Tautomerism, keto-enol proton transfer

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. 

Any reaction that simply involves the intramolecular transfer of a proton is called a tautomerism. Keto-enol interconversion may happen in basic as well as acidic solution. The steps are reversed in the base-catalyzed and acid-catalyzed reactions. In the base-catalyzed reaction, the first step is removal of an a-proton and the... 

The aldehyde or ketone is called the keto form, and the keto enol equilibration is referred to as keto-enol isomerism or keto-enol tautomerism. Tautomers are constitutional isomers that equilibrate by migration of an atom or group, and their equilibration is called tautomerism. Keto-enol isomerism involves the sequence of proton transfers shown in Mechanism 9.2. 

The third type of experiment is photolysis, where the product is one of a tautomer pair [2, 7, 75]. Again, almost aU reactions studied are keto-enol tautomerizations where the proton transfer is not direct but in a number of steps via the solvent Since the first step is often an ionization (proton transfer to solvent molecule), which is thought to be diffusion-controlled [67], it does give some insight into proton transfer reactions, but exact elucidation is hard, since often there are numerous possibiHties for reaction mechanisms and roles of solvent molecules and internal vibrations [76, 77]. In view of the lack of understanding of proton transfer reactions, it would be much better to have a simpler and more direct way to initiate intramolecular proton transfer. This possibility is offered by looking at intramolecular proton transfer reactions in the excited state, which can be initiated much faster and followed on a much shorter timescale than ground-state reactions. 

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 analogous to keto-enol tautomerism ... 

The optical properties of the 8-o-PhOH-purine adducts have provided insight into their ground-state structures at the nucleoside level. These adducts have the ability to phototautomerize, through an excited-state intramolecular proton transfer (ESIPT) process, to generate the keto form. This tautomerization depends on the presence of a intramolecular hydrogen (H)-bond between the phenolic OH and the imine nitrogen (N-7). Figure 14 shows normalized absorption and emission spectra for 8-o-PhOH-dG and 8-o-PhOH-dA in aqueous buffered water and hexane. In water, 8-o-PhOH-dG shows only enol emission at 395 nm, while 8-o-PhOH-dA shows enol emission at 374 nm and phenolate emission at 447 nm. In hexane, both adducts show keto emission at 475 nm 8-o-PhOH-dA also shows a small amount of enol emission and no phenolate emission. These results show that in water, the intramolecular H-bond... 

The photophysics of solid salicylic acid (SA) has been studied by using steady-state and time-resolved spectroscopic techniques [207,208], Dimers of SA form in two possible structures (59 and 60) due to fast ground-state double proton transfer. Dual fluorescence is observed at 380 nm and 440 nm, which are ascribable to the excited-state double proton transfer between different dimeric structures of SA. The enol form is more stable in the ground state. However, in the excited singlet state, the keto form has a lower potential energy [207], This excited enol-keto tautomerism has a barrier height of -1250 cm as is calculated from the dependence of dual fluorescence on excitation wavelength in the... 

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... 

Compare the base-catalyzed and acid-catalyzed mechanisms shown for keto-enol tautomerism. In base, the proton is removed from the a carbon, then replaced on oxygen. In acid, oxygen is protonated first, then the a carbon is deprotonated. Most proton-transfer mechanisms work this way. In base, the proton is removed from the old location, then replaced at the new location. In acid, protonation occurs at the new location, followed by deprotonation at the old location. 

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... 

A,A -Dimethylformamide [DMFH][N03] ion pairs were optimized with the 6-31G Pople basis set and the B3LYP hybrid functional [41]. Subsequently, energies with the 6-311++G basis set were obtained. The enol form of the [DMFH]+ cation was observed to form three stable conformers with the anion, while the cation of the keto form is unstable and the proton transfer occurs to form three kinds of neutral molecule pairs [41], Moreover, the neutral pairs were more stable than the ion pairs, and the ion pairs tended to tautomerize to neutral pairs without barriers, which was interpreted as decomposition of the ILs [41],... 

Rotational isomerization has been described for the phototautomer formed by proton transfer in the excited singlet state of 2,2 -bipyridin-3-ol in hydrocarbon solvents. At room temperature both the primary phototautomer and its rotamer fluoresce, allowing the activation energy for internal rotation to be determined. Excited state tautomerization has also been described for camp-tothecin in acidic aqueous solution and for derivatives of hypericin. Light-induced keto-enol tautomerism has been invoked to explain the fluorescence behaviour of certain benzimidazole compounds. Interconversion of confor-mers of constrained tryptophan derivatives takes place in the first-excited singlet state.The excited state behaviour has been reported for conformationally-distorted porphyrin derivatives. The lifetimes of the S] states of these... 

The presence of the ortho-hydroxy group is essential for the observation of both types of chromisms, and the mechanism involves intramolecular proton transfer via a six-membered-ring transition state, producing enol-keto tautomeric species, with the spectra of the keto forms showing a bathochromic shift (Scheme 16). 

In contrast to keto-enol tautomerism, such enol-enol tautomerism is characterized by extremely rapid hydrogen transfers. It was shown by ab initio calculations that structures 32a and 32b are more stable than the degenerate tautomeric forms 32c and 32e by 104.7 kJ mol as well as by 117 kl mol than symmetric structure 32d. According to these calculations, a synchronous tunneling of two protons must occur in the naphthazarine molecule 32 between the identical structures 32a and 32b with a frequency of 20 to 40 MHz, i.e. approximately 10" to 10" migrations of hydrogen from one oxygen atom to another per second take place. 

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. 

DHFR catalyzes the reduction of 7,8-dihydrofolate (H2F) to 5,6,7,8-tetrahydrofolate (H4F) using nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor (Fig. 17.1). Specifically, the pro-R hydride of NADPH is transferred stereospecifi-cally to the C6 of the pterin nucleus with concurrent protonation at the N5 position [1]. Structural studies of DHFR bound with substrates or substrate analogs have revealed the location and orientation of H2F, NADPH and the mechanistically important side chains [2]. Proper alignment of H2F and NADPH is crucial in enhancing the rate of the chemical step (hydride transfer). Ab initio, mixed quantum mechanical/molecular mechanical (QM/MM), and molecular dynamics computational studies have modeled the hydride transfer process and have deduced optimal geometries for the reaction [3-6]. The optimal C-C distance between the C4 of NADPH and C6 of H2F was calculated to be 2.7A [5, 6], which is significantly smaller than the initial distance of 3.34 A inferred from X-ray crystallography [2]. One proposed chemical mechanism involves a keto-enol tautomerization (Fig. 

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