Tautomeric dynamic studies

In addition to the dynamic study of compound (120), Freyer (77JPR895) has used N-labelled compounds ( H- N coupling constants) to assign the configuration of compounds (123) and (124). For the latter, a /( H- N) coupling constant of 92 Hz establishes the tautomeric structure as (124) (78JPR508). 

Three alkyl derivatives of porphycene, lb, Ic, and le have also been studied using CPMAS NMR [71]. As in the case of parent 1, the tautomerization was found to be so rapid that the rate constants could not be determined from the line shape analysis. It was thus not possible to establish a correlation between the cavity parameters and tautomerization dynamics, lb and Ic revealed narrow doublets, whereas le showed one line that did not broaden, even at 173 K. le has the largest N- N distance among porphycenes and should therefore exhibit the weak-... 

The vast majority of papers devoted to tautomerization dynamics deal with ESIPT reactions. Since Weller s suggestion that the large Stokes shift he measured for salicyhc acid fluorescence was caused by rapid proton transfer in the excited state [62], and the development of techniques to study this on a femtosecond timescale, the field has blossomed. Most of the 2000 papers on tautomerization dynamics is on ESIPT, from both an experimental and a theoretical point of view. The number of compounds exhibiting ESIPT is far too large to discuss here. It ranges from molecules as simple as malonaldehyde to systems as complicated as 3-hydroxyflavone or 2-(2 -hydroxyphenyl)benzothiazole. In particular, substituted salicylic acids and ortho-hydroxybenzaldehydes have attracted much attention from both experimentalists and theoreticians. Weller s idea is depicted in Figure 1.10. 

A good quantum chemical theory of tautomeric equilibrium and tautomerization dynamics is still a long way ofif Fully understanding the process of proton transfer should lead to a fundamental insight into the nature of the interaction between quantum and classical systems. Further experimental and theoretical study of tautomeric equilibrium and tautomerization dynamics is a possible pathway to enhghtenment. 

It must be emphasized that all time-dependent chemical phenomena, such as tautomerism, are sensitive to temperature changes. In this section, we treat classic DNMR (dynamic NMR) studies and cases of changes in the NMR spectra with temperature together. In Table XI we have classified these studies according to the physical state of the sample and to the nuclei... 

Accounting for this effect, it was possible to apply dynamic NMR spectroscopy to measure energy barriers to the prototropic rearrangements of pyrazoles. Temperature-variable spectra of a series of 4-substituted pyra-zoles 5 and 6 have been studied in methanol-d4 solutions and the free energy barriers of the degenerate type 2a 2b tautomerization reported (93CJC1443). 

Abstract This chapter reviews the theoretical background for continuum models of solvation, recent advances in their implementation, and illustrative examples of their use. Continuum models are the most efficient way to include condensed-phase effects into quantum mechanical calculations, and this is typically accomplished by the using self-consistent reaction field (SCRF) approach for the electrostatic component. This approach does not automatically include the non-electrostatic component of solvation, and we review various approaches for including that aspect. The performance of various models is compared for a number of applications, with emphasis on heterocyclic tautomeric equilibria because they have been the subject of the widest variety of studies. For nonequilibrium applications, e.g., dynamics and spectroscopy, one must consider the various time scales of the solvation process and the dynamical process under consideration, and the final section of the review discusses these issues. 

In chapter 1, Profs. Cramer and Truhlar provide an overview of the current status of continuum models of solvation. They examine available continuum models and computational techniques implementing such models for both electrostatic and non-electrostatic components of the free energy of solvation. They then consider a number of case studies with particular focus on the prediction of heterocyclic tautomeric equilibria. In the discussion of the latter they focus attention on the subtleties of actual chemical systems and some of the danger in applying continuum models uncritically. They hope the reader will emerge with a balanced appreciation of the power and limitations of these methods. In the last section they offer a brief overview of methods to extend continuum solvation modeling to account for dynamic effects in spectroscopy and kinetics. Their conclusion is that there has been tremendous progress in the development and practical implementation of useful continuum models in the last five years. These techniques are now poised to allow quantum chemistry to have the same revolutionary impact on condensed-phase chemistry as the last 25 years have witnessed for gas-phase chemistry. 

Lowry is best known to chemistry students through the tradition of eponymony, since the proton theory of acidity is known as the "Bronsted/Lowry theory" of proton donors. His most important experimental investigation likely was a long series of studies on optical rotatory dispersion.49 For our purposes, there is special interest in his discovery of mutarotation in camphor derivatives and his theory of dynamic tautomerism, which led him to an ionic theory of organic reaction mechanisms. 

Nuclear magnetic resonance (NMR) spectroscopy is a most effective and significant method for observing the structure and dynamics of polymer chains both in solution and in the solid state [1]. Undoubtedly the widest application of NMR spectroscopy is in the field of structure determination. The identification of certain atoms or groups in a molecule as well as their position relative to each other can be obtained by one-, two-, and three-dimensional NMR. Of importance to polymerization of vinyl monomers is the orientation of each vinyl monomer unit to the growing chain tacticity. The time scale involved in NMR measurements makes it possible to study certain rate processes, including chemical reaction rates. Other applications are isomerism, internal relaxation, conformational analysis, and tautomerism. 

We have demonstrated that the novel antitumor agent 10-hydroxycamptothecin has remarkable excited-state acidity. In contrast to simple 6-hydroxyquinoline, no tautomerization is observed. The implications for the use of proton transfer dynamics in studying the microenvironment of cells remains to be demonstrated. 

The relationships between tautomeric equilibrium constants and intramolecular hydrogen bonds (IMHB) are well documented. As expected, an IMHB stabilizes the tautomer that presents it in comparison with other tautomers without IMHB. On the other hand, information about the effect of intermolecular hydrogen bonds on the thermodynamic aspect of tautomerism is scarce. These HBs are of paramount importance in the solid state in solution, the situation is more complicated because there are several possible associations that exist in dynamic equilibrium. For this reason we devoted a theoretical paper to this question, studying homo- and heterodimers of 2-pyridone (63, 64, 65) and 2-aminopyridines (66, 67, 68) [84], In the case of pyridone the most stable dimer is 63 for 2-aminopyridine, it depends on the nature of R. 

Mazzola et a/.114 studied azo-hydrazone tautomerism and acid-base equilibria of FD C Yellow 6 (52). The compound exists as a hydrazone below pH 9 and as an azo anion species at pH 14. A dynamic NMR effect was observed at pH 12 (corresponding to pKa according to potentiometric titration), where the midpoint of the azo-hydrazone equilibrium occurs. The observed NMR line broadening is due to slow proton transfer between... 

Another approach of great importance for studies of excited state dynamics is sub-picosecond time resolved spectroscopy. A number of authors have reported femtosecond pump-probe measurements of excited state lifetimes in A, C, T, and G [13-16] and base pair mimics [17]. Schultz et al. have reported time resolved photoelectron spectroscopy and electron-ion coincidence of base pair mimics [18]. these studies can also be compared with similar measurements in solution [19-24], While time resolved measurements provide direct lifetime data, they do have the limitation that the inherent bandwidth reduces the spectral resolution, required for selecting specific electronic states and for selecting single isomers, such as cluster structure and tautomeric form. 

The tautomerism of nitrated 5(6)-fruorobenzofuroxans has been studied by Charushin and colleagues using dynamic H, 13C, 19F NMR spectroscopy [758], It has been discovered that 4-nitro-5-hydroxy-6-fluorobenzofuroxan, on dissolving in DMSO, transforms to 4-hydroxy-5-fluoro-7-nitrobenzofuroxan in a result of the Boulton-Katritzky rearrangement [758],... 

At the onset of this study, we hypothesized that under our reductive amination conditions an a-branched aldehyde substrate would undergo a fast racemization in the presence of the amine and acid catalyst via an imine/enamine tautomerization. The reductive amination of one of the two imine enantiomers would then have to be faster than that of the other, resulting in an enantiomerically enriched product via a dynamic kinetic resolution (Scheme 15 for reviews, see Noyori et al. 1995 Ward 1995 Caddick and Jenkins 1996 Stecher and Faber 1997 Huerta et al. 2001 Perllissier 2003). 

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