4-Pyridone, calculated tautomerism

Repeat your analysis for tautomeric equilibria between 4-hydroxypyridine and 4-pyridone, 2-hydroxypyrimidine and 2-pyrimidone and 4-hydroxypyrimidine and 4-pyrimidone. For each, identify the favored (lower-energy) tautomer, and then use equation (1) to calculate the ratio of tautomers present at equilibrium. Point out any major differences among the four systems and rationalize what you observe. (Hint Compare dipole moments and electrostatic potential maps of the two pyridones and the two pyrimidones. How are these related to molecular stability )... 

The tautomerism of functional derivatives of azines (e.g., pyridones) and other more complex systems (guanines, porphyrins, etc.) has been much studied both experimental and theoretically [40, 76-82], Our contribution to this field has been modest using a combination of 13C and 15N NMR in solution and in the solid state, together with GIAO//B3LYP/6-311++G calculations, the tautomerism of 2-pyri-done, 4(37/)-pyrimidone, uracil, and cytosine were determined [83],... 

Thus, we have studied theoretically the tautomerism of pyridones and 1,2,4-triazoles related to two crown ethers and two crown esters derived from these heterocycles [209], For the four macrocycles 262-265, Bradshaw identified a single tautomer by X-ray crystallography [210-213], To rationalize these findings, a series of calculations from simple models to crown derivatives were carried out. The most interesting case concerns the observation, for the first time, of a 4H-1,2,4-triazole tautomer 265b. 

There appear to be no ERE data for pyridones and related compounds, and although Dewar and co-workers18 have calculated the heats of atomization for a number of structures of this type, the results were used for a discussion of tautomeric equilibria rather than for deriving values for the Dewar resonance energies. Empirical studies on tautomeric equilibria have, however, been used to estimate the difference in ERE of pyridones and pyridine (Section II,A, 4). Beak et al 1 studied the gas-phase 1-methyl-2-pyridone 2-methoxypyridine equilibrium and compared the result with the equilibrium constant for the jV-methylvalerolactam ... 

In an ab initio study of the tautomerism of 2- and 4-hydroxy-pyridines, 4,-hydroxypyridine was calculated to be 2.4 kcal/mol more stable than 4-pyridone. 2-Pyridone was calculated to be 0.3 kcal /mol more stable than 2-hydroxypyridine and this is in good agreement with experimental values obtained from tautomeric studies in the gas phase.61 A study of the bromination of the 2-pyridone/2-hydroxypyridine system has revealed that reaction occurs via the principal "one" tautomer at pH<6 and via the conjugate anion at pH>6. Attack on the "one occurs preferentially at the 3-position, whereas on the anion it probably occurs mainly at the 5-position. The facile formation of 3i5-dibromo-2-pyridone results from the comparable reactivity of the monobromopyridones at pH<1 and pH>4- Practical procedures have been reported for the preparation of 3-bromo-2-pyridone and... 

For many years microwave (MW) spectroscopy has been providing invaluable information about the structure of tautomers in the gas phase. However, more recently, MW spectroscopists have been able to identify several tautomers simultaneously four tautomers of guanine [6] two tautomers of 2-hydroxypyridine/2-pyridone microsolvated with one and two water molecules [7] two tautomers, H and ZH, of 4-vinylimidazole [8] and all five tautomers of cytosine [9]. These data are very useful for theoretical chemists, but reciprocally it should be remembered that MW spectroscopists use high-level theoretical calculations to assign their structures. A cautionary note should be added here about the problem of theoretically calculated entropic contributions and the use of the harmonic approximation [10]. Well-known aspects are the relationships between tautomerism and aromaticity due to the work of some pre-eminent authors Katritzky et al. [11], Schleyer et al. [12], and Krygowski et al. [13]. Another well-understood issue is the influence of intramolecular hydrogen-bonds (IMHBs) on tautomerism [14,15]. 

The most important six-member tautomeric aromatic heterocycles are the pyridine and pyrimidine derivatives. For 2-OH and 4-OH pyridine [59-63], the hydroxy form is the prevalent tautomer in the gas phase. Solvents effect calculations for 2-OH pyridine in cyclohexane, chloroform, acetonitrile, and water predicts unanimously the preference of the 2-pyridone form, (1) and (2), respectively in Figure 6.1, despite the large difference in the solvent polarity. Furthermore, the applied methods were rather diverse FEP/MD [59], ab initio SCRF [60, 62], and MC applying a QM/MM, polarizable pair-potential [61]. Although the oxo-preference was pointed out, predicted relative free energies near the available experimental values were obtained only in [60, 61]. 

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