3- Hydroxybenzo thiophene, tautomerism

The effect of solvent on the equilibrium constants has been studied for the 3-hydroxybenzo[/ ]thiophenes <1986TL3275, 1989JA5346>. The enol is much more stable in hydrogen-bonding solvents than in aptotic solvents. Thus, while enol 213 is barely detected in 060, CCR, or CDCI3, it is predominant in CsDsN and DMSO-i/6. For acid-catalyzed ketonization, the 3-hydroxy monocyclic compounds tautomerize 10-10 times faster than their benzo analogues, presumably via a mesomeric effect due to the lone pair on the heteroatom. 

This can be achieved by an indirect method. The lithio derivative is first reacted with a borate ester. Sequential acid hydrolysis and oxidation yields the corresponding hydroxy derivative. This procedure is illustrated by the conversion of 2-lithiobenzo[6]thiophene to 2-hydroxybenzo[6]thiophene, which exists predominantly in the 2(3//)-one tautomeric form (200) <70JCS(C)1926). 

Equilibrium and rate constants for the keto-enol tautomerization of 3-hydroxy-indoles and -pyrroles are collected in Table 32 (86TL3275). The pyrroles ketonize substantially (103-104 times) faster than their sulfur or oxygen analogues, and faster still than the benzo-fused systems, indole, benzofuran, and benzothiophene. The rate of ketonization of the hydroxy-thiophenes and -benzothiophenes in acetonitrile-water (9 1) is as follows 2-hydroxybenzo[b]thiophene > 2,5-dihydroxythiophene > 2-hydroxythiophene > 3-hydroxybenzo[/ Jthiophene > 3-hydroxythiophene. 3-Hydroxythiophene does not ketonize readily in the above solvent system, but in 1 1 acetonitrile-water, it ketonizes 6.5 times slower than 2-hydroxythiophene (87PAC1577). 

When a cyclization reaction leads to mixtures of two isomeric benzo[6]thiophenes, their relative proportions are readily estimated by examination of the 1H NMR spectrum of the mixture.96 104-106 Mixtures obtained by acetylation98 and bromination 76,90 reactions and by Baeyer-Villiger oxidation of acetylbenzo[6]thiophenes107 have been similarly analyzed. The 19F NMR spectra of several polyfluoro-benzo[6]thiophenes have been examined,103,108-m and used to study the reaction of 4,5,6,7-tetrafluorobenzo[6]thiophene with nucleophiles.108 The tautomerism of 2-amino-,112-114 3-N-phenylamino-,116 and 3-hydroxybenzo[6]thiophene109,116-117 derivatives has been studied by 7H NMR spectroscopy. 

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... 

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