Research On New Benzyne Chemistry And Benzyne Regioselectivity

Benzynes can be broadly applied in the syntheses of natural products, biologically active intermediates and functional materals, which are important intermediates in organic synthesis. However, the harsh reaction conditions for their preparations restricted their applications in the organic synthesis. Rencently, following the developments of mild praparation methods of benzynes, Kobayashi’s method, the great interest has been emerged for the study of novel benzyne reactions. There are three kinds of major reaction patterns of benzynes, namely precyclic reactions, nucleophilic additions and transition-metal catalyzed transformations.Although benzyne chemistry has achieved rapid development, the problems h ave not been solved in the polyfunctionalization and regioselectivity issues. In th e proceding thesis, a series of benzothiazole derivatives can be readily prepared with high yield from TPBT, a new precursor of 3-triflyoxybenzyne designed and prepared in our team. Implementation of different positions occurs on the benze ne ring of TPBT, especially the 1,2-difunctionalized aromatics and 1,2,3-trisubstit uted benzenes. This kind of product has important practical application in pharm aceutical chemistry. Benzothiazole is an important substructure in anti-tumor, anti-e pileptic and anti-inflammatory drugs. It has also been found in antibacterial, anti-in flammatory, and diabete drugs. In recent years, 2,4-disubstituted benzothiazole, esp ecially the structures containing a carboxylic or an amide group in the C-4 positio n of benzothiazole has inhibitory effect to the poly(ADP-ribose)polymerase(PAR P) target, which is a hot target for anti-tumor study in recent years..The second section of this research focuses on the regioselective control of benzyne chemistry by introducing various directing groups and coordinating with metal ions. In the beginning, we have designed a series of directing groups acco rding to the research work in other areas as our starting point. Benzynes, bearin g a directing group, are generated in situ from different benzyne precursors unde r different conditions, which will then be captured by different substrates in situ in cycloaddition reactions. At present, we get a product of the ratio of 1:1.4. Thi s topic has no conclusive results now, and it is awaiting for further investigation.