3- Hydroxyindole, tautomerism

The tautomerism of hydroxyindoles (and mercaptoindoles) has been reviewed (79HC1). As was pointed out previously (76AHCS1, p. 243) 2-hydroxyindoles 120 exist as lactams 121 (indolin-2-ones). The same holds for the corresponding A-hydroxy derivatives (1-hydroxyoxindoles) 121 (R = OH) (86AP1084,86JOC1704 90SC2133 94MI4). 

Although iV-hydroxypyrroles possess in principle several tautomeric forms, e.g. (76), (77) and (78), only the A-hydroxy form (76) has been observed for l-hydroxy-2-cyanopyrrole (73JOC173). In the case of 1-hydroxyindoles, where the potential loss of aromatic resonance energy will be much less, both tautomers (79) and (80) coexist in solution with the relative proportions being dependent on the solvent... 

The chlorosulfonium compounds can also be used for the synthesis of oxindoles, the stable tautomeric form of 2-hydroxyindoles. The a -methylthio ketone is replaced by ethyl methylthioacetate and the products of the Sommelet-Hauser rearrangement are cyclized to 3-methylthiooxindoles. The methylthiooxindoles are reductively desulfurized with Raney nickel (equation 102) (74JA5508). 

The H-NMR spectra (Table I) show no evidence of tautomerism of 1-hydroxypyrroles to 2H- or 3//-pyrrole 1-oxides and are similar to those of corresponding pyrroles. The hydroxyl proton is not always seen, as in the case of 1-hydroxyindole, and is easily exchanged out by deuterium oxide. The H-NMR spectrum of 2-cyano-2-methyl-2//-pyrrole 1-oxide (2) in dimethyl sulfoxide (DMSO) was unambiguous (Table I), but in deuter-iochloroform, the 3- and 4-protons appeared at the same position. 

In the benzo[A] and benzol/] heterocycles 220 and 221, where the loss of ring resonance energy on tautomerism is much less than in the nonannulated heterocycles 217, the oxo tautomers 222 and 223 are energetically preferred. 2-Hydroxyindole 220 (X = NH) exists exclusively as the oxo tautomer 222 (X = NH) (oxindole). The hydroxy form of 2-hydroxybenzo[A]thiophene 220 (X = S) is detectable by NMR spectroscopy when its trimethylsilyl ether precursor is... 

An extreme case is the nitronelhydroxylamine tautomerism between 2-methylindo-lenine-A-oxide (15a) and 2-methyl-A-hydroxyindole (15b) [70]. The position of this equilibrium depends strongly on the proton-accepting and donating abilities of the solvent in pyridine and acetonitrile there exists 0 cmol/mol of form (15a), 33 cmol/mol in tetrachloromethane, but 100 cmol/mol in phenol. Thus, it is possible to observe either (15a) (in phenol) or (15b) (in pyridine) depending on the solvent used. 

Hydroxyindole certainly contribntes in the tautomeric equilibrium with the carbonyl form, though it is the minor component. Indoxyl, 10.46, ° is more acidic than oxindole, the anion produced is ambident reactions with electrophiles at both oxygen and carbon are known. ... 

Another example of the reaction proceeding in a similar manner is the conversion of 2-(5-chloro-2-nitrophenyl)-3-phenylpropionitrile into A-hydroxyindole derivative (Scheme 71) [189]. The intermediate vinyl nitroso compound undergoes electrocyclization, resulting in the formation of nitrone (2//-indole N-oxide), which is tautomerized into A-hydroxyindole. 

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