Amines
The organic bases
Categorizing Amines
„
Amines are categorized by the number of alkyl
groups attached to nitrogen:
1º
2º
3º
4º
(primary amine)
(secondary amine)
(tertiary amine)
(quaternary amine salt)
RNH2
R2NH
R3N
R4N+
1
Naming simple amines
„
Simple 1º amines are named as “alkylamine”
‰
„
Examples:
„ methylamine CH3NH2
„ ethylamine
CH3CH2NH2
„ butylamine
CH3CH2CH2CH2NH2
Symmetrical 2º or 3º amines are named as
“dialkylamine” or “trialkyamine”
‰ Examples:
„
diethylamine (CH3CH2)2NH;
trimethylamine (CH3)3N
Naming more complex amines
„
Amines with more than one type of alkyl group may
be named as N-substituted primary amines. The
longer alkyl chain determines the base name.
‰
Examples
„ N-methylpropylamine CH3NHCH2CH2CH3
„ N,N-dimethylethylamine (CH3)2NCH2CH3
2
Naming more complex amines
„
Amines that have more than one functional group
may be named using “amino” as a substituent on
the parent molecule.
‰
Examples:
„ 2-aminoethanol
H2NCH2CH2OH
„ 4-aminobutanoic acid H2NCH2CH2CH2CO2H
Heterocyclic amines
„
Some amines have a nitrogen as part of a ring.
These generally have common (non-systematic)
names, which should be memorized:
NH2
N
N
N
N
H
aniline
pyridine
pyrimidine
N
N
N
H
quinoline
indole
N
H
imidazole
pyrrole
N
N
H
benzimidazole
3
Structure of amines
„
„
„
Amines have an sp3 hybridized nitrogen
In principle, tertiary amines with three different R
groups should be chiral (i.e., have a stereocenter).
However, rapid pyramidal inversion of the amine
nitrogen prevents isolation of the enantiomers
except where the nitrogen is part of a ring or has
other geometrical constraint.
X
X
N
Y
fast
Z
N
Z
Y
Properties of amines
„
„
„
„
Amines are moderately polar and are capable of
hydrogen bonding.
Low MW amines (up to about C5) are soluble in
water; higher MW amines will dissolve in acidic
solution (as their conjugate acid).
Many amines have foul odors.
Amines are weak bases.
4
Example of biologically active amines
H2NCH2CH2CH2CH2NH2
putrescine
H2NCH2CH2CH2CH2CH2NH2
H2N(CH2)N(CH2)4N(CH2)3NH2
spermine
H
H
H2NCH2CH2CH2CH2NCH2CH2CH2CH2NH2
spermidine
H
H OH
HO
cadaverine
H OH
NHCH3
NH2
HO
HO
HO
NH2
HO
HO
dopamine
epinephrine
(adrenaline)
norepinephrine
(noradrenaline)
More biologically active amines…
H CH3
H CH3
NH2
NHCH3
CH3O
NH2
CH3O
amphetamine
(benzadrine)
OCH3
methamphetamine
(speed)
mescaline
CH2CH2NH2
CO2H
N
N
N
nicotinic acid
(niacin)
CH2CH2NH2
HO
serotonin
H
N
H
histamine
5
More biologically active amines…
H
O
O
H
N
N
CH3CH2O
N
N
N
Cl
CH3
N
CH2CH2CH3
O
O S N
O
diazepam (Valium)
N
O
H2N
C OCH2CH3
CH3
Sildenafil (Viagra)
benzocaine
(a topical anesthetic)
More biologically active amines…
RO
O
H3C
O
N
C OCH
3
H
N
O
H
CH3
R'O
O
N
N
N
O
NCH3
H3C
CH3
C
cocaine
caffeine
O
codeine (R = CH3, R' = H)
morphine (R and R' = H)
heroin (R and R' = COCH3)
CH3
H
N
N
CH3
nicotine
CH3CH2O
C
NCH3
CH3CH2
C
O
O
mepiridine
(Demerol)
C6H5 NCH3
CH3
Methadone
6
More biologically active amines…
H
H
O
(CH3CH2)2N
C
H
N
CH3
N
N
HO
H
H
N
N
O
quinine
N
O
H
strychnine
lysergic acid diethylamide (LSD)
H
N
CH2CH2CH3
H
coniin (the poison from
hemlock used to kill Socrates)
Basicity of amines
„
Amines are slightly basic. This is because they
have a lone pair of electrons to donate to a proton.
This same feature makes them nucleophiles.
RNH2
+
H OH
Kb =
„
RNH3
+
OH
[RNH3 ] [OH ]
[RNH2]
Typical amines have Kb values = 10-3 to 10-4
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Basicity of amines…
„
However, instead of measuring an amine’s basicity
using the above equilibrium, chemists usually refer
to the acidity of the conjugate acid of the amine.
The weaker the conjugate acid, the stronger the
base strength of the amine.
RNH3
RNH2
+
H
Ka =
[RNH2] [H ]
[RNH3 ]
„
Typical amines have Ka values (of their conjugate
acids) of 10-9 to 10-10 (pKa values of 9 to 10.)
pKa values of conjugate acids of amines
CH3NH2
CH3CH2NH2
10.7
10.8
(CH3)2NH
(CH3CH2)2NH
10.7
10.5
(CH3)3N
(CH3CH2)3N
9.8
11.0
All are about the same value.
The same substituent effects
that stabilize carbocations
that are more highly
substituted by alkyl groups
are offset by diminished
stabilization by solvent due to
crowding.
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Some amines that are weaker bases
NH2
N
N
H
aniline
pK = 4.6
„
„
„
pyridine
5.2
pyrrole
0.4
Aniline is a weaker base because the lp of electrons
is delocalized by resonance into the aromatic ring.
Pyridine is weaker because it is an imine (C=N).
Pyrrole is weaker because the lp of electrons is
delocalized with the other π electrons to make 6 π e-.
Substituent Effects on Basicity of Aniline
pKa of
conj. acid:
NH2
NH2
4.6
OCH3
5.3
NH2
NO2
1.0
(much weaker base)
2 explanations of weaker basicity of nitroaniline:
NH2
NO2
NH2
O
N
O
NH2
O
N
O
O
NH2
NH3
N
NO2
O
Resonance stabilizes free base, destabilizes its protonated form (see next slide)
9
Substituent Effects on Basicity of Anilines
O 2N
NH3
Energy
NH3
CH3O
NH3
Reaction progress (protonation)
An amine that is a stronger base
„
„
There is one type of amine
that is a stronger base:
NH
H2N
C
NH2
guanidine
pKa = 13.6
Guanidine is a strong base because its conjugate
acid is stabilized by resonance:
NH2
H2N
C
NH2
NH2
H2N
C
NH2
NH2
H2N
C
NH2
NH2
H2N
C
NH2
A guanidine group is part of the structure of the amino acid arginine.
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