Keto-enol equilibrium proton transfer

The optically active Schiff bases containing intramolecular hydrogen bonds are of major interest because of their use as ligands for complexes employed as catalysts in enantioselective reactions or model compounds in studies of enzymatic reactions. In the studies of intramolecularly hydrogen bonded Schiff bases, the NMR spectroscopy is widely used and allows detection of the presence of proton transfer equilibrium and determination of the mole fraction of tautomers [21]. Literature gives a few names of tautomers in equilibrium. The OH-tautomer has been also known as OH-, enol- or imine-form, while NH tautomer as NH-, keto-, enamine-, or proton-transferred form. More detail information concerning the application of NMR spectroscopy for investigation of proton transfer equilibrium in Schiff bases is presented in reviews.42-44... 

Though the proton transfer of the keto enol equilibrium is only indirectly related to... 

Enols are related to an aldehyde or a ketone by a proton transfer equilibrium known as keto-enol tautomerism (Tautomensm refers to an mterconversion between two struc tures that differ by the placement of an atom or a group)... 

Many nitrogen containing compounds engage in a proton transfer equilibrium that is anal ogous to keto-enol tautomensm... 

The above examples show that proton transfer resulting in keto-enol tau-tomerism cannot be studied separately from the environment. The equilibrium between keto and enol forms, both in solution and in the solid state is a derivative of numerous noncovalent interactions that can stabilize a particular isomer. In this context, host-guest chemistry can shed more light towards understanding of the proton-transfer mechanism in biological systems. 

Keto-enol tautomerism— The change from the keto to the enol form of a molecule generally involves the transfer of a proton from a carbon atom to an oxygen or nitrogen atom and the energy changes incurred in such a process may be studied from the point of view of bond energies. In acetone, for example, there exists an equilibrium between the keto form... 

The time scale of the classical temperature-jump experiment ( l J.s) as originally pioneered by Eigen has been shortened to nanoseconds and very recently to approximately 5 ps using lasers. The classical temperature-jump experiment has found only limited application to biological systems, in spite of its great success in determining, for example, proton transfer rates or keto-enol isomerizations. An important reason for its limited application to enzyme research, apart from experimental difficulties such as optical artifacts as a result of the temperature-jump, is the relatively small deviation from equilibrium (AG = AH —... 

A number of 1,3-elimination processes other than those described above have been observed. Treatment of diketone 282 with hydroxide initially formed 283, but the ring opened to give the enolate anion (284). Proton transfer gave 285 and hydrolysis led to keto-acid 286. 34 xhis particular fragmentation relied on an equilibrium that favored the resonance stabilized enolate anion, and a proton transfer to give the keto-carboxylate. 

The rare imino and enol forms can lead to alternate base-pair combinations and thus cause mutations in replication. This type of mutation is called a tautomeric shift [2, 3]. Possible mismatches include iminoC-A, enolT-G, C-iminoA, and T-enolG. Tautomerization can occur in DNA by single or double proton transfer. In solution equilibrium, generally the keto form dominates, complicating efforts to study the properties of the individual forms. One approach to studying tautomeric properties is double-resonant gas-phase spectroscopy, as this technique offers isomeric selectivity. This chapter summarizes the results from such investigations. 

If we now consider the NMR spectrum of the keto and enol tautomers of dimedone (5,5-dimethylcyclohexane-l,3-dione), another puzzle emerges (Figure 17.8). Despite the fact that there can be no intramolecular hydrogen bond, the enol form still appears to be symmetrical— only one type of CHj. At equilibrium, about 40 % of the material is enolized. It is suggested that under these conditions, the material is part of a dimeric structure, 17.17, in which rapid proton transfers are possible. However, in very dry dimethylsulfoxide, NMR spectroscopy suggests that dimedone is completely enolized, and monomeric, with distinct CHj carbon atoms. 

By means of in situ NMR spectroscopy combined with deuterium incorporation experiments, van Leeuwen has elucidated the mechanism of termination by protonolysis, showing that the fl-chelates are in equilibrium with their enolate form by a p-H elimination/hydride migration process (Scheme 7.19). The enolate intermediates are regioselectively protonated at the C2 carbon atom by either MeOH or H2O to give Pd-OMe or Pd-OH and keto terminated copolymer. The enolate formation has been reported to be rate determining in the chain transfer [19]. 

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