Direct Transition-metal-free C-O Bond Formation For The Synthesis Of Benzoxazoles

Benzoxazole derivatives are a class of privileged heterocyclic structures which are frequently found in a diverse array of compounds such as natural products, biologically and therapeutically active agents and functional materials. Benzoxazoles have been widely used in fungicides, anticancer and antivirus drugs, and so play important roles in medicinal chemistry. Therefore, the efficient construction of benzoxazoles has great significance in both lab research and potential application.This thesis reported on a weak base-promoted intramolecular carbon-oxygen bond formation of o-haloanilides to afford benzoxazoles in high yields. On the reaction examining the effect of various factors, including temperature, solvent and base. The optimum reaction conditions for the intramolecular cyclization of o-haloanilides are 140℃for 8-48h, DMSO as the solvent, K2CO3 as the base, which gives the yields of benzoxazoles up to 96%.With the optimum reactions conditions in hand, this thesis explored the influence of functional groups with different electronic nature to the yields of purpose products. The results indicated that the yields were good to excellent when the substrates with electron-donating or weakly electron-withdrawing groups were used. However there were low yields or even no desired products when the substrates with strongly electron-withdrawing groups were used. Different ortho-halogen substituted substrates had different reactivity, which follows the sequence of I>Br>Cl. In the end this thesis explored the reaction mechanism and proposed benzyne-type mechanism.This thesis has established a practical, inexpensive and easy-to-handle method for direct synthesis of benzoxazoles without transition-metal. This chemical process provides a novel and efficient synthetic protocol for benzoxazole derivatives.