Sciencemadness Discussion Board

Mannich reaction with enolizable aldehydes

Rattata - 15-6-2009 at 16:08

Will the mannich reaction take place with enolizable aldehydes such as acetaldehyde? Organic-chemistry.org claims that only non-enolizable aldehydes such as formaldehyde will partake in the mannich reaction but somebody is swearing to me otherwise and I can't find any (other) references to prove or disprove his claim.

Also he points out that tropinone synthesis reacts an enolizable aldehyde and a carbonyl compound (acetonedicarboxylic acid) which is then decarboxylated to yield tropinone.

Is he right or is organic-chemistry right? :p

[Edited on 16-6-2009 by Rattata]

entropy51 - 15-6-2009 at 16:13

http://pubs.acs.org/cen/news/86/i08/8608notw8.html

Rattata - 15-6-2009 at 16:29

So that states that acetaldehyde (and other enolizable aldehydes?) will react with an amine to form a substituted mannich base in the presence of a catalyst like proline?

Most-interesting :)

Also of interest I'm looking at the strecker amino acid synthesis now which also seems to use a substituted mannich base as an intermediate so I guess that backs it up.

[Edited on 16-6-2009 by Rattata]

Nicodem - 15-6-2009 at 22:53

The example given by Entropy51 is not relevant to your question. If you look more carefully at the referred reaction you will see that acetaldehyde there is the enolic (nucleophilic) counterpart and that the electrophilic aldehyde used is non-enolisable (benzaldehyde).
Essentially the claim at Organic-chemistry.org is correct in its practical aspect, which however does not mean that enolisable aldehydes can not partake the electrophilic role in the Mannich reactions. The problem is only in the selectivity, not in the reaction itself. In short, if the wannabe electrophilic carbonyl compound is enolizable to a similar extent as the wannabe nucleophilic counterpart, then there are no limitations as for their roles to be reversed. As a consequence there is no selectivity and one gets a mess instead of the desired product. But if the difference in between the pKa's of the nucleophilic and electrophilic carbonyl counterparts is big enough (like 7 units or more) then one gets complete selectivity even though the wannabe electrophilic carbonyl compound is enolizable. One such example you gave yourself (the Robinson tropinone synthesis), but there are others as well. On the other hand, if you don't mind both carbonyl compounds to be the same then there is no problem and you get the Mannich product of self condensation (one such example is the synthesis of 2,2,6,6-tetramethylpiperidin-4-one from acetone and ammonia). Essentially, the limitations of the Mannich reaction in this regard are the same as those in the base catalysed aldol condensation.

Nernst - 17-6-2009 at 09:35

The Mannich reaction as I know it, is a 3 component reaction:

1. a secondary amine (primary gives things we don't want)

2. a non enolizable aldehyde

(If you want aminomethylering -> formaldehyde)

3. a enolizable carbonyl..

...just my 2 cents

[Edited on 17-6-2009 by Nernst]

Rattata2 - 22-6-2009 at 23:48

Nicodem thanks for your response, that explains a lot :)

basstabone - 23-6-2009 at 19:12

Quote: Originally posted by Nernst  
The Mannich reaction as I know it, is a 3 component reaction:

1. a secondary amine (primary gives things we don't want)

2. a non enolizable aldehyde

(If you want aminomethylering -> formaldehyde)

3. a enolizable carbonyl..

...just my 2 cents

[Edited on 17-6-2009 by Nernst]


I am kinda curious as to what the product would be when you used a primary amine. I have a reference that states you can use ammonium acetate (what would this be classified as?) or another primary amine.

Paddywhacker - 23-6-2009 at 19:20

Look at the wiki.

basstabone - 23-6-2009 at 20:04

I knew you would get a ring structure based off the reference I have just wasn't quite too sure what he ment when he said products you don't want