Electrochemical Behavior of a Nitrobenzenesulfonyl Derivative of Aniline in Aqueous Solution

O mecanismo de redução do composto N-fenil-4-nitrobenzenosulfonamida foi investigado em meio aquoso por polarografia de corrente direta e pulso diferencial, voltametria cíclica e coulometria a potencial controlado. Em pH < 10, o composto é reduzido em uma única etapa de 4 elétrons. Entretanto duas etapas de redução são verificadas em elevados valores de pH (pH > 11). A redução do grupo ni tro à hidroxilamina na molécula é sempre o processo preponderante no mecanismo eletródico.

Elec tro chem i cal cleav age method us ing con trolled poten tial elec trol y sis at a cath ode un der milder con di tions as a se lec tive way of re mov ing re duc ible pro tect ing groups has been in ves ti gated as a pos si ble al ter na tive to the dras tic meth ods of ten used, such as al kali metal so lu tions, high tem per a ture, and very acidic so lu tions, which can lead to deg ra da tion or racemisation in the mol e cule 1,2 .
The cath odic cleav age of amines and amino-acids protected by a nitrobenzenesulphonyl group has been elec trochem i cally in ves ti gated in re cent years with the aim of study ing a sim ple method of unprotection of the amino func tional group [3][4][5] .In these stud ies, the re duc tion of N-butyl-2-, 3-or 4-nitro-benzenesulphonamide 3 ; N,N-di-n-butyl-4-nitrobenzenesulphonamide; and N-phenyl -2-, 3-, or 4-nitrobenzenesulphonamide 5 , and 4-nitrobenzenesulphonyl-alanine and 4-nitrobenzenesulphonyl-phenylalanine in N,N-dimethyl-formamide 4 has been in ves ti gated.In pre vi ous pa pers it is pos si ble to as cer tain that the elec trochem i cal re moval of the nitrobenzenesulphonyl group in an aprotic sys tem oc curs by S-N bond cleav age (es sen tial for unprotection of amine or aminoacid), but it is greatly affected by the pro ton avail abil ity and fea tures of the R group of the re sult ing amidic group.In gen eral, a re duc tion mecha nism of nitrobenzenesulphonyl de riv a tives of aliphatic amines and amino ac ids in N,N-dimethylformamide (DMF) lead ing to cleav age of the S-N bond af ter a two-electron trans fer is al ways pre pon der ant.How ever, the com pet i tive N-H bond cleav age makes the elec trochem i cal unprotection method un suit able for ar o matic amines, as cleav age of the S-N bond is not the ma jor process.
The pro tec tion of an amine func tion is usu ally car ried out by a re ac tion un der slightly al ka line con di tions.Although the con trol of pH is very im por tant be cause it can fa cil i tate the iso la tion of the elec tro chem i cal cleav age Ar ti cle prod ucts eas ily, there are very few stud ies in volv ing aqueous me dium in the lit er a ture.Thus, it is the aim of the present work to de scribe the elec tro chem i cal be hav ior of an ar o matic amine pro tected by the 4-nitrobenzenesulphonyl group in aque ous so lu tion, as a sim plest model to un derstand com plex or ganic mol e cules.

Ex per i men tal
The N-phenyl-4-nitrobenzenesulphonamide was prepared from the cor re spond ing nitrobenzenesulphonyl chloride and an i line in 5% KOH fol low ing a pro ce dure de vel oped by Schreiber et al. 6 .The prod uct was recrystallized from 95% eth a nol and dried un der vac uum.It was checked for melt ing point, IR, nu clear mag netic reso nance spec tros copy, and el e men tal anal y sis.
The sup port ing eletrolyte used was Britton-Robinson (B-R) buffer, pre pared by mix ing a so lu tion con tain ing 0.04 M orthophosphoric acid, 0.04 M ace tic acid, and 0.04 M bo ric acid with the ap pro pri ate vol ume of 0.2 M so dium hy drox ide so lu tion.
The elec tro chem i cal mea sure ments were made us ing an EG & PAR model 264 A polarographic an a lyzer and an EG & PAR model RE 0031 x-y re corder.An EG & PAR -303 A stand was used in the DME mode for polarography and HMDE for cy clic voltammetry.The three-electrode sys tem was com pleted us ing a glassy car bon aux il iary electrode and an Ag/AgCl (3 M KCl) ref er ence elec trode.The con trolled-potential elec trol y sis was car ried out in a three-compartment cell with a mer cury pool cath ode.The UV spec tra were re corded on a Perkin Elmer Coleman 575 spectrophotometer.
All pH mea sure ments were made with a Metrohm E 500 pH me ter with a Metrohm EA 121 glass elec trode, previ ously cal i brated.
The dif fer en tial-pulse mode was used with a pulse ampli tude of 50 mV, a drop time (t d ) of 1 s and a scan rate of 3 mV s -1 , un less stated oth er wise.

Polarography
The elec tro chem i cal re duc tion of an i line pro tected by a 4-nitrobenzenesulphonyl group was in ves ti gated us ing an aque ous so lu tion in the pH range 2-12.Di rect cur rent (dc) and dif fer en tial pulse (dp) polarograms of 1 x 10 -4 M of N-phenyl-4-nitrobenzenesulphonamide (NBA) ex hibit a sin gle wave in the pH range 2-10, at trib uted to the re duction of the ni tro group, as shown in Fig. 1, Curve I.This peak be comes broader as the pH in creases and be comes a dou ble peak in a so lu tion of pH 12 (Fig. 1, Curve II).The height of the wave (i1) re mains slightly pH-dependent at pH < 9 and grad u ally de creases to one-fifth of its orig i nal height at pH 12 (Fig. 2, Curve b).Con com i tantly the half-wave (E 1/2 ) or peak po ten tial (E p ) shift lin early to more neg a tive val ues (Fig. 2, Curve a), in di cat ing that protonation of the ni tro group was not re stricted to acidic me dia.Slopes of the lin ear seg ments of the E 1/2 = f(pH) or E p = f(pH) were 53 mV and 54 mV re spec tively.
The log a rith mic anal y sis of the waves at pH 2, 4, 6 and 9 re sulted in straight lines and the αn val ues of 1.48 (where n = num ber of elec trons in volved and α = trans fer co ef fi - cient) point to an ir re vers ible be hav ior of the over all electrode pro cess.The ir re vers ibil ity of the sys tem was con firmed by dp polarography.Values of W 1/2 (peak half-width) of ap prox i mately 102 mV were found for the range 2 < pH < 9.
The pro cess was found to be dif fu sion con trolled, as shown by the lin ear plots of lim it ing cur rent (i l , by dc polarography) vs square root of height of the mer cury reser voir and lin ear plots of peak cur rent (i p , by dp polarography) vs. t 2/3 .Also plots of i l and i p vs NBA concen tra tion ex hibit good lin ear ity over the range 2 x 10 -5 to 1 x 10 -3 M.

Cy clic voltammetry
The pH in flu ence on the cy clic voltammetric be hav ior of NBA at a scan rate of 0.05 V s -1 is il lus trated in Fig. 3. On the first cath odic scan (Fig. 3, Curve x and y) only one cathodic peak is seen at 2 < pH < 10.Peak po ten tials of ip c1 are shifted by in creas ing the pH by about 54 mV/pH.The height of this wave di min ishes by in creas ing the pH above 9, as ver i fied pre vi ously.
On the re verse scan with the HMDE, an an odic peak (ip a1 ) at -0.16 V is ob served at 4.5 < pH < 10 (Fig. 3y), but at lower pH val ues this peak is over lapped by the cur rent of mer cury dis so lu tion (Fig. 3x).Lin ear plots of peak cur rents of ip c1 and ip a1 as a func tion of ν1/2 were ob tained at pH 6.8 and 9.3 sug gest ing that the cur rent is dif fu sion con trolled.How ever the peak height (ip a1 ) is only 30% or less of the peak cur rent ip c1 .
On the sec ond tri an gu lar volt age scan (Fig. 4), the peak po ten tial of the cath odic re duc tion of the ip c1 is shifted by about 80 mV.The peak cur rent ip c* in the sec ond cy cle is about 30% lower than in the first.On sub se quent scans, neither the height or po ten tial peaks var ies.How ever, at pH > 4.5 small ad di tional cath odic peaks (ip c4 and ip c3 ) are ob served dur ing the sec ond cy cle at po ten tials more pos itive than ip c1 (Fig. 4, Curve n).The peak ip c4 may be respon si ble for the cor re spond ing re duc tion of the ox i da tion prod uct readily ap par ent on the an odic sweep (ip a1 ).The height of this peak in creases grad u ally with in creas ing pH and con com i tantly its po ten tial is shifted to more neg a tive po ten tial.Whereas the Ep a1 -Ep c4 is al ways 29 mV in di cating a re vers ible pro cess in volv ing 2 elec trons.The ra tio of peak cur rents ip c4 /ip a1 in creases by in creas ing rate of voltage scan ning reach ing lim its of 0.6 at 200 mV/s.The cathodic peak ip c3 is seen only on the sub se quent scans (Fig. 4, Curve n).The an odic peak (ip a3 ) on scan re verse is the mirror im age of the cath odic peak re flected across the po ten tial axis, clearly in di cat ing the shape of the ad sorp tion peaks 7 .This be hav ior sug gests strong ad sorp tion of the prod uct gen er ated in the suc ces sive scans.
Voltammograms re corded at a higher pH range (pH  11) ex hib ited two cath odic peaks at po ten tials cor re -  spond ing to the two polarographic steps (Fig. 3z).A small ox i da tion peak (ip a1 ) cor re spond ing to the reoxidation of the first re duc tion prod uct is readily ap par ent on the re verse scan.The ra tio of the an odic -to -cath odic peak heights for this cou ple in creased with the scan rate, in di cat ing that the prod uct of the first elec tron trans fer re ac tion is con sumed by a slow chem i cal re ac tion.
No sig nif i cant an odic peak re sult ing from reoxidation of the sec ond re duc tion step (ip c2 ) was ob served at any scan rate.Also the ra tio be tween the mag ni tude of the sec ond peak (ip c2 ) and first peak (ip c1 ) is al most con stant.If switching of the neg a tive sweep is held at the po ten tial be tween the sec ond (ip c2 ) and first peak (ip c1 ) be fore the com plete sweep the be hav ior is prac ti cally the same, in di cat ing the in de pend ent na ture of both peaks.No anom a lous be hav ior was ver i fied on the suc ces sive scan, ex cept a de crease in the peak cur rent for both peaks due to dif fu sion prob lems.

Con trolled po ten tial elec trol y sis
Con trolled po ten tial elec trol y ses were car ried out in a 1 mM so lu tion of NBA us ing a mer cury pool elec trode.Taking into ac count the im por tance of un der stand ing the re duc tion mech a nism in sligthly al ka line so lu tion, the electrol y ses were per formed in B-R buffer pH 9.3 at -1.0 V.The vari a tion of cur rent over a pe riod of time was fol lowed and the num ber of elec trons con sumed in the to tal re duc tion was de ter mined.Values of n= 3.90 were ob tained af ter three rep e ti tions.A lin ear plot of log i vs time was ob tained and the re sults show that four elec trons are trans ferred in the re duc tion of NBA.
Aliquots of the elec tro lyzed so lu tion were re moved and nitrobenzensulphinate ion and an i line that could be formed by S-N bond cleav age and nitrobenzene pro duced as a result of the C-S bond cleav age were sought spe cif i cally.Nitrobenzenesulphinate was ex am ined by the Smiles test 8 .An i line and nitrobenzene were in ves ti gated by op ti cal spec tra.These prod ucts were not de tected.How ever, taking into con sid er ation the pos si ble re duc tion of ni tro group to hydroxylamine in aque ous so lu tion, as pre dicted in the lit er a ture 9,10 , the spec tro pho to met ric spec tra of the 1 x 10 -4 M of NBA so lu tion and the elec tro lyzed prod uct were compared (see Fig. 5).At time in ter vals greater than 60 min the absorbance at 268 nm as signed to the ni tro spe cies was com pletely dis ap peared and the in crease in absorbance at 236 nm at trib uted to the hydroxylamino com pound occurred 9 .
The prod uct re duced by elec trol y sis at -1.0 V was titrated potentiometrically us ing po tas sium per manga nate 0.0588 N. The end point oc curs when about 1 equiv of permanga nate is added to the elec tro lyzed so lu tion re sult ing in an 80% yield .This find ing sup ports the con clu sion that the re duc tion of NBA in aque ous so lu tion pro ceeds by pref eren tial re duc tion of the ni tro group to hydroxylamine.

Re duc tion mech a nism
The fore go ing ex per i ments show that in N-phenyl-4-nitrobenzene sulphonamide, in con trast to the re sults ob tained in an aprotic me dium [3][4][5] , the cleav age of S-N; N-H or C-S bonds are not pre dom i nat ing in the process in aque ous so lu tion.On the other hand, as with other nitroaromatic com pounds [9][10][11][12][13][14] , the over all course of the reduc tion of the N-phenyl-4-nitrobenzenesulphonamide in aque ous so lu tion prob a bly in volves the re duc tion of the nitro group to the hydroxylamine in a four elec tron pro cess.The re sults can be ex plained by a scheme of the gen eral mech a nism for re lated ni tro com pounds [9][10][11][12][13][14] At 2 < pH < 10, the ni tro group of NBA is re duced first to a hydroxylamine group in a sin gle four-electron wave (Eqs.1-3).This is con sis tent with n = 4 found by con trolled po ten tial eletrolysis.The pH de pend ence of half-wave poten tials in di cates that re duc tion of NBA in volves preprotonation of the ni tro group.The pro tons in volved in the re ac tion have been de ter mined and val ues of 1.3 were ob tained 15 .It is pos si ble to sug gest a pro cess in volv ing one pro ton (Eq.1), in which a cor re spond ing equi lib rium re action is re spon si ble for the de crease of the wave in al ka line so lu tion and the ap pear ance of an other re duc tion step at more neg a tive po ten tial at pH 12.This in di cates that the sur face preprotonation of the ni tro group in this pH range is not fast enough, and the unprotonated ni tro group is reduced at a more neg a tive po ten tial.
In agree ment with the lit er a ture 13,14 , our ex per i men tal ev i dence un der con di tions of cy clic voltammetry with HMDE in di cates the pres ence of the hydroxylamine de riva tive as main prod uct gen er ated at the first cath odic peak, which can be electrooxidized to a nitrosobenzene de riv ative at -0.17 V (ip a1 peak).The sub se quent cath odic peak (ip c 4 ) cor re spond ing to the re duc tion of the electrogenerated nitroso group is seen on the sec ond forward tri an gu lar volt age sweep 13,14 .The ad sorption/desorption pro cess of these prod ucts is seen in the sucessive scans when the ex per i ments are car ried out with a HMDE elec trode on which the sur face is not re newed (ip c3 , ip a3 peaks).
Al though cath odic deprotection in aprotic me dia forms the ba sis of a use ful pre para tive pro ce dure for the re moval of the nitrobenzenesulphonyl group from amines [3][4][5] , our find ings in di cates that the cleav age of the S-N bond in the N-phenyl-4-nitrobenzenesulphonamide in aque ous so lution is not sig nif i ca tive un der reductive con di tions.The ease with which the ni tro group is re duced to a hydroxylamine group in aque ous so lu tion makes the electro chem i cal unprotection method un suit able for amines pro tected by the nitrobenzenesulphonyl group.

Ac knowl edg ments
The au thors wish to thank CNPq and FAPESP for finan cial sup port and D. Barnes for re view ing the manuscript.