Chemistry Reference
In-Depth Information
The stabilizing effect of alkyl groups appears to
involve overlap of
become more important than the stabilizing effects
of alkyl groups. This is exemplified by the heat-
initiated decomposition of the quaternary ammonium
salt below. The elimination is now governed by
which is the more favourable conformer of the
substrate where a hydrogen atom is positioned
anti
to the quaternary ammonium substituent. Two such
possibilities can be considered. It is apparent that
the conformer set up for 1,2-elimination is more
favourable than the conformer for 2,3-elimination,
since the latter conformer would necessitate a less
favourable
gauche
interaction (see Section 3.3.1). An
alternative conformer for 2,3-elimination has two
unfavourable
gauche
interactions. Thus, it is the
large leaving group that now dictates the direction of
elimination, and the less-substituted alkene (Hofmann
product) predominates. Again, it should be noted that
both products are actually obtained - the effect is not
sufficiently great to produce one product exclusively.
π
system of the alkene, rather as we have seen with car-
bocations (see Section 6.2.1). The more alkyl groups
attached, the more stabilization the alkene derives.
σ
C-H (or C-C) orbitals with the
overlap from
σ
bond
with
π
system
H
H
H
H
H
H
This effect is relatively small and both products are
formed, usually with one predominating. The more-
substituted Saytzeff product typically predominates
when the leaving group is small, e.g. halide. On
the other hand, when there is a large leaving group
present, e.g. quaternary ammonium, then steric effects
H
H
more-substituted alkene
N
,
N
,
N
-trimethyl-
2-butylammonium
hydroxide
heat
1
2
(5%)
3
NMe
3
HO
counter-ion acts
as base
less-substituted alkene
(95%)
H
H
H
Me
Et
H
H
Me
H
and
H
Me
H
Me
H
looking along
C-1,2 bond
looking along
C-3,2 bond
H
NMe
3
NMe
3
NMe
3
less favourable conformer;
gauche interaction
this conformer with two
gauche interactions is even
less favourable
we are showing only one configuration at
C-2; the conformational consequences
are the same in the enantiomer
Note that with some cyclic substrates, the leaving
group may remain as part of the product alkene.
Elimination reactions played an important role in
early structural analysis of alkaloids (typically cyclic
amines). Combination of
N
-methylation followed
by elimination may be used to open up nitrogen
heterocycles, as shown with piperidine.
successive nucleophilic attacks of
amine onto methyl iodide generate
quaternary ammonium salt
repeat methylation and
elimination sequence
base-initiated
elimination
HO
H
− H
+
H
+
HO
−
Me
I
−
E
2
MeI
Me
I
heat
N
N
N
NMe
2
I
Me
I
Me
Me
H
Me
I
Me
piperidine
