STUDIES ON THE SYNTHESIS AND REDOX REACTIONS OF SOME HETEROCYCLIC COMPOUNDS

Abstract

Heterocyclic compounds of medicinal and physiological importance have been the subject matter of basic research for the last many decades. Early studies were mostly centred on their synthesis and characterisation but in later years more critical and comprehensive studies dealing with their spectral properties and redox behaviour were undertaken. Keeping in view the recent developments in the chemistry of heterocycles, the following studies were planned: 1) Synthesis and characterisation of some new biologically active compounds such as 5~(2,-benzothiazolylhydrazono) barbituric and thiobarbituric acids, and 5-(p-sulfamoylphenylhydrazono)- 1,3-dimethylbarbituric acid derivatives. 2) Detailed polarographic study of azo compounds, 5~(arylhydrazono) alloxans and precursors of antidiabetic 2-pyrazolin-5~one s. "v. "The polarographic studies have not only provided useful information about the redox mechanism of these compounds but also brought out clearly the utility of polarographic method in eluci dating the structure of these heterocycles. The thesis is divided into two parts; part I and Part II. This is preceded by the general introduction which gives a detailed account of the chemistry of heterocyclic compounds under investi gation and existing literature on their electrochemical reduction. Part I deals with the synthesis and characterisation of some new and possibly biologically active compounds and is divided into 3 chapters. (ii) The first chapter deals with the synthesis of 5-(2'-benzothiazolylhydrazono) barbituric and thiobarbituric acid derivatives. The second chapter is devoted to the structure elucidation of these compounds on the basis of polarographic investigations. The third chapter deals with the synthesis of 5-(p-sulfamoylphenylhydrazono)- 1,3~dimethylbarbituric acid derivatives. Chapter 1= Synthesis of 5-(2'-benzothiazolylhydrazono) barbituric and thiobarbituric acid derivatives. A number of 2-aminobenzothiazoles were diazotised and then coupled with reactive methylene compounds viz., barbituric acid, 1,3-dimethylbarbituric acid and thiobarbituric acid. 2-aminobenzothiazoles being weak bases could not be diazotised in the presence of hydrochloric acid and, therefore, sulphuric acid was used. The diazonium salts so formed coupled easily to give following three series of compounds! 0 R=H , X=0 • Series-1 JL 'J-NH-N= O^ ^N-R B= -CH3 , X=0 ; Series-2 >-^ ^S^ I R=H , X=S ; Series-3 ^Sf'' R The I.R. spectra of these compounds indicates the presence of -NH- and -C=N- groups and absence of -N=N- group and thus supports the hydrazono structure. Further appearance of absorption peaks of carbonyl groups in position k and 6 of barbituric acid moiety at considerable lower wave number can be accounted for by the conjugation of carbonyl groups with unsaturation, which is possible with the hydrazono and not with azo structure. (iii) Chapter II. Polarographic Structural Studies on Coupled Products of Diazonium salts of 2-Aminobenzothiazoles with 1,3-dimethylbarbituric acid. Polarographic studies on the above compounds were under taken with a view to throw light on the structure of these com pounds. The main findings are: (i) The number of electrons consumed in the reduction was found to be four. (ii) They gave irreversible waves independent of concentration, (iii) The substituent effect on E-,/2 is in consonance with the known reduction mechanism, (iv) Controlled potential electrolysis showed the formation of primary amines as the end products. These findings support the hydrazono structure. . (v) Various cations belonging to the alkali metals do not affect the polarographic waves but (CgEU^N shifts the E./2 towards more negative potential and also reduces the height of the waves. This behaviour can be attributed to the preferential adsorption of tetraethyl ammonium cation on the mercury drop, (vi) The above mentioned effect on E1 ,2 and id was also found with increase in percentage of DMF in the working solution. Chapter III. Synthesis of 5-(p-sulfamoylphenylhydrazono)-1,3- dimethyl barbituric acid derivatives. The sulfa drugs were diazotised in the presence of hydrochloric acid and coupled with 1,3-dimethyl barbituric acid in presence of sodium acetate. The coupled products so formed are assigned the following structure on the basis of elemental, I.R., U.V. and mass spectrum analysis. (iv) 0 II RHN02S-;-/( JJV- NH-N =€T |- CH. CH, Part 11°. Part II deals with the polarographic investigation of known series of biologically important compounds and is divided into 3-chapters viz., Chapter IV, V and VI. Chapter IV deals with the polarographic reduction of benzenesulfonamide, p-[(8-hydroxyquinolyl)azo] and analogous compounds. Chapter V is devoted to the polarographic reduction of antineoplastic 5-(arylhydrazono) alloxans. The polarographic investigation of ethyl-2,3~dioxobutyrate- 2-arylhydrazono-3-semicarbazones is the subject matter of the last chapter (VI) of this thesis. Chapter IV. Polarographic reduction of benzenesulfonamide, p-[(8-hydroxyquinolyl)azo] and analogous compounds. The polarographic studies of these compounds were carried out in B.R. buffers in the pH range 3*3 to 11.2 mainly at concen- -h tration 1.0 x 10 M of the depolariser. The main findings are summarised as below: 1) All compounds gave a single, well defined, diffusion controlled, pH dependent(upto pH 9.9) reduction wave. (v) 2) The number of electrons consumed in reduction was found to be two by millicoulometric method. • 3) The nature of the electrode process was found to be reversible at concentration 0.5 x 10 M but above this concentration viz., 1 x 10 M it deviated from the reversible behaviourk) The E /2 was found to shift towards more negative potential by electron-withdrawing substituents. The mechanism of reduction is proposed. 5) The effect of various cations, anions and solvent compo sition is reported and discussed as in chapter II. Besides this the inhibiting effect of surfactants on polarographic reduction is reported and attributed to slowing down of the 'boundary surface reaction1 due to the decrease in adsorption of depolariser. Chapter V. Polarographic reduction of 5-(arylhydrazono)alloxans. The compounds mentioned above got reduced in B.R. buffers in the pH range 2.5 to 11 A. The polarographic characteristics of these compounds are given below: 1) All compounds gave a single, well defined, irreversible, diffusion controlled, pH dependent reduction wave. 2) The number of electrons transferred during the,reduction process was found to be four by millicoulometric method. 3) The nature of the electrode process was found to be irreversible. (vi) h) p-Chloro aniline and 5-amino-1,3-dimethylbarbituric acid were identified as final reduction products by controlled potential electrolysis. 5) Hammett equation was successfully applied to correlate the effect of substituents on E. ,^. In the light of the above conclusions the possible electrode mechanism is proposed. 6) The effect of ionic strength, cations, solvent composition, surfactants is reported and discussed as in preceding chapter. Besides this, the data on the polarographic reduction in the presence of surfactants have been use fully employed to determine the c.m.c. Chapter VI. Polarographic reduction of precursors of antidiabetic 2-pyrotzolin-5-ones. Ethyl-2,3-dioxobutyrate-2-arylhydrazono-3"semicarbazones which are precursors of antidiabetic ^-arylhydrazono-1-carbamoyl- 3-methyl-2-pyrazolin-5-ones were studied in the pH range 2.2 to 10.6. Although these compounds contained polarographically active semicarbazono and hydrazono group, only the latter group reduced. The polarographic characteristics of these compounds are summarised below: 1) These compounds reduced in a single Melectron transfer, diffusion controlled, irreversible wave. 2) The E1/2 was found to be pH dependent upto pH 9.8 and became independent above this pH. (vii) 3) Plots of E.y2 vs. pH were obtained as two linear segments of different slope, thereby indicating different mechanis tic routes for the electrode process in acidic and alka line range. h) Hammett equation was successfully employed to correlate the effect of substituents on E, ,~. 5) The effect of ionic strength, cations, solvent composition and surfactants is reported and discussed as in the pre ceding chapters.