Stereochemical studies in the 1,3-dioxan series.

Abstract

The studies described in this thesis are principally concerned with an examination of the chair-boat equilibrium in 1,3-dioxans and the nature of the boat (or twist) conformations. Chapter 1 reviews the basic features of conformational analysis, with special reference to 1,3-dioxans, and also describes some of the physical techniques (especially n.m.r. spectroscopy) which were widely used in this work. The 13 C n.m.r. spectra of a number of methyl, gem-diethyl, and phenyl 1,3-dioxans are reported. Using a least squares method substituent chemical shift parameters are evaluated for compounds known to exist in chair conformations. When these parameters are used to calculate chemical shifts for compounds which would have a 2,4 or 6-syn-diaxial interaction in their chair conformations, large differences are noted between the observed and calculated chemical shifts for the compounds with a 2 ,4 interaction, but smaller differences are found for the compounds with a 4,6 interaction. These deviations are considered to demonstrate that the former compounds prefer non-chair conformations whereas compounds with a 4,6 interaction exist with appreciable amounts of chair and twist forms. The conformational equilibria in some 5-methyl-1.3-dioxans are estimated using the methyl group chemical shifts. The 1H n.m.r. spectra of some non-chair 1.3-dioxans are recorded. An analytical scheme is proposed which enables selection of the most stable twist conformation for each molecule. In many cases the vicinal coupling constants are found to be independent of temperature and this, and other features of the spectra, are interpreted as being indicative of conformationally biased twist conformations. A microcalorimetric method for the determination of conformational enthalpies is described. The conformational free energy difference between the cis and trans-2,5-dimethyl-1.3-dioxans is found to be 4.02 ± 0.04 kj mol-1. The chair-boat enthalpy difference for 1,3-dioxan is estimated to be 36.5 kj mol-1 on the basis of assumptions concerning the nature of the twist conformations. The crystal structure of r-2-4 ,4-c-6-tetramethyl 2 -(4’-bromophenyl)-1,3-dioxan is determined and refined to R = 0.12. The 1,3-dioxan ring exists in a severely distorted chair conformation with the phenyl group axial. The conformation, in solution, of this molecule and some related compounds, is discussed. An empirical scheme for the analysis of the boiling points and molar volumes of a homologous series of compounds is described. This method is used to demonstrate the presence of non-chair conformations in some 1,3-dioxans.