Study on the alkylation of p-tert-butylcalix[8]arene. Partially O-alkylated calix[8]arenes

Reactions ofp-tert-butylcalix[8larene (1) with various alkylating agents, includingpuru-substituted benzyl bromides, tert-butyl bromoacetate, and 2-chloro-N,N-dimethylacetamide, were carried out in THF-DMF in the presence of a base. With strong bases (NaH or BaO/Ba(OH)n) octasubstituted derivatives were obtained, usually in good yield, while in the presence of weak bases (K2CO3 or CsF) more or less complicated reaction mixtures were obtained, wherefrom 1,3,5,74etraethers with C4 symmetry were isolated in yields up to 49%. The eight equivalent ArCH& groups ofthese compounds give rise to a singlet in the lH-NMR spectrum, indicating a conformational freedom of the macrocycle, as confirmed by VT-NMR studies. The origin ofthe 1,3,5,7-regioseledivitycan be explained, assuming that alkylation proceeds via a sequence of alternating monodeprotonation and alkylation steps. In each individual monodeprotonation step, those phenoxide monoanions are formed preferentially which are stabilized by two flanking hydrogen bonds. However, this cannot be the whole explanation. In fact, when methyl iodide was used as the electrophile in the reaction with 1, the main products were the l,2,44rimethoxy and 1,2,3,4-tetramethoxy derivatives, whereas the 1,3,5,7-tetramethyl ether was not detected in the reaction mixture. This finding leads us to believe that in the reaction with Me1 some factor other than stability of oxyanions prevails, possibly the molecular dimension of the electrophile. This seems to be confirmed by the observation that n-butyl iodide, of intermediate dimension between Me1 and arylmethyl bromides, gives alkylation products typical of both reaction courses.