Thioacetal: Study with Video Lessons, Practice Problems & Examples

Thioacetals are similar to acetals but utilize thiols (RSH) instead of alcohols (ROH). They can be formed using a dithiol for cyclic structures or two equivalents of thiol for acyclic ones, typically in the presence of a Lewis acid like BF₃. Thioacetals serve as protecting groups and can undergo reduction with Raney nickel, a strong reducing agent, to convert the thioacetal into an alkane by replacing sulfur with hydrogen. This reaction is crucial for removing carbonyls in organic synthesis.

Thioacetals and Raney Nickel Reduction

This is going to be a quick video on thioacetals and Raney nickel reduction. We're not going to spend a whole lot of time on this topic because it turns out that a thioacetyl is really the same exact thing as an acetyl except that instead of using an alcohol, you're using a thiol. A thiol would just be a group that's RSH which is really the same thing as ROH. Remember that S is right below O on the periodic table, so it even reacts very, very similarly. It has those two lone pairs and everything. In this case, you can see that I have my carbonyl and I'm reacting it with what's actually called a dithiol here. You don't always have to react with a dithiol. But if you want to get a cyclic thiazotel, then you need to use a dithiol. If you want to get an acyclic one, then you would use two equivalents of just a regular thiol. The biggest difference being that between this direction and acetyls is that we do use a specific acid instead of how for acetals I told you guys it doesn't really matter. It could be any proton donating acid. For thioacetals, typically we use BF₃ which if you guys remember is actually a strong Lewis acid.

The biggest difference between this mechanism and the Bronsted Lowry mechanism for acetyls is going to be that in your first step instead of protonating the O, the O actually just starts to donate its electrons to the empty orbital which again makes a resonance structure with a positive charge down here. Other than that, the mechanism is really pretty much identical. It's just that you're using a Lewis acid instead of a Bronsted Lowry acid in this case.

Now we get to the thioacetal which is this. Thioacetals are also important protecting groups in organic chemistry. You could use a thioacetal as a protecting group and then that would be it. You would just stop there and then you'd go back when you want to regenerate the carbonyl. But there's a very important secondary

Raney Nickel Reduction

Product A is just going to be the reverse reaction of my acetal leading to the original carbonyl because dilute acid, as we know, is going to be able to carry out the reverse reaction. How do we know what that carbonyl will look like? It's actually not that hard. What I would do is I would split this down the middle and I would say anything past the Os. Actually, I'll split it on the Os. Anything past the Os must have come from the alcohol, and anything on this side must have come from the carbonyl. What that means is that my alcohol originally looked like this. As you can see, the 2 carbons that were in between the Os are still there, and that must have reacted with an R group that looked like this. The only part we're missing is the carbonyl. The carbonyl goes where the acetal is. It would be cyclobutanone. Now I'm going to react that molecule with a thioacetal reaction. What we're working with now is the ketone because the alcohol, I don't care about that can leave. What I care about is the actual carbonyl. Now the carbonyl is going to react with 2 thiols and some kind of acid. It doesn't tell me which one but I don't really need to know. It's catalytic anyway. What this is going to do is it's going to give me structure B which is going to be a thioacetal. What I could do to get this structure is I could just draw the general structure and plug in the R groups. That's what I always do. I would do something like this: Sr, Sr, carbon-carbon. Now I'm just going to swap out the Rs for what the R was in my thiol. My thiol is going to be a propanethiol, 3 carbons. I would do 1, 2, 3 and 1, 2, 3. Now I've got my thioacetal. That's structure B. We have A. We have B. Now what's Raney nickel going to do to this? Oops. Woah. Woah. Woah. Woah. Just a second. I made a mistake an

Here’s what students ask on this topic:

What is a thioacetal and how is it different from an acetal?

A thioacetal is a compound similar to an acetal, but it uses thiols (RSH) instead of alcohols (ROH). The sulfur atom in thiols replaces the oxygen atom in alcohols. Thioacetals can be formed using a dithiol for cyclic structures or two equivalents of a thiol for acyclic ones. The formation typically involves a Lewis acid like BF₃, unlike acetals which can use any proton-donating acid. The key difference lies in the sulfur atom, which is right below oxygen on the periodic table, giving it similar reactivity but distinct chemical properties.

How are thioacetals used as protecting groups in organic synthesis?

Thioacetals are used as protecting groups to temporarily mask carbonyl groups during chemical reactions. This is useful to prevent unwanted reactions at the carbonyl site. Once the desired transformations are complete, the thioacetal can be converted back to the carbonyl group. Additionally, thioacetals can undergo a unique reaction with Raney nickel, a strong reducing agent, to convert the thioacetal into an alkane by replacing the sulfur atoms with hydrogen. This makes thioacetals versatile tools in organic synthesis for both protection and functional group transformation.

What is the role of Raney nickel in the reduction of thioacetals?

Raney nickel is a strong reducing agent used specifically with thioacetals. When a thioacetal is treated with Raney nickel, the sulfur atoms in the thioacetal are replaced with hydrogen atoms, effectively converting the thioacetal into an alkane. This reaction is particularly useful for removing carbonyl groups altogether in organic synthesis. The Raney nickel reduction is a unique feature of thioacetals, making them valuable for specific synthetic applications where complete removal of the carbonyl group is desired.

What is the mechanism for forming a thioacetal from a carbonyl compound?

The formation of a thioacetal from a carbonyl compound involves the reaction of the carbonyl with a thiol (RSH) or a dithiol in the presence of a Lewis acid like BF₃. The mechanism starts with the Lewis acid activating the carbonyl group, making it more electrophilic. The thiol then attacks the carbonyl carbon, forming a hemithioacetal intermediate. This intermediate undergoes further reaction with another equivalent of thiol (or the second thiol group in a dithiol) to form the thioacetal. The overall process is similar to acetal formation but uses sulfur-containing reagents and a Lewis acid catalyst.

Why is BF₃ commonly used in the formation of thioacetals?

BF₃ (boron trifluoride) is commonly used in the formation of thioacetals because it is a strong Lewis acid. It effectively activates the carbonyl group by accepting electron pairs, making the carbonyl carbon more electrophilic and susceptible to nucleophilic attack by the thiol. This activation is crucial for the formation of thioacetals, as it facilitates the initial step of the mechanism. The use of BF₃ ensures a more efficient and controlled reaction compared to using a general proton-donating acid.