Failure of the antiperiplanar lone pair hypothesis in glycoside hydrolysis. Synthesis, conformation, and hydrolysis of α-D-xylopyranosyl-and α-D-glucopyranosyl-pyridinium salts

Abstract

(1) Two series of crystalline α-D-xylopyranosyl-and α-D-glucopyranosyl-pyridinium bromides have been made, by reaction of the acetylated α-bromides with the pyridines in an aprotic solvent in the presence of bromide ion, followed by deacetylation with aqueous HBr at room temperature. (2) 200 MHz ¹H N.m.r. spectra in D₂O of representatives of each series show the xylo-compounds to adopt the ¹C₄ conformation, and the gluco-compounds the ¹S₃ conformation. (3) The hydrolyses of α-D-xylopyranosyl- and α-D-glucopyranosyl-3-bromopyridinium ions in 1.0M-NaCIO₄ at 25.0 °C are described by k_obs/s^–1=4.7 × 10^–8+1.4 × 10^–18/[H⁺] and k_obs/s^–1=2 × 10^–7+1.4 × 10^–17/[H⁺], respectively. (4) The products of pH-independent hydrolysis of the foregoing ions are the sugars and 3-bromopyridine, whereas at pH 12, 10% of both reactions proceed by attack on the pyridine ring: attack on the sugar yields glucose and 1,6-anhydroglucopyranose, but no xylose. (5) The pH-independent hydrolyses display strongly positive entropies of activation: at 25.0 °C, those of five xylo-compounds give a β_lg value of –1.27 ± 0.06, and those of four gluco-compounds one of –1.06 ± 0.12. (6) Arguments are presented, in the light of the low α:β rate ratios for both xylo and gluco pyridinium salts (8–23 and 80, respectively, at 25 °C), that departure of a pyridine from C(1) of an aldopyranose ring does not require a conformation in which the leaving group is antiperiplanar to a lone pair of electrons on O(5). (7) The antiperiplanar lone pair hypothesis is shown to be a special case of the principle of least nuclear motion, which is known not to apply to reactions with very product-(or reactant-) like transition states.