Enolate - Online Tutor, Practice Problems & Exam Prep

Enolates are crucial intermediates in organic chemistry, formed through base-catalyzed tautomerization. The enolate anion, where the negative charge is on the alpha carbon, acts as a strong nucleophile, allowing for new reactions that substitute electrophiles at the alpha position of carbonyl compounds. This contrasts with traditional nucleophilic addition, where the carbonyl carbon is the electrophile. Understanding enolates opens pathways to synthesize alpha-substituted carbonyls, enhancing the scope of carbonyl chemistry significantly.

Formation of Enolates

Now we're going to focus on one of the most important intermediates for all of organic chemistry, and that's called the enolate. Specifically, in the base catalyzed tautomerization mechanism, the base catalyzed version, we form a resonance-stabilized intermediate called an enolate. Let me show you. Remember that in the base catalyzed version, what winds up happening is that my O negative grabs the alpha proton right away. I wind up forming a double bond here and then kicking electrons up to the O. This gives me a possible resonance structure though where, on the one hand, I have the negative charge on the O, but I could easily resonate that down to the carbon. Then, it could resonate back up. Both of these are considered the enolate anion, and both of them are correct. But for the purposes of this section, one of these is going to be far superior in helping us predict what a product will look like. The one that we're going to use is the one where the negative charge rests on the carbon. Why? Because that's going to help us realize that alpha carbons in basic solution are actually good nucleophiles. That's totally different from anything else we've done with carbonyls before. Because up until this point, we've been taking carbonyls and we've been saying that they're good electrophiles, that it's good to add stuff here. But now what I'm telling you is that the alpha carbon is actually a good nucleophile, meaning that the alpha carbon can actually do this. Crazy. We have a whole new set of reactions. A whole new branch of carbonyl chemistry opens up to us when we use enolates. Now, what I want to do is I want to use the next section to compare nucleophilic addition, which is a mechanism we should already be familiar with the mechanism of enolates.

General Reactions

By now, I really hope that you're familiar with nucleophilic addition because it's just that important. Remember that you've got a partially positive carbon on the carbonyl. Nucleophiles can attack it, kick electrons up to the O. I wind up getting a tetrahedral intermediate. Remember that at this point, that O negative has no other choice other than to protonate because it has no good leaving groups that it can kick out. It's just going to protonate instead and make a substituted alcohol. This is the reaction that Grignards undergo, that reduction undergoes, and lots of other negatively charged nucleophiles. But what happens if instead of reacting my carbonyl with any random nucleophile, what if I react it with a base, with a base specifically suited to take off an alpha proton? What's going to happen is that you've got an H. If you use a base to pull off a proton, what you're going to do is you're going to make an enolate anion. This is a completely new reactive species because now if I have a negative charge on that carbon, I can use it to attack random electrophiles. If I can attack electrophiles with my alpha carbon, that means that I'm going to have a way to put things on the alpha carbon, meaning that the products of these enolate mediated reactions are alpha-substituted carbonyls. We actually get things on the alpha carbon, and that's super important. Nucleophilic addition is what we're used to seeing with carbonyls. But the new mechanism that we're going to be using in this section are nucleophiles. You're now going to be substituting nucleophiles. You're now going to be substituting things on the alpha position. Notice that at the beginning, I had an H and I ended up with an E. That's going to be the whole theme of this area. When we deal with enolates, we're going to be using them to substitute hydrogens for whatever electrophiles we want to react with. I hope that made sense. That's the general reaction. Now let's move on to some specific reactions.

Here’s what students ask on this topic:

What is an enolate and how is it formed?

An enolate is a resonance-stabilized anion formed during the base-catalyzed tautomerization of carbonyl compounds. The process begins when a base removes an alpha proton (a hydrogen atom attached to the carbon adjacent to the carbonyl group). This deprotonation results in the formation of a double bond between the alpha carbon and the carbonyl carbon, while the electrons from the broken C-H bond move to the oxygen, creating an O^-. The enolate anion can be represented by two resonance structures: one with the negative charge on the oxygen and another with the negative charge on the alpha carbon. The latter is particularly important because it highlights the nucleophilic nature of the alpha carbon.

Why are enolates considered good nucleophiles?

Enolates are considered good nucleophiles because the negative charge on the alpha carbon makes it highly reactive towards electrophiles. In the resonance structure where the negative charge is on the carbon, this carbon can readily attack electrophiles, leading to the formation of new bonds. This nucleophilic property is crucial for various organic reactions, such as the alkylation and acylation of carbonyl compounds, allowing for the synthesis of alpha-substituted carbonyl compounds. This behavior contrasts with the typical electrophilic nature of carbonyl carbons in nucleophilic addition reactions.

What is the difference between nucleophilic addition and enolate chemistry?

Nucleophilic addition and enolate chemistry differ primarily in the role of the carbonyl compound. In nucleophilic addition, the carbonyl carbon acts as an electrophile, attracting nucleophiles to form a tetrahedral intermediate, which then protonates to yield a substituted alcohol. This is common in reactions like Grignard additions and reductions. In enolate chemistry, however, the alpha carbon of the carbonyl compound becomes a nucleophile after deprotonation by a base. This nucleophilic alpha carbon can then attack electrophiles, leading to the substitution of the alpha hydrogen with various electrophiles, resulting in alpha-substituted carbonyl compounds.

How does base-catalyzed tautomerization lead to enolate formation?

Base-catalyzed tautomerization leads to enolate formation through the removal of an alpha proton by a base. The base abstracts the proton from the alpha carbon, resulting in the formation of a double bond between the alpha carbon and the carbonyl carbon. The electrons from the broken C-H bond move to the oxygen, creating an O^-. This intermediate can resonate to place the negative charge on the alpha carbon, forming the enolate anion. This process is crucial for generating nucleophilic species that can participate in various organic reactions.

What are some common reactions involving enolates?

Common reactions involving enolates include alkylation, acylation, and aldol reactions. In alkylation, the enolate anion attacks an alkyl halide, substituting the alpha hydrogen with an alkyl group. In acylation, the enolate reacts with an acyl chloride or anhydride, leading to the formation of a beta-dicarbonyl compound. The aldol reaction involves the enolate attacking another carbonyl compound, resulting in a beta-hydroxy carbonyl compound, which can further dehydrate to form an alpha, beta-unsaturated carbonyl compound. These reactions are fundamental in organic synthesis for constructing complex molecules.