Polarography of some arylazothiohydantoin derivatives

摘要

J.C.S. Perkin I1 Polarography of Some Arylazothiohydantoin Derivatives By S. Darwish, H. M. Fahmy," M. A. Abdel Aziz, and A. A. El Maghraby, Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt The polarographic behaviour of a series of arylazothiohydantoin derivatives has been investigated at a dropping mercury electrode. Two waves were displayed. The first and predominant one is due to the reductive splitting of the azo-linkage by a 4e irreversible process. The second is assumed to be for the reduction of the CONHCO group in the resulting molecule. A mechanism for the electrode process covering a wide range of pH is proposed, dis- cussed, and clarified via model compounds, identification of the resulting products of electrolysis, pK, determin-ations, and the interpretation of a-euro;3 plots.AROMATICazo-compounds have been the subject of niany investigations during the last de~ade.l-~Kecently heterocyclic azo-conipounds have received xttention .5.ti However, a literature survey revealed the absericc of polarographic data on arylazothiohyclaiitoiiis, a class of compounds which have several interesting applic-ations in the field of nwdicine since they contain tlic thiohydantoin ring.',* In this paper the polarographic beliaviour of 5-arylazo-1 -plimyl-4-tl 1ic )liyclan toin (Ia) ArN=NCH-C=S CH,-C-SI' I CgHgNbsol; C ,NH II 0 a;Ar = C,H, b; Ar = m-CH,C,H, c ,.Ar = p -CH3C,H, d; Ar = p -CIC,H, e ; Ar = p -BrC,H, f ; Ar = p -ocH3C6Hk CJ ; Ar = p -COZHC~H~ h ;Ar = m -NO~C~HL together with seveii of its substituted derivatives (Ib--h) and a structurally related model compound, 1-plienyl-4- thiohydantoin (11),have been investigated in solutions of different hydrogen ion concentration covcring a wide range of pH (2-12) in order to throw liglit on the possiblc clectrorcduction modes of such molcculcs at tlio dropping mercury electrode. EXPETi IMENTAT, S.yntl~eses.-5-A rylazo-1-pl~enyl-4-thinhydaiztoi ns (Ia-11) .An aromatic aniine (0.0068 niol), dissolved in concentrated liydr~~chloricacid (6 inl) antl water (G nil), was cooled to 0 "C ancl then treated with R cold solution of sodium nitrite (0.6 g) in water (6 nil). 'The cliazotized aiiiine was acldecl gradually to an ice-cold solution of 1-plienyl-4-tliioliptlan-toin (11) (1.3 g) dissolved in etlianol (50 nil) containing sodium acetate (2.6g).The mixture was then left aside in cl. colt1 chest for 1 h. The separated product was filtered off, washed with water, and recrystallized from acetic acid. Yields, m.p.s, and elemental analyses for the h-;irylazo-derivatives (la-h) are listed in Table 1, Polarograf~hy.-( a) Apparatus. Polxrog~.aphic curves were recorded with an LP60 polarograph (Laboratorni. l'ristroge, I'rague). A cell of our OUT design with a separated saturated calorie1 electrode wiis used. Tlw capillary poswssctl tlie following characteristics in tlie H,O opcm circuit: 1 3 s drop-1, n? 2.15 mg 5-l for I! 50 cin. (t)) Solutions. 10 :'M-Stock solutions werc prep;irtatl 1)y (lissolving an accurately weighed quantity of material in thc ;ippropriatc volunic of absolute ethanol (n,,2,51.359).nritton-liobin~oii modified univer-s;il buficrs 10 (prepre(1 from AnalaFi gratle c.liemicals) were used :is supporting clectrolyte. (c)Measurenzentq. All experiments were carried at 25 f 2 "C. Tlie half-wave potentials were measured graphically nncl ehpressed vevsus the saturated calomel electrode (s.c.c.) with :in accuracy 5 0.005 V. Tile accuracy of the applied voltage was checked by recording polarograms of standard 7'1 ' in 0.1M-ICNO, solutions for different concmtrations (El,, -0.45 ueYsu.7 s.c.e.). ((1) J'rocPduw. Ethanol atid the appropriate buffer solution were introduced into the po1arogr;Lpfiic cell.Thc solution was then deaeratetl by bubbling x stream of Iiytlrogen euro;or 10 min. The calculated amount of stock solution was then introduced into the cell so that the final concentration was 10 4~ in 10 nil of 40 (v/v) ethanolic buffer. Coutvolled Potential Electrolysis and Identification of the Pvciducts. -Mercury pool electrolysis was carried out 5Oc7i3 v/v etlinnol-10 HC1 solution (200 ml) and substance (la) (200 nig) taken as a typical example. The electrolysis cell was a 250-tnl conical flask in which the reference, auxiliary electrodes, and the gas inlet were added by means of a cork. The potential was cotitrollecl by a Tutorial T6 transistorized potentiostat at -0.8 V ziersus s.c.e. (2.e. on the limiting current plateau of wave A).The progress of the electro- lysis was followed by recording the decrease in current with time and the number of electrons was computed from i-t curves following the procedure outlined by Lingane l1 and found to be 4e. After disconnecting tlie electrolysis cell Erorn the circuit, 1 nil of the resulting solution was with- tlrawn and the presence of aniline in this solution was revealed by a stanclarcl spot test.', The remaining reaction mixture was partially evaporated on a water-bath to half its volume, then allowed to cool to room temperature and cstractecl with ether. The ether layer was in turn evapo- rated. The oil obtained was treated with a few ml of ethanol antl crystals separated ancl were recrystallized from diluted ethanol, 1ii.p.120 "C, v,,,,,. (KRr) 3 300 (NH,), 3 130 (ring NH,), 2 960 (CH), 1770 (C:O), 1720 (CO), and 1600 (NH) cilirl (1;ountl: (', 56.55; H, 4.7; N, 22.0. C,H,N,O, 1981 345 requires C, 56.54; euro;I, 4.71; N, 21.98). The cornpound negative wave b appeared with an i, value equal to half obtained was identified as 5-amino-l-phenylhydantoin. that of wave a (ilca 0.55 PA); with further increases in Tleterrnination of the Acid Dissociation Constants pH the limitillg current of wave b decreased in the form ~lsquo;ott?ntiometry.-rsquo;llsquo;lle phrsquo;, of Our Compounds (Table 2) Were of a well defined dissociation curve 14 and vanished com-tlctcrinined c:onventionally by titrating a 5 x 10-4~ pletely at pH 8, The half-wave potential En:of wave TABLE1 !i-Arylazo-l-pl~enyl-4-tliiohydantoinderivatives (Ia-h) Analysis (yo) C H ldquo;1 r.SlM.p.r------r------7 r-h v r--h v Compound (ldquo;C) Yield (:h) Calc. Found Calc. Found Calc. Found Calc. Found 261 90 60.8 60.9 4.05 4.0 18.9 19.0 10.8 10.7 363 91 62.0 61.9 4.5 4.6 18.05 18.0 10.3 10.3 250 90 62.06 01.8 4.5 4.4 18.05 18.1 10.3 10.4 265 92 54.45 54.4 3.35 3.4 16.95 16.9 9.7 9.7 260 85 48.0 48.1 3.95 2.9 14.95 14.9 8.56 8.4 220 80 58.9 58.8 4.3 4.3 17.15 17.2 9.8 9.8no0 88 56.45 56.5 3.55 3.5 16.45 16.5 9.4 9.5 270 82 52.8 52.7 3.2 3.3 20.5 20.4 9.4 9.4 * Cl: calc. 10.74; found, 10.8. t Br: calc. 21.33; found, 21.4. solution (50 nil; 1: 1 C,H,0H-H20) of each cornpound a shifted towards negative potential values with thc ngainsl n, standrml 2 x lO-M-N;LOHsolution with ;t lrsquo;p~ -increase in pH of the solution.This shift is described by 11nic:iiii rnotlcl 292 MK2 pH meter. two linear segments as shown for compound (Ia),takcn as a typical example, in Figure 2. The shifts of EA with,.1 ARLI? 2 pH for compounds (Ia-h) are compiled in Table 3 in thc Acid dic;socintion c-onstnn ts of 5-arylazo-1-pIicnyl-4-thio-11ydantoin t1criv;ttivcs (T;t-li) and 1 -phcn Vl-4-tIiio-form of linear equations. The Ei-pH plots of thc 11yclantoin (T 1) second wave b also revealed two linear segments inter- Componntl pK, Compound pKa cepting at pH ca. 6 a value which is accord with the pKrsquo; (T4 7.55 (re) 7.77 values l4 (apparent polarographic dissociation constant, (rsquo;19 7.88 (If) 7.98 i.e. pH value corresponding to amp;/2)obtained for the il-(Ic) 7.60 (Ig) 7.10 pH curves (Figure 3).The half-wave potential of wave (1 (1) 7.53 (Ih) 7.30 (ldquo;1 8.45 b in the first segment is little influenced by a change in hydrogen ion concentration and thus is practically in- RESULTS AND DISCUSSION dependent of pH variation (dE,/dpH ca. 0). Shifts of Polarogvafihic Behaviour of (Ia-g) .-The polaro-Ei with the increase in pI-1 for the second segment are grams of 10-4~-(Ia-g) in 40y0v/v ethanolic buffers are given in Table 3. The more positive wave a is diffusion- FIGURE Schematic representation of the polarograms of 10-*~-5-phenylazo-l-phenyl-4-thiohydantoin1 in 40 v/vethanolic Britton- Robinson buffers. All curves start from zero potential represented by those of (Ia) taken as typical example in controlled as shown by the linear dependence of il on Figure 1.In acid solutions of pH 4compounds (Ia- concentration (0.5-3 x 10-4~)at various pH values, and g) displayed a well defined polarographic wave a (i ca. by the values x = 0.45-0.55 in il = khx (h = mercury 1.1 PA) the height of which was practically constant column height). Similarly, wave b was proved to be within the whole pH range (2---12). At pH 4 a more diffusion-controlled in the pH range in which it was wave b wave a11.2 10, -082 XL kl 06-04-02-2 4 6 8 10 12 PH 2FIGURE Et-pH plot for the polarographic wave of 5-phenylazo-1-phenyl-4-thiohydantoin practically constant (i.e. pH independent). Above pH 5 this wave was partly kinetically controlled (x 0.45).Logarithmic analysis of waves a and b at different pH values using the fundamental equation for polarographic waves l5 indicated that the two electrode processes pro- ceed irreversibly; the slopes obtained are compiled in Table 3. PoZarographic Behaviour of (Ih) .-In addition to waves a and b in the polarograms of (Ia-g), compound (Ih) 1.0:1 wave a ~ 0.8 wave b I0.01 I ' 1 , I , f , , , , 2 4 6 8 10 12 PH FIGURE it-pH plot for the yolarographic wave of3 5-phenylazo-1-phenyl-4-thiohydan toin J.C.S.9Perkin I1 showed an additional 4e irreversible diff usion-controlled wave c lying between waves a and b. The effect of pH on E, of the different waves is shown in Figure 4.The behaviour of the additional wave can be described by the linear equation (1). The data for the two other waves Ek = -0.18 -0.08 pH (1) are compiled in Table 3. Since the behaviour of this wave is comparable to that known for a m-nitro-groupl16 18 -wave b16 -14 -wave c 0 2 4 6 8 10 12 PH 4FIGURE E*-pH plots for the polarographic waves of 5-(m-nitrophenylazo)-1-phenyl-4-thiohydantoin it is not unreasonable to attribute this extra wave to the reduction of the nitro-group to a hydroxylamine equ- ation (2).l6 -NO, + 4e-+ 4H+ --NHOH + H,O (2) Polarographic Behaviour of ModeZ Compound (I I) .--Under similar experimental conditions model compound (11) showed no polarographic wave in acid media of pH 7.5.At pH values greater than 7.5 a wave started to appear which increased in height with the increase of pH and became u7ell defined at pH 10. As is clear from Figure 5, of this wave is pH-independent in the range of its appearance. The il-pH plot for this compound is illustrated in Figure 6. The increase of il with the in-crease of pH is in the form of a dissociation curve with a pK' value of 8.7. Assignment of the Polarographic Waves of (Ia-h) .--(1) In the more positive wave a the -N=N-moiety is the reduced species. (2) The more negative reduction step (wave b) corresponds to reduction of the molecule 347 resulting from the reductive splitting of the -N=N-1-phenyl-4-thiohydantoin (IV) is reasonably explained moiety. The following proof is given for these assign- by the fact that (IV) is hydrolysed under mild conditions ments.The shift of Eg with increase of pH given in to (111). This is confirmed by the fact that 2,4-dithio- Table 3 is in good agreement with the reported values for hytlantoin derivatives are known to be easily hydrolysed TABLE3 Polarographic data of 5-arylazo-1-phenyl-4-thiohydantoinderivatives (Ia-h) Wave a Wave b -PH Et-PH Segment 1 Segment 2 RTI Segment 2 RTI Compound (PH 2-71 (PH 8-12) unF * an pHb (PH 5-7) unF u'y2 pHb (Ia) E+= -0.06-0.091 pH Ek = +0.57-0.143 pH 0.150 0.394 6.4 El = -0.78-0.088 pH 0.066 0.895 6.2 (Ib) E+= +0.08--0.091 pH El = +0.75-0.143 pH 0.161 0.367 6.3 Et = -0.60-0.100pH 0.098 0.603 5.7 (Ic) Ed = -0.18-0.077 pH Et = +l.l8-0.200 pH 0.170 0.348 5.9 El = $0.53-0.100 pH 0.071 0.832 6.4 (Id) E+= +0.03 -0.080 pH Ek = f0.96-0.167 pH 0.179 0.330 6.5 Ei = -0.59-0.100 pH 0.066 0.895 5.7 (re) E+= +0.06-0.083 pH Et +0.79--0.167 pH 0.162 0.365 6.4 Eb = -0.59-0.100 pH 0.095 0.622 5.7 (If) Eamp;= -o.o4--o.o9i PH Et = +0.65-0.200 pH 0.180 0.328 5.9 E+= -0.75-0.100 pH 0.070 0.844 6.9 (Ig) E+= +O.l4--0.86 pH EI = +1.05-0.25 pH 0.145 0.408 6.4 E+= -0.75-0.100 pH 0.102 0.579 5.7 (Ih) E+= +O.OP-0.071 pH E+= +0.25-0.167 pH 0.167 0.354 6.0 Ei :-0.97-0.08 pH 0.067 0.882 8.0 a Slope of logarithmic analysis.b Individual pH value at which logarithmic analysis was carried out. Ei in the first segemnt of wave b is pH-independent (dE+/dpH ca. 0). the analogous azobenzeiie deri~atives.l-~ This is also at the 4-position in hydrochloric acid giving 2-thio- confirmed by the fact that when c.p.e. experiments were hydantoin l7 derivatives thus indicating that the thio- carried out on this wave, the main products of electro-carbonyl group in position 4 is very reactive.Schemc 1 lysis were 5-amino-1-phenylhydantoin(111)and aniline, provides an interpretation of these results. At first glance two mechanisms I and 2 (Scheme 2) can be attributed to the electrode process occurring in wave 11. Mechanism 2 is rejected for the following reasons. When c.p.e. was carried out on wave b no ammonia could be detected. Also, if mechanism 2 took place, cornpourid 1.2 -1.0 , 1.0 c bsol; 0.8 I-IN 4r I 0.8-U ? 0.6,-'-.0.4 I, I I IJ 6 8 10 12 0.2-PH FIGURE Et-pH plot for the polarographic wave of the5 tmodel compouiicl 1-phenyl-4-thiohydantoin I1 1#11 1 11 a direct indication that the site attacked is the -N=N-6 8 10 12 group. The identification of the nitro-group in com-PH 6pound (Ih) as the source of the more negative wave is a FIGURE il-pH plot for the polarographic wave of the further indication that the reducible species is in the azo model compound 1-phenyl-4-thiohydantoin and not in the hydrazone form. If this was not correct (11)would be a main product of electrolysis and hence the the nitro-wave would appear first (this is further con-polarograms will consist of three waves in alkaline media firmed by the Hammett relationship). That 5-amino-l- cf.polarographic behaviour of (II). This is not the case phenylhydantoin (111) is the product and not 5-amino- since a third wave did not make an appearance. Thus J.C.S. Perkin I1 mechanism 1most probably explains the results for wave these molecules. The constant value of the transition b. Compounds containing the -CO-NH-CO- structure coefficient (ccn),19a prerequisite for quantitative study of have been reported to be reduced in a similar way.l* the effects of substituents, was ascertained by examina- tion of the data in Table 3. The value was found to be Acid medium pH pXo practically constant at individual pH values. The most reliable E, values at selected pH have been correlated FF2 1Le-3H' ArNH2 + H2NCH--C=S HI-ti20 HlNCH--C=OI I -4 II C6H5Nbsol;C/Nfd -ti,+ C6H5Nbsol;C/NH II ti0 0, (IV) cm, SCHEME1 The fact that in alkaline medium, i.c.at pH pK,, only wave a is observed is because in these media compounds with different Hammett constants.20 Statistical treat- (Ia--h) exist as stabilized anions in which the negative ment of the data was carried out using Jaffe calcul- charge is distributed over tlitl CS, N, and CO functions ations 21 (Tablc: 4). Representative Eb-o plots are Mechanism 1 Mechanism 2 H2NCH-CHOH H2NCH-C-0 II II C6H5N'"-c6H5N'KNH 4-H+ SCHEME2 rendering the molecule electron repelling. This also illustrated in Figure 7. As is clear from these plots and explains why wave b disappears in alkaline media. the data in Table 4 good linearity is obtained.Above Additional support for our electroreduction scheme was pH ca 7 the correlation is weak probably due to the fact found to be necessary. Thus it appeared mandatory that at the vicinity of these pH values (i.e. approximate to study the effect of substituents on the reaction site of pK, values) the studied compound is in the form of a TABLE4 Statistical treatment of Eg -0 data Wave a d 00 cr+ PH r--P h I' -7 s.d. r P h Y s.d. bsol; r-P A Y 7s.d. 4.8 0.266 0.807 5 0.069 0.224 0.586 t0.096 0.207 0.836 amp; 0.084 6.9 7.85 0.244 0.165 0.869 0.514 amp; 0.050*0.098 0.239 0.268 0.736 0.722 amp; 0.068 0.079 0.184 0.136 0.876 0.569 -f 0.0048 amp; 0.094 Wave b 5.8 0.104 0.363 f0.069 0.163 0.383 amp; 0.0681 0.072 0.377 0.068 6.6 0.091 0.357 3-0.065 0.093 0.245 amp; 0.0640 0.062 0.366 0.061 1981 349 wave a and the negative wave b.02-0/916 Received, 16th June, 19803 1.l.I.l.1,I.IIIII 1.0-p 0.244 Azoxy, Rzo and Hydrazo Compounds ' cd. S. Patai, Wiley, New r 0869 York, 1975, ch. 12, p. 443.-El z IV -sd '0.050 C. L. Perrin, ' Mechanisms of Organic Polarography ' in 08-' Organic Polarography ', eds. Y.Zuman and C. L. Perrin, P-KH, Interscience, New York, 1969, p. 203 W. U. Malikand P. N. Gupta, J. Electvounalyt. Chem., 1974,02-54, 417. F. J. Zsoldos, U.S.P. 3 346 446 (Cl. 167-17) (Chem. Abs., 1968. 68. 6082d).'H. Thielen;ann, Su. Pharm., 1971, 39, 8 (Ch~m.Abs., 1971, 75, 5638).3'.Elmore and T.D.A. Toseland, J. Chem. Soc., 1956, 188. !a lo H. T. S. Britton, ' Hydrogen Ions ', Chapman and Hall, London, 4th edn., vol. 1, 1955, p. 365. l1 J. J. vngane, J. nmev. Chem. Soc., 1945, 87, 1916. lBIT. Fcigl, ' Spot Tests ', Elsevier, Amsterdam, 1954, 4th ccln., vol. 2, p. 109. l3 W. M. Clark, ' The Deterinination of Hydrogen lolls ', Bailliere, Tindall and Cox, I,oiidon, 1928, 3rd edn., pp. 15, 22 and ,528. l4 Y.Zuman, ' Thc Elucidation of Organic Electrode Processes,' ed. I.. Meites, Academic Press, New York, 1969, ch. 11, p. 20. l5 J. M. Kolthoff and J. J. Lingane, ' Polarography,' Inter- scicnce, New York, 1952, pp. 202-297, 666-267. l6 H. Lund in M. M. Raizer, ' Cathodic Reduction of Nitro Compounds in Organic Electrochemistry,' Dekker, New York, 1973, ch. VlI, p. 315. l7 H. C. Carrington, J. Chewt. SOC., 1947, 684. I-'. Zuman and I,. Meites, ' Progress in l'olarography,' Wiley-Interscience, Ncw York, 1972, pp. 125--126. lo P. Zuman, ' Substitucnt Effects in Organic P'olarography,' Plenum Press, New York, 1967, p. 45. 20 C. D. Ritchie and W. 1;. Sagar, Prop. Phyr. Ovg. Ckn., 1964, 2, 334. 21 H. H. Jaffd, Chmz. Iw., 1953, 53, 191. p 0.091 r 0.357 s.d. 20.065 1.61 -08 -06 -04 -02 00 +02 +0.4 +06 +0.6 0-F~GURE LA-(r IWatioii for 5-arylazo-l-phcnyl-4-thiohydantoin7 derivatives at different pH values