摘要
吡嗪N-氧化物广泛运用在有机合成、生物医药和含能材料领域。传统合成方法主要是双氧水/乙酸氧化体系,会造成环境污染,同时也限制了对酸敏感底物的使用。因此,发展吡嗪N-氧化物的绿色合成方法变得尤为迫切。以2,5-二甲基吡嗪为模板底物,通过筛选反应的投料比,碱和溶剂,得到了最优的反应条件:以甲醇为反应溶剂,底物、H_(2)O_(2)和NaHCO_(3)的物质的量之比为1.0∶1.2∶3.6,在F_(2)O_(2)S的促进下,于室温反应50 min。合成的11个吡嗪N-氧化物(2a~2k)的产率为10%~84%,其结构通过^(1)H NMR,^(13)C NMR和MS(ESI)确证。2,6-二甲氧基吡嗪的2个氮原子处于不同的化学环境,通过确认氮氧化反应的选择性,对化合物2f进行单晶X-射线衍射实验,确定该氧化反应优先发生在位阻较小的4-位N原子。该反应可以在弱碱性条件下进行,避免了酸的使用,符合绿色化学理念。
Pyrazine N-oxides are widely used in the fields of organic synthesis,biomedicine,and energetic materials.The traditional synthesis method mainly involves the hydrogen peroxide/acetic acid oxidation system,which can cause the environmental pollution and also limit the use of acid sensitive substrates.Therefore,it is urgent to develop a green method for the synthesis of pyrazine N-oxides.In this study,using 2,5-dimethylpyrazine as a template substrate,the optimal reaction conditions were obtained by screening the ratio of raw materials,bases,and solvents.Methanol was used as the reaction solvent,and the ratio of substrate,H_(2)O_(2) and NaHCO_(3) to each other was 1.0∶1.2∶3.6.Under the promotion of F_(2)O_(2)S,the reaction occurred at room temperature for 50 minutes.Eleven corresponding pyrazine N-oxides 2a~2k were obtained with yields ranging from 10%~84%.Their structures were confirmed by ^(1)H NMR,^(13)C NMR and MS(ESI).The two nitrogen atoms of 2,6-dimethoxy-pyrazine are in different chemical environments.By confirming the selectivity of the nitrogen oxidation reaction,compound 2f was characterized by single crystal X-ray diffraction,and it was determined that the oxidation reaction preferentially occurred at the 4-position N atom with low site-resistance.This reaction can be carried out under weakly alkaline conditions,avoiding the use of acids and conforming to the concept of green chemistry.
作者
陈阳
温乐乐
陈文博
CHEN Yang;WEN Lele;CHEN Wenbo(Shanghai Key Laboratory of Materials Protection and Advanced Materials in Electric Power,College of Environmental and Chemical Engineering,Shanghai University of Electric Power,Shanghai 200090,China;CAS Key Laboratory of Energy Regulation Materials,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China)
出处
《合成化学》
CAS
2024年第8期731-736,共6页
Chinese Journal of Synthetic Chemistry
基金
上海市自然科学基金资助项目(20ZR1471600)
上海市科学技术委员会资助项目(19DZ2271100)
中国科学院能量调控材料重点实验室开放基金资助项目(ORFP2020-06)。
