Potential Hydroxyl Group

A great deal of work has appeared on these compounds however, much of it was mutually contradictory and a clear pattern is only now appearing for the tautomerism of compounds of this type. Compounds with potential 5-hydroxyl groups, which could exist as 44a, 44b, or 44c (X = 0 or NR), never appear in the hydroxy form (unless this is stabilized by chelation) the two oxo forms, 44b and 44c, exist in equilibrium. However, compounds with potential 3-hydroxyl groups do exist as such, i.e., as 44d and not as 44e. This 

in Ciba Foundation Symposium on the Chemistry and Biology of Purines (G. E. W. Wolstenholme and C. M. O Connor, eds.), p. 72. Little, Brown, Boston, Massachusetts, 1957. 

Isoxazol-5-ones can exist in three different types of structures, cf. 45-47 (R = H). Early investigators assigned structures to these compounds on the basis of unreliable chemical evidence thus the NH structure 47 was favored because the silver salt of 3-phenyl-isoxazol-5-one reacts with methyl iodide to give a product which was incorrectly (see reference 44) formulated as the iV-methyl derivative45 (cf. also reference 46). Bromine titration data led to assignment of an incorrect structure to 3,4-diphenylisoxazol-5-one cf. article I (Volume 1), Section II,A. Comparison of the dipole moments of 3-phenylisoxazol-5-one with those of the methyl derivatives 45 (R = Me) and 46 

Oliveri-Mandala and A. Coppola, Atti reale accad. Lincei, Rend classe set. 

Recently a definitive study of several isoxazol-5-ones using infrared and ultraviolet spectroscopy (Table I) has shown that the balance between the various tautomers is a delicate one and that all three of the structural types can predominate depending upon the nature of the substituents and the conditions of the experiment.49 50 However, the hydroxy form is only found when it is stabilized by chelation (i.e., a carbonyl substituent in the 4-position). The other compounds exist in the CH form in nonpolar media increasing polarity of the solvent stabilizes increasing amounts of the more polar NH forms. 

Oliv cri-Mandala and A. Coppola, Atti reale accad. Lincei, Rend classe sci. fis. mat. e nat. 20, I, 244 (1911) Chem. Absir. 5, 2100 (1911). 

Hydroxy-pyridines (8) and -azines are both weak acids (cf. phe- 

Heterocyclic compounds carrying potential hydroxyl groups are cyclic amides or vinylogs of amides. There is much physical evidence that acyclic amides exist almost entirely in the oxo form (for references see reference 6), and the apparent contradiction that ultraviolet spectral data appeared to favor the imidol formulation has now been explained on steric grounds. The value of pKr is estimated to be about 7 on the basis of pK measurements for acyclic amides. Extensive evidence, summarized in the following sections, shows that for a- and y-hydroxy heterocyclic compounds, the cyclic amide form usually predominates by a substantial factor, often ca. 10 . 

Cieslak, S. Lewak, and I. Chmielewska, Roczniki Chem. 34, 423 (1960). J. Cieslak, Roczniki Chem. 26, 483 (1952). 

Little is known concerning the tautomerism of glutaric anhydrides and related compounds, although a recent report claims the isolation of the two tautomeric forms (18 and 19) of a glutaconic anhydride derivative, which appears improbable. 

The large differences between the infrared carbonyl frequencies of 

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Diazo coupling is expected to occur only with highly reactive systems, and experiment bears this out. Diazonium ions couple with the anions of N-unsubstituted imidazoles at the 2-position (e.g. 125 yields 126) and with indazoles (127) in the 3-position. In general, other azoles react only when they contain an amino, hydroxyl, or potential hydroxyl group, e.g. the 4-hydroxypyrazole (128), the triazolinone (129) and the thiazolidinedione (130) (all these reactions occur on the corresponding anions). 

I. Other Compounds with Potential Hydroxyl Groups... 

All the available evidence suggests that five-membered heterocyclic compounds containing a potential hydroxyl group between the two hetero atoms in the 1- and 3-positions exist predominantly in the oxo form (cf. 89 90). 

In compounds with several potential hydroxyl groups, such as the oxauracil (17) (79JHC161) and the barbituric acid analogue (53) (61JOC3461), the carbonyl tautomers are usually preferred. 

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