6 Friedel-Crafts Reaction.pdfVIP

WuXi AppTec Friedel-Crafts Reaction Training Committee Jinhua Yang Developed by Charles Friedel and James Crafts in 1877 Friedel-Crafts alkylation is a reversible reaction, alkyl Electrophilic aromatic substitution groups can be removed in the presence of protons and a Two main types: Lewis acid RCl R The product is more nucleophilic than the reactant due to AlCl3, reflux the electron donating alkyl chain: over alkylation will occur anhydrous solvent Fr iedel-Cr afts Alkylation Vinylic halides and aryl halides do not form carbocations O under conditions of the Friedel-Crafts reaction and so can RCOCl or RCO O 2 not be used in place of an alkyl or acyl halide. R AlCl3, reflux anhydrous solvent Not limited to alkyl halides, applicable to any carbocationic intermediate derived from: Friedel-Cr afts Acylation Alkenes or alcohols, enones, epoxides General Mechanism: CH3 0 oC Cl + AlCl3 + + AlCl4- + CH CH CH 3 2 CH3 HF Isopropyl Chloride + H 0 oC + + + HF Carbocation Arenium ion 60 oC + H CH3 + HO C H CH3 + HX BF3 Arenium ion Isopropylbenzene WuXi AppTec Friedel-Crafts Reaction Training Committee Jinhua Yang Rearrangement Acylation C CH CH CCl CH C+ - AlCl3 3 3 CH CH CH 3 + AlCl 3 + AlCl 2 3 2 3 CH C O 4 + CH CHCH Cl O O 3 3 2 2 NOT Acylium ion 66% H H2 H + H CH3 H C C Cl AlCl + CH C+ 3 3 H C CH 3 O 3 2 CH3 CH3 O O + H CH3 Rearrangement will happen if the halide is not on a tertiary O CH3 + H+ Carbon. Relative stability of the tertiary carbocation over the second and primary carbocations. Carboxylic acid anhydrides can also serve as sources of acyl cations in presence of AlCl3. Product determined by the relative stability of the Carbocations. Acyl cations are relatively stable, do not rearrange: How to make the following compound then O O CH CH CH 2 3 2 R R More stable Less stable Hit: consider Friedel-Crafts acylation Due to ele