Potentially tautomeric pyridines. Part IX. The effect of chlorine substituents on pyridone–hydroxypyridine tautomerism

Abstract

Chlorine atoms a to the nitrogen displace the tautomeric equilibrium of pyridones significantly in favour of the hydroxypyridine form, whereas chlorine atoms in other positions have much less effect. a-Monochloropyridones are shown to exist to an increasing extent in the hydroxypyridine form as the dielectric constant of the medium decreases.RELATIVELY little is known of the effect of ring substituents on the tautomerism of simple pyridones. Although a 3-nitro-group has little apparent effect on the tautomeric equilibrium of 4-~yridone,~ we recently disclosed the large effect of a 6-hydroxy-or 6-methoxysubstituent on the tautomerism of 2-pyrid0ne.~ This prompted us to investigate the general effect of substituents on the pyridone-hydroxypyridine equilibrium. We chose chloro-substituted compounds for an initial study because a reasonably representative selection was available. den Hertog et aZ.4 first prepared 2,3,5,6tetrachloro-4-hydroxypyridine, but gave no indication as to its tautomeric structure. 3,4,5,6-Tetrachloro-2hydroxypyridine has previously been reported on several occasions 5-7 and the ultraviolet spectrum in methanol differs from that of the N-methyl analogue, indicating that the hydroxy-tautomer is favoured. The preparation has been reported of 6-chlor0-2-hydroxypyridine,* and 2-chlor0-,~ and 2,6-dichlor0-4-hydroxypyridine,~~ but no evidence is offered as to the structure.Two groups 11, l2 recently concluded from infrared and ultraviolet spectra that 2 , 3,5,6-te t rafluoro-4-hydroxypyridine exists almost completely in the hydroxy-form.Preparation of Comj5ounds.-2-Chloro-4-pyridone was prepared from 2-chlor0-4-nitropyridine.~ 2,6-Dichloropyridine afforded 6-chloro-l-methyl-2-pyridone by successive quaternisation and hydrolysis. Further Nmethylpyridones were prepared from the parent pyridone and methyl iodide and methoxypyridines from the corresponding chloro-compounds and methoxide ions.Attempts to prepare l-methyl-2,6-di-and l-methyl-2,3,5,6-tetra-chloro-4-pyridone failed ; only the methoxy-isomers were obtained by the methyl iodide method, and the attempted deamination by diazotisation of 4-amino-2,6-dichloro-l-methylpyridinium perchlorate f ailed.13 EXPERIMENTAL 6-Chloro-2-hydroxypyridine (Aldrich), m. p. 126-127" (from aqueous ethanol) (lit.,* 128-129") ; 6-chloro-2-meth-* B. p. not previously reported. This structure was confirmed 1 Part VIII, A. R. Katritzky and B. Ternai, J . Chem. SOC. ( B ) , Personal communication from Dr.

The Tautomeric Persistence of Electronically and Sterically Biased 2‐Quinolinones

“…[73] Whereas 2(1H)-and 4(1H)-pyridinone and even 3,5-dichloro-4(1H)-pyridinone [74] exist mainly, if not exclusively, in the lactam form, 6-chloro-2(1H)-and 2-chloro-4(1H)-pyridinone contain appreciable proportions of the hydroxy tautomer if dissolved in moderately polar media (ethanol as opposed to water). [74] The hydroxy forms of 2,6-dichloro-and 2,3,5,6-tetrachloro-4-(1H)-pyridinone and 3,4,5,6-tetrachloro-2(1H)-pyridinone prevail whatever the solvent. [74] Eur.…”

“…[74] The hydroxy forms of 2,6-dichloro-and 2,3,5,6-tetrachloro-4-(1H)-pyridinone and 3,4,5,6-tetrachloro-2(1H)-pyridinone prevail whatever the solvent. [74] Eur. J.…”

Hydrolysis of α-chloro-substituted 2- and 4-pyridones: Rate enhancement by zwitterionic structure

“…These two pyridone derivatives were synthesized as reported. 14 The hydrolysis reactions were carried out in 1.0 M NaOD in D 2 O. The reactions were monitored using NMR spectroscopy to follow the disappearance of the substrates through integration of the pyridine proton absorptions.…”

The crystal and molecular structures of three isoquinoline derivatives: 1-chloro-3-hydroxyisoquinoline, 1-phenyl-2-methyl-3-isoquinolone and 2-(2',6'-dichlorobenzyl)-1-isoquinolone

“…However, the 1-chloro derivative (III) exists as the lactim in all solvent systems. The lactim form of 2-pyridones, for example, is favored by an electronegative substituent at C(6) of the pyridone ring (Katritzky, Rowe & Roy, 1967). Our X-ray crystallographic study of 1-chloro-3-hydroxyisoquinoline (III) was undertaken to confirm the lactim form in the solid state, and to provide bond lengths for the isoquinoline nucleus for which few structural data are available.…”