## 2 Direct \(\alpha\)-Halogenation of Aryl Ketones
### Electrophilic Halogenation
#### 2.1.3 NXS as Halogenation Agents
Another NXS-mediated halogenation in an IL, i.e., 1-methyl-3-(4-sulfobutyl)imidazol triflate ([bmim(SO\({}_{3}\)H)][OTf]), was also developed by [PERSON] (Figure 5, right) [78]. Remarkably, the selectivity of the procedure was highly dependent on the type of halogenation carried out. In general, \(\alpha\)-iodination of aromatic ketones was exclusively obtained, while a mixture of \(\alpha\)- and \(\alpha\),\(\alpha\)-dihalogenated product was observed for the bromination, with the former species as the major product. Upon increasing the reaction time, this ratio could be shifted to selectively obtain the latter product. The chlorination exclusively yielded the dihalogenated aryl ketones. The authors claim that [bmim(SO\({}_{3}\)H)][OTf] could be recycled and reused for up to eight consecutive runs without any observable loss in halogenation efficiency. The sustainable character of this route and its versatility make it stand out from other halogenation routes. Achieving a good reaction performance under solvent-free conditions is an important step forward for any reaction and is good practice for future advancement in sustainable chemistry. [PERSON] reported the solvent-free halogenation of acetophenone derivatives, mediated by sub-stoichiometric amounts of \(p\)TsOH (Scheme 24) [79; 80]. The reagents were ground in a mortar with a pestle, yielding \(\alpha\)-bromo, \(\alpha\)-chloro and \(\alpha\)-iodoketones in satisfactory yields. This procedure could be applied to the bromination, chlorination, and iodination of ketones. In the case of the chlorination, dichlorination of the substrates was a serious issue. Note that thus far, this dichloromethane issue has been mentioned several times. Furthermore, trimethoxy-substituted ketones generated exclusive ring bromination. Interestingly, performing the bromination reactions in an aqueous solvent shifted the selectivity of this route toward ring bromination. Figure 5: Ionic liquids as halogenation solvents. In 2003, [PERSON] and co-workers published a solvent-free iodination of aromatic ketones mediated by NIS (1.2 equiv.) and \(p\)TSMH (1.2 equiv.) [81]. Five \(\alpha\)-iodoketones were obtained within 1-1.2 min in good to excellent yields (75-90%) after irradiation of the reaction mixture in a microwave at 700 W. The system stood out from other direct iodination routes mainly due to its short reaction times and excellent performance. In 2015, [PERSON] and co-workers reported catalyst-free bromination in neat conditions [82]. Under these conditions, the ketone and NBS (1.1 equiv.) were ground in a mortar in order to obtain a homogenous solid mixture, which was subsequently irradiated in the MW at 300 W for 1-4 min. Ten \(\alpha\)-bromoketones were obtained in good to excellent yields (82-93%). This protocol tolerated the presence of electron-donating and -withdrawing substituents on the aromatic ring. However, a significant decrease in bromination yield was observed for dimethoxy- and nitro-substituted aryl ketones. The recycling strategy of NBS, developed by [PERSON], the solvent- and catalyst-free nature as well as the short reaction times, highlighted the sustainable character of this methodology.