hey it's professor Dave, let's talk about Williamson ether synthesis.
so we know what an ether is, it's a functional group with an oxygen atom
bound to two alkyl groups and so now that we know what an ether is we want to
figure out some ways to synthesize ethers and one way that's very common is
the Williamson ether synthesis, and it's actually extremely straightforward
mechanistically. there's not too much going on here, all that we need to do is
we start with some alcohol and we're gonna do an acid-base reaction so we
need to deprotonate that alcohol and a very common base that we're gonna use is
sodium hydride, and the reason is this we don't want any competing chemistry, all
we want to do is deprotonate this alcohol. that's all we want to do and
hydride is great at doing that and what happens is once this hydride grabs that
proton we've got hydrogen gas that's just gonna bubble up and leave solution
and it's not gonna interfere, it's not going to do any more chemistry. so that's
why this is an extremely common base that is used for Williamson ether
synthesis. sodium hydride hydride is gonna grab that proton, we're left with
the alkoxide now an alkoxide we know certainly can do SN2 and so why don't we
just do SN2 on some alkyl halide, in this case ethyl bromide and we can kick that
off and here is that new bond that we formed right we have formed a bond and
we have tacked on these two carbons right here so those two carbons got
added on there and now we have an ether because we do have, we have an ethyl
isopropyl ether, we've got an oxygen bound to two alkyl groups so once again
mechanistically extremely straightforward, all we are doing is
deprotonating an alcohol, we're doing an acid-base reaction with an alcohol to
get an alkoxide and then that alkoxide is going to do SN2 on some alkyl halide
and we're gonna get an ether. so in terms of sterics obviously this is
going to work best when either or both of the alkoxide and the alkyl halide are
relatively unhindered. in this case we do have a primary alkyl bromide so that's
an ideal candidate for this reaction. as you start adding more steric bulk to
either of these reagents it's going to limit your yield, it's not
going to work as well but once again that is our general overview for the
Williamson ether synthesis.
so now that we understand the reaction let's just go over a couple of examples.
some things that look like maybe something you'd see on a test we do need
to be able to look at a substrate and draw a potential product or maybe even
see a product and draw what the substrate must have been, and so this is
a little the only thing that's trickier with this than some of the other
reactions whereas with some of the addition reactions we can identify a
reagent and we know that the only time we see that reagent is for
oxymercuration demercuration and so we can immediately make that make that that
correlation there this is a little tougher because we're not seeing that
maybe with sodium hydride we might recognize it but that just means we have
to think critically right if we see this kind of situation we've got we've got
this alcohol and we know that hydride is going to do an acid-base reaction right
we can look at this, we know that the only acidic proton is that or even
remotely acidic proton is the hydroxyl proton and so we know that we're going
to deprotonate there and then the resulting alkoxide is going to attack
ethyl bromide. so all we have to do is put this on this oxygen so let's draw
that product right we know that when we do Williamson ether synthesis we're
gonna make the alkoxide so after the deprotonation we've got O minus, we've got
the alkoxide and then that is going to go ahead and get to get that two carbon
fragment on there. so that is our product there. alright so once again right
hydroxyl hydride acid base resulting alkoxide will have this two carbon will do
SN2 will get that two carbon fragment on there so that's an ether that we've made.
now looking at this one what if we need to go backwards? this is really not any
more difficult we're just going the other direction, we're saying that we did
some Williamson ether synthesis to produce this ether right so what did we
start from? well what is the what is the alkyl halide that was involved in the
SN2 step, well that's this right here we have got this four carbon fragment right
one two three four carbons that is the that is the alkyl halide that was
involved in the SN2. where is that in the product?
well that's obviously this right it's not that it's not that five membered
ring so we know that an alkoxide attacked this to get that. that means
that this was before it was off the molecule and this was the alcohol so the
rest of the molecule was the alcohol so that means that we must have started
from cyclopentane all right cyclopentanol reacted with sodium hydride
we lost that proton and then that alkoxide attacked right there and we got
that four carbon fragment on to make our product. okay so that's how that's the
logic we want to employ in the opposite direction. let's look at one more
a slightly more interesting situation, let's say we're
doing this in we can even do this just in aqueous base let me just show that
oxygen hydrogen bond right there so let's say we're doing this in aqueous
base we've got hydroxide we've got a hydroxyl we know that that's going to be
a pretty easy equilibrium if those collide we're gonna be able to transfer
that proton so let's say we go ahead and get that proton and now let's make that
alkoxide so we've got this situation here so what can happen here this is a
situation where we've got an alkoxide and an alkyl halide on the same molecule
here so we can do actually an intramolecular reaction, we can have this
alkoxide go ahead and attack right there and this molecule will cyclize now so
how many how many members in the ring how many members will be in that ring
we've got one right that oxygen is going to be in it two three four five we know
that this is going to attack here and we're gonna make a five membered ring
right so that will be this that is our 1 2 3 4 5 this was the carbon that had the
chlorine on there but that got kicked off so this is our way this is the way
that we made a cyclic ether so these are some different
examples now that we understand Williamson Williamson ether synthesis
some examples of what we can do in both the forward and reverse direction