## 2 Direct \(\alpha\)-Halogenation of Aryl Ketones
### Electrophilic Halogenation
#### 2.1.2 I\({}_{2}\) as Halogenation Agent  
In the direct iodination of ketones, [PERSON] and co-workers established an effective iodination route consisting of I\({}_{2}\) (0.5 equiv.) and 30% aqueous H\({}_{2}\)O\({}_{2}\) (0.6 equiv.) in methanol [48]. This system was only effective in the presence of an acid catalyst. The authors compared the efficacy of two catalytic systems; H\({}_{2}\)SO\({}_{4}\) (**cat A**; 0.1 equiv.) and H\({}_{4}\)SiO\({}_{4}\)\(\cdot\)12 WO\({}_{3}\)\(\cdot\)26H\({}_{2}\)O (POM) (**cat B**; 0.06 equiv.). Using both methods, three aromatic \(\alpha\)-iodoketones were obtained in good to excellent yields (Scheme 8). The excellent iodine atom economy of this route should be stressed, as every I-atom is incorporated in the substrate. This method prevented the long-term persistence of harmful HI in the reaction mixture. In 2007, [PERSON] updated the procedure by substituting the aqueous H\({}_{2}\)O\({}_{2}\) with the solid urea-H\({}_{2}\)O\({}_{2}\) (UHP) complex. This yielded a solvent-free direct iodination, though an increase in the I\({}_{2}\) content from 0.5 to 1 equivalent was required [49]. The excellent iodine atom economy was thus not maintained. Furthermore, the iodination yields (22-58%)dropped significantly compared to those obtained from the previous route. Subsequently, it was demonstrated that both the I2/H2O2- and I2/UHP-mediated iodination could be performed in an ionic liquid (IL), thus easing the purification process [50]. The reaction was performed in both water-miscible and water-immiscible ILs, respectively, 1-butyl-3-methyl imidazolium tetrafluoroborate ([bmim]BF4) and 1-butyl-3-methyl imidazolium hexafluorophosphate ([bmim]PF6) (Scheme 9). Experimental data demonstrated that the substrates were less effectively iodinated in both ILs, compared to the solvent-free [49] and MeOH iodination protocols [48]. Additionally, [PERSON] reported a sodium nitrite-catalysed procedure (Scheme 10, method A) [51]. NaNO2 is activated via treatment with silica-supported sulfuric acid. After activation, HNO2 is obtained, which is then oxidised by air to NO2. Since only 0.5 equiv. of I2 is used, after depletion of all I2 molecules, the obtained HI will then react with NO2 to reform I2 and NO; the latter is then again oxidised to NO2 by air. In this manner, 100% of iodine atom economy was achieved as only 0.5 equivalent of iodine was required for the reaction to proceed to completion. The sustainability of this route was further demonstrated, as air was used as the stoichiometric oxidant. Compared to other iodination routes, the purification was more straightforward as it only required separation from the inorganic salts. Due to the inherent health hazards linked to SiO2 [52; 53; 54], this procedure was later modified (Scheme 10, method B) [55]. The iodination was carried out in an aqueous sodium dodecyl sulphate (SDS) solution and promoted by H2 SO4. The SDS micelles acted as an ideal promotor of the \(x\)- iodination of aryl ketones. This route displayed excellent selectivity as side chain functionalisation was exclusively obtained. This could be shifted towards aromatic ring iodination by changing the reaction medium to acetonitrile. The 100% iodine atom economy and the use of an aqueous reaction medium showcased the promising potential of the SDS-promoted route. From an economic point of view, this route is particularly interesting as it employed cheap and abundant reagents. Nonetheless, the presence of H2 SO4 in the reaction medium still limited the substrate scope, as acid-sensitive functional groups (e.g., OH) are not compatible with these experimental conditions. In 2014, an alternative method was developed using NH4 NO3 (0.1-0.25 equiv. ), I2 (0.5 equiv. ), H2 SO4 (0.05-0.125 equiv.) and air in CH3 CN (Scheme 11) [56]. Under these conditions, several ketones were iodinated in moderate to excellent yields (58-90%). In addition, OH-substituted aromatic ketones were successfully transformed into their iodinated analogues.