Mercapto-thione tautomerism

Pyridines and azines with a- or 7-mercapto groups exist predominantly in the pyridinethione, etc., forms, e.g. as (855) rather than in the mercapto form (854). This behavior is analogous to that of the corresponding hydroxypyridines (Section 3.2.3.7) see also Section 2.2.5.1. 

Pyridine-, pyran- and azine-thiones behave as cyclic thioamides or thioesters and show their typical reactions. Thus, they react with electrophiles at the sulfur atom [as exemplified in (i)-(iv)], and with nucleophiles including the typical ketonic reagents at the thione carbon atom [as exemplified in (vi)-(viii)]. 

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A -1,3,4-Thiadiazoline-2-thione, 5-mercapto-3-phenyl-— see Bismuthiol II Thiadiazoline-5-thiones tautomerism, 6, 552... 

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. 

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. 

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 tautomeric equilibrium of 2-thiouracil in dioxane, water and acetonitrile was studied by ab initio calculations using the SCRF theory. The oxo-thione form was predicted to be predominant in all the solvents studied, but the order of tautomer stability was shown to depend on the level of theory and the dielectric constant of the solvent (00MI243). The tautomerism of protonated forms of 2-thiouracil has also been studied (00JPC(A)5122). Semiempirical AMI, PM3 and MNDO calculations of the thiol-thione tautomeric equilibrium 188c 188d predicted the mercapto form... 

In solutions of 3-mercapto-l, 2,4-triazoles the tautomeric equilibrium is shifted to the thione forms 181b (Scheme 65) [76AHC(S1), pp. 404, 415 96UK326]. Such an equihbrium was observed for 3-mercapto-5-ferrocenyl-4-phenyl-1,2,4-triazole 182 (94MI1121 96UK326). The thione tautomers 183 of 5-mercapto-l,2,4-triazoles are predominant [76AHC(S1), pp. 405, 414 97SA(A)699]. 

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]. 

Tlie oxo-thione form 241 is taken for 2-mercapto-4-hydroxyimidazoles (Scheme 83) [76AHC(S1), p. 463]. These tautomeric equilibria were clarified by the consideration of models in which some tautomeric forms were blocked. Thus, for S-alkylated 5,5-diphenyl 242 or 5-spirocyclohexyl 243 derivatives, oxo-thiol forms are the major tautomers [73T3565 76AHC(S1), p. 463]. 

No definite choice between the two tautomeric forms was made in early studies of 5-mercapto-l,3,4-triazolin-2-one 244 (Scheme 84) [76AHC(S1), p. 464]. The oxo-thione form 245, similar to 241, was attributed to 2-mercapto-4-hydroxyoxazole and its derivatives based on IR-spectro-... 

Tautomerism was reviewed quite extensively in CHEC(1984) <1984CHEC(6)545> and CHEC-II(1996) <1996CHEC-II(4)379>. The tautomeric ability of the 2-mercapto-5-methyl-l,3,4-thiadiazole 9 was studied by its reaction with the electrophilic Cl3 FnCSCl <2003JP01>. 2-Mercapto-5-methyl-l,3,4-thiadiazole 9 was considered to exist mainly as the thione tautomer however, electrophilic substitution occurred on the thiol (Scheme 1). 

In the related mercapto derivatives this corresponds to the thione-tliiol tautomerism, illustrated by structures 10 and 11 for the important antitumor agent 6-mercaptopurine. 

Retro-Hantzsch, mechanism of, 84, 85, 102 Rhodanine, alkylation of, 419 ambident reactivity of. 419 reaction with aryldiazonium salts, 419 reaction with halogenothiazoles, 79 Rice cultures, 135, 136, 137 Ring-chain tautomerism, 113 Ring opening, of A-2-thiazoline-5-one, 433 Ring transformation, 5 amino-A-4-thiazo-line-2-thione to 4-mercapto-imidazoline-2-thione, 399 5,5-diphenyl-2,4-thiazolidinedithione, to 4,5-diphenyl-A-4-thiazoline-2-thione, 37 3... 

Hydroxy- (8a), 2-mercapto- (8b) and 2-amino-l,3,4-oxadiazoles (8c) are in equilibrium with the tautomeric oxadiazolines (9a), (9b) and (9c) respectively. Evidence from UV (72CJC3079) and IR (Section 4.23.2.2.3) spectra supports structure (9a) for A2-l,3,4-oxadiazolin-5-ones and structure (9b) for A2-l,3,4-oxadiazoline-5-thiones. The UV and IR spectra, fluorescence and p/iT values of 2-amino-l,3,4-oxadiazoles indicate that the amine tautomer (8c or d) rather than the imine tautomer (9c or d) predominates (69BSF870, 874, 64CR(258)4579>. 

Thiono-mercapto and amino-imino tautomerism of azines. In the same heterocyclic systems, the stability of thiols with respect to the corresponding thione form is considerably higher than hydroxy derivatives with respect to their oxo forms. In the gas phase 2- and 4-mercaptopyridine are the major tautomers, e.g., 191. 15N NMR spectroscopy is useful for estimating the tautomeric composition of mercaptopyridines in solution. 2-Mercaptopyr-idine in acetone or methanol and 4-mercaptopyridine 191 in methanol or acetone/DMSO were estimated to be ca. 95% in the thione form, e.g., 192. This solvent effect can be attributed to the polarity of the thione tautomers <2006AHC(91)1>. 

As will be discussed later (Section V,C), mercapto-1,3,4-thia-diazoles have been shown to exist mainly as the tautomeric thiones. They can be prepared in different ways ... 

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