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: The mechanism of Sulfide Synthesis.4m
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: The mechanism of Disulfide Synthesis.3m