Stereochemical transformations of some seven-membered pyridoxine dimethyl ketals

Theoretical and experimental study on cyclic 6-methyl-2,3,4-tris(hydroxymethyl)pyridin-5-ol acetonides

“…According to the results of ab initio quantum-chemical calculations, in all cases the twist conformation of seven-membered ring turned out to be more energetically favorable, whereas the sixmembered ring is most likely to adopt distorted boat conformation. These findings are consistent with the results of our previous studies on conformations of pyridoxine acetals [4]. In keeping with the calculated energies of formation ΔG f° in the gas phase at 298 K (Table 1), the formation of six-membered acetal III is preferred, while the formation of the other acetals is considerably less probable.…”

“…The mixture was stirred for 20 h at room temperature, the precipitate was filtered off and neutralized with an aqueous solution of potassium carbonate, the solvent was distilled off under reduced pressure, the solid residue was washed with boiling acetone, and the filtrate was evaporated under 566 reduced pressure. Yield 0.76 g (88%), light yellow crystals, mp 161°C[4].5,6-Bis(hydroxymethyl)-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine (III). a.Gaseous hydrogen chloride, 8 g (219 mmol), was passed under stirring through a suspension of 1 g (5.05 mmol) of compound I in 22 ml (300 mmol) of acetone and 8 ml (57.8 mmol) of 2,2-dimethoxypropane.…”

“…The formation, stability, and conformational specificity of cyclic acetals derived from pyridoxine attract both practical and considerable theoretical interest [4]. Pyridoxine can be converted into two cyclic six-and seven-membered acetonides, depending on the concentration of acid catalyst [5,6].…”

“…Compound I was subjected to acetalization with acetone according to standard procedure [4]. At high concentration of acid catalyst (HCl, >25%), pyridinium salt of six-membered acetal III was formed (the product is soluble in acetone).…”

New synthetic method for 2,3,4-tris(hydroxymethyl)- 6-methylpyridin-5-ol

“…Acetonide V alkylated with the methyl chloromethyl ether at the phenol hydroxy group was subjected to XRD analysis that demonstrate the twist form of the sevenmembered ring. The bond distances, bond and torsion angles were virtually identical to the corresponding values in the pyridoxine acetonide [6].…”