chlorine vs anhydride

[reburbia]

Why is chlorine a better leaving group than an acid anhydride? The latter has the more electronegative oxygen and resonance.

If the answer, as it is often in o-chem, "just memorize that sh**"... that's fine. But I wanted to know if there existed an intuitive answer that I may extrapolate to other situations.




**I assume this must have been asked before, but sorry I couldn't find it for the life of me...

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[chiddler]

(don't worry about reasking questions)

acid anhydride leaving group? i'm not sure i've seen that before, nor can i imagine how it is.

do you mean decarboxylation?

 

[SaintJude]

Never heard this myself. I included a pic below, b/c I like to visualize the molecules I'm talking about as we discuss.

Anyway, I know that acyl halides are more reactive than anhydrides, b/c anhydrides are more stable. A water nucleophile can attack the carbonyl compound in anhydrides and the leaving group is actually a carboxylic acid --which is not as good as a leaving group as halogens.

 

[pfaction]

You're right, and here's why [TPR]:

Strong acid conjugate base = unreactive.
Acid = octet will be a good nucleophile.

 

[chiddler]

lol

so the leaving group is not an acid anhydride. it's an ester that was part of an anhydride.

 

[syoung]

The best leaving groups are the ones that are weakly basic (Cl is a weak base because it is the conj base of a strong acid. As the leaving groups become stronger in base, they are also poorer leaving groups. Just look at R-OH. Try making OH- a leaving group!

 

[Buttafuoco]

That probably makes the most sense in terms of trying to make things quantitative. We know that HCl is a much stronger acid that acetic acid, so we should know that the acetate ion is going to want to leave less than a chloride ion.

 

[SaintJude]

Well, if you are indeed asking about reactivity...The greater electronegative-withdrawing power of Cl- will cause the carbonyl group to become even more receptive to nucleophilic attack than the carbonyl carbon of a carboxylic acid.

 

[thestrokes14]

No one seems to have gotten to the root answer here...

Both are good leaving groups because both are weak bases (conjugates of strong and weak acids).

The difference in reactivity is because the anhydride leaving group can act partially as an electron donating group, making the carbonyl carbon less electrophilic. This, along with slight differences in quality of leaving group, is why acid chlorides are the most reactive.

 

[syoung]

If you look at the pka, one is -7 and one is about 4-5, that's a HUGE difference in pka and thus reactivity

 

[reburbia]

No one seems to have gotten to the root answer here...

The difference in reactivity is because the anhydride leaving group can act partially as an electron donating group, making the carbonyl carbon less electrophilic. This, along with slight differences in quality of leaving group, is why acid chlorides are the most reactive.

Hmmm, now that's interesting. Thanks everyone.

Definitely won't be forgetting "Cl better LG than anhydride" anytime soon..