CHE 1502 – General Chemistry

1B
Lecturer In-Charge

Prof. Adewale O. Adeloye

University of South Africa.

Lecture 14

6th July, 2024

 Chemistry of the Amines
Amines: Occurrence, Nomenclature, Classification and Structure;
Physical properties; Reactivity and Basicity.

1. General Introduction to Amines

2. Classification and Nomenclature of Amines
3. Physical properties of Amine
4. Synthesis of Amines
5. Reactivity and Basicity of Amines:
(a) Reaction of Amines with Water
(b) Reaction of Amines with Acids
(c) Reaction of Amines with Alkyl halides
(d) Reaction of Amines with Aldehyde and Ketones
(e) Oxidation of Amines
 1. General Introduction to Amines:
 Amines are organic derivatives of ammonia in the same way
that alcohols and ethers are organic derivatives of water. Like
ammonia, amines contain a nitrogen atom with a lone pair of
electrons, making amines both basic and nucleophilic.
 Amines occur widely in both plants and
animals. Trimethylamine, for instance,
occurs in animal tissues and is partially
responsible for the distinctive odour of
fish; nicotine is found in tobacco; and
cocaine is a stimulant found in the South
American coca bush.
Amino acids are the building blocks
from which all proteins are made, and
cyclic amine bases are constituents of
nucleic acids.
 Cyclic amines are secondary or tertiary amines forming a cyclic
structure. In amines, nitrogen undergoes sp3 hybridisation and
the shape is pyramidal due to the presence of lone pair of
electrons on nitrogen.

2. Classification and Nomenclature of Amines:

 Amines can be either alkyl-substituted (alkylamines) or aryl-

substituted (arylamines) and can be classed as primary (RNH2),
secondary (R2NH), or tertiary (R3N), depending on the number
of organic substituents attached to nitrogen.

For example, methylamine (CH3NH2) is a primary alkylamine

 Note that this usage of the terms primary, secondary, and
tertiary is different from our previous usage. When we speak of
a tertiary alcohol or alkyl halide, we refer to the degree of
substitution at the alkyl carbon atom, but when we speak of a
tertiary amine, we refer to the degree of substitution at the
nitrogen atom.

 Compounds containing a nitrogen atom with four attached

groups also exist, but the nitrogen atom must carry a formal
positive charge. Such compounds are called quaternary
ammonium salts.
 A quaternary ammonium salt

 Primary amines, RNH2, are named in the IUPAC system by

adding the suffix -amine to the name of the organic substituent.

 Amines with more than one functional group are named by

considering the –NH2 as an amino substituent on the parent
molecule.
 Symmetrical secondary and tertiary amines are named by
adding the prefix di- or tri- to the alkyl group.
 Unsymmetrically substituted secondary and tertiary amines
are named as N-substituted primary amines.

 The largest organic group is chosen as the parent, and the other
groups are considered as N-substituents on the parent (N because
they are attached to nitrogen).
3. Physical properties of Amines

 Like alcohols, amines with fewer than five carbon atoms are
generally water-soluble.
Also like alcohols, primary and secondary amines form
hydrogen bonds and are highly associated. As a result, amines
have higher boiling points than alkanes of similar molecular
weight.

 One other characteristic property of amines is their odour.

Low-molecular weight amines such as trimethylamine have a
distinctive fish-like aroma, while diamines such as putrescine
(butane-1,4-diamine) have odours as putrid as their common
names suggest.
 4. Synthesis of Amines:

1. Reduction of Nitriles and Amides

2. Reductive Amination of Aldehydes or Ketones:
 Ammonia, primary amines, and secondary amines can all be
used in the reductive amination reaction, yielding primary,
secondary, and tertiary amines, respectively.

Mechanisms of reaction
3. SN2 Alkylation Reactions of Alkyl Halides:

 If ammonia is used, a primary amine results; if a primary amine is

used, a secondary amine results; and so on. Even tertiary amines
react rapidly with alkyl halides, yielding quaternary ammonium
salts, R4N+ X–.
 However, none of these reactions stops cleanly after a single
alkylation has occurred. Because ammonia and primary amines
have similar reactivity, the initially formed monoalkylated amine
often undergoes further reaction to yield a mixture of mono-, di-,
and trialkylated products.
 A better method for preparing primary amines from alkyl
halides is to use azide ion, N3–, as the nucleophile rather than
ammonia.
 The product is an alkyl azide, which is not nucleophilic, so
overalkylation can not occur. A subsequent reduction of the
alkyl azide with LiAlH4 then leads to the desired primary
amine.
5. Reactivity and basicity
 The chemistry of amines is dominated by the lone pair of
electrons on nitrogen, which makes amines both basic and
nucleophilic.
 They therefore react with acids to form acid–base salts, and
they react with electrophiles in many of the polar reactions

 Amines are much stronger bases than alcohols and ethers,

their oxygen containing analogs.

 Basicity of amines depends on the groups attached to them,

solvation effect and steric hindrance
Arylamines, however, are weaker bases than alkylamines by a
factor of about 106, as is the heterocyclic amine pyridine.
The decreased basicity of arylamines relative to alkylamines is
due to the fact that the nitrogen lone-pair electrons in an
arylamine are shared by orbital overlap with the p orbitals of
the aromatic ring through five resonance forms and are less
available for bonding to an acid.

 In contrast to amines, amides (RCONH2) are nonbasic. Amides

are not protonated by aqueous acids, and they are poor
nucleophiles.
 The main reason for this decreased basicity of amides
relative to amines is that the nitrogen lone-pair electrons are
shared by orbital overlap with the neighboring carbonyl-
group π-orbital.

The nitrogen lone-pair electrons are

shared by orbital overlap with the
neighboring carbonyl-group π-orbital.
 In resonance terms, amides are more stable and less reactive
than amines because they are hybrids of two resonance forms.
This amide resonance stabilization is lost when the nitrogen atom
is protonated, however, so protonation is disfavored.

 It is often possible to take advantage of its basicity to purify

an amine. If a mixture of an amine (basic) and a ketone
(neutral) is dissolved in an organic solvent and aqueous HCl is
added, the basic amine dissolves in the acidic water as its
ammonium ion, while the neutral ketone remains in the organic
solvent.

 Separation of the water layer and neutralization of the

ammonium ion by addition of NaOH then provides the pure
amine
Basicity of amines:
 Being basic in nature, they react with acids to form salts.

 Amine salts on reaction with bases like NaOH regenerate the

parent amine.

 Amine salts are water-soluble but insoluble in organic solvents

such as alcohol and ether. This reaction is the basis for the
separation of amines from non-basic organic compounds which are
insoluble in water.
 The reaction between amines and mineral acids forms ammonium
salts which clearly depicts the basic nature of amines.
 The difference in electronegativity of hydrogen and nitrogen
atom and the presence of a lone pair of electrons on the nitrogen
atom makes the amine reactive.

 The number of hydrogen atoms attached to nitrogen determines

the course of action for the amine. This is the reason why primary,
secondary and tertiary amines undergo different reactions.

 Amines behave like nucleophiles due to the presence of unshared

electrons. Following are the reactions of amines:

(a) Reactions of Amines with Water

 When an amine is dissolved in water, an equilibrium is
established in which water acts as an acid and transfers a
proton to the amine.
 Just as the acid strength of a carboxylic acid can be measured
by defining an acidity constant Ka, the base strength of an
amine can be measured by defining an analogous basicity
constant Kb.

 The larger the Kb and the smaller the pKb, the more favorable
the proton-transfer equilibrium and the stronger the base.

For the reaction:

RNH2 + H2O RNH3++ OH–

As indicated, substitution has relatively little effect on alkylamine

basicity; most simple alkylamines have pKb’s in the narrow range 3
to 4.
(b) Reaction with acids
When reacted with acids, amines donate electrons to form
ammonium salts.

Reaction with acid halides

Acid halides react with amines to form substituted amides.
Reaction of Amines with Acids – Nitrous acid
 Due to the unshared electron pair, amines can act as both bases
and nucleophiles.
 Nitrous acid is unstable and must be prepared in the reaction
solution by mixing sodium nitrite with acid.
 Primary amines react with nitrous acid to yield a diazonium
salt, which is highly unstable and degradates into a carbocation
that is capable of reaction with any nucleophile in solution.

 Therefore, reacting primary amines with nitrous acid leads to a

mixture of alcohol, alkenes, and alkyl halides.
Arenediazonium salts are useful because the diazonio group (–N≡N)
can be replaced by a nucleophile in a substitution reaction.

Many different nucleophiles—halide, hydride, cyanide, and

hydroxide among others—react with arenediazonium salts,
yielding many different kinds of substituted benzenes.
 The overall sequence of (1) nitration, (2) reduction, (3)
diazotization, and (4) nucleophilic substitution is perhaps the
single most versatile method of aromatic substitution.

 Aryl chlorides and bromides are prepared by reaction of an

arenediazonium salt with the corresponding copper(I) halide,
CuX, a process called the Sandmeyer reaction.

 Aryl iodides can be prepared by direct reaction with NaI

without using a copper(I) salt. Yields generally fall between 60%
and 80%.
 Secondary aliphatic and aromatic amines form nitrosoamine
with nitrous acid.
(C). Reaction of Amines with Alkyl halides
 Step 1: The amine N functions as the nucleophile and attacks
the electrophilic C of the alkyl halide displacing the bromide and
creating the new C-N bond.

Step 2: An acid/base reaction. The

base (excess amine) deprotonates
the positive N (ammonium) center
creating the alkylation product,
here a secondary amine.
 Electrophilic Aromatic Substitutions
 An amino group is strongly activating and ortho- and para-
directing in electrophilic aromatic substitution reactions. This high
reactivity of amino-substituted benzenes can be a drawback at
times because it’s often difficult to prevent polysubstitution.

 Reaction of aniline with Br2, for instance, takes place rapidly

and yields the 2,4,6-tribrominated product. The amino group is so
strongly activating that it’s not possible to stop at the monobromo
stage.
 Treatment of an amine with acetic anhydride yields the
corresponding acetyl amide, or acetamide.
 Although still activating and ortho-, para-directing, amido
substituents ( R–N–C=O) are less strongly activating and less basic
than amino groups because their nitrogen lone-pair electrons are
delocalized by the neighboring carbonyl group.
 As a result, bromination of an N-arylamide occurs cleanly to
give a monobromo product, and hydrolysis of the amide with
aqueous base then gives the free amine.
(d) Reaction of Amines with Aldehyde and Ketones

 Aldehydes and ketones react with primary amines to give a

reaction product (a carbinolamine) that dehydrates to yield
aldimines and ketimines (Schiff bases).
 If you react secondary amines with aldehydes or ketones, enamines
form.

(e) Oxidation of Amines:

 Although you can oxidize all amines, only tertiary amines give
easily isolated products. The oxidation of a tertiary amine leads to
the formation of an amine oxide.

 Arylamines tend to be easily oxidized, with oxidation occurring

on the amine group as well as in the ring.
END OF LECTURE 14

QUESTIONS