Institute of Chemistry, Saint Petersburg State University, 7/9 Universitetskaya Nab., 199034 Saint Petersburg, Russia.
Pharmaceutical Technology Transfer Centre, Yaroslavl State Pedagogical University Named after K.D. Ushinsky, 108 Respublikanskaya St., 150000 Yaroslavl, Russia.
Molecules. 2022 Nov 3;27(21):7508. doi: 10.3390/molecules27217508.
We have developed a simple and convenient method for the synthesis of 3-aryl- and 3-hetaryl-1,2,4-oxadiazin-5-ones bearing an easily functionalizable (methoxycarbonyl)methyl group at position 6 via the reaction of aryl or hetaryl amidoximes with maleates or fumarates. The conditions for this reaction were optimized. Different products can be synthesized selectively in good yields depending on the base used and the ratio of reactants: substituted (1,2,4-oxadiazin-6-yl)acetic acids, corresponding methyl esters, or hybrid 3-(aryl)-6-((3-(aryl)-1,2,4-oxadiazol-5-yl)methyl)-4-1,2,4-oxadiazin-5(6)-ones. The reaction is tolerant to substituents' electronic and steric effects in amidoximes. As a result, a series of 2-(5-oxo-3-(-tolyl)-5,6-dihydro-4-1,2,4-oxadiazin-6-yl)acetic acids, their methyl esters, and 1,2,4-oxadiazoles based on them were prepared and characterized by HRMS, H, and C NMR spectroscopy. The structures of three of them were elucidated with X-ray diffraction.
我们开发了一种简便的方法，通过芳基或杂芳基羟胺与马来酸酯或富马酸酯反应，在 6 位具有可易功能化的（甲氧基羰基）甲基的 3-芳基和 3-杂芳基-1,2,4-噁二唑-5-酮的合成。优化了该反应的条件。根据所用碱和反应物的比例，可以选择性地以良好的收率合成不同的产物：取代的（1,2,4-噁二唑-6-基）乙酸、相应的甲酯或杂 3-(芳基）-6-((3-(芳基）-1,2,4-噁二唑-5-基)甲基）-4-1,2,4-噁二唑-5(6)-酮。该反应对羟胺中取代基的电子和空间效应具有耐受性。结果，制备并通过高分辨质谱、H 和 C NMR 光谱对一系列基于 2-(5-氧代-3-(- 甲苯基）-5,6-二氢-4-1,2,4-噁二唑-6-基）乙酸、其甲酯和 1,2,4-噁二唑的它们进行了表征。其中三个的结构通过 X 射线衍射进行了阐明。
