Synthesis and reactions of a 2-chlorocalix[4]arene and a 2,2′-coupled dicalixarene

Treatment of tetramethoxy-p-tert-butylcalix[4]arene with n-butyllithium in THF gives a monolithiated intermediate that reacts with CCl4 to afford 2-chlorotetramethoxy-p-tert-butylcalix[4]arene. The intermediate reacts with BrCH2CH2Br to produce a putative, not isolable, 2-bromotetramethoxy-p-tert-butylcalix[4]arene, which couples in situ with another unit of the lithiated species resulting in a 2,2′-coupled dicalixarene. The chlorocalixarene reacts with nucleophiles (water, isopropylamine, and ethanol) to give 2-hydroxy-, 2-isopropylamino-, and 2-ethoxytetramethoxy-p-tert-butylcalix[4]arene. The 2,2′-coupled dicalixarene undergoes reactions typical of monocalixarenes, being fully demethylated to an octahydroxy species by reaction with HI (generated from iodocyclohexane in situ) in DMF at reflux. This octahydroxy species is fully de-tert-butylated by treatment with AlCl3 and phenol in toluene.