Let's talk about the Claisen condensation so Claisen was a very busy chemist and has
a few reactions named after him, but we are talking about the condensation reaction here
between an ester that has acidic alpha hydrogens and either itself or another ester, so let's
look at what happens when there's actually just two of the same type of ester and see
how the product looks. what we end up with is the nucleophilic attack of the enolate
to the ester which eliminates an alkoxy group to form a beta keto ester so the ester the
enolate part forms the enolate keeps the ester and then the electrophile the second ester
forms the ketone so we say alpha beta theres the alpha beta keto ester so here's the one
position 2,3,4 so sometimes you number that way and you say it's a 3,4 or a 4 keto ester.
That being said between like esters we'll look at the mechanism for that in a moment;
however, in a cross claisen where you have two different esters that are reacting, we
simplify things when we have only one of the two has alpha hydrogens so we want to form
the enolate has alpha hydrogens but the electrophile does not and so here's our electrophile and
we're going to have this solution stirring with base so OR minus there, sodium methoxide,
sodium ethoxide, whatever the R group on the ester is that's what we want...that's what
we want the hydroxide or excuse me alkoxide to be so that we don't have trans esterification
going on in our mechanism so we just kind of make these two guys the same by default.
Alright so we then add dropwise the electrophile or excuse me the nucleophilic enolate forming
ester to the solution we are allowed to use alkoxy groups, this is technically in equilibrium
reaction, here's the line reaction for it we are going to add it dropwise, the thing
with alpha hydrogens forming the enolate so it does it slowly and does not self condensate,
rather it forms the higher percentage product where the nucleophile and the electrophile
are well identified in the reaction so there's what we would get and we can mark, well here's
the phenyl group and the ketone from the electrophile ester and the nucleophile ester here where
we see with the R2 group as well, we can see that formed here. So look at that the enolate
again keeps its ester, so whatever is the enolate ester it keeps its OR group in tact.
Alright so what if we have a crossed Claisen with alpha hydrogens on both its very similar
to the aldol in that we are going to add our first ester that we want to form the enolate,
we add this dropwise to a prepared solution of LDA and THF so that we form the enolate
in entirety, goes to completion there's no equilibrium going on, so this particular one
would form an enolate that looks like this, that's going to go to completion when you
add LDA, lithium diisopropylamide, and so then after that we add our electrophile dropwise
so that we slowly perform this very vigorous reaction and then we workup with a little
bit of acid to make it easier to isolate at the end, we neutralize all that negative base
out of solution so the LDA (want to probably do that dropwise as well since it's quite
vigorous like we said). If we look our enolate ester here that keeps the ester, there it
is with its alpha position attacking our other ester, our crossed group here, so we lose
its ester group, retain the carbonyl make a beta keto ester in the claisen so let's
look at the mechanism of the claisen based on our original example here of this ester,
two different esters here. So we take our OR minus let's actually make this concrete,
let's lose the R groups here and say well what if this was a methyl ester for this compound,
we'll put an ethyl group on the other side, let's then deprotonate our alpha hydrogens
with sodium methoxide and let's highlight an alpha hydrogen that will get deprotonated,
there it is, form the enolate, we don't have to worry about kinetic or thermodynamic here
because there's only one set of alpha hydrogens on the ester possible so we know that we can
only have one possible enolate, okay when that happens we again self condensate, so
we've got another exactly identical to the starting material and we see that when this
enolate comes back down we attack as an electrophile to that position, kicking up the pi bond to
a lone pair so we want to be careful here, we want to draw out our original ester as
is and then at the alpha position where we just attacked starting at this carbon, O minus
where the ester OCH3 and then we had a methyl group or an ethyl group left over, so we've
got to add in all those carbons make sure we've got everything and now we've got a tetrahedral
intermediate here, that can then return to a ketone here or a carbonyl compound, eliminate
the leaving group of the methoxide and we will then see...redraw the original in the
original orientation so we are not losing track of it. Ketone goes here, ester is gone
and what's left over is an ethyl group, so if we mark out where everything came from,
and count our carbons on our exams, then we won't make a mistake here, we have a beta
keto ester from the claisen.