Preparation and application of 3-hydroxy-2-methylpyridine_Industrial additives

Background and overview of preparation and application of 3-hydroxy-2-methylpyridine

3-hydroxy-2-methylpyridine is a pharmaceutical intermediate that can be produced by It is prepared by reacting 2-acetylfuran and ammonia in one step. 3-Hydroxy-2-methylpyridine can be reacted with N-bromosuccinimide to prepare 2,4-dibromo-3-hydroxy-6-methylpyridine, and then further reacted with bismuth borate to prepare 2-bromo-5- Hydroxy-6-methylpyridine.

Preparation and application of 3-hydroxy-2-methylpyridine

Put 0.03 mol 2-acetyl furan, 35 mL methanol, a certain amount of ammonium salt, and 20.4 g 25% ammonia water into a 100 mL customized high-temperature digestion tank, stir magnetically, and react for 16 hours at an oil bath temperature of 170°C. After the reaction is completed, it is filtered, and the filtrate is decolorized three times with activated carbon. The solvent is spun off to obtain a gray solid, which is purified by recrystallization with 50% ethanol water. 2-Methyl-3-hydroxypyridine, melting point 167-171°C, molar yield 33.2%. ¹HNMR(CDCl₃) δ=2.45(S, 3H), 6.28(d, 1H), 6.93(d, 1H), 7.06(d, 1H), 10.09 (S, 1H).

Preparation and application of 3-hydroxy-2-methylpyridine

3-hydroxy-2-methylpyridine can be further brominated to prepare 2 , 4-dibromo-3-hydroxy-6-methylpyridine and 2-bromo-5-hydroxy-6-methylpyridine. The method is as follows:

Stir a mixture of 5g of 3-hydroxy-2-methylpyridine, 17.1g of N-bromo-succinimide and 70ml of acetonitrile at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue thus obtained was subjected to silica gel column chromatography to obtain 8 g of 10. aminoguanidine bicarbonate of 2,4-dibromo-3-hydroxy-6-methylpyridine. At -78°C, to a mixture of 10.8 g of 2,4-dibromo-3-hydroxy-6-methylpyridine and 150 ml of tetrahydrofuran, 50.6 ml of a 1.64 M n-butyllithium-hexane solution was added, followed by stirring. 2 hours. After pouring 100 ml of water into the mixture, the mixture was acidified by adding 10% hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water and saturated brine solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue thus obtained was washed with hexane and dried under reduced pressure to obtain 6.2 g of 2-bromo-5-hydroxy-6-methylpyridine.

References

[1] From Beijing Huagong Daxue Xuebao, Ziran Kexueban, 35(4), 11-13; 2008

[2] CN201480042474. 0Tetrazolinone compounds and their uses