Meso Compound: Study with Video Lessons, Practice Problems & Examples

Meso compounds are unique molecules with two or more chiral centers that exhibit achirality due to internal symmetry. To identify meso compounds, ensure there are at least two chiral centers, the molecule is atomically symmetrical, and the chiral centers are oppositely configured (e.g., one R and one S). This results in identical diastereomers, leading to the application of the 2ⁿ - 1 rule for calculating stereoisomers, where n is the number of chiral centers. Understanding these concepts is crucial for mastering stereochemistry.

Defining meso compounds.

So now I want to talk about another exception to the chirality rules that I taught you. And this exception has to do with the rule about 2 or more chiral centers. Remember that I told you guys that if a molecule has 2 or more chiral centers, that it's pretty much always going to be chiral, just assume that it's chiral. It turns out that there is one exception to that, and that's meso compounds. So let's go ahead and get into this.

Meso compounds are specific types of molecules where you basically have 2 chiral centers that perfectly cancel out, yielding 2 identical diastereomers. What that means is that after forming these stereoisomers, 2 of them are going to wind up being the same, meaning that it's actually going to be achiral.

There are a few facts that you should know about meso compounds. First of all, meso compounds have an internal line of symmetry. Remember test 1 had to do with the internal line of symmetry? So that means many times we actually will be able to use test 1 to predict that they're actually achiral.

But sometimes we're not going to be able to use that test, which is why I'm going to give you guys some other rules specifically for meso compounds. It turns out that because 2 of the stereoisomers are identical, instead of following the 2n rule for the total number of stereoisomers, we're actually going to follow the 2n-1 rule for stereoisomers. What that means is that that minus one accounts for the fact that 2 of these stereoisomers are going to turn out to be identical, so instead of, for example, having 4 total stereoisomers, if I had 2 stereocenters, it would turn out to be 3 instead of 4 because 2 of them would turn out to be identical.

The 3 rules of meso compounds.

But I know what you guys are interested in is these rules. Right? So let's talk about these rules. There are three rules that will help us predict if a molecule is meso. Believe me, this is going to help you so much because in your textbook and according to your professor, it's very difficult to tell when something is meso or not. A lot of times they just expect you to recognize it, but I prefer to have rules. So here are the criteria. First of all, it has to have two or more chiral centers. It can't have less than two. So if it has one, it's not meso. If it has two, maybe it's meso, three, maybe it's meso. Two or more. The second criterion is that it has to be atomically symmetrical. Now, this is actually really tricky to communicate because what that doesn't mean is it doesn't mean perfectly symmetrical. It just means that everything has to be connected in the same way on both sides. Even if wedges and dashes don't match up, that's okay. I just need the atoms to be in place symmetrically. Then finally, I need an even number of the chiral centers to be opposite each other. So that means that if I have two chiral centers, I need two of them to be opposite each other. That means that I need my first one, if it's R, I need the other one to be S. If this first one is S, I need the other one to be R. Why is this? Because this has to do with the part about canceling out that I was talking about. I need for these chiral centers to cancel out, so that overall the molecule, even though it has two chiral centers, it will overall be achiral because they'll perfectly cancel each other out. Okay. So let me go ahead and give you a really simple version of a meso compound and it would be something like this. Let's say that I had a cyclohexane and I had a wedge here and I had a wedge here. Okay? This is an example. There are lots of different meso compounds out there, but this is an example of a meso compound. Why is that? First of all, do I have any chiral centers? Yeah, I happen to have two. This is a chiral center, and this is a chiral center. Okay. So both of these are chiral centers because if you count the groups, the direction if you go around, the directions are different depending on which side you take. So the R groups are different. These are two different chiral centers. Is this molecule chiral? No, it's not. Because if you look, it actually has an internal line of symmetry. Okay. If it has an internal line of symmetry, that means it's achiral. Right? But another way we could tell is by looking at the actual configurations of the chiral centers. And what I would see is if I went ahead and if I went ahead and figured out the chiral centers like the priority 1, 2, and 3, what I would find out is that this one goes around this way. Okay. And then I would find that this one goes around this way. Okay. So what I would find is that one of these is an R and one of these is an S and they're symmetrical to each other. They are both the same distance from the middle. So what that means is that this is another way of proving that it's meso by looking at the configurations and saying, hey, they're opposite and they're symmetrical and there's two or more of them, so this is meso. Alright. Now you guys might be wondering, Johnny, that looks so much more. You can, if it's a ring. But remember, that only really works for rings. For other kinds of compounds, it doesn't work. So for example, A and B, these compounds I'm going to give you down here, you really shouldn't use that test because that test is not going to work very well for these. Okay. So what I want you guys to do is go ahead and start on A and try to figure out the three things: how many chiral centers there are, what their configurations are, and if they're if it's symmetrical. Then once you figure that out, tell me if you think it's meso or if you think it would just be a normal chiral compound. Alright. So go ahead and try to solve, and then I'll show you guys how to do it.

Which of the following molecules are meso?

So let's just go down the list. First of all, how many chiral centers did it have? It had 2. So that's good. Was it atomically symmetrical? Now this is difficult to define a lot of times, but I would say yes. Okay. What I mean by atomically symmetrical just means that we have atoms in the middle that are connected to the same things on both sides. And in this case, yes, that quaternary carbon in the middle is connected to exactly the same things in terms of atoms on both sides, even if the wedges and dashes don't match up. Okay? But that's fine. So I need just to figure out configurations, R and S. So let's go ahead and work with this Chlorine first. The H would be in the back, so this is going to be an easy situation where I have this as my one priority, this as my 2, this as my 3 and the H is my 4. So then I would say, okay, is my 4 in the back? Yeah. So I can go ahead and ignore it and just go ahead and draw 1 through 3, and this side is going to be an R. Okay? Now I do the same thing. I'm going to have to erase a little bit. I'm going to do the same thing with the other one. So let's go ahead and draw our H. This one's going to be in the front this time. So that means that this is going to be my 4, this is going to be my 1, this is my 2, and this is my 3. Okay. So in this case, is my H in the back? No. So I have to cross these out and replace them. So this is the swap. Now that my 4 is in the back, I'm going to go ahead and go from 1 to 2, 2 to 3, 3 to 1. I always ignore 4. That looks like an S but actually it's going to be an R because I had to swap. So this one's going to be RR. So now the question is, are these chiral centers canceling out or are they just building on each other? And the answer is that these are not canceling out. They're both making the molecule chiral. So this would be not meso. And since it's not meso, I'm going to go with my general rule of if I have 2 or more chiral centers, this is chiral. Okay? So remember that the general rule said if you have 2 or more chiral centers, it's chiral, except meso compounds. In this case, since this is not meso, it has to be chiral. Does that make sense? Cool. So I want you guys to do the same thing with this one. Now I do want to clarify the notation a little bit. This is the beginning of what's going to be a Fischer projection. Okay? And Fischer projections are a specific thing that I may or may not teach you later depending on whether your professor and your book wants you to know it. Okay? But in the meantime, just know that these center balls are supposed to be carbons. Okay? So those are carbons. You see that there are things in the front, things in the back. The same rules apply in terms of front and back, so go ahead and try to figure out the R and the S, all that stuff, and then get back to me.

Which of the following molecules are meso?

Alright. So are there 2 chiral centers? Yes, there are. This is a chiral center. This is a chiral center. Okay? So that's good. Are they atomically symmetrical? Now this is rough. But let's look. If I were to split this in half, would it have the same groups on both sides? And actually, yeah, it would. It would have a carbon here and a carbon here. And even if the wedges and dashes don't match up perfectly, the atoms do. Notice that one of the carbons on the top is attached to an OH and a methyl. Notice that the carbon on the bottom is attached to an OH and a methyl. Okay? Same groups, different rotation, but that's fine. At least it's atomically symmetrical. So this is getting 2 checks so far. Now I just need to figure out the R and the S. So let's go ahead and do this. So let's go ahead and number our priorities. For the top one it would be 1. OK. Then this would actually be my 2 down here. OK. The reason is because the carbon in the middle doesn't count, that's just like my chiral center. Okay? And 2 is a carbon with an oxygen on it, whereas 3 is just a carbon with hydrogen. So obviously 2 is going to win over 3 and then this is 4. Cool? Alright, so now let's go ahead is 4 on the dash? No, it's not. So we have to replace. This is going to be 4. This is going to be 1. OK. Now we're going to go ahead and go around, 2 to 1, 2 to 3, 3 to 1. This looks like an S, but actually it's going to be an R because I swapped. Now we're going to do the same thing at the bottom with a new chiral center. I'll make this one red. OK. So my priorities are 1, 2, 3, and 4. Is my 4 on the dash? No. So I'm going to go ahead and cross out and swap. So now this is my 4, this is my 3, I'm going to ignore 1 and I'm going to go around like this. So 1, 2, 3, 3, 1. This looks like an R, but actually it's going to be an S because I swapped. Okay? So this is actually getting 3 check marks. This was 2 or more. It was symmetrical, and it was also opposite. Okay. I know those words are small. Okay. This is getting 3 check marks. What that means is that this actually is meso. Okay? This is a meso compound. If this is a meso compound, what does that mean in terms of chirality? That means that it's actually achiral. So check this out. These rules that I gave you are really clutch, honestly, because of the fact that there's no way that you would have been able to use the internal line of symmetry test to figure this out without doing some major rotating. Rotating is something that I try to avoid in this class because like I said earlier, people struggle with rotation. Okay. So if we can narrow it down to rules like we just did, it makes it better. So somehow, even though this molecule doesn't look like it has a plane of symmetry, it actually does. And the way that it does is you would have to rotate these guys around. So you'd have to rotate this OH here, CH₃ here and H there and then you would get a plane of symmetry. But like I said, I try to stay away from rotation because it can get really tricky rules, you get it right every time. Alright? So I hope that made sense to you guys. Let's go ahead and move on.

Here’s what students ask on this topic:

What is a meso compound in organic chemistry?

A meso compound is a type of molecule that has two or more chiral centers but is achiral due to an internal plane of symmetry. This symmetry causes the chiral centers to cancel each other out, resulting in the molecule being superimposable on its mirror image. Meso compounds are unique because they do not exhibit optical activity despite having chiral centers. An example is tartaric acid, which has two chiral centers but is achiral due to its internal symmetry.

How can you identify a meso compound?

To identify a meso compound, follow these steps: 1) Ensure the molecule has at least two chiral centers. 2) Check for an internal plane of symmetry, meaning the molecule can be divided into two mirror-image halves. 3) Verify that the chiral centers are oppositely configured (e.g., one R and one S). If these conditions are met, the molecule is likely a meso compound and will be achiral despite having chiral centers.

What is the significance of the 2ⁿ - 1 rule in meso compounds?

The 2ⁿ - 1 rule is used to calculate the number of stereoisomers for molecules with chiral centers, where n is the number of chiral centers. For meso compounds, this rule accounts for the fact that two of the stereoisomers are identical due to internal symmetry. For example, a molecule with two chiral centers would typically have 2² = 4 stereoisomers, but if it is a meso compound, it will have 2² - 1 = 3 stereoisomers.

Why are meso compounds achiral despite having chiral centers?

Meso compounds are achiral because they possess an internal plane of symmetry that causes the chiral centers to cancel each other out. This symmetry makes the molecule superimposable on its mirror image, resulting in no net optical activity. The chiral centers in a meso compound are configured in such a way (e.g., one R and one S) that their effects on the molecule's chirality negate each other.

Can a molecule with an odd number of chiral centers be a meso compound?

No, a molecule with an odd number of chiral centers cannot be a meso compound. For a molecule to be meso, it must have an even number of chiral centers that are oppositely configured (e.g., one R and one S) and an internal plane of symmetry. An odd number of chiral centers would prevent the necessary symmetry and cancellation required for the molecule to be achiral.