Fridel-Crafts Reaction

Scheme 5.12. Asymmetric Fridel-Crafts reactions via C—H bond activation.

Whereas the Friedel-Crafts alkylations require only catalytic quantities of the Lewis acidic AICI3 catalyst, Friedel-Crafts acylations of phenols require excess Lewis acids, due to the complex formation of the Lewis acids with the hydroxyl group . Boron trifluoride-phosphoryl chloride, in stoichiometric amounts, is used for the Fridel-Crafts reaction of phenol with /3,/S-dimethylacrylic acid to give the acrylophenone. ... 

The key intermediates for the synthesis of mebendazole (14), flubendazole (15) and ciclobendazole (16) are 4-benzoyl-2-nitrohalobenzene (94a), 4-(4-fluoroben-zoyl)-2-nitrohalobenzene (94b) and 4-cyclopropylcarbonyl-2-nitrofluorobenzene (94c), respectively, which are prepared by Fridel-Crafts reaction of an acid chloride with the appropriate aromatic compounds. These substituted halobenzenes (94a-c) are converted into 14-16 as shown in scheme 4 [137-139]. 

Fig. 16 Iron activation of chiral phosphoric acid for Fridel-Crafts reaction...

In 2010, Xia, Huang and co-workers reported an iron-assisted chiral phosphoric acid catalyst for the Fridel-Crafts reaction between indole and 3-aryl a -hydroxy enones (Fig. 16) [70]. Due to the evidence from electron spray ionization mass spectrometry (ESI-MS) analysis for the presence of iron phosphate salt, an iron/ proton dual activation mechanism was proposed to account the observed reactivity/ selectivity trends. Addition of a third acid component, silver triflate, was shown to be beneficial for the enantioselectivity, presumably by exchanging chloride to the less coordinating triflate anion. 

Types of reactions such as Fridel-Crafts, Grignard, Meerwin-Ponndorf, Cannizzaro, Clemenson. Wolff-Kishner, Hofmann Degradation, Beckman Rearrangement, Simmons-Smith, Piels-Alder, Wurtz-Fitig, etc. may not be household names to everyone, but they are to many organic chemists. More importantly, literature sources can be searched for these classifications to give an overall perspective to a reaction under study. 

This reaction is related to the Fridel-Crafts Acylation. 

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