Download Topic guide 5.4: Chemical behaviour of organic compounds

Unit 5: Chemistry for Applied Biologists
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54
Chemical behaviour
of organic compounds
Organic molecules, based on chains and rings of carbon atoms, make up
the vast majority of the compounds in existence. All have their origins in
chemicals in living systems; some are found naturally in these systems while
others are synthesised by chemists from materials derived from such systems.
Understanding the structure and bonding in these compounds is the key to
making sense of their behaviour, both in the lab and in biological systems.
In this topic you will learn how to recognise and name organic molecules and
understand the nature of the bonds in these molecules and will be introduced
to the main reactions of the different classes of organic compounds.
On successful completion of this topic you will:
•• understand the chemical behaviour of the main classes of organic
compounds (LO4)
To achieve a Pass in this unit you need to show that you can:
•• explain how bonding in organic molecules relates to shape (4.1)
•• relate classes of organic compounds to the functional groups (4.2)
•• relate names of compounds to their structural formulae (4.3)
•• write equations for the main reactions of organic compounds (4.4)
•• relate types of isomerism in organic compounds to shapes (4.5).
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Unit 5: Chemistry for Applied Biologists
1 Bonding in organic compounds
Key term
Orbital: A region of space in which
an electron is likely to be found.
Orbitals are described as s,p,d;
different types of orbitals have
different 3-dimensional shapes.
Diagrams of the shapes are shown in
Figure 5.4.1.
2px
2py
Organic compounds are based on rings and chains of carbon atoms. The way in
which carbon atoms form bonds to each other and other atoms is important in
understanding the behaviour of organic compounds.
Carbon atom bonding
Take it further
Ideas about electrons in atoms and the orbitals that they occupy can be explored further at
http://www.chemguide.co.uk/atoms/properties/atomorbs.html.
2pz
2p
E
2s
1s
Figure 5.4.1: The electron configuration
of a carbon atom shows that the four
unpaired electrons in the 2s and 2p
orbitals can be available for bonding.
The three 2p orbitals are described as
2px, 2py and 2pz to reflect the fact that
the electron densities of these three
orbitals are at right angles to each other.
An isolated carbon atom has four electrons in its outer shell. This shell consists
of four orbitals. Two of these outer shell electrons occupy a 2s orbital and the
remaining two occupy 2p orbitals, so the electronic configuration of this outer
shell is written as 2s22p2.
However, in order to form four covalent bonds (which is energetically the most
favourable situation), the carbon atom needs to have four unpaired electrons.
To achieve this, one of the 2s electrons is promoted to a 2p orbital, so that the
effective electronic configuration of carbon when it forms bonds is 2s12p3. The four
unpaired electrons in this new configuration can now form four covalent bonds.
sp3 hybridisation and the shape of methane
Consider the simplest organic molecule, methane. This has a tetrahedral structure
in which all of the bonds are identical. To account for this, the concept of
hybridisation must be used.
In hybridisation, the mathematical functions describing the four different orbitals
are combined to form four new, identical orbitals. Each orbital is described as an
sp3 hybrid, to reflect the contribution of the original s and p orbitals.
When carbon atoms form bonds with hydrogen in the methane molecule, the
electrons in these sp3 hybrid orbitals overlap with a 1s electron from a hydrogen
atom to form a new molecular orbital, which creates a force of attraction between
the two atoms – a covalent bond. The four identical molecular orbitals will take up
an arrangement in which they each point towards the corners of a tetrahedron to
minimise the repulsion between them (see Figure 5.4.2), producing a bond angle
of 109.5° (109° 28’).
5.4: Chemical behaviour of organic compounds
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Unit 5: Chemistry for Applied Biologists
Figure 5.4.2: Hybridisation can
be used to explain the tetrahedral
shape of a methane molecule.
2s
2px
2py
2pz
Four sp3 hybrid orbitals
σ bond: the overlap of electrons
occurs along the axis between
the C and H atoms
Overlapping with 1s orbitals from
H atoms to form four σ bonds
The four σ bonds (or molecular
orbitals) point to the four corners
of a tetrahedron
The overlapping between the 1s electron from the H atom and the sp3 electron
from the C occurs on an axis directly between the two atoms. Such molecular
orbitals are known as sigma (σ) bonds.
Take it further
There is a helpful website showing hybridisation in a range of simple molecules (and including
a helpful animation) at
http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch02/ch2-3-1.html.
H
H
C
H
C
H
Figure 5.4.3: The structure of ethene.
sp2 hybridisation
When carbon forms four single bonds, the hybridisation in the atomic orbitals
will always be sp3. But in molecules such as ethene (see Figure 5.4.3) the atomic
orbitals can hybridise in a different way.
When an ethene molecule forms, one of the p electrons from the C atom is not
involved in the hybridisation and so there are now only three hybridised orbitals
formed, each described as an sp2 hybrid (see Figure 5.4.4).
Figure 5.4.4: In sp2 hybridisation, three
identical sp2 orbitals are formed and the
remaining electron remains in a p orbital.
2s
2px
2py
2pz
+
three sp2 orbitals
one p orbital
If there are two p orbitals on adjacent carbon atoms, the electrons can overlap to
form a new type of bond (molecular orbital) (see Figure 5.4.5).
5.4: Chemical behaviour of organic compounds
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Unit 5: Chemistry for Applied Biologists
Figure 5.4.5: The formation of σ and
π bonds in an ethene molecule.
p orbital p orbital
H
C
C
H
H
H
π bond formed by overlap
between two p orbitals
H
H
C
C
H
H
σ bond formed by overlap
between an sp2 hybrid orbital
and a 1s orbital
σ bond formed by overlap
between two sp2 hybrid orbitals
The overlapping electrons do not lie on the axis between the two carbon atoms;
bonds like this are known as pi (π) bonds. As this ‘sideways’ overlap of orbitals
produces less overlap than the end-to-end overlap seen in σ bonds, π bonds are
often weaker (and hence more reactive) than σ bonds.
The remaining three electrons in the sp2 orbitals will now form three σ bonds
(molecular orbitals) – two by overlapping with 1s orbitals from hydrogen atoms
and one by overlapping with an sp2 orbital from the other carbon atom.
These three σ bonds will take up a planar arrangement with a bond angle of 120°,
in order to minimise the repulsion between them. This is described as a trigonal
planar structure because each of the σ bonds points to a corner of a triangle, as
shown in Figure 5.4.6.
Figure 5.4.6: The trigonal
planar arrangement of bonds
around a C atom in ethene.
H
120°
C
H
C
H
120°
H
Each σ bond points to
a corner of a triangle
So in ethene the two carbon atoms are held together by a π bond and one of the
σ bonds; this is described as a double bond and will clearly result in a stronger
force of attraction between the atoms than the single bond in ethane, and hence a
shorter bond length.
Key term
Unsaturated: A molecule containing
at least one double or triple carboncarbon bond.
Molecules with double (or triple) carbon-carbon bonds are described as
unsaturated.
Activity
•• The molecule ethane (C2H6) contains two C atoms displaying sp3 hybridisation. Find a diagram
or model that shows the 3-dimensional structure of ethane. Explain the shape of the structure
and the value of the bond angles by considering the number and type of bonds formed by the
carbon atoms.
•• The molecule ethyne (C2H2) contains a triple bond. This is a result of C atoms that display sp1
hybridisation. Describe the bonding and geometry of the ethyne molecule using ideas about
hybridisation and overlap of orbitals.
5.4: Chemical behaviour of organic compounds
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Unit 5: Chemistry for Applied Biologists
Take it further
C=O bonds (in molecules such as propanone) also consist of a σ and a π bond, with the sp2 orbitals
on the C atom resulting in two further σ bonds.
http://www.chemguide.co.uk/basicorg/bonding/carbonyl.html has more information about
the bonding in molecules that contain C=O bonds.
Delocalisation
Many important biological molecules, such as the porphyrin groups present in
haem and chlorophyll as well as the electron carriers NAD+ and FAD, include a
structural feature that displays delocalisation.
Electrons that are delocalised are not associated with a specific bond or atom but
are in an orbital that extends over three or more atoms.
Benzene
The simplest example of a delocalised system of electrons is in the molecule
benzene. The six carbon atoms in the ring display sp2 hybridisation leaving one
electron from each carbon atom in a p orbital.
These six electrons form a delocalised molecular orbital, shown in Figure 5.4.7.
Figure 5.4.7: The six p electrons in the
benzene ring form a delocalised system.
C
C
C
C
C
C
C
C
C
C
C
C
Other examples of delocalisation: conjugation
The delocalisation in benzene arises from the presence of an uninterrupted series
of p orbitals; such a system is described as conjugated.
The most commonly-occurring conjugated systems are those in which double and
single bonds alternate, as in the molecule buta-1,3-diene (see Figure 5.4.8).
Figure 5.4.8: The structure of buta-1,3diene and the overlapping p orbitals
which form a conjugated system.
H2C
CH
CH
CH2
C
C
C
C
Conjugation can also occur if the series of p-orbitals is interrupted by an atom
such as oxygen or nitrogen that possesses a lone pair; this lone pair (which can be
treated as an sp3 atomic orbital) can conjugate in the same way that a p-orbital
does. Figure 5.4.9 shows the structure of furan, which is conjugated in this way.
Figure 5.4.9: The structure of furan
and the overlapping p orbitals,
which form a conjugated system.
5.4: Chemical behaviour of organic compounds
O
p orbitals
O
Lone pair
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Unit 5: Chemistry for Applied Biologists
Figure 5.4.10: The porphyrin ring
in the structure of haem contains
an extensive delocalised system.
CH2
CH3
CH2
H3C
N
N
FeII
Activity
N
N
H3C
Look at the structure of the haem
group in Figure 5.4.10. How many
p orbitals or lone pairs are involved
in the conjugated system?
O
CH3
OH
O
OH
Lone pairs
O
O
Lone pair
O
C
M2+
C
O
Figure 5.4.11: The lone pairs on the
oxygen atoms of this ethanedioate group
allow it to form bonds to a metal ion.
H
H
H
C
C
H
H
Lone pairs
O
H
Figure 5.4.12: The oxygen
atom in an ethanol molecule
possesses two lone pairs.
As noted above, uncharged oxygen and nitrogen atoms in organic molecules
possess lone pairs of electrons. As well as enabling conjugation, as described
above, these lone pairs may influence other important properties of the molecules
that contain them, such as the ability to form bonds to transition metal ions. These
can be clearly seen in the structure of the haem group in Figure 5.4.10 and in
Figure 5.4.11, which shows an ethanedioate (oxalate) ion forming two covalent
bonds to a metal ion.
Lone pairs are also present on halogen atoms in organic molecules, although few
biologically important molecules contain halogen atoms.
The effect of lone pairs on shapes of molecules
Because, in many cases, a lone pair of non-bonding electrons can be treated as an
sp3 hybridised orbital, the three-dimensional arrangement of bonds around atoms
can be predicted even if a lone pair is present.
For example, consider the bonding in the molecule ethanol (see Figure 5.4.12).
sp3 orbital
C
O
σ bond
H
Figure 5.4.13: The three-dimensional
arrangement of the orbitals and bonds
around an oxygen atom in ethanol.
There are two lone pairs (sp3 hybrids) and two σ bonds around the oxygen
atom, so these orbitals will take up a tetrahedral arrangement. The two σ bonds,
therefore, will be arranged in a V-shaped formation, with a bond angle of
around 109° (in reality it is rather less than this because the lone pairs repel the
other orbitals rather more strongly than the σ bonds). The three-dimensional
arrangement of the lone pairs and bonds is shown in Figure 5.4.13.
Portfolio activity (4.1)
Choose some simple organic molecules. Use ideas from this section to comment on the bonding
and shape. Suitable examples could be propan-1-ol, but-2-ene, ethanal and phenol.
In your answer you should:
•• identify the type of hybridisation displayed by some of the C atoms in the structure and the
types of bonds which result from overlap of these hybrid orbitals
•• use ideas about hybridisation to explain the geometry of the bonds around the C atoms
•• identify any delocalised systems of electrons in the molecule
•• identify any atoms that will possess lone pairs.
5.4: Chemical behaviour of organic compounds
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Unit 5: Chemistry for Applied Biologists
2 Classifying organic molecules
Key term
Functional group: An atom or
group of atoms responsible for
the characteristic properties of a
particular class of compounds. For
example, the OH group in alcohols.
In many cases, the name of the
functional group is identical to the
name of the class of compounds that
contains the functional group.
Chemists classify the vast range of organic substances by defining a number
of different classes to which the compounds may belong. In many cases the
classification of a molecule depends on the presence of a particular functional
group. Table 5.4.1 shows some common classes of organic compounds and the
functional groups they contain.
This section, and the following one, is covered in more detail in the presentation
‘Structure and naming of organic compounds’.
Link
There are various ways of showing the structure of organic molecules. These were discussed in
Topic guide 5.1 and are discussed in more detail in sections 3 and 4 of this topic guide and in the
presentation ‘Structure and naming of organic compounds’.
Table 5.4.1: Some common classes
of organic compounds and the
functional groups they contain.
Class of compounds
Functional group present
Example
H
H
alkanes
H
C
(none – contains only C–H and
C–C bonds)
H
C
H
H
C
H
H
H
C
H
H
C
C
H
H
H
hexane
H3C
alkenes
CH
CH
C=C
CH3
but-2-ene
H
H
alcohols
–OH (sometimes called hydroxyl)
H
C
H
C
H
H
C
H
O
H
propan-1-ol
H
H
haloalkanes
–X (X = F, Cl, Br, I)
H
C
H
C
H
H
C
Cl
H
1-chloropropane
O
aldehydes
R
C
O
H3C
C
H
H
ethanal
Continued on next page
5.4: Chemical behaviour of organic compounds
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Unit 5: Chemistry for Applied Biologists
Class of compounds
Functional group present
Example
O
O
R
ketones
H3C
C
C
CH3
R
propanone
O
R
carboxylic acids
O
H3C
C
C
OH
OH
(sometimes called carboxyl)
ethanoic acid
O
O
R
esters
H3C
C
C
O
O
H3C
R
methyl ethanoate
H3C
amines
CH2
NH2
R–NH2
aminoethane OR ethylamine
O
O
amides
R
H3C
C
C
NH2
NH2
ethanamide
Other groups of atoms that are often encountered in biological molecules are the
ether group and the phenyl group (see Figure 5.4.14).
Figure 5.4.14: (a) Ether group
and (b) phenyl group.
(a)
(b)
R1
O
R
R2
Activity
Many molecules contain a wide range of functional groups. Clavulanic acid has been used
alongside penicillins in the treatment of infections caused by some antibiotic-resistant strains of
bacteria.
Look at the structure of clavulanic acid shown in Figure 5.4.15. List the functional groups present
in this molecule.
Figure 5.4.15: Structure
of clavulanic acid.
O
H
COOH
H
N
O
CH2OH
H
5.4: Chemical behaviour of organic compounds
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Unit 5: Chemistry for Applied Biologists
3 Naming organic molecules
This section is covered in more detail in the presentation ‘Structure and naming of
organic compounds’.
Take it further
There are several systems by which organic molecules are commonly named. However, the
International Union of Pure and Applied Chemistry (IUPAC) publishes details of an internationally
agreed set of conventions that enable each molecule to be given a single, unambiguous name to
enable better communication among chemists. These names can then be used in publications,
databases, and so on, which may be intended for wider readership.
Full details of this ‘systematic nomenclature’ can be found at the IUPAC website
http://www.iupac.org/ or at http://www.acdlabs.com/iupac/nomenclature/93/r93_5.htm.
I edit papers submitted to a journal about drug discovery and design. One of my biggest
problems is ensuring that the names of organic molecules referred to in the text are correct and
unambiguous. Researchers will use searching tools to find references to compounds which interest
them in a wide range of publications so it is vital that the correct names appear in our journal.
Chris Powell, Editor
All journals worldwide follow the IUPAC conventions for naming molecules, but the names that
these conventions produce for drug molecules are often very long and complex. Here’s one
example: 9-[(2R,4S,5R)-4-(tert-butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)tetrahydro-furan-2-yl]-6-(2-methylsulfanyl-ethyl)-9H-purin-2-ylamine. To produce these names,
contributors must use computer software to generate the name, but different software can
produce different results – the previously named molecule produced the name 2-amino-9-(3’,5’-diO-tert-butyldimethylsilyl-2’-deoxy-D-ribofranosyl)-6-(2-methylthioethyl)purine when run through
an alternative software package.
My job therefore is to run the structures in the papers through our naming software module and
manually check any cases where the names in the paper seem to be incorrect or ambiguous.
Summary of the rules
The number of carbon atoms in a carbon chain, or in a ring of carbon atoms, is
indicated by the word with which the name begins, as below.
Table 5.4.2: Prefixes indicating
number of carbon atoms.
Number of carbon atoms
Prefix
1
meth-
2
eth-
3
prop-
4
but-
5
pent-
6
hex-
7
hept-
8
oct-
9
non-
10
dec-
5.4: Chemical behaviour of organic compounds
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Unit 5: Chemistry for Applied Biologists
The class to which the compound belongs may be indicated by a number of
possible suffixes (see Table 5.4.3).
Table 5.4.3: Suffixes indicating
class of compounds.
Suffix
Class of compound
alkene
-ene
alcohol
-anol
aldehyde
-anal
ketone
-anone
carboxylic acid
-anoic acid
carboxylate (R–COO-)
-anoate
amine
-anamine
amide
-anamide
The position of the functional group on the carbon chain or carbon ring is
indicated by a number, for example, hexan-2-ol, pent-3-ene, hexan-2-one, as seen
in Figure 5.4.16.
Figure 5.4.16: The skeletal formulae of
hexan-2-ol, pent-2-ene, hexan-2-one.
1
2
OH
5
4
3
5
4
3
6
1
2
1
2
O
4
3
5
6
Activity
Write down the names of these molecules:
•• A four carbon chain with an alcohol on the second carbon atom
•• A six carbon carboxylic acid. Why is it not necessary to indicate where the carboxylic group is?
•• A five carbon chain with an alkene group between carbons 2 and 3.
The presence of other atoms or groups of atoms is shown by adding the name and
position of the group at the beginning of the name (see Table 5.4.4).
Table 5.4.4: Prefixes to indicate presence
of other atoms or groups of atoms.
Group
Prefixes to indicate presence of other atoms
or groups of atoms
halogen
chloro-, bromo-, etc.
amine
amino-
alkyl (hydrocarbon chains)
methyl-, propyl- etc.
hydroxyl
hydroxy-
Examples include: 2-methylpentane, 3-methylbutan-1-ol, 3-hydroxypentanoic
acid, as seen in Figure 5.4.17.
Figure 5.4.17: The shortened structural
formulae of 2-methylpentane,
3-methylbutan-1-ol,
3-hydroxypentanoic acid.
CH3
HO
H3C HC
1
5.4: Chemical behaviour of organic compounds
2
CH2 CH2
4
3
CH3
5
HO
CH2 CH2
2
1
CH CH3
3 4
H3C
C
O
1
CH
2 2
CH CH2
3 4
CH3
HO
5
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Unit 5: Chemistry for Applied Biologists
Representing organic molecules
Activity
The diagram below shows the
shortened structural formula of
2-methylpropan-1-ol. Draw this
structure out as (a) a full structural
formula (b) a skeletal formula.
CH3
H3C HC
CH2OH
You were introduced to full structural, shortened structural and skeletal formulae
in Topic guide 5.1.
•• In a full structural formula, all of the atoms and bonds are shown.
•• In a shortened structural formula, bonds to hydrogen atoms are not shown.
•• In a skeletal formula, only the bonds that make up the skeleton of the
molecule are shown. Carbon atoms and hydrogen atoms are not usually
shown, although other atoms (such as oxygen and nitrogen) are.
Representing groups of atoms
Certain shorthand notations are used to represent particular groups of atoms,
particularly in shortened structural formulae and full structural formulae (see
Table 5.4.5).
Table 5.4.5: Some common
shorthand notations used to represent
particular groups of atoms.
…stands for
Shorthand convention
–CO–
ketone
–CHO
aldehyde
–COO–
carboxylate (e.g. in esters)
Ac–
ethanoate (acetate) CH3COO–
Me–
methyl
Et–
ethyl
Ph–
phenyl
Activity
Activity
Draw out the appropriate
representations of these molecules:
1 a full structural formula of methyl
ethanoate
2 a shortened structural formula of
3-methylbutanoic acid
3 a skeletal formula of
2,3,4-trimethylpentanal.
Use systematic nomenclature to name the following molecules from the formulae shown below.
H
H3C
CH2
CH CH2
CH2OH
H3C
H
H
H
H
C
C
C
H
H
H H
C
H
C
N
H
C
H
Cl
H
Cl
Three-dimensional representations
You learned about the shapes of molecules and the three-dimensional
arrangement of bonds around sp3 hybridised carbon atoms in section 1 of this
topic guide.
Most organic molecules, therefore, have a three-dimensional structure. You should
be aware that full and shortened structural formulae make no attempt to show the
three-dimensional features of the molecules they represent.
Models and computer imagery provide the best way of visualising these molecules
in three dimensions but, in order to show three-dimensional features on a
two-dimensional page, various types of conventions are used.
5.4: Chemical behaviour of organic compounds
11
Unit 5: Chemistry for Applied Biologists
The most common convention is known as a stereochemical formula –
Figure 5.4.18 shows this convention using methane as an example.
Figure 5.4.18: The three-dimensional
structure of methane.
H
H
Key term
Chiral carbon: A carbon atom with
four different groups around it, which
can exist in two non-superimposable
mirror-image arrangements (see
section 5 of this topic guide).
This bond is visualised as pointing
into the plane of the page.
C
H
H
This bond is visualised as pointing
up out of the plane of the page.
This is most commonly used when there is a chiral carbon in the molecular
structure, for which there are two possible three-dimensional arrangements.
Usually, only the bonds surrounding this chiral carbon are shown using the
stereochemical convention, as in Figure 5.4.19.
H
Figure 5.4.19: Stereochemical
representation of R-salbutamol
(used as a bronchodilator).
OH
HO
H
N
CH3
H3C CH3
HO
Fischer projection
Molecules that have several chiral carbon atoms may be difficult or timeconsuming to represent using the stereochemical convention shown above. This
applies particularly to molecules such as sugars.
In these cases, a Fischer projection is often used. This is essentially a drawing
of what the three-dimensional molecule would look like if projected onto a
two-dimensional piece of paper.
Figure 5.4.20: Drawing a
Fischer projection from a
stereochemical structure.
OH
OH
H3C
H
Et
Et
H
CH3
The vertical lines represent bonds
going into the plane of the page.
OH
Et
H
CH3
Fischer projection
The horizontal lines represent
bonds coming out from the plane
of the page.
A Fischer projection can be constructed from a stereochemical structure by
imagining twisting the molecule so that all bonds are pointing either into or out of
the plane of the page. This molecule is then redrawn with vertical and horizontal
lines representing different orientations of the bonds as shown in Figure 5.4.20.
This is much more easily done using models or computer imagery!
5.4: Chemical behaviour of organic compounds
12
Unit 5: Chemistry for Applied Biologists
Portfolio activity (4.2, 4.3)
Lactic acid and valine are the commonly used names of two molecules that occur naturally in
biological systems.
Formulae of these molecules are shown below.
OH
H3C
HC
H2N
C
O
OH
O
lactic acid
HO
valine
Discuss the structures and systematic names of these molecules.
In your answer you should:
•• list the functional groups present in each molecule
•• draw out the full structural formula of each molecule
•• explain how systematic nomenclature can be used to name each of these molecules.
4 Reactions of organic compounds
The reactions of organic compounds can be classified into specific types of
reactions. Many of these types of reactions are used by organisms in metabolic
processes and a much wider range of reactions is used by organic chemists who
devise synthetic routes to design new drugs for use in medicine.
Types of reaction
Substitution
In this type of reaction, one group of atoms is replaced by another, for example, a
reactive Cl group in a halogenoalkane is replaced by an OH group (provided by, for
example, sodium hydroxide solution). Figure 5.4.21 shows an example of this: the
reaction of 1-chloropropane to form propan-1-ol.
Figure 5.4.21: Forming propan-1-ol
from 1-chloropropane in a
substitution reaction.
H
H
C
H
H
H
C
H
H
C
+ OH–
H
Cl
H
H
C
H
C
H
H
C
+ Cl–
OH
H
This is a useful step in organic syntheses as it allows a range of new functional
groups to be inserted into a molecule.
The presence of free radicals can also allow substitution to occur even in normally
unreactive alkyl groups, where the key step is:
CH3CH2CH2CH3 + Cl• ➝ CH3CHClCH2CH3 + H•
Cl• radicals can be generated by the action of ultraviolet radiation on Cl2
molecules.
5.4: Chemical behaviour of organic compounds
13
Unit 5: Chemistry for Applied Biologists
Addition
In an addition reaction two molecules react together to form a single product. This
often occurs in alkenes and other unsaturated molecules. Figure 5.4.22 shows
but-2-ene taking part in addition reactions with hydrogen bromide and with
hydrogen.
H
Figure 5.4.22: Some addition
reactions of but-2-ene.
H
C
C
H
C
H
H
C
C
H
H
H
C
H
C
H
H
C
C
H
+ H2
H
H
H
H
C
H
H
H
H
H
C
H
C
Br
H
H
C
H
+ HBr
H
H
Write an equation to predict the
addition reaction that will occur for
but-2-ene with (a) water (b) Br2.
H
C
H
Activity
H
H
C
H
C
H
H
H
Oxidation and reduction
The oxidation number of a carbon atom increases due to addition of an oxygen
atom, removal of hydrogen or removal of electrons. Figure 5.4.23 shows the
oxidation of a primary alcohol (in this case, ethanol), which can produce an
aldehyde or a carboxylic acid depending on the conditions.
Figure 5.4.23: An alcohol (ethanol) can
be successively oxidised to ethanal (an
aldehyde) and ethanoic acid.
Key term
Primary alcohol: An alcohol in which
the OH– group is at the end of a
carbon chain.
H
H
H
C
C
H
H
H
O
[O]
H
H
C
O
C
H
H
[O]
H
H
C
H
O
C
O
H
Notice that these reactions are represented by reaction schemes, rather than
balanced equations. In a reaction scheme, the reagents are indicated by a label
above the reaction arrow or, in this case, by a general symbol for an oxidising
agent.
Activity
The reaction scheme in Figure 5.4.23 shows the oxidation of a primary alcohol. Research what
happens when secondary or tertiary alcohols are used in these types of reactions.
Link
You learned how to use halfequations to balance redox reactions
involving the reduction of pyruvate in
Topic guide 5.2, section 2.
Reduction is simply the reverse of this process.
In biological systems, reduction occurs when, for example, pyruvic acid (in the
form of pyruvate) is reduced to lactic acid (in the form of lactate). The reaction is
shown in Figure 5.4.24.
Figure 5.4.24: The reduction of
pyruvic acid to lactic acid.
H3C
C
C OH
O
Pyruvic acid
5.4: Chemical behaviour of organic compounds
OH
O
H3C HC
C OH
O
Lactic acid
14
Unit 5: Chemistry for Applied Biologists
Esterification
Key term
Condensation: A reaction in which
two molecules join together with the
elimination of a small molecule in the
process.
Esterification is the formation of an ester from a carboxylic acid and an alcohol. It is
also classified as a condensation (or addition-elimination) reaction. Figure 5.4.25
shows the esterification reaction between ethanoic acid and methanol.
H
Figure 5.4.25: Carboxylic acids
and alcohols react to form esters.
These reactions are reversible.
H
H
O
+ H
C
C
O
H
O
H
Ethanoic acid
C
H
H
O
H
C
C
Hydrolysis
H
+
H
Condensation
C
O
H
H
Methyl ethanoate
Methanol
+ H2O
H
+ Water
In drug design, esterification of carboxylic acid groups in a drug molecule can
significantly increase the ability of a drug to dissolve in lipids and hence cross
the cell membrane (the lipids present in the cell membrane are themselves ester
molecules).
Hydrolysis
Hydrolysis is the breakdown of molecules into simpler components by the action
of water (although most hydrolysis reactions require H+ or OH− ions as catalysts).
Hydrolysis of an ester is the reverse of esterification, as shown in Figure 5.4.25;
amides (or peptide groups) can also be hydrolysed.
An example of a biologically important hydrolysis reaction is the hydrolysis of
ATP to ADP by breaking the phosphodiester bond between two of the phosphate
groups, which is used to release chemical energy to do biological work. This is
shown in Figure 5.4.26.
Figure 5.4.26: The hydrolysis of ATP
to ADP and inorganic phosphate (Pi ).
The reaction is highly exergonic.
O–
O–
O–
–
O–
O P O P O P O CH2
O
O
O
ATP
–
Adenine
H H
H
H
OH OH
+
O–
O P O P O CH2
O
H
H
Water
O
O
ADP
Adenine
H H
H
H
OH OH
+
O–
HO P O–
+ H+
O–
Pi
Acid–base reactions
Link
This links in with the work on the
Brønsted–Lowry theory of acid–base
reactions dealt with in Topic guide 3,
section 4.
Acid–base reactions are those in which H+ ions are transferred.
Carboxylic acids act as acids:
CH3COOH + NaOH ➝ CH3COO−Na+ + H2O
Amines act as bases:
CH3CH2CH2CH2NH2 + HCl ➝ CH3CH2CH2CH2NH3+Cl−
Several amino acid side groups contain carboxyl or amine groups and so these
processes are important in creating charged regions of receptor sites on proteins,
which in turn is important for the mechanism of enzyme action or for binding
between receptors and ligand molecules.
5.4: Chemical behaviour of organic compounds
15
Unit 5: Chemistry for Applied Biologists
Combustion reactions and free radical processes
Alkanes and alkyl groups (such as the chains of saturated carbon atoms which
make up the skeleton of organic molecules) are chemically unreactive to acids
and bases and other ionic reactants. Other than reaction with free radicals (see
earlier in this section), the only other significant reaction of these molecules is
combustion, used to generate heat energy from the burning of biomass:
Activity
Look at the list of reactions below.
Research the reagents and/or
conditions necessary to carry out
these reactions in the laboratory.
1 Substitution reactions of
halogenoalkanes to form alcohols.
2 Addition reactions of alkenes to
form halogenoalkanes.
3 Oxidation of primary alcohols
to form aldehydes, and to form
carboxylic acids.
4 Formation of esters from
carboxylic acids and alcohols.
5 Hydrolysis of esters.
Activity
Find details of the synthesis of
zidovudine (AZT) from thymidine.
Identify any steps in these reactions
that can be classified as substitution,
esterification or hydrolysis.
C6H14 + 9.5O2 ➝ 6CO2 + 7H2O
Take it further
More details of these reactions, including other examples of each of these reactions, can be found
in most level 3 Chemistry textbooks.
Other reactions to research could include:
•• substitution reactions of alcohols with hydrogen halides
•• substitution reactions of halogenoalkanes with ammonia and amines
•• addition reactions of alkenes with water and with bromine
•• oxidation of secondary alcohols.
Write suitable equations to show what happens in any reaction you research.
Portfolio activity (4.4)
Below is a list of several reactions that might be of use to a chemist in developing the synthesis of
new compounds.
1 The reaction of pent-2-ene with bromine
2 The reaction of 2,2-dimethylpropan-2-ol with hydrogen bromide
3 The reaction of propanoic acid with pentan-2-ol.
Describe these reactions. In your answer you should:
•• write out a balanced equation for each reaction, using full or shortened structural formulae
•• state what type of reaction has occurred
•• describe the reagents and conditions required for the reaction to occur.
Case study: Synthetic organic chemistry
Zidovudine (AZT) has become one of the most important drugs in the control of HIV-AIDS. In combination with other drugs it has dramatically
increased the life expectancy of individuals infected with HIV. The global challenge now is to ensure that cheap supplies of the drug can be made
available to developing nations, particularly in subSaharan Africa where infection rates are high.
Synthetic organic chemists devise methods for synthesising specific molecules that are already known to have biological action. Most syntheses are
multi-step processes, starting from a substance that is readily available, either as a natural product or as a cheap derivative of substances extracted
from crude oil. Chemists often design a synthesis by working backwards from the final target, deducing which molecular fragments need to be
combined to produce this target and which functional group conversions need to be carried out. In the case of AZT synthesis, this approach led
them back to the molecule thymidine (related to the nucleotide thymine).
If you look at the synthetic route for AZT production, starting from thymidine (readily available from websites) you will recognise some of the types
of reactions you have encountered in this section, such as esterification, hydrolysis and substitution.
There are often other problems for the synthetic organic chemist to solve – for example, how to allow the substitution of one OH– group, for
example, while leaving other OH– groups unchanged. This often causes synthetic schemes to be quite long and convoluted as these other groups
may need to be protected in some way, for example, by converting them to an ester – and then later on in the synthesis the protection needs to be
removed.
Another issue which makes the synthesis more difficult to design is the need to ensure that the correct stereoisomer is produced; some reactions
produce a mix of isomers while others are much more stereoselective. If a mix of isomers is produced then the required isomer must be separated
before proceeding. Some alternative syntheses of AZT start from a cheaper starting material (D-mannitol), but some of the steps have this problem
of lack of stereoselectivity.
5.4: Chemical behaviour of organic compounds
16
Unit 5: Chemistry for Applied Biologists
5Isomerism
Key term
Some of the material in this section is covered in more detail in the presentation
‘Structure and naming of organic compounds’.
Isomers: Two molecules are isomers
if they have the same molecular
formula but different arrangements
of atoms.
Types of isomerism
The different types of isomerism are summarised in Figure 5.4.27.
OH
OH
OH
Figure 5.4.27: Summary and examples
of the different types of isomerism.
O
The pattern of
branching in a chain of
C atoms is different
Groups are attached to the
chain in different positions
Different functional
groups are present
Chain isomerism
Position isomerism
Functional group
isomerism
Atoms are arranged
in a different order
Structural isomerism
Isomerism
Atoms are arranged in the
same order but are arranged
differently in space
Stereoisomerism
Geometric isomerism
The isomers are locked into different geometric
configurations by a double bond or ring structure
Optical isomerism
The isomers are non-superimposable mirror images,
due to the presence of a chiral carbon atom
OH
cis-but-2-ene
trans-but-2-ene
O
NH2
OH
CH3
H
L-alanine
O
CH3
NH2
H
D-alanine
Take it further
Optical isomers are named according to several different systems: L- and D- are used for molecules
such as amino acids and carbohydrates, while R- and S- are more commonly used for other chiral
molecules. You can read more about the R- S- naming system at
http://www.chem.ucalgary.ca/courses/351/orgnom/stereo/stereo-03.html.
5.4: Chemical behaviour of organic compounds
17
Unit 5: Chemistry for Applied Biologists
Biological examples of isomerism
Two case studies can be used to show how different isomers may have
unexpectedly different biological effects.
Trans fats
O
O
O
O
O
O
Figure 5.4.28: The general
structure of a lipid.
Fats and oils are known collectively as lipids; they are esters formed from glycerol
(propane-1,2,3-triol) and fatty acids (which contain long chains of carbon atoms).
The lipid shown in Figure 5.4.28 is a saturated fat – there are no C=C double
bonds in the carbon chains from the fatty acids.
Many lipids derived from plant sources contain fatty acids with double bonds in
the cis configuration. This configuration results in a lower melting point and hence
these lipids are liquid at room temperature (and are therefore known as oils).
Hydrogenation of the double bonds is carried out industrially to decrease
the unsaturation of the fatty acids and increase the melting point of the lipid.
However, in the process, any remaining double bonds are converted into the trans
configuration (see Figure 5.4.29):
Figure 5.4.29: The formation
of a trans fatty acid.
O
OH
O
OH
trans monounsaturated fatty acid
cis polyunsaturated fatty acid
There are concerns about the health effects of consumption of trans fats as it is
thought that they affect the cholesterol balance in the blood and hence increase
the risk of coronary heart disease.
Thalidomide
Thalidomide is a drug originally developed to alleviate the symptoms of morning
sickness in early pregnancy and was widely prescribed in the 1950s.
It has a chiral carbon and therefore exists as two optical isomers (enantiomers).
These are shown in Figure 5.4.30.
Figure 5.4.30: The two optical
isomers of thalidomide.
O
O
O
O
NH
N
O
R-thalidomide
NH
O
N
O
O
S-thalidomide
Thalidomide was administered as a mixture containing both isomers – with tragic
results. Women taking the drug commonly gave birth to babies with severe birth
defects including missing or deformed limbs and many of them died within a few
months. It is now understood that the R-isomer is the active agent in the antinausea properties of the drug, but the S-isomer seems to be able to bind to the
DNA of several key genes involved in foetal development.
The very different properties of the two molecules reflects the fact that receptor
sites for drug molecules in living systems are themselves chiral – so often only
one enantiomer is able to fit into and bind to receptor sites and cause a biological
reaction.
5.4: Chemical behaviour of organic compounds
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Unit 5: Chemistry for Applied Biologists
Portfolio activity (4.5)
Here are the names of some molecules, some of which have importance in biological systems:
butanal, 4-hydroxybut-1-ene, 2-amino-3-methylbutanoic acid, 2-aminopropanoic acid,
3-aminopropanoic acid.
Discuss the isomerism displayed by these molecules.
In your answer you should:
•• draw out the structures of the molecules
•• identify any pairs of molecules that are structural isomers
•• in the case of these structural isomers, explain what type of isomerism is being displayed
•• identify any molecules that can exist as pairs of geometric or optical isomers
•• draw suitable stereochemical diagrams to illustrate the difference in 3-dimensional
arrangement of the atoms in these molecules.
Checklist
At the end of this section you should be familiar with the following ideas:
 the bonding of C atoms can be explained by using ideas of the hybridisation of atomic
orbitals and the subsequent overlap with orbitals on neighbouring atoms
 the type of hybridisation around a C atom also explains the 3-dimensional geometry of
organic molecules
 electron delocalisation occurs in conjugated systems
 organic molecules are classified into different types of molecules depending on which
functional groups are present
 there are agreed rules for the naming of these molecules
 the different functional groups in organic molecules take part in different types of reactions
 the groups of atoms in organic molecules may be arranged in different ways leading to the
existence of isomers (isomerism)
 isomerism can be due to differences in structure or differences in stereochemical
arrangement of the atoms in the molecule.
Further reading
The University of Calgary Chemistry department has produced a helpful online visualisation of the
formation of hybrid orbitals at
http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch02/ch2-3-1.html.
Chemguide also covers these well (http://www.chemguide.co.uk) in the Basic Organic Chemistry
section, and the rest of this section covers the material on naming and isomerism from this guide.
The section on Properties of Organic Compounds covers the main reactions of organic compounds.
Chapter 5 of Advanced Chemistry (Clugston & Flemming, 2000) covers the material about
hybridisation and shapes of molecules and Chapters 21–29 cover organic reactions in some depth.
5.4: Chemical behaviour of organic compounds
19
Unit 5: Chemistry for Applied Biologists
Acknowledgements
The publisher would like to thank the following for their kind permission to reproduce their
photographs:
Shutterstock.com: Anton Prado Photo.
All other images © Pearson Education
In some instances we have been unable to trace the owners of copyright material, and we would
appreciate any information that would enable us to do so.
About the author
David Goodfellow studied Natural Sciences at Cambridge and spent 20 years teaching A-level
Chemistry in a sixth-form college. He was lead developer for the OCR AS Science in 2008 and for
several years was chief examiner for the course. He now works as a freelance writer and examiner
alongside part-time work as a teacher. Publications include a textbook for the AS Science course,
teaching materials to accompany Chemistry GCSE courses and contributions to textbooks for BTEC
First Applied Science.
5.4: Chemical behaviour of organic compounds
20