Leah here from leah4sci.com and in this video
we're going to look at a quick overview of
the carboxylic acid derivatives and the reactions
to convert between them.
This video follows along with the carboxylic
acid cheat sheet which you can find on my
website linked below or visiting leah4sci.com/carboxylic-acid.
A carboxylic acid is a molecule that has a
carbon chain with a functional group featuring
a carbon double bound to an oxygen single
bound to another oxygen with a hydrogen.
This portion is a carbonyl, this portion is
hydroxy but it's not an alcohol because together
they form one functional group called the
carboxylic acid if we remove that OH and replace
it with different groups, we get a derivative
of carboxylic acid because we're deriving
it from the carboxylic acid molecule and this
leads to a whole new set of reactions that
you can use in synthesis.Some professors will
refer to the derivatives as the carboxylic
acid parent with either a Y or a Z here with
that Y or Z represents the new group which
gives you the specific type of derivative.
Let's look at some common derivatives from
most to least reactive.
If i replace the OH with a Halogen for example
Chlorine, that will give me an acid halide
as a general class or an acid chloride for
the specific molecule.
This is also called an Acyl Chloride or an
Acyl Halide.
If I replace the OH with what looks like another
carboxylic acid without the hydrogen so we'll
just have this portion here giving us an oxygen,
a carbon double bound to an Oxygen and then
a second R-group.
This is called and Acid anhydride or simply
anhydride.
If you think about it, if we split the molecule
in half and add in a water OH and another
H for H2O, that would give me 2 carboxylic
acids to we have the acid without water and
hydride without water, that's how we get the
acid anhydride derivative.
If we replace the OH with an OR group and
it's not just the H that we're replacing with
an R, the entire group got swapped for a brand
new oxygen and R-group, then I get what's
called an Ester.
And if I replace the OH with a Nitrogen for
example NH2 or we can have NHR or NR2, these
are just different substitute in Nitrogen.
We get what's called an Amide or amide.
Let's face it, your professor is not just
taking to the common derivatives, you might
also see some of these less common molecules.
As a reminder, a carboxylic acid starts out
with a carbon double bound to an oxygen.
So if we replace the Y, we get a derivative.
But recognize that what we have here is a
carbon bound 1,2,3 times.
So if we have carbon bound three times to
something else, that would still qualify as
a carboxylic acid derivative for example,
if I remove that oxygen, and instead have
3 bonds to a Nitrogen, that gives me the Nitrile
derivative.
And finally Cyclic Derivatives which are just
cyclic versions of their linear counterparts
but for some reason seeing that ring scare
students.
Don't let this scare you.
If I have a ring with a carbonyl, bound to
an oxygen and then a ring happens to close
in on itself.
Doesn't this look like an Ester where we have
an R-group here, and here, as two separate
chains?
This gives us a cyclic ester which is also
called a lactone.
If I have the same structure with a Nitrogen
instead of an Oxygen alongwith the Hydrogen
because Nitrogen needs 3 bonds where oxygen
needs 2.
You should recognize this as a cyclic amide.
If we take off the bottom, this is simply
carbon chain number 1 for the carboxylic acid
and this would be our second carbon chain
for a substituted amide but the two chains
happen to be connected.
The cyclic amide is also called a lactam,
and this is where students get confused.
The way I remember the difference is the lactone
has the extra O for the cyclic ester, and
the lactam is the cyclic amide which tells
me it has a nitrogen.
You may also come across something that look
like this.
It's a cyclic structure with the oxygen in
the middle but another carbonyl.
You should recognize this as a sideways acid
anhydride.
And in fact, it's just a cyclic anhydride.
And if I take that same cyclic anhydride but
replace the oxygen with a nitrogen, I don't
get a cyclic amide because the linear version
would be called an Imide . Remember an imide
is when you have a carbonyl on either side
of a nitrogen so this would simply be a cyclic
Imide.
When looking at reactions of carboxylic acid
derivatives, it's important to remember that
the acid halide is most reactive then the
acid anhydride then the the ester and least
reactive is the amide.
As a reminder all of these are listed out
on the carboxylic acid derivative cheat sheet
which is linked below.
When you hear most reactive, recognize that
it's going to react the fastest, has the best
leaving group, and therefore is least stable
as is, but most stable when the leaving group
departs.
The amide being the least reactive tells us
that it reacts slower.
It has a bad leaving group and therefore is
least stable when you kick it out.
This is important to recognize because it's
very easy to make a less reactive derivative
from a more reactive derivative but it's going
to take more extreme condition to go from
something less reactive to something more
reactive because it wants to go in that direction.
This video is just an overview of the reactions
so let's see how you go from one to the next.
In doing so, we can forget the carboxylic
acid because as a derivative we also need
to know how to go from a carboxy to any of
the derivatives.
A carboxylic acid will form an acid halide
when reacted with something like SOCl2 which
makes the OH a good leaving group and brings
us a source of chlorine.
To go from a carboxylic acid to an acid anhydride,
you need to detour.
First, you make your acid halide which is
very reactive, then you simply react the acid
halide with a carboxylate or a negative deprotonated
carboxylic acid which will kick out the chlorine
and give us the acid anhydride.
The carboxylic acid is very close to the reactivity
of an ester.
That means it's very easy to go back and forth
between the two depending on the reaction
conditions.
For example, putting this in an acid catalyst,
the more of that derivative component that
you have in solution, the more of the reaction
favors that direction.
To go from an ester to a carboxylic acid we
just need a whole lot of water which is the
conjugate acid of the OH group.
So we'll show H3O+ or water and an acid catalyst.
To go from the carboxylic acid to ester, we
just need a lot of OR so we put an alcohol
solution with an acid catalyst.
To go from the carboxylic acid to the amide,
we react this in ammonia, but it doesn't stop
there.
Another way to make any of the derivatives
especially if you're stuck on an exam synthesis
question and you don't remember the exact
conditions, best way to do it, go from the
carboxylic acid to the acid halide.
Make sure you know the SOCl2 and then just
take that red portion, the derivative portion,
react it with the acid halide and you're good
to go.
We've already shown an acid halide to an acid
anhydride using a carboxylate which is the
red portion of the anhydride.
If I react the acid halide with an alcohol
which gives us the OR portion, I'll get an
ester, and if I react the acid halide with
ammonia or an amine, I will get an amide.
Ammonia would give us just the NH2 amide but
an amine will give us a substituted amide
which would be NRH or NR2.
But it doesn't stop there.
Anytime you want to make something more reactive,
the less reactive group will get you there.
This means the anhydride will react with something
like ammonia to give me the amide and so will
the ester.
Finally the last thing you should look at
is how to go back to the carboxylic acid from
the derivative.
The acid halide is so reactive it reacts with
water to give you a carboxylic acid and so
does the N hydride.
We've already shown that the ester will form
a carboxylic acid using a water and an acid
catalyst.
And finally, the amide is a little tricky.
The NH2 is a bad leaving group, but if we
react it in an acid catalyst now it's not
NH2, it's a protonated better leaving group
and once again that'll bring us back to the
carboxylic acid.
For a complete review of everything we discussed,
make sure you study the carboxylic acid cheat
sheet linked below or visit my website leah4sci.com/carboxylic-acid.
