Organic synthesis

A-Level Chemistry · Topic 21

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21.1

Organic synthesis

Syllabus

for an organic molecule containing several functional groups: (a) identify organic functional groups using the reactions in the syllabus (b) predict properties and reactions
devise multi-step synthetic routes for preparing organic molecules using the reactions in the syllabus
analyse a given synthetic route in terms of type of reaction and reagents used for each step of it, and possible by-products

Source: Cambridge International syllabus

This topic does not add new reactions. Instead it asks you to join up the reactions you already know, so you can build a target molecule in several steps.

White tablets in foil blister packs — Medicines are built up from simple starting materials by multi-step organic synthesis

Identifying functional groups

A molecule may have more than one functional group 官能团. Use the test reactions from the syllabus to identify each one, and then predict how the molecule will behave. For example:

decolourises bromine water → a C=C double bond (an alkene 烯烃).
gives a precipitate with silver nitrate → a halogenoalkane 卤代烷.
orange $\text{K}_2\text{Cr}_2\text{O}_7$ turns green → a primary or secondary alcohol 醇.
orange precipitate with 2,4-DNPH → an aldehyde 醛 or ketone 酮.
fizzes with a carbonate → a carboxylic acid 羧酸.

A three-column table listing each test reagent, the observation it gives, and the functional group it identifies — The standard identification tests: each reagent gives a characteristic observation that points to one functional group

A map of the AS reactions

Each row turns one functional group into another. Learn it as a map you can travel around:

Start	Reagent and conditions	Product
alkene	$\text{H}_2$, Ni	alkane
alkene	$\text{HX}$, or $\text{X}_2$	halogenoalkane
alkene	steam, $\text{H}_3\text{PO}_4$	alcohol
halogenoalkane	$\text{NaOH(aq)}$, heat	alcohol
halogenoalkane	$\text{KCN}$ in ethanol, heat	a nitrile 腈 (adds one carbon)
halogenoalkane	$\text{NH}_3$ in ethanol, pressure	an amine 胺
alcohol	$\text{K}_2\text{Cr}_2\text{O}_7$, distil / reflux	aldehyde / carboxylic acid
alcohol	concentrated acid, heat	alkene
aldehyde or ketone	$\text{NaBH}_4$	alcohol
aldehyde or ketone	$\text{HCN}$, $\text{KCN}$	hydroxynitrile
nitrile	dilute acid, heat	carboxylic acid
carboxylic acid + alcohol	concentrated $\text{H}_2\text{SO}_4$	an ester 酯

A network diagram linking alkene, alkane, halogenoalkane, alcohol, aldehyde, nitrile, amine, carboxylic acid and ester by labelled reagent arrows — A map of the AS reactions: each arrow turns one functional group into another. Work backwards from your target to plan a route

Planning a multi-step route

To devise a synthetic route 合成路线:

compare the target with the starting material — what has changed (the functional group, the number of carbons)?
work backwards from the target: which single reaction could make it, and from what?
repeat until you reach the starting material.
write each step with its reagent 试剂 and conditions.

If you need to add a carbon, the $\text{KCN}$ step is the key — it is the only AS reaction that lengthens the chain.

A synthesis chain from ethene to propanoic acid with the reagent on each forward step, and a large backward arrow showing the planning runs from the target back to the start — Plan a route by working backwards from the target, one reaction at a time, until you reach the starting material

Analysing a route

When you are given a route, for each step state the type of reaction (such as oxidation 氧化, reduction 还原, substitution, addition or elimination) and the reagent used. Also think about possible by-products 副产物 — for example, making an amine from a halogenoalkane also gives a mixture of further-substituted amines, so the yield of the simple amine is low.

A separating funnel clamped above a beaker, holding two coloured liquid layers that do not mix — A separating funnel splits two immiscible layers — how the organic product is recovered from the reaction mixture

For each step in a given route, ask three things: its reaction type, its reagent and conditions, and whether by-products lower the yield — For every step in a given route, ask its reaction type, reagent and by-products

The five reaction types with what each does: oxidation, reduction, substitution, addition and elimination — Name the reaction type at each step: oxidation, reduction, substitution, addition or elimination

Worked example. Devise a route from propene to propanone, $\text{CH}_3\text{COCH}_3$. Work backwards from the target. A ketone comes from oxidising a secondary alcohol, so the step before propanone is propan-2-ol with acidified $\text{K}_2\text{Cr}_2\text{O}_7$ under reflux. Propan-2-ol comes from propene by adding steam over an $\text{H}_3\text{PO}_4$ catalyst - and Markovnikov's rule conveniently puts the $\text{OH}$ on the middle carbon, which is exactly the secondary alcohol needed. So the route is: propene, then steam with $\text{H}_3\text{PO}_4$, giving propan-2-ol; then acidified $\text{K}_2\text{Cr}_2\text{O}_7$ under reflux, giving propanone. Give a reagent and its conditions on every arrow: a route with the right intermediates but no reagents scores very little.

Explore

Reaction map lab

Classify clues that identify functional groups and reaction pathways.

Explore

Synthetic route planning lab

Follow how a target molecule is planned backwards then made forwards.

Vocabulary Train

English
functional group/ˈfʌŋkʃənl ɡruːp/
alkene/ˈælkiːn/
halogenoalkane/ˈheɪləʊdʒnəʊlkeɪn/
alcohol/ˈælkəhɒl/
aldehyde/ˈældɪhaɪd/
ketone/ˈketəʊn/
carboxylic acid/ˌkɑːbəkˈsɪlɪk ˈæsɪd/
nitrile/ˈnaɪtraɪl/
amine/ˈæmaɪn/
ester/ˈestə/
synthetic route/sɪnˈθetɪk ruːt/
reagent/rɪˈeɪdʒənt/
oxidation/ˌɒksɪˈdeɪʃn/
reduction/rɪˈdʌkʃn/
by-product/baɪ ˈprɒdʌkt/

21.1

Exam tips

Learn the reagents and conditions for each conversion — that is exactly what synthesis questions test.
Plan multi-step routes by functional group and watch the carbon count (KCN adds one carbon).
Choose the shortest valid route and state every reagent and condition.