CHEMISTRY FORM 6

ORGANIC CHEMISTRY
CHAPTER 8 : AMINE
9.1 Introduction and nomenclature

Amines are organic compounds with functioning group –NH2 (aminO)

The naming of amine depends on the classification of amine. Table below
shows different class of amine and their naming
Classificatio
Example
n

CH3CH2CH2NH2

3-ethyl-1-
propylamine 2-methylpropylamine methylpentylamine
Primary
amine

4,4-dimethyl Phenylamine
cyclopentylamine cyclohexylamine or Aniline
Secondary
amine
N-propylaniline
N-cyclopentyl
N-ethylpropylamine
cyclohexylamine

Tertiary
amine
N-ethyl-N-methyl N,N-diphenyl N,N-dipropyl
propylamine methylamine ethylamine

Quaternary
salt
Ammonium chloride Tetramethylammonium Tetraethylammonium
bromide hydroxide
9.1 Physical properties of amine

Boiling point of increasing in homologous series

Amine CH3NH2 C2H5NH2 C3H7NH2 C4H9NH2 C5H11NH2

Boiling point oC 4 17 52 83 106
Boiling point
trend Boiling point increase
Explanation :
When going down to homologous series, the boiling point increase. This is
due to the increase in relative molecular mass, which increase the weak Van Der Waals
forces causing boiling point increase.

Classification of
Primary amine Secondary amine Tertiary amine
amine
Example (same
CH3CH2CH2NH2 CH3CH2NHCH3 (CH3)3N
RMM)
Boiling point (oC) 52 34 2
Explanation : Amine can form hydrogen bond between molecules. Straight chain molecule has a
larger total surface area compare to a branched chain molecule. Hence, greater the total surface area
exposed, greater the Van Der Waals forces, higher the boiling point. However, tertiary amine cannot
form hydrogen bond, so their boiling point decrease significantly.
 •Boiling point of different organic compounds
Organic CH3CH2CH2CH3 CH3CH2CH2NH2 CH3CH2CH2OH CH3COOH
RMM 58 57 60 60
Boiling point oC 4 52 78 118
Ethanoic acid has 2 hydrogen bond within their molecules, so their hydrogen bond is the
strongest. Both propylamine and propan1-ol has hydrogen bond, but propan-1-ol has a
stronger hydrogen bond since O is more electronegative than N. Butane is a non-polar
molecule, which is held by weak Van Der Waals forces
B) Solubility of amine

Amine CH3NH2 C2H5NH2 C3H7NH2 C4H9NH2 C5H11NH2

Solubility trend
Solubility DEcrease
Explanation methylamine, ethylamine and propylamine are completely miscible in water as
they can form hydrogen bond with water. However, the LONGER the ALKYL GROUPS
ATTACHED, molecule become MORE HYDROPHOBIC. As a result, HYDROGEN BOND
BECOME LESS SIGNIFICANT and cause the solubility decrease.
C) Basicity of amine
Amine is a weak base. When dissolve in water, it undergoes partial
dissociation where

+ −
[ RNH 3 ][ OH ]
Kb = pK b = − lg K b
[ RNH 2 ]
The pKb of some amine is given in the table below
Amine CH3NH2 C2H5NH2 C3H7NH2 CH3CH2NHCH3
pKb 3.42 3.27 3.03 2.88

(CH3)3N

2.64 9.41 9.58

 All alkyls are electron donating group, which donate electron
density to N in NH2, making N to be more readily to accept proton.
Hence, equilibrium shift more to right, increasing the basicity.
Longer the alkyl chain, greater the electron donating effect, greater
the basicity.

Basicity increase from 10 amine < 20 amine < 30 amine. This is due to, the more the
alkyl group surrounding N, greater the electron donating effect, where N has large
electron density and are more readily to accept proton, causing equilibrium to shift
more to right, increasing the basicity of amine.
phenylamine is a weaker base compare to alkyl amine, due to the
benzene ring is an electron withdrawing group. As a result, N in
amine has lesser electron density and is less readily to accept
proton (conversely more readily to donate proton) which caused
equilibrium shift more to left. This results the basicity of
phenylamine is lesser than alkyl amine. When a ring activator is
bonded to phenylamine, ita activate further the ring and caused
the ring to be more readily to accept proton, hence increase the
basicity. Conversely, if a ring deactivator is bonded to
phenylamine, it deacticate the ring and caused benzene to be
less readily to accept proton, decreasing the basicity
9.2 Preparation of amine
Name of Reagent used
Equation
reaction and condition

Alkylation
Concentrated
of
NH3 1-bromopropane conc. propylamine
haloalkane
Ammonia

Lithium
Reduction aluminium
of nitrile tetrahydride
2-methylbutylnitrile 2-methylbutylamine
LiAlH4

Lithium
Reduction tetrahydrido-
of amide aluminate,
propanamide propylamine
LiAlH4
9.2.1 Chemical reaction of amine
Name of Reagent used
Equation
reaction and condition

Mineral acid
Reaction with
such as HCl ;
mineral acid
H2SO4

HNO2 under
Nitrosation of
certain
amine
condition

Reaction with
R–COCl,
acyl chloride,
acyl chloride
R–COCl
(A) Reaction with mineral acids : Formation of salts

Amine dissolves in aqueous solution of mineral acid to form salt of ammonium.
Example
Class of amine Example Mineral acid Salt

Primary amine CH3CH2NH2 HCl CH3CH2NH3+Cl–

Secondary amine (CH3CH2)2NH HCl (CH3CH2)2NH2+Cl–

Tertiary amine (CH3CH2)3N HCl (CH3CH2)3NH+Cl–

The amine salt form is white crystalline solid dissolve readily in water

When dissolve in alkaline solution, amine is form back

CH3CH2NH3+Cl– (aq) + OH– (aq)
CH3CH2NH2 (aq) + H2O (l) + Cl–
(aq)
(B) Reaction of amine with nitrous acid

Nitrous acid (or nitric (III) acid) is unstable. It can be prepared by reaction of sodium nitrite
and hydrochloric acid

Equation : NaNO2 (s) + HCl (aq)
NaCl (aq) + O=N–OH (aq)

The organic products formed from the reaction between nitrous acid and amine depend on
2 factors

Class of amine used
Condition of the reaction

When aliphatic primary amine reacts with nitrous acid, nitrogen is evolved rapidly and
alcohol is produce as major product along with some side product such as alkene and in
some case, ether.

The reaction of nitrous acid follows the mechanism below
Primary amine :

Amine act as nucleophile and attack nitrosyl cation, the following mechanism of reaction
take place.

diazonium ion

The reaction after the formation of diazonium ion is complex. Depend on the condition of
the reaction, it form various organic compound such as alcohol or alkene. Example :
Secondary amine

Secondary amine reacts with nitrous acid (nitrosyl cation) under room condition to form
nitrosoamine. Unlike primary amine, there’s no nitrogen gas evolve. Example

N–nitrosoamine
Tertiary amine

Tertiary amine dissolve readily in acidic solution of nitrous acid to form salt according to the
equation

(C) Reaction with acyl chloride (refer Chap 8.4)

When acyl chloride reacts with primary amine, it will form a secondary amide

When react acyl chloride with a secondary amine, it will form a tertiary amide

Acyl chloride will not be acylated as it does not has a hydrogen atom to be
substituted.
9.3 Aromatic amine

The simplest form of aromatic amine is phenylamine, which is better known as
aniline

Some of the common naming of aromatic amines are shown below

aniline p-nitroaniline o-methylaniline N-methylaniline

N-ethyl-N-
diphenylamine N,N-diethylaniline phenylmethylamine
methylaniline
9.3.1 Preparation of aniline

Aniline can be prepare by using nitrobenzene. Reagent : conc. HCl catalysed by tin,
Sn.

9.3.2 Chemical reaction of aniline

1. Reaction with acid : the basic properties of aniline

Aniline is considerably weak acid as the pKb = 9.3

This is due to the electron withdrawing effect of the benzene, causes the electron
density of nitrogen decrease. When this occur, nitrogen are more readily to donate
proton rather than accept and equilibrium shift more to the left (Kb decrease)

Though, aniline is able to react with acid by accepting the H+ from acid and form
salt
 Aniline Acid Salt

HCl

H2SO4

H2SO4
in excess

HNO3

• Salts of aniline are colourless, crystalline solid and mostly are soluble in water. When react
with alkali, it give back the phenyl amine with salt and water
2. Reaction of aniline with haloalkane

If aniline is reacted with iodomethane (CH3I) under ethanolic, a secondary amine is first
formed and eventually turns out to become salt

If excess haloalkane is used, the reaction will further to form a tertiary amine and
quaternary salt.

3. Reaction of aniline with acyl chloride (Chapter 8.4)

This is one of the method use to prepare amide as discussed earlier. When acyl chloride
react with amine, a secondary amide is formed

When a secondary amine reacts with acyl chloride, it will form a tertiary amide.

Tertiary amine will not react with acyl chloride as there’s no H substitute out
4. Reaction of aniline with nitrous acid

Similar to the reaction of nitrous acid with alkyl amine, aniline react with the electrophile
nitrosyl cation where the formation of ion follow the mechanism below

When aniline attacks the electrophilic nitrosyl cation, it form benzenediazonium ion.

Benzenediazonium chloride formed is unstable and tends to react with other substances.
Diagram below shows the type of reaction that the benzenediazonium can undergoes
5. Formation of dyes by coupling reaction

The reaction of forming azo dye is via coupling reaction. Diazonium ion react with benzene
attached with strong ring activate group, under alkaline condition, to give bright
colouration of azo dye. Strong ring activate group direct at ortho-para position.

Benzenediazonium chloride phenol 4-hydroxyphenylazobenzene

When react with 1-naphthol, it form a bright scarlet azo dye

When react with another aniline, it form an orange-red precipitate dye.

9.4 Chemical tests for aniline
(1) Reaction with bromine

Similar to phenol, aniline is a strong ring activate group. So, when aniline is reacted
with aqueous bromine solution, it forms a white precipitate.

(2) Reaction with sodium chlorate (I), NaClO

When aniline is added to NaClO, a purple colouration is obtained
(3) Reaction with phenol under alkaline solution

As discuss earlier, when aniline is react phenol under NaOH, a yellow precipitate is
observed.
10.1 Introduction

Amino acid has the general formula of NH2 – CHR –
COOH.

From the general above, we can tell that there are 2
functioning groups of –NH2 (amine) and –COOH
(carboxylic acid).

There are 22 types of amino acids and almost all naturally
occurring amino acids are α-amino acid

The terms α- mean both NH2 and COOH are attached at
the same C. Considering –COOH act as the functioning
group, α-amino acid has the general naming as 2-
aminocarboxylic acid

The simplest form of amino acid is called glycine (2-
aminoethanoic acid)

All amino acids are optical active (except glycine) as they
have 4 different functioning groups (chiral carbon atom).
 Acidic amino acid Neutral amino acid Basic amino acid

The number of COOH is The number of COOH is The number of COOH is less
more than NH2 equal to the number of NH2 than NH2

Since amino acid has both acidic (–COOH) and basic (–NH2) fuctional group, hence
amino acid undergoes 3 types of chemical reaction :

reactions characteristic of the amino group

reactions characteristic of the carboxylic group

reaction due to the presence of both group

Because of both (–COOH) and (–NH2) group, it makes amino acid very soluble in
water. Neutral amino acid such as alanine and glycine are slightly miscible on ethanol
and epoxyethan.

This is due to amino acid exist as polar ion.amino acid exist as a zwitterions,
which carries both positive and negative charge in its molecule. A
zwitterions is formed when –COOH donated its proton to –NH2, according to
Condition Equation Charge

Positive
Acidic
charge

Neutral Zwitterions

Negative
Basic
charge

Isoelectric point – the pH at which amino acid has a net charge of zero.

Amino acids with one –COOH and one –NH2 have isoelectric points in the pH
range 5.5 – 6.5

Acidic amino acid (eg : aspartic acid and glutamic acid) has lower isoelectric point
(lower pH value) while basic amino acids (eg : lysine and arginine) have higher
isoelectric point (higher pH value)
10.2 Chemical Properties of Amino acid
10.2.1 Preparation of amino acid
Name of Reagent used
Equation
reaction and condition

Reaction of
ammonia with Concentrated
α-halo ammonia
carboxylic acid
10.2.2 Formation of peptide lingkage

The reaction which link 2 amino acids together is a condensation reaction where water
is given off and formed a dipeptide. Peptide link is a secondary amide group where the C-
from one amino acid is linked to the –N of another amino acid.

If 3 amino acids joined together, the product is ………………….. When a lot of amino
acids join together, the product is a …………….. When the many chain of peptide formed
…………..…....
10.2.3 Hydrolysis of Protein

Protein could be broken into its constituent amino acids by heating under reflux
with aqueous NaOH or dilute H2SO4 via hydrolysis reaction.

Hydrolysis of protein can be completely or partially hydrolyse.

Complete hydrolysis of protein gives the number and relative amount of amino
acids, but does not provide the information of the order of how they joined together
(the sequence of R)

Partially hydrolysis give fragments which still retain sequence information. When
these fragments are separated and identified, the overall protein structure can be
deduced. Example
10.3 Chemical Test for amino acid

Aminoethanoic acid (NH2CH2COOH) gives the following reactions :

It liberates CO2 when treated with Na2CO3 and NaHCO3.

Form dark red solution when treated with neutral iron (III) chloride solution.

It gives a deep blue solution when treated with copper (II) solution due to the copper
(II) complex.
10.4 Function of Proteins

All proteins are made up of long chains of amino acids.

Each protein is determined by its amino acid sequence (which ranges from 44 amino
acids in the hormone insulin to giant molecules with more than 50,000 amino acids).

Proteins are essential in living systems - animals, plants and micro-organisms.

Proteins are responsible for growth, repair and maintenance of the body.
Types of proteins Function

• provide the framework which defines the size and shape of

cells
structural
• e.g. elastin (in ligament)
proteins
a -keratins (in skin, hair, nails)
collagen (in connective tissue, tendon, cartilage)

• produces mechanical force and movement,

muscle fibres
• e.g. actin and myosin
• move metabolites around the cell or around the whole
transport proteins organism
• e.g. haemoglobin which transports oxygen in blood
• control the level and type of cell activity,
Some hormones
• e.g. insulin which regulates glucose metabolism

• catalyse metabolic processes which produce energy, build

Enzymes
up new cell structures and destroy old ones
10.5 Protein Structures

The structure of proteins are categorised into four levels of complexity:
> primary (1°) structure > secondary (2°) structure
> tertiary (3°) structure > quaternary (4°) structure
10.5.1 Primary (1°) structure

The primary (1°) structure of a protein shows the order (or sequence) of amino acids in a
protein chain

By convention, amino acid sequence is written with free –NH2 on left & free –
COOH on right.

The primary structure includes any covalent cross-linkages, e.g. –S–S– bonds.

The primary structure determines -what the protein is, how it folds, and its
function.

The sequence of R groups determines whether the protein chain will
1. coil with hydrogen bonding between N-H and C=O groups within each
chain (α–helix), or
2. fold with hydrogen bonds formed between two protein chains (β–pleated
sheet).
 Conc. HNO3 catalysed by H2SO4 under reflux
Conc. HCl under tin

C6H5NH2 + HCl
C6H5NH3Cl

Phenylamine is a weaker base than ammonia

Phenyl is an electron withdrawing group, which decrease the electron density of N

Making –N more readily to donate proton
Sodium nitrite, NaNO2 + hydrochloric acid, HCl
0 – 5 0C

Sodium hydroxide
 Iodine in Sodium hydroxide
Yellow precipitate is formed
No changes occur

CH3CH(OH)COOH + I2 + OH-
-OOC–COO- + CHI3 + 3 HI

J (chloropropanoic acid) is stronger acid than propanoic acid

Due to the inductive effect caused by –Cl in the carboxylic acid

CH3CH(NH2)COOH + NaOH
CH3CH(NH2)COONa + H2O

peptide linkage / peptide bond / amide

C6H5COCl

HCl or H2SO4 or NaOH (aq) + heat/reflux

Electrophilic aromatic substitution reaction

Conc. HNO3 catalysed by conc. H2SO4 under reflux

NO2+ H+
reduction

Conc. HCl under tin

PCl5 under room temperature

amide
amide
2 Ag+ + HO–Ph–NH2 + 2 OH-
O=<>=O + H2O + NH3 + 2 Ag

Rodinol is a weaker base than ammonia, since rodinol has an electron withdrawing
benzene ring to reduce the basicity.
Conc. HNO3 in conc. H2SO4 under reflux

reduction

Conc. HCl in tin

Phenol and amide

CH3COCl
Bromine water

amide
 NaNO2 in HCl under 0-50C

To increase its solubility in water or to increase binding to food components (1)

due to ionic solvation or more oxygen atoms to H-bond to H2O/glucose etc (1)