I understand that 2-pyridone derivatives can be synthesized by oxidizing an N-methyl pyridinium salt with $\ce{[Fe(CN)6]^3-}$ under basic conditions. Can a similar method be used to produce 4-pyridones ?
$\begingroup$
$\endgroup$
Add a comment
|
1 Answer
$\begingroup$
$\endgroup$
2
A reliable and old reference on the synthesis of 1-methyl-2-pyridone (Org. Synth. 1935, 15, 41, DOI) does not mention the formation of 1-methyl-4-pyridone as a side product and I doubt that it and can be formed that way.
The synthesis of 1-methyl-2-pyridone starts by reacting equimolar amounts of dry pyridine and dimethyl sulfate to form the N-methyl pyridinium salt. Then, the mixture is diluted with water and solutions of $\ce{NaOH}$ and $\ce{K3[Fe(CN)6]}$ are simultaneously added.
This seems to do the trick: the $\beta$-amino alcohol formed by adding $\ce{OH-}$ ortho to the nitrogen atom is immediately oxidized, which prevents the opening of the pyridinium salt.
For the synthesis of 1-alkyl-4-pyridones, a somewhat classical approach would be to react the corresponding 4-pyranone with a primary amine under more or less drastic conditions, as shown in Can. J. Chem., 1976, 54, 3377.
Altenatively, Grignard reaction of a 2-substituted 4-benzyloxypyridine-N-oxide, followed by debenzylation/methylation with methyl triflate and subsequent treatment with $\ce{NaOH}$ will yield the desired a 1,2,5-trisubstituted 4-pyridone (DOI).
answered May 18, 2015 at 12:12
-
$\begingroup$ Many thanks ! Do you know of any way to make 4-pyridone from pyridine (via n-oxides or otherwise) ? $\endgroup$– J. LSMay 18, 2015 at 14:50
-
$\begingroup$ @J.LS Do you mean the unsustituted parent 4-pyridone? I would buy its tautomer, 4-hydroxypyridine, and dissolve it in a somewhat polar solvent. In solution, the pyridone should dominate. $\endgroup$ May 18, 2015 at 14:58