Leah here from Leah4sci.com and this video were going to look at the reaction mechanism
for actetals, hemiacetals, ketals and hemiketals
In the last video we introduced the acetal and ketal concept along with the trick and
shortcut to help you easily identify reactants and products.
A few things before we look at the mechanism, these are all reversible and can happen under
acidic conditions ideally or non acidic conditions.
We're gonna focus on the acid catalyzed reaction because it's most common to come up in your
class and it's the better faster reaction.
This reaction is typically catalyzed by hydrochloric acid or p-Toluenesulfonic Acid.
Phew!
That's a mouthful!
Don't worry about the acid just recognize that the acid will dissociate to give us a
H+ in solution which means if your reaction happens in an alcohol like methanol, the methanol
will pick up that H+.
You can simply show your alcohol with two hydrogens and a positive charge as the acid
or even just show H+ recognizing that it came from an acid catalyst.
The second thing to keep in mind is why this reaction happens, carbonyls are reactive because
of their resonance if you're not familiar, you can review in the tutorial link below.
This happens because the pi bond between carbon and oxygen can resonate up to that oxygen
atom to give us a molecule that has carbon single bound to oxygen, the two lone pairs
we saw initially on oxygen and another lone pair from the resonance.
A quick formal charge calculation tells us that oxygen has a negative one and carbon
with it's incomplete octet has a charge of plus one.
We're not going to show this, we're simply going to recognize that the resonance hybrid
is a result of these two which means we have the resonance going up and down between carbon
and oxygen with a partial negative charge on oxygen and partial positive on carbon.
This is critical to remember, the partial negative makes this oxygen more reactive than
a standard alcohol oxygen and the partial positive makes this carbon susceptible to
attack by something negative or partially negative.
We'll use simple molecules for this mechanism starting with aldehyde, reacting in an acid
catalyzed ethanol solution, pay close attention to the colors so that you can identify where
each atom came from, where the electrons came from and ultimately be able to follow along.
Now I'm warning you, it looks like a long tedious scary mechanism so two things to remember
before we start: One, pay attention to the why, when trying to figure out the next step
I like to ask myself this question: What's the most positive solution right now, what's
the most negative solution right now and how do those two interact because typically the
charges will be attacked or neutralized going in to the next step.
The second thing is to notice the pattern.
This reaction is intense but it's very similar to many of the other carbonyl reactions that
you see in organic chemistry, so once you learn one and understand the pattern, you
can apply this to all the other crazy reactions you learn later on.
Lets begin
What is the most negative in solution right now?
Well this is an acetic solution that means were typically not going to see negative charges
in fact, it's my pet peeve when students write a positive and a negative oxygen in the same
solution because typically they don't play nicely together, they're going to attack.
In an acid catalyzed solution, the most negative species will be a neutral electronegative
atom for example oxygen with two electron pairs.
What is the most positive?
Well obviously the proton floating around the solution with a positive charge or sitting
on alcohol as ROH2+ again with the positive charge.
Here's the question, which oxygen attacks the proton?
Is it the alcohol?
or is it the carbonyl oxygen?
And before you argue about the alcohol, yes we have a lot more alcohol and solution so
technically it is the alcohol but, once that happens and exists as a positive oxygen it's
still going to be a question of what is ultimately the stronger negative oxygen and that would
be the carbonyl, why? because this oxygen remember has a partial negative charge from
resonance due to the pi bond that has a much greater electron density, so even though this
is is most common because of the volume, we have way more alcohol because it's the solvent
and solution, to start this mechanism, it's ultimately going to be the carbonyl oxygen
electrons that reach for that proton.
Think of this as the activation step, we activated the carbonyl, making it even more reactive
to attack.
How did that happen?
We already saw the resonance has a partial positive charge on carbon and a partial negative
on oxygen, this oxygen was greedy, it reach for a positive hydrogen atom and got it's
wish but now it has regret because oxygen now has three bonds, one lone pair and a formal
charge of plus one.
Oxygen as an electronegative atom is unhappy with that positive charge and starts to pull
on the electrons between itself and carbon even more to try to make up for that positive
charge.
The more oxygen pulls electrons away from carbon, the more partially positive that carbon,
the more susceptible it is to attack.
That's what I mean by an activated carbonyl or what is the most negative solution right
now?
A neutral oxygen atom, for example our solvent.
What is the most positive?
Well this partially positive carbon because oxygen is hogging all the electrons.
So we show one of the solvent molecules attacking the carbonyl carbon to form a new bond between
oxygen and carbon, this puts too many bonds on carbon so it breaks the bond between carbon
and oxygen collapsing the pi electrons onto the oxygen atom just like oxygen wanted.
Our intermediate is called a TCAI, a tetrahedral carbonyl addition intermediate because the
carbon is now bound to four different atoms and is a tetrahedron because of the SP3 hybridization.
Some professors will prefer to the TCAI, make sure you know what they're talking about.
The green oxygen still has the hydrogen atom and one lone pair giving it a formal charge
of plus one.
What is the most positive solution?
The hydrogen atom.
Remember, positive oxygens don't get attacked, they're greedy, they pull electrons from something
nearby, something that's attached making that atom partially positive so even though the
charge sits on oxygen it's hydrogen that's most partially positive and ultimately hydrogen
that gets attacked.
I want to remind you that even though my habit is to draw single-headed arrows, these are
actually reversible.
So what is most positive?
This hydrogen, What is most negative?
An alcohol solution, What does that do?
Well, another alcohol solution with it's oxygen will reach for that hydrogen, collapsing the
electrons back onto oxygen giving me a neutral intermediate.
What's most negative?
Oxygens that are intermediate, What's most positive?
More protons floating around that solution.
At this point you should recognize that we have a hemiacetal because carbon with the
hydrogen is bound to a blue oxygen that's an OH and a green oxygen that's an OR.
This is where a lot of students get confused, if I have protons floating around the solution
we can show that's an H+ or sitting on alcohol, which oxygen grabs it?
Is it the OR group or the OH?
And the answer is technically both.
Remember, it's a reversible reaction, if the OR grabs it, We simply go back to the previous
step where we have a protonated OR and that doesn't help us because we can go back and
forth a million times, so instead, we'll only show the step that takes us forward in our
reaction, showing the OH grabbing the hydrogen, again it's not that only one oxygen grabs
the hydrogen but rather we don't want to waste time going back and forth we simply want to
show the next step in a forward direction.
This gives us a blue oxygen with one lone pair, two hydrogen atoms and a positive charge.
You should remember from previous reactions that protonating an OH turns it into a good
leaving group because OH2+ is not very happy but a water molecule and solution will be
much happier.
Many professors will show it simply breaking away but what you want to show is electrons
from the neutral oxygen collapsing down, remember oxygen is greedy, it never knows when to quit
and when it's neutral it will keep trying to grab more.
When oxygen electrons collapse down, carbon would have five bonds which can't happen so
we used that attack to kick out the water molecule by breaking the bond between carbon
and oxygen, this gives us an intermediate that now has two bonds between the green oxygen
and carbon, for a total of three bonds, one lone pair and a positive charge on oxygen,
along with the side product of OH2 which is a neutral water molecule and solution.
One lone pair from the initial oxygen pair and one lone pair from the bond that broke
away from carbon oxygen.
Water is gone but we're not done.
We have a regretful oxygen atom with a positive charge pulling on the bond between itself
and carbon once again making that carbonyl carbon very partially positive.
What is most negative in solution?
Another alcohol molecule.
Which we'll show attacking the carbonyl with a lone pair and breaking the bond between
carbon and oxygen to collapse the electrons onto the oxygen atom.
The intermediate now has a green neutral OR group and a purple protonated OR group from
the incoming alcohol.
The purple Oxygen has a lone pair and positive charge making the purple hydrogen most reactive,
making it susceptible to attack by another oxygen in solution.
For the final step some professors will show the conjugate base from your initial acid
catalyst grabbing the hydrogen.
Ultimately it doesn't matter.
It's something basic in solution that deprotonates the hydrogen giving the electrons back to
that oxygen atom to give us our final neutral product.
We have the carbon chain with the hydrogen, we have the green neutral OR group and the
purple neutral OR group.
Our final product is an acetal which has the carbon chain with the hydrogen and attached
to the carbon we have 2 neutral OR groups.
The green alcohol from the first attack and the purple from the second.
In solution, you'll notice we have a side product on the final set which is the protonated
alcohol which is the alcohol we used to deprotonate the final Oxygen.
This is important because the rule of a catalyst is that it doesn't get destroyed in a reaction.
A catalyst can get used but has to be regenerated.
We started the reaction with the protonated alcohol as the acid catalyst taking up a proton
from solution.
And we end the reaction with a protonated alcohol holding that hydrogen which if we
dissociate would just be that proton one again floating around in solution.
And again as a reminder, these are reversible steps.
Be sure to join me in the next video where we'll look at the mechanism for a cyclic acetal
protecting group.
You can find this entire video series along with the acetal practice quiz first by giving
this video a thumbs up, then click on the link in the description or visiting my website
leah4sci.com/acetal.