Can the Beta carbons of ketones act as nucleophiles? And one more question.

[MechRocket]

[PLAIN]http://img543.imageshack.us/img543/4545/asdfrr.jpg

I'm wondering what the mechanism would be of the reaction in the pic I've attached. It does seem the Beta carbon acts as a nucleophile and attacks the carboxylic acid.

I have a couple of questions, one general (#1) and one specific to the reaction shown (#2).

1. Does the Beta carbon of alpha, beta unsaturated ketones usually act as nucleophiles? I don't remember seeing any of these types of reactions in my undergrad course. Usually, a nucleophile is attacking the Beta carbon in an addition reaction.

2. Even in the presence of a catalyst, I don't know why this reaction can happen. The benzene ring is strongly de-activated is it not? It has a very electron-withdrawing group attached to it. Could it be because the compound is so extensively conjugated that the cation intermediate that forms (+ charge on the alpha carbon) is still relatively stable? Thanks!

 

[SpectraCat]

[PLAIN]http://img543.imageshack.us/img543/4545/asdfrr.jpg

I'm wondering what the mechanism would be of the reaction in the pic I've attached. It does seem the Beta carbon acts as a nucleophile and attacks the carboxylic acid.

I have a couple of questions, one general (#1) and one specific to the reaction shown (#2).

1. Does the Beta carbon of ketones usually act as nucleophiles? I don't remember seeing any of these types of reactions in my undergrad course. Usually, a nucleophile is attacking the Beta carbon in an addition reaction.

Not sure about that, but I think you are correct. However, when the beta carbon is in an aromatic ring, then the effects of resonance stabilization have to be accounted for.

2. Even in the presence of a catalyst, I don't know why this reaction can happen. The benzene ring is strongly de-activated is it not? It has a very electron-withdrawing group attached to it. Could it be because the compound is so extensively conjugated that the cation intermediate that forms (+ charge on the alpha carbon) is still relatively stable?


Thanks!

The way I was trained to think about these reactions is to consider what can happen first ... in this case, protonation of the OH group of the carboxylic acid would be my choice (proton transfer reactions are generally the fastest processes possible). The protonated OH group (i.e. water) is an excellent leaving group for a substitution reaction, which takes place by the electrophilic substitution mechanism called Friedel-Crafts acylation.

The elimination of water leaves a R-C=O+ group behind, which then attacks at the ortho-position of the aromatic ring (the beta carbon). At this point we have closed the ring, but we still have a cation with an extra proton, but that's fine, because we expect a high degree of protonation of anthaquinione in the highly acidic H2SO4 environment. The proton will rearrange from it's unfavorable site on the beta carbon, to one of the carbonyl groups, restoring the full aromaticity of the molecule.

Part of the facility of this mechanism undoubtedly has to do with the enforced steric proximity of the electrophilic CO carbon to the beta carbon in the aromatic ring.

 

[DrDu]

My organic chemistry is long ago, but isn't that a simple Friedel Crafts acylation?
Edit: Should have read SpectraCat's answer till the end.

 

[MechRocket]

Thanks SC. :)