Acetals as protecting groups and thioacetals | Organic chemistry | Khan Academy

Acetals as protecting groups and thioacetals | Organic chemistry | Khan Academy


Voiceover: We’ve already
seen how to form acetals. If we start with an
aldehyde or a ketone, and we add an excess of alcohol in an acidic environment we can form our acetal. We talked about ways to
increase the formation of your acetal by removing,
in this case, water from your reaction to drive
the equilibrium to the right. But let’s say you increase
the concentration of water, so let’s say you increase
the concentration of this. You would push the equilibrium
to the left, and you would hydrolyze your acetal
and convert it back into your original aldehyde or
ketone and your alcohol. So this can actually be a useful reaction if you want to use an acetal
as a protecting group. And so let’s look at an example
of hydrolyzing an acetal. So, if we have this
acetal over here on the left, which is the same
one that we made in the previous video, let’s
see how to analyze the products that we would
make by hydrolizing it. So we add HCl as our acid catalyst, and we add an excess of water. And so we’re going to get back our original aldehyde and alcohol here. So let’s analyze the structure of this. So this carbon right
here is the important one so let me go ahead and change color here. So this carbon right here
in magenta, if we go back up to here that’s this carbon
we’re talking about here. And so we know that we
have a carbon attached to that so that would be
this R group right here. And then we also have a
hydrogen coming off of that carbon, so that would
be this hydrogen right here. And so immediately we
can work backwards and see we have an R group we have a hydrogen, we’re dealing with an aldehyde right here. Specifically a two-carbon aldehyde, right? So there’s two carbons on this, so acetaldehyde is one of our products. So let’s go ahead and draw acetaldehyde here, a two-carbon aldehyde. And then our other product, we know is going to be an alcohol. So if we analyze the structure
of our acetal, we should be able to figure out what
kind of alcohol it is. So if we look at that,
that’s like this portion right here, which we know
came from our alcohol. So all we have to do is
add on a hydrogen and then we have the structure of
our alcohol product here. So it would be a four-carbon
alcohol, so one, two, three, and four, and the
exact same thing down here. So our other product would be butanol. And we have two equivalents of it. So that’d be one, two,
three, four carbons. So, by looking at our
acetal and thinking about hydrolyzing it and thinking
about where those portions came from, we can easily come up with the products of this
hydrolysis of this acetal. So let’s see how we
could use this reaction in, if we were trying to synthesize this molecule over here on the right. And so, if we’re trying to synthesize this molecule from this
molecule, first you might be able to think you
could figure it out by looking at the functional groups. Alright, so we have a
ketone over here on the left and we want a ketone over
here for our product. We also have a carboxylic
acid over here to the left, and then we have an alcohol
over here on the right. So, if you’re thinking
about how to complete this kind of transformation,
you might think to reduce the carboxylic
acid to form your alcohol. And so, you could do that with something like lithium aluminum hydride. So you might think, and
you could just add some lithium aluminum hydride
here, in the first step. And the second step,
add a source of protons to protonate your alkoxide anion to form your alcohol as your product. The only problem with trying
to do this in one step is lithium aluminum hydride
is also going to reduce your ketone here, to
form a secondary alcohol. And so, this will not work. The first thing you have to
do is protect the ketone, and then you can use your
lithium aluminum hydride. So, we’re going to use,
we’re going to protect our ketone using an acetal, of course. And we’re going to react
it with ethylene glycol. So if we react our
starting compound here with ethylene glycol, and we use an acid catalyst, we’re going to form an acetal. Alright, so the ethylene
glycol is going to react with the ketone
portion of the molecule to form an acetal,
specifically a cyclic acetal. Alright, so over here on the left we still have our carboxylic acid. And over here on the right,
now we’re going to have an oxygen bonded to this
carbon, another oxygen bonded to this carbon, and they
are, of course, connected. And so, that’s our cyclic
acetal, which came from this oxygen, this carbon,
this carbon, and this oxygen. Right, so that’s this oxygen, this carbon, this carbon, and this oxygen. So acetals are stable in basic conditions. And so, now we can add
our lithium aluminum hydride, so we add our lithium aluminum hydride here in the first step. And that is going to
reduce our carboxylic acid. And so in the second
step we can add a source of protons, and we can
add some excess water. And so we can protonate the alkoxide anions to form our alcohol product. And also we can add an
excess of water in an acidic environment it’s going
to hydrolize our acetal. So we’re also going to hydrolize our cyclic acetal here, and get
back our original ketone. And so we’ve now been able
to make our desired product. And so that’s one way to use an acetal as a protecting group. Alright, let’s look at
another type of reaction here. So this one’s formation of a thioacetal. So this is completely analogous to the formation of an acetal. So you start off with
an aldehyde or a ketone. And this time, instead of using an alcohol you’re going to use a thiol, so instead of having an oxygen here, you have a sulfur. So you need acidic conditions, and you can even use something
like boron trifluoride here, which can function as a Lewis acid catalyst for this reaction. And you form a thioacetal as your product. So once again you have
your R double prime group coming from your thiol, and then you have a sulfur here instead of an oxygen. And then you have two of
these to form your thioacetal. And so, one reason you might want to form a thioacetal instead of an acetal, is thioacetals have an
additional reaction that they undergo, and we can use
it in this transformation. So let’s say our goal was
to go from the product on the left to the product on the right. And so you can see that
we have reduced our ketone here to form this
cyclohexene portion. So reducing your ketone. So the first thing we could do, to do this transformation, is to form a thioacetal. So it’s going to be, again, analogous to the formation of an acetal. This time we’re going to
use, instead of a diol, we’re going to use
something with two SH groups instead here, so a dithiol here. So we can use an acidic environment here. And we’re going to form
a cyclic thioacetal. So very similar to what we did before. The ring is here, the carboxylic acid is going to be untouched. And instead of an oxygen
directly bonded to our ring, we’re going to have a sulfur. And the same thing on this side, a sulfur. And then our two carbons. So once again, let’s
follow those atoms here. So, a sulfur, two carbons,
two carbons, and a sulfur. So here’s your sulfur,
two carbons, two carbons and then another sulfur,
so a cyclic thioacetal And then there’s actually
a reaction for converting this compound into our target compound. And this involves a
special kind of nickel, so if we use Raney nickel here. It’s a special kind of
finely divided nickel that has already adsorbed some hydrogens. And what it’s going to do is add some hydrogens to this carbon right here. So we’re going to add two
hydrogens to this carbon. And you can see that we have reduced the thioacetal and we have
formed our desired product. So this is another way
to reduce a ketone here, to this alkane portion of the molecule. And so there are other
ways to do it, and this just gives you another tool that you can use for synthesis problems.

4 Replies to “Acetals as protecting groups and thioacetals | Organic chemistry | Khan Academy”

  1. Why make the video when hardly any arrow pushing is shown. We get tested on those kinds of things and it gives reason to the synthesis

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