The α-Chlorination of Aryl Methyl Ketones under Aerobic Oxidative Conditions

The novel reaction system air/ammonium nitrate/iodine/hydrochloric acid [air/NH4NO3(cat.)/I-2(cat.)/HCl] is introduced as a simple, safe, cheap, efficient and regioselective mediator for the alpha-chlorination of aryl, heteroaryl and alkyl methyl ketones under aerobic oxidative conditions. The inventive use of a catalytic amount of iodine enabled the moderate to quantitative, regioselective chlorination of a comprehensive scope of different methyl ketone derivatives including those bearing oxidizable heteroatom (S, N) substituents, some of which possess declared potential biological and pharmaceutical activity. Air oxygen under a slight overpressure plays the role of the terminal oxidant catalytically activated by redox cycles of nitrogen oxides released from the catalytic amount of ammonium nitrate (NH4NO3) under acidic conditions of hydrochloric acid (HCl) and co-catalyzed by elemental iodine (I-2), which was found to be essential for the high efficiency of the reaction system.