The Preparation and Biological Properties of Certain Amidines

Golombok, Ezra (1947) The Preparation and Biological Properties of Certain Amidines. PhD thesis, University of Glasgow.

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Part I The preparation is described of twelve derivatives of 4-hydroxybenzamidine of the general formulae: (formula redacted) The method of preparation was from the nitrile through the iminoether hydrochloride (Pinner's method) applying modifications as required, e. g. as regards solvent, method of isolation of product, etc. Owing to the failure of the methods attempted for the synthesis of 2- and 4-hydroxy-4'-cyanodiphenylether, the corresponding amidines were prepared by demethylation of the methoxy compounds with 57% hydriodic acid. Similarly, demethylation of 2:4-dimethoxybenzamidine produced the dihydroxy derivative which was not available through the nitrile. A full list of the compounds is given on p. 115. The compounds were submitted to Messrs. I. C. I. , Dyestuffs Division, Blackley, Manchester for test as amoebicidal agents, Emetine hydrochloride being used as a comparative standard. A few of the compounds showed slight activity in concentrations of 1:10,000: the remainder were slightly active at 1:1,000. None of the compounds whowed any promise as a therapeutic agent. The tests are fully reported on p. 115. Part II Two series of amidines were prepared, the phenoxyacetamidines (A), and the aminobenzamidines (B). (Diagram redacted) Both series of compounds are analogous to carboxylic acid growth factors, A to the phenoxyaoetic acid derivatives which are synthetic plant growth factors, and B to the natural bacterial growth factor 4-aminobenzoic acid. Part IIA. Phenoxyacetamidine and four chlorinated derivatives were prepared from the corresponding nitriles, of which only phenoxyacetonitrile has been previously described. These nitriles, which were thermally unstable oils, whowed abnormal reactivity towards alcoholic hydrogen chloride, and it was found necessary to modify the conditions of reaction in order to obtain the iminoether hydrochloride. Using the conditions for iminoether formation developed in Part I, a nitrile such as 2-chloro-phenoxyacetonitrile gave the ester and ammonium chloride. It was shown that the reactivity could be ascribed to the ethereal oxygen atom, and was not effected by ortho substitution in the aromatic nucleus. Concurrent biological tests of each amidine and its carboxylic acid analogue were carried out by the recognised technique on oat seedlings (p. 178). The amidines were found to show distinct growth inhibitory properties, though in varying degree, 4-chlorophenoxyaoetamidine being the most powerful. The carboxylic acids have already beenlisted as plant growth promoting agents. Part IIB. Pour amidine analogues of 4-aminobenzoic acid were prepared, 4-amino-benzamidine itself, and three amidine substituted derivatives, in each case by reduction of the corresponding nitro compound. The parent unsubstituted amidine and the 2-pyridyl and 2-thiazolyl compounds were prepared from 4-nitrobenzonitrile, through the iminoether with excess ammonia or primary amine; the phenyl derivative was most easily made from 4-nitrobenzanilide through the iminochloride and another method consisted in fusion of 4-nitrobenzonitrile with aniline benzenesulphonate. The amines were prepared from the nitroamidines by reduction with stannous chloride or, where applicable, with hydrogen over platinum. The biological tests were carried out using four bacterial organisms which are known to require 4-aminobenzoio acid in their metabolism. The techniques used are standard and are described on p. 198. The organisms were cultured on ordinary agar media and exposed during growth to concentrations of the amidines varying from 1:1,000 to 1:8,000. No indication could be found of interference with growth by any of the four amidines tested. Suggestions for further work. The uniformly negative results of the 4-hydroxybenzemidine series indicate that there is little to be hoped for from the investigation of mono-amidines derived from this compound, at any rate as regards amoebicidal activity. The growth inhibitory properties demonstrated in the phenoxyacetamidine derivatives are of biological significance and it would be of interest to prepare the amidines corresponding to other plant growth factors, many of which are carboxylic acids, e. g. indole-3-acetic acid, naphthoxyacetic acid, the chlorophenoxypropionic and butyric acids, etc.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Organic chemistry
Date of Award: 1947
Depositing User: Enlighten Team
Unique ID: glathesis:1947-79679
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 04 Mar 2020 15:40
Last Modified: 04 Mar 2020 15:40

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