SPECTROPHOTOMETRIC AND ELECTROMETRIC STUDIES ON SOME REDOX REACTIONS OF ORGANIC COMPOUNDS

Abstract

The turn of the last two decades has witnessed the development 1-4 and expansion of research in various fields of electroanalytical chemistry. This period has seen a continued growth in the application of electro chemical techniques to the study of organic compounds. These studies not only included their estimations but such diverse fields as redox behaviour, structure, organo electrochemical synthesis, mechanism of physiological and biochemical reactions, clinical diagnosis etc. From amongst these techniques,polarography which was discovered by Prof. J. Heyrovsky in 1922 had proved to be the most interesting and useful one for such studies. Initially meant for analysing inorganic ions it is now being extensively used to follow chemical reactions and to supple ment other spectral measurements for the purpose of characterisation. The useful redox data on many compounds of biological interest which was lacking due to the obvious limitations of potentiometric method could, however, be made possible by applying polarographic technique. Amongst the useful applications of polarography as an electroanalytical technique for organic compounds the following are worthciting; 5-7 estimation of vitamins in fruits and vegetables , determination of 8 9 sexharmones in urine and blood , oxidation and reduction of ubiquinones vitamin K_ and dihydrovitamin K3 vis-a-vis study of mitocondrial respiratory action . The application of this technique in determining 11 12 riboflavin in fermentation broths , activity of BCG vaccine , oxygen in '1/1 in blood , catecholamines in biological tissue and diagonosis of 15 cancer has also been claimed From the large array of organic compounds, which have been studied by polarographic analysis at the d.m.e. or other suitable electrodes, the nitrogen heterocycles16^ deserve Special mention since they form the main constituents of compounds of medicinal, physiological and biological importance. Diabetes and cancer are serious health problentfarising from the modern way of life. Research on several class*of compounds, e.g., salicylates19, guanidines20, sulfonamides21, sulfonylureas and five membered heterocycle22 have given rise to few antidiabetic character. In the last few years concentrated efforts have been made to enhance the antidiabetic and antieoplastic character of some of these compounds. Studies in the field of pyrazoles, isoxazoles, pyraZoline-5-ones as antidiabetic agents are particularly impressive, because these could provide greater relief to the sufferers of these disease22. 23, Afew such compounds were reported from this laboratory in recent years24' 25. Some of these were subjected to polarographic reduction at d.m.e. to study their redox behaviour with a view to establish the mechaiism of the reduction process and to determine the effect of various substituents °nEl/226' These studies have now been extended to a new series of antidia betic compounds and their precursors and some new antieoplastics, viz., 2-amino-4-aryl-5-phenylazothiazoles. Special emphasis was laid to see the effect of substituents when they are remote from the reduction site. ORGANIC POLAROGRAPHY Organic polarography differs from the inorganic polarography in two main aspects; (1) overlapping of steps and the difficulties arise in removing the interfering steps; (2) the influence of many inactive or difficultly reducible compounds. The first aspect in inorganic analysis is generally done away with by complex ion formation with interfering substance. This, however, is not possible in organic analysis because the functional groups of the organic compounds alone governs their che mical properties. One of the interesting example is that of aliphatic aldehydes. Since all the aldehydes reduce at -1. 70 V VS SCE (except formaldehyde) their estimation in the presence of one another is not a 9 7 practical proposition . Also the choice of the method for dissolving the sample and that of the supporting electrolyte :annot be generalized in organic polaro graphy. For example, incorporation of 30% ethanol in a pH-4 buffer solution, of nitrobenzene shifts the half wave potential from -0.37V 28 to -0.48 V . Moreover the pH of the solution also plays an important role, since the Ejm and the wave height (i<j) may vary with pH. The buffer, selected for the study should also have sufficient capacity to take care of any acid or alkali that may be present in the sample solution because H* ions are often either consumed or produced in the electrode reaction. The nature of the buffer constituents is equally important. In large number of reduction cases where reduction is achieved at very negative potentials special supporting electrolytes like quaternary amines, lithium salts etc. are used, which extend the range of polarographic study29» 30. Irreversible Electrode Process Most of the unsaturated organic compounds, containing particularly conjugate double bond, undergo irreversible reduction. Reversible waves have been cited in the case of azobenzene at low pH For an irreversible electrode process31"33 : 0 + ne~—*• R The expression for the cathodic current is expressed as : 1 = nFAC °K'exp f c<nF(E-E')/RT I c o r L, * where oi is the transfer coefficient, Ais the area of the electrode, K' is the value of the rate constant and C0 is the concentration of the depolarizer. Other symbols have their usual significance. El/2 te rela*ed to Ed e bv tne expression Ed'e " EV2 • 77T- l0g M-i In case where t (the drop time) varies with the change of applied poten tial, the equation is modified as follows : Ed.e+ 0„.2o4„1o2 =-0.y05^91-5,lo_g_ 1.D34o9l/K2°fh - 0?.0g542 !f_,loS _idi -i -0.546 log t "JI The above equation makes it possible to evaluateJ\from the plots of Ed.e vs I log r X -0.546 log t , or from the relationship. a Ex/2 0.02957 d(log t) Kn As most organic compounds get reduced at the expense of H+ ions of the medium, their reduction is shown by the equation : rO ^RHp from which the number of protons, p, involved in the rate determining step can be evaluated. The behaviour of these irreversible waves can therefore, be summarised as follows : 1. The value of Ej/2 changes with concentration as well as with pH. 2. The E^2 value also varies with drop time (t). 3. The value of Kfn although not pertinent in multistep processes, is useful in establishing the nature of the waves. If it exceeds 2x10 cm/sec. the reduction is considered to be reversible whereas it is of the order of 3x10"5 cm/sec. it makes it partially irreversible and values lower than the latter refer to completely irreversible nature. POLAROGRAPHIC REACTIVITY AND STRUCTURE R has been found by several groups of workers that the effects of substituents in many reaction series involving benzene derivatives could be correlated with the acid strengths of corresponding benzoic acids. On these observations Hammett * proposed a general a uantitative relation between the nature of substituent and the reactivity. This relation is known as Hammett equation : E1/2 . EO . SJ5» ^ ( jl£. ). O^OSiP ' n KRHn n P * 6 !og ( k" ) = o-j where K and K0 are rate constants for reactions of substituted and unsubstituted compounds. o~ is substituted constant. P is specific reaction constant. The values of f depends only on the conditions of reaction and nature of side chain whereas that of «r depends solely on the nature and position of substituent. For application in polarography the above equation is simplified as a e1/2 = <r- P where AE1/2 is the difference between the half wave potentials of sub stituted (substance with substituent X) and unsubstituted (substance bear ing a Hydrogen atom instead of X) compounds. A*i/2 = <Ei/2>x - (E1/2)H Since change in half wave potential is the cumulative effect of polar, mesomeric, and steric effects, it can also be represented 39>40 as AE^2 =p + Mt.+ s where P, M^and S represent the shift in half wave potential due to change in polar activationenergy increment, mesomeric energy incre ment and change in steric energy increment. The effect of substituents on half wave potential with respect only to the polar effect is most frequently expressed by using modified Hammett equation39*40 AEl/2 " P = PR^X This equation was first of all used for benzenoid derivatives bear ing an active group and a substituent in the m - or p - positions of the benzene ring. Here I^ is a constant characterizing the polarographically active group R, expressed in volts and is strongly affected by external experimental conditions and<r-x is a constant characterizing the polar effect of substituent X. These constants have been tabulated for large number of substituents. The conditions necessary for a comparison of reactivity and appli cation of Hammett equation in a given series are : (i) the value of transfer coefficient from wave shape must be similar, (ii) the values of dEw2 /dpHfrom E, >2 Vs pH plots must be similar and (iii) the mechanism of electrode process must be similar for the whole series. The useful information obtained by the application of above equation in polarography can be summarized as follows : 1. The sign of reaction constant f-r enables us to distinguish the type of mechanism, e.g., a positive value pcfcjts towards a nucleophilic mechanism and a negative value towards a radical mechanism or dissociation mechanism. 2. The half wave potentials of substance can be predicted. 8 However, the final aim of all such correlationswas the interpre tation of the structure of new compounds on the basis of their reactivity. Surprisingly,attempts in this direction are scarce42. 43 A large number of organic compounds acetophenones , substituted benzaldehyde44, benzophenons34, benzophenone oximes45, monocyclic heterocyclics , azobenzenes49* 50 e^c# have been subjected to quantitative treatment of substituent effects. Since it has been reported that the polarographic reduction of an electroactive group in a side chain of heterocyclic ring usually follows a path analogus to that followed by corresponding benzene derivatives, the effect of substituents in all the compounds studied is expressed quan titatively.