Difunctionalized β-cyclodextrins: synthesis and X-ray diffraction structure of 6I,6II-dideoxy-6I,6II-bis[2-(2-pyridyl)ethylamino]-β-cyclomaltoheptaose

Abstract

The synthesis, solution NMR investigation and solid-state structural characterization of a new difunctionalized β-cyclodextrin (β-CD) are reported. 6^I,6^II-Dideoxy-6^I,6^II-bis[2-(2-pyridyl)ethylamino]-β-cyclomaltoheptaose is synthesized for the first time using a regioselective synthetic procedure. On the basis of an aqueous solution NMR investigation, the intramolecular interaction of the two pyridine rings with the upper rim of the cavity is proposed. 6^I,6^II-Dideoxy-6^I,6^II-bis[2-(2-pyridyl)ethylamino]-β-cyclomaltoheptaose, C₅₆H₈₆N₄O₃₃, crystallizes in the monoclinic P2₁ space group with cell dimension a = 26.303(5), b = 15.670(5), c = 8.276(2) Å and β = 103.60(2)°, and 5.5 molecules of water for each independent β-cyclodextrin molecule. The structure refines to R = 0.103 for 2270 observed reflections [I ≥ 3σ(I)] and represents the first example of a complete structural characterization of a branched difunctionalized β-cyclodextrin. In the solid state, the macrocycle structure maintains an approximate seven-fold symmetry with only small changes occurring in the cyclic carbohydrate conformation where two consecutive primary hydroxy groups are substituted with bulky moieties. The two aminoethylpyridine groups linked to contiguous glucosidic units show different behaviour, with one group extending away from the cavity of the β-CD, the other remaining in the proximity of the ‘mouth’ of the cavity. However, in the crystal the aminoethylpyridine group extending away from the cavity of the β-CD is deeply inserted into the cavity of the adjacent β-CD molecule translated along the c axis, giving rise to long rows of β-CD molecules stabilized by these host–guest interactions. The resulting polymeric arrangement has already been observed in crystal structures of other monosubstituted β-CDs.