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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

Ready for some practice on Aromatic synthesis? You probably have done problems similar to this before but now we want to work specifically using diazo replacement reactions

Concept #1: Proposing Aromatic Synthesis


Now we're going to get some practice proposing aromatic synthesis specifically diazo replacement reactions.
So as you guys know, a big part of this topic is being able to turn a smaller benzene into a bigger one. We must use our knowledge of sequence groups and blocking groups to plan out our synthesis in the correct order.
So guys, you should have already had some practice with this at this point. So I'm going to leave these up to you completely. Go ahead and try to do this one from scratch with everything you know about diazo and then I'll step in and show you guys the answer. So go for it. 

Example #1: Synthesize the target molecule


Alright, so we start off with toluene and we ended up with I guess m-cyanobenzoic acid. So a few things going on here first of all I need to figure out how to turn a methyl group into a carboxylic acid. Not sure if you guys can help me with that. Also I need to add a C N group to the metaposition. So at some point I need to turn this into a metadirector. Also what's the fastest way to add a C N group? This isn't the only way to add C N, but the fastest way is going to be use diazonium because we can't use EAS and any other method is going to take way too long. So diazonium is the way to go.

So that means that I should add at some point I should do a diazonium reaction but only after this thing is a meta director so the first reaction I should use is my hot potassium permanganate. So I should do K M N O 4, base heat and acid. What that's going to give me is a meta director. I'm going to get C O H. Now from there I can go ahead and I can do my diazotisation but I need to first just add something that could even become a diazo so that would be a nitro group. So I have to do a nitration. So I'm going to do H N O 3 and sulphuric acid and that's going to give me a nitro group and then from here just the rest of the reactions take over so then three I would do my reduction which if you used a different reducing agent actually it could be a problem. Actually that's a good point. Guys, this is actually the only reducing agent you're allowed to use, S N C L 2 H 2 O. The reason is because if you use L A, like lithium aluminium hydride, what's going to happen? You're going to reduce the carboxylic acid, remember that carboxylic acids react with lithium aluminium hydride, it's going to turn it into an alcohol or what if you use catalytic hydrogenation? There's still a chance that it could react. You want to use a chemoselective reduction in this case which is your stannous chloride. Alright I'm going to put here chemoselective so you guys remember that really you should get used to using the stannous chloride because it's the only one that really selects specifically for nitrile groups.

So now that's going to give me something like this where I still have my carboxylic acid but now I have an annulene, now my next reagent should be my diazo. That's going to give me a molecule that looks like this, C O H and N 2 positive and finally we're at the end and I can use my fifth reagent which is going to be C U C N and that's going to give me my final product. Alright, so guys that was a five step synthesis which is totally normal that's very common in this section of the text to find five, six, eight step synthesis but what you'll notice is that it's not that hard because the pathway once we got to the nitration part it's always going to be the same reactions over and over so it's not that bad. So go ahead and analyse the next question and see if you can come up with the right synthesis.

Example #2: Synthesize the target molecule


Alright guys, so I think this one might have been a little too hard for you considering that you just learned how to use diazo replacement reactions but I just want to show you an example of a more advanced synthesis that requires pretty much all the different directing effects we've talked about. Before we begin let's look at a few interesting things here. First of all notice that I need to add a chlorine in this position here which is tricky because my end product has a meta director here, this is meta director. So I'm probably going to want to add the chlorine before I turn this into a meta director. Right now this is currently an o, p director so I'm probably going to want to add the chlorine before I turn it into a carboxylic acid, cool? Awesome, what else? Notice that I also have to add an O H here, let's add an OH here, but this chlorine is meta to it so I probably want to have some kind of meta director here before I add that chlorine because once that alcohol is there it's going to switch it to an o, p director. So these are just some things to consider. Also notice that I was able to turn a methyl into carboxylic acid but not a tert-butyl group. Does that make sense? Yeah, that part actually is pretty easy. Remember that tert-butyl groups are going to be immune to K M N O 4 because they don't have any hydrogens to oxidise. Alright, so let's go for it. Our very first that guys is going to be to put a meta director in this position and thankfully I have ortho, para directors on both sides so that's pretty easy. I can use H N O 3 and sulphuric acid. So I can use a nitration. I'm going to try to follow along every step of the way, I'll show you guys what I'm doing. So what I'm going to get here is I'm going to gets a nitrile and my methyl. Now at this point I totally could add the chlorine now if I wanted to because I have a meta director that's going to push my chlorine to form here so why don't we try that? Why don't we do the chlorination now. So I'm going to add F E, oops, C O 2 over F E C L 3, that's going to give me a molecule that looks like this. N O 2 and I have a chlorine here. Notice that all my substituents were synergistic so that's perfect. Cool. So what else? So now I've got that chlorine in place, I eventually got to turn that nitrile group into an alcohol. Do I know how to turn nitro into a phenol? It's a lot of steps but yeah you have to go through the diazo pathway.

Awesome, now on top of that I need to end up with a nitro so I should probably start turning this into a phenol and then add that nitrile later when I have an ortho, para director so we could go ahead and do the next step which is let's reduce this nitro. Now what reducing agent would you guys recommend? If I want to reduce this, I'm trying to reduce the nitro so I can get to an annulene so that I can do a diazo replacement reaction. So I definitely should use stannous chloride. I definitely need to use stannous chloride because that chlorine could actually be reduced by a strong reducing agent to a hydrogen. So I'm going to go ahead and use stannous chloride, that's going to give me a molecule that looks like this and then I'm going to make it a diazo so I'm going to use my nitric acid and that's going to make it C L, now this is going to be N 2 positive tert-butyl and methyl. So now I'm, there's no reason that I can't turn it into the phenol especially because the phenol is going to be an o, p director so it's actually going to be in my best interest to turn it into a phenol. So the reagents to turn it into a phenol are I mean technically I could just use water right so I could just use water, water with a diazo group is going to replace, let's see if I can fit all this in the screen, and turn it into a phenol. Awesome, so guys now notice that, we still need to add a nitrile group and the nitrile group would be synergistic to add here if I was using if I'm looking at this and this group but these two groups disagree. Is there anything I can do to get more groups to agree to that location? Actually, yeah. What I could do now is I could do, oops, I could do my oxidation step to turn this methyl into a meta director so now I have at least one more synergistic group. So what I'm going to do is I'm going to use 6 K M N O 4, base heat and acid and what that's going to give me is it's going to give me a molecule that looks like this, chlorine, O H and now C O O H. And now finally I'm ready to do my nitration. Because I have pretty much all synergistic groups except for one so I'm going to get a high yield and I will just use my sulphuric, you know, my nitration again so that's going to give me a molecule that looks like this. Okay guys, so that one was seven steps. Kind of intense, seven steps is definitely too intense for the level that we are at right now. Definitely this should have been like the tenth question that you saw or eighth question, not the second but I wanted to show you guys an easy one and a hard one just so that you guys would see kind of the ways that EAS and diazo play together and you have to use them together. Now keep in mind that some professors actually do ask for seven step synthesis it just depends on who your professor is and how hard they test but hopefully that made sense. Let's move on to the next topic.