Coaching Centre
Reaction pathways
All the Module 7 reactions on one map, how to plan a multi-step synthesis by working backwards from the target, how to draw a reaction flow chart with reagents and conditions, and why yield, atom economy, cost and safety decide which route industry uses.
Ibuprofen was first made by a six-step route. In the early 1990s the BHC company switched to a three-step route: fewer steps meant less waste, less energy and a higher overall yield, and the process won a US Presidential Green Chemistry Award in 1997. Every organic chemist, whether making a painkiller or a perfume, plans syntheses the same way: start from the molecule you want and work backwards to something you can buy, one known reaction at a time.
The map of Module 7
Almost every reaction in this module converts one functional group into another without changing the carbon skeleton. Put them together and you get a map you can travel around:
| From → to | Reaction type | Reagents and conditions |
|---|---|---|
| alkene → alkane | addition (hydrogenation) | H₂, Ni or Pt catalyst, about 150 °C |
| alkene → dihaloalkane | addition (halogenation) | X₂, room temperature |
| alkene → haloalkane | addition (hydrohalogenation) | HX, room temperature |
| alkene → alcohol | addition (hydration) | H₂O (steam), H₃PO₄ catalyst, ~300 °C, 6–7 MPa; or dilute H₂SO₄ |
| alkane → haloalkane | substitution | X₂, UV light |
| haloalkane → alcohol | substitution | NaOH(aq), warm |
| alcohol → haloalkane | substitution | HX (conc. HCl, or NaBr + H₂SO₄ for HBr) |
| alcohol → alkene | dehydration (elimination) | conc. H₂SO₄ or H₃PO₄, heat (~170 °C) |
| 1° alcohol → aldehyde | oxidation | acidified K₂Cr₂O₇, distil off the aldehyde as it forms |
| 1° alcohol or aldehyde → carboxylic acid | oxidation | acidified K₂Cr₂O₇ or KMnO₄, heat under reflux |
| 2° alcohol → ketone | oxidation | acidified K₂Cr₂O₇ or KMnO₄, heat |
| carboxylic acid + alcohol → ester | condensation (esterification) | conc. H₂SO₄ catalyst, heat under reflux |
| ester → carboxylic acid (or salt) + alcohol | hydrolysis | dilute acid, or NaOH(aq), heat |
| sugar → ethanol | fermentation | yeast, anaerobic, ~30–35 °C |
| alkene → polymer | addition polymerisation | heat, pressure, initiator or catalyst (7L) |
Planning a synthesis
- Compare the start and the target. Count carbons (does the skeleton stay the same, or are two pieces joined, as in an ester?) and identify the functional groups on each.
- Work backwards. Ask "what could I make the target from in one step?" Repeat until you reach the starting material. This is called retrosynthesis.
- Check each step. Will it give the right isomer? Primary or secondary alcohol? Will an unsymmetrical alkene give a mixture?
- Draw the flow chart forwards, with every intermediate named (or drawn) and the reagents and conditions written on each arrow.
Using ethene as the only organic starting material, plan a synthesis of ethyl ethanoate.
Plan a synthesis of propanone from propene.
Choosing between routes
Often there is more than one route. Chemists in industry weigh up:
- Overall yield. Yields multiply. Three steps of 80% give 0.8 × 0.8 × 0.8 = 51% overall; four steps give 41%. Fewer steps are usually better.
- Atom economy: the percentage of the reactants' mass that ends up in the product. Addition reactions score 100%; substitutions and eliminations waste atoms.
- Selectivity. Substitution of alkanes in UV light gives mixtures; addition to a symmetrical alkene gives one product.
- Cost and availability of starting materials, energy needed (high temperatures and pressures cost money), safety of reagents, and waste disposal.
- Explore mode: tap each functional group to see every reaction leaving it. Which group has the most ways out?
- Challenge 1: make ethanol from ethane. How many steps do you need?
- Challenge 2: make ethanoic acid from ethyne. List the hazards the sim flags and say how you would control each one.
- Challenge 3: make propanone from propene. Which step needs a warning about isomers?
- Challenge 5: make ethyl ethanoate from glucose. Write out the full flow chart with conditions from the sim's summary.
Test yourself
Which sequence converts ethane into ethanoic acid?
Ethane → chloroethane → ethanol → ethanoic acid. Alkanes can't be oxidised directly by dichromate.
A three-step synthesis has yields of 90%, 70% and 80%. The overall yield is about
0.90 × 0.70 × 0.80 = 0.504.
Which reagent and condition convert butan-2-ol into but-2-ene?
Dehydration removes H₂O to form a C=C (but-1-ene also forms).
Which reaction type has the highest atom economy?
In an addition reaction every atom of the reactants ends up in the product.
Name the reaction type on each arrow.
Order the intermediates in a synthesis of propanoic acid from propane.
Planning a synthesis by starting from the target and working back is called . A primary alcohol heated under reflux with acidified dichromate gives a . Removing water from an alcohol to make an alkene is . Reacting a haloalkane with aqueous NaOH is a reaction. The overall yield of a multi-step synthesis is found by the yields of the steps.
Using 1-chloropropane as the only organic starting material, construct a flow chart to synthesise the ester propyl propanoate. Name every intermediate, and give the reagents and conditions for each step.
Step 1 (substitution): 1-chloropropane + NaOH(aq), warmed → propan-1-ol + NaCl. Divide the propan-1-ol into two portions.
Step 2 (oxidation): one portion of propan-1-ol + acidified potassium dichromate, heated under reflux → propanoic acid (via propanal, which stays in the flask and is oxidised further). The solution turns from orange to green.
Step 3 (esterification): propanoic acid + the other portion of propan-1-ol, with a few drops of concentrated H₂SO₄ as catalyst, heated under reflux → propyl propanoate + water. Purify by washing with Na₂CO₃ solution, separating, drying and distilling.
Flow chart: 1-chloropropane —(NaOH(aq), warm)→ propan-1-ol —(H⁺/Cr₂O₇²⁻, reflux)→ propanoic acid; propanoic acid + propan-1-ol —(conc. H₂SO₄, reflux)→ propyl propanoate.