"Alternate Alkylation" of p-tert-Butylcalixarene in the Presence of Weak Bases

Article abstract of DOI:10.1021/jo00118a033

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.