Amines

Introduction
• Amines constitute an important class of organic compounds
derived by replacing one or more hydrogen atoms of ammonia
molecule by alkyl/aryl group(s).
• In nature, they occur among proteins, vitamins, alkaloids and
hormones.
• Amines have lot of importance in our day to day life.
• For example:-
o Polymers, dyestuffs and drugs contain amines.
o Two biologically active compounds, namely adrenaline
and ephedrine, both containing secondary amino group,
are used to increase blood pressure.
o Novocain, a synthetic amino compound, is used as an
anaesthetic in dentistry.
o Benadryl, a well-known antihistaminic drug also contains
tertiary amino group.
o Quaternary ammonium salts are used as surfactants.
Diazonium salts are intermediates in the preparation of a
variety of aromatic compounds including dyes.
Classification of Amines as Primary, Secondary & Tertiary
• Amines are classified as primary (1o), secondary (2o) and
tertiary (3o) depending upon the number of hydrogen atoms
replaced by alkyl or aryl groups in ammonia molecule.
• If one hydrogen atom of ammonia is replaced by R or Ar, we get
RNH2 or ArNH2, a primary amine (1o).
• If two hydrogen atoms of ammonia or one hydrogen atom of R-
NH2 are replaced by another alkyl/aryl (R’) group then it is
called as secondary amine.
• The second alkyl/aryl group may be same or different.
• Replacement of another hydrogen atom by alkyl/aryl group
leads to the formation of tertiary amine.

• Amines are said to be ‘simple’ when all the alkyl or aryl groups
are the same, and ‘mixed’ when they are different.
Problem:-
Classify the following amines as primary, secondary or tertiary:

Answer:-
• It is a primary amine because only 1 hydrogen is replaced if we
compare this structure with ammonia.
• It is a tertiary amine as all the 3 hydrogen is replaced.
• It is a primary amine as only 1 hydrogen is replaced.
It is a secondary amine as 2 hydrogens are
Nomenclature of Amines by IUPAC System
Common Names of Amines
• An aliphatic amine is named by prefixing alkyl group to amine,
i.e. alkylamine as 1 word.
• We are considering primary amines.
 • In secondary and tertiary amines, when two or more groups are
the same, the prefix di or tri is added to the before the name of
alkyl group.

• In case of mixed amine, alkyl group are written in alphabetical

order.

IUPAC System
• In IUPAC system, amines are named as alkanamines, derived by
replacement by ‘e’ of alkane by the word amine.
 • For Example: - Methanamine (CH3NH2), Ethan amine (C2H5NH2).
• For naming higher member hydrocarbon, longest chain
containing amino group is selected. C atom to which amino
group is attached is given to lower number.

• In case, more than one amino group is present at different

positions in the parent chain, their positions are specified by
giving numbers to carbon atoms bearing –NH2 groups and
suitable prefix such as di, tri etc. is attached to the amine. The
letter ’e’ of the suffix of the hydrocarbon part is retained.
• For Example:- (Ethane 1,2 diamine) H2N-CH2-CH2-NH2
• Each alkyl group bonded to the N atom is named as N-alkyl
group.
Aryl Amines
• In aryl amines, -NH2 group is directly attached to the benzene
ring.
• C6H5NH2 is the simplest example of aryl amine. It is also known
as aniline.
 • Naming aryl amines according to IUPAC system, suffix ‘e’ of
arene is replaced by ‘amine’.
• For Example: - C6H5-NH2 is named as benzenamine.

Preparation of Amines
• Amines are prepared by the following methods:
• 1. Reduction of nitro compounds
2. Ammonolysis of alkyl halides
3. Reduction of nitriles
4. Reduction of amides
5. Gabriel phthalimide synthesis
6. Hoffmann bromamide degradation reaction

1. 1. Reduction of nitro compounds

• Nitro compounds are reduced to amines by passing hydrogen
gas in the presence of finely divided nickel, palladium or
platinum and also by reduction with metals in acidic medium.
R- NO2 + 3H2 à R-NH2 + 2H2O {In the presence of Ni, Pt or Pd}
Ar- NO + 3H2à Ar- NH2 + 2H2O
• Nitro alkanes can also be similarly reduced to the
corresponding alkanamines.
• Reduction with iron scrap and hydrochloric acid is preferred
because FeCl2 formed gets hydrolysed to release hydrochloric
acid during the reaction.
• Thus, only a small amount of hydrochloric acid is required to
initiate the reaction.
 • Nitro compounds can also be reduced with active metals such
as Fe, Sn, Zn etc. with conc. HCl
R- NO2 + 3H2 à R- NH2 + 2H2O {In the presence of Sn/HCl}
Ar- NO2 + 3H2 à Ar- NH2 + 2H2O

2. Ammonolysis of alkyl halides

• The carbon - halogen bond in alkyl or benzyl halides can be
easily cleaved by a nucleophile.

• Therefore, an alkyl or benzyl halide on reaction with an

ethanolic solution of ammonia undergoes nucleophilic
substitution reaction in which the halogen atom is replaced by
an amino (–NH2) group.
• This process of cleavage of the C–X bond by ammonia molecule
is known as ammonolysis.

• The reaction is carried out in a sealed tube at 373 K. The

primary amine thus obtained behaves as a nucleophile and can
further react with alkyl halide to form secondary and tertiary
amines, and finally quaternary ammonium salt.
• The free amine can be obtained from the ammonium salt by
treatment with a strong base:
• Disadvantages:-
• When ammonia is taken in excess primary amine is formed as
main Product
• When alkyl halide is used in excess quaternary ammonium salt
is formed as main product
• Note: - This method is not suitable for preparation of aryl
amines because aryl amines are relatively less reactive than
alkyl halides towards nucleophilic substitution reactions.
3. Reduction of nitriles
• Nitriles on reduction with lithium aluminium hydride (LiAlH 4) or
catalytic hydrogenation produce primary amines.
• This reaction is used for ascent of amine series, i.e., for
preparation of amines containing one carbon atom more than
the starting amine.

4. Reduction of amides
• The amides on reduction with lithium aluminium hydride yield
amines.

5. Gabriel phthalimide synthesis

• Gabriel synthesis is used for the preparation of primary amines.
• Phthalimide on treatment with ethanolic potassium hydroxide
forms potassium salt of phthalimide which on heating with alkyl
halide followed by alkaline hydrolysis produces the
corresponding primary amine.
 • Aromatic primary amines cannot be prepared by this method
because aryl halides do not undergo nucleophilic substitution
with the anion formed by phthalimide.

6. Hoffmann bromamide degradation reaction

• Hoffmann developed a method for preparation of primary
amines by treating an amide with bromine in an aqueous or
ethanolic solution of sodium hydroxide.
• In this degradation reaction, migration of an alkyl or aryl group
takes place from carbonyl carbon of the amide to the nitrogen
atom.
• The amine so formed contains one carbon less than that
present in the amide.

Physical & Chemical Properties of Amines

General:-
• The lower aliphatic amines are gases with fishy odour.
• Primary amines with three or more carbon atoms are liquid and
still higher ones are solid.
• Aniline and other arylamines are usually colourless but get
coloured on storage due to atmospheric oxidation.
1. Solubility:-
 1. Lower aliphatic amines are soluble in water because they
can form hydrogen bonds with water molecules.
2. However, solubility decreases with increase in molar mass
of amines due to increase in size of the hydrophobic alkyl
part. Higher amines are essentially insoluble in water.
3. Amines are soluble in organic solvents like alcohol, ether
and benzene.
2. Boiling Points:-
• Primary and secondary amines are engaged in intermolecular
association due to hydrogen bonding between nitrogen of one
and hydrogen of another molecule.
• This intermolecular association is more in primary amines than
in secondary amines as there are two hydrogen atoms available
for hydrogen bond formation in it.
• Tertiary amines do not have intermolecular association due to
the absence of hydrogen atom available for hydrogen bond
formation. Therefore, the order of boiling points of isomeric
amines is as follows:
Primary > Secondary > Tertiary
• Intermolecular hydrogen bonding in primary amines is as:-

Chemical Properties of Amines

• Amines behave as nucleophiles due to the presence of
unshared electron pair.
 • Difference in electronegativity between nitrogen and hydrogen
atoms and the presence of unshared pair of electrons over the
nitrogen atom makes amines reactive.
• Primary, secondary and tertiary amines differ in reactions
because of number of hydrogen attached to nitrogen.
Following are the chemical properties of Amines:-
1. Basicity of Amines
1. They are basic in nature and form salts when react with
acids.

1. Amine salts on treatment with a base like NaOH,

regenerate the parent amine.

1. Amine salts are soluble in water but insoluble in organic

solvents like ether.
2. They form ammonium salts when react with mineral
acids.
3. Amines have an unshared pair of electrons on nitrogen
atom due to which they behave as Lewis base.
Why Amines are basic in nature in terms of Kb and pKb values?
• Larger the value of Kb or smaller the value of pKb, stronger is the
base. The pKb values of few amines are given in.
 • pKb value of ammonia is 4.75. Aliphatic amines are stronger
bases than ammonia due to +I effect of alkyl groups leading to
high electron density on the nitrogen atom.
• Their pKb values lie in the range of 3 to 4.22. On the other hand,
aromatic amines are weaker bases than ammonia due to the
electron withdrawing nature of the aryl group.
Structure-basicity relationship of amines
• Basicity of amines to their structure.
1. Alkanamines versus ammonia
1. Reaction of alkanamines and ammonia in order to
compare their basicity.

1. Due to the electron releasing nature of alkyl group, it (R)

pushes electrons towards nitrogen and thus making them
available for the unshared electron pair for the proton of
the acid.
2. The substituted ammonium ion formed from the amine
gets stabilised due to dispersal of the positive charge by
the +I effect of the alkyl group.
3. Hence, alkylamines are stronger bases than ammonia.
Thus, the basic nature of aliphatic amines should increase
with increase in the number of alkyl groups.
4. The order of basicity of amines in the gaseous phase
follows the expected order: tertiary amine > secondary
amine > primary amine > NH3.
5. But this not same in aqueous state, in that the substituted
ammonium cations get stabilised not only by electron
releasing effect of the alkyl group (+I) but also by solvation
with water molecules.
6. The greater the size of the ion, lesser will be the solvation
and the less stabilised is the ion.
7. The order of stability of ions are as follows:

1. Thus, the order of basicity of aliphatic amines should be:

primary > secondary > tertiary, which is opposite to the
inductive effect based order.
2. When the alkyl group is small, like –CH3 group, there is no
steric hindrance to H-bonding.
3. In case the alkyl group is bigger than CH3 group, there will
be steric hindrance to H-bonding.
 4. Therefore, the change of nature of the alkyl group, e.g.,
from –CH3 to –C2H5 results in change of the order of basic
strength.
5. Thus, there is a subtle interplay of the inductive effect,
solvation effect and steric hindrance of the alkyl group
which decides the basic strength of alkyl amines in the
aqueous state.
6. The order of basic strength in case of methyl substituted
amines and ethyl substituted amines in aqueous solution
is as follows:
• (C2H5)2NH > (C2H5)3N > C2H5NH2 > NH3
• (CH3)2NH > CH3NH2 > (CH3) 3N > NH3
1. Arylamines versus ammonia
1. pKb value of aniline is quite high because in aniline or
other arylamines, the -NH2 group is attached directly to
the benzene ring.
2. As a result the unshared electron pair on nitrogen atom
will be less available for protonation as it is in conjugation
with the benzene ring.
3. Aniline is resonance hybrid of 5 resonance structures.

1. On the other hand, anilinium ion obtained by accepting a

proton can have only two resonating structures (kekule).
 1. Aniline is more stable than anilinium ion as it has greater
number of resonating structure.
2. Therefore, the proton acceptability or the basic nature of
aniline or other aromatic amines would be less than that
of ammonia.
3. In case of substituted aniline, it is observed that electron
releasing groups like –OCH3 , –CH3 increase basic strength
whereas electron withdrawing groups like –NO2 , –SO3H, –
COOH, –X decrease it.
1. Alkylation
1. Amines undergo alkylation on reaction with alkyl halides.
1. Acylation
1. The reaction of aliphatic and aromatic primary and secondary
amines with acid chlorides, anhydrides and esters by
nucleophilic substitution reaction is known as Acylation.
2. In this reaction there will be replacement of hydrogen atom of –
NH2 or >N–H group by the acyl group.
3. The products obtained by acylation reaction are known
as amides. The reaction is carried out in the presence of a base
stronger than the amine, like pyridine, which removes HCl so
formed and shifts the equilibrium to the right hand side.
 1. Amines also react with benzoyl chloride (C6H5 COCl). This
reaction is known as benzoylation.

1. They form salts when they react with carboxylic acids at room
temperature.
1. Carbylamine reaction
1. Aliphatic and aromatic primary amines on heating with
chloroform and ethanolic potassium hydroxide form
isocyanides or carbylamines which are foul smelling substances.
2. Secondary and tertiary amines do not show this reaction. This
reaction is known as carbylamines reaction
or isocyanide test and is used as a test or primary amines.

1. Reaction with nitrous acid

1. Different types of amines react differently with nitrous acid
which is prepared in situ from a mineral acid and sodium nitrite.
(i) Primary Amines:-
1. Primary aliphatic amines react with nitrous acid to form
aliphatic diazonium salts which being unstable, liberate
nitrogen gas quantitatively and alcohols.
 2. Quantitative evolution of nitrogen is used in estimation of
amino acids and proteins.

(ii) Secondary Amines:-

1. Aromatic amines react with nitrous acid at low
temperatures (273-278 K) to form diazonium salts, a very
important class of compounds used for synthesis of a
variety of aromatic compounds.

• Secondary and tertiary amines react with nitrous acid in a

different manner.
1. Reaction with aryl sulphonyl chloride
• Reaction with Benzene sulphonyl Chloride: - Benzene sulphonyl
chloride (C6H5SO2Cl), which is also known as Hinsberg’s reagent,
reacts with primary and secondary amines to
form sulphonamides.
2. The reaction of benzenesulphonyl chloride with primary amine
yields N-ethylbenzene sulphonyl amide.

2. The hydrogen attached to nitrogen in sulphonamide is strongly

acidic due to the presence of strong electron withdrawing
sulphonyl group.
3. Hence, it is soluble in alkali.
• Reaction of secondary Amine benzenesulphonyl chloride: - In
this reaction, N, N-diethylbenzenesulphonamide is formed.
5. Since N, N-diethyl benzene sulphonamide does not contain any
hydrogen atom attached to nitrogen atom; it is not acidic and
hence insoluble in alkali.

• Tertiary amines do not react with benzenesulphonyl chloride.

• Note:-
1. Amine reacting with benzenesulphonyl chloride in a
different manner is used for the distinction of primary,
secondary and tertiary amines and also for the separation
of a mixture of amines.
2. These days benzenesulphonyl chloride is replaced by p-
toluenesulphonyl chloride.
1. Electrophilic Substitution
• Bromination :-
• Aniline reacts with bromine water at room temperature to give
a white precipitate of 2, 4, 6-tribromoaniline.
• Because of high reactivity of aromatic amines problems occur
during electrophilic substitution because it occurs at ortho- and
para-positions.
• In order to prepare monosubstituted aniline derivative
activating effect of –NH2 group be controlled done by
protecting the -NH2 group by acetylation with acetic anhydride,
then carrying out the desired substitution followed by
hydrolysis of the substituted amide to the substituted amine.

• The lone pair of electrons on nitrogen of acetanilide interacts

with oxygen atom due to resonance as shown below:

• Hence, the lone pair of electrons on nitrogen is less available

for donation to benzene ring by resonance.
• Therefore, activating effect of –NHCOCH3 group is less than that
of amino group.
• Nitration:-
• Direct nitration of aniline yields tarry oxidation products in
addition to the nitro derivatives.
• Moreover, in the strongly acidic medium, aniline is protonated
to form the anilinium ion which is meta directing.
• That is why besides the ortho and para derivatives, significant
amount of meta derivative is also formed.
 • In order to protect –NH2 group by acetylation reaction with
acetic anhydride, the nitration reaction can be controlled and
the p-nitro derivative can be obtained as the major product.

• Sulphonation:-
• Aniline reacts with concentrated sulphuric acid to form
anilinium hydrogensulphate which on heating with sulphuric
acid at 453-473K produces p-aminobenzene sulphonic acid,
commonly known as sulphanilic acid, as the major product.
• Aniline does not undergo Friedel-Crafts reaction (alkylation and
acetylation) due to salt formation with aluminium chloride, the
Lewis acid, which is used as a catalyst.
• Due to this, nitrogen of aniline acquires positive charge and
hence acts as a strong deactivating group for further reaction.
Diazonium Salts
• General formula of diazonium salts is RN2+X- where R = aryl
group and X- ion can be Cl-, Br-,HSO4- and BF4-.
• Diazonium salts are named by suffixing diazonium to the name
of the parent hydrocarbon from which they are formed,
followed by the name of anion such as chloride,
hydrogensulphate, etc.
• The N2+ group is called diazonium salt.
o For example, C 6H5 N2+ Cl- is named as benzenediazonium
chloride and C6H5N2 +HSO4 – is known as
benzenediazonium hydrogensulphate.
 • Primary aliphatic amines form highly unstable alkyldiazonium
salts. Primary aromatic amines form arenediazonium salts
which are stable for a short time in solution at low
temperatures (273-278 K). The stability of arenediazonium ion
is explained on the basis of resonance.

Preparation of Diazonium Salts

• Benzenediazonium chloride is prepared by the reaction of
aniline with nitrous acid at 273-278K.
• Nitrous acid is produced in the reaction mixture by the reaction
of sodium nitrite with hydrochloric acid.
• The conversion of primary aromatic amines into diazonium salts
is known as diazotisation. Due to its instability, the diazonium
salt is not generally stored and is used immediately after its
preparation.
C 6H5NH2 + NaNO2 + 2HCl à C 6H5N2+Cl- + NaCl +2H2O
(273 – 278K)

Properties of Diazonium Salts

Physical Properties:-
• Benzenediazonium chloride is a colourless crystalline solid.
• It is readily soluble in water and is stable in cold but reacts with
water when warmed.
 • It decomposes easily in the dry state. Benzenediazonium
fluoroborate is water insoluble and stable at room temperature.
Chemical Properties:-
There are 2 reactions into with diazonium salts can be divided:-
• Reactions involving displacement of nitrogen
• Reactions involving retention of diazo group.
Reactions involving displacement of nitrogen
• Diazonium group being a very good leaving group is substituted
by other groups such as Cl–, Br–, I–, CN–and OH– which displace
nitrogen from the aromatic ring. The nitrogen formed escapes
from the reaction mixture as a gas.
• Replacement by halide or cyanide ion:
• The Cl–, Br –and CN– nucleophiles can easily be introduced in the
benzene ring in the presence of Cu (I) ion.
• This reaction is called Sandmeyer reaction.

• Alternatively, chlorine or bromine can also be introduced in the

benzene ring by treating the diazonium salt solution with
corresponding halogen acid in the presence of copper powder.
This is referred as Gatterman reaction.
 • The yield in Sandmeyer reaction is found to be better than
Gatterman reaction.
• Replacement by iodide ion:
• Iodine is not easily introduced into the benzene ring directly,
but, when the diazonium salt solution is treated with potassium
iodide, iodobenzene is formed.
ArN2+Cl- + KI à Ar I + KCl + N2
• Replacement by fluoride ion:
• When arenediazonium chloride is treated with fluoroboric acid,
arene diazonium fluoroborate is precipitated which on heating
decomposes to yield aryl fluoride.
ArN2+Cl- + HBF4 à Ar – N2+BF4- à Ar-F + BF3 +N2
∆
• Replacement by H:
• Certain mild reducing agents like hypophosphorous acid
(phosphinic acid) or ethanol reduce diazonium salts to arenes
and they get oxidised to phosphorous acid and ethanal,
respectively.
ArN2+Cl- + H3PO4 + H2O à ArH + N2 + H3PO3 + HCl
ArN2+Cl- + CH3CH2OH à ArH + N2 + CH3CHO + HCl
• Replacement by hydroxyl group:
• If the temperature of the diazonium salt solution is allowed to
raise upto 283 K, the salt gets hydrolysed to phenol.
ArN2Cl- + H2O à ArOH + N2 + HCl
• Replacement by –NO2 group:
 • When diazonium fluoroborate is heated with aqueous sodium
nitrite solution in the presence of copper, the diazonium group
is replaced by –NO2 group

(B)
Reactions involving retention of diazo group coupling reactions:-
• The azo products obtained have an extended conjugate system
having both the aromatic rings joined through the –N=N– bond.
• These compounds are often coloured and are used as dyes.
Benzene diazonium chloride reacts with phenol in which the
phenol molecule at its para position is coupled with the
diazonium salt to form
p-hydroxyazobenzene.
• This type of reaction is known as coupling reaction.
• Similarly the reaction of diazonium salt with aniline yields
p-aminoazobenzene. This is an example of electrophilic substitution
reaction.