Question

What is the retrosynthesis for the synthesis of ibuprofen? Include the starting materials, reagents used and the reaction conditions involved in both the forward and backward reactions of the synthesis.

Answer 1

Ibuprofen is a widely used nonsteroidal anti-inflammatory drug  NSAID  that can be synthesized through several routes. One of the most common routes is the Boots synthesis, which involves the following retrosynthetic analysis:Target molecule: Ibuprofen1. Starting materials: Isobutylbenzene, acetic acid, and hydrochloric acid2. Reagents: Potassium permanganate  KMnO4 , sulfuric acid  H2SO4 , sodium hydroxide  NaOH , and thionyl chloride  SOCl2 3. Reaction conditions: Heating, reflux, and coolingForward synthesis:Step 1: Friedel-Crafts acylation- Reactants: Isobutylbenzene, acetic acid, and hydrochloric acid- Reagents: None- Conditions: Heating- Product: 4'-isobutylacetophenoneStep 2: Oxidation- Reactants: 4'-isobutylacetophenone- Reagents: Potassium permanganate  KMnO4  and sulfuric acid  H2SO4 - Conditions: Heating and reflux- Product: 4'-isobutyloxybenzoic acidStep 3: Saponification- Reactants: 4'-isobutyloxybenzoic acid- Reagents: Sodium hydroxide  NaOH - Conditions: Heating and reflux- Product: Sodium 4'-isobutyloxybenzoateStep 4: Acidification- Reactants: Sodium 4'-isobutyloxybenzoate- Reagents: Hydrochloric acid  HCl - Conditions: Cooling- Product: 4'-isobutyloxybenzoic acidStep 5: Esterification- Reactants: 4'-isobutyloxybenzoic acid- Reagents: Thionyl chloride  SOCl2 - Conditions: Heating and reflux- Product: IbuprofenRetrosynthesis:Step 1: Ester hydrolysis- Reactants: Ibuprofen- Reagents: Water  H2O  and a base  e.g., NaOH - Conditions: Heating and reflux- Product: 4'-isobutyloxybenzoic acidStep 2: Deprotection of the ester- Reactants: 4'-isobutyloxybenzoic acid- Reagents: Acid  e.g., HCl - Conditions: Cooling- Product: Sodium 4'-isobutyloxybenzoateStep 3: Esterification- Reactants: Sodium 4'-isobutyloxybenzoate- Reagents: Acid  e.g., HCl - Conditions: Heating and reflux- Product: 4'-isobutyloxybenzoic acidStep 4: Reduction- Reactants: 4'-isobutyloxybenzoic acid- Reagents: Reducing agent  e.g., NaBH4 - Conditions: Heating and reflux- Product: 4'-isobutylacetophenoneStep 5: Friedel-Crafts alkylation- Reactants: 4'-isobutylacetophenone- Reagents: Isobutylbenzene, acetic acid, and hydrochloric acid- Conditions: Heating- Product: Isobutylbenzene