Substituent effects and chiral discrimination in the complexation of benzoic, 4-methylbenzoic and (RS)-2-phenylpropanoic acids and their conjugate bases by β-cyclodextrin and 6A-amino-6A-deoxy-β-cyclodextrin in aqueous solution: potentiometric titration and 1H nuclear magnetic resonance spectroscopic study

Abstract

A potentiometric titration study in aqueous solution (l= 0.10 mol dm^–3, KCl) of the complexation of benzoic, 4-methylbenzoic and (RS)–2-phenylpropanoic acids (HA) and their conjugate bases (A^–) with β-cyclodextrin, βCD, and its substituted analogue, 6^A-amino-6^A-deoxy-β-cyclodextrin, βCDNH₂, in which a primary hydroxy group is replaced by an amino group which may be protonated to produce a singly charged species, βCDNH⁺₃, is reported. At 298.2 K the stability constants for the complexes have the values (in dm³ mol^–1) shown in parentheses: benzoic acid ·βCD (K_1HA= 590 ± 60); benzoate ·βCD (K_1A= 60 ± 10); benzoic acid ·βCDNH⁺₃(K_2HA= 340 ± 30); benzoate ·βCDNH⁺₃(K_2A= 120 ± 20); benzoate ·βCDNH₂(K_3A= 50 ± 20); 4-methylbenzoic acid ·βCD (K_1HA= 1680 ± 90); 4-methylbenzoate ·βCD (K_1A= 110 ± 1); 4-methylbenzoic acid ·βCDNH⁺₃(K_2HA= 910 ± 20); 4-methylbenzoate ·βCDNH⁺₃(K_2A= 330 ± 20); and 4-methylbenzoate ·βCDNH₂(K_3A= 100 ± 20). These data indicate that for a given cyclodextrin the guest carboxylic acids form complexes of higher stability than do their conjugate base analogues, and that βCDNH⁺₃ forms more stable complexes with the conjugate bases than do βCD and βCDNH₂. These trends are also observed for the complexation of (RS)-2-phenylpropanoic acid and (RS)-2-phenylpropanoate where the complexes indicated are characterised by the stability constants (in dm³ mol^–1) shown in parentheses: (RS)-2-phenylpropanoic acid ·βCD (K_1RHA= 1090 ± 30, K_1SHA= 1010 ± 40); (RS)-2-phenylpropanoate ·βCD (K_1RA= 63 ± 8, K_1SA= 52 ± 5); (RS)-2-phenylpropanoic acid ·βCDNH⁺₃(K_2RHA= 580 ± 20, K_2SHA= 480 ± 10); (RS)-2-phenylpropanoate ·βCDNH⁺₃(K_2RA= 150 ± 8, K_2SA= 110 ± 10); and (RS)-2-phenylpropanoate ·βCDNH₂(K_3RA= 36 ± 6, K_3SA= 13 ± 7). These data also show that while K_1RHA and K_1SHA, and K_1RA and K_1SA are indistinguishable for (RS)-2-phenylpropanoic acid ·βCD and (RS)-2-phenylpropanoate ·βCD, chiral discrimination is indicated by K_2RHA > K_2SHA for (RS)-2-phenylpropanoic acid ·βCDNH⁺₃, K_2RA > K_2SA for (RS)-2-phenylpropanoate ·βCDNH⁺₃, and K_3RA > K_3SA for (RS)-2-phenylpropanoate ·βCDNH₂. The ¹H NMR spectra of the methyl groups of the enantiomers of (RS)-2-phenylpropanoic acid appear as two separate doublets, indicating chiral discrimination when complexed by βCD or βCDNH⁺₃, but such chiral discrimination is not observed for (RS)-2-phenylpropanoate when complexed by βCDNH⁺₃. The implications of these observations are discussed.