CIE Chemistry A Level

23 : Organic Synthesis
(A Level only)
Notes

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Synthesis of chiral drug molecules

A chiral molecule has ​no plane of symmetry​. A carbon atom with 4 different groups attached is
called a​ chiral centre​.

Stereoisomers have the same structural formula but a ​different arrangement of atoms in space​.
Optical isomers are a type of stereoisomer. Two isomers that show optical isomerism are called
enantiomers​ (molecules which are non-superimposable mirror images) and each enantiomer has
a different effect on a ​plane of polarised light​. The enantiomers will rotate plane polarized light in
opposite directions.
The easiest way to draw the two enantiomers is to draw one and then draw the mirror image on the
other side of the page:

A chiral drug extracted from a ​natural source​ often contains a​ single optical isomer​.

Synthetic drugs often only contain a single optical isomer:

● More effective
● Fewer side effects
● Reduces cost​ long term as money isn’t wasted producing the optical isomer that is
ineffective.

Optical isomers of a molecule have different arrangements of bonds so they have different shapes.
This means that only one of the enantiomers may fit into the ​active site​ (binding site) of an
enzyme. As a result, ​only one of the enantiomers will cause the desirable effect​.

Synthetic routes

Synthetic routes are the routes which can be used to produce a ​certain product from a starting
organic compound​. It is important that you understand the different methods and ​conditions
required to convert convert compounds to other products.

On the following page is a table showing the typical reactions of different functional groups and
how they can be identified.

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Homologous Typical reactions Identification
series

Alkanes Combustion
C-C
Electrophilic substitution/ free radical substitution​ with Br​2
or Cl​2​ (forms haloalkanes)
Cracking​ (forms short chain alkenes and alkanes)

Alkenes Electrophilic addition: React with bromine

C=C - Steam (forms alcohols) water:​ Decolorises in the
- Hydrogen halides (forms haloalkanes) presence of C=C.
- Halogens (forms dihaloalkanes)
- Hydrogen (forms alkanes)
Oxidation​ with H​+​/MnO​4​-​ (forms diols)
Addition polymerisation​ (forms polymers)
Combustion

Haloalkanes Nucleophilic substitution: React with AgNO​3​(aq),

C-F/ C-Cl/ - Hydrolysis (forms alcohols) test precipitate with
C-Br/ C-I - Reaction with ethanolic cyanide (forms nitriles) NH​3​(aq):
- Reaction with ammonia (forms primary amines) AgCl - white ppt soluble in
dilute NH​3​(aq)
Elimination​ of hydrogen halide using ethanolic hydroxide AgBr - cream ppt soluble
ions (forms alkenes) in concentrated NH​3​(aq)
AgI - yellow ppt insoluble
in NH​3​(aq)

Alcohols Combustion React with H​+​/Cr​2​O​7​2-​:

-OH Colour change from
Substitution​ with hydrogen halides, sulfur dichloride oxide
orange​ to ​green​ in the
or phosphorus(III) halides (forms haloalkanes)
presence of primary and
Ethanol and sodium (forms sodium ethoxide and hydrogen secondary alcohols (no
gas) change for tertiary
Oxidation​ with H​+​/Cr​2​O​7​2-​ (forms carbonyls and carboxylic alcohols)
acids)
Dehydration​ using an acid catalyst (forms alkenes)
Esterification​ with carboxylic acids or acyl chlorides

Aldehydes Oxidation​ with H​+​/Cr​2​O​7​2-​ (forms carboxylic acids) React with 2,4-DNPH​:
-CHO A yellow-orange
Reduction​ using NaBH​4​ or LiAlH​4​ (forms primary alcohols)
precipitate is formed in
Nucleophilic addition​ with HCN (forms hydroxynitriles) the presence of a
carbonyl group.
React with Tollens’
reagent: ​A silver mirror is

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 produced if an aldehyde
is present.
React with Fehling’s
reagent: ​The blue
solution forms a brick red
precipitate in the
presence of an aldehyde
React with acidified
potassium
dichromate(VI): ​Orange
solution turns green.

Ketones Reduction​ using NaBH​4​ or LiAlH​4​ (forms secondary React with 2,4-DNPH​: A
RCOR’ alcohols) yellow-orange precipitate
is formed in the presence
Nucleophilic addition​ with HCN (forms hydroxynitriles)
of a carbonyl group.

Carboxylic Reaction with metals, alkalis or carbonates (forms a salt Test pH: ​pH less than 7
acids and inorganic products) when measured using a
-COOH pH probe
Esterification​ with alcohols
React with a carbonate​:
Reduction​ with LiAlH​4​ (forms alcohols)
effervescence as CO​2​ is
Reaction with SOCl​2​ (forms acyl chlorides, sulfur dioxide formed
and hydrochloric acid)
Reaction with phosphorus(V) chloride or phosphorus(III)
chloride (forms acyl chlorides)
Oxidation​ of methanoic acid using Fehling’s or Tollens’
(forms carbon dioxide and water)
Oxidation​ of ethanedioic acid using acidified potassium
manganate(VII) (forms water and carbon dioxide)

Esters Acid hydrolysis​ (forms a carboxylic acid and an alcohol)

RCOOR’
Alkali hydrolysis​ (forms a carboxylate salt and an alcohol)

Amines Reaction with acids (forms a salt)

-NH​2

Nitriles Acid hydrolysis​ (forms a carboxylic acid and a salt)

C≡N
Alkali hydrolysis​ (forms a carboxylate salt and ammonia)

Arenes Electrophilic substitution:

-C​6​H​5 - Halogen (forms chlorobenzene with Cl​2​ and
bromobenzene with Br​2​)
- Nitration (forms nitrobenzene)
Friedel-Crafts ​acylation​ and ​alkylation

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 Oxidation​ of a side chain (forms benzoic acid)
Hydrogenation​ (forms cyclohexane)

Phenol Reactions with strong bases (not acidic enough to react

C​6​H​5​OH with carbonates)
Reaction with sodium (forms sodium phenoxide and
hydrogen gas)
Reaction with diazonium salts (forms azo compounds)
Electrophilic substitution:
- Nitration using HNO​3​ (forms nitrophenol)
- Bromination using Br​2​ (forms bromophenol)

Acyl Hydrolysis​ with water (forms carboxylic acids and HCl)

chlorides
Hydrolysis​ with sodium hydroxide (forms a carboxylate salt
-COCl
and water)
Esterification​ with alcohols or phenol
Reaction with ammonia (forms an amide and HCl)
Reactions with primary amines (forms an N-substituted
amide)

Amides Acid hydrolysis​ (forms a carboxylic acid and ammonium

-CONH​2 ions)
Alkali hydrolysis ​(forms a carboxylate salt and ammonia or
an amine)
Reduction​ using LiAlH​4​ (forms a primary amine)

Multi-stage synthesis
Some organic molecules can be prepared using a ​multi-stage synthesis​. Typically, this involves
two stages: reactant → intermediate → product. It can cover more stages.

Example 1
Below is a diagram showing how ethanoic acid can be formed from chloroethane:

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Example 2
2-propylamine can be formed from propene:

Analysing synthetic routes

When ​synthesising​ an organic compound, several factors are considered before deciding which
synthetic route to use:
● Type of reaction​ - addition reactions are more sustainable than substitution or elimination
reactions as there are no waste products.
● Reagents​ - renewable reagents with few safety concerns are preferred.
● By-products ​- less harmful by-products are favoured as there would be fewer safety and
environmental concerns. If the by-products can be used in another industry, the process is
more sustainable.
● Conditions​ - choose the reaction with the most energy efficient and safe conditions.

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