The assessment of optical stability factors

Abstract

The thesis is concerned with the assessment of optical stability in compounds whose activity is dependent upon restriction of rotation within the molecule. The introduction contains a review of past work in this field and particular reference is made to compounds whose activation energies of racemisation have been determined.In the experimental section, details are given of the determination of rate constants of racemisation of six substituted N-benzoyldiphenylamine 2-carboxylic acids in chloroform containing 2.5% by volume of ethanol. The results were used to estimate the constants E and A of the Arrhenius relationshipand the entropy of activation for each racemisation.As a help to the discussion of these results, determinations were later made of the racemisation of two of these acids in a variety of solvents. Details are also given of the racemisation of 6-nitro-, 4,6'-dinitro- and 4,6,4'-trinitro-diphenic acid together with the estimated E, A and values for the rate constants of racemisation in 2N-sodium carbonate solution.Rate constants for racemisation are discussed in terms of the activation energies and of the energy independentfactors. The discussion of the latter is based upon both the Absolute Reaction Rate theory of Glasstone,Laidler and Eyring, and the dynamical treatment of Slater.The influences on E and A of electrical effects, size effects and hydrogen bonding are considered.The optical stabilities of the three nitrodiphenic acids in alkaline solution are discussed and further compared with the stability of the dimethyl-esters and of the acids in organic solvents.Details of the synthetic work are given in the last section of the thesis.