By now, we are pros at EAS.
We understand electrophilic aromatic substitution very well.
But it turns out that that's not the only substitution mechanism that benzene can undergo.
It turns out that in the presence of strong nucleophiles, benzene can actually be made
to do a nucleophilic aromatic substitution also call SNAr.
Unlike EAS where the addition step is initiated by the presence of a strong electrophile.
Remember that we’re always trying to make that strong e plus and then the benzene attacks.
It turns out that you can also start another addition elimination reaction with benzene
by a strong nucleophile attacking the benzene.
You might imagine, this must be a very strong nucleophile.
It actually attacks such a negative entity.
But the thing is you also need a good leaving group on your benzenes.
You’re going to need something that you can kick out when the electrons get there.
In some ways, this reminds us a little bit of SN2 because remember that SN2 was a backside
attack.
It was nucleophilic substitution.
This is also nucleophilic substitution.
The only thing is that it's not concerted.
It's a two-step reaction.
It’s distinct addition and elimination step.
There are similarities but then there are also differences.
Again, this is called a lot of different things.
It's known as instead EAS, it’s known as nucleophilic aromatic substitution.
It's not abbreviates NAS.
Don’t call it that.
That’s something different.
It’s called SNAr.
The SNAr mechanism is nucleophilic aromatic substitution.
Also in some text, it’s even called the ipso-substitution.
That just refers to the fact that you have two groups sharing a carbon for a little bit
in the intermediate.
Let's go ahead and remind ourselves of EAS.
We don’t really need to but we’ll quickly run through it so you guys can see how SNAr
is similar and different at the same time.
Remember that your first step is always the slow step to create the sigma-complex.
This is a cationic sigma-complex because you get a positive charge.
That positive charge is distributed throughout the entire thing.
We could just draw that as a dotted line with the positive in the middle.
Remember that after the resonance structures, etc. you get an elimination step and that’s
a beta elimination where you grab an H, you reform the double bond and you’d get a substitution
product that we started off by an electrophile, so EAS.
With SNAr, the reaction is really much, much different.
What we get is that the reaction starts off with a nucleophile attacking the benzene.
It’s going to attack the site where there is a strong or a good leaving group.
Unlike SN2, where I immediately would have just kicked out my leaving group and it would
have been backside attack and that’s done.
This is not backside attack because there is no backside.
It’s two steps, meaning that what we're going to do is we're going to break a bond
on the benzene and make an anionic intermediate.
We're going to get instead of a catatonic sigma complex, we’re going to get a negative
charge that’s distributed throughout the same five atoms.
This is what we call the anionic sigma complex.
It’s similar but it's a negative charge instead of a positive charge.
Then what happens?
Eventually the negative charge is going to reform a double bond.
Eventually the negative charge is going to reform a double bond, kick out my X and I'm
going to get in my elimination step, I get my nucleophile substituting where the X was.
As you can imagine, this anionic intermediate is extremely unstable because benzene already
has so many electrons, and putting a negative charge in there, that’s going to suck.
Typically, we're going to need lots of heat and lots of pressure to make these work.
In early example of this was a reaction called the Dow Process that was actually started
by the company Dow.
It was an early method to make phenol.
But they had to work for it.
The way they worked it was they got chlorobenzene and they reacted NaOH, which we know is a
strong nucleophile with 350 degrees Celsius and high-pressure.
We need all that so that we can actually make the intermediate.
Remember the intermediate would look like this.
You attack and then you break off into a lone pair on the top.
What I want to do is draw the resonance structures.
Let's do that.
The resonance structures for this would look for this anionic intermediate would look like
this.
I have Cl, OH, double bond, double bond, negative charge.
That's going to make a bond and break a bond.
I’m going to get something that looks like this.
That is going to again make a bond and break a bond.
Then I'm going to get something like this.
What happens at the end?
At the end, remember I said there’s an elimination step.
The elimination is that it's self-eliminating.
The lone pair reforms a double bond and kicks out the chlorine.
That is going to give us basically phenol.
In this case because it happened in a basic environment, deprotonation does take place.
Usually you’re going to need an extra equivalent of acid to turn the phenoxide into phenol.
This is an early method of making phenols that used the SNAr mechanism.
But it wasn't very efficient.
This is not how modern-day phenols are made.
Made much more simply in other ways.
Now that we understand the general mechanism of SNAr, let's explore a little bit more on
the next page.