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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: Nucleophilic Addition of Solvents


In this next page, I want to give you a big picture view of how a lot of seemingly random carbonyl reactions are actually all related to each other. This section is called the nucleophilic addition of solvents. In general, all the reactions that I’m going to show you on this page are all connected by one thing which is that they’re induced by the extraordinary reactivity of the carbonyl carbon. Remember it has a very strong partial positive, so strong in fact that that partial positive isn't just going to react with negatively charged nucleophiles. It’s also going to react with solvents. I want to put here in parenthesis neutral solvents. That means that the carbonyl can actually get neutral things to attack it through nucleophilic addition.
These reactions aren’t going to happen by themselves. They are going to need catalysts. They’re going to need either acid or base catalysts. In general, almost all of these reactions are going to be acid catalyzed. The mechanism we're going to be focusing on in this section are the acid catalyzed mechanisms. Those are the ones that are the most commonly tested on. One general thing about all these reactions that I'm not going to have to say over and over again because you guys will know it is that they’re all fully reversible in mild acids. You could always use mild acid to go back to the original carbonyl that you started with.
Due to the fact that these mechanisms are mostly acid-catalyzed, whenever you have something that’s an acid-catalyzed mechanism then by definition, protonation should be your first step and deprotonation to regenerate the catalyst should be your last. When you're looking at these daunting mechanisms, some of them are going to be twelve-step mechanisms. When you look at them, at least you should know where to start. You should always think I should protonate before I do anything else because it’s an acid-catalyzed mechanism. Let's go through the list. I'm really just going to be giving you just the general features here and then we’ll focus on the details in each respective reaction when I go to the reaction videos.
The first one and the easiest one. Ketones and aldehydes are so reactive. This partial positive is so reactive that it can even get water to react with it. When water reacts in the presence of acid with a ketone or aldehyde, we call that a hydrate. Notice that your product is basically a gem-diol. We would call this a gem-diol or germinal diol. Just keep that in mind. We're just starting it off with the most shocking solvent which is that even water reacts with carbonyls to form a gem-diol. Meaning that if you have a mixture of ketones and water in your test tube, it's actually not going to be all ketone. Some of it is going to be gem-diol because the water is reacting with it. More on that later.
Hemiacetal. Hemiacetals are produced by the addition of one equivalent of alcohol. One equivalent of alcohol will give you something called a hemiacetal. Two equivalents of alcohol will give you an acetal. So hemiacetal, acetal. Notice the difference is that one of them has an OH group and one of them has an OR group. Basically in one of them, you're only adding one OR from alcohol. In the second one, you’re adding two ORs from two alcohols. The name hemiacetal means half of an acetal because hemi is a prefix that means half like hemisphere, half of the world.
Then we've thioacetals. By the way, these can happen in both acid and base-catalyzed reactions but I’m just going to focus on the reagents right now and then we'll talk about the mechanism like I said in separate videos. Thiocetals happen when you mix BF3 with basically RSH. Instead of an alcohol, notice that it’s the same thing as an alcohol but instead of being an alcohol, it's going to be a thio group, so RSH times two. Notice that this reaction is actually very similar to the one above it, acetal and thioacetal. The only difference is that now I’m getting SH groups instead of OH groups because I’m reacting instead of ROH, it’s RSH. That's it. The acid here in this case is just a little special. It’s a BF3 instead of your normal bronsted lowry acid.
Let’s keep going. What happens if you react amines with carbonyls? It turns out that primary amines. If I have NH2 – R, primary amines. Primary amines will give you an amine product. This functional group is called an imine. It's a double bond N with an R-group at the top. This also works for ammonia or NH3. Primary amines or NH3 is going to give you an imine. On top of that, if we react with instead of NH2 – R, if instead of an R group we add something else like for example a Z-group. That Z could equal a few different things. That Z could be another nitrogen. It could be an alcohol, etc. There’s a lot of different things that we could put there. But if you add something else instead of the R, then you're going to get an imine derivative because instead of getting the R at the top, notice this R is what’s attached here. You're going to get a Z instead. Make sense? That would be what we call an imine derivative because of the fact that it looks like imine but instead of having an R-group, it has a Z-group.
Finally, we know what happens when you react with NH3, what happens when you react with primary amines. What about secondary amines? When you have secondary amines, that would be NH with two R groups, RR. Then you get what’s called an enamine. The reason this is called an enamine is because you’ve got an amine part at the top and you’ve got a double bond, an alkene. Put that together, you get an enamine. Instead of just having one R group attached, you have two.
Notice that the orientation of this double bond is really different than the first one. In the imine, the double bond was facing the N. It was on the N. In the second one, the double bond is now towards a carbon. Why is that? That's something that we're going to have to learn through the mechanisms. When we go to the exact mechanism, you’ll understand. But it’s essentially the same exact mechanism, just with one final step that’s different. That’s the biggest difference between them. That is pretty much the extent of the reactions of solvents with ketones and aldehydes. Notice, I pretty every named every single solvent that’s out there. I mentioned water, I mentioned alcohol in every form. I mentioned thiol. Now, I mentioned amines, all types of amines.
If it has a lone pair, it can react with a carbonyl. Now what I want to do is I want to just really briefly introduce what can happen with these reagents. After you make them, what can you do with them? It turns out that hemiacetals, as we’ll learn later are not very stable. They like to go to full acetals so they barely ever last as hemiacetals. Only cyclic hemiacetals are stable. We’ll see that later. This would be a cyclic hemiacetal because notice that I’ve got a carbon that’s attached. It’s got an H, it’s got an R, and then it’s got the OR here and it's got the OH here. That would be a hemiacetal and we’re going to have to learn how to recognize these. But that would be a hemiacetal because I’ve got a carbon in the middle that has an OR and an OH group on two different sides. This one would actually be stable. But if it's not cyclic, it’s not going to be stable.
Acetals are used as protecting groups. Acetal, specifically when you have a dilol, you get cyclic protecting groups. Notice how this thing is a ring. We’re going to see how later on when we use diols instead of two different alcohols, we can use a diol. You get a cyclic acetal and in general, acetals are used as protecting groups. More on that in another video.
What can you do with a thioacetal? Remember that a thioacetal is just a molecule that has a central carbon with Rs on both sides, Rs or Hs and two SHs, two thiols at the top. It turns out that when you react a thioacetal with a reducing agent called Raney nickel. Raney nickel is going to be able to destroy those thiol bonds and make it into a simple alkane. It’s a form of reduction that essentially turning a carbonyl into an alkane because you’re just adding SHs. It’s a way of getting rid of carbonyls completely.
Imine derivatives. It turns out that imine derivatives when you have specifically if I were to use the NH2Z. Specifically if I were to have this derivative, more on that later. That’s called a hydrazone. We’ll talk specifically about that alter. Remember, this is just the overview. But when you react hydrazine with a strong base and heat, you get what's called a Wolff-Kishner reduction. What we find is that a Wolff-Kishner reduction is another way to add hydrogens to a carbonyl. It’s another way to turn a carbonyl into an alkane. Raney nickel to a thioacetal. Wolff-Kishner to a hydrazone, which is an amine derivative, are really the same reaction in terms of they’ll yield the same exact products and they’re used in very similar situations except one is base-catalyzed and one is acid catalyzed because you’re going to have to use that BF3 to get the thioacetal.
Then finally, this is kind of getting way ahead of ourselves but it turns out that enamines, we're going to find out later love to react without alkyl halides to form what we call alpha-substituted carbonyls. This reaction, we’ll talk about it more in the enamine alkylation section of Clutch videos. But essentially you get a lone pair that jumps down, a double bond that attacks the R. Basically, that’s an SN2 reaction and you wind up getting an R group where that enamine was. This is a huge part of organic chemistry all on its own. It’s just talking about how enamines love to react with alkyl halides and other types of electrophiles to get alpha-substitution.
I know this was overwhelming. To some extent it’s meant to be. What I’m trying to show you is that all these reactions, you're going to learn them in different parts of the text. But they're all related by the sense that it's a neutral compound reacting with a very highly positively charged carbonyl carbon. Now what we're going to do is now that you’ve seen the overview, we're going to go to those individual reactions one by one. We're going to learn mechanisms. It’s going to be fun. Let's go ahead and wrap up this topic and start on to the next topic.