Indian Journal of Chemistry Vol. 3SA, Januaryl999, pp.77-S I

Kinetic and mechanistic studies on the oxidation of

D-cycloserine by sodium N-bromobenzenesulphonamide in

hydrochloric acid medium

Puttas wamy *& S M Mayanna Department of Post-Graduate Studies in Chemistry

Central College, Bangalore Uni versity Bangalore, 560 00 I, India

and H C Sindhu Veerendra

Institute of Wood Science & Technology, Malleswaram, Bangalore, 560 O~, India

Received 18 May 1998; revised 3 November 1998

Oxid ati on of O-cyc lose rin e (C S) by sodium N­bromobenzenesulphonamide or bromamine-B (BAB) in HCI medium (0.1 to 0.6 mol dm·1) and constant ionic strength (O.S mol dm·1) has been investigated at 40°C. The rate is first order in [BABlo and is fractional order each in [CSlo and [W]. The reacti on is catalysed by chloride ion. Addi tion of reaction product, benzene sulphonamide and variati on of ioni c strength of the medium have no effect on rate. The reac ti on fai ls to induce the polymeri sati on of acrylonitril e. The rate constant increases with decrease in the di electri c constant of the medium. The rate increases in O2° medium and the in verse solvent isotope effect k (OP) / k( HP) = 1.70. Proton inventory studies made in HP-0 20 mi xtures have been employed to cal cul ate the isotopic fractionation factors. Composite acti vation parameters for the reaction have been determined from Arrhenius plot. Michaeli s­Menten type of kinetics is observed and acti vation parameters fo r the rate-limiting step have been computed. The proposed mechani sm assumes the simultaneous catalysis by H+ and C( ions and is consistent wi th the observed kineti c results.

Considerab le attention has centred around the chemistry of N-metall o-N-aryl sulphonamides because of their versatility in behav ing as mild ox idants, halogenating age nts and N­anions, which act both as bases and nucleophiles. However, there is meagre in formation in the literature l

-4 on bromamine­

Tand bromamine-B , particularl y with respec t to the ox idati on of antibi oti cs. Bromamine-B can be easil y prepared from the bromin ati on of chloramine-B and is found to be a better oxidi zing agent than the chl oro compound . The drug, 0 -

cycloserine is an antibiotic. The compound and its deri vatives have been oxidized anodically using glassy carbon electrodes; and the information about its kineti c and mechani sti c aspects is scanty. As a part of our mechanistic studies on the oxidation of D-cyc\oserine by N-bromamines , we report here in the

kinetics of oxidati on of D-cycl oserine (CS) with sod ium N­bromobe nzenes ulphonamid e (C"H 5S0~NBrNa 1. 5 Hp; RNBrNa ; bromamine-B or BAB) in HCI medium at 40°C.

Experimental Bromamin e-B (BAB ) was prepared !> by the par ti a l

debromination of dibromamine-B and its purity was checked iodometri ca ll y through its ac ti ve bromine co nte nt. The compound was further charac teri zed by it s DC FT-NM R spec trum (obtained on a Bruker WH 270-MHz nuclear mag netic resonance spectrometer) with D20 as solvent and TMS as the internal standard (ppm relati ve to TMS) 143.38 (C-I , Carbon attached to S atom), 134.30 (CH , para to the hetro atom), 13 1.26 (C-2,6), 129.3 1 (C-3,5). Aqueous sol utions ofBAB were prepared, standardized by the iodometric method and preserved in amber-col oured bottles, to prevent it s photochemical deterioration.

Aqueous solution of analar grade D-cyc\oserine (Sigma) of des ired strength was prepared afresh each time. All other chemicals used were of acceptable grades of purity. The ionic strength of the system was maintained at a constant high va lue (0.8 mol dm-1) using a concentrated solution ofNaCI0

4. Solvent

isotope studies were made with Dp (99 .4%) supplied by the Bhabha Atomic Research Centre, Mumbai, Indi a. Tripl y di stilled water was used for preparing all aqueous so lutions.

Kinetic procedure The kineti c runs were carri ed out in stoppered pyrex glass

tubes whose outer surface were coated bl ack to eliminate photochemical e ffects. Pseudo- first order conditi ons were maintained for the kineti c runs ([substrate]o » [ox idant]o) ' Solutions containing appropriate amounts of the substrate, HCI , NaCI0

4 and water (to maintain a constant total volume fo r all

runs) were taken in the tubes and thermall y equilibrated at 40oC. To thi s so luti on, was added a measured amount of standard BAB solution, also pre-equilibrated at the same temperature, to initiate the reaction. The reac ti on mi xtu re was shaken intermittently for uniform concentration. The progress of the reaction was monitored for more than two half- li ves iodometrica ll y. The pseudo-first order rate co ns tant s, k, calculated were reproducible within ± 3%. Regression analys is of the experimental data was carried out on an EC-75 statistical calculator to obtain the regress ion coeffi cient , r.

Stoichiometl), and product aI/a lysis Vari ous rati os o f BAB to cyc lose rin e ([ox id an t] »

[substrate]) were equ ilibrated in the presence of 0.2 mol dnr l HCI for 48 h. The determinati on of unconsumed BAB ex hi bi ted a 1:4 stoichiometry. (Eq. I)

78 INDIAN J CHEM, SEC. A, JANUARY 1999

- 10.0

- 9.0

i ~

- B.O c: ~ -0

- 7.0 ~ ---- 6.0

5.0 I I I I

a 0.2 0.4 0.6 O.B 1.0

Fig. I - Proton inventory plot for the oxidation of cycloserine by BAB in Hp-Dp mixtures

2 COl + 8 RNHl + 8 NaBr. .. . ( I )

The reduction product of BAB, benzenesulphonamide, among the reaction products was identified7 by thin-layer chromatography, using light petroleum-chloroform-II-butanol (2:2: I, v/v) as the solvent system and iodine as the spray reagent (Rr = 0. 88). The presence of one of the oxidation products, nitrile, was identifiedR by its specifi c colour reacti on with hydroxylamine and ferri c chloride. The evolving CO

2 gas was

detected hy the lime water tes t.

Results and discussion With the substrate in excess, at constant [ HCI J , [CSlo and

temperature, pl ots of log r BAB 1 versus time were linear ( r = 0.9965) indicating a first order dependence of rate on [ BABlf)" The pseudo-first order rate constant ( k = 2.20 X 10-4 s-I ) was increased with increase in [ CS lo from 1.33 X 10-4 to 3.28 X

10-) S-I in the range 0.02-0.07 mol. dm-). A plot of log k versus log [ CS lo was linear ( r = 0.9905 ) with a slope of 0.46, thus indicating a fractional order dependence on [CSlo Further, a plot of k versus [ CS 10 was linear ( ,. = 0.9926) with an intercept, confirming the frac ti onal order dependence on [ CSlo.

At fi xed r BAB land [CS], the rate of reaction increased with increase in [ HCll from 1.35 X 10-4 to 4.60 X 10-" S·I in the range 0. 1- 0.6 mol dn,-3. A pl ot of log k versus log [HCll was linear ( ,. = 0.9984) with a slope of 0.68. Further, a plot of k versus r HCI 1 was linear ( r = 0.9978) with an intercept

indicating a fractional order dependence on [ HCI l. When total [CI-l in the reaction mixture was kept constant at 0.6 mol dm-! by adding NaCI and[ W 1 was varied using HCI, the rate increased from 2.44 X 10-4 to 4.94 X 10-4 S-I with increase in [H+ 1 in the range 0.1 - 0.6 mol dm-!. A plot of log k versus log [W] was linear ( r = 0.9918) with a slope of 0.40 indicating the fractional order dependence on [H+]. At constant [H+] = 0.2 mol dm-! maintained with HCI, the rate increased from 2.20 X 10-4 to 3.45 X 10-4 S-I with the addition of NaCI in the range 0.2 - 1.0 mol.dm-J

. A plot of log k versus 10g[Cn was linear (r= 0.9947) with a slope of 0.28 indicating a fractional order dependence on [Cll Also, a plot of Ilk versus I I [CI-] was linear (r = 0.9948) with an intercept, indicating simultaneous catalysis by Cf ion. But addition of Br' ions in the form of NaBr ( 10 X 10-4

- 50 X 10-4 mol dm-) ) had negligible effect on the rate. Addition of the reaction product, benzene-sulphonamide (5 X 10-4

- 30 X 10 4 mol dm-) had no effect on the rate indicating that it is not involved in the pre­equilibrium with the oxidant. Variation of ionic strength (I ) of the medium by adding NaCI0

4 (0.2 - 1.0 mol dm-) did not

influence the rate. The reaction was studied at different temperatures ( 35-

500C) and from the linear Arrhenius plot (r= 0.9975) of log k versus liT, values of activation parameters, energy of activation (Eo ), enthalpy of activation (t.Ht ), free energy of acti vation (t.Ct ) and entropy of acti vation (t.s t ) for the over all (composite) reaction were calculated as 74.6, 72.0, 98.8 kJ mol-I and -77.3 JK' mol -I respectively. Rate studies in Dp medium showed that the reaction is faster in heavy water. The normal sol vent isotope effect k ( Hp)l k (Dp) = 0. 59 , The reaction was studied in H

20- D

20 mi xtures at 40"C under the

conditions [ BAB ]0 = I 0.0 X 10-4 mol dm-1, [CS]o = 3.0 X 10-2

mol dm -J, [HCI1= 0.2 mol dm-) and 1= 0.8 mol el mo) containing varying deuterium atom fracti ons II (0.000, 0.248, 0.496, 0.744 and 0.992) and proton in ventory pl ot relating the rate constant k""hS with 11 is shown in Fig. l.

The dielectric constant of the medium was varied by adding meth anol (0-40% v/v) to the reac ti on mi xtu re. The rate increased with increase in methanol content and a plot of log k versus liD where D is the relative permittivity ofthe medium was linear (r= 9922) with a positive slope. Bl ank experiments with methanol indi ca ted that oxidati on of methanol was neg li gible « 2%) by BAB under the experiment al conditions. This was taken into account in the calculati on of net reaction rate constant for the oxidati on of cycloserine each time.

Ol efinic monomers such as acrylonitril e and fr es hl y prepared 10% acrylamide soluti on, under nitrogen atmosphere, were add ed to initi ate po lymeri za ti on. The lac k o f polymerizati on indicated the ahsence of free rad icals in the reaclion mixture. Proper control experiments were al so run.

Cycloserine, hav ing zwilleri onic properties simi lar to amino ac idx, possesses two ioni zable groups with pKa, = 4.5 and pKa2 = 7.4. The zwiller ion ' b' is the predominant species in acidic soluti ons while the ani on 'c' and the cat ion 'a' are in excess in bas ic and highl y ac idic, media, respecti vely.

NOTES 79

+ +

a NH3 Ka1 [JNHJ

Ka2 QNH2 ~ -.:.. ....- ° ....,- 0,

'N ° 'N ° NAO H A

Q b c

The experimental rate law was found to be Rate = k[BAB] [CS]X [HC\]Y~ where x and yare fractions . Bromamine-B, being analogous9 to CAT, behaves like a

strong electrolyte in aqueous solutions and dissociates as:

RNBrNa RNBr' + Na+ .. . (2)

The anion picks up a proton in acidic solutions to give the free acid monobromamine-B, RNHBr (N-bromobenzene­sulphonamide):

RNBr' + H+ <=> K . RNHBr ; K, = 1.5 x 10.5 at 25°C. .. . (3)

The free acid has not been isolated . It undergoes disproportionation giving rise to benzenesulphonamide (RNH2) and dibromamine-B (RNBr2):

K~ 2RNHBr <=>

... (4)

Dibromamine-B and the free acid hydroly se to give hypobromous acid (HOBr) :

RNBrl + Hp <=> RNHBr + HOBr .. . (5)

Kh RNHBr + Hp <=> RNH) + HOBr; K" = 4.21 X 10" ... (6)

Finall y HOBr ionizes as

K" HOBr <=> H+ + OBr' ; K, = 2.0 x 10'Y at 25°C .. . (7)

The poss ible oxidizing species in ac idi fied BAB solutions are therefore RNHBr, RNBr2 and HOBr. If RNBr2 were to be the reacti ve species , then from Eq. (4) the rate law should pred ict a second ordcr dependence of rate on [BABJo' which is contrary to experimental observations. Further Eq. (6) indicates that the hydro lys is is sli ght and, ifHOBr is primarily invo lved, a first order retardati on of the rate by the added benzenesulphonamide is expec ted. However, no such effec t was noti ced. It is, therefore, probable that RNHBr is the reacti ve species. Calcul ati ons of Hardy and Johnston I on aqueous BAB and observations of Bishop and JenningsY and Morris et al'" on aqueous CAT soluti ons have clearl y shown that the conju ga te ac id is a predomin ant species in ac id so lutions of haloamines. Hence RNHBr is responsible for the oxidation of cycloserine.

The oxidation of cycloserine by BAB shows first order dependence of rate on [BAB]o and fractional orders in [CSJu'

[H+] and [Cr] . There is no involvement of ben zene­sulphonamide in pre-equilibrium with the oxidant and the absence of any ionic strength effect suggests that neutral species are taking part in the rate-limiting step. Based on the above observations, the mechanism of reaction is best explained by Scheme I which predicts simultaneous catalysis by H+ and cr ions":

KI RNHBr + H+ + CJ <=> RNH

1Br ... CI (i) fast

(X) K)

X+CS <=> X' (ii) fast k,

X' ~ X" (iii) slow & r1s k4

X"+ 3RNHBr ~ Products (iv) fast

Scheme I

Here X' and X" are complex intermediate species whose structures are shown in Scheme 2. Step (iii) determines the overall rate,

rate = -d [BAB)I dt = k, [ X' ) ... (8)

If [BABJ, represents the total concentration of the oxidant, then [BAB}, = [RNHBr) + [X) + [ X' 'J.

from which, solving for [ X J and substituting its value in (8), rate law (9) can be derived:

-d[BAB) rate = - - - .. . (9)

Rate law (9) is in agreement with experimental results. Equation (9) can be transformed as ,

k -k-',K-)-[C-S-] - [ K' [~'][Cl I .. ( I 0)

From the intercepts of the linear double rec iprocal plots of I lk versus I/[CSJo at fi xed [HCll , Ilk versus I/[WJ and Ilk versus II[CIl values of decompositi on constant k, for the rate­limiting step fo und were: 5.00 x 10.4 , 5.88 x 10:4 and 4.08 x 10.4

S· I , respectively, and were therefore comparable. The rate of reaction was fracti onal in [CSJ II' and so Michaeli s-Menten type of kineti cs l2 were followed by varying the [CSJo over a range oftemperature,35-50oC. From plots of Ilk versus I/[CS)o

80 INDIAN J CHEM, SEC. A, JANUARY 1999

12

10

I I

~

x ...., , S2

2

a 20 60 [CSJ -1

.0

0

35°C

80 100

Fig. 2 - Double reciprocal plots of Ilk versus II[CS]o at 35°, 40°, 45° and 50°C. [BAB]II = 10.0 X 10-4 mol dm-' [HCl] = 0.2 mol dm-3; 1= 0.8 mol dm-J •

(Fig.2), values of kl obtained were (x 104s-') : 2.56 (35°), 5.00 (4011 ),6.45 (4511

) a~d 8.33 (50°C). Activation parameters for the rate-limiting step were also computed from the Arrhenius plot of log kl versus I IT (r=0.9905) as Ea = 60.3, MI~= 57.7, t1G;< =81.7 kJ mol -I and ~S;<= -68 .2 JK -I mol-I.

The increase of rate in Dp supports the fast equilibrium hydrogen ion transfer "(step (i) of Scheme I ). The dependence of rate constant (kn ) on n, the atom fraction of deuterium, in a solvent mixture containing H

20 and D

20 is given'4 - '~ by

Eq.(II):

k" W S (l-n+n<1» J

... ( II)

where <1>i and <1>j are the isotopic fractionation factors for isotopically exchangeable hydrogen sites in the transition and reactant states, respectively. It is assumed that the reaction proceeds through a single transition state, Eq( 11) can be transformed into Eq( 12):

[ k" I k n ] 112 = [ I +n (<1> .-1 ) ] J

.. . ( 12)

The plot of (k"l kn )"2 versus 11 (Fig. I ) is linear (r= 0.9918) with a slope (<1> . - I ) = -0.40. The transition factor of H+ is thus

J 0.60, a value in good agreement with the values reported by earlier workers ' 7. 'x.

A detailed mechanistic interpretation of the DCS-BAB reaction in acid medium is presented in Scheme 2, where the interhalogen intermediate species (X) formed from RNHBr and H+ and Cr, reacts with the substrate to form the substrate­BAB complex (X'). This decomposes in a rate limiting step

+0 R-NHBr +H-CI

(±)

R -NH, -Br o a

H (±)

...,

O~/NH~ +R-NH

~N . '

H

(XU)l H,O .

NH

(

H I

R- N -Br (±)I

o H a

(X)

k,

II . HO CH, - C - COOH + NH,OH

loco,

(±) R-NH,-Br o . a

HOCH,-CH=NH +RNIlBr~ HOCH,C ;;: N + RNH,

HO CH, - c;;: N + RNHDr ----7 OHC-C;; N + RNH -IlBr '

2NII,OH + 2 RNHDr ---'- N ° + 2RNH + HCI + H O@ . / 1 J J

Scheme 2

to give a cationic intermediate species (X"), which undergoes hydrolysis and decarboxylation followed by further oxidation to yield the ultimate products.

The rate increases with decrease in dielectric constant of the medium indicating a charge dispersal in the transition state, which is less polar than the reactants. The proposed mechanism is also supported by the moderate values of energy of activation. The fairly high positive value offree energy of activation and enthalpy of activation indicate that the transition state is highly solvated, while high negative entropv of activation sucrcrests

'-' -' bb

the formation of the compact activated complex. The constancy of rate constant on addition of neutral salt or reaction product also supports the proposed mechanism.

References

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6 Ahmed M S & Mahadevappa D S , Talanta , 27 ( 1980) 669.

NOTES

7 Mahadcvappa D S & Gowda N M M , Talall/(I , 22 ( 1975)77 1.

8 Gowda N M M , Rangappa K S & Mahadevappa D S, Analyst, III (1986) 1423; Weintsein B, Chemistry alld bioc/rell1isll), of all1il lO acids peptides alld proteins, Vol I, (Marcel Dekker, New York) (197 1 )24.

9 Bishop E & Jennings V J , Talanla , I (1958) 197.

10 Morri s J C, Salazar J A & Wineman M A , J Alii chem Soc, 70

( 1948)2036.

II Bell R P, Acid-base catalysis , (Oxfo rd Universit y Press, London), 194 1, 49.

12 Laidl er K J , Chem.ical kinetics, (Tata-McGraw Hill , Bombay), (1965)474.

13 Collins C J & Bowman N S, Isotope e.lfect ill chemical reactiolls (Van Nostrand-Rei nhold , New York) , (1970) ,267 .

14 Albery W J & Davies M H , J chelll Soc , Faraday Trail s, 68 (1972) 167.

15 Gopalakri shnan G & Hogg J L , J org Chelll , 50 (1985) 1206

16 Isaccs N S, Physical organ ic chemistl )" (Wiley, New York ), ( 1987)275.

17 Kresge A J & All red A L , JAm chelll Soc, 85 (1963) 1541 .

18 Gold Y., Proc.cliel11 .Soc., Londoll. ( 1963) 141.