Topics

Reaction pathways and synthesis

What a synthesis question asks

You are given a starting material and a target, and must supply the reagents, conditions and structure of the product after each step.
These are the highest-tariff questions on the paper, and they test the reaction map rather than any new chemistry.

Work backwards

Forwards is guessing; backwards is deduction.

Look at the target and ask: what makes this functional group?
Usually there are only one or two answers, so you have immediately halved the problem.
Repeat for that intermediate, and keep going until you reach something you can make from the starting material.
Then write the scheme forwards, with reagents and conditions at every arrow.
For example, to reach an amide the only route on this course is from an acyl chloride — so the step before the amide is fixed before you have thought about anything else.

The routes into each group

To make a...	You need...
haloalkane	an alcohol (conc HCl, HBr, $\text{SOCl}_2$ ) or an alkene (+ HX)
alcohol	a haloalkane ( $\text{NaOH}(aq)$ ), an alkene ( $\text{H}_2\text{O}/\text{H}^+$ ), or a carbonyl ( $\text{NaBH}_4$ )
alkene	an alcohol (conc $\text{H}_2\text{SO}_4$ ) or a haloalkane (KOH in alcohol)
aldehyde	a primary alcohol, oxidised and distilled off
ketone	a secondary alcohol, oxidised
carboxylic acid	a primary alcohol or an aldehyde, oxidised under reflux
acyl chloride	a carboxylic acid + $\text{SOCl}_2$
ester	an acid + alcohol ( $\text{H}^+$ ), or an acyl chloride + alcohol
amide	an acyl chloride + $\text{NH}_3$ or a primary amine
amine	a haloalkane + conc $\text{NH}_3$

Two things that catch people out

Some targets need the starting material in two portions. An ester built from an acid and an alcohol that both derive from the same source needs the material split, with one portion oxidised and the other kept as the alcohol.
Some proposed steps do not exist. An aldehyde does not react with an alcohol to make an ester; you must oxidise it to the acid first. Check every step against the map rather than assuming a plausible-looking conversion is real.

Presenting your answer

Draw a flow scheme, one arrow per step.
Write the reagent and the conditions above each arrow.
Draw the structural formula of the organic product after each step.
Never skip a step to save time — each one carries marks.

Tips and Tricks

Start at the target and work backwards. Almost every functional group has only one or two ways in, so working backwards narrows the options immediately, whereas working forwards from the starting material opens them up.

Write the conditions, not just the reagent. "Oxidise" is ambiguous between an aldehyde and an acid — you must write distil or reflux.

Count the carbons at every step. None of the reactions on this course changes the number of carbons in the chain, so if your target has a different carbon count from your starting material, you have made an error or the question intends two fragments to be joined.

If the target contains two different fragments — an ester or an amide — identify both halves first and ask where each comes from. That often reveals that the starting material must be divided.

Check each proposed step against the map. Aldehyde + alcohol does not give an ester. Neither does acid + amine give an amide directly. Invented steps score nothing however sensible they look.

Worked ExampleA four-step synthesis

Devise a reaction scheme to convert 1-bromobutane into N-methylbutanamide, $\text{CH}_3\text{CH}_2\text{CH}_2\text{CONHCH}_3$ . For each step give the reagents, the conditions and the structural formula of the organic product. Methylamine, $\text{CH}_3\text{NH}_2$ , is available.

Step 1 — Plan by working backwards

The target is an amide. On this course an amide is made in only one way: from an acyl chloride plus ammonia or a primary amine. Since the target has an N-methyl group, the amine must be methylamine.

How do I get butanoyl chloride? An acyl chloride is made from a carboxylic acid with $\text{SOCl}_2$ .

How do I get butanoic acid? A carboxylic acid comes from oxidising a primary alcohol under reflux.

How do I get butan-1-ol? An alcohol comes from a haloalkane with aqueous hydroxide — and 1-bromobutane is exactly that.

The chain of reasoning is complete. Now write it forwards.

Step 2 — 1-bromobutane → butan-1-ol

Reagents and conditions: $\text{NaOH}(aq)$ , warmed. The solvent must be aqueous so that substitution occurs rather than elimination.

$\text{CH}_3\text{CH}_2\text{CH}_2\text{CH}_2\text{Br} + \text{NaOH} \rightarrow \text{CH}_3\text{CH}_2\text{CH}_2\text{CH}_2\text{OH} + \text{NaBr}$

Step 3 — butan-1-ol → butanoic acid

Butan-1-ol is a primary alcohol, so oxidation can go to the acid.

Reagents and conditions: acidified potassium dichromate, $\text{Cr}_2\text{O}_7^{2-}/\text{H}^+$ , heated under reflux with the oxidant in excess.

$\text{CH}_3\text{CH}_2\text{CH}_2\text{CH}_2\text{OH} \rightarrow \text{CH}_3\text{CH}_2\text{CH}_2\text{COOH}$

Reflux is essential. Distilling would remove butanal before it could be oxidised further, and an aldehyde is no use for the next step.

The solution turns orange to green.

Step 4 — butanoic acid → butanoyl chloride

Reagent: thionyl chloride, $\text{SOCl}_2$ .

$\text{CH}_3\text{CH}_2\text{CH}_2\text{COOH} + \text{SOCl}_2 \rightarrow \text{CH}_3\text{CH}_2\text{CH}_2\text{COCl} + \text{SO}_2 + \text{HCl}$

Both by-products are gases, so they escape and the reaction goes to completion.

Step 5 — butanoyl chloride → N-methylbutanamide

Reagent: methylamine, $\text{CH}_3\text{NH}_2$ , at room temperature.

$\text{CH}_3\text{CH}_2\text{CH}_2\text{COCl} + \text{CH}_3\text{NH}_2 \rightarrow \text{CH}_3\text{CH}_2\text{CH}_2\text{CONHCH}_3 + \text{HCl}$

Step 6 — Check the whole scheme

$\text{1-bromobutane} \xrightarrow{\text{NaOH}(aq)} \text{butan-1-ol} \xrightarrow{\text{Cr}_2\text{O}_7^{2-}/\text{H}^+,\ \text{reflux}} \text{butanoic acid} \xrightarrow{\text{SOCl}_2} \text{butanoyl chloride} \xrightarrow{\text{CH}_3\text{NH}_2} \text{N-methylbutanamide}$