Background and overview Original hot melt adhesive imported from Germany[1][2]
2,6-Disubstituted pyridine is an important type of organic synthesis intermediate, especially 2,6-pyridine dimethanol, which has strong applicability. The hydroxyl group can be derivatized into aldehyde groups, halogenated hydrocarbons, amino groups and many other functional groups to synthesize other important compounds. Moreover, due to the substitution of 2 and 6 positions, macrocyclic compounds can also be generated, which are widely used in synthesis and have high research value.
2,6-Pyridine dimethanol
Apply[3]
Preparation of 2,6-pyridine dimethanol nickel complex crystal
Weigh 0.8200g (0.006mol) 2,6-pyridine dimethanol and 0.7358g (0.003mol) NiCl2·6H2O into a 100mL round bottom flask, add 30ml anhydrous methanol, stir to dissolve them, and heat Reflow for 48 hours. After the reaction is completed, filter it while it is hot to allow it to evaporate naturally. Green crystals will precipitate after a few days; after filtration, wash the crystals three times with n-hexane and petroleum ether, and dry in a vacuum to obtain the target product 2,6-nickel pyridine dimethanol. 0.40g of complex crystals, yield: 33%; melting point: >200°C.
Preparation[2]
The classic route for 2,6-pyridinedimethanol is to use 2,6-dimethylpyridine as raw material, oxidize it to 2,6-pyridinedicarboxylic acid, then esterify it, and then reduce the ester to alcohol. , to obtain the target product. This synthesis route is a three-step reaction. In the second step, pyridinedicarboxylic acid is esterified into methyl ester. The classic esterification method requires concentrated sulfuric acid as a catalyst, which is corrosive and requires a long reaction time (usually 24 hours) and the yield is not high. If acid is reacted with thionyl chloride to form acid chloride and then esterified with alcohol, the yield can be increased, but the reagent needs to be treated anhydrous, and thionyl chloride is highly irritating, and SO2 and HCl gas is toxic, harmful and corrosive, and exhaust gas needs to be absorbed, making the operation steps more cumbersome and increasing the difficulty of the reaction.
Specific method:
Synthesis of (1) 2,6-pyridinedicarboxylic acid:
In a 2L flask equipped with a stirrer and a reflux condenser, add 800mL water, 53.5gKMnO4, 16.7g2,6-dimethylpyridine, heat to reflux, when the color of KMnO4 fades, add another 53.5 gKMnO4 and 200mL photoinitiator water, continue to reflux until the color completely fades (about 2h), cool, filter out the MnO2, wash the filtered insoluble matter in 500mL hot water, filter, combine the filtrate, and concentrate the filtrate to 200 -300mL, filtered, then acidified with concentrated HCl, cooled, precipitated, filtered, dried to obtain 2,6-pyridinedicarboxylic acid. Yield: 80%, m.p. 220°C, consistent with literature.
Synthesis of (2) 2,6-pyridine dimethanol:
Add 8.8g (0.05mol) 2,6-pyridinedicarboxylic acid and 200mLTHF into a 500mL three-necked flask, cool to -5 degrees Celsius in an ice-salt bath, and add 3.8g (0.1mol) NaBH4 in batches while stirring. After the addition is complete, react for half an hour until gas is no longer generated. Dissolve 0.05 mol of iodine in 80 mL of THF and drop it into it. After the dropwise addition, remove the ice bath and naturally warm to room temperature. The reaction will stop after 1.5 hours. Add 3 mol/L hydrochloric acid to adjust the pH to neutral, remove the solid by suction filtration, spin the solution to dryness, extract with vibration with ethyl acetate, dry with anhydrous magnesium sulfate and then spin evaporate to obtain 5g of white crystals with a yield of 72%. m.p.111-112℃.
This method mainly simplifies the reduction steps in the preparation process of 2,6-pyridine dimethanol. Using NaBH4/I2 as the reduction system, 2,6-pyridinedicarboxylic acid can be directly reduced to 2,6-pyridinedicarboxylic acid without having to esterify the acid and then reduce it, simplifying the original three-step reaction into two steps. Moreover, the NaBH4/I2 system has a high yield and does not require the use of corrosive and irritating reagents such as concentrated sulfuric acid and thionyl chloride. Compared with existing methods, the method for preparing 2,6-pyridine dimethanol provided by the invention has the characteristics of simplified reaction steps, safe and simple operation, easy product separation, and high yield. It is 2,6-pyridine dimethanol. Products widely used in the fields of basic research and industrial production research provide a route with strong operability and good practical significance and economic value.
Main reference materials
[1] Luo Mei, & Zhang Xin. (2016). A kind of 2,6 pyridine dimethanol nickel complex crystal and its uses.
[2] Qi Donglai, & Wang Xiang. (2016). A preparation method of 2,6-pyridine dimethanol.
[3] Lin Rongbin, Shi Xiaoming, & Liang Dong. (2015). Research on the synthesis process of 2,6-pyridine dimethanol. Chemical Intermediates (11), 22-22.
