Amines

Amines constitute an important class of organic compounds derived by replacing one or more hydrogen
atoms of ammonia molecules by alkyl/aryl group(s). In nature, they occur among proteins, vitamins,
alkaloids and hormones. Synthetic examples include polymers, dyestuffs, and drugs.

Nomenclature

Alkylamine

Primary amines are named in systematic (IUPAC) nomenclature by replacing the -e of the
corresponding parent alkane with -amine.

Simple secondary and tertiary amines are named in common nomenclature by designating the
organic groups separately in front of the word amine.
 In systematic nomenclature, the smaller groups on the amine nitrogen are designated as
substituents and given the locant N.

In IUPAC nomenclature the substituent -NH2 is called the amino group

Aryl Amines

The common arylamines have the following names:

Heterocyclic Amines

The important heterocyclic amines have common names

In IUPAC nomenclature the prefixes aza-, diaza- and triaza- are used to indicate that nitrogen has
replaced carbon in the corresponding hydrocarbon
 The nitrogen is assigned position 1 and the ring is numbered to give the lowest overall set of locants
to the

Preparation of Amines

Amines are prepared by the following methods:

1. Reaction of alkyl halides with ammonia

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

Ammonolysis has the disadvantage of yielding a mixture of primary, secondary and tertiary
amines and also a quaternary ammonium salt. However, primary amine is obtained as a major
product by taking large excess of ammonia. The order of reactivity of halides with amines is RI
> RBr > RCl
2. Reaction of alcohols with ammonia
When a mixture of excess of ammonia and alcohol vapors is passed over a dehydrating catalyst
such as alumina or thoria at 300-400°C, a primary amine result.
H
ThO2
H3C OH + H N H 300-400oC
H3C NH2 + H OH

This reaction does not stop here. The methylamine produced in the first step reacts with a
second molecule of methanol to give a secondary amine. The secondary amine further reacts
with third molecules of methanol to yield a tertiary amine.
ThO2
H3C NH2 + H3C OH
300-400oC
H3C NH
CH3

CH3
ThO2
H3C NH
+ H3C OH
300-400oC
H3C N
CH3 CH3

3. Reduction of nitro alkanes

Nitro compounds are reduced to amines by passing hydrogen gas in the presence of finely
divided lithium aluminum hydride, nickel, palladium or platinum and also by reduction with
metals in acidic medium (Sn/HCl, Fe/HCl). Nitroalkanes can also be similarly reduced to the
corresponding alkanamines.
R O R
LiAlH4
N
+
+ 6H ether
NH2 + 2H OH
–
O
 Reduction with iron scrap and hydrochloric acid is preferred because FeCl 2 formed gets
hydrolysed to release hydrochloric acid during the reaction. Thus, only a small amount of
hydrochloric acid is required to initiate the reaction.
4. Reduction of amides
The amides on reduction with lithium aluminium hydride yield amines.

O R
LiAlH4

R NH2
+ 6H ether
NH2

The amide required in this process can be readily produced by the reaction of the corresponding
acyl halide with ammonia.
O O
H2Cr2O7 SOCl2
H3C H3C H3C
OH OH Cl

O O R
NH3
H3C H3C + NH2
Cl NH2

5. Reduction of nitriles
Nitriles on reduction with lithium aluminum hydride (LiAlH4) or catalytic hydrogenation
produce primary amines. This reaction is used for ascent of amine series, i.e., for the
preparation of amines containing one carbon atom more than the starting amine.

6. Reduction of Oximes
Amines can be obtained by reducing oximes of aldehydes and ketones. The common reducing
agents are sodium and absolute ethanol or hydrogen and nickel catalyst
R R R
N + 2H NH + 2H NH2
R OH R OH R
7. Reductive amination of aldehydes and Ketones
Amine can also be prepared by passing a mixture of an aldehydes or ketones and a large excess
of ammonia and hydrogen over nickel catalyst at 150°C.
NH2
O
Ni
+ NH3 + H2
150oC, R H + H OH
R H 300 atm

NH2
O
Ni
+ NH3 + H2
150oC, R R + H OH
R R 300 atm

8. 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.

9. Gabriel 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.
O O O

R Cl
NH + KOH N K N R

O O O

O O

H OH OH
N R
+
+ R NH2
H OH
O O
 10. From chloramine and Grignard reagent
Amine can also be prepared by coupling between chloroamine and Grignard reagents
Ether
H3C Mg
+ H2N Cl H3C NH2
Cl
Chloroamine required in this process can be derived from ammonia and sodium hypochlorite.

NH3 + ClONa H 2N Cl

Separation of Mixed amines

When the mixture contains salts of primary, secondary, and tertiary amines along with the tetra ammonium
salt, it is just distilled with potassium hydroxide solution. The three amines are salt-free and distill over.
The tetraalkylammonium hydroxide, however, remains unaffected by alkali and being nonvolatile is left
behind.

–
R
+
NH3 Cl + K OH R NH2 + K Cl + H OH

+ –
R NH2 Cl + K OH R NH + K Cl + H OH

R R

R R
+ –
R NH Cl + K OH R N + K Cl + H OH

R R

R
+ –
R N R Cl + K OH No Reaction
R

The distillate contains the three free amines (primary, secondary and tertiary) which may then be
separated by the following methods:

1. Fractional Distillation: A mixture of primary, secondary and tertiary amine can be separated
into individual components by fractional distillation according to their boiling point. For example,
 CH3

H3C NH CH3 H3C N CH3

H3C NH2

B.P: 17oC B.P: 56oC B.P: 98oC

This is the most satisfactory method and is used industrially. The success of this method is
primarily due to the high efficiency of the modern industrial fractionation apparatus which
ensures almost complete separation of the amines.

2. By the reaction with Diethyl oxalate (Holfmann method): The given mixture of 1°, 2° and
3° amines are heated with diethyl oxalate, where,
a. 1° amine forms a dialkyl oxamide which is crystalline solid.

O R O R
C O CH2 CH3 C NH

C O CH2 CH3
+ 2H N H
C NH
+ 2 H3C
O O OH
R
b. 2° amine forms a dialkyl oxamic ester which is an oily liquid

O R
O R
C O CH2 CH3
C N
+ 2 H3C

C O CH2 CH3
+ H N R
C O
R
CH2 CH3
OH
O O
The second ester group does not react because of steric hinderance.
c. 3° amine does not react as it does not contain a replaceable hydrogen atom on nitrogen
O R
C O CH2 CH3

C O CH2 CH3
+ R N R No reaction
O
The reaction mixture is now separated by fractional distillation process. The 3° amine
distils over and forms the first fraction. This is followed by dialkyl oxamic ester which forms
the second fraction. The dialkyl oxamide remains behind in the distillation flask.
The dialkyl oxamide and the dialkyl oxamic ester separated as above are hydrolysed with
KOH to generate the free amines which are distilled off.
 R O K
O
C NH C O
+ K OH + H3C NH2
C NH C O
O O
R K

O K
O R
C O
C N
+ K OH + R NH
R C O R
C O CH2 CH3 O
O K

3. Reaction with Benzenesulphonyl chloride (Hinsberg Method): This method makes use
of the different reaction of 1°, 2° and 3° amines with benzenesulphonyl chloride (Hinsberg reagent).
a. 1° amines forms N-alkyl-benzenesulphonamide which is soluble in base.
O O
Cl NH R
S S
O + H2N R O + H Cl

O
NH R O –
S N R Na+
S
O + NaOH
O
+ H OH

b. 2° amines forms N, N-dialkyl-benzenesulphonamide which is NaOH solution. This is so

because the resulting sulphonamide has no replaceable hydrogen atom to yield the sodium
salt.
R
O O
Cl N R
S R S
O + H N O + H Cl
R
R
O
N R
S
O + NaOH No Reaction

c. 3° amine does not react with benzenesulphonyl chloride at all.

The reaction mixture obtained after treatment with benzenesulphonyl chloride in the
presence of NaOH is now distilled. The 3° amine passes over first. The remaining mixture
 is filtered and the filtrate on acidification gives sulphonamide of 1° amine, while the residue
is the sulphonamide of 2° amine. The two sulphonamide thus isolated are hydrolysed with
HCl to regenerate the individual 1°, and 1° amines which are fractionally distilled.
H
O O
N R OH
S –
H S
O + H OH O + R NH2

R
O O
N R OH
S –
H S
O + H OH O + R NH
R

Physical Properties of Amines

❖ Physical state: Low molecular-weight amines are colorless gases at room temperature. Those
with four or more carbons are volatile liquids. The higher molecular weight amines are colorless
solids.
❖ Odor: Low molecular-weight amines tend to have sharp, penetrating odors similar to ammonia.
Higher molecular-weight amines often smell like rotting fish, and are often found in decaying
animal tissues. Aniline and other arylamines are usually colorless but get colored on storage due to
atmospheric oxidation.
❖ They are all lighter than water.
❖ Boiling point: Simple amines are polar compounds. Primary amines have two polar N-H bonds,
secondary amines have one N-H, while tertiary amines have none.
Therefore, primary and secondary amines are more polar and capable of forming intermediate
hydrogen bonds by virtue of the presence of unshared electron pair on N atom. Tertiary amines are
also polar but they are not capable of intermolecular H bonding.

Tertiary amines have lower boiling points than primary or secondary amines of comparable
molecular weights.
❖ Solubility: Lower aliphatic amines are soluble in water because they can form hydrogen bonds
with water molecules. However, solubility decreases with an increase in molar mass of amines due
to increase in size of the hydrophobic alkyl part. Higher amines are essentially insoluble in water.
❖ Primary and secondary amines can form hydrogen bonds to each other and water. Tertiary amines
cannot form hydrogen bonds to each other but can form hydrogen bonds to hydrogen bond donors
such as water.

❖ Basicity of Amines
o General rule: All amines possess a lone pair of electrons on the nitrogen atom. The basic
character of these compounds depends upon how readily this lone pair of electrons are
available for coordination with a proton. Greater the tendency to donate the lone pair of
electrons, the stronger the base. The basicity of amine is usually expressed by the following
basicity constant Kb also known as the base dissociation constant.

Thus, the basicity of amines is largely dependent on the following factors

• + I and –I effect of alkyl groups

• Hybridization
• Steric effects
• Resonance
Basicity of aliphatic amines: (+I effect of alkyl groups): In the case of methylamine,
the methyl group because of its +I effect helps to stabilize the positive charge on nitrogen
(makes the lone pair of electrons easily available for protonation). The positively charged
ammonium ion is dispersed better because it has a methyl group instead of hydrogen. This
stabilization lowers the potential energy of methyl ammonium cation, thus making it a
strong base than ammonia.
Thus, the more the alkyl groups are attached to positively charged nitrogen, the more stable
the alkyl ammonium cation becomes and the more basic the amine would be. As a result,
in the gaseous phase, tertiary amines are stronger bases in comparison to secondary
amines which in turn would be stronger bases than the primary amine.

Effect of hydrogen bonding and steric effect: Thus, it can be said that the basicity of
amine in the gaseous phase depends largely on the +I effect of the alkyl group. But this
basicity order of amines does not hold true in an aqueous solution. In the aqueous phase,
tertiary amines are weaker bases even in comparison to primary amines. This altered order
of amine basicity in solution is due to the solvation effect.

Alkyl substitution increases the ability of ammonium cation to disperse its positive charge
but it decreases its ability to form hydrogen bonds with water molecules. In the case of
secondary amines, the dialkylammonium cation formed still has two hydrogens to undergo
hydrogen bonding, whereas in case of tertiary amines, the trialkylammonium cation has
only one hydrogen available for hydrogen bonding. As a result, trialkylammonium cation
is less stabilized in comparison to dialkylammonium cation. Besides this, the steric
hindrance of the three-alkyl groups on t-amine also prevents the lone pair of electrons to
be attacked by H+ ions. Hence secondary amines are stronger bases than tertiary amines.
 Basicity of Saturated Arylamines

Arylamines (pKb = 10) such as aniline are far less basic than alkylamines (pK b = 4). For
example, aniline is less basic than cyclohexylamine by nearly a million times.

Aniline is a weaker base than cyclohexylamine because the electron pair on nitrogen of
aniline is delocalized by interaction with the π-system of the aromatic ring and is less
readily available for bonding to a proton. The unshared electron pair in cyclohexylamine is
localized on nitrogen, less strongly held, and therefore available in an acid-base reaction.

Chemical Properties of Amines

1. Formation of Salts with Mineral acids

Presence of unpaired lone pare of electron on Nitrogen, amines act as a Lewis bases. Thus, they react
with aqueous mineral acids to form substituted ammonium salts.
The amine salts are generally well-defined crystalline substances with sharp melting point and are
often useful for the identification and separation of the amine mixture. Amines can be regenerated
when treated with strong alkali such as NaOH
2. Alkylation reaction
The unshared electron pair on the nitrogen atom makes amines behave as strong nucleophiles. Thus,
when a primary amine is treated with alkyl halide in a basic medium such as ammonia, the halogen
atom of alkyl halide is displaced producing dialkylammonium salt. The dialkylammonium salt in the
presence of ammonia at once gives a secondary amine.
 H H
+ –
R N +R Cl R N H + Cl

H R
dialkylammonium cation
H H H H
+ +
R N H + N H R N + H N H

R H R H
2o amine
R

R N +R Cl No reaction

R
3. Acylation reaction
Aliphatic and aromatic primary and secondary amines react with acid chlorides, anhydrides and
esters by nucleophilic substitution reaction. This reaction is known as acylation. You can consider
this reaction as the replacement of hydrogen atom of –NH2 or >N–H group by the acyl group. 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.
H O H O

R N + R C Cl R N C R + H Cl

H N-alkylamide

H O R O

R N + R C Cl R N C R + H Cl

R N, N -dialkylamide

R O

R N + R C Cl No reaction

R
4. Sulphonylation
Sulphonyl chloride are the acid chlorides produced by the reaction of phosphorous pentachloride or
thionyl chloride (SOCl2).
O O
PCl5
R S OH
or SOCl2
R S Cl + H Cl

O O
 They react with amines in a manner similar to acyl chloride. Thus, benzenesulphonyl chloride reacts
with primary and secondary amines to from N-alkyl and N, N-dialkylsulphonamides respectively.
R
O O
Cl NH
H S S
R N + O O + H Cl

H
Benzenesulphonyl chloride N-alkylbenzenesulphonamide
R
R
O O
Cl N
R S S
R N + O O + H Cl

H
Benzenesulphonyl chloride N, N-dialkylbenzenesulphonamide

O
Cl
R S
R N + O No reaction

H
Benzenesulphonyl chloride

Most sulphonamides are crystalline solids. Their preparation and determination of melting point is
used for the identification of primary and secondary amines.
5. Reaction with nitrous acid
Three classes of amines react differently with nitrous acid which is prepared in situ from a mineral
acid and sodium nitrite.
(a) Primary aliphatic amines react with nitrous acid to form aliphatic diazonium salts which being
unstable, liberate nitrogen gas quantitatively and alcohols. Quantitative evolution of nitrogen is
used in estimation of amino acids and proteins.

(b) 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
6. Reaction with Grignard reagent

Primary and secondary amines react with Grignard reagent to form alkanes. Tertiary amines do not
contain a replaceable H atom and not able to react.

H
NH Mg
R N + R Mg R H + R CH3
H Cl Alkane

R R
R N + R Mg R H + N Mg
H Cl Alkane R CH3

7. Carbylamine reaction
Aliphatic and aromatic primary amines on heating with chloroform and ethanolic potassium
hydroxide form isocyanides or carbylamines which are foul smelling substances. Secondary and
tertiary amines do not show this reaction. This reaction is known as the carbylamine reaction or
isocyanide test and is used as a test for primary amines.
Cl
+ –
R NH2 + CH Cl + K OH R N C + K Cl + H OH

Cl Alkyl isocyanide
or carbylamine
8. Halogenation
Primary and secondary amine react rapidly with a solution of hypochlorous acid in the presence of a
base to produce N-chloroamines or N, N-dichloroamines.
Secondary amines gives
H H Cl
H O Cl H O Cl
R N H – R N Cl – R N Cl
HO HO
N-chloroamine N, N-dichloroamine

R R
H O Cl
R N H – R N Cl
HO
N-chloroamine
9. Oxidation of Amines
All types of amines are easily oxidized. The course of the reaction is very variable and depends very
much on the structure of the amine and the specific oxidant used.
a. Primary amines on oxidation with acidified KMnO4 give aldehydes and ammonia.
 O H2O
R CH2 NH2 R CH NH +
R CH O + NH3
Primary amine H
Aldehyde
R R R
O H2O
R CH NH2 R C NH +
R C O + NH3
Primary amine H
Aldehyde
R R O
O +
R C NH2 R C N
R –
R O
Primary amine
b. Secondary amines on oxidation with KMnO4 give tetraalkylhydrazine, while with H2O2 or
peracid they yield dialkylhydroxylamine.
R
KMnO4 R N N R
R N H + O + H2O
Secondary amine R R
tetraalkylhydrazine
R
H2O2 R N OH
R N H + O
or peracid
Secondary amine R
Dialkylhydroxylamine

c. Tertiary amines form amine oxides when oxidized with H2O2 or peracid.
R
R + –
H2O2 R N O
R N R + O
or peracid
Tertiary amine R
Amine oxide

Resonance structure of Aniline

The electronic structure of aniline can be represented as a resonance of the following

four canonical forms.
Diazonium salt

At low temperature (0 – 10°C), aromatic primary amines dissolved in strong acids (HCl or H2SO4),
react with nitrous acids to form water soluble compounds known as Diazonium Salts. Thus,
aniline dissolved in HCl forms the salts, aniline hydrochloride which reacts with nitrous acid to
yield benzenediazonium chloride.

H
H H + –
N H N H Cl

+ H Cl

Aniline Aniline hydrochloride

H
+ –
H N H Cl + –
N N Cl

< 10oC
+ HNO2 + 2 H 2O

Nitrous acid
Aniline hydrochloride

At higher temperature above 10°C benzenediazonium chloride converted/decomposed to phenol.

+ –
N N Cl OH

> 10oC
+ H 2O + H Cl + N2

Reaction of benzenediazonium chloride

1. Substitution of the diazonium group

a. Reaction with water (hydrolysis) at warm condition above 10°C.

+ –
N N Cl OH

> 10oC
+ H 2O + H Cl + N2
 b. Reaction with water potassium iodide solution at warm condition.
+ –
N N Cl I

+ KI + K Cl + N2

2. Coupling reaction of diazonium group

a. Reaction with phenol in presence of basic condition (NaOH) below 10°C
producing azo compound
+ –
N N Cl OH

< 10oC
+ + NaOH N N OH + Na Cl + HO
2

(4-hydroxyphenol)azobenzene)
Yellow