Unusual Formation of 1,2,4-Oxadiazine Core in Reaction of Amidoximes with Maleic or Fumaric Esters
Sofia I. Presnukhina,
Marina V. Tarasenko,
Kirill K. Geyl,
Svetlana O. Baykova,
Sergey V. Baykov,
Anton A. Shetnev,
Vadim P. Boyarskiy
Affiliations
Sofia I. Presnukhina
Institute of Chemistry, Saint Petersburg State University, 7/9 Universitetskaya Nab., 199034 Saint Petersburg, Russia
Marina V. Tarasenko
Pharmaceutical Technology Transfer Centre, Yaroslavl State Pedagogical University Named after K.D. Ushinsky, 108 Respublikanskaya St., 150000 Yaroslavl, Russia
Kirill K. Geyl
Institute of Chemistry, Saint Petersburg State University, 7/9 Universitetskaya Nab., 199034 Saint Petersburg, Russia
Svetlana O. Baykova
Institute of Chemistry, Saint Petersburg State University, 7/9 Universitetskaya Nab., 199034 Saint Petersburg, Russia
Sergey V. Baykov
Institute of Chemistry, Saint Petersburg State University, 7/9 Universitetskaya Nab., 199034 Saint Petersburg, Russia
Anton A. Shetnev
Pharmaceutical Technology Transfer Centre, Yaroslavl State Pedagogical University Named after K.D. Ushinsky, 108 Respublikanskaya St., 150000 Yaroslavl, Russia
Vadim P. Boyarskiy
Institute of Chemistry, Saint Petersburg State University, 7/9 Universitetskaya Nab., 199034 Saint Petersburg, Russia
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)-4H-1,2,4-oxadiazin-5(6H)-ones. The reaction is tolerant to substituents’ electronic and steric effects in amidoximes. As a result, a series of 2-(5-oxo-3-(p-tolyl)-5,6-dihydro-4H-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, 1H, and 13C NMR spectroscopy. The structures of three of them were elucidated with X-ray diffraction.
