2,5-二乙酰氧甲基-3,6-二甲基吡嗪的合成及工艺优化

Synthesis and process optimization of 2,5-diacetoxymethyl-3,6-dimethylpyrazine

目的:对2,5-二乙酰氧甲基-3,6-二甲基吡嗪的合成及工艺进行优化。方法:以川芎嗪为原料,通过H2O2氧化、醋酐酯化两步反应合成目标化合物;以高效液相色谱法,进行目标产物与对照品吸收峰峰面积的对比来计算产率;通过考察反应温度和时间对产率的影响优化两步合成工艺;产物结构经红外光谱、紫外光谱、质谱和磁共振谱确证。结果:合成N,N'-二氧四甲基吡嗪时,98℃反应12h较佳;合成2,5-二乙酰氧甲基-3,6-二甲基吡嗪时,100℃反应4h较佳。结论:时间和温度是影响产率的主要因素,此工艺优化方法具有原料易得、反应设施条件简单、适合车间厂房大批量生产等优点。

Objective：To synthesize 2,5-diacetoxymethyl-3,6-dimethylpyrazine and to optimize technical conditions. Methods：Tetramethylpyrazine and 30% hydrogen peroxide were reacted in glacial acetic acid at 98℃ to yield N,N＇-dioxotetramethylpyrazine, and then heated at 100℃ to get target product, the recovery was monitored by HPLC via chromatographic peak area, the reaction temperature and time were investigated, the structure was identified by UV,IR,NMR and MS. Results：The reaction temperature and reaction time to synthesize N,N＇-dioxotetramethylpyrazine was 98℃ and 12 h, respectively, the reaction temperature and reaction time to synthesize 2,5-diacetoxymethyl-3,6-dimethylpyrazine was 100℃ and 4 h, respectively. Conclusion：Reaction temperature and time are major factors effecting the yields. The method is simple, convient to synthesize 2,5-diacetoxymethyl-3,6-dimethylpyrazine.