Retro-aldol and retrosynthesis - Chemistry Video Lecture - NEET

Voiceover: We've done a lot
of aldol condensations, and in
particular, we've looked at the mechanism
in great detail.
In this video, we're going to think about
doing things in reverse.
So we're going to start with a retro aldol
reaction and
see how that way of thinking can apply to
retro synthesis.
And so let's start with cinnamaldehyde
right here.
And if we do a retro aldol reaction, the
mechanism
is pretty much the exact reverse of an
aldol condensation.
And so if we had a base like
sodium carbonate, we're gonna form
benzaldehyde and acid aldehyde.
A cinnamaldehyde is the molecule that
gives cinnamon its smell, and benzaldehyde
smells like almonds, and so this is a
pretty cool experiment to do.
You can stat with the molecule that smells
like
cinnamon and end with a molecule that
smells like almonds.
Let's analyze our cinnamaldehyde starting
compound here to
see how we would have formed those
products.
We know the carbon next to our carbonyl is
our alpha carbon.
And we know the carbon next to that is the
beta carbon.
And so looking at the structure, all
right, we know
that there's a hydrogen attached to our
alpha carbon like that.
So we think about breaking this double
bonds, right?
We can see this this two carbon setup
over here on the right for acid aldehyde,
right,
so those are the two carbons, and this is
the hydrogen that's bonded to that alpha
carbon there.
Looking at the structure again on the
right, we know that there are two
more hydrogens bonded to that alpha
carbon,
and so therefore, if we're doing things in
reverse, we can think about adding two
hydrogens to this alpha carbon, and then
go ahead and draw two hydrogens right
here, so I'm just going to write H2.
And then we can think about adding an
oxygen to
the beta carbons, and we can think about
adding H2O.
I know there's already a hydrogen on that
beta carbon, so
I could think about this being the
hydrogen on that carbon.
All right and then if I add an oxygen
to that carbon, that would be this oxygen
right here.
So just a, a way of thinking in reverse,
right?
Adding water, right, breaking your double
bond and adding an oxygen and
two hydrogens will, is one way of thinking
about forming your product here.
So or you can think about the reverse.
You can think about losing water from this
portion and sticking
these two fragments together to give you
your aldol condensation product.
So once again, this way of thinking can be
can be very useful
if you're trying to retro synthesize
something, so if you're thinking in
reverse.
So for example, let's say a question on a
test was show how you could
synthesize this enone here, so once again
we're gonna do the same kind of analysis.
We're gonna find our alpha carbon right
here; this
is our alpha carbon, and this is beta
carbon.
All right, so attached to our alpha
carbon, all right, we know that there's
a hydrogen right here, so we're gonna
think about breaking this double bond,
right?
So let's go ahead and draw a retro
synthesis arrow here.
So we're gonna break that double bond, so
on
the left, all right, we're gonna have our
benzine ring.
We're gonna have our carbonyl here.
And then we're gonna have a hydrogen
attached
to this carbon, attached to our alpha
carbon.
And remember, we're gonna add two
hydrogens to our alpha carbon.
So we're gonna add two hydrogens to our
alpha carbon,
and that would give us the ketone that we
would need.
Right, for our beta carbon, we know
there's already
a hydrogen attached right here, and so
we're going to
add an oxygen to this beta carbon on the
left, so this is our way of thinking about
it.
So over here on the right we're gonna have
we're gonna have our carbonyl.
All right, and then we're adding an
oxygen, right, we're adding a oxygen right
here.
And then we had that hydrogen, so I'm
gonna go ahead and draw that hydrogen in
blue.
And then we can go ahead and draw our
ring.
So we have our ring right here.
And then we have our nitro group coming
off over here.
So just to check ourselves and make sure
that this is the right way
of thinking about it in reverse, if we
take water from this portion, right?
And stick those two fragments together.
Then that would give us our conjugated
enone product over here on the left.
And so that's, again, one way of thinking
about how to do these sorts of problems.
And so if they if they wanted you to give
some some reaction
conditions here, you can go ahead and, and
draw what you would need, right?
So you would say, I need to start with
this ketone, right?
Like this and then I would also need
an aldehyde, so I'm redrawing the
4-Nitrobenzaldehyde product, right?
So we have 4-Nitrobenzaldehyde like this.
All right, so this compound, this ketone,
of course, is this compound right here.
And then 4-Nitrobenzaldehyde here is the
same one that we drew right here.
So if you take those two, right, and you,
and
you put them together, you should form
your conjugated enone.
Because remember, thinking about your
alpha protons, right,
there are no alpha protons on our
4-Nitrobenzaldehyde.
Right, so this,this carbon right here
doesn't have any alpha protons, so
the only source for alpha protons would be
this carbon right here.
This is your only alpha carbon with alpha
protons on it.
So in terms of in terms of what else we
would need, we would need a base, all
right, to do our alpha condensation, so we
could
add a something like sodium hydroxide as
our base.
And we could we could create a solution of
sodium
hydroxide and water, and then also ethanol
so if you took
these ketone right in this aldehyde and
use these reaction
conditions, you should form the conjugate
enone as your major product.
And so that how to how to synthesize it,
so once again thinking in reverse.
Let's do another one.
This one's a little bit different because
we don't
have an enone for an enol as our target
compound.
We have an aldol as our target compound.
Well, we can use the same kind of
thinking.
We can find our carbonyl and identify the
carbon next to that as being
our alpha carbon and then thinking about
this as being our beta carbon, right?
And we know that this is the bond that
forms.
So we can think about breaking this bond.
And and we know right, we know that we
have a hydrogen on this
carbon right here, as I'm just gonna see
if I can stick it into there.
So when I think about retrosynthesis, all
right I go
ahead and draw my retrosynthesis arrow in
here, so on the
left, I mean I can see on the left that
I'm
going to have this carbon two, three, four
and five, right?
So I have these five carbons right here
so, we go ahead and draw those in.
So we have our carbonyl, and then we have
our five carbons, and then I already have
this hydrogen in magenta, and we're only
going to add on hydrogen this time.
So let me go ahead and draw in one
hydrogen in green because this isn't the
congregated product.
We stopped at the aldol if you're thinking
about it in reverse.
So we're not going to add two hydrogens,
we're only
going to add one here, and so what else
would we
need; so over here on the right, let's
think about the
fact that there is hydrogen attached to
this carbon right here.
And then how many carbons will we have for
our other
compound, one two three and four, so we
need a 4-carbon carbonyl.
Right, and there's a hydrogen attached to
it, so a 4-carbon, carbonyl.
Let me go ahead and draw that in, one,
two, three
four, and then we have this hydrogen ion
glued to it.
So now, we've identified and thinking
about it in reverse,
what compounds we would need to form this
aldol product.
We would need this ketone and this
aldehyde.
But, in terms of in terms of actually
synthesizing the aldol compound on the
left, we have to be a little bit careful
about how to do it.
We need to do a directed aldol addition
here,
so let's think about starting with this
ketone, all right?
So think about starting with this ketone
here, so let me go ahead and redraw it.
I'm going to draw it in a slightly
different way.
All right, so that's this ketone right
here.
And to that ketone, we're going to add
LDA.
So we're going to form a lithium enolate
here, and once
we've formed our lithium enolate, then we
can add our aldehyde.
So in our second step, we can add our
aldehyde
in here, so we talked about this in
earlier video.
So we have our aldehyde as a 4-carbon
aldehyde, all right, so we're going to add
butanal.
And then that's going to give us a, a
lithium alkoxide, right?
So we need to we need to protonate the
alkoxide,
so in the workup, we can add some water
here.
And that would give us our aldol product,
so that would give
us this, so that is the way to synthesize
our aldol products.
Let me go ahead and draw it in here,
right, so we would form this.
Okay, so a directed aldol addition.
Let's do, let's do one more of this
retrosynthesis approach.
And let's think about how to make this
molecule.
So this is a little bit different than
before.
Okay, but we can do our same stuff.
So we can identify our alpha carbon,
right, the one next to our carbonyl.
And then our beta carbon is the one next
to that, right?
So we can think about breaking this double
bond, all
right, and adding two hydrogens to our
alpha carbon, right?
So let’s go ahead and do that, so we’re
going to break that double bond and add
two
hydrogens to the alpha carbons, so
thinking about this
in terms of retrosynthesis, we have a ring
here.
All right and then let me, let me go ahead
and draw this over here.
We would have two hydrogens over here.
Let me go ahead and get some more room.
All right, so probably easier to think
about adding your
oxygen to your beta carbon first, so let's
do that.
All right, we know we're gonna add an
oxygen to our beta carbon.
So let's go ahead and put in our oxygen on
our beta carbon; I'll do that in green.
Right, and then we're gonna think about
two hydrogens
to our alpha carbons, so we're gonna draw
in
our alpha carbon like that, and we're
gonna add
two hydrogens; I'm gonna put those in
green like this.
And this is a little bit more room, and
then we would have our carbonyl like
that, and then we would have to make sure
count your carbons when we're doing these.
All right?
So let's go ahead and show those carbons.
So this carbon right here is this carbon.
All right.
And then, this carbon is this one right
here.
And then this carbon, our carbonyl one is
right here.
And so you can see this is actually an
intramolecular aldol condensation.
So if you think about losing water right
here, right, and sticking those
two fragments together, you would form
this compound on the left, and so this
is a pretty cool reaction.
Right, we could we could redraw this,
right, so
on an exam, right, you might, I mean, you
could draw it like that, but most of the
time, you would see it in a different
conformation.
All right, so you would see the compound
looking like this.
So let me go ahead and draw that.
So identify your carbons.
Carbon in magenta is the one right here.
Carbon in blue is the one right here.
And the carbon in red is the one right
here, which has your carbonyl.
And then we are going to go ahead and make
our alpha carbon
right here green, so this carbon right
here, so this must have been, this
must have been your starting compound,
right, and so if you add a
base, right, you can convert, you can
convert this molecule into your target
compound.
So once again an intramolecular aldol
condensation.
And we'll talk in more detail about those
in the next video.