Construction of the Benzoxazole Ring

Benzoxazoles are classically created through the cyclization of a 2-aminophenol with a carboxylic acid under highly acidic conditions at elevated temperatures. Alternatively, the amine of a 2-aminophenol is acylated and subsequently subjected to a number of cyclodehydration 

Several reagents have been shown to convert 2-hydroxyaryloximes into benzoxazoles through a Beckmann rearrangement. Zeolite catalysis in a continuous flow reactor has been shown to be successful in benzoxazole formation,as has diethyl chlorophosphate and POCI3. Rindhe and coworkers utilized POCI3 in the formation of pyrazolyl benzoxazoles for use as antimicrobial agents. 

Under solid-phase reaction conditions, benzoxazoles can be prepared through a Mitsunobu reaction. The mild reaction conditions of the Mitsunobu alleviate the hazards associated with other strongly acidic conditions. 

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