Tautomeric equilibria

A-2-Thiazoline-5-one may exist in three tautomeric forms (Scheme 108). The tautomeric equilibrium has been studied by H NMR (446. 453. 457. 464). infrared (453. 464-466). and ultraviolet (453, 464) spectros-... 

This reaction is a clear example of the importance of tautomeric equilibrium studies in this series since, to the extent that the starting thiazolone does not epimerize in the medium, asymmetric induction may be expected in this reaction (453, 455). 

Study of tautomeric equilibrium of azolopyridazines by infrared spectroscopy is in complete agreement with the N-H structure. 

Compounds of this type possess a definite Aj-selenazoline structure, while homologous compounds with at least one labile hydrogen on the 2-amino group can exist as a tautomeric equilibrium (Scheme 64). 

However, in the case of derivatives of the type 2-(phenylamino)-4-oxo-5-phenylselenazoline (Scheme 65), the tautomeric equilibrium is displaced towards the imino form (69, 70) This was also shown by the ultraviolet spectra. 

Cyclic 1,2-diketones demonstrate enolic tautomerism, with solvent polarity affecting tautomeric equilibrium ... 

Dihydropyrroles (2-pyrrolines 231) are in tautomeric equilibrium with the corresponding 1-pyrrolines (232) the latter readily form trimers of type (233). The trimer dissociates in boiling THF to 1-pyrroline (232) trimerization is relatively slow at -78 °C and the monomer can be trapped by reaction with acylating reagents to give (V-acyl-2-pyrrolines (81JOC4791). 

Compounds not in tautomeric equilibrium with aromatic derivatives... 

The mean chemical shifts of A- unsubstituted pyrazoles have been used to determine the tautomeric equilibrium constant, but the method often leads to erroneous conclusions (76AHC(Sl)l) unless the equilibrium has been slowed down sufficiently to observe the signals of individual tautomers (Section 4.04.1.5.1). When acetone is used as solvent it is necessary to bear in mind the possibility (depending on the acidity of the pyrazole and the temperature) of observing the signals of the 1 1 adduct (55) whose formation is thermodynamically favoured by lowering the solution temperature (79MI40407). A similar phenomenon is observed when SO2 is used as solvent. 

The use of UV spectroscopy as an identification method is continuously decreasing in relative importance compared to the use of NMR or mass spectrometry. However, due to the general validity of Beer s law, it continues to be an appropriate method for quantitative studies such as the measurement of ionization constants (Section 4.04.2.1.3(iv) and (v)) and the determination of tautomeric equilibrium constants (Section 4.04.4.1.5). 

In a neutral azole, the apparent rate of formation of an A-substituted derivative depends on the rate of reaction of a given tautomer and on the tautomeric equilibrium constant. For example, with a 3(5)-substituted pyrazole such as (199), which exists as a mixture of two tautomers (199a) and (199b) in equilibrium, the product composition [(200)]/[(201)] is a function of the rate constants Ha and fcs, as well as of the composition of the tautomeric mixture (Scheme 16) <76AHC(Si)l). 

N- Aminoaziridines have been converted to alkenes by reaction with a variety of oxidizing agents (70JA1784). Usually, the deamination reaction is stereospecific. The oxidation of l-amino-2,3-diphenylaziridines with manganese dioxide, however, was not stereospecific. The trans compound gives entirely frans-stilbene, whereas the cfs-aziridine forms a mixture of 85% trans- and 15% c -aikene. cw-Stilbene is not isomerized to trans under the reaction conditions, and the results are explained in terms of an azamine intermediate which can isomerize through a tautomeric equilibrium. 

As pointed out in the introduction, if one of the substituents on the nitrogen atom is a hydrogen atom, tautomeric equilibrium between enamino and imino forms strongly favors the latter form 18,140,141). According to physiochemical measurements, the occurrence of simply substituted /1 -pyrrolines and zl -piperideines is very improbable. The formulation of this type of compound with a double bond in the position (used mainly by early authors) was of formal meaning only, having no experimental evidence (142-144). 

The UV spectrum of 5-phenyl-3 hydroxythiophene is very similar to that of its methyl ether in alcoholic solution, indicating that it exists largely in the enol form in this solvent. The same coincidence of the wavelength maxima was also obtained for 5-phenyl-2-hydroxy-thiophene and its methyl ether. In chloroform solution, the maxima were shifted toward longer wavelengths, suggesting that the tautomeric equilibrium in this solvent is displaced more toward the keto form. ... 

In the case of the bases derived from quaternary heterocyclic ammonium salts, the carbinolamines (5) can react as cyclic aldehyde-ammonias with many reagents with which the amino-aldehyde (7) could react. However, reactions of the carbinolamines which are not characteristic of amino-aldehydes are also known. Carbinolamines can easily be reconverted into the quaternary salts by the action of dilute acids, and they form alkyl ethers very easily with alcohols. If these last reactions do not occur, then this is convincing evidence for the base possessing the amino-aldehyde structure. However, if these reactions do occur this does not provide unambiguous confirmation of the carbinolamine structure. They are also given by the bi-molecular ethers (8), and, in the case of a tautomeric equilibrium... 

The tautomeric equilibrium 151 152 has been discussed by Cromwell and David.Ultraviolet spectral data indicate that 151 predominates in neutral aqueous solution, and infrared data are in essential agreement. It was further concluded that in acid solution the equilibrium favors 152, but no ionization constants were reported,... 

Sheinker and his collaborators have studied the effect of replacing the hydrogen atoms of the acetamido group with halogen atoms on the tautomeric equilibrium of compounds of this type by using infrared and ultraviolet spectroscopy. Table VII summarizes... 

In their acidity, basicity, and the directive influence exerted on electrophilic substitution reactions in benzenoid nuclei, acylamino groups show properties which are intermediate between those of free amino and hydroxyl groups, and, therefore, it is at first surprising to find that the tautomeric behavior of acylaminopyridines closely resembles that of the aminopyridines instead of being intermediate between that of the amino- and hydroxy-pyridines. The basicities of the acylaminopyridines are, indeed, closer to those of the methoxy-pyridines than to those of the aminopyridines, the position of the tautomeric equilibrium being determined by the fact that the acyl-iminopyridones are strong bases like the iminopyridones and unlike the pyridones themselves. Thus, relative to the conversion of an... 

The interesting tautomeric equilibrium 299 300 has not yet been reported for heterocyclic A -oxides, although it has been described for acyclic compounds. ... 

According to a molecular orbital calculation of Veber and Lwowski, isoindole should be favored over its tautomer, isoindolenine, by about 8 kcal/mole. However, the calculated electronic distribution is markedly different in the two oases, particularly at position 1, and it is to be expected that the nature and pattern of substituents will play an important role in determining the position of tautomeric equilibrium between these two species. 

One interesting problem frequently recurring in heterocyclic chemistry, particularly with respect to nitrogen heterocycles, is tautomeric equilibria. Too many methods are available for the elucidation of equilibrium positions and tautomeric equilibrium constants (Kj) to adequately review the whole question here. However, the Hammett equation provides one independent method this method has the advantage that it can be used to predict the equilibrium position and to estimate the equilibrium constant, even in cases where the equilibrium position is so far to one side or the other that experimental determination of the concentration of the minor component is impossible. The entire method will be illustrated using nicotinic acid as an example but is, of course, completely general. 

Thus, estimates of tautomeric equilibrium constants are available without any experimental data except the necessary a- and p-values. 

Although these reactions suggest the possibility of a tautomeric equilibrium between the amide and imidol forms in the A -unsub-stituted compounds, the ultraviolet,fluorescence, and infrared spectra of a series of such compounds support the amide structure only. 

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