Now, what I’d like you to do is have a look
at the following reactions, for the synthesis
of amides. If you recall, I said right at
the very beginning of this particular lecture
set, was that you can’t react a carboxylic
acid directly with an amine; it’s very difficult
to do, not impossible, but very difficult.
And so, the reaction A, shown above, is something
that under normal laboratory conditions would
not take place.
If we look at the third example, this is where
we are converting an amide into an ester,
and I bring you back to a slide which was
only three slides ago, it is very difficult
without a particular activation from a biological
component to convert an amide back into an
ester. And so, this reaction is also not possible
under standard reaction conditions.
However, B, this is possible. We have already
said that an acid chloride can react with
an alcohol to generate an ester and this is
because the leaving group is a good one and
also an alcohol is a good enough nucleophile
to achieve this. In both of the other cases,
either the leaving group isn’t good enough
or the nucleophile itself isn’t strong enough.
Based on your newfound understanding of how
substitution on a carboxylic acid can influence
acidity, the strength of an acid, what I would
like you to now do is to look at the following
structures numbered 1, 2, 3, 4 and 5 and put
them in correct order of decreasing strength
Now, as you can see here, the numbers in green
show the order in terms of strength of acidity
4, 2, 3, 5 and 1. So, in other words, this
is telling us that the strongest acid is the
difluoroacetic acid or ethanoic acid and this
makes a lot of sense because we have two highly
electronegative atoms attached in the alpha
position or the 2 position on our ethanoic
acid. So, this serves to stablise the carboxylate
anion more than, indeed, any other type that
we see here in front of us.
The second one is the monofluoro, bearing
in mind, of course, a fluorine is more electronegative
than either a bromine or a chlorine. Again,
it is still in the alpha position followed
by 3, which is the next alpha or 2 position
substituted acetic or ethanoic acid, where
we have a bromine. Bromine is also more electronegative
than carbon, pulling electron density away,
although not nearly as well as a fluorine.
This serves to stablise the carboxylate and
therefore, makes this relatively acidic.
In the case of 5, we have acetic or ethanoic
acids and of course, this, therefore, having
no substituents on it, is not going to be
the most acidic and it falls in position 5.
And finally, if we look at compound 1, we
can see that it’s a propanoic acid therefore,
because we have three carbons in a row: 1,
2 and 3. And you could look at it in that
way, but you could also look at it as an ethanoic
acid which is substituted by a methyl group
in its 2 position.
As we have said before, in the case of halogens,
they are electronegative, they pull electron
density away, stabilising a carboxylate. In
the case of our methyl group though, it is
a positive inductive effect, donating electrons,
which in the case of generating a carboxylate
from the dissociation in this acid, would
destabilise the resulting conjugate base.
Therefore, propanoic acid, because of this
electron donation, is the weakest acid out…