Upload
trinhhanh
View
259
Download
2
Embed Size (px)
Citation preview
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
THANK YOU