Rattata
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Mannich reaction with enolizable aldehydes
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]
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entropy51
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http://pubs.acs.org/cen/news/86/i08/8608notw8.html
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Rattata
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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]
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Nicodem
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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.
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Nernst
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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]
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Rattata2
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Nicodem thanks for your response, that explains a lot
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basstabone
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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.
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Paddywhacker
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Look at the wiki.
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basstabone
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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
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