Mercapto groups, tautomerism

When PAN-T samples are heated by a gradual increase of temperature, the mercapto groups of the tautomeric form of the thioamide groups, enter into an intramolecular reaction with the nitrile groups in accordance with the following scheme ... 

Thiazoles substituted in the 2-, 4- or 5-position with an amino, hydroxy or mercapto group are in tautomeric equilibrium with the corresponding imino-, oxo- or thioxo-thiazo-lines (Scheme 57). A similar protomerism has been established for (4-phenylthiazol-2-yl)acetone (109 Scheme 58). 

Dihydrothiazoles bearing protomeric amino, hydroxy or mercapto groups in a position corresponding to enamine, enol or enethiol functions are in tautomeric equilibrium (Scheme 60) with these functional groups. 

Ultraviolet spectra of numerous pyrazines have been recorded, but in many cases without regard to the effects of ionization, and in various solvents. All pyrazines are basic and thus have both neutral (e.g., 5) and cationic (e.g., 6) forms. Pyrazines with a substituent containing an ionizable hydrogen, such as a carboxy, hydroxy, or mercapto group, may also exist in the anionic form (e.g., 7), the tautomeric neutral form (e.g., 2, R = H), a potentially zwitterionic form (8, R = H) or an isomeric cationic form (e.g., 9, R = H). Many published spectra are in fact of mixed ionic species to determine the spectrum of each ionic form it is necessary to measure its spectrum in a solution buffered at least two units above or below the pAa value (or values) of the substance. In nonaqueous solvents, the neutral (uncharged) species are favored. The ultraviolet spectra of pure species may then serve to characterize the pyrazine, may permit the correlation of spectra with structure, and may be used in quantitative determinations. 

The chemical behavior of thiourea and its iV-derivatives is determined by the existence of tautomeric forms the mercapto group is almost always the point of attack in chemical reactions. 

Hydroxy and mercapto substituents at the 3- and 5-positions can also exist in tautomeric forms (see Section 4.01.5.2) and can be alkylated at either the substituent or the ring nitrogen atom. 3-Methoxy groups are not replaced by nucleophiles, but both 3- and 5-alkylthio groups react readily, as does 3-methoxy-l,2-benzisothiazole. Alkylthio compounds can be oxidized to sulfoxides and sulfones, and the latter readily undergo nucleophilic replacement. All the hydroxy compounds react with phosphorus pentachloride to give the chloro derivatives. 

In comparison with mercapto-, hydroxy-, and amino-pyridines, methylpyridines should show an even greater tendency to exist in the methyl form [instead of as pyridmethines (297)] than do the amino compounds to exist as such. If the methyl carbon atom carries an electron-withdrawing group, it might be expected that structures of type 297 would be stabilized. Fused benzo groups should also tend to stabilize the methine form, and tautomerism involving 298 has, in-... 

A strictly dehned region of chemical shifts of C2, C4, and C5 atoms in A-oxides of 4A-imidazoles allows to dehne clearly the position of the A-oxide oxygen atom (102). Chemical shifts of the a-C nitrone group in a-N-, O-, and S-substituted nitrones are located in the region of 137 to 150 ppm (388, 413). On the basis of 13C NMR analysis of 3-imidazoline-3-oxide derivatives, the position of tautomeric equilibria in amino-, hydroxy-, and mercapto- nitrones has been estimated. It is shown that tautomeric equilibria in OH- and SH-derivatives are shifted toward the oxo and thioxo forms (approximately 95%), while amino derivatives remain as amino nitrones (413). In the compounds with an intracyclic amino group, an aminonitrone (A) - A-hydroxyaminoimino (B) tautomeric equilibrium was observed (Scheme 2.76), depending on both, the nature of the solvent and the character of the substituent in position 2 of the heterocycle (414). 

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. 

Often, the exact position of tautomeric equilibria (Section III,A,4,a) is uncertain for fused troponoids substituted by hydroxy, mercapto, or amino groups. In such cases the structures preferred by the authors or the most probable tautomeric forms will be used here. 

Table 11 summarizes the main results on the tautomerism of mono-hydroxy-, -mercapto-, -amino- and -methyl-azines and their benzo derivatives, in water. At first sight the equilibrium between 2-hydroxypyridine (71) and pyridin-2-one (72) is one between a benzenoid and a non-benzenoid molecule respectively (71a 72a). However, the pyridinone evidently has a continuous cyclic p- orbital system, containing six it- electrons, the usual aromatic count, if the carbonyl group contributes none. This assumption implies the formula (72b), from which by redistribution of electrons we arrive at (72c), which has the same benzenoid system as (71a). Further canonical forms (71b, 71c) can be drawn of (71) which correspond to the non-benzenoid forms of (72). The elusive property of aromaticity is therefore possessed by both tautomers, although not necessarily by both equally. When the carbonyl oxygen of (72) is replaced by less electronegative atoms, as in the imine tautomers of amino heterocycles, or the methylene tautomers of methyl derivatives, the tendency towards polarization in forms corresponding to (72b) and (72c) is considerably less, and the amino and methyl tautomers are therefore favoured in most instances. 

Simple considerations such as these account adequately for many of the familiar reactions of substituted 7r-deficient heterocycles, such as nucleophilic displacement, tautomerism in hydroxy, mercapto and amino heterocycles, facile deprotonation of alkyl substituents, decarboxylation of carboxymethyl groups and electrophilic substitution of benzo-fused and aryl-substituted heterocycles. These individual effects are discussed separately in the following subsections. 

Aminoimidazoles might be expected to prove more complicated than the analogous hydroxy and mercapto derivatives because of the possibility that an R group on NHR could have a marked effect on the position of tautomeric equilibrium, particularly if R is an acyl or sulfonyl function. However, amines are much weaker acids than hydroxy or mercapto compounds and so it should not be necessary to consider zwitterionic structures to any extent an NH group is not at all likely. 

The most important potentially tautomeric thiophenes and furans are those carrying hydroxyl, mercapto, and amino groups. In these compounds a prototropic shift can occur between the functional group... 

Studies on the tautomerism of pyridazines with potential tautomeric groups have continued. On the basis of recorded ionization constants and UV spectra of 3,4,5-trimercaptopyridazine and its derivatives, it is concluded that the compound exists as 3,4-dimercaptopyridazine-5(2f/)-thione. Tautomerism of hydroxy- and mercaptopyridazines was investigated with the aid of the corresponding anhydro bases as reference compounds. They exist predominantly in the -one or -thione forms. Similarly, the 3-mercapto-pyridazine-6(l/f)-thione structure in aqueous solution has been redeter-... 

The systematic IR studies of the functional group and heteroatom effect on the position of the tautomeric equilibrium indicated that the stability of thiols (with respect to the corresponding thione forms) is considerably higher than the stability of the hydroxy forms (with respect to the oxo forms) in the same heterocyclic systems, so the mercapto tautomers of mercaptopyridines should be more favored in the equilibrium than their oxygen analogs (92JPC6250). 

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