Synthesis of Substituted Benzo[1, 4]oxazine Derivatives from the Reaction of Trichloroacetonitrile-nitro Compound Adduct and 2-Iodophenol.

INTRODUCTION: This study reports a rapid, efficient, and simple ultrasound-assisted protocol for the synthesis of 3-(trichloromethyl)benzo[1,4]oxazine from a one-pot cross-coupling reaction of trichloroacetonitrile-nitro compound adduct and 2-iodophenol in MeCN solvent, by using CuI (10 mol% %) as the catalyst, and KOH as the active base under ultrasonic conditions for 50 minutes at room temperature with optimal efficiency. METHODS: The reaction of nitromethane (or ethane) with trichloroacetonitrile for 10 minutes, with the addition of sodium hydride as base, led to the formation of a nitro compoundtrichloroacetonitrile adduct. The reaction of the formed compound with various 2-iodophenol derivatives having electron-donating and electron-withdrawing groups in the presence of the necessary copper iodide catalyst for the coupling reaction further led to the synthesis of new 3- (trichloromethyl) benzo [1,4] oxazine derivatives. RESULTS: The role of ultrasound is to reduce the reaction time, increase the efficiency of product preparation, and facilitate separation. DISCUSSION: Considering the potential of the synthesized derivatives, which contain the CCl3 group as a leaving group, these compounds were investigated for reactions with isocyanides in MeCN. Some of the advantages of this method include the use of inexpensive, readily available starting materials and catalysts, performing the reaction at room temperature for a short time using ultrasound, easy purification, and high efficiency. CONCLUSIONS: Finally, 19 new heterocyclic compounds from the benzo[1,4]oxazine family were synthesized in this study under ultrasonic conditions, using a simple, rapid, and efficient method.