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Ch. 19 - Aldehydes and Ketones: Nucleophilic AdditionWorksheetSee 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
Naming Aldehydes
Naming Ketones
Oxidizing and Reducing Agents
Oxidation of Alcohols
Alkyne Hydration
Nucleophilic Addition
Organometallics on Ketones
Overview of Nucleophilic Addition of Solvents
Acetal Protecting Group
Imine vs Enamine
Addition of Amine Derivatives
Wolff Kishner Reduction
Baeyer-Villiger Oxidation
Acid Chloride to Ketone
Nitrile to Ketone
Wittig Reaction
Ketone and Aldehyde Synthesis Reactions
Additional Guides
Acetal and Hemiacetal

Concept #1: 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 thioacetal is really the same exact thing as an acetal 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. It even reacts very, very similar. 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 thioacetal, 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 these acetals 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 acetals 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 structured with a positive charge down here. The mechanisms are 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 wanna regenerate the carbonyl. But there's a very important secondary reaction that only thioacetals can undergo that we want to make sure that we learn here. That secondary reaction is when you combine a thioacetal with Raney nickel. Raney nickel is a strong reducing agent. I’m going to put here strong reducing agent that work specifically with thioacetals. What it does is it replaces the entire sulfur ring or the dithioesther ring with Hs. The Raney nickel catalyst is a great way to remove carbonyls altogether. If you’re intention from the begging was just let me get rid of that carbonyl and make it into an alkane, then thioacetal with Raney nickel is the way to go.
I’m going to let you guys do this example here. Notice that there's multiple steps. First I'm actually starting off with an acetal then I’m reacting with dilute acid so you can try to think what's going to go on there. Draw all the structures for A, B, and C. Then we'll be done with this topic. Go ahead and do that and then I’ll do it for you.

Example #1: Raney Nickel Reduction


Alright, so product A is just going to be the reversed 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. So how do you know what that carbonyl will look like? Well 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 O, well actually I'll split it on the O's, anything past the O's must have come from the alcohol and anything on this side must have come from the carbonyl so what that means is that my alcohol originally looked like this. As you can see those two, the two carbons that were in between the O's 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 carbon goes where the acetal now is so it would be cyclobutanol. Now I'm going to get that molecule with a thioacetal reaction and guys 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, so now the carbonyl is going to react with two thiols and some kind of acid, it doesn't tell me which one but I don't really need to know it it's catalytic anyway.

What this is going to do is it's going to give me structure B which is going to be an acetal or a thioacetal. What I could do to get the structure is I could just draw the general structure and plug in the R group so that's what I always do so I would do something like this, S R, S R, carbon carbon. And now I'm just going to change, swap out the R's for what the R was in my thiol so my thiol is going to be I guess a propanethiol, three carbons so I would do one, two, three and one, two, three and now I've got my thioacetal. Cool? So that's structure B. We have A, we have B. Now what's raney nickel going to do this? Oops, whoa, whoa, just a second. I made a mistake and that's okay, we can make mistakes because I forgot one part. The general structure for thioacetal is R R at the bottom. I also have to substitute what those R's are, so what are those R's in particular? Are those are, I sound like a pirate. It's the whole cyclobutanol, so I just replace these R's at the bottom with the square. Now that's correct.

Now when I use raney nickel, raney nickel is a great way to remove carbonyls completely so I'm just going to end up with cyclobutane. Plus I'm going to get whatever reactant the raney nickel and the thioacetal but I don't care about that at this point, I just care about the organic product which is going to be the cyclobutane. Awesome guys, so just a nice little review of thioacetals and raney nickel. Let's move on to the next topic.