Deacylation of 4-nitrophenyl acetate by 6A-(ω-aminoalkyl)amino-6A-deoxy-β-cyclodextrins†

Abstract

The deacylation of 4-nitrophenyl acetate (pNPA) in aqueous solution to give 4-nitrophenolate is significantly accelerated by the 6^A-(ω-aminoalkyl)amino-6^A-deoxy-β-cyclodextrins [βCDNH(CH₂)_nNH₂] which are themselves acylated to give predominantly βCDNH(CH₂)_nNHCOCH₃. The deacylation is characterised by k_dK = 27.4, 35.5, 24.5 and 16.0 dm³ mol^–1 s^–1 at 298.2 K in aqueous 0.05 mol dm^–3 borate buffer and I = 0.10 mol dm^–3 (NaClO₄) when n = 2, 3, 4 and 6, respectively, where k_d (s^–1) is the rate constant for pNPA deacylation through a βCDNH(CH₂)_nNH₂·pNPA complex characterised by a stability constant K (dm³ mol^–1). The inhibition of the deacylation by adamantane-1-carboxylate (AC^–) is consistent with a mechanism where AC^– competes with pNPA in entering the βCDNH(CH₂)_nNH₂ annulus through the formation of a βCDNH(CH₂)_nNH₂·AC^– complex. The latter complex has been qualitatively studied by ¹H NMR ROESY methods, and its structure and that of βCDNH(CH₂)_nNH₂· pNPA have also been force-field modelled. The possibility of the operation of an S_N2 mechanism as an alternative explanation for the deacylation data is also considered.