Topic 16

ALDEHYDES, KETONES AND OPTICAL ISOMERISM

Reactions of aldehydes and ketones

Optical Isomerism
 ALDEHYDES AND KETONES

1. Introduction

Aldehydes and ketones are collectively known as carbonyls and represented by the
general formula CnH2nO. They have the following functional group:

In aldehydes one of the groups attached to the carbon is a hydrogen atom and the other is
a hydrogen atom or an alkyl groups. In ketones both of the groups attached to the carbon
are alkyl groups:

H H H O
O O
H C C C C H
CH3 C H C
H H H H H
ethanal methanal butanal

H H O H H H O H H

H C C C C H H C C C C C H

H H H H H H H
butanone pentan-2-one
2. Redox reactions

The redox reactions involving carbonyls have been discussed at AS level and are
summarized by the following diagram:

primary secondary tertiary

alcohols alcohols alcohols

[O] X
[O] [R]

aldehydes [R]
ketones

[O] X

carboxylic
acids

a) oxidation reactions

Carbonyls are formed by the oxidation of alcohols.

Partial oxidation of a primary alcohol results in the formation of an aldehyde.

Oxidation of a secondary alcohol results in the formation of a ketone.

Primary alcohols, secondary alcohols and aldehydes are oxidized using potassium
dichromate (K2Cr2O7) in sulphuric acid (H2SO4). Gentle warming is necessary to start the
reaction.

When making an aldehyde, care must be taken to prevent further oxidation to the
carboxylic acid. This is achieved by using distillation apparatus so that the aldehyde can
be distilled off as soon as it is formed.

The orange Cr2O72- is reduced to the green Cr3+.

Simplified equations for these oxidation reactions can be written using the symbol [O] as
the oxidant:

Primary alcohol  aldehyde

R-CH2OH + [O]  R-CHO + H2O

Secondary alcohol  ketone

R1-CH(OH)-R2 + [O]  R1-CO-R2 + H2O

Aldehyde  carboxylic acid

R-CHO + [O]  R-COOH

The most important difference in the reactions of aldehydes and ketones is the fact that
aldehydes can be readily oxidized to carboxylic acids but ketones are not readily
oxidized. This is used as the basis for two important distinguishing tests between
aldehydes and ketones.

Ammoniacal silver nitrate, [Ag(NH3)2]+, is known as Tollen's reagent. It is a mild

oxidising agent:
[Ag(NH3)2]+(aq) + e  Ag(s) + 2NH3(aq)

It can be reduced by aldehydes, oxidising them to carboxylic acids:

R-CHO + H2O  RCOOH + 2H+(aq) + 2e

The overall equation for the reaction is:

R-CHO + 2[Ag(NH3)2]+ + H2O  RCOOH + 2Ag + 4NH3 + 2H+

Thus aldehydes give a grey precipitate or "silver mirror" if boiled with ammoniacal silver
nitrate. This is a standard test for an aldehyde, since ketones cannot be oxidised in this
way.

Fehling’s solution is an alkaline solution containing Cu2+ ions. It is a mild oxidizing

agent:
2Cu2+ + 2e + 2OH-  Cu2O + H2O

It is also reduced by aldehydes, and the overall equation for the reaction is:
R-CHO + 4OH- + 2Cu2+  R-COOH + Cu2O + 2H2O

The blue Cu2+ is reduced to the brick-red precipitate Cu2O on gentle warming. This is
another standard test for an aldehyde.
b) reduction reactions

Aldehydes and ketones can be reduced to primary and secondary alcohols respectively
using the reducing agent sodium tetrahydroborate (III), NaBH4.

Simplified equations for these reduction reactions can be written using the symbol [H] as
the reductant:

Aldehyde  primary alcohol

R-CHO + 2[H]  R-CH2OH

Ketone  Secondary alcohol

R1-CO-R2 + 2[H]  R1-CH(OH)-R2

Carboxylic acids cannot be reduced using NaBH4 but can be reduced to primary alcohols
using the stronger reducing agent LiAlH4.

3. Nucleophilic addition

Carbonyls are unsaturated and can thus undergo addition reactions.

The C=O bond is polar so the carbon is a positive centre. Thus carbonyls can react with
nucleophiles:

 -
O
+
C

N u:

Carbonyls therefore tend to undergo nucleophilic addition.

Mechanism of nucleophilic addition:

Example 1: addition of HCN to make hydroxynitriles

NB
 HCN is a very poisonous gas. It is not safe to carry out this reaction in the
laboratory. HCN is not stored, but made in situ by mixing KCN and HCl.
 KCN is also very poisonous but it is safer to store as it is a solid.

Hydrogen cyanide, HCN, is a nucleophile. It reacts with carbonyls as follows:

R1-CO-R2 + HCN  R1-C(CN)(OH)-R2

OH
O

R1 C + HCN R1 C R2

R2
CN

HCN is a very toxic gas, so is generated in situ:

KCN(s) + HCl(aq)  HCN(g) + KCl(aq)

The mechanism consists of three steps:

Step 1: the HCN is a weak acid and dissociates:

HCN  H+ + CN-

The CN- behaves as a nucleophile.

Step 2: The nucleophile attacks the carbonyl:

 -
O
+
R C
1

R 2

:C N -
Step 3: The O atom picks up the H+ ion:

.. H
O-

R2 C CN

R1

Eg propanal + HCN  2-hydoxybutanenitrile

 - O H
+ O H +
+   ..-
- O
C H C H C C H 3 C H 2
C C N
C N 3 2
H C C N
C H 3 C H 2
H H
H

:C N -

Example 2: reduction by NaBH4 to make alcohols

The reduction of aldehydes and ketones as described above is another example of a

nucleophilic addition reaction.
R1-CO-R2 + 2[H]  R1-CH(OH)-R2
OH
O

R1 C + 2[H] R1 C H
R2
R2
NaBH4 contains hydrogen in a negative oxidation state, which can therefore behave as a
nucleophile.

Step 1: the H- ion attacks the δ+ carbon atom:

 -
O O -
+
R 1
C R 2
C H

R 2
- R
H : 1
Step 2: the O- pulls a H atom off a water molecule

H OH
.. H
O- O -
R2 C H + OH
R2 C H
R1
R1

eg propanone + 2[H]  propan-2-ol

 -
H
.. H
O O - O O H
+
-
C H 3 C C H 3
C H C H 3
C H + O H
C H 3 C H
C H 3
- 3
H :
4. Summary of reactions of aldehydes and ketones

Type of reaction Mechanism

1. oxidation (aldehydes only): aldehyde  carboxylic acid n/a

reagents: potassium dichromate (K2Cr2O7) in sulphuric acid (H2SO4)

conditions: warm under reflux
equation: R-CHO + [O]  R-COOH
observation: orange to green

to distinguish between aldehydes and ketones:

either:
add Fehling’s solution and heat
observation: blue solution to brick red precipitate
equation: R-CHO + 4OH- + 2Cu2+  R-COOH + Cu2O + 2H2O
or:
add Tollen’s reagent and heat
observation: colourless solution to silver mirror
equation: R-CHO + 2[Ag(NH3)2]+ + H2O  RCOOH + 2Ag + 4NH3 + 2H+

2. reduction: carbonyl  alcohol Nucleophilic

addition
reagents: NaBH4(aq) (required)
conditions: room temperature
equation: R1-CO-R2 + 2[H]  R1-CH(OH)-R2

3. addition of HCN: carbonyl  hydroxynitrile Nucleophilic

addition
reagents: KCN and HCl(aq) (required)
conditions: room temperature
equation: R1-CO-R2 + HCN  R1-C(CN)(OH)-R2
 OPTICAL ISOMERISM

Isomers are compounds with the same molecular formula but different structures.

Isomerism can be divided into two types; structural isomerism and stereoisomerism.

These in turn can be further subdivided:

There are three types of structural isomerism; positional isomerism, chain isomerism
and functional isomerism.

There are two types of stereoisomerism: geometrical isomerism and optical isomerism.

The different types of isomerism are summarised in the following diagram:

isomerism

structural
stereoisomerism
isomerism

positional chain functional geometrical optical

Many of these different types of isomerism were discussed at AS level.

Optical Isomerism will be introduced in this chapter.

 i) Introduction to Optical Isomerism

Consider the following molecule:

W C Y

It is tetrahedral and is thus more accurately represented in the following way:

X C
W
z

Since the carbon atom is attached to four different groups, it is asymmetric and so cannot
be superimposed on its mirror image:

C X
W
z

These two mirror images cannot be interconverted without breaking covalent bonds.

Molecules which contain a carbon atom which is attached to four different groups are
said to be chiral. Chiral molecules cannot be superimposed on their mirror image.

The two non-superimposable mirror images are optical isomers or enantiomers.

Any molecule which contains at least one carbon atom attached to four different groups
will thus exhibit optical isomerism.
Consider the four structural isomers of C4H9Cl:

Cl

CH3 CH2 CH2 CH2 Cl CH3 CH2 CH CH3

1-chlorobutane 2-chlorobutane

Cl

CH3 CH CH2 Cl CH3 C CH3

CH3 CH3
1-chloro, 2-methylpropane 2-chloro, 2-methylpropane

Of these molecules only 2-chlorobutane shows optical isomerism:

Cl Cl

C C
C2H5 C2H5
CH3 CH3
H H

ii) Distinguishing between the different enantiomers

Optical isomers show identical physical and chemical properties in most respects.
In fact there is only one physical method by which they can be distinguished.

Plane-polarised light is light which has been filtered into a two-dimensional plane:

Light source plane-polarised light

If plane-polarised light is passed through a liquid containing a chiral molecule, the plane
of the light will be rotated. This can be detected using a polarimeter.

Molecules which are not chiral will not rotate the plane of plane-polarised light.

Chiral molecules will rotate plane-polarised light. Two optical isomers will rotate plane
polarised light equally, but in opposite directions.
It is this difference in physical properties which enables them to be distinguished.

It is not possible to predict the direction in which a particular optical isomer will rotate
plane polarised light, but two optical isomers will always rotate plane polarised light in
opposite directions.

A substance which can rotate plane polarised light is said to be optically active.

The isomer which rotates plane polarised light clockwise is given the prefix (+) or D-.
The isomer which rotates plane polarised light anticlockwise is given the prefix (-) or L-.

iii) Importance of optical isomers in biochemistry

Optical isomers show identical chemical properties in most reactions. However, certain
biochemical processes require the molecule to have a specific orientation of groups.
Many drugs and enzymes are chiral and so only one of the optical isomers will be able to
interact effectively with the target molecule in the body. Different optical isomers may
therefore have very different biochemical effects.

iv) racemates

Optical isomers are often found together in a mixture in equal quantities. The opposite
effect they have on the rotation of plane polarised light will thus result in no overall
rotation. An equimolar mixture of two optical isomers will thus have no effect on plane
polarised light and is thus not optically active.
Such mixtures are said to be racemic mixtures or racemates.

A racemic mixture is an equimolar mixture of two optical isomers. Racemic mixtures are
not optically active.

Thus chiral molecules will only show optical activity if one isomer is present in greater
quantities than the other.
It is possible to predict whether a single enantiomer or a racemate will be produced,
provided that the mechanism for the reaction is known.

If the chiral substance is produced by an addition reaction, then the product will always
be a racemate as the attacking nucleophile or electrophile can attack the planar molecule
from above or below with equal probability:

Eg formation of 2-bromobutane from but-2-ene (electrophilic addition)

The bromide ion can attack the carbocation from above or below, producing an equimolar
mixture of the two enantiomers – ie a racemate:

H3C H
C C CH3 H Br
H CH3 + CH3
H C C
CH3 H C C
H Br H
H
H
Br CH3

bromide attacks planar species from above

or

CH3 H CH3
+ CH3
H C C
CH3 H C C
H H
H
Br Br

bromide attacks planar spcies from below

Nucleophilic addition reactions also produce racemates for the same reason. In the
preparation of the chiral molecule 2-hydroxypropanenitrile from ethanal for example, the
cyanide ion can attack the planar carbonyl group from above or below, producing a
racemate.

H+
O-
O

H CN CH3 C
C
CH3 CN
CH3

-CN H
or
-CN

O CN

CH3 C
C H+
H O-
CH3

If the chiral molecule is produced by a substitution reaction and the starting molecule is a
single enantiomer, then the attacking species can only attack from one side and a single
enantiomer will be produced.

Eg preparation of butan-2-ol from 2-bromobutane

CH3 CH3
-
OH
C C C2H5 + Br -
C2H5 Br HO
H
H

The hydroxide ion always attacks from behind, always producing the same enantiomer.

So nucleophilic substitution reactions produce single enantiomers provided that the

substrate was also a single enantiomer. Nucleophilic and electrophilic addition
reactions always produce racemates.