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Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon WorksheetSee 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
Tautomers of Dicarbonyl Compounds
Acid-Catalyzed Alpha-Halogentation
Base-Catalyzed Alpha-Halogentation
Haloform Reaction
Hell-Volhard-Zelinski Reaction
Overview of Alpha-Alkylations and Acylations
Enolate Alkylation and Acylation
Enamine Alkylation and Acylation
Beta-Dicarbonyl Synthesis Pathway
Acetoacetic Ester Synthesis
Malonic Ester Synthesis

Concept #1: Tautomers of Dicarbonyls


In this video, I want to discuss the specific tautomers of dicarbonyl compounds. I’ve already introduced the fact that tautomers happen to carbonyls whether you like it or not. This is just a natural process that occurs at equilibrium. Just because it happens, doesn't mean that it happens at very appreciable amounts. In fact, most carbonyl compounds are going to favor the keto tautomer. Why? Thermodynamic. It’s just more stable. The keto tautomer is more stable than a vinyl alcohol. But beta-dicarbonyls are special because beta-dicarbonyls are shaped in such a way that they’re actually going to favor the enol tautomer. How do we explain that?
Let's look at the beta-dicarbonyl for a second. First of all, let’s define beta-dicarbonyl that you have one carbonyl and another one beta to the one that you currently have. We remember that the alpha-carbon of a carbonyl has a pKa of around 20. These are pKas that we’re talking about here. Does anyone want to take a stab at what the pKa is between a beta-dicarbonyl? What’s the pKa of this hydrogen here? Notice that now it has two carbonyls on both sides. This is going to be a ridiculous pKa of 10, depending – 9, 11, 13 – around that area. How do you explain that? That’s a crazy acidity. That’s as acidic as ammonium, NH4+, with a positive charge. How do you get something that acidic that’s just an alkane? Because of the stability of the enol tautomer. Look at what the enol tautomer is going to look like. The enol tautomer, first of all you’re going to have two tautomers that are possible.
What you're going to get first of all is a bunch of overlapping atoms that can resonate. This is called conjugation. Conjugation makes molecule stable. Conjugation is going to stabilize these. On top of that, we’ve even got hydrogen bonding because the enol from one side is going to be able to hydrogen-bond with the keto from the other. This is the enol side and this is the keto side. It can yield to hydrogen-bond with itself. What winds up happening is that if you take away a proton from the beta-dicarbonyl, the methylene carbon in the middle, you’re actually going to get 75% enol in equilibrium depending on what the R groups are obviously. If these R groups are different things, the number will change a little bit. I'm just letting you know this is an extremely favored tautomerization.
Beta-dicarbonyl compounds are exceptionally acidic due to the high stability of the conjugate base. One thing to keep in mind tis that since this is going to happen so frequently, if you happen to have a chiral center at the alpha-carbon, let’s say that this had been a chiral center. It's not now because I’ve got two Hs. But if it was a chiral center, that chiral center will always be racemized. Wat the heck does that mean? It just means that you can't isolate one enantiomer. You’re going to wind up getting a mixture of both, 50-50. Why? Because when you form the enol, you’re going to lose your stereochemistry. You’re going to turn trigonal planar. You’re going to lose the wedge and dash structure. Then when you add, you could either add the proton from the front or from the back. You're going to get a racemization of any alpha-carbon. That's pretty much as a rule. You’re going to racemize all of your alpha-carbons.
This being said, beta-dicarbonyls are very important for organic synthesis because they're so good at doing tautomerization. Let’s do this problem here. I want you to look at the problem and evaluate which of these beta-dicarbonyls is going to be the most acidic one of all. Think about the one that can form the most tautomers. Do that and then I’ll answer. 

Example #1: Acidic Ketones


Alright, so I'm actually just going to go through these pKa is one by one. So, my first compound, compound a, let's say. Well, it doesn't have anything special about it guys, it has alphas, good, but these are just normal alpha carbons. So, I would expect them to have a pKa of about 20 each, okay? So, that's not going to be the best, B, almost the same exact thing as A, okay? There's really no difference because I just have carbonyls with alpha carbons on both sides. So, it's the same thing, okay?

C, C is special, C is a beta dicarbonyl. So, I would expect that the hydrogen between those is going to be extraordinary acidic, it's going to have a pKa of about 10, okay? So right now that's my winner, but let's keep going, D, anything special about D, actually D just got worse because notice that everything is an alpha, okay? But nothing has is in between two carbons, perfectly between two, it has like a space. So, this one's going to go back to being the same thing as A, okay? Then finally E, what's going on here? Well, guys I actually have one hydrogen, one single hydrogen, that is alpha to 3 carbonyls, guys this is going to be crazy acidic, this might have a pKa as low as 6 to 7, okay? This is going to be the winner for sure, this is the most acidic guys because it can form tautomers with all of those carbonyls, all of those can form enols, this thing is going to be going wild, tautomers everywhere, okay? So, the answer is E. So, obviously E would be a really good molecule to do in an enolate reaction or a reaction that requires tautomerization great. So, let's keep going.