Tautomerism of hydroxypyridines (I): The structure of 2,4‐dihydroxypyridine

Abstract

Syntheses of 2‐hydroxy‐4‐methoxypyridine, 4‐hydroxy‐2‐methoxypyridine, 4‐methoxy‐N‐methylpyridone‐2, and 2‐methoxy‐N‐methylpyridone‐4 are described. The ultraviolet absorption spectra of 50% aqueous ethanolic solutions of the above‐mentioned compounds and of 2,4‐dihydroxypyridine and 2,4‐di‐methoxypyridine are measured. Comparison of these spectra enables the determination of the predominant tautomeric structures of 2,4‐dihydroxypyridine and its derivatives. It appears that the chief structure of 2,4‐dihydroxypyridine in aqueous ethanol is that of 4‐hydroxypyridone‐2. Finally it is shown that the methyl derivative of 2,4‐dihydroxypyridine, obtained by Maquenne and Philippe ) when heating ricinine with hydrochloric acid solution or by conversion of 4‐methoxy‐N‐methylpyridone‐2 with the same reagent according to Späth and Tschelnitz ), is 4‐hydroxy‐N‐methylpyridone‐2.

Tautomer Standardization in Chemical Databases: Deriving Business Rules from Quantum Chemistry

“…For these 71 compounds, predictions with the CBR18 structures yield an average error of −0.46, and an RMSE of 0.93; predictions with the CBR14 structures yield an average error of 2.93 and an RMSE of 4.16. For 1 H -pyridine-2,4-dione, the archetypal compound of this class, experiments show that 4-hydroxy-1 H -pyridin-2-one, the tautomer preferred by CBR18, is the tautomer present in solution, , so it should not be surprising that models include these compounds in this tautomer and that p K a predictions made using this tautomer are more accurate than those made using tautomers less likely to be present in solution. Nevertheless, it does provide a powerful illustration of the extent to which structure-based predictive models can depend on the choice of tautomer and the importance that must be attached to tautomer selection when database structures are being used in predictive models.…”

Synthesis and Biological Evaluation of 3,3-Difluoropyridine-2,4(1H,3H)-dione and 3-Deaza-3-fluorouracil Base and Nucleoside Derivatives

“…A solution of iodomethane (1.14 g, 8.03 mmol) in CH 3 CN (3 mL) was added, and the reaction mixture was heated at 55−60 °C until methylation was complete (3−3.5 h) and then allowed to cool to ambient temperature. AcOH/MeOH (0.1 M) was added, and the mixture was stirred for 1 h. The solid was filtered, washed (CH 2 Cl 2 ), and recrystallized to give 8a (50 mg) (∼45% recrystallization recovery).…”

“…A solution of iodomethane (1.14 g, 8.03 mmol) in CH 3 CN (3 mL) was added, and the reaction mixture was heated at 55-60 °C until methylation was complete (3-3.5 h) and then allowed to cool to ambient temperature. AcOH/ MeOH (0.1 M) was added, and the mixture was stirred for 1 h. The solid was filtered, washed (CH 2 Cl 2 ), and recrystallized to give 8a 16 (50 mg) (∼45% recrystallization recovery). Volatiles were evaporated from the combined organic layers, and the residue was chromatographed (EtOAc/hexanes, 7:3) to give 4-acetoxy-1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)pyridin-2(1H)one (300 mg, 89%) as a white foam: UV max 299 nm, min 247 nm.…”