CN105566169B - A kind of method for preparing nitrone by secondary amine - Google Patents

Abstract

The invention relates to a method for preparing nitrone from secondary amines. 2 mmol of secondary amines are added to a reactor, 4 to 5 mL of water, 0.02 to 0.03 mmol of tetrabutylammonium bromide are sequentially added, and catalyst WO _{3‑ x} 0.02～0.08 mmol and 30%～50% hydrogen peroxide solution 3～6 mmol, stirred at 25～60°C for 2～6 h; or add 2 mmol of secondary amine into the reactor, add polar solvent 3 ～5 mL, add catalyst WO _3‑x 0.02～0.08 mmol and 30%～50% hydrogen peroxide solution 3～6 mmol, stir at 25～60°C for 2～6 h; dilute the reacted mixed solution to 15 ~20 mL, extracted, concentrated, separated by column chromatography, and collected the product. The catalyst of the present invention is WO _3-x nanosheets with oxygen holes, and has high catalytic oxidation activity. The raw material source of the present invention is wide, the reaction conditions are simple, the reaction temperature is low, the yield of nitrone is high, and water is used as the reaction solvent so that the whole reaction step is free. Pollution, green environmental protection, low cost, not only has important industrial application value, but also has important environmental and social significance.

Description

A kind of method for preparing nitrone by secondary amine

technical field

The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for preparing nitrone from secondary amines.

Background technique

Nitrones are a class of organic intermediates with important applications, which can be used in the synthesis of medicine and natural products. The easy way to prepare nitrone is to oxidize the secondary amine to obtain the corresponding nitrone. The most commonly used oxidant is hydrogen peroxide, and the most commonly used catalyst is such as: sodium tungstate (Na ₂ WO ₄ ) (Shun-Ichi Murahashi, Hitoshi Mitsui, Tatsuki Shiota, Tomoyasu Tsuda, and Shoji Watanabe, J. Org. Chem. 1990, 55, 1736-1744.), but using sodium tungstate as a catalyst not only has low catalytic efficiency, but also needs to add a large excess of hydrogen peroxide, and the selectivity is also low. poor. More catalytic systems have been discovered, such as the rare metal rhenium oxide CH ₃ ReO ₃ (Sanny Vermaa, Subodh Kumara, Efrat Shawatb, Gilbert Daniel Nessimb, Suman L. Jain, Journal of Molecular Catalysis A: Chemical 402 (2015) 46– 52) Or metal rhenium oxide supported on graphene oxide (Praveen K. Khatri, Shivani Choudhary, Raghuvir Singh, Suman L. Jain and OmP. Khatri, Dalton Trans., 2014, 43, 8054–8061). Some metallic compounds can also catalyze this reaction such as organometallic titanium complexes (Massimiliano Forcato, Miriam Mba, William A. Nugent, and Giulia Licini, Eur. J. Org. Chem. 2010, 740–748) and organometallic platinum Complexes (MarcoColladon, Alessandro Scarso and Giorgio Strukul, Green Chem., 2008, 10, 793–798). In addition to some metal salts, metal oxides and organometallic compounds, some organic small molecule catalytic systems can also be used to prepare nitrone compounds, such as amine compounds containing polyhydroxyl groups, which can catalyze this type of reaction (MassimilianoForcato, William A. Nugentb and Giulia Licini, Tetrahedron Letters 44 (2003) 49–52), trichloroacetonitrile and hydrogen peroxide can be used to prepare nitrones (Fatemeh Nikbakht, AkbarHeydari, Tetrahedron Letters 55 (2014) 2513–2516). There are some deficiencies in the above-mentioned technical solutions, some need to use expensive rare metals such as rhenium, platinum, etc.; and some catalyst preparation methods are complex and industrially difficult, such as some organometallic titanium or platinum complexes; and organic compounds and The system in which hydrogen peroxide works together to prepare nitrone needs to add a large amount of organic compounds, and the atoms that do not meet the atom economy also cause a certain pressure on the environment.

Chinese patent CN1058702C discloses a new method for the preparation of nitrones, especially a method for the preparation of N-substituted alkylamines, which includes the presence of an oxidizing agent and at least one compound selected from carbon dioxide, nitrogen carbonate and carbonate The following steps are used to form nitrones with secondary amines. However, this patent requires liquid CO ₂ for the reaction, the reaction conditions are harsh, and it is only suitable for the oxidation of specific secondary amines, and its application range is narrow.

Contents of the invention

In order to overcome the above-mentioned defects, the object of the present invention is to provide a method for preparing nitrone from secondary amines, which has a wide range of sources of raw materials, simple reaction conditions, and high yield of nitrone.

To achieve the above object, the present invention adopts the following technical solutions:

A kind of method for preparing nitrone by secondary amine, secondary amine generates nitrone under the effect of catalyst WO _3-x and hydrogen peroxide solution, and its general reaction formula is as follows:

,

or ,

Wherein, R ¹ is hydrogen, aryl, alkyl or heterocycle containing 1-6 carbon atoms, R ² is aryl, alkyl or heterocycle containing 1-6 carbon atoms, R ³ is containing 2- Alkyl group with 6 carbon atoms, R ⁴ is hydrogen, methyl, ethyl or halogen, n=0, 1, 2, 3, 4, ring B is simple hydrogen, substituted benzene ring or substituted pyridine ring.

According to the above method for preparing nitrone by secondary amine, the catalyst WO _3-x is a WO _3-x nanosheet with oxygen holes, and its preparation method comprises the following steps:

a. Dissolve 1-3 mmol of sodium tungstate dihydrate in 10-25 mL of water, stir for 5-20 min, and make a uniform and transparent solution;

b. Add 5-13 mL of ethanol to the solution in step a, and stir for 5-20 min;

c. Add 15-25 mL of concentrated sulfuric acid to the solution in step b, and stir for 5-20 min;

d. Add 0.1-0.6 g of polyethylene glycol 10000 to the solution in step c, and stir for 5-20 min;

e. Transfer the mixed solution after the reaction in step d into a round-bottomed flask, stir at 120-160°C for 3-5 h, and cool to room temperature;

f. Add 300-500 mL of distilled water to the cooled mixture in step e, collect the precipitate, wash it with deionized water and absolute ethanol in turn, and dry it in vacuum to obtain WO _3-x nanosheets with oxygen holes.

According to the above-mentioned method for preparing nitrone by secondary amine, described secondary amine is N-tert-butylbenzylamine, 2-methylbenzyl tert-butylamine, 3-methylbenzyl tert-butylamine, 4-methylbenzyl tert-butylamine, 2-fluorobenzyl tert-butylamine, 3-fluorobenzyl tert-butylamine, 4-fluorobenzyl tert-butylamine, 2-nitrobenzyl tert-butylamine, 3-nitrobenzyl tert-butylamine, 4-nitrobenzyl tert-butylamine, diethylamine, di Propylamine, dibutylamine, diisopropylamine, dibenzylamine, tetrahydropyrrole, tetrahydroquinoline, tetrahydroisoquinoline, morpholine or piperidine.

According to the above method for preparing nitrone from secondary amines, the hydrogen peroxide solution is 30-50% hydrogen peroxide solution.

According to the above-mentioned method for preparing nitrone by secondary amine, comprise following reaction steps:

(1) Add 2 mmol of secondary amine into the reactor, add water 4~5 mL, tetrabutylammonium bromide 0.02~0.03 mmol, add catalyst WO _3-x 0.02~0.08 mmol and 30%~50% 3-6 mmol of hydrogen peroxide solution, stirred at 25-60 °C for 2-6 h to obtain a mixed solution;

(2) Dilute the mixed solution after the reaction in step (1) to 15-20 mL, extract with an organic solvent, concentrate to remove the solvent, separate by column chromatography, and collect the product.

According to the above-mentioned method for preparing nitrone by secondary amine, comprise following reaction steps:

(1) Add 2 mmol of secondary amine into the reactor, add 3-5 mL of polar solvent, add catalyst WO _3-x 0.02-0.08 mmol and 30%-50% hydrogen peroxide solution 3-6 mmol, Stir at 25-60 °C for 2-6 h to obtain a mixed solution;

(2) Dilute the mixed solution after the reaction in step (1) to 15-20 mL, extract with an organic solvent, concentrate to remove the solvent, separate by column chromatography, and collect the product.

According to the above method for preparing nitrone from secondary amines, the polar solvent in step (1) is methanol, ethanol, acetonitrile, acetic acid or N,N-methylformamide.

According to the above method for preparing nitrone from secondary amines, the organic solvent in step (2) is ethyl acetate, diethyl ether, methyl tert-butyl ether, dichloromethane or chloroform.

According to the above-mentioned method for preparing nitrone from secondary amines, the column chromatography separation condition described in step (2) is a 200-300 mesh silica gel column, and the eluent is petroleum ether and ethyl acetate, and the volume ratio of the two is 10 :1～2:1.

Positive beneficial effect of the present invention:

1. The tungsten oxide WO _3-x nanosheets with oxygen holes in the present invention are directly synthesized in one step by using hydrated sodium tungstate as raw material and adding appropriate additives in a certain solvent under acidic conditions. , the present invention has tungsten oxide WO _3-x nanosheets with oxygen holes, the preparation method is extremely simple, the production cost is low, easy to operate, there are oxygen holes in the microstructure, the shape is uniform, the size is small, and the specific surface area is large. Has high catalytic oxidation activity.

2. The present invention has wide sources of raw materials, simple reaction conditions, low reaction temperature, high nitrone yield, and water is used as a reaction solvent to make the whole reaction step pollution-free, green and environmentally friendly, with low cost, not only has important industrial application value, but also It has important environmental and social significance.

detailed description

The present invention will be further described below in conjunction with some specific embodiments.

Example 1

A method for preparing nitrone by N-tert-butylbenzylamine, its general reaction formula is as follows:

Include the following steps:

(1) Add 2 mmol of N-tert-butylbenzylamine into a 25 mL round bottom flask, add 3 mL of acetonitrile, add catalyst WO _3-x 0.02 mmol, 30% hydrogen peroxide solution 5 mmol, stir at 25 °C 3 h, a mixed solution was obtained;

(2) Dilute the mixed solution obtained in step (1) to 20 mL with water, extract with dichloromethane, concentrate to remove the solvent, and separate by column chromatography, 200-300 mesh silica gel column, eluents are petroleum ether and ethyl acetate, The volume ratio of the two was 2:1, and a white solid was obtained with a yield of 96%. ¹ H NMR (400 MHz; CDCl3, δ): 8.39-8.21 (2 H, m), 7.57 (1 H, s), 7.40 (3 H, m), 1.61 (9 H, s).

The catalyst WO _3-x is a WO _3-x nanosheet with oxygen holes, and its preparation method comprises the following steps:

a. Dissolve 1 mmol of sodium tungstate dihydrate in 10 mL of water and stir for 5 min to form a uniform and transparent solution;

b. Add 5 mL of ethanol to the solution in step a, and stir for 5 min;

c. Add 15 mL of concentrated sulfuric acid to the solution in step b, and stir for 5 min;

d. Add 0.1 g of polyethylene glycol 10000 to the solution in step c, and stir for 5 min;

e. Transfer the mixed solution after the reaction in step d into a 100 mL round bottom flask, stir at 140 °C for 3 h, and cool to room temperature;

f. Add 500 mL of distilled water to the cooled mixture in step e, collect the precipitate, wash with deionized water and absolute ethanol in turn, and dry in vacuum to obtain WO _3-x nanosheets with oxygen holes.

Example 2

A method for preparing nitrone by 3-methylbenzyl tert-butylamine, its general reaction formula is as follows:

Include the following steps:

(1) Add 2 mmol of 3-methylbenzyl tert-butylamine into a 25 mL round bottom flask, add methanol 4.0 mL, add catalyst WO _3-x 0.04 mmol, 40% hydrogen peroxide solution 4 mmol, stir at 25 °C 2 hours;

(2) Dilute the above dilute solution to 16 mL with water, extract with ethyl acetate, concentrate to remove the solvent, and separate by column chromatography, 200-300 mesh silica gel column, the eluent is petroleum ether and ethyl acetate, the volume ratio of the two The ratio was 5:1, and a white solid was obtained with a yield of 97%. ¹ H NMR (400 MHz; CDCl3,δ): 8.33 (1 H, s), 7.91 (1 H, d, J= 7.8 Hz), 7.52 (1 H, s), 7.31 (1 H, t, J 7.7 ), 7.22 (1 H, d, J= 7.6 Hz), 2.38 (3 H, s), 1.62 (9 H, s).

The catalyst WO _3-x is a WO _3-x nanosheet with oxygen holes, and its preparation method comprises the following steps:

a. Dissolve 2 mmol of sodium tungstate dihydrate in 21 mL of water and stir for 10 min to form a uniform and transparent solution;

b. Add 8 mL of ethanol to the solution in step a, and stir for 10 min;

c. Add 16 mL of concentrated sulfuric acid to the solution in step b, and stir for 13 min;

d. Add 0.5 g of polyethylene glycol 10000 to the solution in step c, and stir for 20 min;

e. transfer the mixed solution after the reaction of step d into a round bottom flask, stir at 120°C for 5 h, and cool to room temperature;

f. Add 400 mL of distilled water to the cooled mixture in step e, collect the precipitate, wash with deionized water and absolute ethanol in turn, and dry in vacuum to obtain WO _3-x nanosheets with oxygen holes.

Example 3

A method for preparing nitrone by tetrahydropyrrole, its general reaction formula is as follows:

Include the following steps:

(1) Add 2 mmol of tetrahydropyrrole into a 25 mL round bottom flask, add 5.0 mL of acetonitrile, add catalyst WO _3-x 0.06 mmol, 3 mmol of 30% hydrogen peroxide solution, and stir at 30 °C for 2 h;

(2) Dilute the above dilute solution to 15 mL with water, extract with ethyl acetate, concentrate to remove the solvent, and separate by column chromatography, 200-300 mesh silica gel column, the eluent is petroleum ether and ethyl acetate, the volume ratio of the two The ratio was 2:1, and a white solid was obtained with a yield of 62%. ¹ H NMR (400 MHz; CDCl3,δ): 6.88-6.92 (m, 1 H), 3.93-4.05 (m, 2 H), 2.72-2.80 (m, 2 H), 2.20-2.34 (m, 2H) ,.

The catalyst WO _3-x is a WO _3-x nanosheet with oxygen holes, and its preparation method comprises the following steps:

a. Dissolve 2 mmol of sodium tungstate dihydrate in 23 mL of water and stir for 10 min to form a uniform and transparent solution;

b. Add 10 mL of ethanol to the solution in step a, and stir for 10 min;

c. Add 16 mL of concentrated sulfuric acid to the solution in step b, and stir for 13 min;

d. Add 0.5 g of polyethylene glycol 10000 to the solution in step c, and stir for 20 min;

e. transfer the mixed solution after the reaction of step d into a round-bottomed flask, stir at 130°C for 4 h, and cool to room temperature;

f. Add 300 mL of distilled water to the cooled mixture in step e, collect the precipitate, wash with deionized water and absolute ethanol in turn, and dry in vacuum to obtain WO _3-x nanosheets with oxygen holes.

Example 4

A method for preparing nitrone by tert-butylbenzylamine, its general reaction formula is as follows:

Include the following steps:

(1) Add 2 mmol of tert-butylbenzylamine into a 25 mL round bottom flask, add 4 mL of water, add 0.02 mmol of tetrabutylammonium bromide, add catalyst WO _3-x 0.02 mmol, 30% peroxide Hydrogen solution 5 mmol, stirred at 25 °C for 5 h to obtain a mixed solution;

(2) Dilute the mixed solution obtained in step (1) to 15 mL with water, extract with ether, concentrate to remove the solvent, and separate by column chromatography, 200-300 mesh silica gel, and the eluent is petroleum ether and ethyl acetate. The volume ratio was 2:1, and a white solid was obtained with a yield of 84%. ¹ H NMR (400 MHz; CDCl3, δ): 8.39-8.21 (2 H, m), 7.57 (1 H, s), 7.40 (3 H, m), 1.61 (9 H, s).

The catalyst WO _3-x is a WO _3-x nanosheet with oxygen holes, and its preparation method comprises the following steps:

a. Dissolve 1 mmol of sodium tungstate dihydrate in 10 mL of water and stir for 5 min to form a uniform and transparent solution;

b. Add 5 mL of ethanol to the solution in step a, and stir for 5 min;

c. Add 15 mL of concentrated sulfuric acid to the solution in step b, and stir for 5 min;

d. Add 0.1 g of polyethylene glycol 10000 to the solution in step c, and stir for 5 min;

e. Transfer the mixed solution after the reaction in step d into a 100 mL round bottom flask, stir at 140 °C for 3 h, and cool to room temperature;

f. Add 500 mL of distilled water to the cooled mixture in step e, collect the precipitate, wash with deionized water and absolute ethanol in turn, and dry in vacuum to obtain WO _3-x nanosheets with oxygen holes.

Example 5

A method for preparing nitrone by 2-methylbenzyl tert-butylamine, its general reaction formula is as follows:

Include the following steps:

(1) Add 2 mmol of 2-methylbenzyl tert-butylamine into a 25 mL round bottom flask, add 4.6 mL of water, add 0.025 mmol of tetrabutylammonium bromide, add catalyst WO _3-x 0.06 mmol, 30% Hydrogen peroxide solution 4.5 mmol, stirred at 30°C for 4 h to obtain a mixed solution;

(2) Dilute the mixed solution obtained in step (1) to 20 mL with water, extract with ethyl acetate, concentrate to remove the solvent, and separate by column chromatography, 200-300 mesh silica gel column, the eluent is petroleum ether and ethyl acetate, The volume ratio of the two was 2:1, and a white solid was obtained with a yield of 83%. ¹ H NMR (400 MHz; CDCl3, δ): 9.17 (1 H, dd, J= 5.5, 3.9), 7.74 (1 H, s), 7.30-7.25 (2 H, m), 7.23 – 7.17 (1 H , m), 2.39 (3 H, s), 1.62 (9 H, s).

The catalyst WO _3-x is a WO _3-x nanosheet with oxygen holes, and its preparation method comprises the following steps:

a. Dissolve 2 mmol of sodium tungstate dihydrate in 20 mL of water and stir for 10 min to form a uniform and transparent solution;

b. Add 10 mL of ethanol to the solution in step a, and stir for 10 min;

c. Add 20 mL of concentrated sulfuric acid to the solution in step b, and stir for 10 min;

d. Add 0.3 g of polyethylene glycol 10000 to the solution in step c, and stir for 10 min;

e. Transfer the mixed solution after the reaction in step d into a 100 mL round bottom flask, stir at 160 °C for 4 h, and cool to room temperature;

f. Add 400 mL of distilled water to the cooled mixture in step e, collect the precipitate, wash with deionized water and absolute ethanol in turn, and dry in vacuum to obtain WO _3-x nanosheets with oxygen holes.

Example 6

A method for preparing nitrone by 3-methylbenzyl tert-butylamine, its general reaction formula is as follows:

Include the following steps:

(1) Add 2 mmol of 3-methylbenzyl tert-butylamine into a 25 mL round bottom flask, add 4.2 mL of water, add 0.03 mmol of tetrabutylammonium bromide, add catalyst WO _3-x 0.04 mmol, 50% Hydrogen peroxide solution 4 mmol, stirred at 60 °C for 2 h;

(2) Dilute the above dilute solution to 16 mL with water, extract with ethyl acetate, concentrate to remove the solvent, and separate by column chromatography, 200-300 mesh silica gel column, the eluent is petroleum ether and ethyl acetate, the volume ratio of the two The ratio was 2:1, and a white solid was obtained with a yield of 82%. ¹ H NMR (400 MHz; CDCl3,δ): 8.33 (1 H, s), 7.91 (1 H, d, J= 7.8 Hz), 7.52 (1 H, s), 7.31 (1 H, t, J 7.7 ), 7.22 (1 H, d, J= 7.6 Hz), 2.38 (3 H, s), 1.62 (9 H, s).

The catalyst WO _3-x is a WO _3-x nanosheet with oxygen holes, and its preparation method comprises the following steps:

a. Dissolve 2 mmol of sodium tungstate dihydrate in 21 mL of water and stir for 10 min to form a uniform and transparent solution;

b. Add 8 mL of ethanol to the solution in step a, and stir for 10 min;

c. Add 16 mL of concentrated sulfuric acid to the solution in step b, and stir for 13 min;

d. Add 0.5 g of polyethylene glycol 10000 to the solution in step c, and stir for 20 min;

e. transfer the mixed solution after the reaction of step d into a round bottom flask, stir at 120°C for 5 h, and cool to room temperature;

f. Add 300 mL of distilled water to the cooled mixture in step e, collect the precipitate, wash with deionized water and absolute ethanol in turn, and dry in vacuum to obtain WO _3-x nanosheets with oxygen holes.

Example 7

A method for preparing nitrone by 4-methylbenzyl tert-butylamine, its general reaction formula is as follows:

Include the following steps:

(1) Add 2 mmol of 4-methylbenzyl tert-butylamine into a 25 mL round bottom flask, add 5 mL of water, add 0.024 mmol of tetrabutylammonium bromide, add catalyst WO _3-x 0.08 mmol, 30% Hydrogen peroxide solution 6 mmol, stirred at 50 °C for 3 h;

(2) Dilute the above dilute solution to 20 mL with water, extract with ethyl acetate, concentrate to remove the solvent, and separate by column chromatography, 200-300 mesh silica gel column, the eluent is petroleum ether and ethyl acetate, the volume ratio of the two The ratio was 2:1, and a white solid was obtained with a yield of 87%. ¹ H NMR (400 MHz; CDCl3, δ): 8.19 (2 H, d, J = 8.3 Hz), 7.51 (1 H, s), 7.23 (2 H, d, J = 8.2 Hz), 2.38 (3 H , s), 1.61 (9 H, s).

The catalyst WO _3-x is a WO _3-x nanosheet with oxygen holes, and its preparation method comprises the following steps:

a. Dissolve 3 mmol of sodium tungstate dihydrate in 25 mL of water and stir for 20 min to form a uniform and transparent solution;

b. Add 13 mL of ethanol to the solution in step a, and stir for 20 min;

c. Add 25 mL of concentrated sulfuric acid to the solution in step b, and stir for 20 min;

d. Add 0.4 g of polyethylene glycol 10000 to the solution in step c, and stir for 15 min;

e. transfer the mixed solution after the reaction of step d into a round bottom flask, stir at 150°C for 5 h, and cool to room temperature;

f. Add 500 mL of distilled water to the cooled mixture in step e, collect the precipitate, wash with deionized water and absolute ethanol in turn, and dry in vacuum to obtain WO _3-x nanosheets with oxygen holes.

Example 8

A method for preparing nitrone by piperidine, its general reaction formula is as follows:

Include the following steps:

(1) Add 2 mmol of piperidine into a 25 mL round bottom flask, add 4 mL of water, add 0.02 mmol of tetrabutylammonium bromide, add catalyst WO _3-x 0.08 mmol, 30% hydrogen peroxide solution 4 mmol, stirred at 25°C for 6 h;

(2) Dilute the above dilute solution to 18 mL with water, extract with ethyl acetate, concentrate to remove the solvent, and separate by column chromatography, 200-300 mesh silica gel column, the eluent is petroleum ether and ethyl acetate, the volume ratio of the two The ratio was 2:1, and a white solid was obtained with a yield of 64%. ¹ H NMR (400 MHz; CDCl3, δ): 7.28 (1 H,s), 3.78 (2H, m), 2.45 (2H, m), 1.97 (2H, m) 1.66-1.81 (2 H, m).

The catalyst WO _3-x is a WO _3-x nanosheet with oxygen holes, and its preparation method comprises the following steps:

a. Dissolve 3 mmol of sodium tungstate dihydrate in 25 mL of water and stir for 15 min to form a uniform and transparent solution;

b. Add 10 mL of ethanol to the solution in step a, and stir for 20 min;

c. Add 20 mL of concentrated sulfuric acid to the solution in step b, and stir for 15 min;

d. Add 0.6 g of polyethylene glycol 10000 to the solution in step c, and stir for 20 min;

e. transfer the mixed solution after the reaction of step d into a round bottom flask, stir at 150°C for 5 h, and cool to room temperature;

f. Add 400 mL of distilled water to the cooled mixture in step e, collect the precipitate, wash with deionized water and absolute ethanol in turn, and dry in vacuum to obtain WO _3-x nanosheets with oxygen holes.

Claims (7)

1. a kind of method that nitrone is prepared by secondary amine, it is characterised in that secondary amine is in catalyst WO_3-xWith the work of hydrogenperoxide steam generator With lower generation nitrone, its reaction expression is as follows：

Or

Wherein, R¹For hydrogen, aryl, alkyl or heterocycle containing 1-6 carbon atom, R²Alkyl for aryl, containing 1-6 carbon atom Or heterocycle, R³For the alkyl containing 2-6 carbon atom, R⁴For hydrogen, methyl, ethyl or halogen, n=0,1,2,3,4, B ring is simple Hydrogen, substitution phenyl ring or substituted pyridine ring；

Described secondary amine is N- tert-butyl benzyl amines, 2- methyl-benzyls tert-butylamine, 3- methyl-benzyls tert-butylamine, the tertiary fourth of 4- methyl-benzyls Amine, 2- luorobenzyls tert-butylamine, 3- luorobenzyls tert-butylamine, 4- luorobenzyls tert-butylamine, 2- nitrobenzyls tert-butylamine, 3- nitrobenzyl uncles Butylamine, 4- nitrobenzyls tert-butylamine, diethylamine, di-n-propylamine, dibutyl amine, diisopropylamine, dibenzyl amine, nafoxidine, tetrahydrochysene quinoline Quinoline, tetrahydroisoquinoline, morpholine or piperidines；

Described catalyst WO_3-xIt is the WO that there is oxygen vacancies_3-xNanometer sheet, its preparation method comprises the following steps：

A. 1~3mmol Disodium tungstate (Na2WO4) dihydrate is dissolved in 10~25mL water, stirs 5~20min, be made into homogeneous transparent Solution；

B. 5~13mL of ethanol is added into step a solution, 5~20min is stirred；

C. 15~25mL of the concentrated sulfuric acid is added into step b solution, 5~20min is stirred；

D. 0.1~0.6g PEG20000 is added into step c solution, 5~20min is stirred；

E. the reacted mixed solutions of step d are transferred in round-bottomed flask, 120~160 DEG C of 3~5h of stirring are cooled to room temperature；

F. added in the mixture after step e is cooled down in 300~500mL distilled water, collect sediment, deionized water is used successively With absolute ethyl alcohol washing, vacuum drying obtains the WO that there is oxygen vacancies_3-xNanometer sheet.

2. the method according to claim 1 that nitrone is prepared by secondary amine, it is characterised in that described hydrogenperoxide steam generator is 30~50% hydrogenperoxide steam generator.

3. the method according to claim 1 that nitrone is prepared by secondary amine, it is characterised in that including following reactions steps：

(1) 2mmol secondary amine is added in reactor, sequentially add 4~5mL of water, TBAB 0.02~ 0.03mmol, adds catalyst WO_3-x0.02~0.08mmol and 30%~50% hydrogenperoxide steam generator 3~6mmol, 25~ 2~6h is stirred at 60 DEG C, mixed solution is obtained；

(2) step (1) reacted mixed solution is diluted to 15~20mL, organic solvent extraction, concentration removes solvent, post layer Analysis separation, collects product.

4. the method according to claim 1 that nitrone is prepared by secondary amine, it is characterised in that including following reactions steps：

(1) 2mmol secondary amine is added in reactor, adds 3~5mL of polar solvent, add catalyst WO_3-x0.02~ 0.08mmol and 30%~50% hydrogenperoxide steam generator 3~6mmol, stirs 2~6h at 25~60 DEG C, obtains mixed solution；

(2) step (1) reacted mixed solution is diluted to 15~20mL, organic solvent extraction, concentration removes solvent, post layer Analysis separation, collects product.

5. the method according to claim 4 that nitrone is prepared by secondary amine, it is characterised in that the polarity described in step (1) is molten Agent is methanol, ethanol, acetonitrile, acetic acid or N, N-METHYLFORMAMIDE.

6. the method that nitrone is prepared by secondary amine according to claim 3 or 4, it is characterised in that having described in step (2) Machine solvent is ethyl acetate, ether, methyl tertiary butyl ether(MTBE), dichloromethane or chloroform.

7. the method that nitrone is prepared by secondary amine according to claim 3 or 4, it is characterised in that the post described in step (2) Chromatography condition is the silicagel column of 200~300 mesh, and eluant, eluent is petroleum ether and ethyl acetate, and both volume ratios are 10:1 ~2:1.