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Ch. 18 - Reactions of Aromatics: EAS and BeyondWorksheetSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins
Ch. 26 - Transition Metals
Electrophilic Aromatic Substitution
Benzene Reactions
EAS: Halogenation Mechanism
EAS: Nitration Mechanism
EAS: Friedel-Crafts Alkylation Mechanism
EAS: Friedel-Crafts Acylation Mechanism
EAS: Any Carbocation Mechanism
Electron Withdrawing Groups
EAS: Ortho vs. Para Positions
Acylation of Aniline
Limitations of Friedel-Crafts Alkyation
Advantages of Friedel-Crafts Acylation
Blocking Groups - Sulfonic Acid
EAS: Synergistic and Competitive Groups
Side-Chain Halogenation
Side-Chain Oxidation
Birch Reduction
EAS: Sequence Groups
EAS: Retrosynthesis
Diazo Replacement Reactions
Diazo Sequence Groups
Diazo Retrosynthesis
Nucleophilic Aromatic Substitution

Friedel-Crafts Alkylation has several limitations that render it almost useless in the lab. Let's take a look at 4 examples of what these limitations could be.

Concept #1: Limitations


In this video, we’re going to review some of the major important limitations of Friedel Crafts Alkylation. It turns out that Friedel Crafts Alkylation isn’t all it's cracked up to be. The mechanism was simple. The mechanism makes sense. But it turns out it doesn't work that well. Why? There’s actually several reasons. I'll just go into them one by one.
The first limitation just makes sense. It doesn't react with vinyl or aryl halides. If you have a halogen directly on a double bond, that carbocation is going to be far too unstable. You're not going to get that reaction to happen. Here's an example. Let's say that I have a benzene and I’m reacting it with chlorobenzene and AlCl3. We would expect that the first step of this mechanism would be that the chlorine bond gives its electrons to the aluminum. What I wind up getting is a carbocation that looks like this.
What do you think about that carbocation? That’s a really unstable carbocation because it can’t resonate anywhere. It’s stuck. It's on a double bond. That’s one of the worst most unstable carbocation. I’m going to say “too unstable”. The answer here is that if you’re working with an aryl or vinyl alkyl halide, no reaction. You're not going to get a reaction with Friedel Crafts Alkylation. The solution will be to avoid these molecules. There's nothing we can do to get around it. Just avoid those. You can't use them.
Let's go into the next limitation. This one makes sense, guys. It turns out that aniline derivatives are going to ruin the Lewis acid catalyst because if you guys recall, this is the most basic lone pair really possible on a benzene. AlCl3 is one of the strongest acids. It's a strong Lewis acid. Guess what’s going to happen. Usually we would expect that the bond between the alkyl halide would donate to the empty orbital. But that's not what happens because it's going to compete with the lone pair from the nitrogen and the aniline is actually just going to complex with itself. What you wind up getting is a ruined molecule because now what you have is here’s my benzene, here’s my nitrogen, here’s my H’s. It’s actually going to be attached directly to the AlCl3. It’s going to make what we call an adduct. But this is a ruined catalyst because now it's not a catalyst anymore. It just got consumed because good luck separating that bond. We've got a positive. We’ve got a negative. Those things are really attracted to each other. Good luck separating. It’s made an adduct. It’s not separating at all.
The answer here is that if you're trying to run a Friedel Crafts Alkylation on a benzene, make sure that you avoid aniline at all costs. You cannot use aniline and a Lewis acid catalyst. The answer here would actually be the adduct. It would just be the adduct that I showed earlier. But it would not be the right reaction. It would be this thing here. It wouldn’t be the correct thing that you’re waiting for which is actually you put an R-group here. You would not an R-group. That would not happen.
The first thing that you should think is just like avoid these things at all costs. But there is another way that you could prevent this from happening. Some of you guys have learned about acetylation already through my Clutch videos. Some of you haven’t. If you haven't learned about acetylation, don't worry about it because that means I purposely did not teach you that video because your classroom doesn’t it need. But for those of you that did learn the acetylation video, you understand and looking back at that video that acetylation of the aniline wouldn’t work because what you would do is you would form a nitrogen with a carbonyl on it. That nitrogen would not be quite as basic. This one actually could work. If you acetylate it and then reversibly deacetylate it, then that would work. But for most of you guys, if you did not see that content, then just ignore it because that means your professor really doesn't care about that with avoiding the adduct. That’s the second limitation. The first one was you can't use certain alkyl halides. The second one is don't use aniline.
There's more. It turns out that alkylation reactions, because we learned that R-groups are what? They’re electron-donating groups. Remember that R-groups are electron-donating groups. Since they're electron-donating groups, they're going to activate the ring towards further reaction. When you add that first R-group, it’s going to make it more reactive for the second reaction.
Another thing. Alkylation reactions are susceptible to carbocation rearrangements. Remember that because you form a full carbocation they can move around. These limitations are piling up because you're trying to do a synthesis but you've got all these problems. You've got a rearrangement. You've got extra activity which we’ll talk about why that's important in a second. You can’t react with aniline. It turns out that the solution for both of these two guys, for the activation and for the carbocation rearrangements is to acylate instead. What I mean by acylate isn’t what I talked about at the top. That's what I mean is Friedel Crafts Acylation. Friedel Crafts Acylation would be using an acid chloride and a Lewis Acid Catalyst. Acylate instead. How does that work? How does that make sense?
Let's look at these two examples of alkylation versus acylation. Let me show you guys why acylation is better. Alkylation, notice that the intermediate of my alkylated inner of my alkylation reaction is going to be a carbocation, R plus. Notice that the intermediate of my acylation is going to be what we called the acylium ion that looked like this: C double bond O plus R.
First of all, are both of these going to rearrange? No, only one would rearrange. This one has shifts but this one has no shifts. We can see that if we can use acylation, acylation is going to be safer for us to use because we know that acylation we don't have to worry about shifts. That’s the first thing. Now let’s look at the product. What happens when I add these groups? For my benzene ring with the alkylation group, I’m going to get an R group. When I add my acyl group, what I’m going to wind up getting is a ketone.
What's the difference between both of these in terms of activity? There's a huge difference because notice that this is an electron-donating group but notice that a ketone since it has a partial positive is actually an electron-withdrawing group. One is an election-donating group. One is an electron-withdrawing group. Why is that important that? Because if you add an electron-donating group, this is going to be more activated. If it’s more activated, that means that once it sees another alkyl halide, it’s going to want to react again. You're going to wind up getting polysubstitution. You're going to wind up getting a benzene that not only has one R-group but maybe it has two or maybe it has three. This is bad. I’m just going to put a sad face. You’re going to get a polysubstitution because now you’re going to get R-groups everywhere and it's difficult to stop. Remember that I told you guys that toluene is 25 times more reactive than benzene. What do you think happens when I have two toluenes or a xylene? Two R-groups. That’s even more reactive. It almost spirals out of control. You can't stop it. It starts adding R-groups everywhere so you start getting sad. Maybe you shed a tear.
But what happens with electron-withdrawing groups? Electron-withdrawing groups is going to make it less activated. What do you think happens when it sees the second acylium ion? Does it go attack it? No, the answer is this doesn't happen. There's no reaction. It stays at monosubstitution. That makes me happy because that's what I wanted the whole time. The whole time I didn't want some mess of polysubstitution. I wanted just one thing on my benzene ring. That's what I get with acylation. Not only that, I'm also happy because I didn’t have a rearrangement that messed up my yield. I just got exactly what I was looking for.
Now you guys can see. You’re getting a hint of why acylation is more advantageous to use than alkylation. Now what I want to do is really drive home this point of what acylation is better. We're going to learn some extra information of how you can use acylation instead of an alkylation in pretty much all situations. 

Practice: Provide the major product and the correct mechanism for the following reaction. 

Practice: Provide the major product and the correct mechanism for the following reaction.