Thiol Reactions: Videos & Practice Problems

Thiols, the sulfur analogs of alcohols, are more acidic due to the larger size of sulfur, facilitating the formation of thiolate ions when deprotonated. Thiolates can undergo nucleophilic substitution reactions, such as sulfide synthesis via SN2 reactions with alkyl halides, yielding sulfides. Disulfide synthesis involves thiolates reacting with diatomic halogens, leading to disulfide formation through a series of nucleophilic attacks. Understanding these reactions is crucial for grasping sulfur chemistry and its applications in organic synthesis.

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 with a sulfur. How is that going to change the molecule? Is it going to react just like an alcohol? Let's find out. So thiols are more acidic than a typical alcohol. If you think about it, that has to do with the fact that sulfur is a little bit bigger in size, and the size effect says that as the molecules get bigger, it's easier to give up an H and get a lone pair. So, thiols are going to contain a very acidic hydrogen. Okay. So 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 the base. So after you expose it to a base, pull off that hydrogen. It's going to be a great nucleophile. Just so you guys know, that nucleophile, once the sulfur has a negative charge on it, is called a thiolate. So a thiolate nucleophile is going to be capable of forming 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 a base. The base is going to deprotonate the H and make my thiolate anion. Then that thiolate anion performs an SN2 reaction on an alkyl halide and alkylates. So, we wind up getting the sulfide, basically the analog to an ether, just with an 'S' instead of an '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. So in my first step, my base is going to grab the acidic hydrogen of my thiol. Obviously, the hydrogen doesn't want 2 bonds, so I make a bond, I break a bond and I wind

Here’s what students ask on this topic:

What are thiols and how do they differ from alcohols?

Thiols are sulfur analogs of alcohols, meaning they have a similar structure but with a sulfur atom (S) replacing the oxygen atom (O) found in alcohols. This substitution makes thiols more acidic than alcohols because sulfur is larger than oxygen, making it easier to lose a hydrogen ion (H⁺) and form a thiolate ion (RS^-). This increased acidity and the ability to form thiolate ions are key differences that influence their reactivity compared to alcohols.

How is a thiolate ion formed from a thiol?

A thiolate ion is formed when a thiol (RSH) is deprotonated by a base. The base removes the acidic hydrogen atom from the thiol, resulting in the formation of a thiolate ion (RS^-). The reaction can be represented as:

$R_S-+H_{+}$

This thiolate ion is a strong nucleophile and can participate in various nucleophilic substitution reactions.

What is the mechanism of sulfide synthesis from thiols?

Sulfide synthesis from thiols involves two main steps. First, a thiol (RSH) is deprotonated by a base to form a thiolate ion (RS^-). This thiolate ion then undergoes an SN2 reaction with an alkyl halide (R'X), resulting in the formation of a sulfide (RSR'). The mechanism can be summarized as:

1. Deprotonation: $R_{S}H+\mathrm{Base}\to R_S-+H_{+}$

2. SN2 Reaction: $R_S-+R_{\text{'}}X\to R_S{R}_{\text{'}}+X-$

This results in the formation of a sulfide, which is analogous to an ether but with sulfur instead of oxygen.

How are disulfides synthesized from thiols?

Disulfide synthesis from thiols involves a two-step process. First, a thiol (RSH) is deprotonated by a base to form a thiolate ion (RS^-). This thiolate ion then reacts with a diatomic halogen (e.g., Br₂) to form a disulfide (RSSR). The mechanism can be summarized as:

1. Deprotonation: $R_{S}H+\mathrm{Base}\to R_S-+H_{+}$

2. Reaction with Halogen: $R_S-+{\mathrm{Br}}_2\to R_S{S}_R+{\mathrm{Br}}_{-}$

This results in the formation of a disulfide, which is a molecule containing an S-S bond.

Why are thiols more acidic than alcohols?

Thiols are more acidic than alcohols because sulfur is larger than oxygen. This larger size allows the sulfur atom to better stabilize the negative charge on the thiolate ion (RS^-) after deprotonation. The increased ability to stabilize the negative charge makes it easier for thiols to lose a hydrogen ion (H⁺), thus making them more acidic compared to alcohols.