Torand synthesis

This chapter illustrates torand synthesis with the preparation of unsubstituted torand 1 by the route developed for synthesis of tributyltorand 2.1,6,7 The synthesis of 1 is two steps shorter than that of 2 because commercially available 1,2,3,4,5,6,7,8-octahydroacridine, 5, replaces the 9-butyl derivative, which is prepared in two steps.11,12 Many of the intermediates could also be... 

Diketone 12 must be condensed with a third, doubly functionalized octahydroacridine unit in the last step of the torand synthesis (cf Scheme 6.1). The following protocols (8-10) describe the three-step synthesis of torand precursor 15 from octahydroacridine 5. The reagents involved in these three steps are shown in Scheme 6.11. According to Protocol 8, octahydroacridine is condensed with benzaldehyde in the presence of acetic anhydride,24 as in the second stage of Protocol 2 (cf Scheme 6.3). The crystalline product 13 precipitates from the reaction mixture in high yield and purity. Ozonolysis of 13 (Protocol 9) is conducted by the method described in Protocol 7 for conversion of 11 to diketone 12 (cf. Scheme 6.10) and the same precautions apply. The product diketone 1425 requires no further purification after removal of benzaldehyde by trituration with diethyl ether. The third octahydroacridine unit is then readied for torand cyclization in Protocol 10 by condensing diketone 14 with Bredereck s reagent, r-butoxybis(dimethylamino)methane,26 which is commercially available. The bis[p-(dimethylamino)]enone product 15 is easily purified by precipitation from ether/dichloromethane. 

Bell. T.W. Liu. J. Torand synthesis by trimerization— New receptors for guanidinium. Angew. Chem. 1990. 102. 

In Scheme 6.1, outlining the synthesis of torand 1, each of the numbered arrows corresponds to one of the eleven protocols. This approach to 1 sequentially combines three octahydroacridine subunits, whereas the previously... 

In steps 5 and 6 of Scheme 6.1 the torand backbone is built up from two molecules of ketone 9 via Mannich salt 10. Together these reactions constitute the most efficient method known so far for the synthesis of fused pyridines from cyclic ketones. The key intermediates involved in the transformation of 9 to 11 are shown in Scheme 6.7. In Protocol 5, ketone 9 reacts with /V,/V-dimethyl(methylene)ammonium chloride in acetonitrile.21 The HC1 salt of the resulting Mannich compound 10 precipitates from this solvent and the relatively pure product is isolated from the reaction mixture by filtration. 

Of particular importance are oligopyridine ligands such as 2,2 6, 2",2" 6", 2""-pentapyridine. These molecules allow synthesis of helical, inter-finked and knotted molecular arrays.1 7 Similar species with interlocking rings are the catenands and torands.m Some examples of oligopyridines are (9-XVIII) and (9-XIX). Other nitrogen heterocycles are the following ... 

The synthesis of the pyrrole-pyridine-containing expanded porphyrins 4.196 and 4.197 was reported by Bell, et al. in 1993. These macrocycles, termed torands because of their rigid torroidal structure, were prepared via an elaborate linear synthesis, part of which is shown in Scheme 4.6.4. The key macrocyclization step in the synthesis involves the pyrolysis of the bis(semicarbazone) 4.195 to afford torand 4.196 in up to 69% yield. This torand may then be dehydrogenated with... 

A lengthy synthesis of the parent dodecahydrohexaaza-kekulene (1, r =R = H) was reported by Ransohoff and Staab. - The final, macrocyclization step apparently gave the torand in 3% yield as a sparingly soluble solid. 

H-NMR spectroscopy. Anticipating solubility problems with the parent torand, Bell and Firestone developed a method for synthesis of butylated heptacyclic terpyridines and applied it to tributyldodecahydrohexaazakekulene (1, = butyl).The rnacrocyclization step in... 

Fig. 3 Synthesis of expanded torand 2 (R = butyl) by Friedlander trimerization...

Torands and closely related molecules, such as cycloar-enes, sexipyridines, and expanded heterohelicenes (molecular coils), still constitute a relatively small group of known compounds. The main reason for this is purely synthetic fusion of multiple rings requires many synthetic steps and low-yield macrocyclization reactions compound the problem. Clearly, better methods are needed for the synthesis of torands to enable more complete ex-... 

Bell, T.W. Tidswell, J. Torands. In Macrocycle Synthesis A Praetieal Approaeh Parker. D., Ed. Oxford University Press Oxford, 1996 119-143. 

These torand model studies demonstrate that effective complexing agents for alkali metal and alkaline earth ions may be constructed using sp hybridized nitrogen binding sites. In addition, the low solubilities of the model compounds led us to incorporate flexible, solubilizing substituents in our synthetic approaches to fully fused torands (5) We have already reported the synthesis of a soluble heptacyclic terpyridyl... 

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