Main, LyndsayMiles, Christopher O.2026-06-162026-06-161987https://hdl.handle.net/10289/18371The first-order rate constant, kₒbₛ, for the chalcone - flavanone isomerisation has been determined over the pH range 0-14 in water (μ = 1.0 mol 1⁻¹ with KC1) at 30°C for the following 2' ,6'-dihydroxychalcones: 2' ,6'-dihydroxychalcone (34); 2' ,6'-dihydroxy-4-methoxychalcone (38); 2' ,6'-dihydroxy-3,4-dimethoxychalcone (40); 2' ,6'-dihydroxy-3,4,5-trimethoxychalcone (42); 2' ,6'-dihydroxy-2,4,6-trimethoxychalcone (44); 4-chloro-2' ,6'-dihydroxychalcone (46); 2' ,6'-dihydroxy- 4,4'-dimethoxychalcone (32); 2' ,6'-dihydroxy-3,4,4'-trimethoxychalcone (36); and 2' ,4,6'-trihydroxy-4'-rhamnoglucosyloxychalcone (naringin-chalcone) (48). The pH-rate profiles have been analysed in terms of contributions to cyclisation and ring opening of the various ionised chalcone and flavanone species, and individual rate and equilibrium constants for all the contributing reactions have been determined. Rate measurements with D₂O as the solvent (for 32, 34, 36, 38, 40, 42, 44, 46) revealed a large (presumably primary) hydrogen kinetic isotope effect for one of the contributing reactions, the cyclisation of the chalcone mono-anion. Enthalpies and entropies of activation for the mono-anion cyclisation have also been determined for chalcones 34, 36, 38, 42, 44, and 46. ¹H n.m.r. studies of the product from the cyclisation of the mono-anion in D₂O for two chalcones (34, 38) showed little preference in protonation at the 3-position of the flavanone. Mass spectrometry allowed measurement of the preference for protonation over deuteriation at the 3-position of the flavanone during cyclisation of the mono-anions of 32 and 38, under kinetically-controlled conditions in H₂O - D₂O mixtures. The data obtained were not in accord with the those from kinetic isotope effect measurements. The above results were considered in terms of possible mechanisms for the various reactions involved in the isomerisation. Factors contributing to the specially high rate of cyclisation of 2' ,6'-dihydroxychalcones as compared to simple 2'-hydroxychalcones, and to the high stability of the 5-hydroxyflavanones as compared to simple flavanones (relative to their isomeric chalcones) were also considered. The low stability of the 2' ,6'-dihydroxychalcones, compared to the 2'-hydroxychalcones (relative to their flavanones) was found to be due to a highly reactive mono-anion form combined with a lower first pKₐ, and a greatly reduced susceptibility of the flavanone anions to base-catalysed ring opening. By utilising the above kinetic results, new and improved syntheses of 2' ,6'-dihydroxychalcones have been developed in the face of what are shown to be unreliable literature reports. The following compounds have been synthesised and characterised for the first time: (32); (34); (36); (38); 5-hydroxy-4' -methoxyflavanone (39); (40); 5-hydroxy-3' ,4'-dimethoxyflavanone (41); (42); 5-hydroxy-3' ,4' ,5'-trimethoxyflavanone (43); (44); 5-hydroxy-2' ,4' ,6'-trimethoxyflavanone (45); (46); 5-hydroxy-4'-chloroflavanone (47): 6-benzyl-7-benzyloxy-5-hydroxyflavanone (68); 6-benzyl-5,7-dihydroxyflavanone (69); 2 '-hydroxy-6 '-tetrahydropyrany loxy-3, 4, 5-trimethoxychalcone (70); 3'-benzyl-4' ,6'-dibenzyloxy-2'-hydroxychalcone (72); 2' ,3,4' ,6'-tetrahydroxy- 4-methoxychalcone (86); 2'-hydroxy-4' ,6'-dimethoxy-3'-methylchalcone (93). Two new routes to 2' ,6'-dihydroxychalcones were developed. The first involved base-catalysed condensation of acetophenones and benzaldehydes with free phenolic groups protected as their tetrahydro-pyranyl ethers, followed by deprotection at pH 2. The second involved reaction of flavanones with chlorosilanes, in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene, in which ring opening of the O-silylated flavanone was immediately followed by silylation of the resultant phenolate oxygen, thereby preventing recyclisation. The crystal structures of 5-hydroxy-4' ,7-dimethoxyflavanone (33) and 2' ,6'-dihydroxy-2,4,6-trimethoxychalcone (44) were determined by X-ray crystallography, 44 being the first 2' ,6'-dihydroxychalcone for which a crystal structure has been obtained. A computer programme was developed for the analysis of pH-rate data for 2'-hydroxy- and 2', 6'-dihydroxy-chalcones, but which is suitable for the analysis of pH-rate data for most mono- or di-acids in which the contributing reactions are (pseudo) first-order. The programme can also include second-order H⁺-catalysed reaction of the di-acid, and one second-order OH⁻-catalysed reaction, and calculates the concentrations of the various ionised species present on the basis that the two pKₐ values may not be well-separated. This programme has been used to successfully analyse the 2' ,4'-dihydroxychalcone - 7-hydroxyflavanone pH-rate profile previously reported, but not analysed, in the same way as for the 2' ,6'-dihydroxychalcones.enAll items in Research Commons are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.Thesis