阅读说明：本技术 一种4-甲氧基甲基吡啶的合成方法 (Synthesis method of 4-methoxymethyl pyridine ) 是由 倪俊 于 2019-11-26 设计创作，主要内容包括：本发明涉及有机化学领域,特别是一种4-甲氧基甲基吡啶的合成方法,以4-甲基吡啶为原料,通过溴化反应得到4-溴-甲基吡啶；所述4-溴-甲基吡啶与三甲胺反应得到(4-吡啶甲基)三甲基溴化铵；将所述(4-吡啶甲基)三甲基溴化铵溶于甲醇,再加入甲醇钠,在氮气下加热回流1h,得到4-甲氧基甲基吡啶。采用上述合成方法后,本发明以4-甲基吡啶为原料,经溴化反应得到4-溴-甲基吡啶,三甲胺反应得到(4-吡啶甲基)三甲基溴化铵,最后与甲醇钠反应得到4-甲氧基甲基吡啶。本发明的合成方法总收率高、原料价格便宜、反应时间短、条件温和、工艺操作简单。(The invention relates to the field of organic chemistry, in particular to a synthesis method of 4-methoxy methylpyridine, which takes 4-methylpyridine as a raw material and obtains the 4-bromo-methylpyridine through bromination reaction; reacting the 4-bromo-methylpyridine with trimethylamine to obtain (4-picolyl) trimethylammonium bromide; dissolving the (4-picolyl) trimethyl ammonium bromide in methanol, adding sodium methoxide, and heating and refluxing for 1h under nitrogen to obtain 4-methoxymethylpyridine. After the synthesis method is adopted, 4-methylpyridine is used as a raw material, 4-bromo-methylpyridine is obtained through bromination reaction, (4-picolyl) trimethyl ammonium bromide is obtained through trimethylamine reaction, and finally the 4-methoxymethylpyridine is obtained through reaction with sodium methoxide. The synthesis method has the advantages of high total yield, cheap raw materials, short reaction time, mild conditions and simple process operation.)

1. The synthesis method of 4-methoxymethyl pyridine is characterized by comprising the following steps;

4-bromomethylpyridine is obtained by bromination reaction by taking 4-methylpyridine as a raw material;

reacting the 4-bromo-methylpyridine with trimethylamine to obtain (4-picolyl) trimethylammonium bromide;

dissolving the (4-picolyl) trimethyl ammonium bromide in methanol, adding sodium methoxide, and heating and refluxing for 1h under nitrogen to obtain 4-methoxymethylpyridine.

2. The process for the synthesis of 4-methoxymethylpyridine according to claim 1, which comprises: in the bromination reaction, the molar ratio of 4-methylpyridine to liquid bromine is 1:1.2-1.5, and the reaction temperature is 70-80 ℃.

3. The method for synthesizing 4-methoxymethylpyridine according to claim 2, wherein: the molar ratio of the 4-bromo-methylpyridine to the trimethylamine is 1: 1.1-1.5, and the reaction temperature is 40-60 ℃.

4. A process for the synthesis of 4-methoxymethylpyridine according to claim 3 which comprises: the molar ratio of the (3-picolyl) trimethyl ammonium bromide to the sodium methoxide is 1: 1.2-2.

5. The method for synthesizing 4-methoxymethylpyridine according to claim 4, wherein:

4-methyl pyridine is used as a raw material, and is subjected to bromination reaction to obtain 4-bromine-methyl pyridine, wherein the molar ratio of the 4-methyl pyridine to liquid bromine is 1:1.2, the reaction temperature is 70 ℃, and the stirring is carried out for 1 hour to complete the reaction;

the molar ratio of the 4-bromo-methylpyridine to the trimethylamine is 1: 1.1, reacting for 2h to obtain (3-picolyl) trimethyl ammonium bromide;

dissolving the (4-picolyl) trimethyl ammonium bromide in methanol, adding sodium methoxide, wherein the molar ratio of the (4-picolyl) trimethyl ammonium bromide to the sodium methoxide is 1:1.2, and heating and refluxing for 1h under nitrogen to obtain 4-methoxymethylpyridine.

6. The method for synthesizing 4-methoxymethylpyridine according to claim 4, wherein:

4-methyl pyridine is used as a raw material, and is subjected to bromination reaction to obtain 4-bromine-methyl pyridine, wherein the molar ratio of the 4-methyl pyridine to liquid bromine is 1:1.5, the reaction temperature is 80 ℃, and the stirring is carried out for 1 hour to complete the reaction;

the molar ratio of the 4-bromo-methylpyridine to the trimethylamine is 1:1.5, reacting for 2h to obtain (4-picolyl) trimethyl ammonium bromide;

dissolving the (4-picolyl) trimethyl ammonium bromide in methanol, adding sodium methoxide, wherein the molar ratio of the (4-picolyl) trimethyl ammonium bromide to the sodium methoxide is 1:2, and heating and refluxing for 1h under nitrogen to obtain 4-methoxymethyl pyridine.

7. The method for synthesizing 4-methoxymethylpyridine according to claim 4, wherein:

4-methyl pyridine is used as a raw material, and is subjected to bromination reaction to obtain 4-bromine-methyl pyridine, wherein the molar ratio of the 4-methyl pyridine to liquid bromine is 1:1.3, the reaction temperature is 72 ℃, and the stirring is carried out for 1 hour to complete the reaction;

the molar ratio of the 4-bromo-methylpyridine to the trimethylamine is 1: 1.4, reacting for 2h to obtain (4-picolyl) trimethyl ammonium bromide;

dissolving the (4-picolyl) trimethyl ammonium bromide in methanol, adding sodium methoxide, wherein the molar ratio of the (4-picolyl) trimethyl ammonium bromide to the sodium methoxide is 1:1.8, and heating and refluxing for 1h under nitrogen to obtain 4-methoxymethylpyridine.

8. A process for the synthesis of 4-methoxymethylpyridine according to any one of claims 5 to 7 which comprises: the mass percent of the sodium methoxide is 20%.

Technical Field

The invention relates to the field of organic chemistry, in particular to a synthetic method of 4-methoxymethyl pyridine.

Background

4-methoxymethyl pyridine is used as an important medical intermediate and a fine chemical raw material, and has wide application range and wide market prospect. In medicine, 4-methoxymethylpyridine which is an important medical intermediate can be used for synthesizing laxative bisacodyl and also is a raw material for synthesizing organophosphate antidote fossilene, and recently, 4-methoxymethylpyridine is reported to be used as a raw material for synthesizing anti-HIV protease inhibitor; in agriculture, 4-methoxymethylpyridine is an essential intermediate for synthesizing some acaricides; in the light-sensitive industry, 4-methoxymethylpyridine is used for synthesizing nitrogenous heterocyclic color photographic materials. Therefore, research on a preparation method of 4-methoxymethylpyridine, which has low cost and high yield and is suitable for industrial production, has been the direction of effort.

Disclosure of Invention

The technical problem to be solved by the invention is to provide an environment-friendly and low-cost synthesis method of 4-methoxymethylpyridine.

In order to solve the technical problem, the synthesis method of 4-methoxymethyl pyridine of the invention comprises the following steps:

4-bromomethylpyridine is obtained by bromination reaction by taking 4-methylpyridine as a raw material;

reacting the 4-bromo-methylpyridine with trimethylamine to obtain (4-picolyl) trimethylammonium bromide;

dissolving the (4-picolyl) trimethyl ammonium bromide in methanol, adding sodium methoxide, and heating and refluxing for 1h under nitrogen to obtain 4-methoxymethylpyridine.

Furthermore, the mol ratio of the 4-methylpyridine to the liquid bromine in the bromination reaction is 1:1.2-1.5, and the reaction temperature is 70-80 ℃.

Further, the molar ratio of 4-bromo-methylpyridine to trimethylamine is 1: 1.1-1.5, and the reaction temperature is 40-60 ℃.

Furthermore, the molar ratio of the (3-picolyl) trimethyl ammonium bromide to the sodium methoxide is 1: 1.2-2.

Further, 4-methyl pyridine is used as a raw material, and is subjected to bromination reaction to obtain 4-bromine-methyl pyridine, wherein the molar ratio of the 4-methyl pyridine to liquid bromine is 1:1.2, the reaction temperature is 70 ℃, and the reaction is completely stirred for 1 h;

the molar ratio of the 4-bromo-methylpyridine to the trimethylamine is 1: 1.1, reacting for 2h to obtain (3-picolyl) trimethyl ammonium bromide;

dissolving the (4-picolyl) trimethyl ammonium bromide in methanol, adding sodium methoxide, wherein the molar ratio of the (4-picolyl) trimethyl ammonium bromide to the sodium methoxide is 1:1.2, and heating and refluxing for 1h under nitrogen to obtain 4-methoxymethylpyridine.

Further, 4-methyl pyridine is used as a raw material, and is subjected to bromination reaction to obtain 4-bromine-methyl pyridine, wherein the molar ratio of the 4-methyl pyridine to liquid bromine is 1:1.5, the reaction temperature is 80 ℃, and the stirring is carried out for 1 hour to complete the reaction;

the molar ratio of the 4-bromo-methylpyridine to the trimethylamine is 1:1.5, reacting for 2h to obtain (4-picolyl) trimethyl ammonium bromide;

dissolving the (4-picolyl) trimethyl ammonium bromide in methanol, adding sodium methoxide, wherein the molar ratio of the (4-picolyl) trimethyl ammonium bromide to the sodium methoxide is 1:2, and heating and refluxing for 1h under nitrogen to obtain 4-methoxymethyl pyridine.

Further, 4-methyl pyridine is used as a raw material, and is subjected to bromination reaction to obtain 4-bromine-methyl pyridine, wherein the molar ratio of the 4-methyl pyridine to liquid bromine is 1:1.3, the reaction temperature is 72 ℃, and the stirring is carried out for 1 hour to complete the reaction;

the molar ratio of the 4-bromo-methylpyridine to the trimethylamine is 1: 1.4, reacting for 2h to obtain (4-picolyl) trimethyl ammonium bromide;

dissolving the (4-picolyl) trimethyl ammonium bromide in methanol, adding sodium methoxide, wherein the molar ratio of the (4-picolyl) trimethyl ammonium bromide to the sodium methoxide is 1:1.8, and heating and refluxing for 1h under nitrogen to obtain 4-methoxymethylpyridine.

Further, the sodium methoxide is 20% by mass.

After the synthesis method is adopted, 4-methylpyridine is used as a raw material, 4-bromo-methylpyridine is obtained through bromination reaction, (4-picolyl) trimethyl ammonium bromide is obtained through trimethylamine reaction, and finally the 4-methoxymethylpyridine is obtained through reaction with sodium methoxide. The synthesis method has the advantages of high total yield, cheap raw materials, short reaction time, mild conditions and simple process operation.

Detailed Description

The present invention will be further described with reference to specific embodiments.