professor Dave here let's talk about claisen condensation.
so we've learned a few things about enolate chemistry, we learned about aldol condensation and now
it's time to learn a similar reaction it's called claisen condensation and so
here the the key thing that we want to see right off the bat is that whereas
aldol condensation was operating on aldehyde or ketone substrates here we
are working with an ester substrate okay so once again an ester if we recall that
is an ester group is a carbon can that is a a carbonyl connected to OR right
so if it was OH it would be a carboxylic acid but it's OR meaning O and then
more alkyl, that is an ester substrate and so we are operating with an ester
again we're going to be using strong base one key feature we should point off
right at the start here is that this this alkoxide right here this
OR and this OR must match these must be the same if we're gonna do claisen
condensation effectively because the thing is where as we are gonna do
enolate chemistry this base is going to get this alpha proton we're gonna do
enolate chemistry when we have an ester there is the opportunity for
competing transesterification so we know that something like an alkoxide could
attack this carbonyl, pop that up pi bond could come back down kick that off
and we would get a different R group so if these do not match then we're gonna
get a mess in solution there's gonna be a lot of different products but if these
do match then if an alkoxide does do that it doesn't matter it's not going to
change the substrate right OR attacks kicks this one off it's just another of
it's the same molecule so that's one thing to be aware of in claisen
condensation the alkoxide must match this alkoxy group in the ester so with
that understood let's go ahead and go through the mechanism we've got an
alkoxide base and we're gonna go and do really this doesn't change the chemistry
very much at all we're just gonna go ahead and do enolate chemistry we're
gonna make our enolate so here we have formed our enolate and
then just the way that when we did aldol condensation we could have an aldehyde
attack another molecule of itself or a ketone attack another molecule of itself
same thing here this ester that we've enolized can just go ahead and
attack another equivalent of the same thing and so it's an ester but it's no
different, we are going to have the enolate attack the carbonyl carbon right
there and we're gonna kick that pi bond up there and so here is where it starts
to get a little bit different because unlike the aldol condensation we have an
intermediate here where this OR group is there because we've attacked an ester
and so this gets a little bit different this is actually going to go ahead and
come down we're gonna reform that carbonyl and we're gonna kick off that
alkoxy group okay so the the enolate attacked the carbonyl but then because
of the presence of this alkoxy group we were able to reform that second carbonyl
so this is our product this is the product of the claisen condensation just
to be very thorough mechanistically we must understand that from here we still
do have a lot of alkoxide in solution and this, these two protons here right
we've got some protons here these are now alpha to two carbonyls so whereas
we've got a certain pKa up here this is going to be several orders of magnitude
more acidic because the resulting enolate that you could form if you
grabbed one of these we've got pi electron density distributed all allowed
all along a much larger portion of the molecule so if we have strong base we
have base that's strong enough to get this proton you better believe that
we're gonna enolize that so in solution we can't stop that that is going to go
ahead and we've got alkoxide we are gonna enolize and we can just leave once
again there is a lot of resonance to speak of there that could be delocalized
all around there but we'll just draw this resonance structure so we are going
to deprotonate there and then just to be very clear in terms of when we're doing
chemistry it's not until aqueous acidic workup right
we've got our solution the chemistry is done and then that's when we pour in
some ammonium chloride or something like that where we're just going to very
lightly protonate any anions in solution to get a neutral product so that is just
that is just gonna go and get that proton from whatever this whatever this
acid is upon workup and that is going to give us our beta dicarbonyl compound so
beta because if this is one of them then two carbons away right alpha beta at the
beta position we have another carbonyl that is a beta dicarbonyl compound a
claisen condensation will always operate on an ester substrate and it will give
us a beta dicarbonyl compound as our product so that is the mechanism for the
claisen condensation so we just saw what happens when we do Claisen
condensation where one ester is reacting with another molecule of itself but just
like the way we can have crossed aldol condensation where we have two different
aldehydes or ketones we can also have crossed claisen condensations so we can
have two different esters reacting so we have this ester and this other ester and
in order to understand what's going to happen we have to be aware of the fact
that whichever of these esters is going to become the enolate must
be enolizable it must be able to be enolized
it must have protons that are available for enolization and so we look at this
here and what do we notice about this compound here where are the alpha
protons well here's the carbonyl so the position alpha to the carbonyl is here
but there are no implied hydrogens there are no hydrogens at all
right this carbon is participating in four bonds to other carbons right one
two this way and the fourth that way so there are no hydrogens there there is
no alpha proton that is not enolizable this cannot become the enolate this on
the other hand it absolutely can because we do have three alpha protons right
here so that's going to be fine so we've got our ethoxide base notice that it
must be ethoxide because in this case we've got these ethoxy groups on
these esters if it was something else we could be getting transesterification
that would be a mess in solution but we've got our ethoxide so let's use our
ethoxide and let's go and get a proton
and let's make our enolate so we've made that pi bond and there we are there and
now let's go ahead and react with this guy this is going to preferentially do
the crossed claisen and we're going to react with this so let's draw that here so
we've got this coming down here this enolate is going to attack right there
pop that open so what do we have we've got this we've got O minus up there we've
got OEt up there and then it was this carbon here that attacked right so this
is the new bond this is the new bond right here this rest of the molecule was
this and now this is connected to a two carbon ester right so let's draw those
okay so this is the key step this is the carbon-carbon bond forming step so we
have to understand that it is this carbon here right just as with aldol
condensation or any other kind of enolate chemistry we're looking at this
pi bond reformed this carbon is now attached to this carbon so this red bond
this red sigma bond represents this arrow right there we have formed that
new bond this was a carbonyl and we kicked that pi bond up over to make O
minus and now if we recall the mechanism the next thing that's going to happen
this is going to come down here to reform the carbonyl and we're gonna kick
off at oxide we're gonna kick off that ethoxide and we are gonna get our
claisen condensation product which is a beta dicarbonyl and we will get
ethoxide there right we did lose that ethoxide so this is our beta dicarbonyl
product. now with the mechanism again there's more ethoxide in
solution we would deprotonate that and then we would with aqueous acidic workup
reprotonate but right now we're just really concerned with what the product
is. mechanistically we do want to be aware that that is happening in solution
but this is the product this is our claisen condensation product it is a
beta dicarbonyl compound and it is a crossed claisen condensation. let's look
at just one more example of a claisen condensation and this is an interesting
case here let's say we have this substrate notice that we have two ester
groups on here and let's see what's going to happen we've got ethoxide
again this ethoxide matches the ethoxy groups on the esters and
at first nothing is going to be too surprising right we have we have some
protons this is a symmetric molecule so it doesn't matter where we get the alpha
protons from so let's take our ethoxide and let's go and get this one and let's
make our enolate and so here is our enolate
so now this is an interesting situation though because we have an enolate here
and we know that the enolate during claisen condensation is going to
attack an ester it's going to attack another ester and we have ester
functionality on that molecule already and so we have the opportunity to do an
intramolecular reaction here and any time intramolecular chemistry is
possible it's going to be much much faster than any intermolecular chemistry
because in order for an intermolecular reaction to occur
the two reagents have to find each other in solution and that takes
time because they're drifting aimlessly they need to collide. here what this
wants to react with is tethered to the molecule already so they're gonna find
each other as these sigma bonds are rotating this is sneaking around this is
going to get into proximity of that carbonyl very quickly in solution so the
intramolecular reaction is gonna happen way before it's gonna find some other
ester right another molecule of this and do an intermolecular reaction so let's
show the intramolecular possibility here and now this this is the step that can
usually be confusing to many students let's make sure that oh sorry actually
this was not from here let's have this go down there and then this pi bond
right and so if this pi bond is attacking remember that we're reforming
the carbonyl here this carbon is the one that is doing the attacking so let's see
how many members are in our ring right if we are doing an intramolecular
reaction there's going to be a cyclization and we can see that carbon
one is attacking carbon five so we're gonna produce a five membered ring right
so here is our five membered ring and let's say let me draw that a little
better
let's say that we call this carbon one let's go ahead and number these one two
three four five so that's just to that's just to
help us understand what's going on we said that carbon one right this pi bond
flipped out and attacked carbon five that means that this is the new bond
right there that's the bond that was formed by the cyclization and so carbon
one also had the rest read this ester group reformed so let's draw that we
have got that ester group there okay so that carbonyl reformed and that ester
group is intact. carbon five now however has O minus and O ethyl right because this
carbonyl right we have that O minus there now so let's draw that
and so really mechanistically it's not that much different just like a claisen
condensation a regular one this is going this is going to this gonna pop that
ethoxy group off there
so that extra group once again is intact and we have reformed that carbonyl so
this is still a beta dicarbonyl compound right we've got this carbonyl alpha beta
two away but this was a cyclization reaction and as it happens when we do a
cyclic when we do an intramolecular claisen condensation or cyclization
reaction this is called a dieckmann condensation so that's just a little bit
of a different name that indicates that it is an intramolecular reaction it is a
cyclisation but really mechanistically it's the same we are starting with an
ester substrate it's just that the ester that is being attacked is on the same
molecule and we do end up with a beta dicarbonyl compound as our product and
so that's what we need to know about claisen condensation and dieckmann condensation.