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CHAPTER 13
Hofmann Rearrangement
BY,
G.DEEPA
The Hofmann Rearrangement
Treatment of amides with bromine in basic solutiongives an amine with loss of the carbonyl carbon.
RCNH2
OBr2
HO–RNH2 + CO3
2–
Examples
(94%)
(CH3)3CCH2CNH2
OBr2, NaOH
H2O(CH3)3CCH2NH2
Br
CNH2
OBr2, KOH
H2O
Br
NH2
(87%)
Mechanism of the Hofmann Rearrangement
•The Hofmann rearrangement involves 6 steps in 3 stages.• 1. formation of an N‐bromo amide (2 steps)• 2. conversion of the N‐bromo amide to an
isocyanate (2 steps)• 3. hydrolysis of the isocyanate (2 steps)
RCNH2
O
RCNHBr
O
RNCO RNH2
Step 1
O•• ••
– ••H
••
RC
O
N
••
•• H
H
Step 1
O•• ••
– ••H
H
O••••
H
••
RC
O
N
••
•• H
H
RC
O
N
••
••
–
H
••••
Step 2
••••
••Br Br•• ••
••
RC
O
N
••
••
–
H
••••
Step 2
••••
••
••
RC
O
N
••
•• Br
H••••
••Br Br•• ••
••Br•••• ••••
–
RC
O
N
••
••
–
H
••••
Step 3
••
RC
O
N
••
•• ••••
••Br
H
O•• ••
– ••H
Step 3
••
RC
O
N
••
•• ••••
••Br
H
O•• ••
– ••H
••
H
O•• H
C
O
N
••
••
–••••
••••
••Br
R
Step 4
••
C
O
N
••
••R
Br•••• ••••
–
C
O
N
••–
••
••
••••
••Br
R
••
Steps 5 and 6
••
C
O
N
••
••R
H2O
HO–
••
C
O
N
••
••R
O
H
••••••
–
+ CO32–NH2R
••
Mechanism of Diazonium salt formation
H O N O + H +
H 2 O
+
nitrosoniumion
R NH 2
N O++
R NH
H
N O+
N-nitrosoammoniumion
R NH
H
N O+
+ H 2 O R N
H
N O + H 3 O +
N-nitrosamine
R N
H
N Otautomerization
R N N OH
a diazenol
R N N OH + H + R N N OH
H
R N N OH
HR N N + H 2 O
+
a diazoniumion
N OOH
H
+
N OOH
H
+
+
+
N O+
Basicity of amines
The greater the availability of the lone pair electrons on nitrogen, the greater the base.
Kb = [RNH3+] [OH-] / RNH2
In the old days, pKb was a measure of base strength.
pKb = - log Kb
The stronger the base the lower the pKb
EFFECTS ON AMINE BASICITY
1. INDUCTIVE EFFECT - ALKYL SUBSTITUTION
METHYL GROUP INCREASES ELECTRON DENSITY ON N
3.36 3.28 2 METHYLS ARE BETTER THAN ONE
WATCH OUT THREE METHYL GROUPS DECREASES BASICITY pKb = 4.26 - Steric inhibition of solvation of HOH with the NH+ of the R3NH+ cation.
The greater the availability of the lone pair electrons on nitrogen, the greater the base.
Kb = [RNH3+] [OH-] / RNH2
In the old days, pKb was a measure of base strength.
pKb = - log Kb
The stronger the base the lower the pKb
EFFECTS ON AMINE BASICITY
1. INDUCTIVE EFFECT - ALKYL SUBSTITUTION
METHYL GROUP INCREASES ELECTRON DENSITY ON N
3.36 3.28 2 METHYLS ARE BETTER THAN ONE
WATCH OUT THREE METHYL GROUPS DECREASES BASICITY pKb = 4.26 - Steric inhibition of solvation of HOH with the NH+ of the R3NH+ cation.
Reimer‐Tiemann Reaction Mechanism
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