Ch. 12 - Alcohols, Ethers, Epoxides and ThiolsWorksheetSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins

Alcohols are terrible leaving groups. So we’re going to learn an entire class of reagents whose sole job is to convert alcohol into better leaving groups. 

Concept #1: Why do we need to convert Alcohol into a good leaving group?

Transcript

As you guys might have figured out by now, alcohols are a pretty important functional group for organic chemistry. But there's one major limitation of alcohols and that's that they make terrible leaving groups. Remember that the definition of a good leaving group is something that once it leaves, it's stable.
Well, alcohol, after it leaves, it becomes OH-. OH- is the same as a hydroxide base, which is a very unstable molecule. It's a very strong base. That means that whenever we have an alcohol, we're a little bit stuck. We don't know exactly what to do with it because a lot of reactions in organic chemistry require leaving groups and alcohol isn't a good option.
But wait. There is a solution. It turns out that the major topic that we're going to discuss in this section is how to turn alcohol into a good leaving group. It turns out that there's two major options – like a fork in the road, we can take two major pathways and that they're both going to lead to awesome outcomes. They're both going to lead to alcohol being a much better leaving group. Let's go ahead and talk about the first one.
The first option that we have is to convert alcohol simply into an alkyl halide. Remember that alkyl halides have the molecular formula RX. The reason that they're such good leaving groups is because X negative, once it takes off is very stable. X could stand for iodine or bromine or chlorine. These are very electronegative atoms that don't mind having a negative charge. So alkyl halides are an awesome option.
But another option that we also have that we'll discuss in a little bit is sulfonate esters. Now you might have learned already that sulfonate esters make great leaving groups. I actually have talked about that before. But now what we're going to learn is how to actually turn an alcohol into a sulfonate ester so that it can become a great leaving group. 

We’re aiming to turn alcohols into alkyl halides or sulfonate esters. Let’s explore the different ways to accomplish this. 

The simplest way to theoretically convert alcohols into alkyl halides is just to react them with a strong halohydric acid (HX). There are some complications associated with this conversion however.

 

Can you predict what they are? (Three major complications given below).  

Concept #2: Using HX acids via SN1 reaction.  

Transcript

So let's start off with this page. I just want to do the alkyl halides and later one we'll talk about sulfonate esters.
It turns out that the degree of your alcohol is going to determine which method you use to turn it into an alkyl halide. That has to do with the mechanism. The reagent might be the same actually, but the mechanism's going to be slightly different.
For a secondary or a tertiary alcohol, what's common to both of those is that they both make relatively good carbocations. If I were to kick the OH off, somehow make it stable and kick it off completely, I would get a carbocation that's pretty stable. It turns out that secondary and tertiary alcohols proceed with an SN1 mechanism. Remember that SN1 is a two-step mechanism that makes the carbocation first and then it's nucleophilically attacked.
Let's go ahead and kind of figure out what's going to happen. In the first step, what I'm going to do is I'm going to protonate my alcohol with my strong acid, HX. We're always going to use HX, a strong acid, to turn alcohol into a good leaving group. Let's just say that the X stands for Br. I have HBr.
In my first step what I'm going to get is alcohol grabbing a proton and kicking out the Br. What that's going to make is that's going to make a water where the alcohol used to be. Now keep in mind that that water is now way better. In terms of it's a much better leaving group.
What's going to happen in the next step – we just protonated. What happens in the next step is that just leaves completely on its own. Why? Because this is an SN1 reaction. Remember than in an SN1 reaction, you need to make a carbocation. What we're going to do now is we're just going to draw out our carbocation. The reason that we knew that it would make a carbocation is because if you'll notice, I started off with a tertiary alcohol. Remember that I told you tertiaries and secondaries are going to do SN1.
One question you guys might have is, “Johnny, the methyl group on the red structure used to be on the dash and now you just drew it on a stick. Did you do that on purpose? Did you mess up?” Actually, I did that on purpose. The reason is because remember, carbocations are trigonal planar. So you should draw everything on the same plane. It's actually not correct to keep it on the dash. You should just draw everything on the same plane.
Now you might have guessed it. What's going to happen to this positive charge? Well, keep in mind that it could rearrange. If it was unstable, it could have rearranged. Would this carbocation want to rearrange? It's already tertiary. It's happy. So let's go ahead and attack it with the Br. What I'm going to get at the end is an alkyl halide that looks like this.
Now one note, I purposefully didn't include stereochemistry here. The reason is because I don't know which side it's going to attack. It can attack the front or the back. Technically, you're going to get enantiomers from this attack. You're going to get a Br on the front and a Br in the back. But typically, that doesn't really matter too much because we're going to be usually making this leave anyway later.
Now you might also be wondering, “Johnny, what was the point of this?” Well, I'll tell you the point, the point is that alcohol wasn't going to do anything. It was just going to sit there forever, so by reacting it with HX, what we were able to do is turn it into an alkyl halide, which is much more convertible. Alkyl halides are much more functional. They can do a lot more things. I just made my alcohol more functional by turning it into an alkyl halide.
Now, there is one more note that I have to say which is that the X in HX can equal two things. It can either equal iodine or it can equal bromine. What about chlorine and fluorine? Well, just so you know, fluorine is too weak to react. I'm just going to put F doesn't happen. It can't be F. HF is not a strong enough acid to make this happen.
But how about HCl? Well, HCl, the Cl is still a pretty strong nucleophile, but it's not strong enough to make this reaction happen in full yield, in a high yield. So what we usually do is if we really want to have a Cl instead of the Br, we're going to couple that with a Lewis acid catalyst that is zinc and two chlorines together. What that's going to do is it's actually going to make the leaving group stronger.
Let me just show you really quick how that works. By the way, this together, having HCl and the zinc complex together is going to be called the Lucas reagents. Some professors don't care that you know that. Some books don't really teach it. But, in general, it is kind of widely known as the Lucas reagent. Really it's going to do the same exact thing as what we just did, except it just has one extra step which is this.
Basically what we do is we take our alcohol. I'm going to draw it a little bit smaller. And what's going to happen is that the Lewis acid, remember that a Lewis acid is a proton acceptor. I'm sorry. A Lewis acid is an electron pair acceptor. It has an empty orbital. What's going to happen is that the Lewis acid is actually going to couple to the oxygen. The oxygen is going to donate electrons to the zinc. What that's going to make is something that looks like this, where I now have O, H, zinc with two chlorines and that O is going to have a positive charge.
What's great about that is that now that is a much better leaving group than just water by itself. Remember that over here I also had OH2+. But this one's even better. What that means is that the Cl when it comes in, it's going to have an easier time attacking there. What's basically going to happen is that it's going to have an easier time leaving by itself. So once it leaves, what I'm going to wind up getting is a carbocation that is then easier for my Cl to attack.
That's the first situation I want to tell you guys about. 

This is the predominant mechanism for strong halohydric acids with 2° and 3° alcohols. 

Concept #3: Using HX acids via SN2 reaction.

Transcript

What about a primary alcohol? Well if we have a primary alcohol then the only thing that really changes is the mechanism, primary alcohols are really good at having a backside and they're really bad at doing making carbocation so I means if I use HX once again I'm going to protonate in my first step, so what I'm going to wind up getting is OHH positive, OK? But if this left by itself and then obviously I would get the X leaving by itself so I'd get plus X negative but the problem is that this can't just leave and make a stable carbocation so instead we're going to do is we can do a straight up back side attack where the X hits the back side and kicks out the water, OK? Now the reason this is possible here but it wasn't possible with the other situation is because the primary alcohol has a much better backside, it has a good back side since it has a good back side it's easy for my X to just kick out the water all in one step so what we're going to get here is an Alkyl Halide once again but in this case my mechanism was different I used SN2 instead of SN1, alright? Same exact thing would apply if I used each HCL and the Lucas regent what I would wind up getting is 0H with then a zinc and 2 chlorines and a positive charge and what you would get in the second step is that my chlorine or not in the second step but well yea technically in the second step my chlorine would do a backside attack and kick out the entire complex so then in this case if I was reacting specifically with those reagents I would get a chlorine, alright? So really this isn't that bad I just went through the mechanism so you guys will understand it but really all you need to know is Hx it's really that easy you just take HX and you can convert an alcohol to an Alkyl halide, alright? Awesome so let's go ahead and move on to the next topic.

This is the predominant mechanism for strong halohydric acids with 1° alcohols.

Complications: Strong HX acids conversions come with three major complications.

  1. Regiochemistry of products: Carbocation intermediates can rearrange.
  2. Stereochemistry of products: Racemic products are non-stereo specific.
  3. Competition of Elimination mechanisms: Some product won’t even be an alkyl halide.   

These complications render this method mostly useless. Sorry not sorry.