Keto-enol tautomerism estimation

Enolization and ketonization kinetics and equilibrium constants have been reported for phenylacetylpyridines (85a), and their enol tautomers (85b), together with estimates of the stability of a third type of tautomer, the zwitterion (85c). The latter provides a nitrogen protonation route for the keto-enol tautomerization. The two alternative acid-catalysed routes for enolization, i.e. O- versus Af-protonation, are assessed in terms of pK differences, and of equilibrium proton-activating factors which measure the C-H acidifying effects of the binding of a proton catalyst at oxygen or at nitrogen. 

Estimation of Enol Modification in a Compound exhibiting Keto-enol Tautomerism... 

Pulse radiolysis studies using optical detection suggested the main species in equilibrium to be the ot-aminoalkyl radical (31) and the A -protonated ot-aminoalkyl radical (32) whereas results from ESR studies were indicative of protonation at the a-carbon site to form the iV-centered radical cation (30). A subsequent study showed that these results could be attributed to kinetic and thermodynamic factors [84]. Thus iV-protonation resulting in the formation of 32 is kinetically favored and is hence observed in the short time-scales involved in pulse-radiolysis systems. In the longer times involved in ESR measurements the thermodynamically more stable N-centered radical cation will be observed. The pA a of 30 and 32 were estimated as 8.0 and 3.6 by use of pulse radiolysis [84]. Using the equation for similar keto enol tautomerism of barbituric acid [97], the ratio of 30/32 was estimated to be 10 /10 = 10", indicating the N-centered radical (30) to be the predominant protonated species. 

In solution, isotopic incorporation of deuterium from deuterated solvents into metal-bound hydrogen is common, e.g., reaction of acetone-reaction occurs between the Os complex and acetone even at reflux temperature thus the isotopic exchange with acetone-isotopic exchange may therefore occur via a deprotonation/reprotonation pathway coupled with a keto-enol tautomerization. 

It also has become clear that the protons of the amino and imino groups of the base derivatives can exchange directly in non-aqueous atomosphere, if appropriate conditions are satisfied. Although the experiment were carried out on the monomer systems, there is no reason to deny the proton exchange in interior of nucleic acids. The exchange is possibly due to the presence of the keto-enol tautomerism, and we may estimate the frequency of tautomerism from the present date. 

Energy estimations have been carried out for these compounds at HE, B3LYP and MP2 levels (Table 2), the keto form is more stable than the enol form at aU levels. The keto-enol energy difference at MP2(full)/6-31 + G level in 1 (24.04 kcal/mol) is much larger than the same in acetaldehyde (16.23 kcal/mol). Higher values of A and 1,3-H shift barriers suggest the enol content in 1 should be less than that of acetaldehyde. Hence, keto-enol tautomerism in glitazones is not expected to be a very favorable process. 

Trifluoroacetylketene (91) has been generated in aqueous solution by flash photolysis. Rates of hydration to form the enol of 4,4,4-trifluoroacetoacetic acid (92e) have been measured, and also rates of the subsequent ketonization to the /3-keto acid (92k). Extensive rate and equilibrium constant data are reported for these reactions and for the ionizations of the tautomers. For example, the enol (92e) has acidity constants (in -logio form) of 1.85 and 9.95, for the acid and enol OH groups, respectively. Rates of enolization of (92k) have also been measured (by bromination) and, combined with an estimate of the hydration constant (K = 2900) of (92k), suggest that the keto-enol tautomeric constant is ca 0.5, about 100 times greater than that of its unfluorinated analogue. 

An interesting type of keto-enol tautomerism, called cyclic anhydride-end tautomerism (Scheme 5.14), was published [45]. NMR spectroscopy was employed to estimate the equilibrium the ratio of the anhydride tautomer 20a and the enol form 20b was 7 1 [45]. 

The keto-enol tautomerism of 2-nitroalkanones was restudied by NMR spectroscopy [5(0-H) 14.5-15.0ppm 5(a-CH2) 4.5-5.0ppm] and the equiHbrium constants Kp were calculated at 25 °C [48]. When employing similarly the 5(OH) signal in estimating tautomerism, it should be considered that potential moisture and acidic traces could be risky. 

It is also possible to examine the effect of oxygen substituents on the stability of arenonium ions. Wirz has studied keto-enol equilibria for phenol,151 naphthol (Wirz J, Personal communication), and anthrol.152,153 The tautomeric constants may be combined with p/y,s for protonation of the keto tautomer and ionization of the phenol to provide pifas f°r protonation of the aromatic ring of phenol and the phenoxide ion. As illustrated in Scheme 18 the unstable keto tautomer of phenol 22 was produced by photolysis of the bicyclooctene dione 21. Except in the case of the anthrone a pA a for protonation of the keto tautomer has not been measured directly. However, values can be estimated from the pfor protonation of the 4,4-dimethylated analog136 with a correction for the substituent effect of the methyl groups. 

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