Molecular Recognition by Azacalix[3]arenes

Abstract

The azacalix[3]arene macrocycles 1 are ideal hosts for the binding of metal ions and alkylammonium ions due to the presence of heteroatoms in the macrocycle ring and the ease of modifying their structure through the R, R', and R" substituents. Synthetic routes to the azacalix[3]arene macrocycles will be discussed from the perspective of their ability to generate the azacalix[3]arenes 1 free from the corresponding azacalix[4]arenes 2.Azacalix[3]arene macrocycle 1a exhibits the ability to bind trivalent metal ions and form complexes where the macrocycle is either a neutral (H 3 L) or a trianionic (L 3-) donor. Crystal structures of well-defined yttrium(III) [3: Y(H 3 L)Cl 3 ] and lanthanum(III) [4: La(L)] complexes are reported. Molecular recognition studies have been performed on the azacalix[3]arenes 1.In contrast with the O-unsubstituted macrocycles (1, R"= H) which exhibit no detectable binding of alkali or ammonium ions, the O-methylated macrocycle 1j is observed to extract alkali metal and alkylammonium picrates.The hexahomotriazacalix[3]arene macrocycles 1 (Figure 1), abbreviated to azacalix[3]arenes in this paper, are interesting targets for molecular recognition and ion separation studies since their structure can be modified at not only the upper-rim (R) and lower-rim (R"), but also within the macrocycle cup at the inner-rim (R') (/-4). The azacalix[3]arenes have received only limited attention for their molecular recognition behavior; this is probably due to the difficulty of synthesizing the macrocycles free from the corresponding cyclic tetramers, the azacalix[4]arenes 2 (/).Takemura and co-workers first reported that the azacalix[3]arenes lb-e could be synthesized (Eq. 1) by heating 2,6-bis(hydroxymethylphenols) 5 in the presence of a primary amine in refluxing toluene (2-4). The azacalix[3]arenes were reported to be isolated without contamination by the corresponding azacalix[4]arenes 2. They also reported that azacalix[3]arene lb could be O-alkylated with picolyl chloride to yield macrocycle If but the cone vs. partial-cone selectivity of this reaction was not discussed (4). Macrocycle lb was reported to extract U0 2 2+ from aqueous solutions.

A Convergent Synthesis of Hexahomotriazacalix[3]arene Macrocycles

“…The synthesis of the aldehyde starting material 3 was accomplished by protection of 2,6-bis(hydroxymethyl)-4-methylphenol 6 as its acetonide 7 and oxidation with pyridinium chlorochromate (PCC) to yield the protected aldehyde 8 (Figure ). , A one-pot reaction for deprotection and chlorination of 8 with concentrated HCl resulted in the aldehyde 3 in high yield.

3 Preparation of aldehyde 3 .

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“…The C 3 symmetric arrangement of hydrogen-bond acceptors present in the cup of the azacalix[3]arene macrocycles resembles the structure of 1,7,13-triaza-18-crown-6 which has been reported by Lehn to complex ammonium and alkylammonium ions more strongly than alkali metal ions . We have previously reported that azacalix[3]arene 1i binds trivalent metal ions (Sc, Y, La) with the macrocycle acting as either a neutral or trianionic ligand to the metal center . Takemura and Vicens and their co-workers recently reported the binding of Nd(III) by azacalix[3]arene 1h …”

“…Calixarenes and related macrocycles have received considerable attention in recent years from many research groups as host molecules in host−guest chemistry. − Our interest in the synthesis of the hexahomotriazacalix[3]arenes 1 , abbreviated to azacalix[3]arenes in this paper, is due to their potential of being hosts for the binding of metal ions and alkylammonium ions. − The structure of the azacalix[3]arene macrocycles is shown in Figure . The C 3 symmetric arrangement of hydrogen-bond acceptors present in the cup of the azacalix[3]arene macrocycles resembles the structure of 1,7,13-triaza-18-crown-6 which has been reported by Lehn to complex ammonium and alkylammonium ions more strongly than alkali metal ions .…”