Synthesis and conformational studies of tetrahydroxy[3.1.3.1]metacyclophanes and electrophilic aromatic substitution of their tetramethoxy derivatives

Abstract

Base-catalysed condensation of 1,3-bis(5-tert-butyl-2-hydroxyphenyl)propane 5 with formaldehyde in xylene has been carried out to form the novel propane-bridged calixarene-type macrocyclic compound, tetrahydroxy[3.1.3.1]metacyclophane 6. The optimum yield (90%) of 6 is obtained with NaOH as the base, the use of other alkali-metal hydroxides giving lower yields. AlCl ₃ –MeNO ₂ -catalysed trans-tert-butylation of 6 in benzene affords 7 in 80% yield. Intramolecular hydrogen bonding has been observed in the tetraols 6 and 7 as comparable to calix[4]arene. Methylation of 7 with MeI affords the tetramethoxy derivative 11a. The stability of multi-membered carbon skeletons permits the interconversion of functional groups at the lower and upper rims without special regard to ring-opening side-reactions on the upper rim. For example, the introduction of Br, formyl and acetyl substituents has been achieved by electrophilic aromatic substitution of the tetramethoxy derivative 11a. The ¹ H NMR spectral behaviour of these macrocyclic metacyclophanes is also discussed.