Carboxylic Acid Derivatives - Online Tutor, Practice Problems & Exam Prep

Intro to Carboxylic Acid Derivatives

Hey everyone. On this next page, we're going to define 2 extremely important concepts that are going to be essential for this next topic. The 2 things we're going to define are what a carboxylic acid derivative is, a category of molecule, and the mechanism that it undergoes, NAS or nucleophilic acyl substitution. Let's start off with the first question. What is a carboxylic acid derivative? It's simply defined as any carbonyl that has an electronegative Z group in the alpha position. It's kind of a lot to chew on. Let's break that down.

Remember that in ketones and aldehydes, by definition, you're stuck with an R or an H. Now, R and H are not electronegative at all. In fact, they make terrible leaving groups. If you think about H negative, that's a strong base; R negative, that's an even stronger base. These are not good leaving groups. What we find is that there's a certain mechanism that they tend to undergo, which we'll see in a second. Whereas, Z groups are defined as something that's slightly electronegative even to very electronegative.

Here are all the Z groups that we're going to be working with in this section. We've got chlorine. We've got basically an ester, OR-OH, NH2. That's a typo. That should actually be NH2-. Sorry about that. Even tutors make mistakes sometimes. Those are our Z groups. Now notice that they're not all quite as good as electronegative groups. For example, chlorine is very electronegative, while nitrogen, not so much. But the reason that we cluster them all together is because they are much better than R groups and hydrogen no matter what.

It turns out that by definition, these Z groups are going to allow these carbonyls to follow a new mechanism that's different from the mechanism that we would see in a ketone and aldehyde called NAS or nucleophilic acyl substitution. A few more definitions about carboxylic acid derivatives: By definition, anything that we call a carboxylic acid derivative can be hydrolyzed back to carboxylic acid using a combination of water with acid or base.

If I ever tell you that this is a carboxylic acid derivative, that is me saying that you could use water to hydrolyze it back to carboxylic acid which, as you see, carboxylic acid would be if I used an OH-. Carboxylic acid is also a Z group; it's just a specific one. Carboxylic acid, you could think of as the mother of all of the other carboxylic acid derivatives because you can always turn those derivatives back into carboxylic acid with hydrolysis.

Another really interesting fact here is that nitriles also fall into this category due to their ability to be hydrolyzed. We're going to see later that notice that I don't have nitrile on my list but nitriles look like this, carbon-nitrogen like that. It turns out that they can be hydrolyzed using basically water and acid or base to carboxylic acids. We consider nitriles to also be carboxylic acid derivatives.

In this next video, what I'm going to do is show you guys the differences between nucleophilic addition, which is the mechanism that ketones and aldehydes undergo, versus nucleophilic acyl substitution, which is what carboxylic acid derivatives undergo.

Intro to Nucleophilic Acyl Substituion

All right guys. So even if you haven't studied your ketones and aldehydes chapter yet, you should still know about nucleophilic addition because there are even some reactions for organic chemistry 1 that had nucleophilic addition. First, what I want to show you is what happens when a nucleophile interacts with a ketone or an aldehyde. What we get is that a nucleophile attacks the carbonyl carbon. Why? Because it's highly positively charged. You've got a strong dipole pulling away from that carbon. If we make that bond, we have to break a bond. We're going to break a bond up to the O and what we're going to do is we're going to get this very famous intermediate called a tetrahedral intermediate. That tetrahedral intermediate is now going to have a new nucleophile attached to it, whatever you want, whatever had the negative charge. This tetrahedral intermediate is going to protonate. The reason is that there's nothing else that it can do. If it were to try to reform a double bond, first of all, it would break the octet here if you try to make a double bond again. But also, it would have no bond to break. Remember that if you make a bond, you could try to break a bond to preserve the octet. But all of these leaving groups suck. If you notice, R would make an R negative if I try to break it. Is R negative a good leaving group? Guys, it blows. It's the worst ever. How about the nucleophile? The nucleophile is the thing that attacked. Obviously, it's not going to want to come off now. That's what started the reaction. Anyway, this negative is stuck. It's going to protonate with some acid and we get a substituted alcohol. This is the mechanism that organometallics undergo, that most reducing agents undergo. This should be somewhat familiar to you at this point.

Now let's look at some interesting changes that happen when you add a Z group. Let's say we're just using the same exact nucleophile. The nucleophile is still going to be attracted to the same exact carbon because it's still electrophilic. In fact, maybe even more so because notice that now we have a Z group. That Z group could be even activating it more towards attack. The difference is with the tetrahedral intermediate because what we're going to get is a negative and a nucleophile. This negative is different than the last one because the last one was stuck. There's nothing it could do because if it tried to reform a double bond, it would violate an octet. It didn't have a good leaving group. But Z groups can leave depending on the environment. We can make Z groups leave. In this mechanism, instead of protonating, your negative charge actually reforms the double bond and kicks out the Z group. This acidification step, the pronation step doesn't happen because it's just going to reform the carbonyl. What we wind up getting is a double bond here. Draw that in. I want you to draw this in for yourself. You get the new nucleophile. Notice what just happened. I started off with 1 substituent on the carbonyl and I ended up with another. I just did we're going to get we're going to get a substituted carbonyl because you preserve the carbonyl. You just change the R group.

This mechanism is called not nucleophilic addition. It's called nucleophilic acyl substitution. This is the mechanism that all carboxylic acid derivatives undergo It's going to be the subject of an entire field of chemistry that has to do with carboxylic acid derivative chemistry. These mechanisms start off the same but they end off very different because of the presence of that Z group. Let's move on.