Hydroxypyrroles tautomerism

The tautomeric 2-hydroxypyrroles undergo base-catalyzed reactions probably through deprotonation to the ambident conjugate base (Scheme 71). 2-Hydroxyfurans (e.g. 178) similarly exist in ketonic forms (179) and (180), the most favoured tautomer being the conjugated 2(5//)-furanone (180)... 

Since the last review (76AHCS1, p. 243), progress has been made both in the synthesis as well as in tautomerization studies of 3-hydroxypyrroles (for a review see 92HC525).The parent compound can exist in at least two tautomeric forms (110 and 111). According to MINDO/3 and PM3 calculations (79JOC374 99UP1) 110 is more stable than 111 [AAHf =2.3 kcal/mol (PM3)]. 

A -Acylated 3-hydroxypyrroles prefer the oxo form (87TL4395 90LA 397). Compounds of type 116 [5-(2-acylhydrazino)-4-ethoxycarbonyl)-2-oxo-2//-pyrrole-3-acetate] are in a tautomeric equilibrium with the corresponding acylhydrazones 117 (95H1479). 

Hydroxypyrroles are thought to exist in oxo forms such as 51 or 52 structure 53 illustrates a third possible oxo form. Chemical evidence for tautomerism in the hydroxypyrroles has been reviewed by Fischer and Orth. " Since 2-hydroxypyrrole itself is unstable and... 

The tautomeric behavior of compounds of type 59 has been discussed by Meyer and Vaughan. An intramolecularly hydrogen-bonded 0X0 structure has been assigned to 60 on the basis of its infrared spectrum," whereas unambiguous chemical evidence, i.e., ozo-nolysis to succimide, confirmed the isolation of 61 in the oxo form. The foregoing results may be summarized as follows potential a-hydroxypyrroles exist as pyrrolones. Substituents in the 3-position and in the 5-position favor the A and the A -pyrrolone structure, respectively, as is to be expected. For 3,4,5-trisubstituted compounds, such as 61b, the A -sti ucturc appears to be preferred. An electron-... 

The enol form 10 of pyrrolam A 10 could not be detected despite its aromatic character <2004JOC6105>. Also, its pyrrolinone analogues 34 exist mainly as /3-enaminones <1985TL833> the tautomeric hydroxypyrrole 34 was only observed when R = C02Et (Scheme 1) <1988JOC5680>. 

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 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. 

Three l-hydroxy-3-phenylpyrroles (46) were formed (72JOC1561) in 26-44% yields, instead of the anticipated 6//-oxazines, when the corresponding E-oximes (44) were treated successively with one equivalent of sodium hydride in dimethylformamide (DMF) followed by triphenylvinylphosphonium bromide Z-benzil oxime gave no pyrrole. The cyclization probably proceeds via cyclization to the N-oxide 45 and tautomerism to the 1-hydroxypyrrole. 

A number of important families of heterocycles belong to this class and many of the important systems are oxo derivatives. 2-Hydroxyfuran 64 exists almost exclusively as the equilibrating 3H- and 5//-furan-2-one tautomers 66 and 67. Tautomerism favoring the nonconjugated isomers also occurs in hydroxypyrroles and hydroxythiophenes. Similar behaviour is observed with simple amino derivatives 2-aminofuran 65 is too unstable to be detected <2006AHC (92)1 >. The 3-oxo tautomer 68 is the preferred form of 3-hydroxyfuran. 

Acidic hydrolysis or methanolysis of 5-(l-ethoxyethoxy)-l//-pyrroles 1403, assembled from lithiated l-(l-ethoxy-ethoxy)-2-heptyne 1402 and isothiocyanates in one-pot (Scheme 269), leads to 2-hydroxypyrroles 1404 that, unlike the 3-hydroxy-2-(alkylsulfanyl)-l//-pyrroles 1400, exist exclusively in the form of the tautomeric l,5-dihydro-2//-pyrrol-2-ones 1405 (IR and NMR data). An unprecedented inertness of W-(2-vinyloxy)ethyl group under conditions of acidic hydrolysis (dioxane/H20, HCl, 0°C, 5min) was revealed <2002RJ0907>. 

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