Functionalization of p-tert-butylcalix[5]arene by alkylation with 2-(chloromethyl)pyridine hydrochloride

A study of the base-catalyzed alkylation of p-tert-butylcalix[5]arene (1) with 2-(chloromethyl)pyridine hydrochloride (PicCl . HCl) in DMF has led to the isolation and identification of the 7 possible pyridinyl homologues of 1 in the cone conformation. Reactions of 1 with limiting amounts of alkylating agent (2 to 4 equiv) and base (CsF, KHCO3, BaO/Ba(OH)(2), K2CO3, NaH) produced invariably complex mixtures, which were separated into the pure components by chromatographic means. Regioselective 1,2,4- or 1,2,3-tri-O-alkylation has been achieved in moderate yield (21-22%) by an appropriate choice of molar ratios, solvent, and base. Pentaethers 8-10, endowed with 2-pyridinyl, 3-pyridinyl, and 2-quinolylmethyl pendant groups at the lower rim, respectively, have been also prepared in good yield. The cone conformation in solution for all new compounds has been established by NMR spectroscopy and confirmed for 1,2,3-tri-O-alkylated 5 by a single-crystal X-ray analysis. In the solid state the cone conformation of 5 is mainly determined by the presence of intramolecular hydrogen bonds between adjacent phenolic oxygens, and between the phenolic oxygen and the proximal pyridinyl nitrogen.