F_(2)O_(2)S促进吡嗪N-氧化物的合成  

F_(2)O_(2)S Promoted The Synthesis of Pyrazine N-Oxides

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)

机构地区：[1]上海电力大学环境与化学工程学院上海市电力材料防护与新材料重点实验室,上海200090 [2]中国科学院上海有机化学研究所中科院能量调控材料重点实验室,上海200032

出　　处：《合成化学》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)。

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.

关 键 词：吡嗪 F_(2)O_(2)S H_(2)O_(2) 氧化 绿色合成 N-氧化物 弱碱 

分 类 号：O621.3[理学—有机化学]