Hexahomotrioxacalix arenes synthesis

The Petrolite method for calixarene synthesis also leads to dihomooxacalix[4]arenes, as represented by the p-tert-butyl compound 9. Proton-NMR spectra and TLC data indicate that the mixture obtained from p-terf-butylphenol and paraformaldehyde contains appreciable amounts of 9, but it is difficult to obtain a pure sample of 9 from this mixture 23,2, 28>. Compound 9 is much more readily accessible by the thermally-induced dehydration of the (u. v(hydroxymethyl)tetramer 46 which can be readily prepared by the convergent synthesis outlined in Scheme 5 followed by bis hydroxymethylation 62), as shown in Scheme 6. Other oxacalixarenes can also be obtained by thermally-induced dehydration. For example, 2,6-6 (hydroxymethyl)-phenols (42) yield hexahomotrioxacalix[3]arenes (43)28,62,101 > j cfroxymethyl)... 

Synthesis, conformational studies and inclusion properties of tris[(2-pyridyl-methyl)oxy]hexahomotrioxacalix[3]arenes, T. Yamato, M. Haraguchi, J.-I. Nishikawa, S. Ide and H. Tsuzuki, Can. J. Chem., 1998, 76, 989. 

Besides the large number of symmetrical hexahomotrioxacalix[3]arene upper rim derivatives (la-i) previously reported [2], asymmetric analogues of 1 were obtained by Fuji and coworkers [6,7]. Compounds 2 (a few examples are illustrated below), bearing different substituents on their upper rims, were prepared by a stepwise synthesis based on the cyclization of the corresponding linear trimers under acidic high-dilution conditions. This procedure was later improved [7], involving a condensation reaction between p-substituted phenol dimers and a monomer. These methods have been useful in the preparation of chiral homooxacalix[3]arenes. 

As an extension of the previous work, the Fuji group [8] introduced several functional groups on the upper rim of hexahomotrioxacalix[3]arenes. Selective debromination of 2a under formic acid reduction conditions yielded the mono-unsubstituted derivative 3, which allowed the direct introduction of several new groups in the vacant para-position (Scheme 17.1). Through a four step synthesis... 

Besides homooxacalix[3, 4]arenes, larger macrocyclic compounds such as the homooxacalix[6]arenes with two (82, 83) or three (84) CH2OCH2 bridges and the octahomotetraoxacalix[8]arene 85 were reported by Masci in reference 2. Only the synthesis and the stmctural analysis of these parent compounds have been described. One rare example of lower rim functionalization of a large homooxa compound is the tetrahomodioxacalix[6]arene hexamethyl ester 86 [77]. Its X-ray crystal sfructure was determined and H NMR studies indicated that it is a poor extractant for the alkali metal ions. Dihomooxacalix[5]- (87) [78] and -[6]arene (88) [79], hexahomotrioxacalix[9]arene (89) [79] and tetrahomodioxacalix[10] arene (90) [78] were also reported. 

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