Hydroxy-oxo tautomerism

For hydroxy- and mercaptoazoles, hydroxy-oxo and thiol-thione tautomeric equilibria depend strongly on the orientation of the substituents and heteroatoms. Most 2- and 5-hydroxy(mercapto)azoles exist mainly as 0X0 (thione) tautomers, but the corresponding 3- and 4-isomers often prefer the hydroxy (mdrcapto) forms. 

Finally, we note that Karelson et al. [295] have used the D02 model with small cavity radii to consider aqueous solvation effects on other tautomeric equilibria of substituted pyridines. In particular, they examined methyllmethylene, amino/imino, hydroxy/oxo, and mercapto/thiono substitution at the 2-, 3, and 4-positions of pyridine. They observed methyl/methylene equilibria to be only slightly perturbed by aqueous solvation. Amino/imino equilibria were slightly more perturbed, followed by hydroxy/oxo equilibria. Mercapto/thiono equilibria were very significantly affected by aqueous solvation Karelson et al. predicted pK shifts of up to 16 units. This sensitivity of the thiono group to solvation is also discussed in the next section. Overall, the tautomeric equilibria of 3- and 4-substituted pyridines were more sensitive to aqueous solvation than were those of 2-substituted pyridines. 

OH hydroxy or tautomeric oxo form. b Mucochloric acid (decarboxylation). c R-7 = pyridyl, thienyl. d Meldrum s acid derivative. 

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. 

This reaction was extended to prepare 7-nitro- and 9-nitro derivatives of pyrido[l,2-a]pyrimidinone 119 (R = N02, R1 = H R = H, R1 = N02) when the appropriate starting material 118 was heated in boiling dichloro-methane in the presence of triethylamine or when it was stirred in aqueous sodium hydroxide at 20°C (92AJC1825) or treated with sodium azide in aqueous tetrahydrofuran (92AJC2037). Semiempirical molecular orbital calculations (AMI) indicated that the 2-hydroxy-4-oxo tautomeric forms 119 are more stable than the alternative 4-hydroxy-2-oxo tautomeric forms. 

The decarboxylation of 5,7-dihydroxy-3-methylisoxazolo[4,5-6]pyridine (179) was readily accomplished and gave compound (180) (92%) (Scheme 13) <82JCS(Pl)239l>. It was postulated, based upon the infrared spectra bands (vOH 3300-2300 and vco 1660 cm-1), that in the solid state the product exists in the 7-hydroxy-5-oxo tautomeric form (180). In solution it most probably exists as a mixture of tautomers (180)-(182) since in the H NMR spectrum in (CD3)2SO solution the... 

Substituents on C-5 and C-7, respectively R and R mean (possibly substituted) alkyl, aryl, heterocyclyl, and H OH means hydroxy or tautomeric oxo form. 

According to UV and IR spectroscopy, the unsubstituted acridone exists in the vapor phase and in water predominantly in the oxo form (KT — (NH/OH) > 10 in the gas phase) (76JA171). Acridone crown ethers 30 (R = Me, /-Bu) also prefer the oxo tautomeric form in MeCN solution however, on complexation with Pb2+ the shift of the tautomeric equilibrium toward the hydroxy form associated with intermo-lecular interactions and strong hydrogen bonding is observed (04T(A)1487). 

The structure of hydroxy-substituted pyridazino[4,5-<7]pyridazincs with respect to the tautomeric equilibrium has been studied by IR, NMR and UV methods.12,13 In the case where one hydroxy group is present in one of the pyridazine rings, the oxo form always prevails, whereas in the case where two hydroxy groups are present in one pyridazine ring, the spectra are best explained by the mixed hydroxy-oxo form. 

While many different structural types are known for heterocycles containing arsenic, antimony, or bismuth, structural diversity comes from the expanded CN that are available with these heteroatoms. Throughout the Chapter, the letter E, as used in the ring, represents As, Sb, or Bi and its use is explained in the text. Scheme, or Equation. In general, few ring systems exist that contain ring bound heteroatom substituents, and as a result, hydroxy-oxo, amino-imino, and thiol-thioxo tautomerism is nearly nonexistent. 

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