Leaving Group Conversions Summary - Online Tutor, Practice Problems & Exam Prep

Understanding the conversion of alcohols to good leaving groups is crucial in organic chemistry. Secondary and tertiary alcohols can undergo SN1 reactions with HX, yielding racemic mixtures due to carbocation formation. For inversion of configuration, primary alcohols can react with HX, SOCl₂, or PBr₃ via SN2 mechanisms. Tertiary alcohols cannot achieve inversion due to steric hindrance. Retention of configuration is achieved using sulfonyl chlorides, applicable to all alcohol types. Mastering these mechanisms and their stereochemical outcomes is essential for success in organic synthesis.

Comparing and contrasting the Alcohol Conversions.

So here's what I hope will be a helpful cheat sheet for you guys to compare the different types of alcohols you could start with and the stereochemistry that you'll get at the end. All of these reactions, remember, are going to convert alcohols to good leaving groups, but they are going to proceed with different stereochemistry. So, because this section has so much to do with stereochemistry, that's why I made this entire axis all about just stereochemistry. All right. So let's go ahead and start off with what if we want a good leaving group. We want to convert alcohol to a good leaving group and we want the end product to be racemic. Well, if that's the case, then we could start with a secondary or a tertiary alcohol and we could use HX in an SN1 reaction. HX is the only reaction in an SN1 that gives us 2 enantiomers. That gives us a combination of products. Okay? Now you might be wondering, well, why is it grayed out here? Why can't I also use that on a primary alcohol? Okay. Well, remember because primary alcohols don't form good carbocations. And in order to make a racemic mixture, you need the carbocation. I'm just going to write here can't make carbocation. And if you can't make the carbocation, that means you're going to do an SN2 mechanism, not an SN1. So that's why it's grayed out. Now one more thing I just want to add. Remember that if what happens in the case of HCl? Can I also just use HCl by itself? No. Remember, we use the Lucas reagent. HCl over zinc chloride, the Lewis acid catalyst. Cool. So let's keep going. What if I'm starting with an alcohol and I want to get inversion of configuration at the end? I don't really care what the leaving group is as long as it's inverted. Well, if it's primary alcohol, then I can use HX or SOCl₂ and PBr₃. So just so you know, SOCl₂ and PBr₃ are always good options for inversion because of the fact that you get a backside attack every time. Why did I only put the HX SN2 here? Why did I not put it in the secondary position? Because if you guys remember, HX will actually, if you do it with a secondary, it's actually going to wind up giving you an SN1 reaction. So that's why we can't use it in the secondary position. We can only use it in the primary position. If you have a primary alkyl halide, you will get an SN2. You will get inversion. But if it's secondary, remember you make your carbocation again and you would form a racemic mixture. Okay? You might be wondering, well, why is this grayed out? Why can't I just do an inversion of configuration on a tertiary as well? Why can't I use SOCl₂? Because remember, you can't do a backside attack on a tertiary. It's too crowded. Okay? So I'm just going to put here bad backside. Since it's a bad backside, I can never do an inversion configuration on a tertiary. Cool? All right. So lastly, what if I want retention of Well, anytime You want retention of configuration, you're going to use your sulfonyl chlorides to turn your alcohol into a sulfonate ester. Okay? This one's really easy because it doesn't matter what degree your alcohol is. It's always the same thing. You're going to wind up getting a sulfonate ester and it's that easy. And then later on, you can react it. So hopefully, that helps you guys to kind of organize the different ways we can convert alcohol to good leaving groups. Professors love to test on stereochemistry here and that's why I would really emphasize knowing the differences in stereochemistry between these options. All right. 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 are the common reagents used to convert alcohols to good leaving groups?

Common reagents used to convert alcohols to good leaving groups include HX (where X is a halide like Cl, Br, or I), SOCl₂ (thionyl chloride), PBr₃ (phosphorus tribromide), and sulfonyl chlorides. HX can be used for secondary and tertiary alcohols in SN1 reactions, while SOCl₂ and PBr₃ are effective for primary alcohols via SN2 mechanisms. Sulfonyl chlorides are versatile and can be used for primary, secondary, and tertiary alcohols to achieve retention of configuration.

How does the stereochemistry of the product differ when using HX in SN1 versus SN2 reactions?

In SN1 reactions with HX, the stereochemistry of the product is racemic due to the formation of a planar carbocation intermediate, which allows for attack from either side, producing a mixture of enantiomers. In contrast, SN2 reactions with HX result in inversion of configuration because the nucleophile attacks from the opposite side of the leaving group, leading to a single enantiomer with inverted stereochemistry.

Why can't tertiary alcohols undergo inversion of configuration using SOCl₂ or PBr₃?

Tertiary alcohols cannot undergo inversion of configuration using SOCl₂ or PBr₃ because of steric hindrance. The bulky groups around the tertiary carbon prevent the nucleophile from performing a backside attack, which is necessary for inversion. As a result, these reagents are ineffective for tertiary alcohols in achieving inversion of configuration.

What is the role of sulfonyl chlorides in the conversion of alcohols to good leaving groups?

Sulfonyl chlorides are used to convert alcohols into sulfonate esters, which are excellent leaving groups. This reaction retains the configuration of the original alcohol and is applicable to primary, secondary, and tertiary alcohols. The resulting sulfonate ester can then participate in various nucleophilic substitution reactions, making sulfonyl chlorides a versatile reagent in organic synthesis.

Why are primary alcohols not suitable for SN1 reactions with HX?

Primary alcohols are not suitable for SN1 reactions with HX because they do not form stable carbocations. The formation of a carbocation intermediate is crucial for the SN1 mechanism, and primary carbocations are highly unstable. Therefore, primary alcohols typically undergo SN2 reactions with HX, where the nucleophile directly displaces the leaving group in a single, concerted step.