Clutch Prep is now a part of Pearson
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

Hydroxycarboxylic acids and aminocarboxylic acids can be made to cyclize, forming lactones and lactams, respectively. 

Concept #1: Lactones and Lactams


Now I want to discuss lactones, lactams and cyclization reactions.
It turns out that esters and amides can be made to form rings. When you have a cyclic ester or a cyclic amide, these molecules have their own names that are very prevalent in organic chemistry that you should be aware of. A cyclic ester is called a lactone. A cyclic amide is called a lactam. The way that you get these is through the cyclization of either hydroxycarboxylic acids. Here I have an example, a hydroxyl group on a carboxylic acid or amino carboxylic acids as I have here. These molecules are going to form rings spontaneously when the rings can be five and six-membered. Why? Because these are very stable rings. For example, here I have delta-hydroxyvaleric acid. Notice that when delta-hydroxyvaleric acid cyclizes, what happens is that this O comes in, attacks the carbonyl, you get a tetrahedral intermediate. But eventually, you kick out this OH. It would just be basically an esterification reaction. Notice that the size of your ring is going to be six, and that's exactly what we would expect. We got a six-membered ring. These equilibrium arrows that I drew are purposeful. Actually, they're pretty much in perfect equilibrium because if you can make a five or six-membered lactone, that’s definitely going to form an equilibrium. In fact, that actually happens in our bodies. Our body’s sugars are forming lactones all the time. Sugars can form six-membered rings and they form lactones all the time in your body.
Now let’s go on to lactams. Lactams, same idea. Nitrogen could come in, do a nucleophilic acyl substitution, eventually you kick out the OH. You can make a four-membered ring. This equilibrium arrow is also purposeful because notice that I'm making a ring smaller than five members. In this case I’m making a four-membered ring. That is much, much less stable. In fact, there's a possibility that this doesn't happen on its own at all because of the fact that it's just so strain that it would prefer to exist as a chain. It might take some extra help, some extra reagents to make it into a four-membered ring. Makes sense so far? Five and six is good. Anything less than that is bad. Also anything bigger than that, also not very favored.
Now we get into naming. How do we name these guys? It turns out that the functional group of a lactone or a lactam can also be specifically named by the size the ring. But instead of saying it's a six-carbon lactone, what we do is we use the Greek symbols from where the original substituent would have been. For an alcohol, to make this lactone here a six-membered ring, that means that my alcohol would have had to be on the delta-carbon. Since my alcohol was originally on the delta-carbon, this would be called a delta-lactone. If you’re ever confused about what type of lactone or lactam you have, you could always just start counting from scratch. You could just say the carbon next to the carbonyl is my alpha and then you can just go from there. Just remember that you only count carbon. This is a delta-carbon. Same thing with lactams, exactly the same except that now since this one is smaller, this is what we would call a beta-lactam.
Not bore you, but beta-lactams are really important because beta-lactams are found in pharmaceuticals all the time, in antibiotics. Beta-lactam are extremely good at disrupting the cell membranes of bacteria that's why they work really well in your body. That's what penicillin is. It’s a beta-lactam. That is really all you need to know in terms of the general features of lactones and lactams. Why don’t you guys go ahead and try to cyclize this molecule. See what you get and see if you can generalize what the functional group is. I don't need you to name it because that’s way beyond the scope this course. You don’t need to name the exact molecule but tell me what type of functional group it is and the Greek letter in front of it. Do that now.  

Note: If you're thinking that the β-lactam is missing a hydrogen on the N, you are right! 

Example #1: Cyclization Reaction


Alright, so just following the general mechanism of nucleophilic acyl substitution, my nitrogen could attack, I would eventually get a tetrahedral intermediate, which would then kick out the OH, okay? So, in terms of the size of the ring the size of the Ring would be 1, 2, 3, 4, 5. So, there's a chance that this could form spontaneously. So, what I would get is a five membered ring with a nitrogen on one side, okay? And I just have to add the leftover group. So, I know that I would now have a methyl group on that nitrogen, and I would have a double bond between the two and the three that looks like it's right there, we're done, okay? Oh, wait no, I messed up, right? Because it was two and three, it wasn't, it was between three and four so it would actually be right here, right? okay? So, you might be wondering, what happened to this H? don't worry about it, it got lost in the mechanism, okay? So, now if we have to categorize this functional group in general, what we call it? I don't want the name, the name is very complicated, we would call it an alpha beta gamma, this is going to be a gamma-Lactam not quite as cool as beta lactam, sorry, cool. Awesome guys. So, now I just want to talk about on one more reaction then we don't in this page.

Concept #2: Cyclic Anhydrides and Imides


So the whole point of the sequence of reactions behind me is it for you to memorize this exact sequence, that's not what I'm interested in. I'm just trying to give you an overview of different cyclizations that we might have missed to this point, so the first one is really important, which says that you can use a diacid, okay? 10 points for whoever can remember what's the name of that diacid. Remember, Oh my science, this would be the four carbon diacid. So, this would be succinic acid, okay? So, succinic in the presence of heat can self cyclize and make a cyclic anhydride. Remember, I was telling you guys that anhydrides could be made by the combination of two carboxylic acids coming together, and that's what would happen, when the diacid accept, it would be a ring, okay? So, that's the first part.

So, it turns out that anhydrides, if you use a combination of amine with water, okay? You could make a compound that has both a combination of amide on one side and carboxylic acid on the other, okay? Now, how does that work exactly? Well, think about it like, imagine that you have two equivalents of your ammonia, and by the way, this is supposed to be NH3. So, Wow my apologies guys this was NH3 and not NH2. So, let's say you have two columns of NH3, you have them on both sides and you get two amides, okay? like a diamide, then you could use water to replace only one of them. So, you get an amide on one side and a carboxylic acid on the other. Now, what's interesting about that, is that if you had a situation where you have an amide in a carboxylic acid on the same chain, you can then use heat to bring those together and make what's called an Imide, okay? An imide is a new functional group that we haven't talked about, think of it almost like a anhydride with a nitrogen in the middle, okay? So, it's like a anhydride with nitrogen, okay? Makes sense? Now, guys it turns out that this imide is actually kind of important because this imide is made out of a succinic acid, right? Succinic acid, so that means that this is actually called succinimide, has anyone heard of, Oh and that's right where I am, has anyone heard of succinimide before? does that name sound familiar? Guys, it turns out that our reagent that we've used a lot in organic chemistry so far was succinimide. You guys remember NBS, NBS, what did NBS stand for? NBS was n-bromosuccinimide, okay? So, it's literally this compound but instead of having an H there, having a Br there, isn't that cool? So, now you guys know how to make a succinimide by using a diacid, alright? Awesome, again I'm not asking you to memorize this whole sequence, just to be familiar with the parts of it, okay? Awesome. So, let's move on to the next video.