Study On Multicomponent Reactions For The Synthesis Of 1,3-oxazines And Hydropyridines

Heterocyclic compounds containing nitrogen or oxygen atoms generally have a broad biological activities, such as 1,3-oxazine compounds having a wide range of antitumor, anticancer and analgesic, antiseptic, insecticidal bioactivity. Therefore, the research of these compounds having become one of the hottest topics in the research and development of new drugs and new pesticides, which have a broad application prospect in the field of medicine and pesticide. In order to study the heterocyclic compounds containing nitrogen and oxygen atoms with high biological activity, and with the aim of the synthesis of functionalized 1,3-oxazine and pyridine, we developed several efficient mutlcicomponent reactions for synthesis of a novel multi-substituted 1,3-oxazine and hydropyridine derivatives.1. The multicomponent reaction of N-arylimines, dimethyl acetylenedicarboxylate and substituted isatins in anhydrous acetonitrile at room temperature afforded polysubstituted spiro[indoline-3,6’-[1,3]oxazines]. Under same conditions, the reaction with some quinones shuch as p-benzoquinone,1,4-naphthoquinone, acenaphthenequinone, and phenanthrenequinone gave diverse spirocyclic [1,3]oxazines]. The advantages of this reaction are broad substrates, simple raw materials, mild reaction conditions, and high yields. The structures of 32 obtained compounds were characterized by IR,’H NMR,13C NMR, HRMS spectra and the single crystal structures of four compounds were determined by single crystal diffraction method.2. The [2+2+2] cycloaddition reactions of N-arylimines, dimethyl acetylenedicarboxylate and arylidene malononitriles in anhydrous acetonitrile revealed a series of novel functionalized tetrahydropyridines. When isatylidene malononitriles were introduced in the reaction, the polysubstituted spiro[indoline-3,4’-pyridines] were produced in good yields and with high diastereoselectivity. Here,48 new tetrahydropyridines were successfully prepared and their structures were elucidated through IR,1H NMR,13C NMR, HRMS spectra. Six single crystal structures were determined by X-ray diffraction method.3. The multicomponent reaction of N-arylimine, dimethyl acetylenedicarboxylate and arylidene 1,3-indanedione resulted in spiro[indene-2,3’-pyridine] derivatives in good yields. Additionally, the three-component reaction of aromatic amine, dimethyl acetylenedicarboxylate and 2-amino-benzothiazole (2-aminothiazole) in dry methylene dichloride afforded benzothiazolyl connected imidazole derivatives. Here, the structures of 21 new heterocyclic compounds was identified by IR,’H NMR, 13C NMR, HRMS spectra and confirmed by determination of two single crystal structures.