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Section 9: Amines – Chapter 20
Practice Problems:
None! (yay!)
N
Amines: Nomenclature
H3CN
HH
H3CN
HCH3
H3CN
CH3CH3
1o amine 2o amine 3o amine
H3CN
CH3CH3
CH3
X
a quaternary ammonium salt
NH2
t-butylamine
NH2
cyclohexylamine
NH2
aniline
N
diisopropylethylamine( Hünig's base )
OHH3C
H3CH3C NH2
H3C
H3CH3C
a 3o alcohol a 1o amine
Don't be confused...
Amines: Heterocyclic Amines
NN
H
N
N
N
H
NH
N
N
N
H
NH
Pyridine Pyrrole
QuinolineImidazole
Indole
Pyrimidine
Pyrrolidine
Piperidine
Amines: Structure
RN
R''R'
close to 109o
sp3 ~ tetrahedral
note: if R, R’, R’’ are different, the amine is technically chiral, but…
RN
R''R'
fast RN
R''R'
Amines: Smell
Et3Ntriethylamine - "fishy smell"
H2N NH2
cadaverine
H2NNH2
putrescine
H2N
HN NH2
spermidine
Amines: Basicity
N H A N H A
RNH3+ + H2O RNH2 + H3O
+
K a =[RNH2][H3O
+]
[RNH3+]
pK a = log K a
Basicity is often reported as the pKa of the conjugate acid:
Amines: Basicity
Some representative pKa values:
Et3N NH3 Ph NH2 NH
10.8 9.3 4.6 0.4pKa of
conjugate acid:
triethylamine ammonia aniline pyrrole
Don't be confused...
N H
pKa of the amineitself ~ 35
pKa of theconjugate acid
~ 11
Amines: in Biology
NH3C OCH3
O
O
OCocaine
N
NN
NH3C
CH3
CH3
O
O
Caffeine
O
NH
HN
HN
O
NH
O
O
HN
O
NH
HN
O
NH
O
O
HN
NH
OHN
O
O
NH
OOH
NH
OH
OH
NH2
NH
NH2HN
NH2O
NNH
OHO
Protein
N
S
OOH
OO
HN
Penicillin
Amines: in Biology
N
NH
CH3
N O
H
Lysergic acid diethylamide
N
NN
N
NH H
O
O
O
P OON N
H
O
O
CH3
N
NO
O
O
P OO
N
N
O
H
N
H
H
N N
N
O
H
Hadenine
thymine
guanine
cytosineO
O
O
PO O
O
O
O
PO O
DNA
NH
O
H H
H
NHO
Propecia
O
HO
HO
H
H H
NCH3
Morphine
OCH3
H
NH3C
Dextromethorphan
Amines: Preparation
A. Reduction of nitriles / amides / nitro compounds
RC
N 1. LiAlH4
2. H3OR NH2
R N
O
R'
R''
1. LiAlH4
2. H3O
R N
R''
R'
NO2SnCl2
H3ONH2
Amines: Preparation
B. SN2 reactions
H3N + R X R NH3
X
baseR NH2
X = Cl, Br, I...
H2N + R X R NH2
X
baseR NH
R R R
But...
Hard to stop here!!
R X
NRR
R
OK to stop here
R XR4N
X
If you want to go from a 2o amine to a 3o amine, rxn with R-X is usually OK. Otherwise, consider an alternative approach.
Amines: Preparation
C. Attack with NaN3
R X
X = Cl, Br, I...
Na N3+SN2
R NN
N R NH2or
LiAlH4
PPh3
D. Gabriel Synthesis
R X
X = Cl, Br, I...
+SN2
NH
O
Ophthalimide
N
O
O
KOH
R N
O
O
R NH2or
H2NNH2
MeOH
NaOHH2O
Amines: PreparationE. Reductive amination
R R'
O
ketoneor aldehyde
H2NR''
NaBH3CN
CH3OHR R'
NR''H
BH2CNH (i.e. "H ")
R H
N HHR'
Great reaction!!
e.g.
H
O
NaBH3CN
CH3OH
NH
CH3H2NCH3
O
NaBH3CN
CH3OH
H3N
NH2
O
HNH
CH3H3C
NaBH3CN
CH3OH
N
H
H3C CH3
CH3
CH3
Ch. 20 - 14
4D. Preparation of Primary Amines through the Hofmann and Curtius Rearrangements
O
R NH2
Br2, NaOH
H2OR NH2
+ NaBr + Na2CO3
Hofmann rearrangement
Ch. 20 - 15
(1) NH2
O
Br2
NaOH
NH2
Examples
(2)
NH2
O
NH2Br2
NaOH
Ch. 20 - 16
Mechanism
O
R N
H
HOH O
R N
H
Br Br O
R N
H
Br
HO
O
R NBr
O C NR (Hofmann
rearr.)(isocyanate)
HOO C
N
OH
R
O C
N
O
R
H
+ CO2H
NR
H OHR NH2
Ch. 20 - 17
Curtius rearrangement
O
R Cl
NaN3O
R N N NO C N
R+ N2 (g)
heat
R NH2
H2O
CO2 (g) +
O
Cl 1. NaN3
2. heat3. H2O
NH2
e.g.