Study On Synthesis Of2H-1,4-Benzoxazine Derivatives

2H-1,4-benzoxazine derivatives are an important class of heterocyclic molecules, most of them have biological activity. It is great significance to explore a quick and efficient method for the preparation of these derivatives. This dissertation studied them from two parts. The first part was on [5+1] cycliaztion reactions for synthesis of2,3-dihydro-1,4-benzoxazines. The second part was about a highly diastereoselective synthesis of novel spirooxindol-containg2H-1,4-benzoxazine compounds.2,3-Dihydro-1,4-benzoxazines are an important class of molecules, which are a common heterocyclic scaffold in biologically active and medicinally significant compounds. A series of functionalized2,3-dihydro-1,4-benzoxazines were obtained in moderate to excellent yields (53%-87%) via domino [5+1] annulations of2-halo-1,3-dicarbonyl compounds with imines using KOH as base and CH3CN as solvent. Application of this method in the synthesis of bioactive analogues, such as functionalized tetracyclic-1,4-benzoxazines which contain two new heterocyclic rings (benzopyran and2,3-dihydro-1,4-benzoxazine) and one quaternary carbon center has also been developed. In addition, we also have successfully demonstrated the first asymmetric synthesis with fair to good enantioselectivities, employing readily available chiral quaternary ammonium salts as organocatalysts. The absolute configuration of the substituted2,3-dihydro-1,4-benzoxazines were confirmed by the single-crystal X-ray analysis.The indole moiety represent the core structure of many important natural products and biologically active compounds. A series of novel spirooxindol-containg2H-1,4-benzoxa zine derivatives were obtained via domino Mannich-alkylation reaction of a-halocarbonyl compounds (2-bromoacetophenone and3-chloro-2,4-pentanedione) with Isatin-imines using t-BuOK as base and CH2Cl2as solvent. The advantages of this method include good yields (up to88%), high diastereoselectivity (up to99:1) and broader substrate scope. The relative stereochemistry of products were established by a single crystal X-ray analysis.