Leah here from leah4sci.com and in this video we're going to look at acetals, hemiacetals,
ketals and hemiketals from the reaction overview to a simple shortcut so you can easily get
the product or reactants on exams.
Acetal sounds like a scary topic because of the mechanism but if you understand the steps,
it's actually not as difficult as you think.
A quick google search tells us that an acetal is the condensation of an aldehyde which we
have here as a carbonyl with 2 alcohols.
But actually when you're looking at a topic of acetals you're technically looking at 4
different intermediates or products.
We have an acetal or hemiacetal, a ketal or hemiketal.
So what does it mean and what's the difference between them?
In this video we'll do a quick overview of the reactions so you understand what's going
on along with a shortcut and then on the subsequent videos we'll look at mechanisms for acetal
ketal formation, as well as using acetals as protecting groups for advance synthesis
reactions.
This reaction starts with a carbonyl that gets attacked with an alcohol which is an
Oxygen nucleophile at the carbonyl carbon.
We can start out with an aldehyde or with a ketone.
When the oxygen nucleophile attacks we break the carbonyl so that the oxygen is still bound
along with the incoming alcohol.
Reacting this with one more alcohol will ultimately displace the OH group and give us a second
OR on the molecule.
When starting with an aldehyde, the final product still has an H and 2 OR groups.
When starting with the ketone the final product has 2 carbons and 2 OR groups.
Let's also pay attention to what we lost.
Everytime we added an OR we had to cut an H off the alcohol so that's one hydrogen,
2 hydrogen and of course the initial oxygen that we lost which means both reactions will
also have water as a side product.
So what do we have here?
Technically this entire class of reactions is called acetal.
With what we're actually looking at is an aldehyde reacting first with one alcohol to
give us half of product where a hemiacetal then we're reacting with another alcohol to
give us a full acetal.
If however you start with a ketone and react it with one alcohol, you get a half not quite
acetal, you get a hemiketal.
And if you react the hemiketal with another alcohol you get a full ketal.
The difference being an Aldehyde starting molecule will give you an acetal product.
A ketone starting molecule will give you a ketal product.
Some professors will lump all of these together and simply call it the acetal topic and they
will call the ketals an acetal.
So how do we justify that?
I want you to imagine that you're referring to different types of living organisms.
There's feline which would refer to tigers and lions and cats.
There's canine which would refer to all kinds of dogs.
And then there's man that refers to humans.
Does it mean that man also refers to male humans?
No, we're simply classifying humans as man but it technically includes male and female.
So think of acetal as man, as the overall category but it technically includes both
the acetal from the aldehyde starting molecule and the ketal from the ketone starting molecule.
Note that both of these reactions are reversible.
if you're trying to identify a molecule, here's how to quickly recognize them.
When you have a carbon that has a hydrogen and 2 OR groups attached, that's how you recognize
an acetal.
If you have a carbon with 2 R groups attached and 2 ORs, that is how you recognize a ketal
but if the carbon that has 2 oxygens attached has an OH and an OR, that's your hemi, if
there's a hydrogen, it's hemiacetal, if there are 2 R groups it's a hemiketal.
Even though we show the hemiacetal and hemiketal intermediates, these reactions while reversible
will prefer one way or the other.
The one stable, hemi intermediate is a cyclic compound, for example glucose.
In this drawing D-glucose we have a heterocyclic ring because of that oxygen but if you look
at this carbon over here called the anomeric carbon, you'll recognize that carbon is bound
to 2 oxygen atoms, one is an OH group, the other is an OR group but there's also a hydrogen.
When you see carbon with hydrogen, OH and OR, the hydrogen tells us it came from an
aldehyde, the OH and OR tells us it's a hemi, making this a hemiacetal, a very stable hemiacetal,
going back to the reactions, notice that we have double headed arrows to show that it's
an equilibrium but this is tricky.
In most cases, equilibrium for an aldehyde will favor the acetal but with the ketone,
will not favor the ketal, it will favor the ketone.
If you specifically want to drive the reaction in one direction remember Le Chatelier's principle,
if we add a reactant, we push the reaction forward, if we remove a product, we also push
the reaction forward.
This means that if the reaction takes place in alcohol, it does drive the reaction forward
or if we do something like remove water from the product, we'll keep pulling the reaction
forward and the reverse is also true.
If we remove alcohol or add product, the reaction would favor the reactant, pushing it in the
reverse direction
In the next video, we'll look at the mechanism, but what if you simply need to identify reactants
or products for short answered questions on your exam?
Say we have a starting ketone, reacting in an acid catalyzed methanol solution, we'll
just show H+ for the catalyst but this could be HCl or palatoluenesalicylic acid just write
H+ . The product is going to have 2 OR groups attached in this case 2 OCH3 and of course
the water molecule side product.
If you're given a reactant and you need the product, here's what you do, you simply cut
off the carbonyl oxygen because that comes off as a water, you cut off the 2 hydrogens
from alcohol because that comes off with water and you add the OR group or whatever that
oxygen is carrying to the carbon that holds the carbonyl.
Which is exactly what we see here.
We have the starting carbon chain and the 2 OR groups.
This works no matter how complex you're starting material or alcohol in this case we have cyclohexanol
so we cut off the oxygen, we're reacting in it in a isopropyl solution so we cut off the
hydrogen, redraw your carbon chain and the carbon that used to hold the carbonyl will
now get 2 bonds to oxygen, on the oxygen, simply add the alcohols carbon chain.
In this case an isopropyl group and an isopropyl group, a similar shortcut works if you want
to reverse the reaction, say we're starting with an acetal or in this case technically
a ketal and we want to know the starting carbonyl and alcohols, identify that acetal or ketal
carbon, the carbon that has 2 bonds to OR.
Draw a carbonyl on that carbon and break the bonds and bind it to the OR groups, for every
OR you cut off, simply add a hydrogen to reform the alcohol.
What does that give us?
We have the carbon chain, now double bound to a carbonyl at the central carbon and we
have 2 CH3OH molecules, this was simple, so let’s try reversing that second reaction
once again, identify the acetal or ketal carbon the carbon that has 2 bonds to OR and draw
a carbonyl down the middle.
Break the bond between that carbon and oxygen and give each oxygen or hydrogen atom to reform
the alcohol.
What does that give us?
We have a cyclohexane with a carbonyl now on that upper carbon along with 2 molecules
that consists of an isopropyl group bound to an oxygen, bound to the hydrogen that we
added back in, one final trick before we look at mechanisms.
We said that acetals are relatively stable and that means if they're difficult to attack,
they can be used as protecting groups, when we want something else on the molecule to
get attacked but not an aldehyde or not the ketone.
So how do we protect the carbonyl?
We simply react it with 2 alcohols to form an acetal.
Again, let's use the trick, cut off the carbonyl, the carbon that has the carbonyl gets 2 oxygens,
1 for each of the alcohols and then we attach the R group and on purposely writing it like
this.
In this situation we use 2 different alcohols so we have 2 oxygen atoms bound to carbon
and 2 R groups.
But who said the R groups can't be attached to each other?
What if I have a reaction where I have an alcohol and another alcohol on the same molecule,
everything else still works exactly the same, a very common protecting group that you're
going to see is an aldehyde or ketone reacting with ethylene glycol.
Ethylene glycol or 1,2 ethanediol is a 2 carbon vicinal diol meaning the alcohols are a neighboring
carbons, if we react this with an aldehyde or ketone, we treat it the same exact way,
imagine that this is the first alcohol you add, this is the second alcohol and they just
happen to be bound to each other.
How do we come up with a product?
Take away the carbonyl carbon and redraw the skeleton, the carbon that used to hold the
carbonyl is now bound to 2 oxygens atoms, let's make one carbon green for the green
oxygen and one carbon blue for the blue oxygen.
Again, 2 different alcohols that were adding but the R group from the left is a blue carbon
atom, the R group on the right is a green carbon atom and they happen to be bound to
each other and a good way to remember that this is a protecting group is to add some
eyes and now it looks like a gasmask.
Anytime you want to protect the carbonyl, give it gas mask, proceed with your reaction
and then all you have to do is react this with acid to remove the protecting group because
remember, all of these reactions are reversible.
Be sure to join me in the next video where we look at the step by step mechanism for
the acetal and hemiacetal formation.
You can find this entire video series along with the acetal practice quiz by visiting
my website, Leah4sci.com/acetal