Synthesis of substituted benzene rings I

Now that we know all of our reactions, let's see if we can put those reactions together to synthesize some simple organic compounds. And so our goal is to make this molecule from benzene. And one approach that you can use is the concept of retrosynthesis. So you try to think backwards, and you think to yourself, what can be an immediate precursor to this molecule? Well, to do that, we have to analyze the groups that are attached to our ring. And so if I look at this bromine up here, I know this bromine is an ortho/para director, because I know it has lone pairs of electrons around it. So this bromine is an ortho/para director. But look at the nitro group. I know this is a meta director. I know it's meta because there's a plus 1 formal charge on that nitrogen. And then, over here, for this acyl group attached to our ring, I know this is also a meta director, because this carbonyl carbon right here, is partially positive, like that. And so when we try to figure out which of these groups was added last, it makes sense that the bromine was added last because this bromine right here is meta to both our nitro group and our acyl group. And so we can go ahead and draw the precursor. We go ahead and just take the bromine off. So we're left with a benzene ring. And we have an acyl group on our ring, and we also have a nitro group. So next we just have to remember how to put a bromine on a benzene ring, and of course it's a bromination reaction. So you would need some bromine and a catalyst, so something like iron bromide. So FeBr3 will work for that. All right, let's see if we can figure out the next precursor here. So what could we do to make this molecule? Well, once again, we have two groups on here. We have a nitro group, and we have an acyl group. So we could do a nitration to put the nitro group on, and we could do a Friedel-Crafts acylation to put this acyl group on our ring. So the question is which one of these comes first? And it turns out that you can't really do a Friedel-Crafts alkylation or acylation with a moderate or strongly deactivating group already on your ring. And this nitro group here is strongly deactivating, which means we can't put the nitro group on first and then add our acyl group. The acyl group must come on before the nitro group, which means in this step, we're going to put on the nitro group. So the immediate precursor to this molecule-- we just take off our nitro group, and we're left with our benzene ring and an acyl group attached to our benzene ring like that. And so we need to do a nitration, which requires, of course, concentrated nitric acid and also concentrated sulfuric acid like that. All right, now all we have to do is go from benzene to this molecule. And we know how to do that, of course. That's a Friedel-Crafts acylation reaction. And so when we think about what kind of acyl chloride we're going to use, just count the number of carbons here, so 1, and then 2. So we need a 2 carbon acyl chloride. So we're going to draw here a 2 carbon acyl chloride like that. And then we need a catalyst. Something like aluminum chloride will work for our catalyst. So our synthesis is complete. We start with a Friedel-Crafts acylation. And the acyl group is a meta director, which would direct the nitro group to the meta position. And then, finally, we have two meta directors, which we now brominate, which would direct the bromine to the final position. And we are complete. Let's do another problem here. And, actually, it's the exact same groups that we just saw in the previous problem, but this target molecule looks a little bit different. And so we're going to need to do the reactions that we did in the previous synthesis in a different order here. So once again, let's start by analyzing the groups. So once again, we know that this bromine is an ortho/para director because of the lone pairs of electrons on it. We know the nitro group is a meta director because of the plus 1 formal charge. And our acyl group is a meta director because of the partial positive charge on our carbonyl carbon, right here. So when we look at those groups, and we think about which of those reactions was done last, it makes sense that this nitration was done last. And that's because this nitro group is meta to our acyl group, because our acyl group is a meta director, and our bromine, more importantly, is an ortho/para director. And of course the nitro group is ortho to the bromine. And so it makes sense the last reaction was a nitration reaction. So, to draw the precursor to this, all we do is take off that nitro group, and we would have our benzene ring, like this. And we would have a bromine on our ring, and would already have our acyl group on our ring, like that. So our last reaction was a nitration reaction. So we need to add, once again, concentrated nitric acid and concentrated sulfuric acid for our nitration. So when we think about the precursor to this molecule-- so once again, we have an ortho/para director on our ring, and we have a meta director on our ring. And we have our groups. Our bromine and our acyl group are para to each other, which means that the ortho/para director directed the acyl group to the para position as the major product. And so we can think about doing a Friedel-Crafts acylation reaction here. So that means that we're taking off the acyl group. So we're left with bromobenzene to start with over here, like that. So we have bromobenzene, and we're doing a Friedel-Crafts acylation. And, once again, we need 2 carbons on our acyl group. So let me just point that out, 1 and 2. So we need a 2 carbon acyl chloride. So go ahead and put on a 2 carbon acyl chloride, like that. Once again, our catalyst, something like aluminum chloride, will work. And you might think to yourself that I know that the halogen, the bromine, is deactivating. So how can we do a Friedel-Crafts acylation with a deactivating group on there, even though it's an ortho/para director? Well, remember, it's only weakly deactivating. And so you can't do an alkylation or acylation with a moderate or strongly deactivating group. And so it turns out, since this is weakly deactivating, you can still do this, and you'll get the para product as your major product over here. So I'm sure you'd get a little bit of ortho as well. All right, so now all we have to do is go from benzene to bromobenzene And, of course, that's really simple. It's just a bromination reaction again. So we have our bromine, and then we have our catalyst, and then our synthesis is complete. So for this time, we start out with a bromination reaction to form bromobenzene. The bromine is an ortho/para director. This is an ortho/para director. And so it's going to put to this acyl group on our ring in the para position as our major product, here. And then, of course, we nitrate it, and we have an ortho/para director and a meta director, which means the nitro group will end up in this position. And we're done. So that's how to think about the synthesis problem, so retro synthesis, working backwards, thinking about target molecules. And we'll do two more in the next video, which are maybe a little bit harder than these two.