Chemistry Reference
In-Depth Information
Acetyl chloride must always be stored under
anhydrous conditions, because it readily reacts with
moisture and becomes hydrolysed to acetic acid.
On the other hand, if one wanted to convert ethyl
chloride into ethanol, this nucleophilic substitution
reaction would require hydroxide, with its negative
charge a better nucleophile than water, and an
elevated temperature (see Section 6.3.2). It is clear,
therefore, that the carbonyl group is responsible
for the increased reactivity, and we must implicate
this in our mechanisms. Although it is easier to
draw a mechanism as an S
N
2 style substitution
reaction, this is lazy and wrong, and the two-
stage addition - elimination should always be shown.
There is ample experimental evidence to show that
a tetrahedral addition intermediate does participate
in these reactions. The S
N
1 style mechanism is
also incorrect, in that few reactions, and certainly
none that we shall consider, actually follow this
pathway.
O
O
O
correct
addition-elimination
L
L
L
Nu
Nu
Nu
O
O
incorrect S
N
2 style
L
L
Nu
Nu
O
O
O
Nu
incorrect S
N
1 style
L
Nu
L
O
O
shorthand style
sometimes encountered
L
L
Nu
Nu
A shorthand addition - elimination mechanism some-
times encountered is also shown. This employs a
double-headed curly arrow to indicate the flow of
electrons to and from the carbonyl oxygen; we pre-
fer and shall use the longer two-step mechanism to
emphasize the addition intermediate.
The reaction may also be considered as acylation
of the nucleophile, since an acyl group RCO- is
effectively added to the nucleophile; this description,
however, conceals the fact that the electron-rich
nucleophile is actually the attacking species in the
reaction.
Since this reaction, an overall substitution, depends
upon the presence of a suitable
leaving group
in the substrate, it is not surprising to find that
the level of reactivity depends very much upon
the nature of the leaving group. We have already
seen that weak bases, the conjugate bases of strong
acids, make good leaving groups (see Section 6.1.4).
Conversely, strong bases, the conjugate bases of weak
acids, are poor leaving groups. We can now see
why aldehydes and ketones react with nucleophiles
to give addition products. This is because the
tetrahedral anionic intermediate has no satisfactory
leaving group apart from the original nucleophile.
The alternative possibilities, hydride in the case of
aldehydes or an alkyl carbanion in the case of
ketones, are both very poor leaving groups; both
are the conjugate bases of very weak acids, namely
molecular hydrogen (p
K
a
35) or an alkane (p
K
a
50)
respectively. Therefore, in the forward reaction,
the alkoxide intermediate instead reacts with an
electrophile, usually by abstraction of a proton from
solvent, and the overall reaction is addition.
aldehydes / ketones
leaving group
p
K
a
conjugate acid
H
(conjugate base of H
2
)
35
O
O
(conjugate base of R-H)
R
50
R
H
R
R
Nu
Nu
are poor leaving groups
therefore, alkoxide picks up a proton, get
addition
