Concept: Concept: Sequence Groups6m
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.
Predict the major product for the following reaction
Predict the product of the following multi-step synthesis. Show the intermediates resulting from each step. Assume that each reaction will occur.
Provide the reagents necessary to effect the following transformation: