Studies relating to the hydrolysis of aliphatic amides (1950)
AuthorsMcKenzie, W. D.show all
The work described in this thesis is concerned with problems connected with the hydrolysis of the amide group but, although the whole investigation thus has a common theme, it falls conveniently into three divisions, dealing with γ amino butyramide, malonic acid amides and oxalic acid amides respectively. A study of the hydrolysis of γ amino butyramide was desirable in order to obtain more evidence on the mechanism of hydrolysis of glutamine, the molecule of which bears a strong structural resemblance to that of the butyric acid derivative. A satisfactory method for the preparation of this compound was not arrived at in the present work and the relevant portion of this thesis deals with attempts to prepare the compound. The hydrolysis in acid solution of malonic acid amides was initiated by results obtained in this Department on the effect of substituents on the rate of hydrolysis of C- substituted malonamides. Such results indicated the need for data on the kinetics of hydrolysis of the mono-amide of malonic acid and the correlation of such data with that obtained for the corresponding diamide. The studies on oxalic acid amides arose directly from this work, the interest lying in the fact that in these derivatives the carbonyl groups are directly bonded. In connection with the kinetic studies it should be pointed out that the hydrolysis was believed to occur by an essentially bimolecular reaction involving, initially, the addition of a proton to the carbonyl group. The amides studied were found to hydrolyse at measureable rates at 97°C to 98°C in a range of hydrochloric acid from 0 to .5 molar. First order kinetics for the hydrolyses were obtained in this range when the concentration of acid molecules was kept very much greater than that of amide molecules (greater than 100/1). The amide was then present in semi-micro quantities which could be determined conveniently by the methods developed for similar systems by Penfold(1) and Sanders(37) from methods used by Taylor(5) and Krieble and Holst(4). As the kinetics of first order reactions have received simple and adequate treatment the possibility of consecutive reactions in the hydrolysis of the diamides could also be considered. It has been convenient to treat, under the following headings, each amide investigated:- (i) Preparation, in which the preparation of the amide used in the hydrolysis is discussed. (ii) Method of analysis, in which (a) the reasons for the choice of the method used and (b) any difficulties experienced, are discussed. (iii) Kinetics of Hydrolysis, in which the results obtained, as described the section on “The Expression of Results”, are given. The complete hydrolysis of each diamide is discussed in a section immediately following those containing full information from the hydrolysis of the mono- and di-amide. General conclusions on the hydrolysis of amides are discussed in the final main section.