Syntheses and studies in organo-selenium compounds

Dingwall, David (1962) Syntheses and studies in organo-selenium compounds. PhD thesis, University of Glasgow.

Abstract

The object of this work was to synthesize selenium analogues of biologically-active sulphur compounds in the hope that they would show similar activity. Part I deals with the preparation and physical properties of the compounds synthesized and Part II with the spectrophotometric determination of selenium in organic compounds. A survey of the biological properties of selenium in relation to animals and man leads to a brief account of isosterism and bio-isosterism with particular reference to these relationships involving oxygen, sulphur and selenium. A more detailed account of the selenium analogues of biologically-active sulphur compounds shows the changing interest from the toxic properties to the possible utilization of organo-selenium compounds stimulated by the suggestion that selenium may be a previously unknown essential trace element. A brief account of the biological properties of oxasolidines and thiasolidines concludes the introduction. Initially, the synthesis of the selenium analogues of the barbiturates was attempted but was concluded when these compounds were reported. As an alternative, the synthesis of selenium analogues of hydantions was attempted but was unsuccessful. A series of 5-mono-substituted-4-selenazolidones was prepared from a-halo acids and selenoureas, together with the hydrolysis products, the selenasolid-2,4-diones. The cyclisation was shown to take place by the initial formation of an isoselenohydantoic acid which could be isolated and cyclized to the expected product. Disubstitution led to unstable products, and only 5,5-dimethylselenasolid-2,4-dione could be isolated in a state of purity. Acetylation was successful only in the case of 2-imino-4-selenasolidone which also formed sulphonamide derivatives, but all attempts to prepare 5-alkylidene derivatives were unsuccessful. 5-Alkylidene derivatives were prepared from 2-acetylamino-4-selenazolone and selenasolid-2,4-dione. Methylation of each series took place in the 3-position and the products, together with the 2-dimethylamino compounds were used as models in the investigation of tautomerism. 2-Alkylidenehydrazones of the selenasolid-2,4-diones were also prepared. Se-Benzylselenouronium chloride, picrats and p-toluenesulphonate were isolated but the attempted preparation of the formate, acetate and benzoate was unsuccessful. Se-Methylselenouronium iodide and picrate were also isolated. The attempted titration of the 2-imino-4-selenazolidones and the 2-amino-4-selenazolones showed that these compounds were too weakly basic to allow the calculation of pka values but the 3-methyl derivative isolated readily titrated as also did the selenazolid-2,4-diones. The ultraviolet absorption spectra of the 2-imino-and 2-amino-coupounds were measured in water and at different pH values. Comparison of the ultraviolet and infrared absorption spectra showed that the 2-imino form predominated in the 2-imino-4-seleazolidones. The tautomerism of the ring system in related compounds is discussed. In Part II the various methods used for determination of selenium in organic compounds are surveyed and a spectrophotometric method described, in which the organo-selenium compound is oxidized to selenious acid which gives a golden-brown sol on reduction with ascorbic acid using chloropromzzine hydrochlorid as stabilizer. This reaction could be used for the microdetermination of selenium by measuring the extinction of the golden-brown solution at 420 mu. Chloropromazine hydrochloride was compared with other known stabilisers but only cetomacrogol appeared to be as efficient. The incomplete biological testing of representative selenazolidine derivatives shows that these are unlikely to prove of any medicinal value.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Biochemistry, Organic chemistry
• Date of Award: 1962
• Depositing User: Enlighten Team
• Unique ID: glathesis:1962-72896
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 11 Jun 2019 11:06
• Last Modified: 11 Jun 2019 11:06
• URI: https://theses.gla.ac.uk/id/eprint/72896