Preparation method of 2-pyridinemethanol_Industrial additives

Background and overview^[1]

As an important pharmaceutical intermediate and fine chemical raw material, 2-pyridinemethanol has a wide range of applications and a broad market. In medicine, 2-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.

Preparation^[2]

The synthesis method of 2-pyridinemethanol is characterized in that it includes the following synthesis steps:

1) Synthesis of 2-methyl-3,5-dinitropyridine

Take 23.25g 2-methylpyridine as the synthetic raw material, add 24.8ml 98% concentrated sulfuric acid, stir and heat to 70°C, then add 75.6ml mixed acid dropwise to it, after the dropwise addition is completed, raise the temperature to 90-92°C and keep it for 2.2 h, then cool it in an ice-water bath, add 250 mL of ice water, dropwise add 23.2g of 30% sodium hydroxide solution for neutralization, stir for 1.5 h, then extract with ethyl acetate, recover the solvent by distillation under reduced pressure, and use organic reagents Recrystallize, filter and dry to obtain 43.21g of 2-methyl-3,5-dinitropyridine, with a yield of 94.4%;

2) Synthesis of 2-methyl-3,5-dinitropyridine-N-oxide

Add 36.62g of 2-methyl-3,5-dinitropyridine prepared in step 1) into 85ml of glacial acetic acid, stir and raise the temperature to 85±1°C, continue stirring for 20 minutes, and then slowly add it dropwise 29.2g of 30% hydrogen peroxide. After the dropwise addition is completed, the temperature is raised to 90°C at a certain rate and kept for 2.5 hours. The acetic acid solvent is then distilled under reduced pressure, recrystallized using organic reagents, filtered and dried to obtain 2-methyl- 3,5-dinitropyridine-N-oxide 38.3g, yield 96.2%;

3) Synthesis of 2-chloromethyl-3,5-dinitropyridine

Take 29.87g of 2-methyl-3,5-dinitropyridine-N-oxide prepared in step 2), dissolve it in 80ml of chloroform, and add an appropriate amount of 22.6g of trichloride thereto under low temperature conditions. Phosphate, after completion, keep stirring at 2.5±0.5℃ for 1.5h, distill under reduced pressure to remove the solvent, and obtain 30.58g of 2-chloromethyl-3,5-dinitropyridine, with a yield of 93.7%;

4) Synthesis of 2-pyridinemethanol

Take 21.76g of 2-chloromethyl-3,5-dinitropyridine prepared in step 3), dropwise add 4.5% ammonia water to it for neutralization and hydrolysis, then add iron powder to it and heat it at 165°C Reduction reaction for 1 hour, filter and decolorize, then add dilute nitrous acid dropwise to the solution to adjust the pH, stir the reaction at 0-2°C for 1 hour, normalize to room temperature, and then use organic reagents for recrystallization to obtain 2-pyridinemethanol 10.45 g, yield 95.8%.

References

[1] [Chinese invention] CN201711082534.3 A synthesis method of 2-pyridinemethanol

[2] [China invention, China invention authorization] CN201710435985.4 Synthesis method of 2-pyridinemethanol [Public]/Synthesis method of 2-pyridinemethanol [Authorization]