[DonOctagon]

Hi guys.

I am only missing one question from graduating from university. I havent passed my organic chemistry 2 course and the last question I need to answer is the following.

1) Ethyl acetoacetate reacts with formaldehyde unde acidic conditions in an aldol-like-condensation reaction.
2) The product from reaction 1) reacts with unreacted ethyl acetoacetate in a Michael-addition.
3) The product from 2) is decarboxylized and the result is 3-methyl-4(C3O2H5)-cyclohexan-1-on , with a doublebond between carbon atoms 2 and 3 (Hagemanns esther)

Does someone know how this reaction occurs? Ive tried to figure it out, searched the net, the books, asked masters of organic chemistry but nowbody is able to give me an answer. I would need a complete answer, where you can see where every single electron and bound goes/breaks.

Thanks a million,
PS. Sorry for the 4(C3O2H5) "name" I dont know the equivalent systematic nomenclature.

[discodermolide]

Try looking up the Knovenagel reaction for the first step

[orgopete]

Are you sure of the reaction conditions? I know there are acid catalyzed aldol condensations, but they are rare. I thought Hagemann's ester was produced under basic conditions, a standard aldol type of reaction, active methylene and carbonyl compound.

[discodermolide]

Are you sure of the reaction conditions? I know there are acid catalyzed aldol condensations, but they are rare. I thought Hagemann's ester was produced under basic conditions, a standard aldol type of reaction, active methylene and carbonyl compound.

The Knovenagel reaction involves an active methylene compound and an aldehyde, I have used ammonium acetate as the acid source. The intermediate Aldol eliminates water to give the alpha-beta unsaturated carbonyl compound

[orgopete]

I have been searching for a good acid catalyzed aldol condensation to complete acid and base catalyzed examples. Upon searching for examples, I discovered they are reasonably rare. I believe this is because the pKa of a protonated carbonyl compound is fairly low. The low concentration contributes to a low concentration of enol to form from it upon deprotonation. That enol then has to add to a protonated carbonyl. I reasoned that the equilibria for all of these steps happening at once resulted in the rarity of acid catalyzed aldol reaction occurring in good preparative reactions.

I knew that acetone can give mesityl oxide by treatment with acid, but that seems like a rather messy reaction. Upon searching, indeed Hagemann's ester can be prepared by an acid catalyzed cyclization of the bis-ester. That seems in line with other examples I had found of acid catalyzed aldol reactions, namely intramolecular cyclizations.

If ammonium acetate constitutes acid catalysis, that has a different connotation of the words "acid catalysis" than I use. Water is an acid source to methyllithium, but it hardly catalyzes a Fischer esterification of a carboxylic acid. The pKa of ethyl acetoacetate is so low that a low concentration of enol is present without acidification. I would virtually surmise that treatment with acid may actually reduce the enol content, though I haven't thought greatly about this. None the less, I really really doubt that ammonium acetate is protonating the carbonyl compound, especially formaldehyde to make it more reactive under acidic conditions. I can see it forming an even more reactive imminium salt, but again, I wouldn't use formation of an imminium salt with acid catalyzed.

Given the nature of the question being asked, "Ethyl acetoacetate reacts with formaldehyde under acidic conditions in an aldol-like condensation" and the next step is the Michael addition, I tried answering in what I thought informative to the poster understanding the chemistry. For example, see question #4, an exam question about the preparation of Hagemann's ester or as suggested a Knoevenagel condensation. In neither case would I call these acid catalyzed. That was my point.