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Ch. 20 - Carboxylic Acid Derivatives: NAS 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
Carboxylic Acid Derivatives
Naming Carboxylic Acids
Diacid Nomenclature
Naming Esters
Naming Nitriles
Acid Chloride Nomenclature
Naming Anhydrides
Naming Amides
Nucleophilic Acyl Substitution
Carboxylic Acid to Acid Chloride
Fischer Esterification
Acid-Catalyzed Ester Hydrolysis
Lactones, Lactams and Cyclization Reactions
Decarboxylation Mechanism
Additional Guides
Carboxylic Acid

Carboxylic acid derivatives are defined as any carbonyl with a single electronegative group (–Z) in the α-position. 

Concept #1: Intro to Carboxylic Acid Derivatives


On this next page, we're going to define two extremely important concepts that are going to be essential for this next topic. The two things we’re going to define is what is a carboxylic acid derivative? So, 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. That'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. 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 things 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 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 negative. Those are our Z groups.
Notice that they're not all quite as good electronegative groups. For example, chlorine is very electronegative. Nitrogen, not so much. But the reason that we cluster them altogether 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 or an 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 it’s a specific one. Carboxylic acid you could think of it 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 strange little fact here is that nitriles also fall into this category due to their ability to be hydrolyzed. We’re going to see later, notice that I don’t have nitrile on my list but nitriles look like this. It turns out that they can be hydrolyzed using basically water, an acid or base to carboxylic acid. We consider nitriles to also be carboxylic acid derivatives. In this next video, what I’m going to do is I’m going to 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 underago. 

Concept #2: Intro to Nucleophilic Acyl Substituion


Alright 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 one that had a nucleophilic addition, okay? So, first I want to show you is what happens when a nucleophile interacts with a ketone or an aldehyde? Well, 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. Now, if we make that bond, we have to break a bond. So, we're going to break up on 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, okay? That tetrahedral intermediate is now going to have a new nucleophile attached to it. Alright, whatever you want it, whatever had the negative charge. Now, this tetrahedral intermediate is going to protonate, the reason is because there's nothing else that it can do, okay? if it were to try to reform a double bond it would first of all it would break the octet here, it'd 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 and R negative if I try to break it, okay? Is R negative a good leaving group? guys it blows, it's the worst ever, okay? How about the nucleophile? Well, guys the nucleophile is the thing that attacked. So, obviously it's not going to want to come off now, that's what started the reaction. So, anyway this negative is stuck is going to protonate with some acid and we get a substituted alcohol, okay? And, this is the mechanism that organometallics undergo, that most reducing agents undergo. So, this should be somewhat familiar to you at this point, okay?

Now, let's look at some interesting changes that happen when you add a z group, so guys the nucleophile, 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, so that Z group could be even activating it more towards attack, the difference is with the tetrahedral intermediate guys, because what we're going to get is a negative and a nucleophile and this negative is different than the last one because the last one is stuck, there's nothing I could do because if it tries to reform a double bond it would violate an octet, it didn't have a good liter group but Z groups can leave, depending on the environment, we can make Z groups leave. So, in this mechanism instead of protonating, your negative charge actually reforms the double bond and kicks out the Z group, okay? So, this acidification step, the protonation step doesn't happen because it's just going to reform the carbonyl. So, we wind up getting is a double bond here. So, draw that in guys, I want you to draw this in for yourself and you get the new nucleophile. Now, notice what just happened guys I started off with one substituent on the carbonyl and I ended up with another, I just did a substitution, how I changed Z for whatever my nucleophile was. So, instead of getting what we called a substituted alcohol at the top, we're going to get a substituted carbonyl because you preserve the carbonyl, you just change the R group, okay? So, this mechanism is called not nucleophilic addition, it's called nucleophilic acyl substitution, this is the mechanism that all carboxylic acid derivatives undergo, okay? And it's going to be the subject of an entire field of chemistry that has to do with carboxylic acid derivative chemistry, okay? So, these mechanisms start off the same but they end off very different because of the presence of that Z group, alright? So, let's move on.