What is organic synthesis?
Synthesis means building something. In organic synthesis we build a target molecule from simple, cheap starting materials (often from crude oil or plants) using one or more reactions.
Each reaction usually changes a functional group, the reactive part of a molecule (for example –OH in alcohols or –COOH in acids). Changing one group into another is called functional group interconversion.
The ideas you need: which reactions link which families, what reagent to add, what conditions to use, and how to separate and purify the product.
The map: links between families (genetic links)
- Alkene → alkane: H₂, nickel catalyst, about 150 °C (hydrogenation).
- Alkane → haloalkane: Cl₂ or Br₂, UV light (free-radical substitution).
- Alkene → haloalkane: HBr, room temperature (electrophilic addition).
- Alkene → alcohol: steam, H₃PO₄ catalyst, 300 °C, 60 atm (hydration).
- Haloalkane → alcohol: NaOH(aq), heat under reflux (nucleophilic substitution).
- Haloalkane → alkene: NaOH in ethanol, heat (elimination).
- Haloalkane → amine: excess NH₃ in ethanol, heat in a sealed tube.
- Haloalkane → nitrile: KCN in ethanol, reflux. This adds one carbon to the chain; the nitrile can be hydrolysed to an acid.
- Alcohol → alkene: conc. H₂SO₄ or hot Al₂O₃ (dehydration).
- Primary alcohol → aldehyde → carboxylic acid: acidified K₂Cr₂O₇; secondary alcohol → ketone.
- Acid + alcohol → ester: conc. H₂SO₄ catalyst, heat (esterification).
Because each family can be made from another, chemists call these the genetic links between classes of organic compounds.
Choosing reagents and conditions
The same reagent can give different products under different conditions:
- Oxidising ethanol with acidified dichromate: distil off the product as soon as it forms → ethanal (aldehyde). Heat under reflux (vapour condenses and drips back) → ethanoic acid.
- Bromoethane + NaOH: in water → ethanol (substitution); in ethanol → ethene (elimination).
Good choices also think about selectivity (only the wanted group reacts), safety (avoid toxic KCN if another route exists), cost and energy. Sometimes a reactive group is protected during a step and freed later.
Planning backwards: retrosynthesis
Start from the target and ask: "Which compound could I make this from in one step?" Repeat until you reach something simple you can buy. Then read the chain forwards.
Example: target ethyl ethanoate (an ester). Ester ← ethanoic acid + ethanol. Ethanoic acid ← ethanol (oxidise under reflux). Ethanol ← ethene + steam. So from ethene alone: make ethanol, oxidise part of it to the acid, then react acid + ethanol.
Count carbons! If the target has one more carbon than the start, you need a C–C bond-forming step (for example making a nitrile).
Yield, atom economy and green chemistry
Percentage yield = actual mass ÷ theoretical mass × 100. In a multi-step route, the overall yield is the product of the step yields: three steps of 80% give 0.8³ = 51.2%.
Atom economy = mass of wanted product ÷ total mass of all products × 100. Addition reactions have 100% atom economy; substitutions and eliminations waste atoms.
Green chemistry: fewer steps, safer solvents (water), catalysts instead of large amounts of reagents, renewable starting materials, less waste and energy.
In the lab: make, separate, purify, check
- React: heat under reflux so volatile liquids do not escape.
- Separate: distillation, or a separating funnel to remove the water layer; filter a solid.
- Purify: wash with sodium carbonate solution to remove acid, dry with anhydrous salt, redistil; recrystallise a solid from minimum hot solvent.
- Check purity: a sharp melting point or boiling point that matches the data book; one spot on thin-layer chromatography; IR or NMR spectra.
Try it: plan a route
Use the free-play step. Pick "Carboxylic acid" and write the reagents for each step before reading the caption. Then set the yield to 70% and predict the overall yield before checking. Challenge: plan a route from ethane to ethyl ethanoate on paper. How many steps? What overall yield at 80% per step?
Key formulas and definitions
- CH₂=CH₂ + H₂O → CH₃CH₂OH (H₃PO₄, 300 °C, 60 atm)
- CH₃CH₂OH + [O] → CH₃CHO + H₂O (distil)
- CH₃CHO + [O] → CH₃COOH (reflux)
- CH₃COOH + CH₃CH₂OH ⇌ CH₃COOCH₂CH₃ + H₂O (conc. H₂SO₄)
- CH₃CH₂Br + NaOH(aq) → CH₃CH₂OH + NaBr
- CH₃CH₂Br + KCN → CH₃CH₂CN + KBr (adds one carbon)
- Overall yield = y₁ × y₂ × y₃ × …
- Atom economy = M(wanted product) ÷ M(all products) × 100%
Worked examples
1. Suggest a two-step route from ethene to ethanoic acid, with reagents and conditions.
Step 1: ethene + steam, H₃PO₄ catalyst, 300 °C, 60 atm → ethanol. Step 2: ethanol + acidified potassium dichromate, heat under reflux → ethanoic acid (orange → green).
2. A route has steps with yields 90%, 75% and 60%. Find the overall yield.
0.90 × 0.75 × 0.60 = 0.405, so 40.5%.
3. How can you make propanoic acid (3 C) from bromoethane (2 C)?
You need one more carbon. Step 1: bromoethane + KCN in ethanol, reflux → propanenitrile, CH₃CH₂CN. Step 2: hydrolyse by heating with dilute acid → propanoic acid, CH₃CH₂COOH.
4. Calculate the atom economy for making ethanol from bromoethane: C₂H₅Br + NaOH → C₂H₅OH + NaBr. (C₂H₅OH = 46, NaBr = 103)
Atom economy = 46 ÷ (46 + 103) × 100 = 46 ÷ 149 × 100 ≈ 30.9%. The hydration of ethene gives ethanol with 100% atom economy, so it is greener.
Common mistakes
- Writing only the reagent and forgetting conditions. "K₂Cr₂O₇/H⁺" alone does not tell whether you get aldehyde or acid; say "distil" or "reflux".
- Adding yields instead of multiplying them. Three steps of 80% give 51.2%, not 80% or 240%.
- Forgetting to count carbons. Most interconversions keep the chain length; you need a C–C step (such as KCN) to add a carbon.
- Mixing aqueous and ethanolic NaOH: aqueous gives substitution (alcohol), ethanolic gives elimination (alkene).