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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
Ch. 26 - Transition Metals
Alcohol Nomenclature
Naming Ethers
Naming Epoxides
Naming Thiols
Alcohol Synthesis
Leaving Group Conversions - Using HX
Leaving Group Conversions - SOCl2 and PBr3
Leaving Group Conversions - Sulfonyl Chlorides
Leaving Group Conversions Summary
Williamson Ether Synthesis
Making Ethers - Alkoxymercuration
Making Ethers - Alcohol Condensation
Making Ethers - Acid-Catalyzed Alkoxylation
Making Ethers - Cumulative Practice
Ether Cleavage
Alcohol Protecting Groups
t-Butyl Ether Protecting Groups
Silyl Ether Protecting Groups
Sharpless Epoxidation
Thiol Reactions
Sulfide Oxidation
Additional Guides
Hydroxyl Group

Thiols are more acidic than their oxygen-containing analogs, alcohols. Therefore, acid-base reactions will highly influence their reactivity, with the formation of a thiolate anion usually being the first step.

Concept #1: The mechanism of Sulfide Synthesis.


Now we're going to discuss reactions of thiols. If you guys remember, thiols are the sulfur analog of alcohols, meaning that they look exactly like alcohols except that the oxygen is replaced for a sulfur. How's that going to change the molecule? Is it going to react just like an alcohol? Let's find out.
Thiols are more acidic than a typical alcohol. If you guys think about it, that has to do with the fact that sulfur is a little bit bigger in size and the size effect said that the bigger the molecules get, the easier it is to give up an H and get a lone pair. Thiols are going to contain a very acidic hydrogen. What that means is that it's going to be easy to pull off that hydrogen and easy to make it a nucleophile after it's exposed to base. After you expose it to base, pull off that hydrogen, it's going to be a great nucleophile.
Just so you guys know, that nucleophile, when the sulfur has a negative charge on it, is called a thiolate. A thiolate nucleophile is going to be capable of performing a few different reactions. That's what we want to go over right now.
We can do sulfide synthesis through a thiol and we can also do disulfide synthesis. Let's start off with the easier one, which is sulfide synthesis. In sulfide synthesis, I start off with my thiol. That looks just like an alcohol except it's got the S and I react it with base. The base is going to deprotonate the H and make thiolate anion. Then thiolate anion performs an SN2 reaction on an alkyl halide and alkylates. So what we wind up getting is a sulfide. Basically, the analog to an ether, just with an S instead of the O for the ether.
Let's go ahead and look at how this full mechanism. Let's draw it out and make sure that we're all on the same page. In my first step, my base is going to grab the acidic hydrogen of my thiol. Obviously, the hydrogen doesn't want to have two bonds, so I make a bond and break a bond and I wind up getting – what is this called? My negative charge on my S. This is my thiolate anion. Cool?
So I've got my thiolate anion. Now, what can that do when exposed to an alkyl halide? Well, if it's exposed to the right type of alkyl halide, I'm going to be able to do an SN2. Now, what do I mean by right type? Well, obviously, if this is a tertiary alkyl halide, would that be able to work? No. Because remember that tertiary alkyl halides cannot perform an SN2 reaction. But in most cases, if it's primary or secondary, it's going to work. So I'm just going to add here that this would have to be a primary or a secondary alkyl halide.
So now I've got my backside attack, my SN2 reaction and what I'm going to get as my product is simply a sulfur with now whatever that R group was. Now whatever that R group, it could be whatever I wanted. I just pick the alkyl halide of choice. Cool?
That's how we make a sulfide out of a thiol. Not bad at all, right?

Concept #2: The mechanism of Disulfide Synthesis.


Now let's talk about Disulfides, Disulfides are a little more tricky so notice that once again I'm starting off with a Thiol which looks a lot like an alcohol if that had been O that would be methanol, right? So this is methane thiol because it's an SH, OK? So I got my Thiol, I've got my base again, so notice that the first step is going to be exactly the same my first step is going to be a base reacting with my Thiol to take off the H, the weird thing is that then I've got this halogenation going on, this BR2, OK? So let me explain how that works just through the mechanism, OK? So it's cool down to the Disulfides synthesis mechanism we're going to find is that the first step everyone should be able to draw, OK? Your OH grabs the acidic hydrogen and you wind up getting that this very familiar intermediate what is this called? This is my Thiolate, OK? So now we got that Thiolate now we expose that to a diatomic halogen and this is interesting, the diatomic halogen is going to be able to be attacked, OK? So my Sulfur will grab one of the BRs kick the other one out what I wind up getting a something looks like this where I've got Sulfur BR, OK? And then I've got a BR negative just hanging out, Cool so far? Awesome So now here's the interesting thing, OK? Not only am I going to make one Thiolate but I could make several Thiolate, OK? Because I'm going to excess base so it's going to basically deprotonate all of that most of those hydrogens, OK? So what happens in the next step is we're just going to go ahead and bring this down over here, OK? And what we're going to find out is that a second Thiolate so this would be my x2 this is my second thiolate can actually do a backside attack on this sulfur, OK? And it would kick out believing group so what you're going to wind up getting at the end of this is a Disulfide we have S and S and then a symmetrical disulfide, Ok? You would have a Disulfide product and that Disulfide would be symmetrical because of that the fact that you're going to use the same thiolate twice so you get your disulfide and you would get more BR leaving group, OK? So it doesn't really matter we're not paying any attention to the BR we're really paying it's an organic product which is our Disulfide, cool? So none of these reactions are hard I know we're not used to dealing a lot with sulfur but it's really not that tricky, OK? So I hope that made sense those are the two really common reactions that Thiols undergo and if you have any questions let me know but if not let's move on.