Studies in organo arsenicals

Abstract

The present thesis consists of four parts, preceded by “A Brief Résumé of the Literature on Organo?Arsenicals.” Under this heading, various aspects of the problems of organo?arsenicals have been considered in good detail, namely: (i) Occurrence of arsenic; (ii) Relation of the elements in the periodic table with pharmacological properties; (iii) History of the development of these drugs; (iv) Methods of synthesis; (v) Relation of structure to activity; (vi) Compounds accepted as chemotherapeutic agents and their specificity. This introductory article concludes with a general remark.

PART I Part I deals with the preparation of Carbarsone and Stovarsol, in improved yields, and of the starting materials required for their production in good detail. These official drugs are all patented, and detailed procedures are not available in the literature.

PART II Part II deals with the preparation of some quinoline?arsenicals. Several quinoline arsonic acids are known in the literature and have been prepared by Bart's reaction in the usual way; however, this method is tedious and generally gives poor yields. In searching for ideal amoebicidal drugs, several substituted quinoline?arsenicals have been synthesised using the Dobner and Miller process, a method not previously used for such condensations. According to many clinicians, no single drug—namely, Vioform, Chiniofon, Yatren, Carbarsone, or Stovarsol—can always eradicate chronic infections. Hence, derivatives of 8?hydroxyquinoline (the nucleus of Chiniofon, Vioform, and Yatren) and of the fundamental nucleus of Carbarsone and Stovarsol have been combined.

PART III Part III deals with a new method of estimation of arsenic in official arsenicals, preceded by a review of the literature on arsenic estimation in organo?arsenicals. Several methods exist for estimating official arsenicals. A reliable method involving decomposition of organic matter by potassium permanganate and alkali, followed by oxidation in the presence of acid, has been successfully attempted. The results have been compared with well?known established methods.

PART IV Part IV consists of two sections, A and B. Section A Section A deals with the synthesis of sulphonyl esters of hydroxyphenyl arsonic acids. The study records the action of: (i) benzenesulphonyl chloride, (ii) p?toluenesulphonyl chloride, (iii) p?chlorophenyl?sulphonyl chloride, (iv) p?acetamino?phenyl?sulphonyl chloride, and (v) ??naphthalene?sulphonyl chloride on: (a) 4?hydroxy?, (b) 3?nitro?4?hydroxy?, and (c) 3?acetamino?4?hydroxy?phenyl arsonic acids. During these reactions, it was observed that the yield of the final products is influenced by the substituent groups in the 3?carbon position, which has been explained using electronic interpretations. Section B Section B deals with the synthesis of aryl azo?arsonic acids.