Philip Keehn

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Synthesis of p-t-butylcalix[8]arene (4) was achieved in near quantitative yield by ‘7+1’ and ‘3+1’ convergent addition reactions with trifluoroacetic acid as catalyst. Other convergent additions examined also gave rise to 4 in lower than quantitative yields. Similarly, elusive p-t-butylcalix[5]arene (7) was obtained in 15% from a ‘3+2’ convergent addition.

The action of trifluoroacetic acid (TFA) on 2,4,6-trimethoxybenzyl alcohol 3 affords the title tetrameric compound in high yield as a maroon TFA complex, 4; trituration of which with acetone gives the free, colorless, calix[4]phloroglucinarene (5) that can also be directly isolated by treating the reaction mixture with base. The novelty of compounds 4 and 5 is that they possess four additional methoxy groups, which occupy the cavity of the known calix[4]resorcinarene octamethyl ether (2). Ultraviolet-visible spectroscopic analysis shows that TFA-complex 4 exhibits transannular charge-transfer interactions between the opposite aromatic rings. The (1)H-NMR spectrum of the TFA-complex 4 does not change over a wide temperature range, strongly suggesting that it adopts a saddle (1,3-alternate) structure. The conformation of the free phloroglucinarene 5 is temperature-dependent, as determined by variable temperature (1)H NMR spectroscopy. Tetramer 5 adopts a partial cone conformation at low temperatures, but at elevated temperatures is similar to that of the TFA complex 4 (saddle). Tetramer 5 is conformationally mobile at ambient temperature, but generally has a flattened cone (boat) conformation. The ΔG(≠) for inversion in 5 between partial cone and boat conformation is 12.5 Kcal mol(-1), while that between boat and saddle conformation is 14.3 Kcal mol(-1). Conformational changes are also dependant on pH.

Treatment of 2,4-dimethoxybenzyl alcohol with trifluoroacetic acid (TFA, 5% in CHCl3) affords, in almost quantitative yield calix[4]resorcinarene octamethyl ether, which on demethylation and acetylation yields the derived octa-acetate.

Treatment of 2,4-dimethoxybenzyl alcohol with TFA affords, in almost quantitative yield, calix[4]resorcinarene octamethyl ether 3, which on demethylation and acetylation yields the derived octa-acetate 6.

Halogenated trisalicylide derivatives 1-6, representing three-fold symmetric C3 “home trimmers” as well as dissymmetric C1 “mixed trimers” have been synthesized. Clathration studies indicate that these halogenated TOT analogs do not form clathrates. Reductive removal of the halogen was demonstrated for analog 2, providing a new entry to TOT-based host molecules.

Halogenated TOT and TSBS have been synthesized. Clathration studies indicate that these halogenated TOT analogs do not form clathrates. Reductive removal of the halogen provided a new entry to TOT-based host molecules.

In order to improve the relatively low yield (ca. 35%) previously observed in the synthesis of tri-o-thymotide (TOT, 1) from o-thymotic acid (2), the cyclodehydration was studied using a variety of conditions. The low yield is due to the formation of di-o-thymotide (DOT, 3), previously reported, and at least three other products (4-6), which apparently result from the acid-catalyzed decarboxylation of 2 and subsequent condensation with thymol (7). Using pyridine as a solvent, side-product formation is inhibited. Under appropriate conditions, namely, neat POCl3 at 50 °C, the yield of 1 is 93%. Other salicylic acid derivatives also give high yields of the corresponding “trimers” under these conditions, thus providing a general, improved preparation of a family of potential clathrate host substances.