Mercapto compounds tautomerism

Many mercaptoazoles exist predominantly as thiones. This behavior is analogous to that of the corresponding hydroxyazoles (cf. Section 3.4.3.7). Thus oxazoline-, thiazoline- and imidazoline-2-thiones (677) all exist as such, as do compounds of type (678). However, again analogously to the corresponding hydroxy derivatives, other mercaptoazoles exist as such. 5-Mercaptothiazoles and 5-mercapto-l,2,3-triazoles (679), for example, are true SH compounds. 

The pattern of reactivity is similar to that discussed for the azolinones is Sections 3.4.1.1.4 and 3.4.3.7.I. A difference is the greater nucleophilicity of sulfur, and thus most reactions of the ambident anion with electrophiles occur at sulfur. 

Many azolinethiones show reactions typical of thioamides in particular, they react with electrophiles at the sulfur atom. 

Reactivity of Five-membered Rings with Two or More Heteroatoms 

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Apparently no data are available for mercapto compounds with hetero atoms-1,2 or for 4-(or 5)-mercapto compounds with hetero atoms-1,3. From the data available, the tautomerism of potential... 

The tautomeric preferences of mercapto compounds are to be compared with the behaviour in the respective parent heteromonocycle. 

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 tautomerism of the rarely assayed OH-, SH-, and NH2 cinnolines (46) was reinvestigated in DMSO-d, solution (Scheme 5.37). Multinuclear NMR studies, especially N N M R spectra, proved the presence of both the hydroxy and mercapto compounds (46, X = O, S) in the -one(thione) form, while aminocinnohne prefers the amino form 46b [86]. 

The mercapto form is much more strongly favored than is the hydroxy form for the corresponding oxygen compounds. A pertinent comparison in this respect is the greatly reduced inclination of enethiols to tautomerize to the corresponding thiocarbonyl compounds, in contrast to the facile ketonization of vinyl alcohols. 

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-... 

The methods outlined, of course, are readily applicable to a wide variety of substituted heterocycles like the carboxyl, hydroxy and mercapto derivatives of pyridines, pyridine 1-oxides, pyrroles, etc. The application to amines and to diaza compounds such as pyrimidine, where the two centers are basic, is obvious except that now 23 takes the role of the neutral compound, 21 and 22 the roles of the tautomeric first conjugate bases, and 20 the role of the second conjugate base. Extensions to molecules with more than two acidic or basic centers, such as aminonicotinic acid, pyrimidinecarboxylic acids, etc., are obvious although they tend to become algebraically cumbersome, involving (for three centers) three measurable Kg s, four Ay s, and fifteen ideal dissociation constants (A ), a total of twenty-two constants of which seven are independent. 

The tautomerism of 3-mercapto-l,2,5-triazole 184 has not been studied thus far. Very little information is available on the structure of 2-mercapto-1,3,4-triazole and its selenium analog, but apparently the thione 185 and se-lenone 186 forms are preferred for these compounds [76AHC(S1), pp. 408, 414]. 

Tliese derivatives quite generally exist in the oxo or thioxo tautomeric forms. Monocyclic compounds are rare for instance, Lavergne et at reported that compound 58 exists as the thioxo tautomer 58a and not as the more antiaromatic mercapto tautomer 58b on the basis of the similarity of the NMR spectra of 58 with that of 59 (80RTC301). 

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). 

The PE spectra of hydroxy- and mercapto-pyridines have been examined, together with the model iV-alkyl and S- or O-alkyl compounds, to elucidate the tautomeric equilibria in the vapor phase (77JCS(P2)1652) (Section 2.04.4.2). Figure 21 and Table 13 show details of the PE spectra of l-methylpyridin-2-one, 2-methoxypyridine and the tautomeric mixture at equilibrium of pyridin-2-one and 2-hydroxypyridine. This indicates that there is approximately 25% of oxo form present once adjustment has been made for the expected influence of methylation, similar measurements reveal ca. 10% of the thione form in the mercapto-thione equilibrium. Other spectra indicate that 3- and 4-hydroxy- and 3- and 4-mercapto-pyridine exist in the vapor phase with less than 5% of the alternative tautomer present. 

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