Keto-enol tautomerization, hydrogen

A carbonyl compound with a hydrogen atom on its a carbon rapidly equilibrates with its corresponding enol (Section 8.4). This rapid interconversion between two substances is a special kind of isomerism known as keto-enol tautomerism, from the Greek Canto, meaning "the same," and meros, meaning "part." The individual isomers are called tautomers. 

After succeeding in the asymmetric reductive acylation of ketones, we ventured to see if enol acetates can be used as acyl donors and precursors of ketones at the same time through deacylation and keto-enol tautomerization (Scheme 8). The overall reaction thus corresponds to the asymmetric reduction of enol acetate. For example, 1-phenylvinyl acetate was transformed to (f )-l-phenylethyl acetate by CALB and diruthenium complex 1 in the presence of 2,6-dimethyl-4-heptanol with 89% yield and 98% ee. Molecular hydrogen (1 atm) was almost equally effective for the transformation. A broad range of enol acetates were prepared from ketones and were successfully transformed into their corresponding (7 )-acetates under 1 atm H2 (Table 19). From unsymmetrical aliphatic ketones, enol acetates were obtained as the mixtures of regio- and geometrical isomers. Notably, however, the efficiency of the process was little affected by the isomeric composition of the enol acetates. 

Al-Soufi W, Grellmann KH, Nickel B (1991) Keto-enol tautomerization of 2-(2 -hydroxy-phenyl)benzoxazole and 2-(2 -hydroxy-4 -methylphenyl) benzoxazole in the triplet state hydrogen tunneling and isotope effects. 1. Transient absorption kinetics. J Phys Chem 95 10503-10509... 

Although Eibner elucidated the structure between 1904 and 1906, it was only through IR and nuclear magnetic resonance spectroscopy (NMR) that the chro-maticity of these molecules could be attributed to keto-enol tautomerism and simultaneous hydrogen bond formation (structures 137a = 137b) [2]. 

Scheme 16. Keto—Enol Tautomerism and Hydrogen-Bonding...

Dibenzoylmethane (8b) has been the subject of much interest as regards the possibility that its polymorphism is associated with keto-enol tautomerism. Chemical and spectroscopic studies showed that this is not so (33a). This compound had previously been reported to be trimorphic (33b), but one form appears, in fact, to be a eutectic mixture of the other two. The molecules in these two polymorphs are both in the same state of tautomerism they differ in the torsional angle about the (CH)-(CO) bond and in the type of hydrogen bonding in which they participate. It is noteworthy that solutions prepared from these forms at low temperature have differences in chemical and spectroscopic properties that are maintained for some time. For example, such solutions prepared and held at —35° react at different rates with FeCl3. 

IR spectra of substituted acetophenones, p-XC6H4COMe, in chloroform suggest the presence of hydrogen-bonded dimers for X = H and NO2, but not OMe ° such association may play a role in keto-enol tautomerization. 

The details of the organic chemistry of the reaction of ethylene with PdCl2 (equation (1) above) are also known and are shown in Fig. 9.2. The palladium ion complexes with ethylene and water molecules and the water adds across the bond while still complexed to palladium. The palladium then serves as a hydrogen acceptor while the double bond reforms. Keto-enol tautomerism takes place, followed by release of an acetaldehyde molecule from the palladium. 

Even for a simple reaction, involving just one reactant species and one product species, such as a keto-enol tautomerism or a cis-trans isomerization, the above equation for a given solvent is complicated. StUl, in specific cases it is possible to unravel the solvent effects of cavity formation, for the solute species have different volumes, polarity/polarizability if the solute species differ in their dipole moments or polarizabilities, and solvent Lewis acidity and basicity if the solutes differ in their electron-pair and hydrogen-bond acceptance abilities. 

An investigation of keto-enol tautomerism for perfluorinated keto-enol systems was undertaken. N-methylpyrrolidone (NMP) catalyzes equilibration of the keto and enol forms, but if used in more than trace amounts, it drives the equilibrium strongly toward enol because of hydrogen bonding to the amide. The enol is much more thermodynamically stable than its ketone, and it was found that in mildly Lewis basic solvents, such as ether, THE, acetonitrile, and NMP, the enohzation equilibrium lies too far right to allow detection of ketone (Correa et al., 1994). 

Cyanuric acid exists in two tautomeric forms corresponding to keto-enol tautomerism in carbonyl compounds. The keto form predominates, and most of the reactions of cyanuric acid have their counterparts in the chemistry of the cyclic imides. Many of the reactions involve the replacement of all three imido hydrogens (Scheme 31). Usually, the reaction cannot be controlled to produce the mono- or di-substituted isocyanurates specificially, but there are exceptions, e.g. the reaction between cyanuric acid and aziridine (Scheme 31) (B-79MI22001, 63JOC85, 63AHC(2)245). 

X,Y=0,S,Se,Te], has been undertaken.628 The stabilities of different tautomeric forms of 4-hydroxycoumarins have been evaluated629 by MNDO calculations, and the four lowest-energy oxo-hydroxy tautomers of 5-fluorouracil have been studied630 using density functional methods. Semiempirical calculations have been carried out on the keto-enol tautomerism of triazolopyrimidines.631 A base-catalysed keto-enol tautomer-ism has been proposed632 to be responsible for the observed deuterium exchange of the hydrogens at the 3-position of diazepam when the molecule is treated with alkaline deuteriated methanol. 

Activation energies for unimolecular 1,3-hydrogen shifts connecting ketones and enols are prohibitive, so that thermodynamically unstable enols can survive indefinitely in the gas phase or in dry, aprotic solvents. Ketones are weak carbon acids and oxygen bases enols are oxygen acids and carbon bases. In aqueous solution, keto-enol tautomerization proceeds by proton transfer involving solvent water. In the absence of buffers, three reaction pathways compete, as shown in Scheme 2. 

The keto-enol tautomerization in the excited triplet state of 2-methylacetophenone is associated with hydrogen transfer in the CH O fragment ... 

Charge density analysis has been carried out for three reaction paths involving intramolecular hydrogen transfer the keto-enol tautomerism of acetaldehyde, the pinacol rearrangement of protonated ethane-1,2-diol, and the unimolecular decomposition of methanediol, reactions involving H-transfer between C O, C C, and O O atoms.288... 

When a terminal alkyne is treated with an excess of hydrogen halide the halogens both end up on the more substituted carbon (Fig. F). This is in accordance with the Markovnikov s rule which states that the additional hydrogens end up on the carbon which already has the most hydrogens. The same rule applies for the reaction with acid and mercuric sulphate which means that a ketone is formed after keto-enol tautomerism instead of an aldehyde (Fig. G). 

Acid-catalysed hydrogen-deuterium exchange in norcamphor has also been investigated by Werstiuk and Banerjee (1977) (DOAc—D20—DC1 medium). It was observed that exo-deuteron addition to the enol is also preferred, but with a slightly smaller selectivity (x 190). This would mean that, if torsional factors cause preferential base-catalysed exo-exchange, they also occur for acid-catalysed keto-enol tautomerism. However, the absence of important torsional strain effects on the rate constants of acid-catalysed enolisation of cyclic and bicyclic ketones contradicts this assumption. 

In addition to its mechanistic importance, keto-enol tautomerism affects the stereochemistry of ketones and aldehydes. A hydrogen atom on an a carbon may be lost and regained through keto-enol tautomerism such a hydrogen is said to be enolizable. 

Bulky H should not diffuse or show marked oscillational movement as indicated by magnetic resonance studies. The hydridic model actually provides a reasonable explanation for the mean amplitude of H vibrations (ca. 0.2 A.) and is noncommittal about diffusion. Conceivably, the barrier to diffusion comprising an Is2- configuration about the proton is in effect lowered by the distance of the barrier from the mean position of the nucleus. If the movement of hydrogen is quasitautomeric—for example, in keto-enol tautomerism—one may consider that it moves from one potential well to another as a proton. 

In the proteins and nucleic acids the configurational mechanism has to be invoked to explain any hydrogen-bond disorder involving )N-H or NH groups where there is no orientational flexibility. This is shown in the two examples, below (the second describing amino/imino and keto/enol tautomeric states) ... 

For acetone and the majority of cases in which this keto-enol tautomerism is possible, the keto form is far more stable and little if any enol can be detected. However, with j8-diketones and j8-ketoesters, such factors as intramolecular hydrogen bonding and conjugation increase the stability of the enol form and the equilibrium can be shifted significantly to the right. 

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