Chemical Synthesis and Design
What you must understand
Synthesis questions test whether you can plan a route from available starting materials to a target, choosing reagents and conditions and justifying them. You need functional group interconversions: oxidation of primary alcohols to aldehydes then carboxylic acids, secondary alcohols to ketones, reduction of aldehydes, ketones and carboxylic acids, esterification, hydrolysis, and addition or substitution on alkenes and haloalkanes. Know the reagents: acidified dichromate or permanganate for oxidation, LiAlH₄ or NaBH₄ for reduction, concentrated H₂SO₄ with an alcohol and carboxylic acid for esterification.
Design is judged on more than the product: consider yield, atom economy, safety, cost, waste, reaction conditions (temperature, pressure, catalyst) and purification (distillation, recrystallisation, filtration, chromatography). You should calculate percentage yield and atom economy and explain why one route is preferable.
Traps to watch
- Primary alcohols oxidise past the aldehyde unless distilled as formed; write "distil immediately" for aldehyde isolation.
- NaBH₄ is milder than LiAlH₄ and generally does not reduce carboxylic acids.
- Atom economy differs from percentage yield - a high-yield reaction can have poor atom economy if by-products are large.
- Acidified dichromate changes colour orange to green - a useful observation, but do not confuse it with pH indicator behaviour.
Worked example
Atom economy for esterification: CH₃COOH + C₂H₅OH → CH₃COOC₂H₅ + H₂O. Molar masses: 60.05 + 46.07 → 88.11 + 18.02. Atom economy = 88.11/(60.05 + 46.07) × 100 = 83.0%. Water is the by-product; a route with no by-product would have 100% atom economy.
Rule of thumb: for each step, state reagent, condition, functional group change and one reason the route is preferred.