[gingi85]

Why can the benzoin condensation be catalyzed by cyanide and thiamine? Why won't other strong bases/nucleophiles work as well?

[macman104]

The nucleophile that attacks must also be quite electron withdrawing to stabilize the negative charge that forms.  Did you have another base/nucleophile in mind that you were told would not work?

[gingi85]

Apparently sodium hydroxide doesn't work. Is the hydroxide less electron withdrawing than cyanide?

[macman104]

I would believe that the reason is not the lack of it's electron withdrawing ability, but it's leaving group ability.  At the end of the mechanism, whatever attacked the aldehyde needs to be able to leave.  A hydroxide is a horrible leaving group, whereas the cyanide is kicked with relative ease.

[azmanam]

Is the hydroxide less electron withdrawing than cyanide?

Hydroxide is electron donating.

[Nitrous_Acid]

Yes. Bases are electron donating but I dont think that this is a MAIN case with electron donation or withdrawing. I think its a case with the ability of bond formation! CN- ion can form bonds easier than OH- ions!

Hope this helps
http://individual.utoronto.ca/ekwan/benzoin.pdf

[azmanam]

but I dont think that this is a MAIN case with electron donation or withdrawing.

I agree, but will modify your reasoning slightly.  It's not so much the bond formation that explains the reason cyanide works so well.  It is a mixture of leaving group ability and anion stability as mentioned above.

I think the most important role of the cyanide is to provide stability to make the proton that was originally the aldehyde proton in the starting material acidic.  In theory, if you could just deprotonate that aldehyde proton, the reaction would take place without the need for cyanide, and any base would work.  But the aldehyde proton is not acidic.  Removing that proton would put a full negative charge on the carbonyl carbon.  Carbonyl carbon atoms have a partial positive charge as a result of the charge-separated resonance structure that can be drawn for the carbonyl group.  Because the carbonyl carbon atom is so typically electropositive (it has a partial positive charge), the carbonyl carbon atom is rarely thought of as nucleophilic.

The cyanide is used to allow the carbonyl carbon to be nucleophilic.  It adds to the carbonyl carbon to form a cyanohydrin.  The proton that used to be the aldehyde proton (now the alpha proton of the cyano group) is now acidic, due to the resonance stability of the anion which results from deprotonation.  The proton can be removed and the carbanion is nucleophilic and can participate in the benzoin reaction.  The ability to turn an atom with a partial positive charge into a nucleophile is call umpolung - polarity reversal (http://en.wikipedia.org/wiki/Umpolung).

That the cyano group is also a good leaving group after the reaction is complete is the driving force behind using it (as opposed to something else that turns carbonyl groups umpolung) in this reaction.  That cyanide can kill you is probably the driving force behind using thiamine (vitamin B1) instead.

Umpolung is the key here.

[gingi85]

Thank you for your help, everyone!

I would have to agree with azmanam that the reason for using cyanide is because of its stabilizing affect on the carbanion.  This would also explain the use of thaimin which would allow for multiple resonance forms for the deprotonated carbon.

I don't think the leaving group ability is an issue here since we are dealing with a catalyst. The resulting cyanide anion is stabilizing by its positively charged counter cation (Na+, K+, etc.) This would be the case in any nucleophile that would be regenerated in the last step of the reaction.

I think that leaving group ability is only an important factor in substitution (or elimination) reactions, where we compare the stability of the product against the stability of the starting material based on the stability of the leaving group involved.

[azmanam]

I don't think the leaving group ability is an issue here since we are dealing with a catalyst

No, It's precisely because it's catalytic that it needs to be a good leaving group.  If it wasn't a good leaving group, it wouldn't leave, the catalyst wouldn't turn over, and the reaction would stop after 10% (or however much cyanide is present).