阅读说明：本技术 一种2-甲基吡啶-n-氧化物合成方法 (Synthesis method of 2-methylpyridine-N-oxide ) 是由 张升 张宽宇 万红根 张太亮 刘进水 于 2021-06-08 设计创作，主要内容包括：本发明公开了一种2-甲基吡啶-N-氧化物合成方法,属于农药/医药化学品中间体技术领域。该合成方法以苯作溶剂,反应过程中使用氧化钼和TEBA为复合催化剂,包括以下步骤：(1)将2-甲基吡啶溶于苯中,得到反应液A；(2)在低温条件下,向反应液A缓慢滴入过氧化氢,同时添加氧化钼和TEBA进行反应,跟踪反应3-5小时,使2-甲基吡啶的含量控制在0.5％以下,所述的低温条件为50℃；(3)反应完成后,减压蒸苯,对反应液进行冷冻,得到2-甲基吡啶-N-氧化物。该方法以苯为溶剂,以氧化钼和TEBA作为复合催化剂,缓慢滴入过氧化氢,有效控制了副反应的发生,直接反应的产品纯度高达99％以上。(The invention discloses a method for synthesizing 2-methylpyridine-N-oxide, belonging to the technical field of pesticide/pharmaceutical chemical intermediates. The synthesis method takes benzene as a solvent, uses molybdenum oxide and TEBA as a composite catalyst in the reaction process, and comprises the following steps: (1) dissolving 2-methylpyridine in benzene to obtain a reaction solution A; (2) slowly dropping hydrogen peroxide into the reaction liquid A under the low temperature condition, simultaneously adding molybdenum oxide and TEBA for reaction, tracking the reaction for 3-5 hours to control the content of 2-methylpyridine to be below 0.5 percent, wherein the low temperature condition is 50 ℃; (3) after the reaction is finished, benzene is evaporated under reduced pressure, and the reaction liquid is frozen to obtain the 2-methylpyridine-N-oxide. The method takes benzene as a solvent, takes molybdenum oxide and TEBA as a composite catalyst, slowly drops hydrogen peroxide, effectively controls the occurrence of side reaction, and the purity of the product of direct reaction reaches more than 99 percent.)

1. A method for synthesizing 2-methylpyridine-N-oxide is characterized in that benzene is used as a solvent, molybdenum oxide and TEBA are used as composite catalysts in the reaction process, and the method comprises the following steps:

(1) dissolving 2-methylpyridine in benzene to obtain a reaction solution A;

(2) slowly dropping hydrogen peroxide into the reaction liquid A under the low temperature condition, simultaneously adding molybdenum oxide and TEBA for reaction, tracking the reaction for 3-5 hours to control the content of 2-methylpyridine to be below 0.5 percent, wherein the low temperature condition is 50 ℃;

(3) after the reaction is finished, benzene is evaporated under reduced pressure, and the reaction liquid is frozen to obtain the 2-methylpyridine-N-oxide.

2. The method for synthesizing 2-methylpyridine-N-oxide according to claim 1, wherein the volume ratio of 2-methylpyridine to benzene in step (1) is 1: 2.

3. the method for synthesizing 2-methylpyridine-N-oxide according to claim 2, wherein the mass ratio of molybdenum oxide to TEBA in the step (2) is 1: 3, the adding amount of the composite catalyst is 3-4 wt% of the total mass of the raw materials.

4. The process for synthesizing 2-methylpyridine-N-oxide according to claim 3, wherein the mass fraction of hydrogen peroxide in the step (2) is 27.5 wt%.

Technical Field

The invention belongs to the technical field of pesticide/pharmaceutical chemical intermediates, and particularly relates to a method for synthesizing 2-methylpyridine-N-oxide.

Background

The methylpyridine nitrogen oxides are important organic chemical intermediates, have wide application in the aspects of pesticides, medicines, dyes, insecticides, synthetic resins and the like, and particularly have strong physiological activity in the application aspect of novel pesticides and medicines. In particular, the 2-methylpyridine-N-oxide is an important drug intermediate of the new coronavirus, and the purity is required to be high, the content of acetic acid is less than or equal to 0.5 percent, and the water content is less than or equal to 0.5 percent. The nitrogen-oxygen group increases the activity of both nucleophilic and electrophilic substitution reactions at 2, 4 on the pyridine ring due to the presence of the oxygen atom in the methylpyridine nitroxide, which can act as both an electron donor and electron acceptor under different reaction conditions.

The current major methods for the synthesis of 2-methylpyridine-N-oxide: peroxide direct oxidation and catalytic oxidation. The first direct oxidation method: for example, chinese patent application No.: 201810030946.0, filing date: 1, 12 months and 2018, the invention and creation name is: a method for preparing 3-methylpyridine-N-oxide, said method comprises mixing 3-methylpyridine and hydrogen peroxide in the micromixer fast and finishing oxidizing in the microreactor under the high-temperature condition, 3-methylpyridine-N-oxide solution produced gets the product through further flashing, the oxide is apt to explode.

The second catalytic oxidation method: for example, korean patent application No.: KR1020030027253, filing date: in 2003, 29 months and 4, the invention and creation names are: a process for producing 2-methylpyridine-N-oxide which comprises reacting 1 equivalent of 2-methylpyridine with 1.0 to 1.5 equivalents of acetic acid and 1.0 to 2.5 equivalents of hydrogen peroxide in the presence of a strong-acid cation exchange resin catalyst, wherein the amount of the strong-acid cation exchange resin is 0.2 to 0.5g per 1g of 2-methylpyridine; the reaction temperature is 70-100 ℃; the reaction time was 3 hours.

Again, as with chinese patent application No.: 201210223680.4, filing date: 6/29 of 2012, the name of invention creation is: a preparation method of methylpyridine nitrogen oxide; chinese patent application No.: 201510554713.7, filing date: the invention is named as: an oxidation synthesis method of methylpyridine nitrogen oxide; chinese patent application No.: 201510365861.4, filing date: on 29 months 6 in 2015, the invention is named as: a preparation method of pyridine nitrogen oxides by high-efficiency heterogeneous catalysis; chinese patent application No.: 201710004690.1, filing date: 1, 4 days in 2017, the name of the invention is: a catalytic synthesis method of 3-methylpyridine nitrogen oxide. In these patents, hydrogen peroxide is generally used as the oxidizing agent, wherein the mass fraction of hydrogen peroxide is between 25% and 30%. Under the action of catalyst (titanium-silicon molecular sieve, transition metal oxide or its salt, etc.), under the condition of heating it reacts with 3-methylpyridine raw material in the presence of catalyst to obtain 3-methylpyridine-N-oxide.

In addition, non-patent literature also discloses some preparation methods, for example, Zhou Jie et al in 3-methyl pyridine nitrogen oxide catalytic synthesis research "discloses in the 3-methyl pyridine catalyst dosage of 4.5%, reaction time of 2H, 3-methyl pyridine and H₂O₂And the amount of acetic acid is in the ratio of 1: 1.5: 1.5-1: 1.6: 1.6, the reaction effect is best when the reaction temperature is 80 ℃, and the conversion rate of the 3-methylpyridine can reach 98.1%. In 2006, Suman l.jain [ Jain, s.; joseph, j.; sain, B. Alumia supported MoO₃:an efficient and recyclable catalyst for selective oxidation of tertiary nitrogen compounds to N-oxides using anhydrous TBHP as oxidant under mild reaction conditions[J]. Cayalysis.Lett.2007,115:8-12.]Topic groups reported the use of alumina-supported MoO₃The catalyst catalyzes and oxidizes tertiary amine compounds under the action of a new oxidant, namely tert-butyl hydroperoxide (TBHP), to synthesize a series of target products, the system can oxidize the tertiary amine compounds well, the substrate universality is good, the yield is high, the catalyst can be used indiscriminately, but the reaction temperature is also high, and the energy consumption is high. In 2010, brave [ Ding, y.; the oxidation of pyridine and alcohol using the Keggin-type mammary polysaccharides as a temporal-controlled phase transfer catalyst system [ J].J.Mol.Catal.A:Chem.2011,337:45-51.]The subject group began using a temperature-controlled phase transfer catalyst, namely Keggin-type porous polytungstophosphate. The catalyst is characterized in that the catalyst is in a solvent state when the temperature of the system is overhighI.e. homogeneous phase, to promote the reaction; when the temperature is reduced to room temperature, the precipitate is separated out again and is in a heterogeneous state, which is beneficial to the separation of the system. The catalyst can be used repeatedly, is environment-friendly, and utilizes the system to research the oxidation of alcohols.

It can be found that the above-mentioned common method is that glacial acetic acid is used as solvent, and hydrogen peroxide is added dropwise, and the defects are that: (1) the reaction time is long, 2-3% of the raw material 2-methylpyridine is not completely reacted, and excessive hydrogen peroxide is required to be added; (2) the reaction temperature is relatively high, and because the 2-methylpyridine-N-oxide is unstable when heated, the explosion possibility can occur when the 2-methylpyridine-N-oxide is heated, particularly in an acetic acid and hydrogen peroxide system: (3) glacial acetic acid and water in the 2-methylpyridine-N-oxide are not easy to remove; (4) the pollution is large. The market demand of the 2-methylpyridine-N-oxide is large, so that the significance of developing an environment-friendly, efficient and economic synthesis method of the 2-methylpyridine-N-oxide is great.

Disclosure of Invention

1. Technical problem to be solved by the invention

Aiming at the problems of high preparation temperature, much pollution, low product purity and high water content of the existing 2-methylpyridine-N-oxide, the invention provides a method for synthesizing the 2-methylpyridine-N-oxide, wherein the conversion rate of the raw material 2-methylpyridine can reach 99%, the product purity can reach 99%, and the water content is less than or equal to 0.5%.

2. Technical scheme

In order to achieve the purpose, the technical scheme provided by the invention is as follows:

the synthesis method of the 2-methylpyridine-N-oxide takes benzene as a solvent, uses molybdenum oxide and TEBA as a composite catalyst in the reaction process, and comprises the following steps:

(1) dissolving 2-methylpyridine in benzene to obtain a reaction solution A;

(2) slowly dropping hydrogen peroxide into the reaction liquid A under a low-temperature condition, simultaneously adding molybdenum oxide and TEBA for reaction, tracking the reaction for 35-hours, and controlling the content of 2-methylpyridine to be below 0.5 percent, wherein the low-temperature condition is 50 ℃, and the low-temperature condition is relatively, the invention is limited to use 50 ℃ as a boundary, and the temperature is higher than 50 ℃ and lower than or equal to 50 ℃;

(3) after the reaction is finished, benzene is evaporated under reduced pressure, and the reaction liquid is frozen to obtain the 2-methylpyridine-N-oxide. The freezing temperature of the reaction liquid is below 0 ℃, the melting point of the 2-methylpyridine-N-oxide is 41-45 ℃, and the reaction liquid is a light yellow crystal after being frozen.

In one possible embodiment of the invention, the volume ratio of 2-methylpyridine to benzene in step (1) is 1: 2. by controlling the volume ratio of the 2-methylpyridine to the benzene, on one hand, the 2-methylpyridine is fully dissolved in the benzene, and on the other hand, the time for subsequent benzene distillation under reduced pressure can be reduced.

In one possible embodiment of the present invention, the mass ratio of the molybdenum oxide to the TEBA in step (2) is 1: 3, the adding amount of the composite catalyst is 3-4 wt% of the total mass of the raw materials. The optimal mass ratio of molybdenum oxide to TEBA is 1: 3, when it exceeds or falls below the mass ratio, the reaction rate of the reaction is lowered. The main reason is that the organic chemical reaction process is relatively complex and cannot be accurately controlled, so that the inventor considers that the reaction speed is relatively high under the proportional condition through a large number of experiments. The molybdenum oxide in the reaction mainly plays a role in (1) promoting H₂O₂Decomposing to generate molecular oxygen; (2) and a composite carrier is formed with TEBA, the specific surface area of the catalyst is increased, atomic oxygen is fully contacted with the lutidine, and the reaction is accelerated.

The TEBA is a phase transfer catalyst, so that the reaction rate is improved, and because organic phases such as 2-methylpyridine and benzene and aqueous phases of water and hydrogen peroxide exist in the reaction system, the reaction belongs to heterogeneous reaction, the reaction needs to be carried out through a phase interface, the mass transfer between the phases is relatively slow, the TEBA can be simultaneously dissolved in the aqueous phase and the organic phase, active oxygen can be transferred from the aqueous phase to the oil phase, the transfer rate of active oxygen atoms is accelerated at the oil-water interface, and the reaction rate and the conversion rate are improved; adding quaternary ammonium salt to H₂O₂With MoO₃The formed active intermediate is conveyed to an oil phase to be fully contacted with 2-methylpyridine; in addition, TEBA has a polarization effect on 2-methylpyridine, and the reactivity of the 2-methylpyridine is improved.

In the invention, MoO is utilized₃Promotion of H₂O₂Active oxygen is generated and is easy to escape, so that the interface energy between the active oxygen (gas phase) and the system (organic phase) of the invention is reduced by utilizing the phase transfer catalyst, the active oxygen is transferred in time and is combined with the 2-methylpyridine, therefore, the specific surface area of the catalyst can be effectively increased by adding the composite catalyst, and the reaction rate is promoted.

In one possible embodiment of the invention, the mass fraction of hydrogen peroxide in step (2) is 27.5 wt.%. The concentration of hydrogen peroxide should not be too high, otherwise, it will cause local peroxidation and generate other substances, thus resulting in low purity of the product and improved safety of the reaction.

3. Advantageous effects

Compared with the prior art, the technical scheme provided by the invention has the following remarkable effects:

(1) according to the synthesis method of the 2-methylpyridine-N-oxide, benzene is used as a solvent, molybdenum oxide and TEBA (benzyltriethylammonium chloride) are used as composite catalysts, hydrogen peroxide is slowly dropped, side reactions are effectively controlled, and the purity of a product obtained by direct reaction is up to more than 99%;

(2) according to the synthesis method of the 2-methylpyridine-N-oxide, the final accounting of the product shows that the conversion rate of the 2-methylpyridine reaches more than 99%, the raw material residue is less, the discharge amount of three wastes is less, and the possibility of pollution is reduced;

(3) according to the synthesis method of the 2-methylpyridine-N-oxide, benzene is used as a solvent (almost no water) instead of glacial acetic acid, so that the water content in the product is low, dehydration is not needed, and energy conservation and emission reduction are facilitated;

(4) according to the synthesis method of the 2-methylpyridine-N-oxide, the reaction process is carried out at low temperature, so that explosion is avoided as far as possible, safety accidents are reduced, and the production is safe and reliable.

Drawings

FIG. 1 is a gas chromatogram of the product of example 1 of the present invention.

Detailed Description

For a further understanding of the contents of the present invention, reference will now be made in detail to the following examples.

In which tables 1 to 6 show the results of examining 2-methylpyridine-N-oxide obtained in examples 1 to 6.

Example 1

The synthesis method of 2-methylpyridine-N-oxide of this example, which uses benzene as solvent and molybdenum oxide and TEBA as composite catalyst in the reaction process, includes the following steps:

(1) dissolving 2-methylpyridine in benzene, wherein the volume ratio of the 2-methylpyridine to the benzene is 1:2, so as to obtain a reaction solution A;

(2) under the low-temperature condition, slowly dropping hydrogen peroxide into the reaction liquid A, adding excessive hydrogen peroxide, and simultaneously adding molybdenum oxide and TEBA for reaction, wherein the mass ratio of the molybdenum oxide to the TEBA is 1: 3, the adding amount of the composite catalyst is 3 percent of the total mass of the raw materials; tracking the reaction for 3 hours to control the content of the 2-methylpyridine to be 0.5 percent, wherein the low-temperature condition is 50 ℃; the mass fraction of hydrogen peroxide is 27.5%;

(3) after completion of the reaction, benzene was distilled under reduced pressure (a conventional method, which is not limited herein), and the reaction solution was frozen in a refrigerator to obtain 2-methylpyridine-N-oxide.

Analyzing the finally obtained 2-methylpyridine-N-oxide product by using an analytical instrument: linghua GC9890B, column type: SE-5430m 0.32mm 0.4 um;

A. the instrument conditions were as follows:

a. column temperature: 140 ℃; a detector: 280 ℃; vaporization temperature: 280 ℃; sensitivity: 3;

b. hydrogen gas: 0.1 Mpa; air: 0.1 Mpa; carrier gas (nitrogen): 0.08 MPa;

B. temperature programming:

keeping at 140 deg.C for 1min, heating to 280 deg.C at 20 deg.C/min, and keeping for 5 min.

C. Sample treatment:

taking 0.1g of sample, adding 10mL of methanol to completely dissolve the sample, injecting 0.1uL of the sample by using a 10uL sample injector, sampling for 15min, and measuring the content by an area normalization method, wherein a chromatogram is shown in figure 1, the purity of the product is up to 99.07%, the purity is very high, the requirement of a medical intermediate is met, the problem that the purity of the product is not high enough in the prior art is solved, benzene is used as a solvent, molybdenum oxide and TEBA (benzyltriethylammonium chloride) are used as composite catalysts, hydrogen peroxide is slowly added, the reaction is easy to control, less waste liquid is generated, and less side reactions are generated.

The data for detecting the obtained 2-methylpyridine-N-oxide are as follows, and the chromatogram is shown in FIG. 1:

TABLE 1 examination result of 2-methylpyridine-N-oxide obtained in example 1

Example 2

The synthesis method of 2-methylpyridine-N-oxide of this example, which uses benzene as solvent and molybdenum oxide and TEBA as composite catalyst in the reaction process, includes the following steps:

(1) dissolving 2-methylpyridine in benzene, wherein the volume ratio of the 2-methylpyridine to the benzene is 1:2, so as to obtain a reaction solution A;

(2) under the low-temperature condition, slowly dropping hydrogen peroxide into the reaction liquid A, adding excessive hydrogen peroxide, and simultaneously adding molybdenum oxide and TEBA for reaction, wherein the mass ratio of the molybdenum oxide to the TEBA is 1: 3, the adding amount of the composite catalyst is 3.5 percent of the total mass of the raw materials; tracking the reaction for 3 hours to control the content of 2-methylpyridine to be 0.4 percent, wherein the low-temperature condition is 50 ℃; the mass fraction of hydrogen peroxide is 27.5%;

(3) after completion of the reaction, benzene was distilled under reduced pressure (a conventional method, which is not limited herein), and the reaction solution was frozen in a refrigerator to obtain 2-methylpyridine-N-oxide.

Analyzing the finally obtained 2-methylpyridine-N-oxide product by using an analytical instrument: linghua GC9890B, column type: SE-5430m 0.32mm 0.4 um;

A. the instrument conditions were as follows:

a. column temperature: 140 ℃; a detector: 280 ℃; vaporization temperature: 280 ℃; sensitivity: 3;

b. hydrogen gas: 0.1 Mpa; air: 0.1 Mpa; carrier gas (nitrogen): 0.08 MPa;

B. temperature programming:

keeping at 140 deg.C for 1min, heating to 280 deg.C at 20 deg.C/min, and keeping for 5 min.

C. Sample treatment:

taking 0.1g of sample, adding 10mL of methanol to completely dissolve the sample, injecting 0.1uL of sample by using a 10uL sample injector, sampling for 15min, measuring the content by an area normalization method, wherein the purity of the product is as high as 99.2 percent, the purity is very high, the requirement of a medical intermediate is met, the problem that the purity of the product is not high enough in the prior art is solved, benzene is used as a solvent, molybdenum oxide and TEBA (benzyltriethylammonium chloride) are used as a composite catalyst, hydrogen peroxide is slowly dropped in, the reaction is easy to control, less waste liquid is generated, less side reactions are generated, and the method has absolute advantages compared with the prior art.

The data for the detection of the resulting 2-methylpyridine-N-oxide are as follows:

TABLE 2 examination of 2-methylpyridine-N-oxide obtained in example 2

Example 3

The synthesis method of 2-methylpyridine-N-oxide of this example, which uses benzene as solvent and molybdenum oxide and TEBA as composite catalyst in the reaction process, includes the following steps:

(1) dissolving 2-methylpyridine in benzene, wherein the volume ratio of the 2-methylpyridine to the benzene is 1:2, so as to obtain a reaction solution A;

(2) under the low-temperature condition, slowly dropping hydrogen peroxide into the reaction liquid A, adding excessive hydrogen peroxide, and simultaneously adding molybdenum oxide and TEBA for reaction, wherein the mass ratio of the molybdenum oxide to the TEBA is 1: 3, the adding amount of the composite catalyst is 4 percent of the total mass of the raw materials; tracking the reaction for 4 hours to control the content of the 2-methylpyridine to be 0.4 percent, wherein the low-temperature condition is 50 ℃; the mass fraction of hydrogen peroxide is 27.5%;

(3) after completion of the reaction, benzene was distilled under reduced pressure (a conventional method, which is not limited herein), and the reaction solution was frozen in a refrigerator to obtain 2-methylpyridine-N-oxide.

Analyzing the finally obtained 2-methylpyridine-N-oxide product by using an analytical instrument: linghua GC9890B, column type: SE-5430m 0.32mm 0.4 um;

A. the instrument conditions were as follows:

a. column temperature: 140 ℃; a detector: 280 ℃; vaporization temperature: 280 ℃; sensitivity: 3;

b. hydrogen gas: 0.1 Mpa; air: 0.1 Mpa; carrier gas (nitrogen): 0.08 MPa;

B. temperature programming:

keeping at 140 deg.C for 1min, heating to 280 deg.C at 20 deg.C/min, and keeping for 5 min.

C. Sample treatment:

taking 0.1g of sample, adding 10mL of methanol to completely dissolve the sample, injecting 0.1uL of sample by using a 10uL sample injector, sampling for 15min, measuring the content by an area normalization method, wherein the purity of the product is as high as 99.25 percent, the purity is very high, the requirement of a medical intermediate is met, the problem that the purity of the product is not high enough in the prior art is solved, benzene is used as a solvent, molybdenum oxide and TEBA (benzyltriethylammonium chloride) are used as a composite catalyst, hydrogen peroxide is slowly dropped in, the reaction is easy to control, the generated waste liquid is less, the side reaction is less, and compared with the prior art, the method has absolute advantages.

The data for the detection of the resulting 2-methylpyridine-N-oxide are as follows:

TABLE 3 examination results of 2-methylpyridine-N-oxide obtained in example 3

Example 4

The synthesis method of 2-methylpyridine-N-oxide of this example, which uses benzene as solvent and molybdenum oxide and TEBA as composite catalyst in the reaction process, includes the following steps:

(1) dissolving 2-methylpyridine in benzene, wherein the volume ratio of the 2-methylpyridine to the benzene is 1:2, so as to obtain a reaction solution A;

(2) under the low-temperature condition, slowly dropping hydrogen peroxide into the reaction liquid A, adding excessive hydrogen peroxide, and simultaneously adding molybdenum oxide and TEBA for reaction, wherein the mass ratio of the molybdenum oxide to the TEBA is 1: 3, the adding amount of the composite catalyst is 4 percent of the total mass of the raw materials; tracking the reaction for 3 hours to control the content of 2-methylpyridine to be less than 0.5 percent, wherein the low-temperature condition is 50 ℃; the mass fraction of hydrogen peroxide is 27.5%;

(3) after completion of the reaction, benzene was distilled under reduced pressure (a conventional method, which is not limited herein), and the reaction solution was frozen in a refrigerator to obtain 2-methylpyridine-N-oxide.

Analyzing the finally obtained 2-methylpyridine-N-oxide product by using an analytical instrument: linghua GC9890B, column type: SE-5430m 0.32mm 0.4 um;

A. the instrument conditions were as follows:

a. column temperature: 140 ℃; a detector: 280 ℃; vaporization temperature: 280 ℃; sensitivity: 3;

b. hydrogen gas: 0.1 Mpa; air: 0.1 Mpa; carrier gas (nitrogen): 0.08 MPa;

B. temperature programming:

keeping at 140 deg.C for 1min, heating to 280 deg.C at 20 deg.C/min, and keeping for 5 min.

C. Sample treatment:

taking 0.1g of sample, adding 10mL of methanol to completely dissolve the sample, injecting 0.1uL of sample by using a 10uL sample injector, sampling for 15min, measuring the content by an area normalization method, wherein the purity of the product is as high as 99.21 percent, the purity is very high, the requirement of a medical intermediate is met, the problem that the purity of the product is not high enough in the prior art is solved, benzene is used as a solvent, molybdenum oxide and TEBA (benzyltriethylammonium chloride) are used as a composite catalyst, hydrogen peroxide is slowly dropped in, the reaction is easy to control, the generated waste liquid is less, the side reaction is less, and compared with the prior art, the method has absolute advantages.

The data for the detection of the resulting 2-methylpyridine-N-oxide are as follows:

TABLE 4 examination of 2-methylpyridine-N-oxide obtained in example 4

Example 5

The synthesis method of 2-methylpyridine-N-oxide of this example, which uses benzene as solvent and molybdenum oxide and TEBA as composite catalyst in the reaction process, includes the following steps:

(1) dissolving 2-methylpyridine in benzene, wherein the volume ratio of the 2-methylpyridine to the benzene is 1:2, so as to obtain a reaction solution A;

(2) under the low-temperature condition, slowly dropping hydrogen peroxide into the reaction liquid A, adding excessive hydrogen peroxide, and simultaneously adding molybdenum oxide and TEBA for reaction, wherein the mass ratio of the molybdenum oxide to the TEBA is 1: 3, the adding amount of the composite catalyst is 3.5 percent of the total mass of the raw materials; tracking the reaction for 4 hours to control the content of the 2-methylpyridine to be 0.35 percent, wherein the low-temperature condition is 50 ℃; the mass fraction of hydrogen peroxide is 27.5%;

(3) after completion of the reaction, benzene was distilled under reduced pressure (a conventional method, which is not limited herein), and the reaction solution was frozen in a refrigerator to obtain 2-methylpyridine-N-oxide.

Analyzing the finally obtained 2-methylpyridine-N-oxide product by using an analytical instrument: linghua GC9890B, column type: SE-5430m 0.32mm 0.4 um;

A. the instrument conditions were as follows:

a. column temperature: 140 ℃; a detector: 280 ℃; vaporization temperature: 280 ℃; sensitivity: 3;

b. hydrogen gas: 0.1 Mpa; air: 0.1 Mpa; carrier gas (nitrogen): 0.08 MPa;

B. temperature programming:

keeping at 140 deg.C for 1min, heating to 280 deg.C at 20 deg.C/min, and keeping for 5 min.

C. Sample treatment:

taking 0.1g of sample, adding 10mL of methanol to completely dissolve the sample, injecting 0.1uL of sample by using a 10uL sample injector, sampling for 15min, measuring the content by an area normalization method, wherein the purity of the product is as high as 99.30 percent, the purity is very high, the requirement of a medical intermediate is met, the problem that the purity of the product is not high enough in the prior art is solved, benzene is used as a solvent, molybdenum oxide and TEBA (benzyltriethylammonium chloride) are used as a composite catalyst, hydrogen peroxide is slowly dropped in, the reaction is easy to control, the generated waste liquid has few side reactions, and compared with the prior art, the method has absolute advantages.

The data for the detection of the resulting 2-methylpyridine-N-oxide are as follows:

TABLE 5 examination of 2-methylpyridine-N-oxide obtained in example 5

The invention and its embodiments have been described above schematically, without this being limitative. Therefore, if the person skilled in the art receives the teaching, without departing from the spirit of the invention, the person skilled in the art shall not inventively design the similar structural modes and embodiments to the technical solution, but shall fall within the scope of the invention.