Friedel-Crafts acylation reactions solubility

Mikami s group has also demonstrated the advantage of the fluorous super-Lewis acids such as lanthanide tris(perfluorooctanesulfonyl)methide and perfluorooctane-sulfonimide complexes with respect to temperature-dependent solubility [13bj. For example, these complexes can be re-used for the Friedel-Crafts acylation reaction without fluorous solvents [Eq. (11)]. After the reaction mixture of anisole has been heated with acetic anhydride in 1,2-dichloroefhane in the presence of ytterbium perfluorooctanesulfonimide (10 mol%) at 80 °C for 6 h, the mixture is allowed to stand at -20 °C for 30 min to precipitate the ytterbium complex. The liquid phase is decanted and the residual lanthanide complex is re-used without isolation. No loss of activity is observed for the catalyst recovered. The total isolated yield of the product, which is combined from the three runs, is 78%. 

Cross-linked polystyrene can be acylated with aliphatic and aromatic acyl halides in the presence of A1C13 (Friedel-Crafts acylation, Table 12.1). This reaction has mainly been used for the functionalization of polystyrene-based supports, and only rarely for the modification of support-bound substrates. Electron-rich arenes (Entry 3, Table 12.1) or heteroarenes, such as indoles (Entry 5, Table 15.7), undergo smooth Friedel-Crafts acylation without severe deterioration of the support. Suitable solvents for Friedel-Crafts acylations of cross-linked polystyrene are tetrachloroethene [1], DCE [2], CS2 [3,4], nitrobenzene [5,6], and CC14 [7]. As in the bromination of polystyrene, Friedel-Crafts acylations at high temperatures (e.g. DCE, 83 °C, 15 min [2]) can lead to partial dealkylation of phenyl groups and yield a soluble polymer. 

Hafnium(IV) bis(perfluorooctanesulfonyl)amide complex Hf[N(S02C8F17)2]4 is a highly reactive and recyclable Lewis add catalyst in Friedel-Crafts acylation and Prins reactions in fluorous biphasic systems at low catalyst loadings (<1 mol%) (Equation 4.23). In these reactions, Hf[N(S02C8F17)2]4 is selectively soluble in the fluorous phase and can be recovered after reaction by simple phase separation. In addition, the catalyst can be reused without any loss of activity [44],... 

The high reactivity of ferrocene toward electrophilic substitution was described earlier. Similar reactions of arene Ti-complexes result in the cleavage of the complexed bonds. For example, Friedel-Crafts acylation, metalation with butyllithium, mercuration, or nitration of ditoluenechromium, which is more soluble in organic solvents than the slightly soluble dibenzenechro-mium, failed to give any substitution products. 

The reusability of the catalyst is one of the major advantages of using RE(OTf)3 as a Friedel-Crafts catalyst. RE(OTf)3 can be easily recovered from the reaction mixture by simple extraction. The catalyst is soluble in the aqueous layer rather than in organic layer, and is recovered by removing water to give a crystalline residue, which can be re-used without further purification. The efficiency of recovery and the catalytic activity of the reused RE(OTf)3 were examined in the reaction of 1 with acetic anhydride using Yb(OTf)3 and Sc(OTf)3. As shown in Table 7, more than 90% of Yb(OTf)3 and Sc(OTf)3 were easily recovered, and the yields of acylation product 2 in the second and the third uses were almost the same as in the first. 

Di- and poly-acylated products are often water soluble, and so require care in isolation. Low recoveries of desired products from aliphatic Friedel-Crafts monoacylations may suggest that over reaction is leading to water-soluble products that have not been recognized, and therefore lost during work up. 

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