18: Organic Chemistry III

18A. Arenes
All of the organic substances we have
There are two major classes of organic chemicals
looked at so far have been aliphatic
aliphatic : straight or branched chain organic substances
aromatic or arene: includes one or more ring of six carbon Benzene belongs to the aromatic class.
atoms with delocalised bonding.

Benzene’s Structure In 1865 Kekule suggested the following

The simplest arene is benzene. It has the molecular formula C6H6 structure for Benzene consisting of
Its basic structure is six C atoms in a hexagonal ring, with one H alternate single and double covalent
atom bonded to each C atom bonds between the carbon atoms
Each C atom is bonded to two other C atoms and one H atom by H
single covalent σ-bonds. This leaves one unused electron on each
C atom in a p orbital, perpendicular to the plane of the ring. H C H
The Six p electrons are delocalised in a ring structure above and C C
below the plane of carbon atoms
C C
H C H
H H H H
H
H H H H
This structure is not correct. Evidence
suggests that all the C-C bonds are the
H H H H
same length.

In formulae we draw a circle to show

this delocalised system The six electrons in the pi bonds are delocalised and spread out
over the whole ring. Delocalised means not attached to a particular
atom.

Benzene is a planar molecule.The evidence suggests all the C-C

Abbreviated bonds are the same and have a length and bond energy between a
formula C-C single and C=C double bond

Displayed formula The H-C-C bond angle is 120o in Benzene

Enthalpies of Hydrogenation
Theoretically because there
+ H2  H = -120 kJ/mol are 3 double bonds one might
enthalpy

expect the amount of energy H = -152kJ/mol

cyclohexene cyclohexane x3 to be 3 times as much. delocalisation
energy
-360 kJ/mol
+ 3H2  H = -360 kJ/mol Theoretical
However, the real amount of value
Non delocalised energy is less. The 6 pi
structure electrons are delocalised and H = -208kJ/mol
not arranged in 3 double bonds actual value
+ 3H2  H = -208kJ/mol
This when represented on an energy level
delocalised diagram shows that the delocalised benzene
structure is more thermodynamically stable.

The increase in stability connected to delocalisation is called

the delocalisation energy

Reactions of Benzene
Benzene does not generally undergo addition reactions because these would involve breaking up the delocalised
system. Most of Benzene’s reactions involve substituting one H for another atom or group of atoms. Benzene has
a high electron density and so attracts electrophiles. It reactions are usually electrophilic substitutions

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Naming aromatic molecules

Naming aromatic compounds can be complicated. The simplest molecules are derivatives of benzene and have
benzene at the root of the name

CH3 C2H5 Cl Br NO 2 CO2H CHO

Methylbenzene ethylbenzene chlorobenzene bromobenzene nitrobenzene benzenecarboxylic benzaldehyde

acid

If two or more substituents are present on the benzene ring, their positions must be indicated by the use of
numbers. This should be done to give the lowest possible numbers to the substituents. When two or more
different substituents are present, they are listed in alphabetical order and di, tri prefixes should be used.

CH3 CH3
CH3
COOH
O 2N NO2

CH3
Cl NO2
OH
1,3-dimethylbenzene
1-chloro- 4-methylbenzene 4-hydroxybenzenecarboxylic acid 2,4,6-trinitromethylbenzene

In other molecules the benzene ring can be regarded as a substituent side group on another molecule, like
alkyl groups are. The C6H5- group is known as the phenyl group.
O
NH2 CH CH2 CH3
H3C CH CH2 CH3 O
C
H3C C O

phenylamine phenylethene
2-phenylbutane
phenylethanone phenylethanoate
OH

OH
1-phenylpropane-1,2-diol 3-phenylpropanal

Toxicity of Benzene
Benzene is a carcinogen (cancers causing molecule) and is banned for use in schools.

Methylbenzene is less toxic and also reacts more readily than benzene as the methyl side group releases
electrons into the delocalised system making it more attractive to electrophiles.

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Reactions of Benzene
Combustion
Benzene will combust with a very sooty flame.
Benzene + oxygen  carbon dioxide + water
The lower the carbon to hydrogen ratio the
C6H6 (l) + 7.5 O2  6 CO2 + 3 H20
sootier the flame.
Halogenation of Benzene
Change in functional group: benzene  bromobenzene This reaction can be done with chlorine.
Reagents: Bromine The catalyst can be AlCl3 or FeCl3
Conditions: Iron(III) bromide catalyst FeBr3
It is possible to create the iron(III)
Mechanism: Electrophilic substitution
bromide in situ by reacting iron with
bromine
Overall Equation for reaction Br
Equation for Formation of electrophiles:
+ HBr (Learn!)
+ Br2  AlCl3 + Cl2  AlCl4– + Cl+
FeBr3 + Br2  FeBr4– + Br+

Mechanism Cl
Cl+
H Cl
+

The H+ ion reacts with the AlCl4- to H+ + AlCl4-  AlCl3 + HCl

reform AlCl3 catalyst and HCl.

Nitration of Benzene
Change in functional group: benzene  nitrobenzene
Reagents: conc nitric acid in the presence of concentrated Importance of this reaction
sulfuric acid (catalyst) Nitration of benzene and other arenes is
Mechanism: Electrophilic Substitution an important step in synthesising useful
Electrophile: NO2+ compounds
e.g. explosive manufacture (like TNT,
Overall Equation for reaction trinitrotoluene/ 2,4,6-
NO2
trinitromethylbenzene)
+ NO2 +  + H+ and formation of amines from which
dyestuffs are manufactured. (The reaction
for this is covered in the amines section.)
Equation for Formation of electrophile: (Learn!)
HNO3 + 2H2SO4  NO2+ + 2HSO4- + H3O+

Mechanism This reaction is done at 60oC.

NO 2 On using higher temperatures
HSO4-
NO2+ NO 2 a second nitro group can be
H substituted onto different
+ positions on the ring

If the benzene ring already has

The horseshoe shape of the a side group e.g. methyl then
intermediate must not extend the Nitro group can also join on
beyond C’s 2 to 6 different positions. A-level does
not require knowledge of what
The H+ ion rejoins with the HSO4- to H+ + HSO4-  H2SO4 positions the groups go on.
reform H2SO4 catalyst.

3
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Hydrogenation of Benzene

Reaction: benzene  cyclohexane Ni

Reagents: Hydrogen Catalyst
+ 3H2
Conditions: Nickel catalyst at 200C and 30 atm
Type of reaction: Addition and reduction

Friedel Crafts Alkylation

Change in functional group: benzene  alkylbenzene

Reagents: chloroalkane in the presence of anhydrous Any chloroalkane can be used RCl where
aluminium chloride catalyst R is any alkyl group Eg –CH3 , -C2H5.
Conditions: heat under reflux The electrophile is the R+.
Mechanism: Electrophilic Substitution

Formation of the electrophile.

AlCl3 + CH3CH2Cl  CH3CH2+ AlCl4-

Overall Equation for reaction

CH2CH3
CH3CH2+ AlCl4- + + AlCl3 + HCl

ethylbenzene

Mechanism
+CH CH
2 3 CH 2CH 3
CH2CH3
H
+

The H+ ion reacts with the AlCl4- to

H+ + AlCl4-  AlCl3 + HCl
reform AlCl3 catalyst and HCl.

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Friedel Crafts Acylation
Change in functional group: benzene  phenyl ketone
Reagents: acyl chloride in the presence of anhydrous Any acyl chloride can be used RCOCl where
aluminium chloride catalyst R is any alkyl group e.g. –CH3 , -C2H5. The
Conditions: heat under reflux (50OC) electrophile is the RCO+.
Mechanism: Electrophilic substitution

Equation for Formation of the electrophile.

AlCl3 + CH3COCl  CH3CO+ AlCl4-

Overall Equation for reaction These are important

O
reactions in organic
C synthesis because they
CH3CO+ AlCl4- + CH3 + AlCl3 + HCl introduce a reactive
functional group on to the
benzene ring
phenylethanone

Mechanism O O
+ O
C CH3 C CH3
C
CH3
H
+
The H+ ion reacts with the AlCl4- to
H+ + AlCl4-  AlCl3 + HCl
reform AlCl3 catalyst and HCl.

Effect of side groups on benzene ring

Electron releasing side groups such as alkyl groups, phenols and amines releases electrons into the
delocalised system making a higher electron density in the ring and it more attractive to electrophiles.
They will therefore carry out the substitution reactions more readily with milder conditions.

Effect of delocalisation on side groups with lone pairs

If a –OH group, a Cl atom or an NH2 group is directly attached to a benzene ring the
delocalisation in the benzene ring will extend to include the lone pairs on the N,O and Cl. This
changes the properties and reactions of the side group.
Cl NH2
OH

chlorobenzene
phenylamine
phenol
The C-Cl bond is made stronger.
Typical halogenoalkane Delocalisation makes the C-O Less basic than aliphatic
substitution and elimination bond stronger and the O-H bond amines as lone pair is
reactions do not occur. Also the weaker. Phenol does not act like delocalised and less
electron rich benzene ring will an alcohol- it is more acidic and available for accepting a
repel nucleophiles does not oxidise proton

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Phenols

In a phenol the OH group is directly attached to the CH2OH

benzene ring.
OH
In a phenol the lone pair of electrons on the
oxygen is delocalised with the electron
charge cloud of the arene ring.
The delocalised bonding changes the
This is not a phenol, but is
reactivity of the OH group and the arene ring.
an alcohol because the
OH group is attached to an
alkyl group rather than the
Phenols are very weakly acidic. They are weaker acids than carboxylic acids. benzene ring.
Both phenols and carboxylic acids will react with sodium metal and sodium
hydroxide. Only carboxylic acids will react with sodium carbonate as a phenol
is not strong enough an acid to react.

-
OH + Na O Na+ + ½ H2

The sodium phenoxide

- compound is more soluble
OH + NaOH O Na+ + H2O
than the original phenol. So
solid phenol dissolves on
sodium phenoxide addition of NaOH solution.

Reaction of Phenol with Bromine

Reagents: Bromine water

Conditions: room temp Comparison with benzene
Phenol does not need a FeBr3
OH OH catalyst like benzene and
undergoes multiple substitution
Br Br whereas benzene will only add
one Br.
+ 3 Br2 + 3 HBr

The product in this reaction is a

Br white solid.
2,4,6 –tribromophenol

In phenol the lone pair of electrons on the oxygen (p- orbital) is

partially delocalised into the ring. The electron density in the ring
increases and the Br2 is more polarised.

Phenols are used in the production of plastics,

antiseptics, disinfectants and resins for paints.

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18B. Amines, Amides and Amino Acids
Naming

H H H
Amines H2N O
These end in –amine. H C C C NH2 If there is another
There is, however, rather confusingly CH C
priority functional group
two ways of using this suffix. H H H
as well as the amine H3C O H
The exam board tend to use the propylamine group then the prefix
common version where the name Or propan-1-amine 2-aminopropanoic acid.
amino is used.
stem ends in -yl propylamine.
The IUPAC version of the same
chemical is propan-1-amine. (This is
used in the same way as naming
alcohols)

If the amine is secondary and has two alkyl CH3CH2CH2NHCH3

groups attached to the nitrogen, then each N-methylpropylamine (common name)
chain is named and the smaller alkyl group N-methylpropan-1-amine (IUPAC name)
is preceded by an –N which plays the same
role as a number in positioning a side alkyl CH2 CH2
chain H3C NH CH3

Diethylamine (common name- does not use N if

In the common naming version if the chains are same length)
chain lengths are the same an –N is N-ethylethanamine (IUPAC name does still use N)
not used

CH3CH2 CH2 N CH3

If a tertiary amine similar rules apply,
and each alkyl side group is given an CH3
N N,N-dimethylpropylamine (common name)
N,N-dimethylpropan-1-amine (IUPAC name)

H H
N (CH2)6 N It could also be named
1,6-diaminohexane
H H
hexane-1,6-diamine

Amides

O Secondary and tertiary amides

Add –amide to the stem are named differently to show the O
name CH3 C two (or three) carbon chains.
NH2 The smaller alkyl group is
preceded by an –N which plays H3C CH2 C NH CH3
ethanamide the same role as a number in
N-methylpropanamide
positioning a side alkyl chain

O CH3
CH3 O CH3
H3C CH2 C N CH3
H3C CH C N CH3
N,N-dimethylpropanamide N,N,2-trimethylpropanamide

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Properties of Amines
Amines have a characteristic fishy smell H δ+
δ- δ+ δ-

Small amines can form hydrogen bonds with water

CH3 N H O
δ+
and therefore can dissolve readily in water.
H
Base Properties
H δ+
Primary aliphatic amines act as Bronsted-Lowry Bases because the
lone pair of electrons on the nitrogen is readily available for forming a CH3NH2 +H2O  CH3NH3+ +OH-
dative covalent bond with a H+ and so accepting a proton.

Primary aliphatic amines are stronger bases than ammonia as the

alkyl groups are electron releasing and push electrons towards the NH3 (aq) +H2O (l)  NH4+(aq) +OH-(aq)
nitrogen atom and so make it a stronger base.

Secondary amines are stronger bases than primary amines because they have more alkyl groups that are
substituted onto the N atom in place of H atoms. Therefore more electron density is pushed onto the N atom (as
the inductive effect of alkyl groups is greater than that of H atoms).
One might expect using the same trend that tertiary amine would be the strongest amine base but the trend does
not hold. The tertiary amines and corresponding ammonium salts are less soluble in water and this makes them
less strong bases than the secondary amines. (This point will not be examined)

Base strength of aromatic amines NH2

Primary aromatic amines such as phenylamine do not form basic solutions because the
lone pair of electrons on the nitrogen delocalise with the ring of electrons in the benzene
ring. This means the N is less able to accept protons. phenylamine

Reactions with acids

Amines as bases react with acids to form ammonium salts.

CH3NH2 (aq) +HCl (aq)  CH3NH3+Cl-(aq) Addition of NaOH to an ammonium salt
Methylamine methylammonium chloride will convert it back to the amine
2CH3NH2 (aq) +H2SO4 (aq)  (CH3NH3+)2 SO42- (aq)
These ionic salts will be solid crystals, if
the water is evaporated, because of the
The ionic salts formed in this reaction means that the strong ionic interactions.
compounds are soluble in the acid.
e.g. Phenylamine is not very soluble in water but
phenylammonium chloride is soluble.

Making a basic buffer from an amine

Basic buffers can be made from combining a weak base with a salt of that weak base
e.g. Ammonia and ammonium chloride
Methylamine and methylammonium chloride
Ethylamine and ethylammonium chloride
Formation of complex ions
The lone pair of electrons on the nitrogen enable amines to act as ligands and form dative covalent bonds
into transition metal ions to form coloured complex ions.

4 CH3CH2NH2 + Cu(H2O)62+ [Cu(CH3CH2NH2)4(H2O)2] 2+ +4H2O

This is a similar ligand exchange reaction to the one where ammonia acts as the ligand.

4NH3 + Cu(H2O)62+ [Cu(NH3)4(H2O)2] 2+ + 4H2O

light blue solution deep blue solution
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Reaction of primary amines with halogenoalkanes forming secondary amines

Amines will react with halogenoalkanes in a similar way to the reaction of ammonia with
halogenoalkanes via a nucleophilic substitution reaction.

2CH3CH2NH2+ CH3CH2Br CH3CH2NH2CH2CH3+ CH3CH2NH3Br

H
+
H3C C Br H3C CH2 NH2 CH2 CH3 Br -
H
:

CH3CH2NH2
+
H3C CH2 NH CH2 CH3 H3C CH2 NH CH2 CH3 + CH3CH2NH3Br
:NH2CH2CH3
Diethylamine
H

The secondary amine formed can also then react with more halogenoalkane to form a tertiary
amine and subsequently on to what is called a quaternary ammonium salt
Where RX is the halogenoalkane

H R R
H
RX RX RX
+
H N: R N: R N: R N R

R R R R

Reaction with primary amines with acyl chlorides

Change in functional group: acyl chloride  secondary amide

Reagent: primary amine
Conditions: room temp.

RCOCl +2CH3NH2  RCONHCH3 + CH3NH3+Cl-

O O

CH3 C + 2CH3NH2  CH 3 C NH CH 3 + CH3NH3+Cl-

Cl N-methylethanamide

Paracetamol is made by the reaction of an aromatic amine with

an acyl chloride to produce an amide.
O
CH3 C
Cl O
HO NH2 HO NH C CH3

Paracetamol

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The preparation of primary aliphatic amines
1. Forming a primary amine in a one step reaction of halogenoalkanes with ammonia

Primary amines can be formed by the nucleophilic substitution reaction between halogenoalkanes and ammonia in
a one step reaction. However, as the lone pair of electrons is still available on the N in the amine formed, the
primary amine can react in the same nucleophilic way in a successive series of reactions forming secondary, tertiary
amines and quaternary ammonium salts.
This is therefore not a good method for making a primary amine because of the further reactions. It would mean the
desired product would have to be separated from the other products.

CH3CH2Br + 2NH3  CH3CH2NH2 + NH4Br Ammonia dissolved in ethanol is the initial nucleophile
H H
+ In the first step of the mechanism the nucleophile
H3C C Br H3C C NH3 Br -
attacks the halogenoalkane to form an intermediate.
H
3HN:
H
H H
+ In the second step of the mechanism a second
H3C C NH2 H3C C NH2 + NH4Br ammonia removes a proton from the
:NH3 intermediate (acts as base) to form the amine.
H H H

Using an excess of ammonia can limit the further

subsequent reactions and will maximise the amount of
primary amine formed.

2. Preparing Amines from Nitriles

Using the method above of reacting halogenoalkanes and ammonia is not an efficient method for preparing a
high yield of the primary amine because of the further substitution reactions that occur.
A better method is to use the following two reactions.
Step 1. convert halogenoalkane to nitrile by using KCN in ethanol (heat under reflux)

CH3CH2Br + CN-  CH3CH2CN + Br -

Step 2. reduce nitrile to amine by using LiAlH4 in ether or by reducing with H2 using a Ni catalyst.

CH3CH2CN + 4[H] CH3CH2CH2NH2

A disadvantage of this method is that it is a two step reaction that may therefore have a low yield. Also
KCN is toxic.

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Reducing nitroarenes to aromatic amines
The nitro group on an arene can be reduced an amine group as follows

Reagent: Sn and HCl or Fe and HCl NO 2 NH2

Conditions: Heating + 6[H] + 2H2O
Mechanism: Reduction

phenylamine
nitrobenzene

As the reaction is carried out in HCl the salt C6H5NH3+Cl- will be formed.
Reacting this salt with NaOH will give phenylamine.

The phenylamine formed in this reaction is best

separated from the reaction mixture by steam distillation.

Forming Amides
Aliphatic amines and phenylamine can react with acyl chlorides to form amides in a nucleophilic
addition-elimination reaction- see chapter 17C for more details.

Change in functional group:

acyl chloride  secondary amide
Reagent: primary amine
Conditions: room temp.

RCOCl +2CH3NH2  RCONHCH3 + CH3NH3+Cl-

O O
+ -
CH3 C + 2CH3NH2  CH3 C NH CH3 + CH3NH3 Cl
Cl
N-methylethanamide

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Condensation Polymerisation
In condensation polymerisation there are two different monomers
The two most common types of that add together and a small molecule is usually given off as a
condensation polymers are side-product e.g. H2O or HCl.
polyesters and polyamides which
involve the formation of an ester The monomers usually have the same functional group on both ends
linkage or an amide linkage. of the molecule e.g. di-amine, di carboxylic acid, diol, diacyl chloride.

Forming polyesters and polyamide uses these reactions we met earlier in the course

Carboxylic Acid + Alcohol  Ester + water Carboxylic Acid + Amine  amide + water
Acyl chloride + Alcohol  Ester + HCl Acyl chloride + Amine  amide + HCl

If we have the same functional group on each end of molecule we can make polymers so we have the
analogous equations:
dicarboxylic acid + diol  poly(ester) + water dicarboxylic acid + diamine  poly(amide) + water
diacyl dichloride + diol  poly(ester) + HCl diacyl dichloride + diamine  poly(amide) + HCl

Using the carboxylic acid to make the ester or amide would need an acid catalyst and would only give an
equilibrium mixture. The more reactive acyl chloride goes to completion and does not need a catalyst but does
produce hazardous HCl fumes.

Terylene- a common polyester

O O
O O
n + n HO CH CH OH C C O CH2 CH2 O + 2n-1 H2O
C C 2 2
n
HO OH Ethane-1,2-diol
The -1 here is because at
Benzene-1,4-dicarboxylic acid
each end of the chain the H
Terylene fabric is used in clothing and tire cords. and OH are still present

O O O O
n C (CH2)3 C + n HO OH + 2n-1 HCl
C (CH2)3 C O O
Cl Cl n
Pentanedioyl dichloride Benzene-1,4-diol

Nylon 6,6 - a common polyamide

O O
O O H H
N (CH2)6 N
n C (CH2)4 C +n C (CH2)4 C N (CH2)6 N + 2n-1 H2O
H H
HO OH
hexanedioic acid Hexane-1,6-diamine H H
n
The 6,6 stands for 6 carbons in each of the monomers. Different length carbon chains produce different
polyamides
Kevlar- a common polyamide

O O
n HO2C CO2H + n H2N NH2 + 2n-1 H2O
N N C C
H H n

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Note on classification for condensation polymers
If asked for type of polymer: It is polyamide or polyester
Whereas type of polymerisation is condensation
It is also possible for polyamides and polyesters to form from one monomer, if that monomer
contains both the functional groups needed to react

O O O O
HO (CH2)3 C O (CH2)3 C O (CH2)3 C O (CH2)3 C
Cl
3 repeating units

O O O O
H2N C
N C N C N C
OH
H H H
3 repeating units

Chemical reactivity of condensation polymers The reactivity can be explained by the presence of
polyesters and polyamides can be broken down by polar bonds which can attract attacking species
hydrolysis and are, therefore, biodegradable such as nucleophiles and acids

Hydrolysis
Polyesters and polyamides can be hydrolysed by acid and alkali
The hydrolysis will result in the original monomers forming- although the carboxylic acid or amine group
will be in salt form depending on whether the conditions are alkaline or acidic

O O
O
+
HCl OH H 3N +
C (CH2)4 C N (CH2)6 N
HO
+ NH 3
H H O
n

NaOH O
-
-CO(CH2)4CONHC(CH3)2CH2O- - O
O + H2N
This polymer has both an amide and O
OH
ester link

Intermolecular bonding between condensation polymers chains

Polyesters have permanent dipole forces between the Cδ+=Oδ- groups in the different chains in
addition to the London forces between the chains.

Polyamides (and proteins) have hydrogen δ-

:

O Oδ- O
bonding between the lone pairs on oxygen in δ-
N C N C Nδ- C
Cδ+=Oδ- groups and the H in the Nδ- —Hδ+ δ+ δ+
H H δ+ H δ+
groups in the different chains.
There are also Permanent dipole-permanent
dipole forces because the polar C=O
:

O δ- Oδ- O
bond and polar C-N bond δ- δ-
N C N C N C
There are also London forces which are large δ+ δ+
because there are many electrons in the H H Hδ+
δ+
molecule
Polyamides will therefore have higher melting
points than polyesters.

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Amino Acids

The simplest amino acid is

General structure of an amino acid NH2 CH2 CO2H
glycine, where the R is an H
NH2 CH CO2H

R
The R group can be a variety of
different things depending on what
amino acid it is.

Naming amino acids

CO2H Some amino acids have an extra CO2H
You do not need to know any carboxylic acid or an amine
CH2 CH2
common names for the 20 group on the R group. These are
essential amino acids. We NH2 C CO2H classed as acidic or basic NH2 C CO2H
should, however, be able to H 2-aminobutanedioic acid (respectively) amino acids H
name given amino acids using Aspartic acid
IUPAC organic naming OH
CO2H
CH2
H C (CH2)4 NH2
NH2 CH2 CO2H NH2 C CO2H Lycine (basic)
H 2-amino-3-
H2N 2,6-diaminohexanoic acid
(2-)aminoethanoic acid
hydroxypropanoic acid

Zwitterions
R R
The no charge form of an amino acid never occurs. + -
The amino acid exists as a dipolar zwitterion. H2N C CO2H H3N C CO2
H H
Amino acids are often solids Zwitterion
The ionic interaction between zwitterions explains the relatively high melting points of amino acids as
opposed to the weaker hydrogen bonding that would occur in the no charge form.

Acidity and Basicity

The amine group is basic and the carboxylic acid group is acidic. Amino acids act as weak buffers and will
only gradually change pH if small
R OH- R H+ R amounts of acid or alkali are added to the
- + - +
H2N C CO2 H3N C CO2 H3N C CO2H amino acids.
+NH -CH -CO - + HCl  Cl- NH3+-CH2-CO2H
H H H 3 2 2
H+ OH-
+NH -CH -CO - + NaOH  NH2-CH2-CO2-Na+ +H2O
Species in Species in Species in 3 2 2
alkaline solution neutral solution acidic solution
High pH Low pH

-
The extra carboxylic acid or amine groups COO
on the R group will also react and change CH2 Aspartic acid in high pH
form in alkaline and acid conditions -
NH 2 C COO
H

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Chromatography of Amino Acids
A mixture of amino acids can be separated by Method
chromatography and identified from the amount Take chromatography paper
they have moved. and draw a pencil line 1.5cm
from bottom.
With a capillary tube put a small
Rf value = distance moved by amino acid
drop of amino acid on pencil line
distance moved by the solvent Roll up paper and stand it in a
large beaker.
Each amino acid has its own Rf value. The solvent in the beaker
Compare an unknown amino acid’s Rf should be below the pencil line.
value with known values in a data book to Allow to stand for 20 mins and
identify the amino acid mark final solvent level
Spray paper with ninhydrin and
put in oven

If ninhydrin is sprayed on an amino acid and then heated for 10 minutes then red to blue spots appear.
This is done because amino acids are transparent and cannot be seen.

Optical Activity Optical isomers have similar

All amino acids, except H H
physical and chemical
glycine, are chiral because properties, but they rotate
there are four different groups C C
H2N CO2H HO2C plane polarised light in
around the C NH2 different directions.
CH3 CH3
They rotate plane polarised light.

Proteins CH3

Proteins are polymers made from H3C CH3 S

combinations of amino acids. CH HS CH2
The amino acids are linked by peptide links,
CH3 O CH2 O CH2 O CH2 O
which are the amide functional group.
H N CH C N CH C N CH C N CH C O H
O O O H H H H
NH CH C NH CH C NH CH C

R R R

Dipeptides
Dipeptides are simple combination molecules of For any two different amino acids there are two possible
two amino acids with one amide (peptide) link. combinations of the amino acids in the dipeptide.

HO HO
HO
CH3 H
Can make CH3 H CH2 CH2 CH3
CH2 or
H2N C CO2H +
H2N C C N C CO2H H2N C C N C CO2H
H H2N C CO2H
H H H O H
O
H

N Goalby chemrevise.org 15
 O δ- O
Importance of hydrogen bonding in proteins

:
δ-
N CH C N CH C
The 3D arrangement of amino acids with the δ+
polypeptide chain in a corkscrew shape is held in δ+
H R H R
place by Hydrogen bonds between the H of –Nδ-

:
—Hδ+ group and the –O of Cδ+=Oδ- δ-
O O
δ-
N CH δ+ C N CH C

H R H R

Hydrolysis of di-peptides/proteins
If proteins are heated with dilute acid or alkali they can be The composition of the protein
hydrolysed and split back in to their constituent amino acids. molecule may then be deduced by
using paper chromatography
H3C CH3
CH H3C CH3
CH
CH3 O CH2 O CH3 O
H+
H N CH C N CH C O H + CH2 O
H3N CH C O H + +
H3N CH C O H
H H

O H 3C CH 3
CH
C OH O H 3C CH 3

CH2 O H 2C O - CH
C O
NaOH
H N CH C N CH C O H CH2 O H 2C O
+
- -
H 2N CH C O H 2N CH C O
H H

Other reactions of amino acids

The carboxylic acid group and amine group in amino acids can undergo the usual reactions of these functional groups met
in earlier topics. Sometimes questions refer to these.
e.g. Esterification reaction
CH3
CH3 O
H+ +
H2N C CO2H + CH3OH H3N C C O CH3 + H2O

H H
CO 2 H O
If the R group contains
CO2H H C (CH 2) 4 NH C CH 3 a amine or carboxylic
H C (CH2)4 NH2 + 2CH3COCl NH acid then these will do
H2N the same reactions as
C O the α amine and
CH3 carboxylic groups

N Goalby chemrevise.org 16
 18C. Synthetic Routes
KOH aqueous
dihalogenoalkane heat under reflux
Nucleophilic substitution

poly(alkene) diol
Br2, Cl2 KMnO4
room temp oxidation
Electrophilic addition

high pressure
alkane
Catalyst Br2, Cl2
H2, Nickel Catalyst
polymerization UV light
addition/reduction
alkene HBr, HCl
Free radical Substitution
room temp
Electrophilic addition
KOH alcoholic heat
halogenoalkane
conc. H3PO4 under reflux
H2O (g) Elimination
Catalyst: Elimination,
dehydration
Conc H3PO4
P Cl5, NaBr/H2SO4 P + I2 CN– and
ethanol
,

Heat under reflux

Nucleophilic
substitution KOH aqueous Alcoholic NH3 substitution
heat under reflux heat under pressure
Nucleophilic substitution Nucleophilic

LiAlH4
alcohol substitution

Reduction Caboxylic acid + H2SO4

heat amine LiAlH4
nitrile
LiAlH4 K2Cr2O7/H+ esterification
Reduction
Reduction
LiAlH4
If primary If secondary Reduction halogenoalkane
heat gently and distill heat under reflux NuSub
partial oxidation oxidation
Acyl chloride
2o amine room temp
3o amine Nu add/elim
aldehyde ketone
HCN + KCN secondary
Nucleophilic addition amide
K2Cr2O7/H+
heat under reflux + Esters and amides
excess oxidising agent can be hydrolysed
Oxidation hydroxynitrile by NaOH and acids

1o amine
Alcohol + H2SO4 room temp Primary
heat ester amide
carboxylic acid esterification

Alcohol
PCl5 room temp NH3 room temp
H2O room
temp Acyl chloride
Acid hydrolysis
Heat with HCl

N Goalby chemrevise.org 17
 Aromatic synthetic routes

Br

CH2CH3

chloroalkane and
anhydrous AlC3
Hydrogen Electrophilic catalyst
Nickel substitution
catalyst Br2
FeBr3

conc nitric acid +

conc sulfuric acid
Electrophilic NO2
substitution
Sn and HCl NH2
NH CH3
reduction CH3Cl
Nu sub
acyl chloride in the presence
of anhydrous aluminium
chloride catalyst
Electrophilic substitution
O CH3COCl

C
CH3 O
NaCN + H2SO4 NH C CH3
Nu Add

LiAlH4 H
Red Nu Add
O
H
C CN
O
CH CH 3
CH3

HCl/heat
H
O O
CH3CO2H + H2SO4
heat C C
esterification OH
CH3
O
H3C CH O C CH3

N Goalby chemrevise.org 18
Grignard Reactions
Grignard Reagent is used to increase the length of the carbon chain in a molecule

Preparing Grignard Reagent

A halogenoalkane is dissolved in dry ether and reacted with magnesium to
produce the reactive Grignard Reagent

This Grignard reagent is highly reactive and the

CH3CH2I + Mg  CH3CH2MgI
alkyl group can be considered to have a
Ethyl magnesium iodide negative charge. The R- [+MgI] and so contains
Grignard Reagent
a nucleophilic carbon atom

Reactions of Grignard Reagent

Reactions with carbonyls

With methanal will produce a primary alcohol
H2O
CH3CH2MgI + HCHO  CH3CH2CH2OH + Mg(OH)I

RMgI + HCHO  RCH2OH + Mg(OH)I

With other aldehydes will produce secondary alcohols

CH3
H2O
CH3CH2MgI + CH3CHO  H3C CH2 C OH + Mg(OH)I
H
H2O
RMgI + R’CHO  RCH(OH)R’ + Mg(OH)I

With ketones will produce tertiary alcohols

CH3
H3C CH3 H2O
CH3CH2MgI + C  H3C CH2 C OH + Mg(OH)I

O CH3
H2O
RMgI + R’COR”  RR’C(OH)R” + Mg(OH)I

Reaction with carbon dioxide

With CO2 will produce a carboxylic acid

H2O
CH3CH2MgI + CO2  CH3CH2CO2H + Mg(OH)I

The carbon chain can also be increased by the introduction of a nitrile group into a compound by either
reacting a halogenoalkane with KCN (see chapter 6D) or producing hydroxynitriles from carbonyls (see
chapter 17B)

N Goalby chemrevise.org 19
 Organic techniques
It’s important to be able to
draw and label this
Distillation apparatus accurately.
thermometer Don’t draw lines between
In general used as separation technique to separate an flask, adaptor and
organic product from its reacting mixture. Need to condenser.
collect the distillate of the approximate boiling point
range of the desired liquid.

Classic AS reaction using distillation Liebig condenser

Reaction: primary alcohol  aldehyde
Reagent: potassium dichromate (VI) solution and
dilute sulfuric acid.
Conditions: use a limited amount of dichromate
and warm gently and distil out the aldehyde as it
forms [This prevents further oxidation to the Water
carboxylic acid] out
CH3CH2CH2OH + [O]  CH3CH2CHO + H2O
Round Water in
Observation
bottomed
Orange dichromate solution changes to green
flask
colour of Cr3+ ions
Heat

Reflux
Reflux is used when heating organic reaction mixtures for long Water out
periods. The condenser prevents organic vapours from escaping
by condensing them back to liquids.
condenser
Never seal the end of the condenser as the build up of gas
pressure could cause the apparatus to explode. This is true of any
apparatus where volatile liquids are heated

Classic AS reaction using reflux

Reaction: primary alcohol  carboxylic acid Water in
Reagent: potassium dichromate(VI) solution and dilute
sulfuric acid
Conditions: use an excess of dichromate, and heat
under reflux: (distil off product after the reaction Round
has finished using distillation set up) bottomed
CH3CH2CH2OH + 2[O]  CH3CH2CO2H + H2O flask
Observation
Orange dichromate solution changes to green colour of
Cr3+ ions
Heat

Anti-bumping granules are added to the flask in both distillation and reflux to prevent vigorous,
uneven boiling by making small bubbles form instead of large bubbles

It’s important to be able to draw and label this apparatus accurately.

• Don’t draw lines between flask and condenser.
• Don’t have top of condenser sealed
• Condenser must have outer tube for water that is sealed at top and bottom
• Condenser must have two openings for water in and out that are open

N Goalby chemrevise.org 20
 Purifying an organic liquid General method

• Put the distillate of impure product into a separating

funnel
• wash product by adding either Sodium hydrogencarbonate will
• sodium hydrogencarbonate solution , shaking neutralise any remaining reactant acid.
and releasing the pressure from CO2 produced. Sodium chloride will help separate the
• Saturated sodium chloride solution organic layer from the aqueous layer

•Allow the layers to separate in the funnel, and then run and The layer with lower density will Separating
discard the aqueous layer. be the upper layer. This is usually funnel
the organic layer
•Run the organic layer into a clean, dry conical flask and add
three spatula loads of drying agent (e.g. anhydrous sodium
The drying agent should
sulfate, calcium chloride) to dry the organic liquid. When dry
•be insoluble in the organic liquid
the organic liquid should appear clear.
• not react with the organic liquid
• Carefully decant the liquid into the distillation flask
Decant means carefully pour off organic liquid
•Distill to collect pure product leaving the drying agent in the conical flask

Purifying an organic solid: Recrystallisation Used for purifying aspirin

Step Reason

1. Dissolve the impure compound in a minimum An appropriate solvent is one which will dissolve both
volume of hot (near boiling) solvent. compound and impurities when hot and one in which
the compound itself does not dissolve well when cold.
The minimum volume is used to obtain saturated
solution and to enable crystallisation on cooling (If
excess (solvent) is used, crystals might not form on
cooling)
2. Hot filter solution through (fluted) filter paper This step will remove any insoluble impurities and
quickly. heat will prevent crystals reforming during filtration
3. Cool the filtered solution by inserting beaker in ice Crystals will reform but soluble impurities will remain
in solution form because they are present in small
quantities so the solution is not saturated with the
impurities. Ice will increase the yield of crystals
4. Suction filtrate with a buchner flask to separate The water pump connected to the Buchner flask
out crystals reduces the pressure and speeds up the filtration.
5 Wash the crystals with distilled water To remove soluble impurities

6. Dry the crystals between absorbent paper

Loss of yield in this process

• Crystals lost when filtering or washing
• Some product stays in solution after recrystallisation
• other side reactions occurring Buchner flask

If the crystals are not dried properly the mass will be larger
than expected which can lead to a percentage yield >100%

N Goalby chemrevise.org 21
Steam distillation steam
in

In steam distillation steam is passed into

the mixture and the product vapour is
distilled off with the water and condensed

Advantage of steam distillation:

The product distils at a lower temperature
which can prevents decomposition of the
product if it has a high boiling point

Water
out

Water
in

Solvent extraction

Mix organic solvent and oil-water mixture in a

separating funnel then separate the oil layer.
Distil to separate oil from organic solvent
Add anhydrous CaCl2 to clove oil to dry oil
Decant to remove CaCl2
Separating funnel

Safety and hazards

A hazard is a substance or procedure that can has the RISK: This is the probability or chance that
potential to do harm. harm will result from the use of a
Typical hazards are toxic/flammable /harmful/ hazardous substance or a procedure
irritant /corrosive /oxidizing/ carcinogenic

Irritant - dilute acid and alkalis- wear googles Hazardous substances in low
Corrosive- stronger acids and alkalis wear goggles concentrations or amounts
Flammable – keep away from naked flames will not pose the same risks
Toxic – wear gloves- avoid skin contact- wash hands after use as the pure substance.
Oxidising- Keep away from flammable / easily oxidised materials

N Goalby chemrevise.org 22
Measuring melting point
One way of testing for the degree of purity is to determine the melting
“point”, or melting range, of the sample.
Thermometer with
If the sample is very pure then the melting point will be a capillary tube
sharp one, at the same value as quoted in data books. strapped to it
containing sample
If impurities are present (and this can include solvent from the
recrystallisation process) the melting point will be lowered and Heating oil- needs
the sample will melt over a range of several degrees Celsius to have boiling point
higher than samples
melting point and
Melting point can be measured in an electronic melting point low flammability
machine or by using a practical set up where the capillary tube is
strapped to a thermometer immersed in some heating oil.
In both cases a small amount of the salt is put into a capillary tube.

Heat
Comparing an experimentally determined melting point
value with one quoted in a data source will verify the
degree of purity.

Sometimes an error may occur if the temperature on the thermometer is not the same as the temperature in
the actual sample tube.

Measuring boiling point

Purity of liquid can be determined by measuring a boiling point. This can be
done in a distillation set up or by simply boiling a tube of the sample in an To get a correct measure
heating oil bath. of boiling point the
thermometer should be
Pressure should be noted as changing pressure can change the boiling above the level of the
point of a liquid surface of the boiling liquid
and be measuring the
temperature of the
Measuring boiling point is not the most accurate method of identifying a saturated vapour.
substance as several substances may have the same boiling point.

N Goalby chemrevise.org 23
Combustion Analysis
0.328 g of a compound containing C,H and O was burnt completely in excess oxygen,
producing 0.880 g of carbon dioxide and 0.216 g of water. Use these data to calculate
the empirical formula of the compound.

Work out moles of CO2 = Mass of CO2/Mr of CO2

= 0.88/44
=0.02mol
Moles of C in compound = moles of CO2 Mass of C in = mol of C x 12
= 0.02 mol compound =0.02 x12
=0.24g
Work out moles of H2O = Mass of H2O /Mr of H2O
= 0.216/18
=0.012mol

Moles of H in compound = 2 x moles of H2O Mass of H in = mol of H x 1

= 0.024 mol compound =0.024 x1
=0.024g

Work out mass of O = mass of compound – mass of C – mass of H

in compound = 0.328 – 0.24 -0.024
=0.064

Work out moles of O = Mass of O /Ar of O

in compound = 0.064/16
= mol 0.004

Work out molar ratio

of 3 elements (divide C = 0.02/0.004 H = 0.024/0.004 O = 0.004/0.004
by smallest moles) =5 =6 =1

empirical formula = C5H6O

See notes in chapter 19 on spectroscopy for mass spec, IR, and NMR

N Goalby chemrevise.org 24
Bringing it all together
C H O
1. Work out empirical formula
66.63/12 11.18/1 22.19/16
Elemental analysis C 66.63% H 11.18% O 22.19%
=5.5525 =11.18 =1.386875
=4 =8 =1

2. Using molecular ion peak m/z value from mass

spectrum calculate Molecular formula Mr empirical formula C4H8O = 72
molecular ion peak m/z value= 144 If Mr molecular formula 144 then
compound is C8H16O2

3. Use IR spectra or functional group C8H16O2 could be an ester, carboxylic acid or combination of
chemical tests to identify main alcohol and carbonyl. Look for IR spectra for C=O and O-H
bonds/functional group bonds

There is a C=O but no

O-H absorptions, so
must be an ester.

C-H
C=O

CH3

4. Use NMR spectra to give details of carbon chain singlet of area 9 H3C C H
At δ =0.9 CH3
4 peaks – only 4 different environments. Means 3 CH3 groups
9

Peak at δ 4 shows H–C–O Peak at δ 1.2

Peak at δ 2.2 shows H–C=O
shows R-CH3
Area 2 suggests CH2 Area 2 suggests CH2 Area 3 means CH3
Quartet means next to a Singlet means adjacent to Triplet means next
CH3 C with no hydrogens to a CH2
H H3C CH3
H O
H3C O C H
H3C O C C H 2
2 3
H
H

5 4 δ ppm 3 2 1

Put all together to give final structure

CH3 O
H3C C CH2 C O CH2 CH3
CH3

N Goalby chemrevise.org 25
 Testing for Organic Functional Groups

Functional group Reagent Result

Alkene Bromine water Orange colour

decolourises
Alcohols + carboxylic acids PCl5 Misty fumes of HCl
produced
Alcohols, phenols, Sodium metal Effervescence due to H2
carboxylic acids gas
Carbonyls 2,4-DNP Orange/red crystals
produced
Aldehyde Fehling’s solution Blue solution to red
precipitate
Aldehyde Tollen’s reagent Silver mirror formed

Carboxylic acid Sodium carbonate Effervescence of CO2

evolved
1o 2o alcohol and Sodium dichromate and Orange to green colour
aldehyde sulfuric acid change
chloroalkane Warm with silver nitrate Slow formation of white
precipitate of AgCl
Acyl chloride Silver nitrate Vigorous reaction- steamy
fumes of HCl- rapid white
precipitate of AgCl

Tollen’s Reagent Fehling’s solution

Reagent: Tollen’s Reagent formed by mixing aqueous Reagent: Fehling’s Solution containing blue Cu 2+ ions.
ammonia and silver nitrate. The active substance Conditions: heat gently
is the complex ion of [Ag(NH3)2]+ . Reaction: aldehydes only are oxidised by Fehling’s
Conditions: heat gently Solution into a carboxylic acid and the copper ions
are reduced to copper(I) oxide .
Reaction: aldehydes only are oxidised by Tollen’s
reagent into a carboxylic acid and the silver(I) Observation: Aldehydes :Blue Cu 2+ ions in solution
change to a red precipitate of Cu 2O. Ketones do
ions are reduced to silver atoms not react
Observation: with aldehydes, a silver mirror forms
coating the inside of the test tube. Ketones result CH3CHO + 2Cu2+ + 2H2O  CH3COOH + Cu2O + 4H+
in no change.

CH3CHO + 2Ag+ + H2O  CH3COOH + 2Ag + 2H+

The presence of a carboxylic acid can be tested by

addition of sodium carbonate. It will fizz and produce
carbon dioxide
2CH3CO2H + Na2CO3  2CH3CO2-Na+ + H2O + CO2

N Goalby chemrevise.org 26