Indian Journal of ChemistryVol. 28A, March 1989, pp. 202-205

Electrochemical Oxidation of Sulphathiazole at Pyrolytic Graphite Electrode

R N GOYAL*, ANOOP KUMAR & ALOK MIITALDepartment of Chemistry, University of Roorkee, Roorkee 247 667

Received 17 March 1988; revised and accepted 23 May 1988

The electrochemical oxidation of sulphathiazole has been studied in the pH range of 1.2-10.7 at pyrolytic graphite elec-trode. Two well-defined pH dependent peaks are observed. The various products isolated and the observed voltamrnetric,coulometric and spectral results have been rationalised. One of the products obtained from electrooxidation is an azo com-pound.

Andreoli and coworkers' studied the polarographicreduction of several sulphadrugs in protic andaprotic media and found that Nl-substituentscaused large shift of half-wave potentials. Voorhiesand Adams? studied the electrooxidation of sulpha-drugs at a rotating platinum electrode and esta-blished a method for their quantitative determina-tion in the range of 4 x 1O-s to 1 X 10-4 M. The vol-tammetric behaviour of some sulphonamides at theglassy carbon electrode was studied by Mombergand coworkers.' and the method was applied for theanalysis of selected mixtures in a drug formulation.However, no attempt has been made in these re-ports to study the mechanism of electrochemical ox-idation of sulphadrugs and hence the present studywas undertaken.

Materials and MethodsSulphathiazole(Sigma Chemicals, USA) was used

as received. Phosphate buffers" of ionic strength 1.0M in the pH range of 1.2 to 10.2 were preparedfrom reagent grade chemicals. Pyrolytic graphiteelectrodes prepared had an area of 2.2 mm". Allpotentials refer to SCE at 25°C.

The equipment used for linear and cyclic sweepvoltammetry, coulometry and controlled potentialelectrolysis has been described elsewhere". The UVspectra were recorded using Specord (C.Zeiss, Ze-na) spectrophotometer and IR spectra were re-corded on a Beckmann IR-20 spectrophotometer.

Stock solution (5 m M) of sulphathiazole was pre-pared in doubly distilled water and the working so-lutions were prepared by mixing 5.0 ml of the solu-tion with 5.0 ml of the buffer of appropriate pH. Pu-rified nitrogen gas was bubbled for 5 to 8 min beforerecording the voltammograms.

For product identification the substrate (8-10 mg)was electrooxidised in a three-compartment cell atpotential more positive to peak lla in the buffer of

202

desired pH employing pyrolytic graphite plate (6ern x l em), platinum gauze cylinder and SCE asworking, counter and reference electrodes respect-ively. As electrolysis progressed a precipitate start-ed appearing in the solution. The progress of elec-trolysis was monitored by recording cyclic voltam-mograms at different time intervals. When the peakcurrent for the oxidation peak disappeared, electro-lysis was stopped and the electrolysed solution wasfiltered. The light yellow precipitate was dried andcharacterised by (TLC, m.p. and IR). The filtratewas lyopholised and extracted with ether. The con-centrated ether extract was also investigated for anyorganic product.

Results and DiscussionLinear sweep voltammetry of sulphathiazole in

the pH range of 1.2-10.2 exhibited two well-definedoxidation peaks (Ia and Ila) at a sweep rate of1OmVs-l. The peak potential of the oxidation peakwas dependent on pH and shifted towards less posi-tive potential with increase in pH. The E, versus pHrelation for peak Ia exhibited one break at aroundpH 6.7 whereas peak Ila, exhibited two breaks atpHs 2.9 and 7.4.

Sulphathiazole has an aromatic amino group anda substituted sulphonamide group which can under-go oxidation at PGE. That only amino function wasoxidised was supported by the fact that cyclic vol-tammograms of benzenesulphonamide did not ex-hibit any peak in the pH range of 1.2 to 10.2.

In cyclic sweep voltammetry at a sweep rate of150 mvs", sulphathiazole exhibited two oxidationpeaks in the pH range of 1.2-8.7 when sweep was in-itiated in the positive direction. The peak potentialsof the two peaks were so close that at pH > 8.7 onlyone oxidation peak was noticed. In the reversesweep two cathodic peaks (I1Ic, IYc) were observedat pH < 4.4, and peak IIIc formed a quasi-reversi-

GOYAL et al.: OXIDATION OF SULPHATHIAZOLE AT PYROLYTIC GRAPHITE ELECTRODE

ble couple with anodic peak IIIa observed in subse-quent sweep towards anodic potential. The peakpotentials of peaks IIIc and IVc were also dependenton pH and shifted towards more negative potentialwith increase in pH. At pH > 4.4 only one reduc-tion peak (IVc) was observed in the reverse sweep.Peaks Ia and IIa were clearly observed at a sweeprate below 50mVs-J whereas at higher sweep ratepeak Ia was observed as a break and at pH > 8.7,only one oxidation peak was observed. The quasi-reversible couple IlIc/IlIa was observed only in thepH range of 1.2 to 4.4 and at a sweep rate >50mVs-J.

The peak currents for the oxidation peaks la andIIa increased with increase in sulphathiazole con-centration up to about 3mM. At concentration <2mM the current versus concentration plot was al-most linear indicating involvement of adsorption inthe electrode process. This was also confirmed bythe increase in peak current function (ip/ ACYI!2)with sweep rate". This adsorption prevents evalua-tion of the number of electrons transferred in theelectrode reaction on the basis of peak current mea-surement.

The UV spectra of 0.05mM solution of sulphathi-azole were recorded in the pH range of 1.2-10.2 andpis values were obtained from absorbance versuspH curves at selected wavelengths. Sulphathiazoleexhibited one well-defined peak at 285 nm with ashoulder at 260 nm at pH < 3.0. In the pH range of3.0- 7.5, the shoulder at 260 nm appeared as a bandand at pH > 7.5, only one band was observed at260 nm. The absorbance at 260 nm was plottedagainst pH and the resulting dissociation curve gaveinflections at pH 2.7 and 7.3. In sulphathiazole twoacid-base centres, viz. the basic amino group andacidic amide group are present. The first inflectionat pH 2.7 corresponds to the pKa of the protonatedamino group. Thus below pH 2.7, sulphathiazoleexists as a protonated species. The second inflectionat around pH 7.3 represents the acid dissociation atamide. The inflections observed in absorbance ver-sus pH plots were practically similar to the breaksobserved in E, versus pH plot. An identical behav-iour has also been observed by other workers in thecase of sulphonamides and arylsulphonamides+".

Electrolysis of stirred sulphathiazole solution(2mM) generally took more than 4 hr for completeelectrooxidation. The plot of current versus timedecreased exponentially and reached a plateau after90 min of electrolysis. The value of n was deter-mined by graphical integration of current-timecurve as reported by Lingane et al" and was foundto be 2.0 ± 0.15 in the entire pH range employed inthis study.

The progress of electrolysis was also monitoredby U'V, The UV spectrum of sulphathiazole at pH8.0 exhibited a well-defined maximum at 260 nm.When a potential more positive to peak IIa was ap-plied the absorbance at Amax systematically dec-reased whereas the absorbance in the lower wave-length region (215-240 nm) as well as higher wave-length region (300-350 nm) increased (Fig. 1). After4 hr electrolysis the solution exhibited two bands at225 and 310 nm. Thus itis concluded that no in-termediate with sufficient half-life is generated dur-ing the electrooxidation of sulphathiazole and syste-matic increases in absorbance at longer and shorterwavelengths are due to the formation of product/soAs the product of electrooxidation absorbed atlonger wavelength in comparison to the startingcompound, it was concluded that the product hasextensive n-chromophore system.

An almost identical behaviour was observed atpH 3.0, with the only difference that the increase inabsorbance at shorter wavelength was much less incomparison to that observed at pH 8.0.

The progress of electrooxidation was also moni-tored by recording cyclic voltammograms at differ-ent time intervals. Cyclic voltammogram of sulpha-thiazole solution immediately after initiating oxida-tion at pH 7.6 exhibited peaks la, IIa and IVc. Withprogress of electrolysis, peaks Ia and IIa systemati-cally decreased whereas the peak current for peaklYe remained the same. At the end of electrolysisthe cyclic voltammogram revealed almost samepeak current as that for peak IVc. This cyclic vol-tammogram did not change even when the solutionwas left at room temperature for several morehours. Hence it is clear that electrooxidation pro-duct(s) of sulphathiazole is electroactive in nature.However, slightly different behaviour was observedin cyclic voltammetry at pH 3.. With progress of

1.0..--------.,----------,

ILl

~ 0.5..•CDcroonCD..•

0.1

200

Fig. I-UY spectral changes observed during the electrooxida-tion of 0.05 mM sulphathiazole at pH S.lO. [Curves were re-corded at (1) 0; (2) 10; (3) 20; (4) 30; (5) 45; (6) 60; (7) 120; (S)

150; (9) ISO and (10) 240 min of electrolysis 1

203

INDIAN J CHEM, SEe. A, MARCH 1989

electrolysis the peak currents for peaks IDc, IDa andIVc did not increase. At the end of electrolysis peaksIlIe and IDa were visible together with peak IVc.Hence it was concluded that productis) of elec-trooxidation of sulphathiazole at pH 3.0 and 7.6 aredifferent and the origins of the peaks IDc and IDaare due to some side reaction and they are not dueto the main e1ectrooxidation product of sulphathia-zole.

Product CharacterizationThe products of electrooxidation of sulphathia-

zole at pH 3.0 and 7.6 were characterised. At pH 3.0the light yellow precipitate obtained was filtered offand the filtrate was lyopholised. The yellow productin TLC (benzene-methanol 4:1) gave only one spotwith R, = 0.40. The product obtained from the filtr-ate was extracted with ether (2 x 10 rnl) and theether extract on TLC also gave one spot withRj= 0.19. Thus it is clear that in the electrooxidationof sulphathiazole two products are formed. The 1Rspectrum of the insoluble product (m.p. 208°) didnot display bands at 3420 and 1300 cm:' corre-sponding to v NH2 modes of sulphathiazole. Thispoints to the e1ectrooxidation of aromatic aminogroup of sulphathiazole. The appearance of a srongband at 1600 cm:', assignable to the azo group indi--ates that the product of electrooxidation is an azo

. ompound. The presence of azo product is furtherconfirmed by the mass spectrum of the product,which exhibited a clear molecular ion peak at mlz506.

The 1R spectrum of the second product obtainedfrom the ether extract exhibited two sharp bands at1400 and 1460 ern"! corresponding to the presence

PClak la •

RHN~S-@-NHOH + Ii

(y)

Peak 1IIC1l Peak Ilia2e+2H+ -2e-2H+

of - NHOH linkage in the molecule as reported inthe literature 10. The product exhibited a meltingpoint of 167° and is believed to be p-hydroxylamin-obenzene-N-(2-thiazolyl) sulphonamide.

The controlled potential electrolysis of sulphathi-azole at pH 7.6 also gave a yellow precipitate. Theyellow product was found to be identical with theazo product obtained at pH 3.0. However, the filtr-ate on lyopholisation followed by extraction withether did not give any compound. Hence it was con-cluded that at higher pH only azo compound is ob-tained as the major oxidation product.

MechanismThe two-electron electrooxidation can occur in

two different ways; a single two-electron oxidationstep or a one-electron process followed by secondelectron transfer. In order to account for the ob-served electrochemical, spectral and coulometricresults, it seems reasonable to conclude that Ie, 1H+oxidation of sulphathiazole (I) readily. gives a freeradical species(Il) (Scheme 1). A similar Ie, 1H + oxi-dation step has also been suggested during the elec-trochemical oxidation of aniline and substituted ani-lines11•12• The free radical (II) can undergo deactiva-tion (Scheme 1) in a variety of ways. However, theformation of azo compound is possible by combina-tion of two species (II) to give a hydrazo molecule(ill). As hydrazo compounds are susceptible to elec-trooxidation!', it further undergoes 2e, 2H+ oxida-tion to give an azo product (IV). As azo compoundshave been reported 14 as electroactive in nature,compound (IV) undergoes reduction at potentialcorresponding to peak IVc to give hydrazo com-pound back. It is expected that as the electrolysis

1RHN02S~NH--NH~S02NHR

(nIl

RHN02?-@-NO

C!2I)N

Whara R= [["J(5 NH2

Scheme L Tentative mechanism proposed for the elechooxidation of Sulphathiazole.

204

GOYAL et al.:OXIDATION OF SULPHATHIAZOLE AT PYROLYTIC GRAPHITE ELECTRODE

progresses peak current of peak IVc should increasedue to formation of electroactive azo compound.But the precipitation of azo compound in aqueoussolution does not permit the increase in peak cur-rent of peak lYc. The consumption of four electronsper two molecules of sulphathiazole gives an overalltwo-electron oxidation reaction to give azo com-pound (IV) as the final product of the electrodereaction.

The free radical species (II) can also be deactivat-ed by the hydrolysis to give p-hydroxylaminoben-zene-N-(2-thiazolyl)sulphonamide (V) as observedat pH 3.0. As hydroxylamino compounds are elec-troactive in nature's, couple IIlc/IlIa was observedin the cyclic voltammery in the pH range of 1.2-4.4.Further electrooxidation of V to give nitroso mole-cule (VI) is a side reaction involving 2e, 2H + ob-served in peaks IlIe/IIla. The complete electrooxi-dation of sulphathiazole (1) to give nitroso product(VI) requires three electron per molecule and hencethe formation of hydroxylamino product (V) is aside reaction observed in the pH range of 1.2-4.4.

AcknowledgementThe authors are thankful to M/s Pfizer, USA for

the gift of pyrolytic graphite. One of the authors

(AM) is thankful to ICMR, New Delhi for the awardof a junior research fellowship.

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