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Organic synthesis (A Level)

A-Level Chemistry 9701 · Topic 36 revision notes

Everything from the 1 lessons of this topic on a few pages: the key idea of each lesson, the diagram to remember, the points to learn and the traps examiners set. Read it, cover it, test yourself.

  1. Multi-step organic synthesis

1Multi-step organic synthesis

Syllabus 36.1

Organic synthesis means getting from a starting material to a target using reactions you know. First identify every functional group in each molecule (arene, phenol, alcohol, halogenoalkane, alkene, aldehyde or ketone, carboxylic acid, ester, acyl chloride, amine, amide, nitrile) and predict how each reacts with the reagent given. Then work backwards from the target: what group must the previous compound have had? Each step needs a reagent, conditions and a reaction type (electrophilic substitution, nucleophilic addition, reduction, oxidation, hydrolysis, condensation). Nucleophilic addition to a planar C=O, such as HCN with ethanal, can create a chiral centre as a racemic mixture, but drugs are often needed as a single enantiomer. Yields multiply: the overall yield is the product of the step yields, so short routes are better.

benzeneC₆H₆ nitrobenzeneC₆H₅NO₂ phenylamineC₆H₅NH₂ azo dyeC₆H₅N=NC₆H₄OH methylbenzeneC₆H₅CH₃ benzoic acidC₆H₅COOH benzoyl chlorideC₆H₅COCl ester or amideC₆H₅COOR propanoneCH₃COCH₃ hydroxynitrile(CH₃)₂C(OH)CN hydroxy acid(CH₃)₂C(OH)COOH achiral: two CH₃on the same C 123 456 78 1 conc. HNO₃ + conc. H₂SO₄, 25–60 °C 2 Sn + conc. HCl, reflux; then NaOH(aq) 3 HNO₂ below 10 °C; then phenol, OH⁻ 4 hot alkaline KMnO₄; then dilute H⁺ 5 SOCl₂ or PCl₅ 6 ROH (ester), RNH₂ (amide) 7 HCN with KCN catalyst 8 dilute HCl(aq), heat under reflux numbers on the arrows match the reagent key
Fig. 1: three A Level routes on one reaction map, with reagents for each numbered step

Groups, reagents, types, yield.

  • Label every group before choosing a reagent.
  • Work backwards from the target, one group at a time.
  • Each step: reagent, conditions, reaction type.
  • Overall yield: multiply the step yields.

Watch out!

Do not add or average step yields: multiply them. Give conditions as well as reagents (reflux, temperature, catalyst) and say dilute or concentrated. Diazotisation must be kept below 10 °C or the diazonium salt decomposes. Sn/HCl reduction needs NaOH(aq) afterwards to free the amine from its salt. Check whether a carbonyl product is chiral before claiming a racemic mixture, and remember that one reagent attacks every group that responds to it.

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