Question

The following scenario occured:

Vanillin and acetone were stirred on ice bath. Then HCL was added and the mixture was stirred on ice for 2 h. At the end of stirring, cold DI water and acetic acid were added. The solution incubated for 1 week, but the reaction did not yield product.

Why did product not form? Can a crossed-aldol condensation reaction occur under acidic conditions? If so, why not?

Answer 1

Acid catalysis is extremely useful, but it leads to a lot of arrow pushing.

Vanillin reacts fairly readily with acetone at room temperature, but (unlike benzaldehyde and other nonphenolic aromatic aldehydes) its too slowly to finish in one laboratory period. Presumably, anions of phenolic aldehydes are less readily attacked by the acetone enolate ion than neutral molecules would be. When we are operating under acidic conditions, H₂O isn’t a good base and a poor leaving group to make the reaction possible.