Question

Design a retrosynthetic pathway to synthesize ibuprofen starting from methylcyclohexane. Show all necessary reagents and the key steps involved in the synthesis.

Answer 1

To synthesize ibuprofen from methylcyclohexane, we can follow these retrosynthetic steps:1. Convert the carboxylic acid group of ibuprofen to an aldehyde.2. Disconnect the benzene ring from the aliphatic chain.3. Convert the benzene ring to a cyclohexane ring.Here is the forward synthesis pathway:1. Oxidation of methylcyclohexane to cyclohexanone:   Reagents: KMnO4, H2O, H2SO4  dilute    Conditions: Reflux, 1-2 hours2. Baeyer-Villiger oxidation of cyclohexanone to -caprolactone:   Reagents: mCPBA  meta-chloroperoxybenzoic acid  or H2O2, trifluoroacetic acid  TFA    Conditions: Room temperature, 1-2 hours3. Hydrolysis of -caprolactone to 6-hydroxyhexanoic acid:   Reagents: H2O, H2SO4  dilute    Conditions: Reflux, 1-2 hours4. Oxidation of 6-hydroxyhexanoic acid to adipic acid:   Reagents: KMnO4, H2O, H2SO4  dilute    Conditions: Reflux, 1-2 hours5. Wittig reaction of adipic acid with benzyltriphenylphosphonium chloride to form the alkene:   Reagents:  a  PPh3, benzyl bromide, K2CO3, DMF  to form benzyltriphenylphosphonium bromide               b  n-BuLi, THF  to form the phosphonium ylide               c  Adipic acid, THF   Conditions:  a  Room temperature, 1-2 hours                b  -78C, 1 hour                c  -78C to room temperature, 1-2 hours6. Hydrogenation of the alkene to form ibuprofen:   Reagents: H2, Pd/C   Conditions: Room temperature, 1-2 hoursThis synthesis pathway involves six steps, starting from methylcyclohexane and using various reagents and conditions to achieve the desired product, ibuprofen.