And tautomerization

Fast transient studies are largely focused on elementary kinetic processes in atoms and molecules, i.e., on unimolecular and bimolecular reactions with first and second order kinetics, respectively (although confonnational heterogeneity in macromolecules may lead to the observation of more complicated unimolecular kinetics). Examples of fast thennally activated unimolecular processes include dissociation reactions in molecules as simple as diatomics, and isomerization and tautomerization reactions in polyatomic molecules. A very rough estimate of the minimum time scale required for an elementary unimolecular reaction may be obtained from the Arrhenius expression for the reaction rate constant, k = A. The quantity /cg T//i from transition state theory provides... 

Mechanism of the initial reaction, known as alkaline peeling, is shown in equation 4. EnoHzations and tautomerizations take place easily because of the contiguous hydroxyl groups. The hydroxyl or substituted hydroxyl on the second, ie, P-carbon, from a carbonyl group is released from the molecule by P-elimination. 

The UV spectra have been used in studies of protonation and related covalent hydration, structural assignments and tautomerism (see appropriate Sections), as well as in studies of bridgehead addition to 5-deazapterins (79MI21500, 78TL2271) and related 5-deazaflavin derivatives (80JA1092). 

The differential effects of sterlc hindrance and tautomeric content in the imidazole series are illustrated in Scheme 6 (80AHC(27)24i). 

Theoretical methods ranging from the now obsolete HMO studies to ab initio calculations have been used extensively on pyrazoles. Although not emphasized in earlier reviews (66AHC(6)347,67HC(22)l), the most recent publications (B-76MI40402,79RCR289) contain several references to theoretical studies. Some publications related to structural studies are to be found in the following sections, especially in connection with NMR spectroscopy (Section 4.04.1.3.4), UV spectroscopy (Section 4.04.1.3.6), PE spectroscopy (Section 4.04.1.3.9) and tautomerism (Section 4.04.1.5). 

Theoretical and structural studies have been briefly reviewed as late as 1979 (79AHC(25)147) (discussed were the aromaticity, basicity, thermodynamic properties, molecular dimensions and tautomeric properties ) and also in the early 1960s (63ahC(2)365, 62hC(17)1, p. 117). Significant new data have not been added but refinements in the data have been recorded. Tables on electron density, density, refractive indexes, molar refractivity, surface data and dissociation constants of isoxazole and its derivatives have been compiled (62HC(17)l,p. 177). Short reviews on all aspects of the physical properties as applied to isoxazoles have appeared in the series Physical Methods in Heterocyclic Chemistry (1963-1976, vols. 1-6). 

The mechanism of the Fiesselmann reaction between methylthioglycolate and a,P-acetylenic esters proceeds via consecutive base-catalyzed 1,4-conjugate addition reactions to form thioacetal Enolate formation, as a result of treatment with a stronger base, causes a Dieckmann condensation to occur providing ketone 8. Elimination of methylthioglycolate and tautomerization driven by aromaticity provides the 3-hydroxy thiophene dicarboxylate 9. 

This information coupled with the proposed mechanism of the Conrad-Limpach reaction, reasonably lead to the below proposed mechanisms. Conjugate addition of aniline and elimination of alcohol provides the P-anilinoacrylate 14, which upon heating to 180-320 °C gives species, like 34a,b, which undergo 6n-electrocyclization to 35 or 36, respectively. Loss of ethanol from 36 gives 35 and tautomerization provides 4-... 

Early investigators adduced various kinds of chemical evidence in support of a monohydroxy-dioxo structure for barbituric acid (112) (a) reaction with diazomethane afforded a mono-O-methyl deriva- iye,i59,i6o barbituric acid and its 5-alkyl derivatives are much stronger acids than the 5,5-dialkyl derivatives, and (c) the 5-bromo and 5,5-dibromo derivatives have different chemical properties. - The early physical evidence also appeared to substantiate the monoenol structure, this formulation having been suggested for barbituric acid in 1926 on the basis of its ultraviolet spectrum and again in 1934, In the 1940 s, ultraviolet spectroscopic studies led to the suggestion of other monohydroxy and dihydroxy structures for barbituric acid, whereas its monoanion was assigned structure 113 (a clear distinction between ionization and tautomerism was not made in these papers). 

In comparison with mercapto-, hydroxy-, and amino-pyridines, methylpyridines should show an even greater tendency to exist in the methyl form [instead of as pyridmethines (297)] than do the amino compounds to exist as such. If the methyl carbon atom carries an electron-withdrawing group, it might be expected that structures of type 297 would be stabilized. Fused benzo groups should also tend to stabilize the methine form, and tautomerism involving 298 has, in-... 

P3Timidines, and pyrido[4,3-< ]pyrimidines. The experimentally determined values have been used for studies of covalent hydration, structural assignments, - and tautomerism. -... 

One interesting problem frequently recurring in heterocyclic chemistry, particularly with respect to nitrogen heterocycles, is tautomeric equilibria. Too many methods are available for the elucidation of equilibrium positions and tautomeric equilibrium constants (Kj) to adequately review the whole question here. However, the Hammett equation provides one independent method this method has the advantage that it can be used to predict the equilibrium position and to estimate the equilibrium constant, even in cases where the equilibrium position is so far to one side or the other that experimental determination of the concentration of the minor component is impossible. The entire method will be illustrated using nicotinic acid as an example but is, of course, completely general. 

Generation of reaction networks with RAIN resonance structures and tautomerism Solid-state NMR studies of reversible 1,5-H shifts Tautomeric equilibria (AMI, MNDO, PM3)... 

Resonance energies and tautomerism of substituted aromatic heterocycles and their benzo derivatives Reaction-field-supermolecule approach to calculation of solvent effects... 

G. Reactions and Tautomerism of Quinoxaline-2-thione and Quinoxaline-2,3-dithione (2-Meecapto- and 2,3-Dimercapto-quinoxaline)... 

Several other review articles cover various aspects of tautomerism in six-membered heterocycles. Various aspects of prototropic tautomerism have been covered in a review article by Katritzky [91H(32)329] types of tautomerism, methods of study of aromatic tautomerism, and tautomeric equilibria in pyridines and other six-membered rings. Some generalizations have also been made. Another review article by Kurasawa, which appeared in two parts in 1995, covers, for the most part, the work of that author [95H(41)1805 95H(41)2057]. 

No data on tautomerism of dihydropyiimidines were available at the time of the early summary (76AHCS1), but much has been done since then. The results of tautomeric studies carried out during the period between 1976 and 1984 were reviewed comprehensively in [85AHC(38)l,pp. 63-77]. Later, Weis and vanderPlas published an excellent review on the synthesis, structure, and tautomerism of dihydropyrimidines [86H(24)1433], where the tautomeric interconversions of these compounds were discussed in detail. In a more recent review on dihydropyrimidines (94MI1), the question of tautomerism in partially hydrogenated pyrimidines was also included. 

An illustrative example of the Michael reaction is that of the thiirene dioxide 19b with either hydroxylamine or hydrazine to give desoxybenzoin oxime (87) and desoxybenzoin azine (88), respectively, in good yields6 (see equation 29). The results were interpreted in terms of an initial nucleophilic addition to the a, j8-unsaturated sulfone system, followed by loss of sulfur dioxide and tautomerization. Interestingly, the treatment of the corresponding thiirene oxide (18a) with hydroxylamine also afforded 86 (as well as the dioxime of benzoin), albeit in a lower yield, but apparently via the same mechanistic pathway6. 

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