Organic Synthesis and Reaction Pathways

Organic synthesis is the art and science of building target molecules from simpler starting materials using a sequence of reactions. This lesson brings together all the reactions and functional group interconversions from the course into coherent reaction pathway maps. Understanding these pathways — and being able to plan multi-step syntheses — is one of the highest-level skills tested at A-Level.

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Key Functional Group Interconversions

The table below summarises the major reactions and the reagents/conditions needed to convert between functional groups. This is your "toolkit" for synthesis planning.

Starting material	Product	Reagents and conditions	Reaction type
Alkane	Halogenoalkane	X₂ (Cl₂ or Br₂), UV light	Free radical substitution
Alkene	Alkane	H₂, Ni catalyst, 150°C	Catalytic hydrogenation (addition)
Alkene	Halogenoalkane	HBr (or HCl, HI)	Electrophilic addition
Alkene	Dihalogenoalkane	Br₂ (or Cl₂)	Electrophilic addition
Alkene	Alcohol	H₂O, H₃PO₄ catalyst, 300°C, 60 atm	Electrophilic addition (hydration)
Halogenoalkane	Alcohol	NaOH(aq), reflux	Nucleophilic substitution
Halogenoalkane	Nitrile	KCN in ethanol, reflux	Nucleophilic substitution
Halogenoalkane	Amine	Excess NH₃ in ethanol, heat in sealed tube	Nucleophilic substitution
Halogenoalkane	Alkene	NaOH in ethanol, reflux	Elimination
Alcohol (1°)	Aldehyde	K₂Cr₂O₇ / H₂SO₄, distil	Oxidation
Alcohol (1°)	Carboxylic acid	Excess K₂Cr₂O₇ / H₂SO₄, reflux	Oxidation
Alcohol (2°)	Ketone	K₂Cr₂O₇ / H₂SO₄, reflux	Oxidation
Alcohol	Alkene	Conc. H₂SO₄ or H₃PO₄, heat	Elimination (dehydration)
Alcohol + carboxylic acid	Ester	Conc. H₂SO₄ catalyst, reflux	Esterification (condensation)
Alcohol + acyl chloride	Ester	Room temp	Acylation
Aldehyde	Primary alcohol	NaBH₄(aq)	Reduction
Ketone	Secondary alcohol	NaBH₄(aq)	Reduction
Aldehyde/ketone	Hydroxynitrile	HCN (KCN + dilute H₂SO₄)	Nucleophilic addition
Nitrile	Carboxylic acid	Dilute HCl or H₂SO₄, reflux	Hydrolysis
Nitrile	Primary amine	LiAlH₄ in dry ether	Reduction
Carboxylic acid	Primary alcohol	LiAlH₄ in dry ether	Reduction
Carboxylic acid + amine	Amide (+ H₂O)	Heat	Condensation
Acyl chloride + amine	Amide (+ HCl)	Room temp	Acylation
Benzene	Nitrobenzene	Conc. HNO₃ + conc. H₂SO₄, <55°C	Electrophilic substitution
Nitrobenzene	Phenylamine	Sn + conc. HCl, reflux; then NaOH	Reduction
Benzene	Bromobenzene	Br₂ + AlBr₃ catalyst	Electrophilic substitution
Benzene	Alkylbenzene	RCl + AlCl₃ catalyst, reflux	Friedel-Crafts alkylation
Benzene	Acylbenzene	RCOCl + AlCl₃ catalyst, reflux	Friedel-Crafts acylation

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Reaction Pathway Map — Aliphatic Compounds

The following shows how the major aliphatic functional groups are interconnected:

                         Alkane
                           |
                   X₂, UV light (free radical sub.)
                           |
                           v
    Alkene <---------- Halogenoalkane ----------> Nitrile
      |   NaOH/ethanol     |    KCN/ethanol       |
      |   (elimination)     |                       |
      |                     | NaOH(aq)              | dil. acid/reflux
      |                     | (nucleophilic sub.)   |       | LiAlH₄
      |                     v                       v       v
      +--------------> Alcohol              Carboxylic   Primary
      H₂O/H₃PO₄           |                  acid       amine
      (addition)           |
                    K₂Cr₂O₇/H₂SO₄
                     /           \
              distil              reflux
               /                     \
              v                       v
          Aldehyde              Carboxylic acid
              |                       |
         NaBH₄ (red.)          + alcohol/H₂SO₄
              |                       |
              v                       v
        1° Alcohol                 Ester

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Retrosynthetic Analysis

Retrosynthetic analysis works backwards from the target molecule to available starting materials. The key steps are:

1. Identify the target molecule and its functional group.
2. Work backwards: what functional group could be converted into the target? What reagents and conditions would be needed?
3. Continue working backwards step by step until you reach available (simple) starting materials.
4. Write the synthesis forwards with all reagents and conditions.

Worked Example 1: Synthesise propan-1-ol from propene

Target: CH₃CH₂CH₂OH (propan-1-ol, a primary alcohol)

Retrosynthesis:

• Propan-1-ol ← hydrolysis of 1-bromopropane ← addition of HBr to propene (anti-Markovnikov)

But wait — Markovnikov's rule predicts that HBr + propene gives mainly 2-bromopropane (the H goes to the terminal C, Br to the middle C). To get 1-bromopropane as the major product, we would need anti-Markovnikov conditions (peroxide initiator). At A-Level, a more reliable route is:

Better route:

• Propene + H₂O / H₃PO₄ → propan-2-ol (Markovnikov addition)
• To get propan-1-ol specifically: propene + HBr → 2-bromopropane; then we are stuck because this gives the wrong isomer.

Alternative route via two steps:

• Propene + HBr → CH₃CHBrCH₃ (2-bromopropane, Markovnikov)
• This gives propan-2-ol upon hydrolysis, not propan-1-ol.