Chemistry Reference
In-Depth Information
+ H
2
18
O
−
H
2
O
H
3
C
exchange labelling
demonstrates
intermediacy of hydrate
H
3
C
18
OH
H
3
C
18
O
H
2
18
O
O
H
3
C
OH
H
3
C
H
3
C
7.4 Sulfur as a nucleophile:
hemithioacetals, hemithioketals,
thioacetals and thioketals
As a consequence, thiols are preferred to alcohols
for the protection of aldehyde and ketone groups in
synthetic procedures. Thioacetals and thioketals are
R
R
OH
R
′
SH
R
′
SH
R
SR
′
The reaction of thiols with aldehydes and ketones
parallels that of alcohols. However, the reactions are
more favourable because sulfur is a better nucleophile
than oxygen (see Section 6.1.2). Electrons in larger
atoms are more easily polarizable and it becomes
easier for them to be donated to an electrophile.
O
H
SR
′
H
SR
′
H
+
H
+
H
thioacetal
hemithioacetal
excellent protecting groups. They are more readily
formed, and are more stable to hydrolytic conditions
than acetals and ketals.
S
HS
H
+
+
O
+
H
2
O
S
HS
propan-1,3-dithiol
cyclic thioketal
cyclohexanone
7.5 Hydride as a nucleophile:
reduction of aldehydes and
ketones, lithium aluminium
hydride and sodium borohydride
The carbonyl group of aldehydes and ketones may
be reduced to an alcohol group by a nucleophilic
addition reaction that appears to involve hydride as
the nucleophile. The reduction of the carbonyl group
may be interpreted as nucleophilic attack of hydride
onto the carbonyl carbon, followed by abstraction of
a proton from solvent, usually water.
This is not strictly correct, in that hydride, from
say sodium hydride, never acts as a nucleophile, but
because of its small size and high charge density
it always acts as a base. Nevertheless, there are a
number of
complex metal hydrides
such as
lithium
aluminium hydride
(LiAlH
4
; LAH) and
sodium
borohydride
(NaBH
4
) that deliver hydride in such
a manner that it appears to act as a nucleophile. We
have already met these reagents under nucleophilic
substitution reactions (see Section 6.3.5). Hydride is
also a very poor leaving group, so hydride reduction
reactions are also irreversible (see Section 7.1.2).
abstraction of
proton from water
nucleophilic addition of
hydride on to carbonyl
HOH
this is an
oversimplification
of the process
O
O
OH
H
H
H
alcohol
Whilst the complex metal hydride is conveniently
regarded as a source of hydride, it never actually
produces hydride as a nucleophile, and it is the
aluminium
transfer of the hydride. Then, the resultant negatively
charged intermediate complexes with the residual
Lewis acid AlH
3
.
hydride
anion
that
is
responsible
for
