阅读说明：本技术 一种2,6-二氯甲基吡啶盐酸盐的制备方法 (Preparation method of 2, 6-dichloromethylpyridine hydrochloride ) 是由 倪俊 于 2019-11-25 设计创作，主要内容包括：本发明属于有机合成领域,具体涉及一种2,6-二氯甲基吡啶盐酸盐的制备方法,该方法包括以下步骤：(1)以2,6-二甲基吡啶为原料,制备2,6-吡啶二甲酸；(2)2,6-吡啶二甲酸与甲醇在酸性条件下生成2,6-吡啶二甲酸二甲酯；(3)2,6-吡啶二甲酸二甲酯还原为2,6-吡啶二甲醇；(4)2,6-吡啶二甲醇与氯化亚砜反应得到目的产物2,6-二氯甲基吡啶盐酸盐。采用本发明的有益效果是：本发明采用常用的含有吡啶环的化工原料进行乙酰基化反应,反应步骤少,成本低,毒性小,收率高,适于工业化生产。(The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of 2, 6-dichloromethylpyridine hydrochloride, which comprises the following steps: (1) 2, 6-pyridine dicarboxylic acid is prepared by taking 2, 6-dimethyl pyridine as a raw material; (2)2, 6-pyridine dicarboxylic acid and methanol generate dimethyl 2, 6-pyridine dicarboxylate under an acidic condition; (3) reducing 2, 6-pyridine dimethyl dicarboxylate into 2, 6-pyridine dimethanol; (4)2, 6-pyridine dimethanol reacts with thionyl chloride to obtain the target product 2, 6-dichloromethylpyridine hydrochloride. The beneficial effects of the invention are as follows: the method adopts the common chemical raw materials containing pyridine rings to carry out the acetylation reaction, has the advantages of few reaction steps, low cost, low toxicity and high yield, and is suitable for industrial production.)

1. A preparation method of 2, 6-dichloromethylpyridine hydrochloride is characterized by comprising the following steps:

(1) 2, 6-dimethylpyridine is used as a raw material, water is used as a solvent, and the raw material is oxidized into 2, 6-pyridinedicarboxylic acid by potassium permanganate, wherein the molar ratio of the 2, 6-dimethylpyridine to the potassium permanganate is 1:4-5, the oxidation temperature is maintained at 75-80 ℃, the heating is carried out for 35min, the reaction solution is adjusted to be acidic after the reaction is finished, and then the reaction solution is cooled to 20-25 ℃ to obtain the 2, 6-pyridinedicarboxylic acid;

(2)2, 6-pyridinedicarboxylic acid and methanol generate 2, 6-pyridinedicarboxylic acid dimethyl ester under acidic condition, wherein the molar ratio of the 2, 6-pyridinedicarboxylic acid to the methanol is 1: 2.5-3;

(3) reducing 2, 6-pyridine dimethyl dicarboxylate into 2, 6-pyridine dimethanol;

(4) the 2, 6-pyridinedimethanol reacts with thionyl chloride to obtain the target product 2, 6-dichloromethylpyridine hydrochloride, and the molar ratio of the 2, 6-pyridinedimethanol to the thionyl chloride is 1: 2.2-2.5.

2. The process according to claim 1, wherein the reaction is carried out in the presence of a solvent selected from the group consisting of: the potassium permanganate in the step (1) is added in batches at the temperature of 80 ℃.

3. The process according to claim 1, wherein the reaction is carried out in the presence of a solvent selected from the group consisting of: in the step (1), the PH value of the reaction solution is adjusted to 3-4 by using 2mol/l hydrochloric acid.

4. The process according to claim 1, wherein the reaction is carried out in the presence of a solvent selected from the group consisting of: the temperature for cooling and filtering in the step (1) is 25 ℃.

5. The process according to claim 1, wherein the reaction is carried out in the presence of a solvent selected from the group consisting of: the reducing agent adopted in the step (3) is sodium borohydride, and the molar ratio of the dimethyl 2, 6-pyridinedicarboxylate to the sodium borohydride is 1: 6-8, and adding Lewis acid in the reduction reaction.

6. The process according to claim 5, wherein the reaction mixture comprises the following components: the Lewis acid is aluminum trichloride.

7. The process according to claim 5, wherein the reaction mixture comprises the following components: the solvent adopted in the reduction reaction is formed by mixing THF and toluene according to the volume ratio of 1: 1.

Technical Field

The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of 2, 6-dichloromethylpyridine hydrochloride.

Background

Pyridine and its derivatives are widely distributed in nature. Many plant components such as alkaloids contain pyridine ring compounds in their structures, which are the basis for the production of many important compounds, which are essential raw materials for the production of pharmaceuticals, pesticides, dyes, surfactants, rubber aids, feed additives, food additives, adhesives, etc.

2, 6-dichloro methyl pyridine hydrochloride is an important intermediate of medicine and pesticide, and the currently adopted method is to methylate pyridine and then react with expensive noble metal chemical raw materials such as methyl lithium, methyl iodide and the like; or direct ring synthesis of methyl in 2, 6-position, and chlorination reaction with chlorine. But the raw materials of methyllithium, methyl iodide and the like are high in cost, and the recovery of noble metals and iodine elements is troublesome; the use of dimethyl sulfate has high toxicity and is dangerous for feeding operation.

Disclosure of Invention

The invention aims to overcome the technical defects of high cost and large raw material toxicity in the prior art, and provides a preparation method of 2, 6-dichloromethylpyridine hydrochloride, which has low cost and short route and is suitable for industrial production.

In order to solve the technical problems, the technical scheme adopted by the invention is as follows:

a preparation method of 2, 6-dichloromethylpyridine hydrochloride comprises the following steps:

(1) 2, 6-dimethylpyridine is used as a raw material, water is used as a solvent, and the raw material is oxidized into 2, 6-pyridinedicarboxylic acid by potassium permanganate, wherein the molar ratio of the 2, 6-dimethylpyridine to the potassium permanganate is 1:4-5, the oxidation temperature is maintained at 75-80 ℃, the heating is carried out for 35min, the reaction solution is adjusted to be acidic after the reaction is finished, and then the reaction solution is cooled to 20-25 ℃ to obtain the 2, 6-pyridinedicarboxylic acid;

(2)2, 6-pyridinedicarboxylic acid and methanol generate 2, 6-pyridinedicarboxylic acid dimethyl ester under acidic condition, wherein the molar ratio of the 2, 6-pyridinedicarboxylic acid to the methanol is 1: 2.5-3;

(3) reducing 2, 6-pyridine dimethyl dicarboxylate into 2, 6-pyridine dimethanol;

(4) the 2, 6-pyridinedimethanol reacts with thionyl chloride to obtain the target product 2, 6-dichloromethylpyridine hydrochloride, and the molar ratio of the 2, 6-pyridinedimethanol to the thionyl chloride is 1: 2.2-2.5.

Further, potassium permanganate in the step (1) is added in batches at the temperature of 80 ℃.

Further, in the step (1), the pH value of the reaction solution is adjusted to 3-4 by using 2mol/l hydrochloric acid.

Further, the temperature for cooling and filtering in the step (1) is 25 ℃.

Further, the reducing agent used in the step (3) is sodium borohydride, and the molar ratio of the dimethyl 2, 6-pyridinedicarboxylate to the sodium borohydride is 1: 6-8, and adding Lewis acid in the reduction reaction.

Further, the Lewis acid is aluminum trichloride.

Furthermore, the solvent adopted in the reduction reaction is formed by mixing THF and toluene in a volume ratio of 1: 1.

The reaction equation of the invention is as follows:

the beneficial effects of the invention are as follows: the method adopts the common chemical raw materials containing pyridine rings to carry out the acetylation reaction, has the advantages of few reaction steps, low cost, low toxicity and high yield, and is suitable for industrial production.

Detailed Description

The present invention is further illustrated by the following specific examples. These examples are purely illustrative and are intended to be a detailed description of the invention and should not be taken as limiting the invention.