Transcript The von Richter Reaction: A Case History

The von Richter Reaction:
A Case History
In 1871, von Richt er report ed the following observations:
NO 2
Z
NO 2
KCN
COOH + KNO 2
EtO H/H2 O
reflux
KCN
EtO H/H2 O
reflux
COOH + "acidic t ars" + KNO 2
Z
5%-50% yields
Based on t he above:
1. Direct displacement of t he nit ro group is eliminated from considerat ion.
2. A benzyne interm ediat e is ruled out . In t he case of para-subst it uted nit robenzenes,
benzyne intermediates would give bot h m et a- and para-subst it uted benzoic acids.
von Richter Reaction:
Bunnett Mechanism (1954)
In 1954, Bunnett et al. proposed the following mechanism to account for the known
facts pertaining to the von Richter reaction:
H
NO 2 + CN-
Z
Z
NO 2
H
H OH
H
Z
CN
CN
NO 2 + CNH
CN
H
H2 O
reflux
Z
H + NO 2
Z
O
Z
CN
O
C NH 2
H
H2 O
reflux
Z
C OH
H + NH 3
von Richter Reaction:
Bunnett Observations (1956)
Observat ion I:
COOH
NO 2
KCN
EtO H/H2 O
reflux
CN
COOH
KCN
not obt ained
EtO H/H2 O
reflux
(a pr esumed interm edia te)
Observat ion II:
NO 2
COOH
KCN
EtO H/H2 O
reflux
Cl
Cl
O
CN
EtO H/H2 O
reflux
Cl
Quest ion:
C
KCN
Cl
NH 2
incomplet e hydrolysis
t o acid product under
identical reaction
conditions
What can one conclude from the above observations?
von Richter Reaction:
Revised Bunnett Mechanism
-
O
-
O
+
N
O
+
O
-
-
O
+
N
N
O
C N H
C N H OH
H
+ CN-
H
CN
-
O
+
N
-
O
C O
-
O
N
-
O
O
N
C O
hydrolysis
-
O
C N H
( NH 3 )
H OH
O
+
N
H
O
C O
-
H
O
C
N O
O
an acyl nitrite
hydrolysis
COOH
+ NO 2
-
Rosenblum Observations (1960)
Observation I:
Instead of nitrite, molecular nitrogen was a by-product of the von Richter
reaction. Apparently, in the 1871 von Richter paper, nitrite had never
been demonstrated to be a by-product. It had been deduced based on
stoichiometry considerations.
Point of Interest:
In the revised Bunnett mechanism, ammonia and nitrite are
stipulated by-products of the von Richter reaction. Am monia
and nitrite can react to form amm onium nitrite which, upon
heating, decomposes to give m olecular nitrogen and water.
15
However:
Upon addition of NH3 to an on-going von Richter reaction,
the only molecular nitrogen obtained contained no nitrogen-15!
15
If the revised Bunnett mechanism were correct, the added NH3
and the expelled NO 2 (from the last step)should have produced
15
N
14
N.
Observation II:
COOH
15
Cl
Conclusion:
NO 2
KCN
EtO H/H2 O
reflux
Cl
+
15
N
14
N
One nitrogen atom must come from the nitro group, and the
second must com e from the cyano group intr am olecular ly
!
Accepted Mechanism for the von Richter Reaction
-
O
-
O
+
N
O
+
O
-
-
O
N
N
+ CN
N
C
N
OH
C O
O H
N
N2 +
H2 O
C NH
CN-
NH
C O
CNCOOH
O
O
H2 O
H2 O
O
N
H
HO
N
-
O
C NH
C N H OH
H
-
N
+
COOH
N
HO H
O
C NH
Supporting Evidence for the
Rosenblum Mechanism
Ullman & Bartkus (1962):
NH
N
NH
C
Pb(OA c)4
O
N
C
KCN
EtO H/H2 O
reflux
+
N2
COOH
O
hydrazide
diazene
Ibne-Rasa & Koubek (1963):
NH 2
RCO3 H
N
O
C NH 2
C NH 2
O
O
o-nitrosobenzamide
KCN
EtO H/H2 O
reflux
+
COOH
N2