Now that we understand a little bit about the SNAr mechanism, let's talk about something
called the Meisenheimer Complex.
As mentioned earlier, the Dow Process was a typical SNAr reaction but it required tons
of heat and pressure to proceed forward.
This is due to the instability of the anionic intermediate.
But it turns out that scientists figured out that there are ways to naturally stabilize
the antibiotic intermediate that are going to make it require less heat and less pressure.
The rule that we use for that is WHOP.
It's going to be withdrawing groups or heteroatoms in the ortho para positions will stabilize
the intermediate.
We're basically looking for things.
Remember that that anionic intermediate goes to the ortho and para positions relative to
the nucleophile.
That's exactly what we're trying to do here.
What we're trying to do is we're trying to use atoms in those ortho and para positions
to stabilize that negative charge.
A classical trinitrobenzene.
Think about it.
Is nitro a good withdrawing group?
It’s the best.
It's one of the best electron-withdrawing group.
If you use a trinitrobenzene Meisenheimer complex, the reaction can actually proceed
forward at room temperature.
What is a Meisenheimer complex?
A Meisenheimer complex is just what I'm saying, a WHOP.
A Meisenheimer complex is like an ultimate WHOP where you have a molecule that has either
heteroatoms or withdrawing groups in the ortho and para position.
I'm going to just say that that's literally those are synonyms of each other.
A Meisenheimer complex is just any benzene that is in a WHOP formation.
Let's take a look at this.
Here I have, once again, a strong nucleophile, OCH3- and I have a leaving group.
But notice that on my ortho and para positions, I have all withdrawing groups.
Normally for the Dow Process, I would have required 350 degrees Celsius to proceed forward.
But it turns out these withdrawing groups are so stable, are so strong that I'm actually
going to be able to proceed forward at room temperature.
35 is a little bit warm for room but it could be a hot room.
Let's look at this mechanism.
Basically your negative is going to attack the leaving group but you're going to make
an anionic intermediate.
You're going to make a negative charge that's now stabilized by my withdrawing group and
we can draw resonance structures for this.
We would have resonance structures, tons of resonance structures.
Let me just show you a few of them.
We're not going to draw all of them because there's a lot – Cl, OCH3.
Notice what's going to happen is that nitro looks like this.
Not only will the negative charge be able to resonate through the ring, it can even
resonate with the nitro group.
We can get something that looks like this.
We can get resonance structures that form within the nitro groups
giving us something like this.
By the way, that was supposed to have a plus.
See how that resonance structure exists.
We can also draw resonance structures of the negative charge moving to the next nitro.
Then that would be another resonance structure.
Altogether there's going to be like six resonance structures.
We're not going to draw all of them, that's for sure.
But I'm just trying to show you guys how a Meisenheimer complex works.
Anywhere that this negative charge goes, it's stabilized by withdrawing groups.
Eventually what winds up happening is that the negative charge is going to reform a double
bond and it's going to kick out the CO.
What you're going to wind up getting is an SNAr product because you've got a substitution
that occurred but it was for a nucleophilic reason.
It wasn't for an electrophilic molecule.
It’s for a nucleophilic molecule that had occurred.
That's what a Meisenheimer Complex is.
It doesn't just have to look like this.
It could be any combination of withdrawing groups and heteroatoms.
That means if I just put a nitrogen inside the ring here, that would qualify as a heteroatom
because now I have a non-carbon atom inside the ring and non-carbon atoms are more electronegative.
They're also good at stabilizing negative charges.
It's not just withdrawing groups.
It’s also heteroatoms that will help.
We're going to look at the following two reactions that says use resonance structures to determine
which of the following ipso-substitutions is more favored.
Remember that ipso-substitution is just another name for SNAr.
Go ahead and look at both of these.
Try to draw resonance structures and then figure out which one is going to be the more
favored reaction.