positive charges on carbonyl groups, the nucleophilic addition reaction is completed, an intermediate alpha-hydroxylamine compound is formed, and then the intermediate alpha-hydroxylamine compound is further dehydrated to form Schiff base, wherein the Schiff base is shown in formula 1:
the imine compound formed by the aliphatic aldehyde and the amine is extremely unstable and can be rapidly decomposed after being generated, and the Schiff base formed by the aromatic aldehyde is relatively stable due to the conjugated structure and can be separated to obtain the compound. If substituted hydrazines are used instead of amines to react with aromatic aldehydes, hydrazino schiff base compounds can be obtained, which are in turn referred to as hydrazones. The hydrazone compounds have wide application in medicine, and show bacteriostatic, antitumor, tumor treating and antioxidant activities.
Thiazole is a five-membered heterocyclic compound containing one sulfur and one single atom and has the chemical formula C3H3NS is colorless or light yellow liquid with special odor, and thiazole structure is widely distributed in organism to exert huge physiological activity, such as vitamin B1 (shown as formula 2). Thiazoles are also useful as organic synthesis reagents for the synthesis of pharmaceuticals, dyes, rubber accelerators, film formers, bactericides, dyes and the like. The ring system of the thiazole has certain stability and also shows certain aromaticity;
therefore, thiazole compounds are proved to have better pharmacological and biological activities and are widely applied to the fields of tumor resistance, sterilization, virus resistance and the like.
On the basis, the thiosemicarbazide contains a hydrazine group, and can be subjected to ring closure with 2-bromoacetophenone under certain conditions to generate a thiazole compound (shown as a formula 3), so that the thiosemicarbazide is an ideal molecular building block for connecting the aromatic aldehyde and the thiazole.
In 2021, Chenshang 38040of Jiangxi agricultural university, etc. (CN113880786A) invented a synthesis method of a campheylaldehyde group thiazole hydrazone derivative, which uses camphene as a raw material in the process of synthesizing camphor from alpha-pinene to synthesize a series of thiazole hydrazone derivatives through Vilsmeier-Haack formylation, condensation and cyclization reactions, and carries out an antioxidant activity test on the thiazole hydrazone derivatives, wherein the antioxidant capacity of a plurality of compounds is stronger than that of a positive control Trolox (water-soluble vitamin E), and the DPPH free radical clarity is only 20.50mg/L at the strongest.
Disclosure of Invention
In view of the above, the present invention aims to provide a 2- (substituted indol-3-yl) -hydrazone-4-phenylthiazole, a preparation method and an application thereof, wherein the 2- (substituted indol-3-yl) -hydrazone-4-phenylthiazole has a high DPPH radical scavenging rate at a low concentration.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole which has a structure shown in a formula I:
wherein R is1Is composed of
The invention also provides a preparation method of the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole in the technical scheme, which comprises the following steps:
when R is1Is composed of
mixing N, N-dimethylformamide and phosphorus oxychloride, carrying out a first ice-bath reaction, adding a solution of a compound with a structure shown in a formula II, and carrying out a second ice-bath reaction to obtain a compound with a structure shown in a formula III;
mixing a compound with a structure shown in a formula III, thiosemicarbazide, ethanol and glacial acetic acid, performing a first reflux reaction, adding 2-bromoacetophenone, and performing a second reflux reaction to obtain the 2- (substituted indol-3-yl) -hydrazone-4-phenyl;
the compound having the structure shown in the formula II is
The compound having the structure shown in the formula III is
When R is1Is composed of
The preparation method of the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole comprises the following steps:
mixing indole-5-formaldehyde, thiosemicarbazide, ethanol and glacial acetic acid, performing a first reflux reaction, adding 2-bromoacetophenone, and performing a second reflux reaction to obtain the 2- (substituted indole-3-yl) -hydrazone-4-phenyl.
Preferably, the concentration of the solution of the compound with the structure shown in the formula II is 0.75-2 mmol/mL; the solvent of the solution of the compound with the structure shown in the formula II is N, N-dimethylformamide;
the molar ratio of the compound with the structure shown in the formula II in the solution of the N, N-dimethylformamide, the phosphorus oxychloride and the compound with the structure shown in the formula II is (15-25) to (1.1-1.5): 1.0.
preferably, the time of the first ice-bath reaction is 30-60 min; and the time of the second ice-bath reaction is 1-3 h.
Preferably, the molar ratio of the compound with the structure shown in the formula II, the thiosemicarbazide and the 2-bromoacetophenone is 1:1: 1.
Preferably, the dosage ratio of the thiosemicarbazide to the ethanol is 1mmol (10-15) mL.
Preferably, the temperature of the first reflux reaction is 70 ℃, and the time is 5-7 h;
the temperature of the second reflux reaction is 70 ℃, and the time is 1-2 h.
The invention also provides application of the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole prepared by the technical scheme or the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole prepared by the preparation method in the technical scheme in the field of oxidation resistance.
Preferably, the application comprises the preparation of anti-aging drugs, anti-aging skin care products or food antioxidant additives.
The invention provides 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole which has a structure shown in a formula I:
wherein R is1Is composed of
The 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole contains three aromatic ring structures including an indole ring, a thiazole ring and a benzene ring, and the aromatic ring structures are connected with one another by alternate single double bonds to form a large conjugated structure, so that the orbital energy level difference between the highest occupied orbit and the lowest empty molecular orbit in the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole is reduced, the reaction activity is increased, and the free radical scavenging capacity is enhanced. Thus, the DPPH radical scavenging rate is higher at lower concentrations.
Detailed Description
The invention provides 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole which has a structure shown in a formula I:
wherein R is1Is composed of
The invention also provides a preparation method of the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole in the technical scheme, which comprises the following steps:
when R is1Is composed of
The preparation method of the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole comprises the following steps:
mixing N, N-dimethylformamide and phosphorus oxychloride, carrying out a first ice-bath reaction, adding a solution of a compound with a structure shown in a formula II, and carrying out a second ice-bath reaction to obtain a compound with a structure shown in a formula III;
mixing a compound with a structure shown in a formula III, thiosemicarbazide, ethanol and glacial acetic acid, performing a first reflux reaction, adding 2-bromoacetophenone, and performing a second reflux reaction to obtain the 2- (substituted indol-3-yl) -hydrazone-4-phenyl;
the compound having the structure shown in the formula II is
The compound having the structure shown in the formula III is
When R is1Is composed of
The preparation method of the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole comprises the following steps:
mixing indole-5-formaldehyde, thiosemicarbazide, ethanol and glacial acetic acid, performing a first reflux reaction, adding 2-bromoacetophenone, and performing a second reflux reaction to obtain the 2- (substituted indole-3-yl) -hydrazone-4-phenyl.
In the present invention, all the starting materials for the preparation are commercially available products known to those skilled in the art unless otherwise specified.
When R is1Is composed of
The method comprises the following steps:
the method comprises the steps of mixing N, N-dimethylformamide and phosphorus oxychloride, carrying out a first ice bath reaction, adding a solution of a compound with a structure shown in a formula II, and carrying out a second ice bath reaction to obtain a compound with a structure shown in a formula III.
In the present invention, the mixture of N, N-dimethylformamide and phosphorus oxychloride is preferably: under the conditions of ice bath and stirring, phosphorus oxychloride is dropwise added into N, N-dimethylformamide. The stirring process is not particularly limited, and may be performed by a method known to those skilled in the art. In the invention, the molar ratio of the N, N-dimethylformamide to the phosphorus oxychloride is preferably (15-25) to (1.1-1.5), and more preferably (20-25): (1.2-1.3), and most preferably 25: 1.2.
In the invention, the temperature of the first ice bath reaction is preferably 0 ℃, and the time is preferably 30-60 min, and more preferably 40-50 min. In the invention, in the first ice bath reaction process, N-dimethylformamide reacts with phosphorus oxychloride to generate a chloroimine cation intermediate, and after the first ice bath reaction is finished, the color of the reaction solution is changed into pink.
In the present invention, the solute of the solution of the compound having the structure represented by formula II preferably includes the compound having the structure represented by formula II and N, N-dimethylformamide. In the invention, the concentration of the solution of the compound with the structure shown in the formula II is preferably 0.75-2 mmol/mL, and more preferably 1 mmol/mL. In the invention, the molar ratio of the phosphorus oxychloride to the compound with the structure shown in the formula II is preferably (1.1-1.5): 1.0, more preferably (1.2 to 1.3): 1.0, most preferably 1.2: 1.0.
in the invention, the temperature of the second ice bath reaction is preferably 0 ℃, and the time is preferably 1-3 h, and more preferably 1 h.
After the second ice-bath reaction is completed, the invention also preferably comprises post-treatment, and the post-treatment process is preferably as follows: and slowly returning the obtained reaction liquid to room temperature, quickly pouring the reaction liquid into ice blocks, adjusting the pH value to 10 by using a sodium hydroxide solution with the concentration of 5mol/L, heating to 80 ℃ for 1 hour, cooling, adjusting the pH value to 4 by using a hydrochloric acid solution with the concentration of 2mol/L, separating out solids, washing with water, filtering, and naturally drying for 24 hours.
After the compound with the structure shown in the formula III is obtained, the compound with the structure shown in the formula III, thiosemicarbazide, ethanol and glacial acetic acid are mixed, after a first reflux reaction is carried out, 2-bromoacetophenone is added, a second reflux reaction is carried out, and the 2- (substituted indole-3-yl) -hydrazone-4-phenyl is obtained.
In the present invention, the ethanol is preferably anhydrous ethanol; the mol ratio of the compound with the structure shown in the formula II, the thiosemicarbazide and the 2-bromoacetophenone is 1:1: 1; the dosage ratio of the thiosemicarbazide to the ethanol is preferably 1mmol (10-15) mL, and more preferably 1mmol (12-13) mL. In the invention, preferably, 2-3 drops of glacial acetic acid are dropped into every 10mL of ethanol.
The mixing process is not particularly limited, and may be performed by a method known to those skilled in the art.
In the invention, the temperature of the first reflux reaction is preferably 70 ℃, the time is preferably 5-7 h, and more preferably 5 h.
In the present invention, the substituted indole-3-carbaldehyde is subjected to dehydration condensation with thiosemicarbazide during the first reflux reaction to form a 2- ((substituted indol-3-yl) methylene) hydrazine-1-thioamino intermediate.
In the present invention, the progress of the first reflux reaction is preferably monitored by TLC plates.
In the invention, the temperature of the second reflux reaction is preferably 70 ℃, and the time is preferably 1-2 h, and more preferably 1 h.
In the present invention, the progress of the second reflux reaction is preferably checked by TLC plates.
After the second reflux reaction is finished, the invention also preferably comprises the step of carrying out post-treatment on the obtained product system; the post-treatment preferably comprises: and cooling the product system overnight, pouring the reaction solution into cold water, separating out a large amount of solids, performing suction filtration, washing for 3 times, and naturally drying by adopting tetrahydrofuran: after washing with a mixed solution of n-hexane and 1:9, the reaction mixture was washed with tetrahydrofuran: the mixed solution of n-hexane and 1:19 was recrystallized.
The invention also provides application of the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole prepared by the technical scheme or the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole prepared by the preparation method in the technical scheme in the field of oxidation resistance.
In the invention, the application comprises the preparation of anti-aging drugs, anti-aging skin care products or food antioxidant additives. The method of the present invention is not particularly limited, and the method may be performed by a method known to those skilled in the art.
The following examples are provided to illustrate the 2- (substituted indol-3-yl) -hydrazone-4-phenylthiazole and the preparation and use thereof in detail, but they should not be construed as limiting the scope of the present invention.
Example 1
Preparation of 2-methylindole-3-carbaldehyde:
the synthetic route is as follows:
slowly and dropwise adding phosphorus oxychloride (1.2mmol, 0.1840g and 0.112mL) into N, N-dimethylformamide (25mmol, 1.827g and 1.93mL) under the conditions of ice bath and stirring at 0 ℃, keeping the ice bath for 30min, dissolving 2-methylindole (1.0mmol and 0.1312g) in 1mL of N, N-dimethylformamide until the color of the solution turns to pink, slowly dropwise adding the solution into the solution, reacting for 1h in the ice bath, slowly returning to room temperature, quickly pouring the reaction liquid into ice blocks, adjusting the pH to 10 by using a 5mol/L sodium hydroxide solution, heating to 80 ℃, keeping for 1h, cooling, adjusting the pH to 4 by using a 2mol/L hydrochloric acid solution, precipitating a large amount of solid, washing by using a large amount of water, filtering off insoluble substances, naturally drying for 24h in a drier, and reserving for later use.
Synthesis of 2- ((substituted indol-3-yl) -hydrazone-4-phenylthiazole:
the synthetic route is as follows:
in a 25mL round-bottom flask, heating all the 2-methylindole-3-formaldehyde solid obtained in the above steps, thiosemicarbazide (1mmol, 0.0911g), 10mL of anhydrous ethanol and 2-3 drops of glacial acetic acid as a catalyst to 70 ℃, carrying out reflux reaction for 5h, monitoring the reaction process by using a TLC (thin layer chromatography) spot plate, after the reaction is completed, adding 2-bromoacetophenone (1mmol, 0.1991g), continuing the reflux reaction for 1h at 70 ℃, monitoring the reaction process by using the TLC spot plate, cooling overnight after the reaction is completed, pouring the reaction liquid into cold water, precipitating a large amount of solid, carrying out suction filtration, washing for 3 times, naturally air-drying, washing with a tetrahydrofuran-n-hexane-1: 19 mixed liquid, washing the filter residue with a tetrahydrofuran-n-hexane-1: 19 mixed liquid, and recrystallizing to obtain the target compound, wherein the yield reaches 76%.
Examples 2 to 15
The preparation method is as described in example 1, except that 2-methylindole is replaced by a compound having a structure represented by formula II, and the prepared 2-methylindole-3-carbaldehyde corresponds to a compound having a structure represented by formula III, as shown in Table 1:
TABLE 1 structural formulas of the compound having the structure represented by the formula II and the compound having the structure represented by the formula III in examples 2 to 15
Test examples in vitro antioxidant activity assay:
1. preparation work
1-1 preparation of different concentrations of drugs:
1. the drug concentration in the first tube was 400 μ g/mL, i.e. 1.6mg of test compound was added to the 1 st tube in a 1:9 mixture of dichloromethane and ethanol.
2. The mixture was centrifuged in 7 tubes (No. 2 to No. 8), and 2mL of a mixture of dichloromethane and ethanol (1: 9) was added thereto.
3. 2mL are taken to second centrifuging tube after the first tub of medicine mixes, 2mL are taken to third centrifuging tube after the second centrifuging tube mixes to analogize to 8 th centrifuging tube, all need to change the rifle head to low concentration by the high concentration at every turn.
4. The drug concentrations were 400. mu.g/mL, 200. mu.g/mL, 100. mu.g/mL, 50. mu.g/mL, 25. mu.g/mL, 12.5. mu.g/mL, 6.25. mu.g/mL and 3.125. mu.g/mL in this order.
5. Centrifuge tubes with concentrations of 400. mu.g/mL and 200. mu.g/mL (i.e., the 1 st centrifuge tube and the 2 nd centrifuge tube) were discarded, and only 6 concentration gradients of 100. mu.g/mL to 3.125. mu.g/mL were used for the experiments.
Preparation of 1-2DPPH working solution
2.5mg of 2,2-Diphenyl-1-picrylhydrazyl radical (2,2-Diphenyl-1-picrylhydrazyl, DPPH) is dissolved in 100mL of a mixture of dichloromethane and ethanol (1: 9), and the mixture is stored at low temperature in the dark for later use.
Preparation of 1-3 vitamin C positive control solution
Vitamin C (10mg) is dissolved in 40mL of absolute ethanol to prepare 250mg/L vitamin C stock solution, and the stock solution is diluted to be gradient control solutions of 0mg/L, 10mg/L, 25mg/L, 50mg/L, 75mg/L and 125mg/L respectively by using the absolute ethanol.
2. Determination of DPPH radicals:
1. taking a covered 96-well plate;
2. the concentration of the drug in the first column is 400 mug/mL, the concentration of the drug in the last column is 3.125 mug/mL, the samples are loaded from right to left in one column, 150 mug/well, each concentration is provided with 8 multiple wells, and each 96-well plate can be used for preparing 2 samples.
3. Adding samples from top to bottom row by row, arranging 4 repeated holes, and respectively adding DPPH working solution and mixed solution of dichloromethane and ethanol in a ratio of 1: 9;
4. the last 96-well plate used vitamin C positive control.
5. The 96-well plate was placed in a biochemical incubator at 37 ℃ for 30min in the dark.
6. And (3) putting the 96-well plate into a multifunctional microplate reader, and setting the absorption wavelength to be 510nm to measure the absorbance. The clearance was calculated using a formula.
3. DPPH radical scavenging results
TABLE 2DPPH radical scavenging results for positive control L-ascorbic acid
Linear fitting is carried out to obtain a regression equation y of 1.1218x +5.945, and the IC50 of the L-ascorbic acid under the experimental condition can be calculated to be 39.27 mug/mL;
the IC50 values for the 2- (substituted indol-3-yl) -hydrazone-4-phenylthiazole compounds of examples 1 to 16 were calculated according to the following formula:
TABLE 3 DPPH radical scavenging Rate and IC50 value for 2- (substituted indol-3-yl) -hydrazone-4-phenylthiazole described in examples 1 to 16
As can be seen from Table 3, the DPPH radical scavenging rate of the 2- (substituted indol-3-yl) -hydrazone-4-phenylthiazole is significantly higher than that of the L-ascorbic acid control or equivalent to that of the L-ascorbic acid in examples 1 to 15, and the 2- (substituted indol-3-yl) -hydrazone-4-phenylthiazole in example 16 is slightly inferior to that of the L-ascorbic acid, and the compounds have stronger DPPH radical scavenging ability.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (9)
1. A2- (substituted indol-3-yl) -hydrazone-4-phenylthiazole, which has a structure represented by formula I:
wherein R is1Is composed of
2. A process for preparing 2- (substituted indol-3-yl) -hydrazone-4-phenylthiazole according to claim 1, comprising the steps of:
when R is1Is composed of
The preparation method of the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole comprises the following steps:
mixing N, N-dimethylformamide and phosphorus oxychloride, carrying out a first ice bath reaction, adding a solution of a compound with a structure shown in a formula II, and carrying out a second ice bath reaction to obtain a compound with a structure shown in a formula III;
mixing a compound with a structure shown in a formula III, thiosemicarbazide, ethanol and glacial acetic acid, performing a first reflux reaction, adding 2-bromoacetophenone, and performing a second reflux reaction to obtain the 2- (substituted indol-3-yl) -hydrazone-4-phenyl;
the compound having the structure shown in the formula II is
The compound having the structure shown in the formula III is
When R is1Is composed of
The preparation method of the 2- (substituted indole-3-yl) -hydrazone-4-phenylthiazole comprises the following steps:
mixing indole-5-formaldehyde, thiosemicarbazide, ethanol and glacial acetic acid, performing a first reflux reaction, adding 2-bromoacetophenone, and performing a second reflux reaction to obtain the 2- (substituted indole-3-yl) -hydrazone-4-phenyl.
3. The preparation method according to claim 2, wherein the concentration of the solution of the compound having the structure represented by the formula II is 0.75 to 2 mmol/mL; the solvent of the solution of the compound with the structure shown in the formula II is N, N-dimethylformamide;
the molar ratio of the compound with the structure shown in the formula II in the solution of the N, N-dimethylformamide, the phosphorus oxychloride and the compound with the structure shown in the formula II is (15-25) to (1.1-1.5): 1.0.
4. the preparation method according to claim 2 or 3, wherein the time of the first ice bath reaction is 30-60 min; and the time of the second ice-bath reaction is 1-3 h.
5. The preparation method according to claim 2, wherein the molar ratio of the compound having the structure shown in the formula II, the thiosemicarbazide and the 2-bromoacetophenone is 1:1: 1.
6. The preparation method according to claim 2, wherein the dosage ratio of the thiosemicarbazide to the ethanol is 1mmol (10-15) mL.
7. The preparation method according to claim 2, 5 or 6, wherein the temperature of the first reflux reaction is 70 ℃ and the time is 5-7 h;
the temperature of the second reflux reaction is 70 ℃, and the time is 1-2 h.
8. The 2- (substituted indol-3-yl) -hydrazone-4-phenylthiazole as claimed in claim 1 or the 2- (substituted indol-3-yl) -hydrazone-4-phenylthiazole prepared by the preparation method as claimed in any one of claims 2 to 7, and the application thereof in the field of oxidation resistance.
9. The use according to claim 8, wherein said use comprises the preparation of an anti-aging medicament, an anti-aging skin care product or a food antioxidant additive.
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