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

Abstract

The novel reaction system air/ammonium nitrate/iodine/hydrochloric acid [air/NH 4 NO 3(cat.) / I 2(cat.) /HCl] is introduced as a simple, safe, cheap, efficient and regioselective mediator for the a-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 heteroA C H T U N G T R E N N U N G atom (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 (NH 4 NO 3 ) 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.

Palladium‐Catalyzed C–C Ring Closure in α‐Chloromethylimines: Synthesis of 1H‐Indoles

“…Regular α‐chloromethyl aryl ketones 1 were commercially available. Branched α‐chloromethyl alkyl ketones 1e–f containing one quaternary α′ carbon were readily prepared by reacting the corresponding ketone with a chlorine source (Scheme , Equation (1)).…”

High-yielding aqueous synthesis of chloroacetophenones and aroyl chlorohydrins

“…51,52 The yields for the synthesis of these products reported in the literature are in the range of 36-100% and all the procedures utilize volatile organic solvents and require aqueous workups and chromatography to purify the products. 13,[34][35][36][37][38][39][40][42][43][44][45]53 In this study, external heating, organic solvents as reaction media and as elutes for chromatography were saved.…”

“…Chloroacetophenones and aroylchlorohydrins are two important intermediates in organic synthesis [27][28][29][30] and the latter are bioactive compounds. [31][32][33] Chloroacetophenones are accessible via the oxidation of acetophenones using chloride sources such as N-chlorosuccinimide, 13,34 HCl, 35,36 Cl 2 (ref. 37) or NaCl 38,39 and oxidants such as O 2 , 35 H 2 O 2 (ref.…”

Synthetic Access to Aromatic α-Haloketones

“…Stavber and co-workers demonstrated the versatility of an NH 4 NO 3 - and I 2 -based system in air [ 96 ]. The procedure yielded seven α-chloroketones in moderate to good yields ( Scheme 34 ).…”