CN111056992A - Synthetic method of 2-chloromethylpyridine hydrochloride - Google Patents
Synthetic method of 2-chloromethylpyridine hydrochloride Download PDFInfo
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- CN111056992A CN111056992A CN201911181932.XA CN201911181932A CN111056992A CN 111056992 A CN111056992 A CN 111056992A CN 201911181932 A CN201911181932 A CN 201911181932A CN 111056992 A CN111056992 A CN 111056992A
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- chloromethylpyridine hydrochloride
- acetic acid
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- pyridine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
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- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention belongs to the field of organic synthesis, and particularly relates to a synthetic method of 2-chloromethylpyridine hydrochloride, which comprises the following steps: (1) the method comprises the following steps of taking 2-methylpyridine as a raw material, and reacting with hydrogen peroxide under the condition of acetic acid to generate nitrogen oxide-2-methylpyridine, wherein the molar ratio of the 2-methylpyridine to the acetic acid to the hydrogen peroxide is 1:1-1.1:1.3-1.5, the temperature of the oxidation reaction is 70-80 ℃, and the reaction time is 10-14 hours; (2) 2-picoline oxynitride reacts with glacial acetic acid to generate 2-picoline acetate; (3) 2-pyridine methyl acetate is hydrolyzed into 2-pyridine methanol; (4) reacting the 2-pyridinemethanol with thionyl chloride to obtain the target product 2-chloromethylpyridine hydrochloride, wherein the molar ratio of the 2-pyridinemethanol to the thionyl chloride is 1: 1.1-1.3. The preparation method provided by the invention has the advantages of high yield, low cost, mild reaction conditions and easiness in industrial production.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a synthetic method of 2-chloromethylpyridine hydrochloride.
Technical Field
The 2-chloromethyl pyridine hydrochloride is an important chemical raw material for various pesticides, medical intermediates, insecticides, herbicides and bactericides. The prior production method adopts pyridine to directly add methyl, uses methyl lithium and other noble metal chemical raw materials or directly synthesizes 2-position methyl by cyclization, and then carries out chlorination reaction by chlorine. In some techniques, pyridine nitroxide is methylated with dimethyl sulfate, re-oxidized to obtain 2-hydroxymethylpyridine, and re-chlorinated to obtain 2-chloromethylpyridine hydrochloride. The pyridine is easier to be connected with other groups after chloromethylation to synthesize chemical raw material intermediates and raw material medicaments with high added values. However, the use of methyllithium or the like as a raw material is expensive, troublesome in recovering noble metals, and dangerous to the operator due to the toxicity of dimethyl sulfate.
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 synthetic method of 2-chloromethylpyridine hydrochloride, which has low cost, high yield and mild reaction conditions.
The invention provides a synthetic method of 2-chloromethylpyridine hydrochloride, which comprises the following steps:
(1) taking 2-methylpyridine as a raw material, and reacting with hydrogen peroxide to generate 2-methyl pyridine oxynitride under the condition of acetic acid, wherein the molar ratio of the 2-methylpyridine to the acetic acid to the hydrogen peroxide is 1:1-1.1:1.3-1.5, the temperature of the oxidation reaction is 70-80 ℃, and the reaction time is 10-14 h;
(2) 2-methyl pyridine oxynitride reacts with glacial acetic acid to generate 2-pyridine methyl acetate;
(3) 2-pyridine methyl acetate is hydrolyzed into 2-pyridine methanol;
(4) reacting the 2-pyridinemethanol with thionyl chloride to obtain the target product 2-chloromethylpyridine hydrochloride, wherein the mass ratio of the 2-pyridinemethanol to the thionyl chloride is 1: 1.1-1.3.
Further, the molar ratio of the 2-methyl pyridine oxynitride to the glacial acetic acid in the step (2) is 1: 1.5-2.
Further, the hydrolysis of step (3) is performed under alkaline conditions.
Further, the alkaline condition of the step (2) is sodium hydroxide solution or potassium hydroxide solution, and the concentration of the sodium hydroxide solution or the potassium hydroxide solution is 25%.
Further, the reaction time of the step (2) is 2-3 h.
Further, the solvent of the step (4) is methanol.
The reaction equation of the method of the invention is as follows:
the technical scheme adopted by the invention has the beneficial effects that: the method has the advantages of few reaction steps, low cost, high purity, high yield and safe operation, and is suitable for large-scale industrial production.
Detailed Description
In order to further illustrate the invention, some examples are given below. 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.
Example 1
2-methylpyridine (18.6g,0.2mol), glacial acetic acid (12g, 0.2mol) and hydrogen peroxide (8.84g, 0.26mol) are added into a 250ml flask, the mixture is reacted for 10h at 70 ℃, the mixture is subjected to thin-layer chromatography tracking analysis, after the reaction is completely converted into 2-methylpyridine oxynitride, the mixture is reacted with glacial acetic acid (18g, 0.3mol), the mixture is subjected to thin-layer chromatography tracking analysis, after the reaction is completely converted into 2-picolyl acetate, the mixture is hydrolyzed by using 25% sodium hydroxide aqueous solution, the mixture is subjected to thin-layer chromatography tracking analysis, after the reaction is completely converted into 2-pyridinemethanol, the mixture is reacted with thionyl chloride (26.18g, 0.22mol) in a methanol solution, the thin-layer chromatography tracking analysis is performed, after the reaction is completely converted into 2-chloromethylpyridine hydrochloride, the reaction is stopped, and suction filtration is carried out, so that 26.2 g.
Example 2
2-methylpyridine (18.6g,0.2mol), glacial acetic acid (12.6g, 0.21mol) and hydrogen peroxide (9.52g, 0.28mol) are added into a 250ml flask, the mixture is reacted for 10h at 70 ℃, the mixture is subjected to thin-layer chromatography tracking analysis, the mixture is reacted with glacial acetic acid (20.4g, 0.34mol) after the reaction is completely converted into 2-methylpyridine oxynitride, the mixture is subjected to thin-layer chromatography tracking analysis, the mixture is hydrolyzed by a 25% sodium hydroxide aqueous solution after the reaction is completely converted into 2-picolyl acetate, the mixture is subjected to thin-layer chromatography tracking analysis, the mixture is reacted with thionyl chloride (28.56g, 0.24mol) in a methanol solution after the reaction is completely converted into 2-chloromethylpyridine hydrochloride, and the reaction is stopped after the thin-layer chromatography tracking analysis, and suction filtration is carried out, so that 26.9g of a product is obtained, and the yield is 82% (molar yield).
This embodiment is the best mode.
Example 3
Adding 2-methylpyridine (18.6g,0.2mol), glacial acetic acid (13.2g, 0.22mol) and hydrogen peroxide (10.2g, 0.3mol) into a 250ml flask, reacting for 10h at 70 ℃, performing thin-layer chromatography tracking analysis, reacting with glacial acetic acid (24g, 0.4mol) after all the reactions are converted into 2-methylpyridine oxynitride, performing thin-layer chromatography tracking analysis, hydrolyzing with 25% sodium hydroxide aqueous solution after all the reactions are converted into 2-picolyl acetate, performing thin-layer chromatography tracking analysis, reacting with thionyl chloride (30.94g, 0.26mol) in a methanol solution after all the reactions are converted into 2-chloromethylpyridine hydrochloride, performing suction filtration to obtain a product of 25.6g and yield of 78% (molar yield).
Claims (6)
1. A synthetic method of 2-chloromethylpyridine hydrochloride is characterized by comprising the following steps:
(1) taking 2-methylpyridine as a raw material, and reacting with hydrogen peroxide to generate 2-methyl pyridine oxynitride under the condition of acetic acid, wherein the molar ratio of the 2-methylpyridine to the acetic acid to the hydrogen peroxide is 1:1-1.1:1.3-1.5, the temperature of the oxidation reaction is 70-80 ℃, and the reaction time is 10-14 h;
(2) 2-methyl pyridine oxynitride reacts with glacial acetic acid to generate 2-pyridine methyl acetate;
(3) 2-pyridine methyl acetate is hydrolyzed into 2-pyridine methanol;
(4) reacting the 2-pyridinemethanol with thionyl chloride to obtain the target product 2-chloromethylpyridine hydrochloride, wherein the mass ratio of the 2-pyridinemethanol to the thionyl chloride is 1: 1.1-1.3.
2. The method for synthesizing 2-chloromethylpyridine hydrochloride according to claim 1, wherein the method comprises the following steps: the molar ratio of the 2-methyl pyridine oxynitride to the glacial acetic acid in the step (2) is 1: 1.5-2.
3. The method for synthesizing 2-chloromethylpyridine hydrochloride according to claim 1, wherein the method comprises the following steps: the hydrolysis of step (3) is carried out under alkaline conditions.
4. The method for synthesizing 2-chloromethylpyridine hydrochloride according to claim 3, wherein the method comprises the following steps: the alkaline condition of the step (2) is sodium hydroxide solution or potassium hydroxide solution, and the concentration of the sodium hydroxide solution or the potassium hydroxide solution is 25%.
5. The method for synthesizing 2-chloromethylpyridine hydrochloride according to claim 3, wherein the method comprises the following steps: the reaction time of the step (2) is 2-3 h.
6. The method for synthesizing 2-chloromethylpyridine hydrochloride according to claim 1, wherein the method comprises the following steps: the solvent in the step (4) is methanol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911181932.XA CN111056992A (en) | 2019-11-27 | 2019-11-27 | Synthetic method of 2-chloromethylpyridine hydrochloride |
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|---|---|---|---|
| CN201911181932.XA CN111056992A (en) | 2019-11-27 | 2019-11-27 | Synthetic method of 2-chloromethylpyridine hydrochloride |
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| CN111056992A true CN111056992A (en) | 2020-04-24 |
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| CN201911181932.XA Withdrawn CN111056992A (en) | 2019-11-27 | 2019-11-27 | Synthetic method of 2-chloromethylpyridine hydrochloride |
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Application publication date: 20200424 |
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| WW01 | Invention patent application withdrawn after publication |