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Melissa Zimmerman

2-Pyridone tautomer ratio

Dan Vasii  Follow

One factor to consider is the role of hydrogen bonding.

In the gas phase at low pressure there is no hydrogen bonding because the molecules are too isolated; then the hydroxyl form with a pure cyclic conjugation = maximum aromaticity is more stable. In the neat liquid or in a polar solvent, the keto form will have stronger hydrogen bonding due to the carbonyl group being more electron-rich, thus a better proton-acceptor, and the N-H hydrogen with a positive charge on nitrogen acting as a better proton donor for the bond.

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Jill Grant  Follow
«Neat liquid» is synonym to «the pure compound itself» (i.e., no solvent added); and then (for 2-hydroxypyridine vs 2-pyridone), the form of the pyridone is dominant over the other.More
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Ellie Rebellon  Follow
If its given in a question where solvent is not mentioned (I have never seen solvent being given when asked to compare keto-enol forms) then which one to mark, I mean which is the general state where we consider tautomerism?More
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Alexander Streng  Follow

Why not start with the corresponding entry in Wikipedia as suggested in the comment by @Maurice? There, it discerns the solid state

«The predominant solid state form is 2-pyridone. This has been confirmed by X-ray crystallography which shows that the hydrogen in solid state is closer to the nitrogen than to the oxygen (because of the low electron density at the hydrogen the exact positioning is difficult), and IR-spectroscopy, which shows that the C=O longitudinal frequency is present whilst the O-H frequencies are absent.»

from the one of the liquid/in solution:

«The tautomerization has been exhaustively studied. The energy difference appears to be very small. Non-polar solvents favour 2-hydroxypyridine whereas polar solvents such as alcohols and water favour the 2-pyridone.

The energy difference for the two tautomers in the gas phase was measured by IR-spectroscopy to be $2.43$ to $\pu{3.3 kJ/mol}$ for the solid state and $\pu{8.95 kJ/mol}$ and $\pu{8.83 kJ/mol}$ for the liquid state.»

Don't forget $\Delta{}G = -RT \ln{}K$ when accessing the primary references both sections point to, too.

There equally are databases about keto-enol equilibria. The authors of Tautobase for example deposit the extracted data into a public repository on GitHub. 1680 pairs may comfortably read and searched e.g., by (sub)structure with DataWarrior. In the present case, the equilibrium tabulated lists for 2-pyridone in water an estimated $\log{}K = 3.5$ (while the gaseous state is listed with $\log{}K = -0.4$):

enter image description here

Note related earlier posts about this topic here on chemistry.se, like this, or this, too.

References:

Wahl, O.; Sander, T. Tautobase: An Open Tautomer Database. J. Chem. Inf. Model. 2020, 60, 1085-1089; doi 10.1021/acs.jcim.0c00035.

Sander, T.; Freyss, J.; von Korff, M.; Rufener, C. DataWarrior: An Open-Source Program For Chemistry Aware Data Visualization And Analysis. J. Chem. Inf. Model. 2015, 55, 460-473; doi 10.1021/ci500588j.

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Gary Karaff  Follow
Likely you got me wrong when I used a quote of yours.More
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Ian Brooks  Follow
March states that "In other heterocycles, the hydroxy-form predominates. 2-Hydroxypyridone and pyridone-2-thiol are in equilibrium with their tautomers, 2-pyridone and pyridine 2-thione , respectively. In both cases, the most stable form is the hydroxy tautomer." By which I think he means that solvent has no effect on this as in the line before he stated how solvent affected the other tautomerism and in this he said that it dominatesMore
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James M. Potter  Follow
The same database (again, estimated for an aqueous solution) lists for pyridine-2-thiol vs. the thione a $\log{}K = 4.6$ (i.e., thione is the favoured form, too), while pyridine-2-amine is favoured as amine (listed as $\log{}K = -6.5$). Maybe, on occasion, the databases listing of $\log{}K$ - while text books tend to use $pK_a = - \log{}K$ - might pass unnoticed. In line with the database and against «2-Hydroxypyridone and pyridone-2-thiol [...] the most stable form is the hydroxy tautomer» is e.g., Barans yearly hetchem lecture (More
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John Bittlestone  Follow
Didnt get you sir, the video you linked says keto form better due to c=o etc..as mentioned in clayden so which one is right, it didnt mention about solvents igMore
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Gokul Bhandari  Follow
, 25:47).More
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