Compounds in tautomeric equilibrium with aromatic derivatives

2 Compounds in tautomeric equilibrium with aromatic derivatives 

Padwa 88JOC2232 has described the aromatization of 4-methylene-A -pyrazoline (158) into pyrazole (159) using a trace of acid or base and into pyrazole (160) on exposure to light. 

Aran has studied the reactivity of 1,1-disubstituted indazol-3-ylio oxides 93JCS(Pl)ill9 , for instance, treatment of these compounds with hydrochloric acid affords the corresponding 3-hyd-roxyindazoles the Wawzonek rearrangement (formation of 1,2-disubstituted indazolinones) was also observed. 

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Heterocyclic compounds are ubiquitous in biology, medicine, and biochemistry, and the azoles form an important class of nitrogen heterocyclic compounds with five-membered aromatic rings that can contain one to five nitrogen atoms (other heteroatoms can also be present). Many drugs and pharmaceuticals are derived from azole structures. The structures of representative azoles are shown in Figure 6.1. Note that some of these compounds exist in tautomeric equilibrium in solution. 

The study of the enamine structure may be associated, to a certain degree, with the problem of the so-called pseudobases an instructive, but somewhat specialized, review of these compounds was contributed by the late Professor Beke 47 to the first volume of this series. The name pseudobases was given by Hantzsch,48 towards the end of the last century, to those a-aminocarbinols which undergo a structural change during salt formation and yield salts with the loss of one molecule of water. The liberation of pseudobases from their salts is accompanied by rehydration. This behavior has been observed with a,/3-unsaturated heterocyclic compounds and, to a certain degree, with aromatic heterocyclic pyridine derivatives. As formulated by Gadamer,49 the pseudobases represent a potential tautomeric system of three components, the quaternary hydroxide A, the carbinolamine B, and the open-chain amino-carbonyl derivative C, in which all three components exist in a mobile equilibrium ... 

The stability of the pyrazolinone tautomers was related to their scale of aromaticity.Experimental values for the tautomerism of pyrazolinone derivatives were obtained by flash vacuum pyrolysis (FVP), which allowed the calculation of the effect of the temperature on the equilibrium between tautomers. The variation of Kj with the temperature was determined by H NMR in solution for the model compound l-phenyl-3-methyl-2-pyrazolin-5-one (Scheme 25), showing that at 0 K the only tautomers present are either the NH or the OH ones. Temperature and solvent effects on the prototropic equilibrium of the model compound in solution showed that... 

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