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SN2 Reactions of Amines
H
Me2NH
Br
N
- Br-
Me2NH
Me
Me Br
NH2
NMe2
CH3I
CH3I
N
Me +
Me2NH2
Br
Me
NHMe
CH3I
NMe3 I
exhaustive methylation
Because of this problem, alkyl halides react with amine
surrogates to make amines.
cyanide, azide, nitro, phthalimide
Reductive Amination
O
NH3 , H2-Ni
NH2
Form imine in situ, which is
then reduced with hydrogen
gas to give the amine
N-H
Me2NH
Pd-C , H2
O
CHO
NMe2
N
CH3CH2NHMe
NaBH3CN
MeOH
sodium cyanoborohydride
PhCHO
NH2
reverse the order
NaBH3CN
MeOH
Ph
NH
Hofmann Rearrangement
Ignore Curtius rearrangement
Hofmann rearrangement
C
O
Br2 , NaOH
NH2
N
H2O
H2O
N
NH–
H
C
OH
H
N
H
Br-Br
H
H
O
O
C
N
– CO2
H
HO–
C
O
C
O
C
OH2
H2O
NH-Br
–OH
O
August Wilhelm von Hoffmann (1818-1892)
C
O
N-Br
N
H
C
O
Reactions of Amines
Alkylation: problem of exhaustive methylation.
Acylation:
CH3CH2NH2
Cl
NHEt
O
Hofmann elimination:
Hb
Ha
Br
NMe3
O
Quaternary ammonium salt
Hb
Ha
NMe3+ Br–
Ag2O
H2O
Hb
Ha
NMe3+ OH–
heat
Hb
– Ha
In water or alcohol - E2, but steric hindrance leads to removal
of Ha in preference to Hb
NMe +
NMe +
3
H
Hb
H
Ha
3
H
–OH
HO– Hb
H
CH2Ha
Syn Elimination
If the ammonium salt is heated without solvent
the base (hydroxide) is tethered to the leaving group
so the !-H is removed in a syn conformation
NMe3 OH
Ha
H
Me2HC
•
H
H
Hb OH
NMe3
H
Me
•
Form C=C to less
substituted carbon
Me
Me
OH
Me3N
- HOHa
Ha
- NMe3
H
Me2N
MeI
Me3N I
H
Me3N OH
AgO
H2O
Ha
Hb
200°C
- Me3N , - HaOH
Hb
Electrophilic Aromatic Substitution
NH2
H2N
FeBr3
Br2 , FeBr3
The amine N is a Lewis base and reacts with the Lewis acid
However,
aniline is so activated that it reacts with bromine without a catalyst
NH2
NH2
Br2 , H2O
Br
Br
Br
Modulate reactivity by converting amine to amide
Acetanilide
O
O
NH2
HN
Ac2O
CH3
Br2
HN
CH3
= ortho
FeBr3
Br
Diazonium Salts
NH2
N!N HSO4
HNO2
H2SO4
aryl diazonium hydrogen sulfate
HNO2 + H2SO4
HONO
nitrous acid
N!N HSO4
X
X = nucleophile
X
+ H2O + HSO4
Sandmeyer Reaction
I
Br
CN
CuBr
HBr
NH2
HNO2
H2SO4
NaI
KCN
CuCN
OH
N!N HSO4
Cu2O , H2O , Cu(NO3)2
H3PO2
or NaBH4
Traugott Sandmeyer (1854-1922)
Diazonium Coupling
N!N HSO4
OH
N
N
OH
p-hydroxyazobenzene
(orange)
N!N HSO4
NMe2
N
N
Azo dyes
NMe2
p-(dimethylamino)azobenzene
(yellow)
The proper chemical name for Red40 is:
6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid
Other Azo Dyes
Congo Red
sodium salt of benzidinediazo-bis-1-naphtylamine-4-sulfonic acid.
Methyl Orange
sodium p-dimethylaminoazobenzenesulfonate
Finis
Read 24.9
Spectroscopy:
IR: NH 3300-3500 cm–1 (3° amines, no NH)
1° amines (2 peaks)
2° amines (1 peak)
NMR:
N-H between 1-5 ppm - exchanges with D2O
CH-N
2.2 - 2.6 ppm
Mass Spec:
odd number of N, odd mass