Question

Using retrosynthesis, propose a viable route for the synthesis of ibuprofen, starting from benzene. Include all the necessary reagents and reaction steps.

Answer 1

Ibuprofen is an arylpropionic acid derivative with the chemical structure 2- 4-isobutylphenyl propanoic acid. To synthesize ibuprofen from benzene, we can follow these steps:1. Friedel-Crafts Alkylation:Reagents: Isobutyl chloride  CH3 2CHCH2Cl, AlCl3Reaction: Benzene +  CH3 2CHCH2Cl  4-isobutylbenzene2. Friedel-Crafts Acylation:Reagents: Propionyl chloride  CH3CH2COCl , AlCl3Reaction: 4-isobutylbenzene + CH3CH2COCl  4-isobutylacetophenone3. Reduction of the carbonyl group:Reagents: NaBH4 or LiAlH4Reaction: 4-isobutylacetophenone + NaBH4  4-isobutyl-1-phenylpropan-1-ol4. Oxidation of the alcohol to carboxylic acid:Reagents: Jones reagent  CrO3, H2SO4, H2O  or PCC  Pyridinium chlorochromate Reaction: 4-isobutyl-1-phenylpropan-1-ol + Jones reagent  2- 4-isobutylphenyl propanoic acid  Ibuprofen In summary, the synthesis of ibuprofen from benzene involves Friedel-Crafts alkylation with isobutyl chloride, followed by Friedel-Crafts acylation with propionyl chloride, reduction of the carbonyl group with NaBH4 or LiAlH4, and finally oxidation of the alcohol to the carboxylic acid using Jones reagent or PCC.