STUDY ON THE ALKYLATION OF P-TERT-BUTYLCALIX[8]ARENE - PARTIALLY O-ALKYLATED CALIX[8]ARENES

Reactions of p-tert-butylcalix[8]arene (1) with various alkylating age nts, including para-substituted benzyl bromides, tert-butyl bromoaceta te, and 2-chloro-N,N-dimethylacetamide, were carried out in THF-DMF in the presence of a base. With strong bases (Nail or BaO/Ba(OH)(2)) oct asubstituted derivatives were obtained, usually in good yield, while i n the presence of weak bases (K2CO3 or CsF) more or less complicated r eaction mixtures were obtained, wherefrom 1,3,5,7-tetraethers with C-4 symmetry were isolated in yields up to 49%. The eight equivalent ArCH 2Ar groups of these compounds give rise to a singlet in the H-1-NMR sp ectrum, indicating a conformational freedom of the macrocycle, as conf irmed by VT-NMR studies. The origin of the 1,3,5,7-regioselectivity ca n be explained, assuming that alkylation proceeds via a sequence of al ternating monodeprotonation and alkylation steps. In each individual m onodeprotonation step, those phenoxide monoanions are formed preferent ially which are stabilized by two flanking hydrogen bonds. However, th is cannot be the whole explanation. In fact, when methyl iodide was us ed as the electrophile in the reaction with 1, the main products were the 1,2,4-trimethoxy and 1,2,3,4-tetramethoxy derivatives, whereas the 1,3,5,7-tetramethyl ether was not detected in the reaction mixture. T his finding leads us to believe that in the reaction with Mel some fac tor other than stability of oxyanions prevails, possibly the molecular dimension of the electrophile. This seems to be confirmed by the obse rvation that n-butyl iodide, of intermediate dimension between MeI and arylmethyl bromides, gives alkylation products typical of both reacti on courses.