Preparation of 4-pyridinemethanol_Industrial additives

Background and overview^[1][2]

4-Pyridinemethanol is also known as: pyridine-4-methanol, ω-hydroxy-4-picoline, 4-(Hydroxymethyl)pyridine, 4-Pyridinemethanol, 4-Pyridylcarbinol, ω-Hydroxy-4-picoline, in recent years Since then, 4-pyridylmethanol has been widely used as an intermediate for pesticides and pharmaceuticals.

4-pyridinemethanol

Apply^[3]

As an important pharmaceutical intermediate and fine chemical raw material, 4-pyridinemethanol has a wide range of applications and a broad market. In medicine, 4-pyridinemethanol, as an important pharmaceutical intermediate, can be used to synthesize bisacodyl for exchange transfusions, and is also a raw material for the synthesis of organophosphate antidote pralidoxime. In agriculture, 4-pyridinecarboxaldehyde is a necessary intermediate for the synthesis of some acaricides; in the photosensitive industry, 4-pyridinecarboxaldehyde can be used to synthesize nitrogen-containing heterocyclic color photographic materials.

Preparation^[2]

Currently, there are four methods for synthesizing 4-pyridinemethanol from different raw materials: (1) Bromination method. After a bromination reaction of 4-methylpyridine at 150°C, it is hydrolyzed with alkali to obtain pyridinemethanol. . This method requires pressurized equipment during bromination, and the corrosion is serious. The yield of 4-pyridinemethanol is very low, and the post-treatment method is complicated, so it is not easy to implement. (2) Lithium aluminum tetrahydride reduction method. This method uses 4-pyridine acetic acid as the raw material, methylene chloride as the solvent, and lithium aluminum tetrahydride as the reducing agent to perform the reduction reaction. Then it is hydrolyzed to obtain 4-methanolpyridine. The recovery rate of 4-pyridinemethanol in this method is more than 80%. However, since 4-pyridineacetic acid and lithium aluminum tetrahydride are expensive and even need to be imported, this method is only suitable for laboratory preparation and is not easy to achieve industrialization. (3) Triisobutylaluminum reduction method, using 4-picolinate methyl ester as the raw material, triisobutylaluminum as the original agent, and then hydrolyzing to obtain pyridinemethanol. The recovery rate of 4-pyridinemethanol in this method can also reach more than 80%, but at the same time, because triisobutylaluminum is relatively expensive, the process is unstable and the operation is difficult, and it is only suitable for laboratory applications. (4) High-pressure hydrogenation method, using Raney-Ni (or Co) as a catalyst, hydrogenating cyanopyridine under a pressure of 1.96 to 6.86MPa to obtain methylamine pyridine, and then directly adding sodium nitrite and hydrochloric acid to the filtrate Carry out diazotization reaction and then remove nitrogen. After hydrolysis, 4-pyridinemethanol is obtained. This method uses many raw materials, has complex processes, high reaction pressure, and large catalyst consumption, making it difficult to achieve industrialization. (5) N-oxide esterification and hydrolysis method. 4-methylpyridine is oxidized with hydrogen peroxide, and then esterified with acetic acid and then hydrolyzed with alkene. This method has N-oxides that are prone to explosion. After hydrolysis, extraction is difficult. difficulty. The yield is low and the quality is poor.

Method 1:

Use 4-pyridinecarboxylic acid as the raw material, hydrogen and hydrochloric acid as the reactants, and an alloy prepared from 45% molecular sieve, 2% nickel, 3% cobalt, 4% palladium and 46% carbon as the catalyst. 4-Pyridine carboxaldehyde is prepared from carboxylic acids under 4-pyridinecarboxaldehyde is reduced to 4-pyridinemethanol.

Method 2:

(a) The 4-methylpyridine reacts with glacial acetic acid and hydrogen peroxide. The reaction temperature is 70°C, the reaction time is 14 hours, and the molar ratio of the 4-methylpyridine, glacial acetic acid, and hydrogen peroxide is 1:3.5: 3. Obtain 4-pyridine nitrogen oxide;

(b) The 4-pyridine nitrogen oxide reacts with acetic anhydride, the reaction temperature is 85°C, the reaction time is 6 hours, and the molar ratio of the 4-pyridine nitrogen oxide and acetic anhydride is 1:2.5, to obtain 4-Pyridylmethyl acetate;

(c) The 4-pyridine methyl acetate reacts with the potassium hydroxide solution. The reaction time is 4 hours. The molar ratio of the 2-pyridine methyl acetate to the potassium hydroxide solution is 1:1.5. The reaction gives Potassium dihydrogen phosphate 4-pyridine industrial antioxidant methanol.

Main reference materials

[1] Lu Lei, Li Dacheng, & Dou Jianmin. (0). Synthesis and structure of 2-pyridinemethanol manganese complex. The 16th National Academic Symposium on Organometallic Chemistry.

[2] Li Hongxia. (2014). Effects of chromium pyridinemethanol on the growth, muscle quality and anti-stress ability of tilapia. (Doctoral dissertation, Shandong Agricultural University).

[3] Wang Huisheng, Le Lin, Pan Min, Zhong Wenda, Tu Wei, & Pan Zhiquan. (2016). Heptanuclear manganese complex with mixed ligands of 2-pyridinemethanol and 1,1,1-trihydroxymethylethane Synthesis, crystal structure and magnetism of substances. Journal of Inorganic Chemistry, 32(01), 153-160.