2-mercapto-, tautomers

Infrared and NMR spectra show that for the A-benzyl derivative the mercapto tautomer 173a (R = CHaPh) is preferred in chloroform solution, while in the solid this compound exists as the thione 173b [76AHC(S1), p. 395]. 

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). 

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). 

The relative stabilities of O-alkyl 2-thiouracil and (9-alkyl 4-thiouracil were calculated at the SCF/3-21G level. (9-Alkyl 2-thiouracil is predicted to exist exclusively as the thiol tautomer (AE — 5.45 kcal/mol) in good agreement with the experimental data, whereas the energy difference between the tautomers of (9-alkyl 4-thiouracil is much smaller (AE — 0.98 kcal/mol) and the coexistence of both tautomers in ratio thiokthione = 3 1 is predicted (90JA1504). Both semiempirical AMI and MNDO methods predict the predominance of the mercapto tautomer of (9-methyl 4-thiouracil in agreement with the experimental data (89JCS(P2)1507). 

Mercapto derivatives of furan, thiophene, selenophene (77ACS(B)198) and pyrrole (72AJC985) all exist predominantly in the thiol form. 2-Mercaptobenzothiophene is also a thiol (70JCS(C)243i) whereas 2-mercaptoindole is mainly indoline-2-thione (89) (69CPB550). The finely balanced nature of this system is indicated by the fact that a 3-aryl, but not a 3-alkyl, substituent will stabilize the 2-thiol form, whereas for 3-aryl-fV-methyl derivatives the 2-thione tautomer is preferred (71CC836). 

The known 3-mercapto derivatives of furan, thiophene, selenophene (77ACS(B)198), ben-zothiophene (70JCS(Q243i) and indole (69TL4465) all exist as the 3-thiol tautomers. 

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]. 

A similar conclusion has also been reached in the case of 5-mercapto-1,2,4-thiadiazoles 207 [76AHC(S1), pp. 405, 414 96CHEC-II(4)307] although the question remains open of which of the three possible thione forms is the energetically favored tautomer (Scheme 70). 

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]. 

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 reaction is carried out in both acidic and basic media. Thus, for example, the interaction of 4-diethylaminobut-3-en-2-one with thiocarbamide is performed at 75°C for 30 h (EtOK, EtOH) to result in 54% yield of the major product. The existence of two tautomers 274 and 275 was proved for 2-mercapto-4-methylpyrimidine (Y = S) by IR and H NMR spectroscopy (76ZOR2063). 

Amino and 5-amino-l,2,4-thiadiazoles both exist predominantly in the amino forms. The IR spectrum of 5-mercapto-l,2,4-thiadiazole does not show a clear SH absorption as would be expected for structure 6 and therefore the thione tautomers 7 and 8 have been suggested (Scheme 2). Similarly, IR evidence suggests that perthiocyanic acid exists as the dithione 9 as opposed to stmcture 10 <1984CHEC(6)463>. 

Mercapto-l,2,4-thiadiazoles exist as an equilibrium of tautomers with the equilibrium favoring the thione tautomer. They are acidic with a pA a of around 5. A variety of methylating agents (e.g., diazomethane, dimethyl sulfate and methyl iodide) give S-methylated products and no N-methylation has been observed. They are readily oxidized to sulfoxides and sulfones with either z-chloroperbenzoic acid or hydrogen peroxide in acetic acid <1996CHEC-II(4)307>. There have been no new publications on S-linked substituents since the publication of CHEC-II(1996). 

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). 

Mercapto-l,2,4-thiadiazoles are distinctly acidic. The pK of 5-thio-3-methyl-l,2,4-thiadiazole at 25°C is 5.18 <65AHC(5)119>. The position of equilibrium in the tautomers of 5-thio-l,2,4-thiadiazoles (10) (R = H) appears to be on the thione side (11) or (12). The solid state IR spectrum of (10) (R = Ph) shows no sign of SH absorption <92PS(66)32i>. However, treatment of (10) (R = Ph, / -Tol) with diazomethane does not produce any A-methylated products, but only the 5-methyl derivatives (137) (R = Ph, /)-Tol). Methylation of (10) (R = Ph) with methyl sulfate and with methyl iodide in sodium hydroxide gives only the S-methyl derivatives (137) (Scheme 31) <92PS(66)321>. In 1989 Yousef et al. reported that (10) (R = Ph) reacted with aromatic sulfenyl chlorides and with formaldehyde to give the A-substituted products (26) and (27) (Scheme 31). At the same time, alkylation... 

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. 

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. 

Analogous to MOT the yellow 7-mercapto compound proves to be the thioxo tautomer (59JOC779). In 5,7-dialkyl-2-amino-TPs any imino structure is excluded by IRand NMR spectra (71AP856,71T3247) aminoa-zaindolizines generally behave similarly (91H(32)329). 

In the majority of cases, the equilibrium lies predominantly in favor of the carbonyl tautomer, and for this reason these compounds are considered in the present section. (Most amino and mercapto analogues, while also tautomeric, exist predominantly as such, and they are therefore considered as substituted aromatic compounds.)... 

The tautomers of azole and azine derivatives, stabilized as a result of complex formation, are widely found [11,15,16,18,261-269]. Thus, the metal-cyclic structures with anionic ligands are formed in chelates of 2-hydroxy- 436, 438) and 2-mercapto-substituted (484, 485) derivatives of these nitrogen-containing heterocycles described above. At the same time, the ketone (thion) isomers are stabilized in molecular adducts. In this respect, the syntheses (4.64) [266], (4.65) [267], and (4.66) [269] are quite representative for this group ... 

---