Guest complexes ammonium salts

Apart from complex formation involving metal ions (as discussed in Chapter 4), crown ethers have been shown to associate with a variety of both charged and uncharged guest molecules. Typical guests include ammonium salts, the guanidinium ion, diazonium salts, water, alcohols, amines, molecular halogens, substituted hydrazines, p-toluene sulfonic acid, phenols, thiols and nitriles. 

A system exhibiting chiral recognition. The chiral macrotricyclic tet-raamide (250) (Lehn, Simon Moradpour, 1978) has been used for the complexation, extraction and transport of primary ammonium salts. The tetraamide was used rather than the corresponding tetraamine because of the lower basicity of the nitrogens in the former ligand. This avoids the possibility of proton transfer occurring from the primary ammonium substrates R-NH3+ used as guests. In a typical experiment, a solution of a primary ammonium salt, such as naphthylethyl ammonium or phenylalanine methylester hydrochloride in hydrochloric acid was... 

The maximum observed free energy difference between two enantiomeric host-guest complexes in which one 1,1 -dinaphthyl element is the only source of chirality in the crown ether is about 0.3 kcal mol-1. Improvement of the free energy difference can be achieved by introduction of two such elements. Unfortunately crown ethers with three 1,1 -dinaphthyl groups did not form complexes with primary ammonium salts (de Jong et al., 1975). The dilocular chiral crown ether [294] forms complexes of different stability with R- and 5-cr-phenylethylammonium hexafluorophosphate. The (J )-J J -[284] complex was the more stable by 0.3 kcal mol-1 at 0°C (EDC value 1.77) (Kyba et al., 1973b). Crown ether [284] also discriminates between the two enantiomers of phenylglycine methyl ester hexafluorophosphate and valine methyl ester... 

After we synthesized CB[10] we wanted to investigate its abilities as a host molecule. We found that CB[10] forms host-guest complexes with many of the guests typically used with the smaller members of the CB[n] family (e.g., ammonium salts of alkyl and arylamines, adamantanes, viologens, and ferrocene derivatives like 14-19). 

Di- and polytopic host-guest systems have provided a convenient starting point for the construction of larger assemblies and many systems of this type are now known. For example, in an early study Kimura et synthesised the catecholamine complex 17. The crown ether unit of this ditopic host was known to be an effective receptor for primary alkyl ammonium salts, whereas the partially protonated form of the hexamine ring had been documented to bind anionic substrates (such as car-boxy lates) or electron-donor substrates (such as catechols). Accordingly, this host forms stable 1 1 complexes with zwitterionic guests such as amino acids, pep-... 

In the last few years, Tabushi et al. (27), Koga and co-workers (24, 28), Jarvi and Whitlock (29), Breslow and co-workers (30), Diederich and coworkers (31, 32), and Vogtle and co-workers (33, 34) as well as our group (35) have shown that azacyclophanes in the form of their ammonium salts can very effectively complex lipophilic substrates. Even hydrocarbons bind with association constants of 1000 or more in aqueous solutions. Our own studies of such host-guest systems were initiated by the desire to use complexations of alkanes for the selective functionalization of paraffins (23, 36) [in addition to our interest (37, 38) in conformations of complex ring systems and their study by NMR methods as well as by force field model calculations]. 

A strange observation was reported on the catalytic H/D exchange of 15 in acidic D2O solution of 13 and 14 Although either of these hosts form complexes with this guest, only 13 displays catalytic H/D exchange. Since no quantitative data were given the question whether this observation bears on differences in complex structure, ammonium salt acidities or indicates an unexpected change in mechanism must remain unanswered at present. 

Enantioselective complexation between chiral host molecules and racemic guests was also achieved. One enantiomer of phenylethylammonium cation can be selectively complexed by optically pure i>A(binaphtho)-22-crown-6. The racemic ammonium salt, dissolved in water, and the chiral crown, dissolved in an immiscible solvent such as CHCI3, are shaken together. If one of the two diastereomeric complexes is favored, it can be detected (e.g., by NMR) or separated. When the chiral macrocycle is bound to a resin, a multi-plate, chiral organic separation is possible. 

Phosphonium salts are also able to form host-guest complexes. An electrospray ionization mass spectrometric study of the interactions between crown ethers and tetramethylammonium and tetramethylphosphonium cations has revealed that, in solution, the complexes are based exclusively on C-H...0 hydrogen bonds and that formation of the complexes with (CH3)4N is favoured over formation of the complexes with (CH3)4P (the latter can be favoured for larger benzo-crown ethers when a solvent of low polarity is used, as a result of the participation of cation-7i interactions). Moreover, in the gas phase, the complexes of crown ethers with the ammonium cation are essentially more stable than those with a phosphonium... 

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