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Relative stability of amides, esters, anhydrides, and acyl chlorides

Relative stability of amides, esters, anhydrides, and acyl chlorides. Created by Sal Khan.

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  • blobby green style avatar for user pslattery522
    You keep calling them ETHERS instead of ESTERS. They are ESTERS, as the title indicates, correct?
    (24 votes)
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  • blobby green style avatar for user tomasajdari
    Chlorine is less electronegative than oxygen, so his reasoning is wrong and there must be another reason.
    (7 votes)
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    • blobby green style avatar for user Dion AE Silverman
      When determining the "stability" of a molecule with respect to a reaction (Molecules can be more or less stable depending on whether they are reacting nucleophilically or electrophilically. The best approximation of absolute stability would be a measure of bond energies. ) one must compare it to the stability of the product. The chloride anion is a better leaving group because it is better able to stabilise a negative charge than an oxygen. This is because although oxygen is more electronegative, the oxygen-R bond is stronger due to oxygen's smaller radius. This is why –OH is a better base than Cl–; the resulting O-H bond is stronger than the H-Cl bond. The same hold true with R-OH and R-Cl.

      Or so is my guess...
      (4 votes)
  • blobby green style avatar for user Anirudh Deshpande
    At Doesn't the fact that anhydride has two equivalent resonating structures make it a pretty stable molecule??
    (4 votes)
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    • piceratops ultimate style avatar for user David Jou
      It would seem to make sense, but keep in mind each resonance structure is reactive because the central oxygen in each structure will only have a pi bond on one side making the other side more reactive. Minimizing the spread of charges will make a resonance structure more significant and the charges in the anhydride resonance structures are relatively spread out as the electrons move throughout the compound.

      Alternatively, you can think about the stability of the leaving groups when each carboxylic acid derivative undergoes a nucleophilic attack and subsequent elimination. For the acyl chloride, the chlorine anion does a great job of holding on to the negative charge since it is relatively large, electronegative, and the conjugate base of a strong acid (so very unreactive/stable). The carboxyl leaving group from the anhydride has two resonance structures and will be quite unreactive/stable as well. The alkoxide leaving group from the ester will be a strong base and thus reactive/unstable. Finally, the amine anion from the amide will be a very strong base/unstable.
      (3 votes)
  • blobby green style avatar for user ajwestonpeters
    I apologise for any inconveniences caused, but I would like to challenge one or two of the suggestions made in the video. Whilst the video was most informative on the reactivity of carboxylic acid derivatives, I cannot help but feel that Mr Khan has made a mistake. When explaining why acyl chlorides were the least stable acid derivatives, Mr Khan focused on the electronegativity of the Chlorine atom, however I would like to point out that with an electronegativity value of 3.0 on the Pauling scale, Chlorine is less electronegative than Oxygen, which has a value of 3.5. Chlorine is also as electronegative as Nitrogen as this element also has a value of 3.0. As mentioned in the video, atoms of Oxygen and Nitrogen are very capable of donating electron pairs to the Carbonyl Carbon atom, whilst the Chlorine atom is incapable of doing this. Perhaps Mr Khan should have focused on the size of the Chlorine atom instead. The Chlorine atom is larger than the Nitrogen and Oxygen atoms. Therefore the Carbon - Chlorine bond would be weaker than the Carbon - Nitrogen and Carbon - Oxygen bonds, as it has the greatest bond length and the smallest percentage overlap of p-orbitals. This is why acyl chlorides are the most reactive carboxylic acid derivatives of the four mentioned in the video. The size of the Chlorine atom may also explain why acyl chlorides do not have a resonance structure. The Chlorine atom may well have a lower electron density than atoms of Oxygen and Nitrogen, making Chlorine atoms weak Lewis acids. In other words, this explains why the Chlorine atom is unable to donate a lone pair of electrons to the adjacent Carbon atom, even though it has three lone pairs to spare.
    (5 votes)
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  • leaf blue style avatar for user Benjamin Tedeschi
    .... sorry, why would an electronegative atom such as nitrogen donate an electron to carbon, which is less electronegative?
    (2 votes)
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    • spunky sam blue style avatar for user Ernest Zinck
      It isn't that the N wants to give its electrons to C, but that it can give its electrons to C.
      The N can still keep 8 electrons in its valence shell if the lone pair electrons are in a π bond with the C. This is not ideal, because the N had complete ownership of the lone pair electrons, while in the π bond the C controls one of them.
      In the resonance hybrid, the structure with a plus charge on the N is a minor contributor, because N doesn't want to give up its electrons. But even this reluctant contribution adds stability to the molecule.
      (4 votes)
  • leaf blue style avatar for user Benjamin Tedeschi
    With all of these carboxylic acid derivatives, why doesn't Sal discuss the possible resonance structures that result in a double bond between the carboxyl-group carbon and the carbon adjoining it in the R-group? Isn't this a possible resonance structure for all of these as well?
    (2 votes)
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    • spunky sam blue style avatar for user Ernest Zinck
      You won't get resonance between the C=O group and the C atom attached to it unless that C atom is also unsaturated.
      Thus, in CH3CH2-CONH2, there is no resonance between the CH2 group and the C=O group, because the CH2 carbon has no π electrons.
      In CH2=CH-CONH2, the π electrons in the CH2=CH group can interact with the π electrons in the C=O group, and you do have resonance.
      At this point in the course, Sal is just interested in explaining the stabilities of carboxylic acid derivatives. The properties of conjugated carbonyl compounds are a topic for another video.
      (3 votes)
  • leaf green style avatar for user DHMO
    It's not related to the video.
    If I have a molecule with condensed formula: CH3CH2COOCH3

    and my teacher gave us the structural formula of this cpd but it's inverted. (I mean the the single bonded O is at the left of the carbon atom with the double bond O.)
    The question is: how to write the condensed formula of that molecule given by my teacher? Can I still write CH3CH2COOCH3?
    Is there a way I can write it from left to right? I know CH3COOCH2CH3 is wrong because the single bond O will be at wrong position. Is CH3OCOCH2CH3 ok? or CH3OOCCH2CH3?
    (2 votes)
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  • piceratops seed style avatar for user Muhammad Ashar
    can't the oxygen atom in the middle (in acetic anhydride) form two double bonds (one to the left and one to the right) in the same resonance structure?
    (2 votes)
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  • blobby green style avatar for user fazbamdad
    But doesnt More Resonance structures possible mean a more stable / lower energy / less reactive molecule ... ? And in this case its not a conjugate base or anything so a more stable conjugate which usually means a more reactive original molecule wouldnt apply here..
    (1 vote)
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  • leaf yellow style avatar for user Raisin5488
    Where is the carboxylic acid on the hierarchy? Cause I thought they were the most stable, but at Sal seems to say otherwise.
    (2 votes)
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Video transcript

I want to make a quick correction to the last video where we introduced the carboxylic acid videos, and then we can actually compare them in terms of their relative stability. And that one mistake I did is when I named the ester, all I did is I named the main carbon backbone. I didn't actually tell you how many carbons you have attached to the oxygen over here. Acetate really just refers to this part over here, knowing that it is bonded to-- or maybe I should say it refers to this part over here. But you also have to specify how many carbons you have over here. So this molecule that we drew over here is actually methyl acetate. Or if you want it's systematic name, it's methyl ethanoate. And this is where we get the methyl from. It is methyl ethanoate. Now, with that out of the way, let's actually compared these carboxylic acid derivatives, and I'll compare the derivatives of acetic acid. So the first one we saw was the amide acetamide. Acetamide looks just like this. This is acetamide. Then the next one we looked at was the ether. And that's the one I just pointed out the mistake on. So this was ethyl acetate. You have CH3 right here. This is methyl acetate. This is where the methyl part comes from. So this is methyl acetate. And then we will compare that to the anhydride version. So this is acetic anhydride. Let me do this in a new color. Acetic anhydride looks like this. And finally, we had the acetyl chloride. Acetyl chloride looked just like this. And, of course, these are all derivatives of acetic acid, which we drew at the top of the last video, which is right over there. Now, let's think about which of these may or may not be more stable. And to think about it, we're going to think about any resonance structures that these molecules might have. So if we first focus on acetamide, we know that nitrogen forms three bonds and then has two extra electrons that form another lone pair. And it's actually electron rich, because it's a good bit more electronegative than the hydrogens here and actually reasonably more electronegative then the carbon it's attached to. So you could imagine a situation where a nitrogen could donate an electron to this carbon right over here, and then that carbon can let go of one of the electrons in a double bond with the oxygen. And so it could go back to the oxygen and you would have a resonance structure that would look like this. Let me actually use the same colors. This oxygen just gained an electron up there. And, actually, let me draw the electron. Well, actually, I'll just put the negative charge due to that electron. And then we had this bond right over here to the nitrogen. But the nitrogen just a gave an electron to this carbon right here, the carbonyl, or what was the carbonyl carbon, and so now we have a double bond over here. And the nitrogen just to gave an electron, so it now has a positive charge. But this is a resonance structure of acetamide, so pretty stable. So this is maybe I should even say quite stable. Now, let's think about an ether here, and we could probably do something fairly similar. So if we think about this ether here, oxygen has two extra lone pairs. It is more electronegative than the things that it is bonded to, so it could do a very similar thing to what this nitrogen did. It could give an electron to this carbon right over here, and then that carbon can give back an electron to the carbonyl oxygen, to that oxygen over there. And so it's resonance structure would look like this. It would have a resonance structure, so it's almost the exact same thing is as what we saw with the amide. So it would have a resonance structure. This oxygen just gained an electron. Now it will have a negative charge. This bond to the oxygen is still there, but this oxygen just gave another electron, formed another bond with what was the carbonyl carbon. It actually forms a new carbonyl group, if you want to view it that way, and so it will look like this. And this oxygen gave away an electron so now it has a positive charge. So this seems like a pretty good resonance structure. So the question is which of these two are going to be more stable? And the answer there really just comes out of the Periodic Table. If you look at nitrogen and oxygen, they're right there. They're both near the top right. They're both pretty electronegative, but oxygen is more electronegative. It is to the right of nitrogen. So because oxygen is more electronegative, remember, electronegativity is just the tendency to hog electrons. How much do you like to hog electrons? Oxygen likes to hog electrons more than nitrogen likes to hog electrons. So it would be less likely, marginally less likely, to give away an electron than nitrogen would be, so this resonance structure is a little bit less likely, or when you think of it probabilistically, it's going to happen a little bit less frequently than this resonance structure. So this one right here, this is going to stabilize it less. So this is going to be a little bit less stable then the amide. So if we called this quite stable, I'll just say this is just stable over here. Now let's think about what's going to happen with the anhydride. The anhydride, once again, we have an oxygen right here. It's got its spare electrons. It's more electronegative than the things that it's bonded to. So it seems like you could do something very similar to what we saw with the actual ether. It could donate an electron to this bond right over here, in which case, you would have a resonance structure that looks like this. And if it donates an electron to this carbon over here, then an electron can be taken away from the carbon and given back to that oxygen. So that would give us a resonance structure that would look like this. That guy now has a negative charge. We now have a double bond to this oxygen. it still has another bond to the other acyl group, just like that. And now this oxygen gave away an electron, so it has a positive charge. So it seems like a very similar situation to what we saw with an ether. But there's another resonance structure here. You could also have a situation where instead of the electron being donated to this carbon bond and that happening, you could have a situation like this, where the electron gets donated to that carbon bond and then this electron gets taken back by that oxygen, so you would have this situation. You would have a situation where this acyl group still looks the same bonded to this oxygen, but now we have a double bond over here. This guy took away an electron. So one of the bonds in the double bonds goes away. It now has a negative charge, and then you have the rest of the molecule. So you actually have these two resonance structures. And, of course, this is now a positive charge since it gave away electron. So you might say, hey, more resonance structures, more stability. But the key here is to realize that both resonance structures are dependent from the same oxygen. They essentially have to share this oxygen's electrons. So each one of these individually is less likely to occur than just what occurs with the ether. You can kind of view it as both of these bonds have to share what in the ether this one gets on its own. And we even saw that this is still less likely to occur than this over here. So in this situation, in an anhydride, if one guy's getting the double bond, the other guy's-- if there's a resonance structure on one side of the anhydride, the other side is still reactive. If there's a resonance structure on the left side, then the right side is still reactive, so we'll call this less stable. This right here is less stable. Then finally, you have your acetyl chloride. And acetyl chloride, there really is no resonance structure here. Chlorine is so electronegative that it is unlikely to give away an electron. It is sitting pretty with eight electrons. That's actually true from these other characters right here. But chlorine is very, very unlikely to contribute a resonance structure here. So this gets no stability, so this is the least stable of the carboxylic acid derivatives that we're looking at. Now, why am I even bothering with all of this hierarchy of stability for carboxylic acid derivatives? And I'm bothering with it because we know-- or we don't know quite yet, but I've already shown you some mechanisms that can take us from a carboxylic acid to an ether or carboxylic acid to an acyl halide. And, in general, you can go between all of these and a carboxylic acid. But since we know their relative stabilities, we know that if you start with an acetyl chloride, you're much more likely to go to an acetamide if you have the proper ingredients in there. If you have some amides floating around than the other way around. You're much more likely to go from that to that, because this is much less stable than that, then you are to go from acetamide to acetyl chloride. Likewise, you're much more a likely to go from a carboxylic acid to-- let me put it this way. You're much more likely to go from a carboxylic acid to an acetamide, and I haven't drawn the carboxylic acid here, but this has better resonance than even its original carboxylic acid than the other way around. Or you're much more likely to go from an anhydride to an ether. So that's why I'm doing this hierarchy. You're much more likely to go from something on the right to something on the left. And we'll explore some of those mechanisms in the next few videos.