Amines
Structure and Classification of Amines
• Classification
• 1°, 2°, or , 3° amines: Amines in which 1, 2,
or 3 hydrogens of NH3 are replaced by alkyl or
aryl groups.
• Amines are further divided into aliphatic,
aromatic, and heterocyclic amines.
• Aliphatic amine: An amine in which nitrogen is
bonded only to alkyl groups.
• Aromatic amine: An amine in which nitrogen is
bonded to one or more aryl groups.
• Heterocyclic amine: An amine in which nitrogen is
one of the atoms of a ring.
sp3 Nitrogens as Stereocenters
• An acyclic sp3 nitrogen atom with three different
groups and a lone pair of electrons is
asymmetric.
• Even so, an amine with an asymmetric nitrogen
atom is rarely a stereocenter, leading to
enantiomers.
• Acyclic amines interconvert into their own mirror
images billions of times per second in a process
called pyramidal inversion.
• Thus acyclic amines are not chiral.
• Cyclic amines and quaternary ammonium salts
can be chiral since they are unable to undergo
pyramidal inversion.
• When the Cahn-Ingold-Prelog rules are used to
priorize groups to determine stereoisomers, the
electron lone-pair is last.
Nomenclature of Amines
• Aliphatic amines: replace the suffix -e of the
parent alkane by -amine.
• To name a secondary or tertiary amine, the alkyl
branches need to be named and “numbered”
using “N” to designate the branching.
N,N-dimethyl-3-ethyl-3-pentanamine
N-ethyl-2-propanamine
3,N-dimethyl-2-butanamine
• For aromatic amines, the IUPAC system retains
the common name aniline.
• Among the functional groups, -NH2 has one of
the lowest priorities.
• Thus –NH2 is often referred to as an amino
group and is given the amino- prefix.
• Common names for most aliphatic amines are
derived by listing the alkyl groups bonded to
nitrogen in one word ending with the suffix -amine.
• Alkyl groups are listed alphabetically.
• When four groups are bonded to the nitrogen
atom, we name the compound as a salt (with
cation and anion) of the corresponding amine.
• Use the suffix –ium to name tetraalkyl amine
cation.
• i.e., ammonium, pyridinium, anilinium, etc…
• Include the counterion (chloride, bromide,
etc…) in the name.
Physical Properties of Amines
• Amines are polar compounds, and both 1° and 2°
amines form intermolecular hydrogen bonds.
• N-H- - - -N hydrogen bonds are weaker than O-H- - - -O
hydrogen bonds because the difference in
electronegativity between N and H (3.0 - 2.1 = 0.9) is
less than that between O and H (3.5 - 2.1 = 1.4).
• Amines generally smell bad.
• Trimethylamine is responsible for the smell of rotting
fish.
Applications of Amines
• Amines are used as precursors to make dyes.
• Mauveine
• The first synthetic
dye invented by
William Perkin
when he was 18.
• Acid Orange 7
• It is used in hair
coloring formulations.
• Aniline Yellow
• It is used in inkjet
printer inks.
• Alkaloids are naturally occurring amines many
with medicinal properties. Many are 3o
heterocyclic amines.
nicotine
• Many important neurotransmitters are amines.
Basicity of Amines
• All amines are weak bases; thus, aqueous
solutions of amines are basic.
• The reaction of the weak base with water is
quantified with the base-dissociation constant, Kb.
CH3 NH3   OH  
Kb 
CH3 NH 2 
• It is also common to discuss the basicity of
amines by reference to the acid-dissociation
constant of its corresponding conjugate acid.
• For any conjugate acid-base pair, the pKa and
pKb are deeply connected to each other.
• Using values of pKa, we can predict the position
of equilibrium in acid-base reactions.
• Acetic acid is the stronger acid and, therefore, the
position of this equilibrium lies to the right.
• Aliphatic amines have about the same base
strength, pKb 3.0 – 4.0 and are slightly
stronger bases than NH3.
• Aromatic amines are considerably weaker
bases than aliphatic amines.
• Aromatic amines are weaker bases than
aliphatic amines because the resonance
stabilization of the base is lost on protonation.
• That is, the conjugate acid of an aromatic
amine is a stronger acid than the conjugate
acid of the aliphatic amine.
• Electron-withdrawing groups, such as halogen
atoms, the nitro group, and the carbonyl group,
decrease the basicity of aromatic amines by
decreasing the availability of the electron pair on
nitrogen.
• Guanidine (pKb = 0.4) is the strongest base
among neutral organic compounds.
• Its basicity is due to the resonance delocalization
of the positive charge over the three nitrogen
atoms.
Reactions of Amines (Summary)
• Formation of ammonium salts with strong acids.
• Reduction of nitro group to form amino group.
(Formation of primary amine)
• Reagent in nucleophilic substitution.
• Formation of benzenediazonium salt from aniline
with HNO2.
• Reaction of benzenediazonium salt with various
reagents to make substituted benzenes.
Formation of Ammonium Salts
• All amines, whether soluble or insoluble in
water, react quantitatively with strong acids to
form water-soluble salts.
• Many drugs that are water-insoluble are made soluble
through the reaction with hydrochloric acid.
Norepinephrine is used to treat hypotension (low blood pressure).
Synthesis of 1° Amines
• Most 1° aromatic amines are synthesized by
nitration of an aromatic ring followed by
catalytic reduction of the nitro group to an
amino group.
Amines in Nucleophilic Substitution
• Reaction of an amine with an alkyl halide can be
used to form a new covalent bond.
• Step 1: Reaction of a nucleophile with an
electrophile to form a new covalent bond.
• Step 2: Take a proton away. Unreacted base
deprotonates the substrate, converting the
amine salt to a free amine.
• In Step 2, a new 2° amine was produced.
• The new amine can then also act as a
nucleophile.
• Thus the final reaction mixture will consist of
varying ratios of RNH2, R2NH, R3N, and R4N+Cl–.
• These ratios are difficult to control and,
therefore, amines are avoided as nucleophiles in
nucleophilic substitutions reactions.
Formation of the Benzenediazonium Salt
• Aniline reacts with sodium nitrite and
hydrochloric acid to produce an important
intermediate substrate, benzenediazonium salt.
NH2 + NaNO2 + HCl
Anilin e
(a 1° aromatic
amin e)
Sodium
n itrite
H2 O
0°C
+
N N Cl + H2 O
Ben zenediazoniu m
chloride
• Once formed, the benzenediazonium salt can
further react with a large variety of reagents to
yield a substituted benzene compound.
+
N N Cl + H2 O
Ben zenediazoniu m
chloride
OH + N2
Ph enol
Reactions of the Benzenediazonium Salt
• Benzenediazonium salt reacts with water and an
acid catalyst when heated to form phenol.
N
N
H2O
OH
H+, heat
• Benzenediazonium salt reacts with
tetrafluoroboric acid when heated to form
fluorobenzene.
N
N
HBF4, heat
F
Reactions of the Benzenediazonium Salt
• Benzenediazonium salt reacts with copper(I)
chloride, copper(I) bromide or copper(I) cyanide
to form chloro-, bromo-, or cyanobenzene.
CuCl, CuBr, CuCN
N
N
X
• Chemists sometimes think of cyanide as an honorary
halogen ion.
• Recall that R – C ≡ N is called a nitrile.
• Benzenediazonium salt reacts with potassium
iodide to form iodobenzene.
Reactions of the Benzenediazonium Salt
• Benzenediazonium salt reacts with
hypophosphorous acid, H3PO2, to replace the
diazonium group with hydrogen to form
benzene.
N
N
H3PO2
H
O
H
P
H
O
H
Reactions of the Benzenediazonium Salt