Right. Preparation of amines.
Nucleophilic substitution on alkyl halides
by ammonia looks relatively straightforward
at the end of the day. We have an alkyl halide
which, from earlier on in this particular
module, you should have been familiar with.
And this is where we have a chloro, bromo,
or iodo group attached to an alkane, again,
creating this dipole. You should also have
been aware, when we were talking about nucleophilicity,
that ammonia and nitrogen-based amines are
also very nucleophilic anyway, so they’re
more likely or able to displace a chloride,
bromide or iodide.
And this is the reaction that we see in the
presence of ammonia. We have one equivalent
of an alkyl halide or halogenic alkane reacts
with the ammonia and we get a primary amine.
Another equivalent and we get a secondary
amine. And then a third equivalent and here
we have a tertiary amine. Primary, secondary
Now, the highest yields are given by those
substrates which favour an SN2 type of attack.
Bear in mind, what we’re looking at here
is an SN2 reaction on a haloalkane. And so,
therefore, the order of reactivity, in this
case, is primary haloalkane reacts faster
than secondary reacts faster than tertiary.
This is because of the nucleophilicity of
the nitrogen in the NH3 and NH2 groups.
There is, however, a problem with this. This
is a rather facile way of looking at it because
the reality is, when you actually get to the
primary and secondary amines, secondary in
particular, this actually becomes more nucleophilic
than the starting ammonia. So, the results
of this is that the reaction can give a mixture
of different amines as the alkylated amines
obtained as a product are stronger nucleophiles
than the starting ones and can give a second
nucleophilic substitution on the haloalkane
or alkyl chloride.
However, a way around this potentially is
either via operating with a large excess of
ammonia or occasionally as it’s something
that’s done actually protecting one of those
hydrogens as an amide in order that there
is only one hydrogen available for substitution.
But, that’s beyond the terms of reference
The chemical behaviour of the amines is due
to the tendency of nitrogen to share its lone
pair of electrons. So, what that means is
we’ll be able to look at the basicity of
amines because this is what happens when electrons
from the lone pair attack a H+. The reactivity
of the amines as nucleophiles in substitution
reactions… And here we go. So, here we have
an idealised amine. We have an alkyl group
(shown here as “R”), it could be alkyl or
aryl, it doesn’t really matter and in the
presence of an acid, such as hydrochloric
acid (shown here as “HCl”), the electron pair
from the nitrogen can be donated onto the
H+. This gives you an ammonium chloride salt.
Now, the free amine, apart from those shortchanged
ones which we talked about a little earlier,
are insoluble in water. However, if you make
the ammonium chloride, it does become soluble
in water and the reason for this is hopefully
you can appreciate is now we have a formal
ionic compound. We have the organic part,
which has been converted into something which
bears a positive charge and we have the counter-ion,
which is Cl-. This facilitates ion hydrogen
bond interactions with water, which is what
makes it soluble.
Now, of course, depending on the basicity
of the amine is going to influence how readily
it is protonated, as we’ll see. Different
types of amines have different degrees of
basicity, depending on their degree of substitution.
So, to recap, the R-NH3+ ion is known as the
ammonium ion and it’s produced when an amine
is present… in the presence… sorry, is
made in the presence of an acid.
So, let’s have a look at the alkylation
of amines again, shall we? So, if we take
our idealised amine, which is shown here as
RNH2 and we have our, again, model haloalkane,
R’X, in the first instance, what happens
is the nitrogen lone pair attacks and displaces
the halogen from our haloalkane and this actually
can result in the formation… well, it does
result in the formation of HX.
There is a problem inherent to this is that
HX, which is itself an acid in this particular
scenario, if X was chlorine, it would be hydrochloric
acid, can go on to protonate our newly substituted
and therefore, more basic secondary amine.
This in itself can prevent further substitution
since it removes the nucleophilicity of the
nitrogen by converting it into a positively
charged species. So, this reaction can be
used to produce amines having different alkyl
groups on the nitrogen.
Right. Now, we also talked, in the previous
lecture set, about the acylation of amines,
specifically, their reaction with things like
acid chlorides and acid anhydrides in order
to produce amides. So, here, again, is an
example of this. We have our idealised alkyl
or aryl amine and we have, again, our model
acid chloride shown here, with the alkyl group
correlating to R’.
The reaction is nucleophilic addition elimination,
which is exactly the same reaction mechanism
as we saw in the previous lecture. So, this
is the synthesis of an amide via nucleophilic
substitution on a carboxylic acid derivative.
And in fairness, this is one of the easiest
ways to make an amide.