CN105439969B - A kind of method for preparing the triazole of 3,5 dioxo 1,2,4 - Google Patents

Abstract

The present invention proposes the method that one kind prepares the triazole of 3,5 dioxo 1,2,4, is characterized in the WO of oxygen vacancies be present_3‑xNanometer sheet adds appropriate additive as raw material in a solvent using tungstic acid hydrate sodium in acid condition, directly synthesized with solvent heat or the step of direct-fired method one, the tungsten oxide nanometer sheet that oxygen vacancies be present is made first, tungsten oxide nanometer sheet catalysis oxidation sulfilimine is prepared 3 again, 5 dioxos 1,2,4 triazoles.Reaction condition of the present invention is simple, and cost is low, pollution-free, not only with important industrial application value, and has important environment and social effect.

Description

A method for preparing 3,5-dioxo-1,2,4-triazole

technical field

The present invention relates to organic chemistry, in particular to a method for preparing 3,5-dioxo-1,2,4-triazole, which refers to a method for catalyzing the oxidation of _urazole into 3,5 - The method of dioxo-1,2,4-triazoles.

Background technique

3,5-dioxo-1,2,4-triazoles are a class of important biologically active organic compounds with a wide range of biological activities, some 3,5-dioxo-1,2,4-triazoles Azole derivatives not only exhibit anti-tumor, anti-virus, antibacterial and other activities, 3,5-dioxo-1,2,4-triazole derivatives can also be used to interact with active amino acids, polypeptides, proteins, The combination of vaccines (PCT patent, WO2013009564) has important clinical applications. Usually 3,5-dioxo-1,2,4-triazoles are prepared by oxidation of the corresponding urazoles. Currently commonly used oxidants are dinitrogen tetroxide, nitric acid immobilized on silica, tetrabutylammonium periodate, sodium periodate + tetrabutylammonium bromide, chlorine gas, iodine chloride, silver nitrate, persulfate Salt, etc. These oxidants are volatile and highly corrosive, such as dinitrogen tetroxide, chlorine gas, iodine chloride, etc.; some are expensive, such as silver nitrate, high point salt, etc. As a result, all of the above oxidants do not meet the requirements of atom economy, and have disadvantages such as complicated operations, many by-products, unfavorable product purification, easy pollution of the environment, and high cost. Therefore, the development of a pollution-free, low-cost green oxidation method that can oxidize urazole to 3,5-dioxo-1,2,4-triazole is not only of great industrial application value, but also has important environmental and Social Significance.

Contents of the invention

The technical problem to be solved by the present invention is to provide the preparation of 3,5-dioxo-1,2,4-triazole compounds by using WO _3-x nanosheets with oxygen holes as a catalyst to oxidize urazole with hydrogen peroxide Methods.

In order to solve the above-mentioned technical problems, the technical solution adopted by the present invention is: a method for preparing 3,5-dioxo-1,2,4-triazole, which uses WO _3-x nanosheets with oxygen holes Under acidic conditions, sodium tungstate hydrate is used as a raw material to add appropriate additives to the solvent, and it is directly synthesized in one step by solvothermal or direct heating. The preparation method steps are as follows:

(1) Dissolve 1-3 mmol of sodium tungstate dihydrate in 15-25 ml of water, stir for 5-20 minutes, and make a transparent solution;

(2) Add 6-13 ml of ethanol to the above solution, and stir for 5-20 minutes;

(3) Add 15 to 25 milliliters of sulfuric acid to the above solution, and stir for 5 to 20 minutes;

(4) Add 0.1 to 0.6 grams of polyethylene glycol 10000 to the above solution, and stir for 5 to 20 minutes;

(5) Transfer the above mixture into a 100 ml reaction kettle lined with polytetrafluoroethylene and seal it, stir at 120-200°C for 3-5 hours, and cool to room temperature;

(6) Pour the above-mentioned cooled reaction mixture into 500 ml of distilled water, collect the precipitate, wash it with deionized water and absolute ethanol in turn, and dry it in vacuum to obtain tungsten oxide (WO _3-x ) nanometer with oxygen holes. piece;

WO _3-x nanosheets catalyze the oxidation of urazole compounds to prepare 3,5-dioxo-1,2,4-triazole, the reaction formula is:

The specific process is:

(1) Add 1 mmol of urazole compound into the reactor, add 1 to 5 milliliters of solvent, add 0.005 to 0.05 mmol of catalyst (WO _3-x ), 1 to 3 mmol of 30% hydrogen peroxide , Stir at 20-100°C for 10-120 minutes, the reaction formula is:

(2) Dilute the above to 10 ml, extract with ether, concentrate to remove the solvent, perform flash column chromatography, and use the obtained pure product to calculate the yield.

The solvent refers to a polar solvent, including methanol, ethanol, acetonitrile, acetic acid, and N,N-methylformamide.

The present invention adopts a method for preparing 3,5-dioxo-1,2,4-triazole designed by the above technical scheme. The method has simple reaction conditions, low cost and no pollution, and not only has important industrial applications value, and has important environmental and social significance.

Detailed ways

The method for preparing 3,5-dioxo-1,2,4-triazole of the present invention is to use WO _3-x nanosheets with oxygen holes under acidic conditions and use hydrated sodium tungstate as a raw material in a certain solvent Appropriate additives are added to the compound, and it is directly synthesized in one step by solvothermal or direct heating.

Example 1

(1) Dissolve 1 mmol of sodium tungstate dihydrate in 15 ml of water, stir for 5 minutes, and make a transparent solution;

(2) Add 6 milliliters of ethanol to the above solution, stir for 5 minutes;

(3) Add 15 milliliters of sulfuric acid in above-mentioned solution, stir 5 minutes;

(4) Add 0.1 gram of polyethylene glycol 10000 to the above solution and stir for 5 minutes;

(5) Transfer the above mixture into a 100 ml reaction kettle with a Teflon liner and seal it, stir at 120°C for 3 hours, and cool to room temperature;

(6) Pour the above-mentioned cooled reaction mixture into 500 ml of distilled water, collect the precipitate, wash it with deionized water and absolute ethanol in turn, and dry it in vacuum to obtain tungsten oxide (WO _3-x ) nanometer with oxygen holes. piece.

Example 2

(1) Dissolve 2 mmol of sodium tungstate dihydrate in 20 ml of water, stir for 10 minutes, and make a transparent solution;

(2) Add 10 milliliters of ethanol to the above solution, stir for 10 minutes;

(3) Add 20 milliliters of sulfuric acid in above-mentioned solution, stir 10 minutes;

(4) Add 0.3 grams of polyethylene glycol 10000 to the above solution, and stir for 10 minutes;

(5) Transfer the above mixture into a 100 ml reaction kettle with a Teflon liner and seal it, stir at 160°C for 8 hours, and cool to room temperature;

(6) Pour the above-mentioned cooled reaction mixture into 500 ml of distilled water, collect the precipitate, wash with deionized water and absolute ethanol in turn, and vacuum dry to obtain blue-purple WO _3-x nanosheets with oxygen holes.

Example 3

(1) Dissolve 3 mmoles of sodium tungstate dihydrate in 25 ml of water, stir for 20 minutes, and make a transparent solution;

(2) Add 13 milliliters of ethanol to the above solution, and stir for 20 minutes;

(3) Add 25 milliliters of sulfuric acid in above-mentioned solution, stir 20 minutes;

(4) Add 0.6 grams of polyethylene glycol 10000 to the above solution, and stir for 20 minutes;

(5) Transfer the above mixture into a 100 ml reaction kettle with a polytetrafluoroethylene liner and seal it, stir at 200°C for 5 hours, and cool to room temperature;

(6) Pour the above-mentioned cooled reaction mixture into 500 ml of distilled water, collect the precipitate, wash it with deionized water and absolute ethanol in turn, and dry it in vacuum to obtain tungsten oxide (WO _3-x ) nanometer with oxygen holes. piece;

Example 4

The WO _3-x nanosheets of the present invention catalyze the oxidation of N-(4-alkyne-1-pentyl)urazole to prepare N-(4-alkyne-1-pentyl)-3,5-dioxo-1,2, 4-triazole, the reaction formula is:

The specific steps are:

(1) Add 1 mmol of N-(4-alkyne-1-pentyl) urazole into the reactor, add 2 ml of acetonitrile, add 0.02 mmol of catalyst (WO _3-x ), 30% peroxide Hydrogen 2 mmoles, stirred at 30°C for 1 hour;

(2) Dilute the above dilute solution to 10 ml with water, extract with ether, concentrate to remove the solvent, and perform flash column chromatography to obtain N-(4-alkyne-1-pentyl)-3,5-dioxo-1,2 , 4-triazole, red solid, yield 93%; ¹ H NMR (400MHz; CDCl ₃ ,δ): 7.58-7.40 (m, 5H).

Example 5

The WO _3-x nanosheets of the present invention catalyze the oxidation of N-phenylurazole to prepare N-phenyl-3,5-dioxo-1,2,4-triazole, and the reaction formula is:

The specific steps are:

(1) Add 1 mmol of N-phenylurazole into the reactor, add 1 ml of water, add 0.05 mmol of catalyst (WO _3-x ), 3 mmol of 30% hydrogen peroxide, stir at 70°C 3 hours;

(2) Dilute the above dilute solution to 10 ml with water, extract with ether, concentrate to remove the solvent, and perform flash column chromatography to obtain N-phenyl-3,5-dioxo-1,2,4-triazole, red Solid, yield 84%; ¹ H NMR (400 MHz; CDCl ₃ , δ): 7.58-7.40 (m, 5H).

Example 6

The WO _3-x nanosheets of the present invention catalyze the oxidation of N-phenylurazole to prepare 4-(4-alkyne-pentyl)-3,5-dioxo-1,2,4-triazole, and the reaction formula is:

The specific steps are:

(1) 1 mmol of N-(4-alkyne-pentyl) urazole is added to the reactor, 1 milliliter of acetonitrile is added, 0.03 mmol of catalyst (WO _3-x ), 30% hydrogen peroxide 2 millimole, stirred at 30°C for 1 hour;

(2) Dilute the above dilute solution to 10 ml with water, extract with ether, concentrate to remove the solvent, and perform flash column chromatography to obtain 4-(4-alkyne-pentyl)-3,5-dioxo-1,2,4 -Triazole, red solid, yield 86%; ¹ H NMR (400MHz; CDCl ₃ ,δ): 4.02(t, J=7.6Hz, 2H), 2.50(t, J=7.6Hz, 2H), 1.96 (s,1H),1.75(m,2H).

In the foregoing embodiments, the solvent generally refers to a polar solvent, including methanol, ethanol, acetonitrile, acetic acid, N,N-methylformamide, and the like.

Claims (2)

1. A method for preparing 3,5-dioxo-1,2,4-triazole, which _is characterized in that 3,5 -Dioxo-1,2,4-triazole compounds, in which urazole compounds are 3,5-dioxo-1,2,4-triazole compounds are The reaction formula is: Wherein, R is phenyl or 3-(ethynyl) propyl; The specific process is: (1) Add 1 mmol of urazole compound into the reactor, add 1 to 5 milliliters of solvent, add 0.005 to 0.05 mmol of catalyst (WO _3-x ), 1 to 3 mmol of 30% hydrogen peroxide , stirring at 20-100°C for 10-120 minutes; (2) Dilute the above to 10 milliliters, extract with ether, concentrate to remove the solvent, perform flash column chromatography, and calculate the yield with the obtained pure product; The WO _3-x nanosheets with oxygen holes are synthesized by using sodium tungstate hydrate as a raw material under acidic conditions, adding appropriate additives in a solvent, and solvothermal or direct heating. The preparation method steps are: (1) Dissolve 1-3 mmol of sodium tungstate dihydrate in 15-25 ml of water, stir for 5-20 minutes, and make a uniform and transparent solution; (2) Add 6-13 ml of ethanol to the above solution, and stir for 5-20 minutes; (3) Add 15 to 25 milliliters of sulfuric acid to the above solution, and stir for 5 to 20 minutes; (4) Add 0.1 to 0.6 grams of polyethylene glycol 10000 to the above solution, and stir for 5 to 20 minutes; (5) Transfer the above mixture into a 100 ml reaction kettle lined with polytetrafluoroethylene and seal it, stir at 120-200°C for 3-5 hours, and cool to room temperature; (6) Pour the above-mentioned cooled reaction mixture into 500 ml of distilled water, collect the precipitate, wash it with deionized water and absolute ethanol in turn, and dry it in vacuum to obtain tungsten oxide (WO _3-x ) nanometer with oxygen holes. piece. 2. A method for preparing 3,5-dioxo-1,2,4-triazole according to claim 1, characterized in that said solvent refers to methanol, ethanol, acetonitrile, acetic acid, or N, N-Methylformamide.