Leaving Groups - Online Tutor, Practice Problems & Exam Prep

Nucleophiles and leaving groups are crucial in organic chemistry. Alkyl halides are the most common leaving groups, but sulfonate esters, such as tosylates, mesylates, and triflates, are also significant due to their resonance stabilization, making them effective leaving groups. Water can become a good leaving group when alcohols are protonated by strong acids, allowing them to leave as water. Understanding these concepts is essential for mastering nucleophilic substitution reactions and their mechanisms.

The 3 important leaving groups to know.

At the beginning of this topic, I made some generalizations about nucleophiles and about leaving groups. If you remember about leaving groups, what I said was that there's a lot of different types, but the most common is alkyl halides. Right? And that's what we've been using this entire topic. Another generalization I made was with nucleophiles when I said that just think that a negatively charged nucleophile is strong and a neutral one is weak. And I just said let's just say that for now. Okay? What I want to do for this topic is to go more in-depth on leaving groups and nucleophiles, so that we can really understand all the different types instead of just making generalizations. Alright? So let's get started with the leaving groups first. Okay? As I said before, alkyl halides are the most common leaving groups of organic chemistry, so 90% of the time, you're just going to see alkyl halides. And that's why you've been dealing with them so much because they literally are so ubiquitous. Alright? They're everywhere. But it turns out that there's other types of leaving groups as well. Another really common one being sulfonate esters. Okay? Now, these don't show up as often as alkyl halides, but they do show up a good amount. What a sulfonate ester is, is it's a molecule with the general formula SO3R. Okay? Now typically, we wouldn't and this is actually the way it looks by the way. The sulfonate ester general structure is that you have your chain, let's say this is my chain here. Okay? And let's say that this is attached. And it's going to be an O with then an S and 2 O's and then an R. Now, typically, would we expect O to be a good leaving group? No. Remember that O is not as electronegative as an alkyl halide. It's actually, you know, further this way. So we would expect that O- would not be a good leaving group and O- would be bad. But this molecule is special because it can resonate so much. Okay? And I did talk about this earlier when we were talking about leaving groups that we could once I get a negative charge there, this would be able to resonate and make double bonds and distribute that negative charge everywhere. So Sulfonate Esters turn out to be really, really good leaving groups, even better than alkyl halides in some cases because they have so much resonance available, so it's going to stabilize the leaving group just like a conjugate base would be stabilized by the resonance effect. Okay? Remember that parallel that I drew between conjugate bases and leaving groups? It's the same thing. So it turns out that the sulfonate ester, you might just see it drawn as SO3R, in which case you need to know what that is. Okay? You also might have seen it drawn OSO2R. Same thing. Okay? That's just the way it's actually drawn out. There's an O first. Okay? You need to be able to recognize that that's a leaving group. But on top of that, you could see a special type of sulfonate esters. Turns out sulfonate esters is the general category, but there's actually 3 unique types of sulfonate esters. Okay? And those are tosylates, mesylates and triflates. Okay? Now the difference between those 3 actually just has to do with the R group. Okay? So everything else is the same. The S is the same. The O's are the same. Everything. The only thing that changes is the identity of the r group. So let's go really quickly into that. Okay? If that r group is just a methyl group, which is this middle situation, that's going to be called a mesylate or a mesyl group or a mesylate once it has the negative charge and it's abbreviated MS. Okay? So if you see that, you know it's a sulfonate ester. How about if it's a benzene ring with a methyl group on it? If it's a benzene ring with a methyl group, that's going to be called a tosylate and that's abbreviated TS. And then if it's a C with 3 F's instead of 3 H's, then that's called a triflate or trifluate if it has the negative charge. Okay? Now, I know you guys might be wondering when do I use the word tosyl, when do I use tosylate? The ending -ate just means that there's a negative charge and we're gonna that's common throughout lots of chemistry. We say instead of like, I don't know, instead of instead of I don't know. In organic chemistry 2, we use it a lot more, that naming system. It just means if you have an 8 at the end, it just means you have a negative anion. Alright? So anyway, the whole point here is I don't need you to memorize exactly each sulfonate ester. Okay? I don't want you to be able to draw it if I if I give it to you. But what I do want you to be able to do is recognize that if you see these weird letters like OMs or whatever, that you're going to know, hey, that this is a sulfonate ester, so it's a really good leaving group. Okay? Now, I did notice one little error here. This should have been OMS, not OTS. So I am going to change that. But anyway, you guys get the whole point that basically, if you see one of these things, consider it the same as an alkyl halide. Okay? So if there's an RX, it's the same thing as an OMS or whatever. Alright? So that's the first leaving group that I want to tell you guys about. It's important. Don't pay too much attention to it. Just treat it the same as you would an alkyl halide. Alright? So if I see a secondary mesylate, that's the same thing as a secondary iodide or whatever.(MethodImplOptions taking about water is actually a pretty common leaving group that we're going to use, in a little bit. We haven't used it yet. But the way that we do it, the way we get water as a leaving group is to protonate alcohol with a strong acid. Okay? So what you'll notice here is I have alcohol. Is alcohol a good leaving group? No. Typically, it is not because once I kick off that O, what I'm going to get is O- and that's very unstable. That's actually a really strong base. So that's not a good leaving group. But if I can protonate the alcohol first with a strong acid, like for example, sulfuric acid, which is a really common one that's used, then it's going to leave as water. Let me show you. So if the first step is let's say, let's choose an easier one. Let's just use HCl. Okay? If my first step is to expose the alcohol to my strong acid, guess what's going to happen? My alcohol is going to grab the H and it's going to become protonated. Once it's protonated, it looks like this, OH2+. That's not very happy the way it is because it has a formal charge now. So now guess what can happen in the next step? It can leave all on its own just like an alkyl halide would in a mechanism. And then what you're gonna get is you're gonna get, let's say, a carbocation, if this is an SN1 reaction or an E1, plus water. Is water a good leaving group? Is it stable? Yeah. It's super stable because it's just neutral. Alright? So see that by protonating my alcohol first, I could turn it from a bad leaving group to actually a really good leaving group. So now you guys know overall general idea here. Alkyl halides are the most important. You're going to see them al

Here’s what students ask on this topic:

What are the most common leaving groups in organic chemistry?

The most common leaving groups in organic chemistry are alkyl halides. These include compounds like chlorides (Cl^-), bromides (Br^-), and iodides (I^-). Alkyl halides are prevalent because they are generally good at stabilizing the negative charge after leaving. Another significant category of leaving groups is sulfonate esters, which include tosylates (TsO^-), mesylates (MsO^-), and triflates (TfO^-). These are particularly effective due to their resonance stabilization. Additionally, water can act as a good leaving group when alcohols are protonated by strong acids, allowing them to leave as neutral water molecules.

Why are sulfonate esters considered good leaving groups?

Sulfonate esters, such as tosylates (TsO^-), mesylates (MsO^-), and triflates (TfO^-), are considered good leaving groups because of their ability to stabilize the negative charge through resonance. The general structure of a sulfonate ester is R-SO₃R', where the sulfonate group can delocalize the negative charge over multiple oxygen atoms. This extensive resonance stabilization makes sulfonate esters even better leaving groups than many alkyl halides. Their effectiveness as leaving groups is crucial in facilitating nucleophilic substitution reactions.

How does protonation of alcohols improve their leaving group ability?

Alcohols are typically poor leaving groups because the hydroxide ion (OH^-) is a strong base and unstable. However, protonation of alcohols with a strong acid, such as HCl or H₂SO₄, converts the hydroxyl group into a better leaving group. The protonation process forms a positively charged oxonium ion (R-OH₂⁺), which can leave as neutral water (H₂O). This transformation makes the leaving group much more stable and facilitates nucleophilic substitution reactions.

What is the difference between tosylates, mesylates, and triflates?

Tosylates, mesylates, and triflates are all types of sulfonate esters, differing mainly in their R groups. Tosylates (TsO^-) have a benzene ring with a methyl group (p-toluenesulfonate). Mesylates (MsO^-) have a simple methyl group (methanesulfonate). Triflates (TfO^-) have a trifluoromethyl group (trifluoromethanesulfonate). Despite these differences, all three are excellent leaving groups due to their resonance stabilization, making them highly effective in nucleophilic substitution reactions.

How do alkyl halides compare to sulfonate esters as leaving groups?

Alkyl halides and sulfonate esters are both effective leaving groups, but they differ in their mechanisms of stabilization. Alkyl halides, such as chlorides (Cl^-), bromides (Br^-), and iodides (I^-), stabilize the negative charge primarily through the electronegativity of the halogen. Sulfonate esters, including tosylates (TsO^-), mesylates (MsO^-), and triflates (TfO^-), stabilize the negative charge through extensive resonance. This resonance makes sulfonate esters sometimes even better leaving groups than alkyl halides, especially in reactions requiring high leaving group stability.