20 Chapter Amines
Amines are organic bases. They are found widely in nature.
Trimethylamine occurs in animal tissue while the distinctive odor
of fish is due to amines. Amines isolated from plants are called
aNomenclature of which are pharmacologically important.
lkaloids, many
primary
1o-amine
R2NH
secondary
2o-amine
:
RNH2
:
:
Amines are classified
according to the number of R
groups around the nitrogen.
R3N
tertiary
3o-amine
The R groups may be alkyl or aryl.
Alkyl Group Names
Simple amines are named by naming the alkyl group or groups
attached to the nitrogen followed by "amine." The prefixes "di"
and "tri" are used as needed.
Systematic Names
The systematic name is derived from the alkane name by
dropping the "e" and adding the suffix "amine."
Examples
primary amines
CH3
CH3CNH2
CH3
NH2
CH3NH2
methylamine
(methanamine)
cyclohexylamine
(cyclohexanamine)
tert-butylamine
(2-methyl-2-propanamine)
secondary amines
In the systematic name, the second R group is indicated as "N-,"
followed by the systematic amine name of the first group.
CH3NHCH2CH3
ethylmethylamine
(N-methylethanamine)
CH3CH2NHCH2CH3
diethylamine
(N-ethylethanamine)
tertiary amines
(CH3) 3N
trimethylamine
(N,N-dimethylmethanamine)
N(CH3)2
cyclopentyldimethylamine
(N,N-dimethylcyclopentanamine)
The "Amino" Group
When -NH2 is a substitutent, it
is named as an "amino" group
in the systematic name.
H2NCH 2CH2COOH
3-aminopropanoic acid
CH3CHCH2CH2OH
NH2
3-amino-1-butanol
Arylamines
CH3
NH2
Aromatic amines are often named
as derivatives of aniline.
aniline
Heterocyclic Amines
N
CH3
N,N-dimethylaniline
Heterocycles are cyclic structures where one or more carbon atoms are
replaced by N,O or S. A few important nitrogen heterocycles are:
:
:
:
N
H
pyrrole
piperidine
:
N
N
pyridine
N
H
pyrrolidine
Structure
The nitrogen atom in most amines is similar to that in ammonia and
can be considered to be sp 3 hybridized. The nonbonding electron
pair is in an sp 3 orbital.
:
R'
R''
N
R'''
sp3 hybridized N
The geometry is described
as trigonal pyramidal.
Bond angles are close to
109.5o.
Stereochemical Features
When there are three different groups attached to the nitrogen, the
structure is chiral. But because of very fast inversion at the stereocenter
(the inversion rate in NH3 is close to 1011 s-1), it is not possible to resolve
a chiral amine.
R'' R'
N
R'''
R'
fast
:
:
R''
N
R'''
interconversion of amine enantiomers by
fast inversion at the nitrogen center
Chiral Tetravalent Nitrogen Compounds
Chiral tetravalent ammonium salts (quaternary ammonium salts)
display stereochemical features similar to chiral tetravalent carbon.
R''
R'
+
NR
R'''
R'
X
+
RN
R''
R'''
chiral quaternary ammonium salts can be resolved
R'' R'
CR
R'
X
R''
RC
R'''
R'''
chiral carbon compounds can be resolved
Interconversion of enantiomers requires bond breaking.
Basicity of Amines: Amine Salts
Amines are relatively weak bases. They are stronger than
water bases and alcohols, but weaker bases than hydroxide and alkoxide
ions and most carbanions.
R-O: < R-N-R'' <
H
R'
-
R-O
-
:
:
:
relative
base
strength
< R-C-R''
R'
Conjugate Pairs
Tables often list the acidity constants, Ka, of the conjugate acids.
Remember that RNH2 and RNH3+ are conjugate pairs.
:
RNH2
base
+ H2O
RNH3+ + HOconjugate
acid
Estimating Base Strength from pKa Values
It follows that strong bases (large values for Kb) have weak conjugate
acids, and weak bases have strong conjugate acids.
Some Examples of Bases with pKa Values of Conjugate Acids
NH3
pKa values
of conjugate
acids
CH3NH2 CH3CH2NH2
9.26
10.64
10.75
..
Protonation of primary,
secondary or tertiary amines
produces aminium salts.
NH2
10.64
+
-
+
-
RNH2 + HX
RNH3 X
R2NH + HX
R2NH2 X
..
..
R3N + HX
+
-
R3NH X
aminium salts
In all of the above aminium salts, there is one or more H attached to the
tetravalent nitrogen. Aminium salts are not basic because there is no
nonbonding electron pair on the nitrogen atom.
Aryl Amines are Weaker Bases than Alkyl Amines
The base strengths are illustrated by comparing
cyclohexylamine and aniline:
..
NH2
pKa of conjugate acid
10.64
..
NH2
4.58
Ka
2.3 x 10-11
2.6 x 10-5
Kb
4.3 x 10-4
3.8 x 10-10
weaker
base
stronger
base
A Comparison of Aliphatic and Aromatic Amines
+
:
NH 3
NH2
+ HO-
+ H2O
+
:
NH3
NH2
+ H2O
stabilization
energy
+ HO-
lost stabilization
energy
In cyclohexylamine, the nonbonding electrons are localized on the
nitrogen, and there is no special stabilization of the electronic
structure.
In aniline, interaction of the nonbonding electrons with the aromatic
-electron system provides a degree of stabilization that is lost in the
anilinium ion.
Resonance Theory Description of Stabilization by
-Electron Delocalization in Aniline
..
+
NH2
=
-
NH2
=
NH2
NH2
=
NH2
+
+
..
-
usual Kekule' structures
stabilization by -electron delocalization
(an extra component of stabilization)
In the anilinium ion (the conjugate acid), this extra stabilization due
to delocalization of the nonbonding electron pair is not possible. The
only resonance stabilization is from the Kekule' structures:
+
NH3
anilinium ion
+
NH3
Therefore, for the equilibrium:
:
+
NH3
NH2
+ HO-
+ H2O
larger component
smaller component
of resonance stabilization
of resonance stabilization
The free base state is stabilized by resonance
relative to the conjugate acid state.
+
:
NH3
In neither cyclohexylamine
nor its conjugate acid is
resonance a factor.
NH2
+ H2O
no resonance
stabilization
+
no resonance
stabilization
HO-
Quaternary Ammonium Salts
When there are four R groups
(alkyl or aryl) attached to the
nitrogen, the function is called a
quaternary ammonium ion.
R
R' N+ R''' XR''
a quaternary
ammonium salt
Quaternary ammonium salts are prepared by the
exhaustive N-alkylation of amines:
SN2 reactions: "exhaustive" N-alkylation
R-NH
R'
R'X
(-HX)
:
:
:
R-NH2
R'X
(-HX)
R-N-R'
R'
R'X
(-HX)
R'
+
R-N-R' XR'