Resonance keto-enol tautomerism

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]. 

The difference in conjugation between neutral molecules and their ion-radicals can also be traced for keto-enol tautomerism. As a rule, enols are usually less stable than ketones. Under the equilibrium conditions, enols exist only at a very low concentration. However, the situation becomes different in the corresponding cation-radicals, where gas-phase experiments have shown that enol cation-radicals are usually more stable than their keto tautomers. This is because enol cation-radicals profit from allylic resonance stabilization that is not available to ketones (Bednarek et al. 2001, references therein). 

Keto-enol-tautomerization is not resonance. The ketone and enol forms are different compounds that are in equilibrium. 

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. 

The coordination of transition metals is known to influence the keto-enol tautomerism in the condensed phase" . The effect of coordination of bare Fe+ ions on the keto-enol equilibrium of phenol was investigated by means of generation of various cyclic [Fe,Cg, He, 0]+-isomers. These isomers were characterized by collisional activation (CA) and Fourier transform ion cyclotron resonance (FTICR) mass spectrometry" . It was shown that the energy difference between the phenol-iron complex 65 and the keto isomer 66 is not perturbed by the presence of the iron cation in comparison with the uncom-plexed isomers 3 and 4 (equation 25). Thus, the energy difference for both the neutral and the Fe+-coordinated systems amounts to ca 30 kJ moC in favor of the phenolic tautomer. 

Alpha hydrogens are hydrogens on carbons directly attached to a carbonyl group. They are weakly acidic and can be abstracted by base to form a carbanion. The carbanion is called an enolate ion and is resonance stabilized. Neutralization of the enolate ion results in an enol, a compound in which an alcohol group is directly bonded to a carbon involved in a carbon-carbon double bond. The enol is in equilibrium with the original aldehyde or ketone in an equilibrium referred to as keto-enol tautomerism. The equilibrium usually favors the keto form. 

The process by which enols are converted to aldehydes or ketones is called keto-enol isomerism (or keto-enol tautomerism) and proceeds by the sequence of proton transfers shown in Figure 9.6. Proton transfer to the donble bond of an enol occurs readily because the carbocation that is produced is a very stable one. The positive charge on carbon is stabilized by electron release from oxygen and may be represented in resonance terms as shown on the following page. 

Phosphoenolpyruvate (PEP), a molecule we shall encounter when we look at glycolysis, tops the list. It is a very high-energy compound because of the resonance stabilization of the liberated phosphate when it is hydrolyzed (the same effect as that seen with ATP) and because keto-enol tautomerization of pyruvate is a possibility. Both effects increase the entropy upon hydrolysis (Figure 15.8). 

PEP is a high-energy compound because energy is released upon its hydrolysis, owing to the resonance stabilization of the inorganic phosphate released and the possible keto-enol tautomerization of its product, pyruvate. See Figure 15.8. 

Here, we are dealing specifically with keto-enol tautomerism (Figure 6.17). Generally, in aliphatic compounds, the keto form is in great predominance for example, in acetone less than 10 % is in the enol form. At the other extreme is the phenolic stmcture, where there is no evidence for the existence of the keto form. This would not be unexpected because a loss of the resonance energy of stabilization would be entailed. 

Figure 10.49. A comparison of (a) the conventional ID spectrum of ethyl acetoacetate (60 pmol, 3000 scans, 400 MHz) with (b) the DNP-enhanced spectrum (bOpmol, single scan, 400 MHz). The resonance labelled with an asterisk is missing in trace (a) due to deuteration of the centre as a result of keto-enol tautomerism see text (data courtesy of Oxford Instruments Molecular Biotools).

Exper- imental Funda- mental Opposing resonance primary complementary Electrostatic repulsion Keto-enol tautomerism Free energy of ionization Total... 

This map indicates that the acyl carbon and the carbon atom at the end of the C=C unit (resonance contributors 37B and 37C) are most likely to react with chloride ion to form a product. If chloride ion reacts at the terminal carbon (37C), the product is an enol, which tautomerizes to the final product, 39. Keto-enol tautomerization was introduced in Chapter 10 (Section 10.4.5) and discussed again in Chapter 22 (Section 22.1). An alternative mechanism is possible in which HCl reacts with the C=C unit of 10 to generate 38 directly, and subsequent reaction with chloride ion gives 39. Experimental evidence suggests that 37 is the more likely intermediate that leads to 39. 

Keto-Enol Tautomerism (Section 16.9B) The keto form predominates at equilibrium, except for those aldehydes and ketones in which the enol is stabilized by resonance or hydrogen bonding. 

The enol and ketone are said to be tautomers, which are constitutional isomers that rapidly interconvert via the migration of a proton. The interconversion between an enol and a ketone is called keto-enol tautomerization. Tautomerization is an equilibrium process, which means that the equilibrium will establish specific concentrations for both the enol and the ketone. Generally, the ketone is highly favored, and the concentration of enol will be quite small. Be very careful not to confuse tautomers with resonance structures. Tautomers are constitutional isomers that exist in equilibrium with one another. Once the equilibrium has been reached, the concentrations of ketone and enol can be measured. In contrast, resonance structures are not different compounds and they are not in equilibrium with one another. Resonance structures simply represent different drawings of one compound. 

Keto-enol tautomerism is NOT resonance. The two compounds shown above are NOT two representations of the same compound. They are, in fact, different compounds. These two compounds are in equilibrium with each other. 

Carbons involved in keto-enol tautomerism can experience large cbemical shift differences according to the tautomer present. For example, for acetylace-tone the carbonyl carbon resonates at 201.1 ppm in the keto form but is at 190.5 ppm in the enol form. Similarly, the carbon which is a methylene group in the keto form with a shift of 56.6 ppm moves to 99.0 ppm as an olefinic carbon in the enol form. 

Kol tsov, A. and Kheifets, G. (1971) Investigation of Keto-Enol tautomerism by nuclear magnetic resonance spectroscopy. Russ. Chem. Rev., 40, 773 -788. 

Phenol can be considered as the enol of cyclohexadienone. While the tautomeric keto-enol equilibrium lies far to the ketone side in the case of aliphatic ketones, for phenol it is shifted almost completely to the enol side. The reason of such stabilization is the formation of the aromatic system. The resonance stabilization is very high due to the contribution of the ortho- and / ara-quinonoid resonance structures. In the formation of the phenolate anion, the contribution of quinonoid resonance structures can stabilize the negative charge. 

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