ALTERNATE ALKYLATION OF P-TERT-BUTYLCALIX[8]ARENE IN THE PRESENCE OF WEAK BASES

Alkylation of p-tert-butylcalix[8]arene in the presence of weak bases has been investigated using p-methylbenzyl bromide as an electrophile and CsF as a weak base in THF/DMF. Initially, a sequence of monoalkylation steps on progressively more alkylated compounds has been carried out, leading to the isolation and characterization of 13 p-methylbenzyl ethers ranging from mono- to octasubstituted. Successively, the time course of the composition of the reaction mixture has been determined at regular time intervals by chromatographic analysis and products isolation, in order to have a semiquantitative dynamic picture of the whole process. The reaction path goes mainly through the formation of mono-, 1,3-di-, 1,3,5-tri-, 1,3,5,7-tetra-, 1,2,3,5,7-penta-, 1,2,3,4,5,7- and 1,2,3,5,6,7-hexa-, and heptasubstituted derivatives. This result agrees with an ''alternate alkylation'' mechanism based on the preferential formation of monoanions stabilized by two flanking hydrogen bonds. However, the isolation of appreciable amounts of 1,2,4-tris(p-methylbenzyl) ether indicates that less stable monoanions can also be formed, possibly due to either temporary conformational preferences or the conformational mobility of the calix[8]arene macrocycle, resulting in a less effective hydrogen-bonding stabilization of anionic intermediates.