Recent advances in the use of oxone ® in organic synthesis Maria Carla Marcotullio, Francesco Epifano and Massimo Curini Dipartimento di Chimica e Tecnologia del Farmaco-Sez. Chimica Organica, Università degli Studi, Via del Liceo, 1, 06123 Perugia, Italy 1. Abstract Oxone ® (potassium monopersulfate) is a cheap, easy to handle oxidant that can be used either in homogeneous and in heterogeneous conditions. In these last years it has been extensively employed in organic synthesis to perform a variety of transformations such as protection and deprotection of functional groups, oxidation of heteroatoms, cleavage of carbon-carbon double bonds, preparation of useful intermediates for the synthesis. 2. Introduction Persulfuric acid (H 2 SO 5 ), commonly called Caro s acid, [1] and its potassium salt are oxidasing agents known from a long time, but they have been not largely used in organic synthesis due to their explosive character. The first report for the preparation of a stable mixture of potassium persulfate, potassium hydrogen sulfate and potassium sulfate is a 1957 U.S. Patent. [2] In these last years there has been a renewed interest, expecially in potassium monopersulfate (KHSO 5 ), as it is commercially avalaible as a triple salt (2KHSO 5 KHSO 4 K 2 SO 4 ) with the registered name of Oxone ® (Dupont). Oxone ® is a white crystallin solid, easy to handle, not toxic, soluble in water and, above all, cheap and stable. The commercial triple salt contains only about 50% of active oxidant per mol and in 2002 a new procedure has been developed to prepare pure potassium monopersulfate.[3] In the past twenty years it has been used to perform a great number of oxidations in water or water miscible solvents such as methanol or DMF. To overcome the lack of solubility in common organic solvents more recently organic salts of Oxone ® have been prepared. One of the oldest is tetrabutyl ammonium persulfate (TBA-OX).[4,5] Recently Hajipour prepared a new soluble salt: benzyl-triphenyl phosphonium monopersulfate.[6,7,8] Another way to use Oxone ® in organic solvents is to support it on different solids such as Al 2 O 3 .[9] One of the most common reaction of Oxone ® is the interaction with carbonyls, with the formation of dioxiranes, or with imines, with the formation of oxaziridines, largely used in organic synthesis.[10] Beside Oxone ® itself has been used to perform several interesting oxidations some of which will be reviewed herein. 3. Halide oxidation In 1960 Kennedy and Stock studied the oxidative properties of Oxone ® towards several substrates and they reported the conversion of toluene into benzyl halide by interaction of Oxone ® with metal halides.[11] Today it is well established that Oxone ® can easily oxidise halides to halogens or hypohalite. 3.1 Halogenation of aromatic compounds Halogenation of aromatic compounds constitutes an important reaction and usually it is performed using molecular halogen in the presence of Lewis or mineral acids. This methodology is not environmetally friendly as suffers from the production of halogens and hydroalous acids. To avoid the use and the production of toxic and corrosive waste several different methods have been developed, e.g. the use of metal halides in combination of oxidants such as m-CPBA, H 2 O 2 , NaClO 2 . Recently it has been reported that treating 1 mmol of an activated arene with 1 mmol of potassium or sodium halides and 1 mmol of Oxone ® in a 3:1 [12] or 1:1 [13] mixture of acetonitrile-water at room temperature it is possible to achieve regioselectively p- substitution.