Study On Synthetic Methodologies Of Oxazoles

Synthesis and bioactivity study of oxazoles, benzoxazoles and 2-acylbenzoxa- zoles is one of the most important fields in heterocycle pesticide, medicinal, optical material and fire-proof material. Recently more and more synthetic chemists paid attention to the synthetic methodologies of oxazoles,benzoxazoles and 2-acylbenzox- azoles.In continuation of our studies towards heterocycle compounds, we studied the reaction of N-(2-hydroxyphenyl)propionamide under POCl₃/DMF and got 2-acyl- benzoxazole with a yield of 20.8%. After mechanism investigation, we found that 2-acylbenzoxazole was converted from 2-ethylbenzoxazole which from N-(2-hydroxy- phenyl)propionamide under POCl₃/DMF condition. Whileα-acetamidone under the same condition, 2, 4, 5-trisubstitued oxazoles was formed.In the course of preparation of the starting materialα-acetamidone fromα-oxo-oxime, the sterically hindranceα-oxo-oxime was converted to ketone under Zn/HOAc condition. The transformation commences from the reduction ofα-oxo- oxime toα-aminoketone mediated by Zn/HOAc followed by a deamination.Aliphatic acids, aromatic acids andβ-aryl-α,β-unsaturated acids reacted with o-aminophenol under POCl₃ in refluxing CHCl₃, 2-alkyl, 2-aryl and 2-styryl benzoxazoles was formed respectively. The optimization of reaction conditions, including reaction temperature, solvent, carboxylic acid's activity and the ratio among the reagents was then investigated. The results shown that the carboxylic acid's activity played an important role among the reaction conditions. Under the optimal conditions, reactions of a range of carboxylic acid with POCl₃ were carried out in CHCl₃ at refluxing. All the reactions proceeded to afford the corresponding 2-alkyl, 2-aryl and 2-styryl benzoxazoles correspondingly. Whileα- acetamidones under the same condition, 2, 4 ,5-trisubstitued oxazoles formed in good to excellent yields.