Tautomerism in Heterocyclic Systems

A topic which has attracted an inordinately large research effort over the years is the determination of precise structure of heterocyclic molecules which are potentially tautomeric - the pyridinol/pyridone relationship (section 1.2.4) is one such situation. In principle, when an oxygen is located on a carbon a or 7 to nitrogen, two tautomeric forms can exist the same is true of amino groups. 

Early attempts to use the results of chemical reactions to assess the form of a particular compound were misguided, since these can give entirely the wrong answer the minor partner in such a tautomeric equilibrium may be the one which is the more reactive, so a major product may be actually derived from the minor component in the tautomeric equilibrium. Most secure evidence on these questions has come from 

After all the effort that has been expended on this area, the picture which emerges is fairly straightforward a and 7 oxy-heterocycles generally prefer the carbonyl form amino-heterocycles nearly always exist as amino tautomers. Sulfur analogues -potentially thiol or thione - tend to exist as thione in six-membered situtations, but as thiol in five-membered rings. 

The establishment of tautomeric form is perhaps of most importance in connection with the purine and pyrimidine bases which form part of DNA and RNA, and, through H-bonding involving carbonyl oxygen, provide the mechanism for base pairing (cf. section 24.1). 

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Valence tautomerism of heterocyclic systems containing tetrazole rings has received much attention [76AHC(S1), p. 498 84CHEC-I(5)791 96CHEC-1I(4)621], The latest contributions to this area are considered in Section IV,C, which is concerned with the topic of azido-tetrazole tautomerism. 

Solvation may have a dramatic effect on tautomeric equilibria, especially in heterocyclic systems.1 13,3i4 por instance, the equilibrium constant for the... 

Molecular design of tautomeric systems 81ACR210 77MI3. Metallotropic tautomerism in heterocyclic complexes 81 UK 1304. Ring-chain tautomerism of heteroeycies 85MI13 78MI7. 

Small unsaturated rings are usually very reactive undergoing ring opening in a number of ways, and this characteristic has been utilized in heterocyclic synthesis. In their role as dienophiles or dipolarophiles, the initial cycloaddition is usually followed by a valence tautomerism resulting in a six-membered or larger ring system. Several examples exist, however, where this does not occur, and these are described below. 

The manifold possibilities for tautomerism in. seven-membered heterocyclic systems are virtually unexplored cf., however, A. H. Rees, J. Chem. Soc. p. 3111 (1959). 

Tlie first two chapters in this volume continue the survey of heteroaromatic tautomerism that was the topic of Volume 76 of Advances in Heterocyclic Chemistry. Tliis whole subject was first dealt with comprehensively in Volumes 1 and 2 of our series, which date back to 1963 and 1964.Tlie area was updated in a special supplementary volume of the series that appeared in 1976 but is now seriously out of date. Tire chapters in Volume 76 deal with a general introduction and the tautomerism of tive-membered monocyclic rings systems. 

Tautomeric equilibrium in amino-substituted 1,2,6-thiadiazine 1,1-dioxides fused with five- or six-membered nitrogen heterocycles has been extensively studied by Goya and colleagues. No amino group participation in tautomeric equilibria in these systems has been observed. 

In a study of tautomeric heterocycle systems Zubatyuk et al. [39] concluded that the position of tautomeric equilibrimn is controlled by the aromaticity of the heterocycle. They have also shown a strong correlation between the strength of the a intramolecular hydrogen bond and the aromaticity of a resonant spacer. In DPGUAN03, where two symmetry independent molecules, establish similar hydrogen bonds, the lowest aromaticity corresponds to the strongest intermolecular H-bonds. 

The general class of triazolopyridines includes five heterocyclic systems. Three have bridgehead nitrogen, compounds 1-3 and two do not, compounds 4 and 5. In general these two major divisions reflect differences in synthesis or in properties. Compounds 4 and 5 can exist in several tautomeric forms there is little direct evidence on the major tautomer, and the compounds are therefore shown throughout in the 1H form. 

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