2-氯甲基-4-甲氧基-3,5-二甲基吡啶盐酸盐的合成

Synthesis of 2-Chloromethyl-4-methoxy- 3,5-dimethylpyridine Hydrochloride

2,3,5 三甲基吡啶用双氧水/冰醋酸氧化制得2,3,5 三甲基吡啶 N 氧化物,收率91%;该氧化吡啶与发烟硝酸/浓硫酸反应得4 硝基 2,3,5 三甲基吡啶 N 氧化物,收率80 4%;将其与甲醇钠反应得到4 甲氧基 2,3,5 三甲基吡啶 N 氧化物,收率91%;4 甲氧基 2,3,5 三甲基吡啶 N 氧化物与乙酸酐反应得到2 乙酰基氧甲基 4 甲氧基 3,5 二甲基吡啶,收率66 6%;2 乙酰基氧甲基 4 甲氧基 3,5 二甲基吡啶在碱性条件下水解得2 羟甲基 4 甲氧基 3,5 二甲基吡啶,收率93%;再用氯化亚砜氯代制得2 氯甲基 4 甲氧基 3,5 二甲基吡啶盐酸盐,收率90 6%。通过TLC、IR、1HNMR对产物进行了表征。

2,3,5-Trimethylpyridine was oxidized to 2,3,5-trimethylpyridine N-oxide(Ⅰ) in 91% yield by treatment with hydrogen peroxide in hot acetic acid.Ⅰ was nitrated with fuming nitric acid in conc. sulfuric acid to give 2,3,5-trimethyl-4-nitropyridine N-oxide(Ⅱ) in 80.4% yield.Treatment of Ⅱ with sodium methoxide afforded 4-methoxy-2,3,5-trimethylpyridine N-oxide(Ⅲ) in 91% yield.Heating Ⅲ with acetic anhydride gave 2-acetoxymethyl-4-methoxy-3,5-dimethylpyridine(Ⅳ) in 66.6% yield.Then Ⅳ was hydrolyzed to 2-hydroxymethyl-4-methoxy-3,5-dimethylpyridine(Ⅴ) in 93% yield.Finally,Ⅴ was halogenated with thionyl chloride to give 2-chloromethyl-4-methoxy-3,5-dimethylpyridine hydrochloride(Ⅵ) in 90.6% yield.Structure of Ⅵ was primarily identified by TLC,IR and ~1HNMR.