2- hydroxy-, prototropic tautomerism

The nature and position of the cyclic heteroatoms within the five-membered rings of azoles can affect the positions of the prototropic tautomeric eqihbria, particularly of hydroxy and mercapto derivatives. 

Examples of the fixation of very minor prototropic tautomeric forms on complexation are known in the series of complexes of l-(2 -pyridyl)-5-hydroxypyrazoles 383 [76AHC(S1), p. 333 70ZOB1114] and 2-[2 -hydroxy (A-tosylaminophenyl)]benzazoles 385 (Scheme 142) (98ZOB496). 

C. Prototropic Tautomerism of Amino-, Hydroxy-.Vfercapto-l,3,4-thiadiazoles. ... 

Thiazoles bearing hydroxy, thio, or amino groups at C-2, C, or C-5 are in tautomeric equilibrium with the corresponding oxo, thioxo, or imino thiazolines. Thiazoles bearing more than one of these groups also display similar prototropic tautomerism, although with some restrictions. 

The reactivity of this class of compounds is discussed either in Section 3.06.5, whether the transformation occurs at the aromatic ring level or in Section 3.06.7, when the protomeric group (hydroxy, thio, or amino) is responsible for the reactivity. Thiazoles substituted by two of these groups also present prototropic tautomerism although with some restrictions (see Section 3.06.4). The reactivity of those compounds is discussed in Section 3.06.5 and Section 3.06.7, in a similar fashion to the monosubstituted derivatives. 

The prototropic tautomerism of 2-hydroxypyridine (1 2) is frequently considered as a prototype for oxo hydroxy tautomerization processes in heterocycles, which resulted in comprehensive studies of this heterocycle by a wide variety of theoretical and experimental methods. 

Next, the substituent effect on the tautomeric preference should be considered. For example, ortho-derivatives of pyridine with substituents which have an acidic proton may participate in prototropic tautomerism (Scheme 12 2002A(11)198). Stabihty of the particular tautomeric form depends on an additional substituent and intermolecular H-bonding (Scheme 13). Moreover, tautomeric preferences can be changed by a solvent. For 6-X substituted 2-hydroxypyridines, the tautomeric equihbrium is stron y affected by substituents which can change the Tt-electron structure of fragments involved in the prototropy. For example, it was found that 2-hydroxy-6-chloro-and 2-hydroxy-6-methoxy-pyridines exist mainly in the aromatic form a... 

Heterocyclic hydroxyl derivatives can be divided into two groups according to whether or not the hydroxyl group is exocyclic. Heterocyclic compounds having a hydroxyl substituent in the ring can have hydroxy or oxo tautomeric forms, and in many cases the oxo form is predominant. Nevertheless, regardless of the position of the prototropic equilibria the compounds will be treated under this heading. 

The substitution reaction may occur on a prototropic nonaromatic form. Both types of tautomerism, i.e., that prevailing in the parent heterocycles (pyrrole-pyrrolenine, indole-indolenine) and that typical of the hydroxy and amino derivatives, must be considered. 

The bottom line on monocyclic aromatic compounds with re-electron sextet is that so far, among six-membered systems only benzene, the azines with 1 through 4 nitrogen atoms, phosphabenzene and arsaben-zene, pyrylium, azapyrylium, chalcogenopyrylium cations (with or without exocyclic groups such as hydroxy, amino and corresponding tautomeric or prototropic forms), and the metallabenzenes with platinum family metals have been proved to afford stable molecules under normal conditions. The list is richer for five-membered systems. 

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