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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

We've learned about blocking groups before with sulfonic acid (SO3H), but now let's see how we can use a diazo group (N2) to function the same way. 

Concept #1: Sequence Groups


Now that we know about diazo replacement reactions, we have to take that into account when we think about sequence groups.
As you guys might recall, sequence groups are groups that have the ability to alter the sequence of an aromatic synthesis. They’re groups that can be easily transformed from one type of director to another. We have examples of this in EAS. But now, we have diazo reactions as well that you have to take into account. Here's another definition. Blocking groups. It’s a blocking group. Remember that a blocking group is a group that really only acts to direct the other reactions and then it's completely removed. The only way that you would know that it was there is because you can see what it did. But not because it’s actually there anymore.
It turns out that now that we know about H3PO2 or hypophosphorous acid, that group is used to block the para position and force ortho substitution. How? Because we know that we can remove diazo with H3PO2. That means that we can use diazo compounds as blocking groups and then easily remove them after.
Let's talk about some that we already know.
Clemmensen reduction. Clemmensen reduction takes a meta-director. When you react zinc and mercury over HCl, you’re going to get an o,p-director. That’s a sequence group because I just changed the directing effects of my substituent.
Side chain oxidation. I know that I can oxidize an R-group using KMnO4 and base and heat and acid. I can oxidize it to a benzoic acid. Meaning that it starts off as an o,p-director and it ends off as a meta-director.
We know that another sequence group would be reduction of amide and nitro groups. In this case, I'm doing a nitro but amides can reduce as well. We’ll learn more about that in your amines chapter. Don’t worry too much. But anyway, we know that reducing agents love to reduce nitro groups. Obviously we could use lithium aluminum hydride. There’s a few others that we've learned. You guys know my favorite. We could use the stannous chloride. That would reduce my nitro to an aniline. But now here we go.
Here's the diazo reaction specifically. For diazo, I could start off with diazo. Notice that this is a meta-director because of the fact there's a full positive charge. What type of director would that be? You’d have to be meta because it’s a strong deactivator. After I change it out with the replacement reaction, I could make it into a donating group or an ortho,para-director.
Can you think of a diazo replacement reaction that could make a donating group instead of a withdrawing group? Can you think of one that would turn it into an ortho,para-director? Just so you guys know, there's plenty that you could use. But one of the easiest would be just water. What would water do as an example? I’m just going to put here ie because this is just an example. Water would turn my diazo into phenol. Once it’s phenol, what kind of director is that? Ortho para. You can see there's a lot of other ones that we could choose that are ortho,para-directors.
Finally, we have diazo substitution with a proton. You start off with diazo. That’s a meta-director but you could use it as a blocking group. If you react it with H3PO2, you’re going to wind up replacing it with H and this is our blocking group because what you do is you block that site from reaction. You can react something else somewhere else and then take it off.
These are things that we have to keep in mind when we do synthetic synthesis with diazo reactions. We have to keep all of these sequence groups in mind. Let’s move on to the next topic.