SYNTHESIS AND POLAROGRAPHIC REDUCTION OF PYRAZOLES, PYRAZOLINES AND COUPLED PRODUCTS OF 2-AMINO BENZOTHIAZOLES IN DIFFERENT SOLVENT AND SOLUBILISED SYSTEMS

Abstract

Over a period of last many years azo and hydrazono compounds have attracted wide attention because of their application in the preparation of various heterocycles and also in view of their importance in biology and medicine . Recent developments in the field of pharmaceuticals are accredited to researches on these compounds. The main purpose of the present investigations has been to study the redox "behaviour of compounds containing azo and hydrazono groups attached to the heterocyclic ring or the substituted cyclohexane ring. The polarographic technique for various reasons, was considered the best method for this purpose. Many compounds new and already reported ones,were synthesised in the laboratory,fully characterised and were then later subjected to thorough polarographic analysis at the d.m.e. Chapter II describes the results of the synthesis of some condensation products of 2,3*4- pentnnetrione-^- arylhydrazones with phenylthiosemicarbazide and 2,3-dioxobutyrate- 2-phenylhydrazone with phenylthiosemicarbazide. Two series of the following compounds and their derivatives were synthesised by coupling diazotised aromatic amine with acetylacetone or ethylacetoacetic ester with subsequent cyclisation of hydrazones. -11- First series include 3? 5-d.iutothyl-4-?henylazo-N,-aryl thiocarbamoylpyrazoles and its following derivatives, 4_(2-methylphenylazo),4-(3-methylphenylazo),4-(4-methylphenyl azo),4-(2-methoxyphenylazo), 4t(4-methoxyphenylazo), 4-(2-ethoxyphenylazo), 4-(4-ethoxyphenylazo), 4-(2-chlorophenylazo), 4-(3-ehlorophenylazo) , 4-(4-chlorophenylazo), 4-(2-nitrophenylazo), 4-(4-nitrophenylazo), 4-(4-bromophenylazo), and 4-(2,5-dichlorophenylazo)- N' -thiocarbamoylpyrazoles. Another series of 4-arylhydrazono-N1-phenylthiocarbamoyl- 3-methylphenylthiocarbamoyl-/4-methylphenylthiocarbamoyl- / 3-methoxyphenylthiocarbamoyl-/ 4-methoxyphenylthiocarbamoyl-3- methyl-2-pyrazolin-5-ones were prepared in a similar way by taking suitable substituted phenylthiosemicarbazide and ethylacetoacetic ester. The results of the above mentioned studies are embodied in the thesis chapter II. The third chapter is devoted to systematic study of the reduction of 3,5-dimethyl-4-arylazo-N'-thiocarbamoyl pyrazoles with special emphasis on the mechanism of electrode reaction, quantitative relationship between Ey2 and effect of substituents, effect of solvent composition and ionic strength All the compounds gave well- defined, single two-electron transfer irreversible reduction waves and the value of specific reaction constant (? ) obtained from the plot of -111- Ey2 vs r* (Hammett constant) was positive thereby indicating a nucleophilic mechanism of the electrode process. With increase in the organic (non-aqueous) content of the solution, Ey2 shifted towards more negative potential with a decreased limiting current. Change in the ionic strength of the base solution did not show any marked effect although the increase in the size of the cation, the value of specific reaction constant ( J ) did increase. The shift in Ey2 was found to follow the order (C2V4) N+) Rb+) K+) Na+) Li+ which is the same as that of the increasing ionic radii , The chapter IV deals with the polarographic reduction of (A) 5,5-dimethylcyclohexane-2-benzothiazolylhydrazono-1 ,3- diones and (B) 2-benzothiazolylhydrazonocyanoethanoates. A number of compounds of series (A) having substituents in the benzothiazole ring viz., H,4-methyl,6-methyl,6-methoxy and 6-ethoxy and of series (B) having substituents H,3-methyl, 4-methyl,2-methoxy,4-methoxy-4-nitro and 2,3-dimethyl were selected for these investigations. The results of polarographic studies in B.R. buffers in the pH range 2.0-11.0 are summarised as follows. -iv- (1) These compounds gave a single well defined, irreversible, diffusion controlled reduction wave except in the case of nitro substituted compound in which one more 4-electron wave at a much less negative potential was realised over the entire pH range. The wave heights were found to be pH independent. (2) The number of electrons, determined by millicoulometry, involved in the reduction was found to be 4 for all the compounds under investigation . (3) Since reduction of the thiazoles was pH dependent and the limiting current pH independent upto pH 8,3, it was concluded that both acidic and basic forms of the compounds are electroactive and proton transfer reaction; precede* the electrode process . (4) The effect of the size of the cations on the reduction of these thiazoles were determined and it was observed that the specific reaction constant ( / ) increases with increase in the size of cations (5) On increasing the percentage of D.M.E. progressively from 30$ to 80$ , it was observed that Ey2 shifted to more negative potential with increasing concentration of organic solvent in the mixture . The shift in Ey2 was also correlated with viscosity. -VThe polarographic method has been specially employed for differentiating between four tautomeric forms. Its possible use for the purpose was considered in the cases of some 4-arylhydrazono-lT '- arylthiocarbamoyl-3-methyl-2-pyrazolin- 5-ones. Hydrazono structure has been proposed on the basis of the four electron reduction as evideneaiby polarographic and coulometric studies. This is further prove out by the fact that for the reduction of the azo group the number of electrons involved in the reduction should be two unless an activating group such as -OH or- NH? is present in the p-position. In the I.R. spectra presence of characteristic peaks for -NH-N = C - and cyclic C = 0 group strongly support the hydrazono structure of these compoundG. The last chapter viz., chapter VI is devoted to the polarographic reduction of some compounds of the above mentioned series (Nl-phenylthiocarbamoyl-3,5-dimethyl -4- arylazopyrazoles) in the presence of surface active compounds. These studies have been divided into two parts (a) the effect of surfactants on the polarograms (Ey2, i-, , kinetic parameters etc ), (b) polarographic reduction in solubilised system with the aim to evolve conditions and environments similar to those in aqueous solution in the case of water insoluble compounds.