CHAPTER 27.

ORGANIC NITROGEN D r . YO S R A
BELGHITH
COMPOUNDS
PL AN
PL AN
I. AMINES
1. CLASSES OF AMINES
• Amines are compounds with the -NH2 (primary amine), -NH (secondary amine) or -N
(tertiary amine) group
Amine functional group

• Classification of amines

 In primary amines, the N of the amine group is

bonded to one R group (and two hydrogen
atoms)

 In secondary amines, the N of the amine group is

bonded to two R groups (and one hydrogen atom)

 In tertiary amines, the N of the amine group is bonded to

three R groups
I. AMINES
1. CLASSES OF AMINES
I. AMINES
2. BASICITY OF AMINES
• Chemical properties
– Due to the lone pair of electrons on the nitrogen, amines are basic compounds
– Ammonia molecule is a primary amine with one of its H atoms replaced by an alkyl or aryl group.
– Ammonia and the amines act as bases because of the lone pair of electrons on the nitrogen atom.
– (Remember that a base is a proton acceptor)
– The nitrogen atom donates its lone pair to an H+ ion, forming a co-ordinate (dative) bond.

– Dilute hydrochloric acid reacts with ammonia and with amines to produce salts.

– Ammonia and the amines have different strengths as bases.

I. AMINES
2. BASICITY OF AMINES
I. AMINES
2. BASICITY OF AMINES
– Ethylamine is a stronger base than ammonia because the ethyl group is electron-donating: it has a
positive inductive effect. By releasing electrons to the N atom, the ethyl group makes the lone pair
more readily available to bond with an H+ ion than it is in ammonia.

– Ammonia just has three H atoms bonded to N atom, and no alkyl groups.

Ethylamine is a
stronger base than
ammonia

– Ammonia is a stronger base than phenylamine because one of the p orbitals on the nitrogen atom in
phenylamine overlaps with the p bonding system in the benzene ring. This causes the lone pair of the N
atom in phenylamine to be delocalised into the benzene ring. This then makes the lone pair less
available to form a co-ordinate (dative) bond with H+ ion than it is in ammonia.

Phenylamine is a very
weak base
I. AMINES
2. BASICITY OF AMINES

• Physical properties
– The lone pair on the N of the amine group means that they can form
hydrogen bonds

– They are often soluble in water because they form hydrogen bonds
with water molecules

– The smaller amines are very soluble in water, but their solubility
decreases as the non-polar hydrocarbon chain gets longer

– They often have a fishy smell, especially as the size of the amines
increases
EXERCIC
E1
PAGE 573
PL AN
II. FORMATION OF AMINES
• Primary amines are organic compounds that have an -NH2 functional group
attached to an alkyl or aryl group

• Secondary amines have two alkyl or aryl groups attached to an -NH group

Primary and secondary amines

• Primary and secondary amines can be prepared from different reactions
including :
Nucleophilic Substitution Reaction
• The reaction of halogenoalkanes with ammonia
• The reaction of halogenoalkanes with primary amines
• The reduction of amides
II. FORMATION OF AMINES
 Reaction of halogenoalkanes with ammonia
• This is a nucleophilic substitution reaction in which the nitrogen lone pair in
ammonia acts as a nucleophile and replaces the halogen in the
halogenoalkane

• When a halogenoalkane is reacted with excess, hot ethanolic ammonia under

pressure a primary amine is formed

Formation of primary amine

II. FORMATION OF AMINES
 Reaction of halogenoalkanes with primary amine
• This is also a nucleophilic substitution reaction in which the nitrogen in the
primary amine acts as a nucleophile and replaces the halogen in the
halogenoalkane
• When a halogenoalkane is reacted with a primary
amine in ethanol and heated in a sealed tube, under pressure a secondary
amine is formed

Formation of secondary amine

II. FORMATION OF AMINES
 Reduction of nitriles
• Nitriles contain a -CN functional group which can be reduced to an -NH2 group
• Nitriles are prepared by reacting a halogenoalkane with the CN- ion.
• To carry out the reaction, a solution of potassium cyanide, KCN, in ethanol is
heated under reflux with the halogenoalkane:

CH3Br + CN-hea  CH3CN +

Bromomethane t Ethanenitr
-
Br ile
• Note that we start with bromomethane, not bromoethane, as the cyanide group adds a
carbon atom to the alkyl group.
• We can then reduce the ethanenitrile to make ethylamine.
II. FORMATION OF AMINES
 Reduction of nitriles
• The nitrile vapour and hydrogen gas are passed over a nickel
catalyst or LiAlH4 in dry ether can be used to form a primary amine

Nitriles can be reduced with LiAlH4 or H2 and

II. FORMATION OF AMINES
 Reduction of amides
• Amines can also be formed from the reduction of amides by LiAlH 4 in dry ether
• Whether a primary or secondary amine is formed depends on the nature of the
amide

Amides can be reduced by LiAlH4 to form

II. FORMATION OF AMINES
 Preparing phenylamine
• Phenylamine is an organic compound consisting of a benzene ring and
an amine (NH2) functional group
• It can be produced in a three-step synthesis reaction followed by the separation
of phenylamine from the reaction mixture
• Step 1: Benzene undergoes nitration with concentrated nitric acid (HNO3)

and concentrated sulfuric acid (H2SO4) at 25 to 60°C to form nitrobenzene

• Step 2 : Nitrobenzene is reduced with hot tin (Sn) and concentrated
hydrochloric acid (HCl) under reflux to form an acidic mixture that contains
the organic product C6H5N+H3
• Step 3 : Sodium hydroxide (NaOH) is added to the acidic reaction mixture
to form phenylamine
II. FORMATION OF AMINES
 Preparing phenylamine

The overall reaction of formation of phenylamine from

benzene
Multi-step synthesis of phenylamine from
EXERCIC
E2
PAGE 574
II. FORMATION OF AMINES
 Reactions of phenylamine

• Both the benzene ring as well as the -NH2 group in phenylamine can
take part in chemical reactions

• These reactions include

o The bromination of phenylamine
o Formation of a diazonium salt
II. FORMATION OF AMINES
 Reactions of phenylamine
Bromination of phenylamine

• Phenylamines react in electrophilic substitution reactions in a similar way

as phenols
• The lone pair of electrons on the nitrogen atom in phenylamines donate electron
density into the benzene ring
• In phenols, the oxygen atom donates its lone pair of electrons instead
• The delocalisation of the electrons causes an increased electron density in the
benzene ring
• The benzene ring, therefore, becomes activated and becomes more readily
attacked by electrophiles
• The incoming electrophiles are directed to the 2,4 and 6 positions
II. FORMATION OF AMINES
 Reactions of phenylamine
Bromination of phenylamine

Bromination of phenylamines gives 2,4,6-

tribromophenylamine
II. FORMATION OF AMINES
 Reactions of phenylamine
Formation of diazonium salts

•Diazonium compounds are very reactive compounds containing an -N2+ group

•The amine (-NH2) group of phenylamines will react with nitric(III) acid (HNO2) at
a temperature below 10 °C to form diazonium salts
• Since nitric(III) acid is unstable, it has to be made in the test-tube by
reacting sodium nitrite (NaNO2) and dilute acid (such as HCl)
•These diazonium salts are so unstable that they will upon further warming with
water to form a phenol
II. FORMATION OF AMINES
 Reactions of phenylamine
Formation of diazonium salts

Phenylamine can form an unreactive diazonium salt

which thermally decomposes to a phenol
II. FORMATION OF AMINES
 Reactions of phenylamine
Azo compounds “Azo dye”
•Azo (or diazonium) compounds are organic compounds that have an R1-

N=N-R2 group
•They are often used as dyes and are formed in a coupling
reaction between the diazonium ion and an alkaline solution of phenol

Azo compounds are characterized by the

presence of an R1-N=N-R2 group
II. FORMATION OF AMINES
 Reactions of phenylamine
Azo compounds “Azo dye”
 Coupling of benzenediazonium chloride with phenol
in NaOH

•Azo compounds can be formed from the coupling reaction of

a benzenediazonium chloride salt with alkaline phenol
•Making an azo dye is a multi-step process
Formation of azo compounds table
Reaction mechanism of the formation of azo
II. FORMATION OF AMINES
 Reactions of phenylamine
Azo compounds “Azo dye”
 Coupling of benzenediazonium chloride with phenol
in NaOH

•The delocalised electrons in the π bonding systems of the two benzene rings
are extended through the -N=N- which acts as a bridge between the two rings
•As a result of the delocalisation of electrons throughout the compound, azo
compounds are very stable
II. FORMATION OF AMINES
 Reactions of phenylamine
Azo compounds “Azo dye”
 Making other azo dyes
•Other dyes can be formed via a similar route as described above
•For example, the yellow dye can be formed from the coupling
reaction between benzenediazonium chloride and C6H5N(CH3)2 instead of

phenol (C6H5OH)

The yellow azo dye is formed via a coupling reaction

between benzenediazonium chloride and C6H5N(CH3)2
II. FORMATION OF AMINES
 Reactions of phenylamine

 Coupling reaction :  Diazotisation :

The reaction between a diazonium The reaction between phenylamine
salt and an alkaline solution of phenol and nitrous acid (HNO2) to give a
(or similar compound) to make an azo diazonium salt in the first step in
dye. preparing an azo dye.

 Azo dyes :
Coloured compounds formed on the
addition of phenol (or another aryl
compound) to a solution containing a
diazonium ion.
EXERCIC
E3
PAGE 576
 I. Amines

II. Formation of amines

PL AN
III. Amino-acids

IV. Peptides

V. Reactions of the
amides

VI. Electrophoresis
III. AMINO ACIDS

•Amino acids are organic compounds that contain two

functional groups:
o A basic amino (-NH2) group
o An acidic carboxylic acid (-COOH) group
•Due to the presence of both a basic and acidic group in amino
acids, they are said to be amphoteric
o They can act as both acids and bases
III. AMINO ACIDS
Naturally occurring amino acids

•2-aminocarboxylic acids are a type of amino acids in which the amine (-

NH2) group is bonded to the carbon atom next to the -COOH group
•These type of amino acids form the ‘building blocks’ that make up proteins
•There are 20 naturally occurring amino acids with the general structural
formula of RCH(NH2)COOH

General structural formula of amino acids

III. AMINO ACIDS
Naturally occurring amino acids

• The R group varies in different amino acids and can be:

o Acidic
o Basic
o Neutral

The R group varies in different amino acids

III. AMINO ACIDS
 Reactions of amino acids
 Acid / base properties of amino acids

•Amino acids will undergo most reactions of amines and carboxylic acids
including acid-base reactions of:
o Amines with acids
o Carboxylic acids with bases
•However, they can also interact intramolecularly (within themselves) to form
a zwitterion
•A zwitterion is an ion with both a positive (-NH3+) and a negative (-COO-)
charge
•Because of these charges in a zwitterion, there are strong intermolecular
forces of attraction between amino acids
III. AMINO ACIDS
 Reactions of amino acids
 Acid / base properties of amino acids

An amino acid molecule can interact within

itself to form a zwitterion
III. AMINO ACIDS
 Reactions of amino acids
 Isoelectric point

•A solution of amino acids in water will exist as zwitterions with

both acidic and basic properties
•They act as buffer solutions as they resist any changes in pH
when small amounts of acids or alkali are added
•If an acid is added (and thus the pH is lowered):
o The -COO- part of the zwitterion will accept an H+ ion to reform the -
COOH group
o This causes the zwitterion to become a positively charged ion
•If a base is added (and thus the pH is raised):
o The -NH3+ part of the zwitterion will donate an H+ ion to reform the -
III. AMINO ACIDS
 Isoelectric point

A solution of amino acids can act as a buffer

solution by resisting any small changes in pH
III. AMINO ACIDS
 Isoelectric point

• The pH can be slightly adjusted to reach a point at which neither

the negatively charged or positively charged ions dominate and the
amino acid exists as a neutral zwitterion
o This is called the isoelectric point of the amino acid

The isoelectric point of amino acids is the pH at which the amino acid exists
IV. PEPTIDES

 Isoelectric point :
The pH value at which there is overall charge
on a particular amino acid in its aqueous
solution.
EXERCIC
E4
PAGE 577
 I. Amines

II. Formation of amines

PL AN
III. Amino-acids

IV. Peptides

V. Reactions of the
amides

VI. Electrophoresis
IV. PEPTIDES

• Each amino acid contains an amine (-NH2) and carboxylic acid (-

COOH) group
• The -NH2 group of one amino acid can react with the -COOH group
of another amino acid in a condensation reaction to form
a dipeptide
o The new amide bond between two amino acids is also called
a peptide link or peptide bond
• Since this is a condensation reaction, a small molecule (in this case
H2O) is eliminated

• The dipeptide still contains an -NH2 and -COOH group at each end of
the molecule which can again participate in a condensation reaction
IV. PEPTIDES

A peptide bond is an amide bond between

IV. PEPTIDES
• A polypeptide is formed when many amino acids join together to form a long
chain of molecules

A polypeptide is a long chain of amino acid molecules joined

together
IV. PEPTIDES
 Amide bond :
The group of atoms, made up of
carbonyl group and an amine group (-
CONH-), that join together the amino
acids in peptides and proteins.

 Dipeptide :
A compound formed from the
condensation reaction between two  Tripeptide :
amino acids. A compound made by combining three
The –COOH group of one amino acid amino acids.
reacts with the –NH2 group of another
amino acid.
EXERCIC
E5
PAGE 578
 I. Amines

II. Formation of amines

PL AN
III. Amino-acids

IV. Peptides

V. Reactions of the
amides

VI. Electrophoresis
V. REACTIONS OF AMIDES
• Amides are formed from the condensation reaction of carboxylic acids or acyl
chlorides with ammonia or amines
• The amide group (CONR2) in these compounds can undergo reactions
including
o Hydrolysis with aqueous alkali or aqueous acid
o Reduction with LiAlH4
V. REACTIONS OF AMIDES
1. Preparing an amide
•Amides are organic compounds with an -CONR2 functional group
•They can be prepared from the condensation reaction between an acyl
chloride and ammonia or amine
•In a condensation reaction, two organic molecules join together and in the
process eliminate a small molecule
•In this case, the acyl chlorides and ammonia or amine join together to form
an amide and eliminate an HCl molecule
V. REACTIONS OF AMIDES
1. Preparing an amide
 Condensation reaction

•The chlorine atom in acyl chlorides is electronegative and draws electron density from
the carbonyl carbon
•The carbonyl carbon is therefore electron-deficient and can be attacked by nucleophiles
•The nitrogen atom in ammonia and amines has a lone pair of electrons which can act as
a nucleophile and attack the carbonyl carbon
•As a result, the C-Cl bond is broken and an amide is formed
•Whether the product is a substituted amide or not, depends on the nature of
the nucleophile
o Primary and secondary amines will give a substituted amide
o The reaction of acyl chlorides with ammonia will produce a non-substituted amide
•Note that amides can also be formed from the condensation reaction
between carboxylic acids and ammonia or amines
 Acyl chlorides undergo condensation
reactions with ammonia and amines to form
V. REACTIONS OF AMIDES
2. Hydrolysis of amides
• The -CON- group in substituted amides links two hydrocarbon sections of
their molecules together
• This amide link can be broken down by hydrolysis by refluxing it with
an acid or alkali
• The products of a non-substituted amide are:
o Carboxylic acid
o Ammonia
• The products of a substituted amide are:
o Carboxylic acid
o Primary amine
V. REACTIONS OF AMIDES
2. Hydrolysis of amides

Hydrolysis of substituted and non-

V. REACTIONS OF AMIDES
2. Hydrolysis of amides
• Ammonia will react in excess acid to form an
ammonium salt
• Carboxylic acid will get deprotonated in excess
base to form a carboxylate ion

Amides are hydrolysed to carboxylic acids

and ammonia or primary amine when
V. REACTIONS OF AMIDES
3. Reduction of amides

• The C=O group in amides can be reduced by the strong

reducing agent LiAlH4 to form an amine
• The products of a non-substituted amide are:
o A primary amine and water
• The products of a substituted amide are:
o A secondary amine and water
V. REACTIONS OF AMIDES
3. Reduction of amides

Amides can be reduced to amines using

EXERCIC
E6
PAGE 579
 I. Amines

II. Formation of amines

PL AN
III. Amino-acids

IV. Peptides

V. Reactions of the
amides

VI. Electrophoresis
VI. ELECTROPHORESIS
1. How electrophoresis work?
•Electrophoresis is an analytical technique which separates ions by placing
them in an electrical field
o This method is often used in biochemical
analysis to identify and purify proteins
•A sample of amino acids is placed between two oppositely charged electrodes
o The positively charged ions will move towards the negative electrode
o The negatively charged ions will move towards the positive electrode
•The rate (how fast) at which the ions move towards the electrodes depends on:
o The size of the ions: larger ions move more slowly
o The charge of the ions: highly charged ions move more quickly
•An electropherogram is the series of bands which are observed on the paper or
gel after electrophoresis has occurred
VI. ELECTROPHORESIS
2. Separating mixtures of amino acids by varying the pH
• The charge on the amino acid ions depends on the pH of the solution
• The movement of the ions to the electrodes during electrophoresis will therefore
be affected by the pH
• Consider a sample which consists of a mixture of three amino acids at pH 7
o Amino acid A: lysine, side-chain is positively charged
o Amino acid B: glycine, side chain is neutral
o Amino acid C: glutamic acid, side chain is negatively charged

The sample consists of a mixture of three amino acids which are separated
using electrophoresis
VI. ELECTROPHORESIS
2. Separating mixtures of amino acids by varying the pH
• The charge on the amino acid ions depends on
the pH of the solution
• The amino acids in this mixture can be separated
by electrophoresis
o Amino acid C will move towards
the positive electrode
o Amino acid B will remain in the well where
the sample is applied to the gel
o Amino acid A will move towards
the negative electrode
Separation of a mixture
• Since glutamic acid is larger than lysine, it will
of amino acids by
travel towards the positive electrode at a slower electrophoresis
EXERCIC
E7
PAGE 580
 THANK
YO U F O R
YO U R
AT T E N T I O N