Now that we know about diazole 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, and there are groups that can be easily transformed from one type of director to another. We have examples of this in Electrophilic Aromatic Substitution (EAS). But now we have diazole reactions as well that you have to consider. Here's another definition, guys: Blocking groups. What's a blocking group? Remember that a blocking group is a group that really only acts to direct 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 H3P1O2 or hypophosphorus acid, that group is used to block the para position and force ortho substitution. How? Because we know that we can remove a diazole group with H3PO2. That means that we can use diazole compounds as blocking groups and then easily remove them afterward.
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 ortho, para director. It's a sequence group because I just changed the direction of 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 started off as an ortho, para director and ends off as a meta director. We know that another sequence group would be reduction. We learned 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 are a few others that we've learned. You guys know my favorite. We could use stannous chloride. That would reduce my nitro to an aniline. But now here we go. Here's the diazole reaction specifically. For diazole, I could start off with diazo. Notice that this is a meta director. Because of the fact that there's a full positive charge, what type of director would that be? It has 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 guys think of a substitution, or I'm sorry, a diazole 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 how about just water? What would water do as an example? I'm just going to put here i.e., because this is just an example. Water would turn my diazole into phenol. Once it's phenol, what kind of director is that? Ortho, para. Cool? So you guys can see and there are a lot of other ones that we could choose that are ortho, para directors. Then finally, we have diazole substitution with a proton. You start off with diazole. That's a meta director. But you could use it as a blocking group. So 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. So you can react something else somewhere else and then take it off. These are the 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.
