Iodosobenzoate-Microemulsion Reagents for the Cleavage of a

Sep 15, 2016 - Bu, and Oct), cleaved p-nitrophenyl diphenyl phosphate (PNPDPP) ... with second order cleavage rate constante ranging from 31 to 531 M-...
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Langmuir 1993,9, 2902-2906

2902

Iodosobenzoate-Microemulsion Reagents for the Cleavage of a Reactive Phosphate Robert A.

MOSS,*

Ryoji Fujiyama,’ Hongmei Zhang, Yong-Chan Chung, and Karen McSorley

Department of Chemistry, Rutgers, The State University of New Jersey, News Brumwick, New Jersey 08903 Received April 30, 1993. In Final Form: July 12, 1 9 9 9 The N-alkyl-N-methyl-N~-bis(3-carboxy-4-iodoso)benzyla”oniumbromides, 4-OH (R = Me, Et, Bu, and Oct),cleavedp-nitrophenyldiphenyl phosphate (PNPDPP)in micellar cetyltrimethylammonium (CTA) chloride at pH 8,25 “C, with second order cleavage rate constante ranging from 31 to 531 M-’s-l. For the most reactive catalyst, 4-OH (R = Oct), we observed a 300-fold rate enhancement, relative to the rate in the absence of both 4-OH (R= Oct) and CTAC1; the contributionof the iodoso reagent was a factor of 92, relative to micellar CTACl alone. The same reagentswere also examined in a microemulsionof 4.5 % CTABr, 4.5% N-methylpyrrolidone,1%toluene, and 90% pH 9.3-9.4 aqueow borate buffer. Catalysis by 4-OH was reduced in the microemulsion,with the maximum second-orderrate constant for PNPDPP cleavage (4-OH,R = Oct) = 21 M-I s-l. However, 5-foldexcess substratecouldbe cleaved with no diminution in rate constant; i.e., the catalyst turned over rapidly.

Introduction Ten years ago, we reported that an aqueous micellar solution of cetyltrimethylammonium chloride (CTAC1) and o-iodosobenzoate (IBA), in its closed, 1-oxido-1,2benziodoxolin-&one valence tautomeric form (l),was a potent nucleophile and true catalyst for the hydrolysis of reactive esters or phosphates, e.g., p-nitrophenyl diphenyl phosphate (PNPDPP, 2Is2Given that the destruction or

decontamination of phosphate and phosphonate toxins is a pressing and ongoing problem: and that micellar IBA is catalytically active against several nerve agents: there has been continuing interest in the development of new IBA reagents. In addition to intensive studies of micellar IBA systems,- alternative vehicles for IBA delivery have been examined, including liquid crystals: cationic latex dispersions,1° and vesicles,l’ as well as IBA immobilized by covalent attachment to silica ge1,12titania,13nylon,13 a Abstract

published in Advance ACS Abstracts, September 15,

1993. (1) Visiting Professor from Kochi University, Kochi, Japan. (2) Moss, R. A,;Alwis,K. W.; Bizzigotti, G. 0.J. Am. Chem. SOC.1983, 105,681. (3) Chem. Br. 1988, No. 7 (July), 657-691. Ember, L. R. Chem. Eng. News 1990 (Aug. 13), 9-19. (4) Hammond, P. S.;Forater, J. S.; Lieske, C. N.; Durst, H. D. J. Am. Chem. SOC.1989,111, 7860. (5) Moss, R. A.; Alwis, K. W.; Shin, J. S. J. Am. Chem. Soc. 1984,106, 2651. (6) Moss, R. A.; Kim, K. Y.; Swarup, S. J. Am. Chem. SOC.1986,108, 788. .

(7) Katritzky, A. R.; Duell, B. L.; Durst, H. D.; Knier, B. L. J. Org. Chem. 1988,53,3972. (8) Bunton, C. A.; Mhala, M. M.; Moffatt, J. R. J. Phys. Chem. 1989, 93, 854. (9) Ramesh, V., Labes, M. M. J. Chem. SOC.,Chem. Commun. 1988, 891, and references therein. (10)Ford, W. T.; Yu, H. Langmuir 1991, 7,615. (11) Moss, R. A.; Ganguli, S. Tetrahedron Lett. 1989,30, 2071. (12) Moss, R. A.; Chung, Y.-C.; Durst, H. D.; Hovanec, J. W. J.Chem. SOC.,Perkin Trans. 1 1989,1350. (13) Moss, R. A.; Chung, Y.-C. J . Org. Chem. 1990,55, 2064.

0743-7463/93/2409-2902$04.00/0

polymers,14or ion exchange resins.I6 IBA analogues have also been studied.ls Solid-immobilized IBA derivatives may be applicable to the decontamination of small ‘spills” of toxic agents, but the destruction of large quantities (‘stockpiles”) will require IBA formulationswith very substantialsolubilizing capacity for both IBA and the agent. From this practical viewpoint, IBA-microemulsionscommand a t t e n t i ~ n . ’ ~ - ~ ~ An oil in water microemulsion(ME) is generallycomposed of water, “oil” (eg., a hydrocarbon), an ionic surfactant, and a cosurfactant (often an alcohol, but see below)J2Its internal structure may be described as a stable collection of 60-600 A diameter oil droplets surrounded by 20-30 A thick surfaces composed mainly of surfactant ions and cosurfactant.22aThis region is roughly comparable to the Stern layer of surfactant micelles,and it is at this interface that polar reactions are expected to occur. On the other hand, hydrophobic substrates will be solubilized within the ‘oil droplet” interior and will have to emerge to the interface region to react with polar or ionic reagents. Moreover,the “concentration”of reactant and substrate in the larger ME will be less effectively translated into kinetic enhancement than in the smaller micellar aggregates. As a trade-off for its enhanced solubilizationcapacity, we thus expect lower reaction rate constants in the ME in comparisonto analogousmicelles.’7 The group at the US. Army Chemical Research Development and Engineering Center, Aberdeen Proving Ground, has intensivelyexamined ME’Sas media for IBA~~

(14) Moss, R. A.;Bolikal, D.; Durst, H. D.; Hovanec, J. W. Tetrahedron Lett. 1988,29, 2433. (15) Moss, R. A.; Chung, Y . 4 . Langmuir 1990, 6, 1614. (16) Moss,R. A.; Chattejee, S.;Wilk, B. J.Org. Chem. 1986,61,4303. (17) Mackay, R. A.; Longo, F. R.; Knier, B. L.; Durst, H. D. J.Phys. Chem. 1987, 91, 861. (18) Burnside, B. A.; Szafraniec, L. L.; Knier, B. L.; Durst, H. D.; Mackay, R. A.; Longo, F. R. J. Org. Chem. 1988,53, 2009. (19) Burnside, B. A.; Knier, B. L.; Mackay, R. A.; Durst, H. D.; Longo, F. R. J. Phys. Chem. 1988,92,4505. (20) Garlick, S. M.; Durst, H. D.; Mackay, R. A.; Haddaway, K. G.; Longo, F. R. J. Colloid Interface Sci. 1990,135, 508. (21) Panetta, C. A.; Garlick, S. M.; Durst, H. D.; Longo, F. R.; Ward, J. R. J. Org. Chem. 1990,55,5202. (22) (a) Mackay, R. A.; Letts, K.; Jones, C. In Micellization, Solubilization, and Microemulsions; Mittal, K. L., Ed.; Plenum Press: New York, 1977; Vol. 2, pp Solf. (b) Fendler, J. H. Membrane Mimetic Chemistry; Wiley: New York, 1982; pp 69f.

0 1993 American Chemical Society

Idosobenzoate-Microemulsion Reagents catalyzed hydrolysis of PNPDPP. In an oil in water ME composed of 18% CTABr surfactant, 18% 1-butanol cosurfactant, 4% n-hexadecane oil, and 60% 0.03 M aqueous borate buffer, IBA catalyzed the cleavage of PNPDPP with an average rate constant of 1.22 f 0.07 M-' s-l between pH 8.5 and 10.5, about twice as fast as in water, and 10-fold faster than the background PNPDPP hydro1ysis.l' Catalytic IBA turnover was demonstrated, but CTACl micellar IBA was -loo0 times more reactive toward PNPDPP than IBA in the CTABr ME'8.l' Further studies varied the ME composition and IBA structure to optimized substrate solubilization and hydrolytic rate. A ME composed of 19.7% CTAC1,17.9% Adogen 464 cosurfactant (a mixture of octyldecyltrimethylammoniumchlorides), 13.1% hexadecane, and 49.2 % 0.03 M aqueous borate at pH 8.96 gave ~ I B A = 10.1 M-l s-1 for the cleavage of PNPDPP.19 From the kinetic perspective, Adogen was a better cosurfactant than N,Ndibutylformamideor 1-butanol. Increasing the aqueous componentto 89 % enhanced ~ I B Ato 20.3 M-l s-l, with the ME probably approximating the structure of a CTA micelle.19 It was also observed that p-nitro-IBA was a somewhat better catalyst than IBA in a CTACl/Adogen/ hexadecane ME.19 Continued refinement led to the introduction of a CTABr,N-methylpyrrolidone(NMP),toluene, and borate buffer ME formulation. The NMP cosurfactant afforded effective penetration of polystyrene and poly(methy1 methacrylate), so that NMP-containing ME'S should be useful against nerve agents "thickened" with these polymers and resistant to simple aqueous decontaminants. Moreover, 90% aqueous CTABr-NMP-toluene ME'S afforded kmA 25 M-' s-l for PNPDPP cleavage, so that the kinetic properties were also excellent. Of particular interest to the present study is the report of Panetta et al. concerning PNPDPP cleavage in a ME consisting of 8% CTABr, 8% NMP, 4 % toluene, and 80% 0.03 M aqueous borate at pH 9.4.21 The catalyst was IBA or a 4-alkyl IBA derivative, 3. Surprisingly, the kinetic potency of 3 decreased as R increased in length; kmA was maximized at R = Et. The observed rate constants (M-l s-l) were as follows (R=): H, 12.4;Me, 18.6;Et, 22.9; n-Pr, 0.013, n-Pent, 0.026, n-Oct, insoluble.21

-

R

In these ME IBA/PNPDPP reactions, the PNPDPP substrate mainly resides in the ME'Soily interior, whereas the IBA, which is anionic at pH > 8 (PKa = 7-7.6), is partitioned between the CTA head group (Stem layer) region and the aqueous phase.19v20 IBA-PNPDPP reactions will occur at the oil/Stern layer interface and will be sensitive to factors that affect the phase distribution of the IBA. Presumably, the hydrophiliehydrophobicbalance of 3, R = Et, is optimal to set the average binding site of the catalyst near the critical interface. As R decreases (Me or H), the IBA locus presumably moves outward toward the aqueous phase, whereas, if R lengthens (Pr, Pent), the IBA may be taken deeper into the oily interior. In either event, reaction'with the PNPDPP, will be inhibited.21 We have also designed an IBA reagent with adjustable hydrophobicityfor depolymentin a ME. In our approach, we decided not to vary the IBA residue,2l which is

Langmuir, Vol. 9, No.11,1993 2903 Scheme I RNHMe. THF.

5, THF 8090°C. 3-8 d. waled tube

o c , 3-4 d, sealed tube. then lC%a?.NSHcQ 80.90

5

\

\

-

7

R

-

4-OH

Me. Et. Bu. o*

syntheticallydemanding. Rather, we constructed a family of ammonium ions derivatized with IBA residues. The "duplex" iodosobenzoate reagents, 4, are net anionic in their reactive form, readily synthesized, hydrophobically adjustable by the selection of R, reactive toward PNPDPP in ME'S, and exhibit a relatively "normal" dependence of reactivity on the chain length of R.

0. R

-

' 2

4

Me, Et, Bu, Oct

Results synthesis. Reagents 4 were prepared as shown in Scheme I. An alkylmethylamine was quaternized with 5,= in THF (EtOH ethyl 5-(bromomethyl)-2-iodobenzoate, when R = Me) affording the tert-amine hydrobromide,6. Without purification, 6 was neutralized and quatemized a second time with 5 to give the bis(iodobenz0ate)quaternary salt, 7. Oxidation of 7 with 32% peracetic acid24yielded the desired iodosobenzoic acid, 4-OH.26 Compounds 7 were purified by recrystallization and characterized by NMR spectroscopy and elemental analysis. Compounds 4-OH were purified by repetitive washing with water, followed by lyophilization. Iodometric titration26gave 96-107 % of iodoso activity for 2 equiv of "14". pa.. The PKa values of iodosobenzoic acids, in their closed, benziodoxolinone form, generally fall in the range of 7-82*5*27 in CTA micellar solution. Indeed, when the PKa of 4-OH (R = Me) was assessed by means of a pHrate constant profile,S~~~ the expected result was obtained. Thus, 1 X 10-4 M 4-OH (R = Me) in 0.02 M aqueous phosphate buffer ( p = 0.08, NaCl, 25 OC), containing 5 X 10-4M CTAC1, was used to cleave 1X 106 M PNPDPP at six different pH values ranging from 7.0 to 8.5. Pseudofirst-order rate constants were spectrophotometrically determined by following the release of p-nitrophenoxide ion (PNPO-) at 400 nm, affording the correlation of log k ~vs, pH that appears in Figure 1. The clear discontinuity at pH 7.54 can be taken as the systemic pKaof 4-OH (R= Me) under the micellar reaction conditions. This PKa is consistent with previous observations for "closed", benzidoxolinone-formiodosobenzoic (23) Synthesis of the methyl eater analogue of 6 ia described in detail in ref 13. The preparation of 6 waa identical except for an esterification step that employed ethanol in place of methanol. (24) Sharefkin, J. G.;Saltzman, H. AM^. Chem. 1963,36,1428. (25) For the direct oxidative conversion of iodobenzoata eaters to iodosobenzoates, aee: Moss, R. A,; Scrimii, P.; Bhattacharya, 5.; Chatterjee, S. Tetrahedron Lett. 1987,28,5005. (26) Lucas, H.J.; Kennedy,E. R.;Formo,M.W. In Organic Syntheses; Horning, E. C., Ed.;Wiley: New York, 1956; Collect. Vol. 3, p 483. (27) Moes,R.A.;Wilk,B.;KroghJeapersen,K.;Blair,J.T.;Westbrook, J. D.J. Am. Chem. SOC.1989,111, 250.

Moss et al.

2904 Langmuir, Vol. 9,No.11,1993

The problem is eased by our further observation that an analogoustitration of iodosobenzoicacid itself (1-OH), fist adjusted to pH 2.8by the addition of HC1, also affords adibasic acid titration curve, very similar to that of Figure 2,with pK,‘s at 4.0 and 7.6. Here, we suggest that the lower pKa reflects the formation of 8a, or a derivative thereof. Note that 8a could come from (dihydroxyiod0)arene, 8b, formed from 1-OH at low pH.30 The higher pH

-2.4

-2.5

Y

-

-2.6

-2.7

8a

-2.E

7 5

7 0

8 0

8 5

9.0

PH

Figure 1. pH-rate profile for the cleavage of PNPDPP by 1 X 10-4M 4-OH (R = Me) in 5 X 10-4 M CTAC1: log kt (d)vs pH. The discontinuity at pH 7.5 may be taken as the systemic pK, of 4-OH (R = Me). See text for other reaction conditions. ’-

I

I

8b

neutralization corresponds to the usual 1-OH * 1 ionization. The latter, of course, is crucial to the catalytic activity of the iodosobenzoates.2 Moreover, we suggest that the titration behavior of 4/4-OH (Figure 21,which is analogousto that of l/l-OH, can be similarly interpreted. We need therefore consider only the 4-OH +4 equilibrium in our pH 8 kinetic studies. Although the (higher) PKa values of 4-OH (R = Me, Et, Oct) fall in the normal iodosobenzoate range, it is interesting to note that they are 0.6-1 unit higher than that of surfactant iodosobenzoate9, which has an unusually low PKa (6.45)in micellar CTAC1.6 Both 9 and 4 have ammonium ion centers located near their iodosobenzoate residues. The cationic centers should lower their pKa)s. However, 9 and 4 differ in charge type: 9 is a zwitterion at pH 8,whereas ionization of both iodosobenmateresidues of 4-OH would.render 4 anionic. This difference may account for the latter’s higher PKa. We also imagine that binding to and ion pairing with the CTA cations of the micelles should mitigate some of the unfavorable electrostatic interaction between the two anionic iodosobenzoate residues of 4. U

I

2 1

0

1

3

2

4

5

mL NsOH

Figure 2. Titration curve for 4-OH (R = Oct): pH vs mL of

NaOH titrank see text for conditions. The apparent pK.’s are 3.8 and 7.1.

a ~ i d s , 2and ~ ~suggests ~ ~ ~ -that ~ the iodmbenzoate moieties of 4-OH would be about 74% ionized to the catalytically active 1-0- form (4) at pH 8. Surprisingly,however, classical titrations of 4-OH (R = Et or Oct) indicated two ionizations,with pK2s at 3.7-3.8 and 7.1-7.3. In these experiments, 1 X 103 M 4-OH in 0.01 M aqueous CTACl solution, 0.08 M in NaC1, was titrated with 0.0128 N NaOH against a glass/calomel combination electrode. The titration curve for 4-OH (R = Oct) is illustrated in Figure 2;very similar results were obtained for the R = Et analogue. Two equivalence points are plainly visible in Figure 2, with corresponding half-neutralization points (pK,’s) at 4.2 and 7.1. The total titrant required for both neutralizations corresponds to 110 9% of 2 equiv, calculated for a dibasic acid form of 4. Whereas the high pKa is in reasonable agreement with both literature precedent29sin-* and the experimentalvalue determined from the pH-rate constant profile (Figure l), the lower value is unexpected and correspondsto a considerablystronger acid than 4-OH.

-

(28) Baker, G.P.; Mann, F. G.; Sheppard, N.; Tetlow, A. J. J. Chem. SOC. 1966,3721, and references therein. (29) Katritzky, A. R.;Savage, G. P., Palenik, G. J.; Qian, K.; Zhmg, 2.;Durst, H. D.J . Chem. Soc., Perkin Trans. 2 1990, 1657.

Kinetic Studies. The phosphorolytic properties of the duplex iodosobenzoates, 4, were assessed in both CTACl micellar solutions and ME’S. For purposes of comparison the CTACl studies were carried out under conditions ~~J~~~~ identical to those of several prior i n v e ~ t i g a t i o n s : ~141 = 1X 10-4 M, [PNPDPPI = 1 X 1 P M, pH 8.0,0.02 M phosphate buffer, p = 0.08 (NaCl),25 OC. The reactivities of 4 were then determined from full rate constant[surfactant] profiles, where [CTAClI was varied over 11 concentrations that ranged from 5 X 10-5 to 2 X le2M. The results for 4 (R = Et, Bu, and Oct) appear in Figure 3; the behavior of 4 (R = Me) was very similar to that of ita Et analogue. All of the catalysts displayed their maximum kinetic activity at [CTACl] = (3-5) X 10-4 M. In Table I, we collect the key kinetic data for the micellar cleavage reactions. Duplicate rate constant determinations generally agreed to within 5-10%. Judged either from k+ or from the “catalytic” rate constants (weighted for [41), catalyst 4 (R = Me) appears to be slightly more reactive toward PNPDPP than 4 (R = Et), but the anticipated31 increased reactivity of the longer chain reagents clearly appears in the ordering (R=)Oct > Bu > Me Et.

-

~~~

(30) An equilibrium between 8b and the “open”,iodosyl form of 1/1OH should exist in acidic water: Varvoglis, A. The Organic Chemistry ofPolycoordinated Zodine;VCH Publishers, Inc.: New York, 1992;p 131. (31) Fendler, J. H.;Fendler, E. J. Catalysis in Micellar and Macromolecular Systems; Academic Press: New York, 1975; pp 98ff.

Idosobenzoate-Microemulsion Reagents

Langmuir, Vol. 9, No. 11, 1993 2905

50

40

30

20

10

0 4

0

9

14

24

19

lWO[CTACl],M

Figure 3. Pseudo-first-order rate constants (k+,s-l) for the cleavage of PNPDPP by 1 X 1 V M 4-OH (R= Et), (R= Bu), and (R = Oct), aa a function of [CTACl] at pH 8.0. See text for reaction conditions and Table I for k+- values. Table I. Cleavage of PNPDPP by Iodosobenzoate 4 in Micellar CTACP

R in 4 103k&-,b s-l Me Et Bu Oct

3.06 2.38 8.93 53.1

lOWTAC11,’ M l@ko,d s-l 5.0 1.80 3.0 1.51 3.0 1.80 5.0 f

M-l s-l 30.6 23.8 89.3 531

k2f

Conditions: pH 8.0,0.02 M phosphate buffer, p = 0.08 (NaCl), 25 “C, [4] = 1 X l0-l M,[PNPDPP] = 1 X lo-4 M. Maximum observed pseudo-fiit-order rate constant for PNPDPP cleavage; see Figure 3. These data are not corrected for the extent of ionization of 4-OH to 4. To correct for complete ionization, divide by -0.73. [CTACI] at which k+- was observed. ko is the rate constant in the absence of CTACl. e k2 = k*-/ [4]. f ko could not be determined due to the insolubility of 4 (R = Oct). Table 11. Cleavage of PNPDPP by Iodosobenzoate 4 in a Microemulsion.

R in 4 Me Et Bu Oct

103k&,b s-l 0.87e 0.46 0.66 2.1

k2: M-1 s-l 4.3 4.6 6.6 21

103kd (excess PNPDPP)? 5-1 0.45 0.47 0.75 2.3

O4.5% CTABr, 4.5% NMP, 90% pH 9.3-9.4 0.03 M aqueoua sodium borate, 1% toluene, [4] = 1 X 10-l M, [PNPDPP] = 1 X 106 M. Observed pseudo-fiit-order rate constant for PNPDPP cleavage. kz = k+/[4]. 141 = 1 X 1@M, [PNPDPP] = 5 x 10-l M.e 141 = 2 X 10-l M, [PNPDPP] = 2 X 10-5 M.

From the k+”/ko ratios, we can ascertain the extent of micellar catalysison the 4/PNPDPP cleavages. The ratios are (R=) Me, 17;Et, 16;and Bu, 50. (ko could not be determined for 4 (R = Oct) due to its insolubilityin water.) Again, as expected,3l the reactivity of the catalyst with the longest hydrocarbon chain is most strongly amplified by the CTACl micelles. Next we examined the duplex iodosobenzoatesin a ME composed of 4.5% CTABr, 4.5 5% NMP, 1 % toluene, and 90% aqueous borate buffer, pH 9.3-9.4.20Borate buffer was used to provide continuity with previous studies.19-21 In this ME, Garlicket al. observed a cleavage rate constant of 25.1 M-l s-l for the reaction of 1 with PNPDPP, the maximum value observed over many different compositions of this ME.20 This kinetic result was also superior to those obtained with iodosobenzoate in CTACl/Adogen/ hexadecane/water ME’s.l9 Our ME results appear in Table 11. Under conditions where 141> [PNPDPP], k+ and kp are considerablysmaller in the ME than in micellar CTACl, and the disparity increases with increasing chain length of R. The ratios

k+(ME)/&+(CTACl) are (R=) Me, 0.28;Et, 0.19;Bu, 0.074; and Oct, 0.040 (cf. Table I1 vs Table I). We caution, however, that although k+ has been optimized in the micellar cases, the rate constants obtained in the ME are not necessarily maxima because only a single ME composition was examined (albeit the composition that produced a maximum rate constant for the l/PNPDPP cleavage20). Finally, to test the ME under “combat conditions”,we examined the cleavage reaction with excess substrate, i.e. where [PNPDPPI/[4] = 5. Except for the case of 4 (R = Me), the longer chain catalysts exhibited no reduction in k+ when the [substratel/ [catalyst] ratio was increasedfrom 1:lO to 5:l. Moreover, no ”burst kinetics” were observed under the latter conditions,so that the continuingcleavage of PNPDPP was not rate limited by the hydrolyticturnover of phosphorylated 4.32 Burst kinetics are generally not found for CTACl catalyzed PNPDPP cleavage by 1or its 5-octyloxy derivative2I6but surfactant iododsobenzoate 9: as well as certain immobilized iodo~obenzoates,~~J5 do exhibit this behavior.

Discussion Reagents 4 are effective catalysts for the cleavage of PNPDPP in micellar or ME aggregates. These Yduplex* iodosobenzoateswere designed with ease of hydrophobic/ hydrophilic adjustment and their capacity toward excess substrate as our key concerns; absolute reactivity was a secondary factor. Accordingly, in micellar CTAC1, the most reactive example of 4 (R = Oct) is only about as reactive as the parent iodosobenzoate,1: = 0.053s-l for cleavage of PNPDPP by 4 (R = Oct), whereas it is 0.064 s-l for l.2J Indeed the micellar reactivity of 4 (R = Oct) is far less than that of 5-octyloxy-1 (k+” = 1.03s - ~ ) ~ or surfactant iodosobenzoate 9 (1.14 s-~).~In the latter case kineticcomparison of kp’s gives an advantage of 285oO/ 531 = 54 in favor of 9 over 4. From Table I, we can assess the extent of the micellar amplification of the reactivityof 4 as a functionof [CTACl]; ratio varies from 16-17 (4, R = Me or Et) to the k+max/k~ -295 for R = O C ~This . ~ “normal” ~ micellar response to increasing chain length28most likely reflects the greater hydrophobicity and enhanced binding of the octyl derivative of 4. In the absence of 4, but in the presence of (2-8) X 10-4 M CTAC1, the cleavage of PNPDPP shows k+ 5.8 X 10-4 s - ~ .The ~ contribution of 4 to the rate enhancement in micellar CTACl therefore ranges from 4.1 (R = Et) to 92 (R = Oct). In the CTAB/NMP/toluene/borate ME (Table 11), iodosobenzoates4 are 5 (R = Et) to 25 (R = Oct) times less reactive toward PNPDPP than they are in micellar CTAC1. This loss of reactivity in the ME is typical17but is a necessary trade-off to obtain the enhanced solubilizing power of the ME relative to the micelle.17 In the absence of 4, the cleavage of PNPDPP in the ME proceeds with k+ = 2.4 X 10-4d,so that the catalysis due to 4 in the ME ranges from -2 (R = Et) to -8.8 (R = Oct). Of particular importance is the ability of 4 (R = Oct) to catalyze the cleavage of &fold excess PNPDPP with turnover and with no decrease in kobsewed when [41 > [PNPDPP]. This is encouraging for the practical utility of 4-ME against fluorophosphonate nerve a g e ~ ~ t s . ~ * ~ Moreover, although simplealkyliodosobenzoates, 3, do not respond to chain length in a “linear”fashion,2l the duplex

-

(32) Reactions in the presence of excess substrate were followed to 46% of total PNPDPP cleavage, with UV monitoring at 450 nm. (33) We assume that ko = 1.8 s-I for 4 (R = Oct); ko show little

dependence on chain length, so that we take the ko value for the octyl derivative as comparable to that of its butyl analogue.

Moss et al.

2906 Langmuir, Vol. 9, No. 11, 1993

catalysts, 4, exhibit the same Oct > Bu > Et kinetic sequencein the ME'S as in the CTACl micelles. It remains to be seen whether still longer R groupswill further enhance the reactivity of 4.34

Vacuum drying afforded 7-OH (R= Oct), mp 146147 OC (dec). NMR (6, DMSO-de): 0.85 (crude t, 3 H, Oct-CHa), 1.24 (m, 8H, 2.96 (s,3 H, MeN+), 3.12 (m, (CH2)4), 1.6-2.0 (m, 4 H, (CHZ)~), 2 H, CHzCHzN+),4.72 (ABq, J = 12 Hz, 4 H, 2ArCH2N+), 7.93 (d, J = 7.9 Hz), 8.11 (d, J = 7.9 Hz), 8.20 (8). The latter three resonances are 2H each, aromatic protons. Experimental Section N,N-Dimet hyl-N,N-bis( 3-carboethoxy-4iodo)benzylammonium bromide, 7 (R = Me). This material was obtained General Methods. Melting points and boiling points are from 5 and amine 6 (R = Me) by reflux in 40 mL of dry EtOH uncorrected. NMR spectra were determined on a Varian VXRfor 30 h. Recrystallization 3 times from acetonitrile/ether 200 instrument at 200 MHz; chemical shifts are reported relative afforded 60% of 7 (R = Me), mp 186-188 OC. NMR (6, DMSOto internal Mersi in CDCl3 or DMSO-de. A Beckman Model &): 1.32 (t,J = 7 Hz, 6 H, ~ O C H Z C H2.91 ~ ) , (s,6 H, 2 X MeN+), 3560 digital pH meter was used to obtain the titration curve 4.33 (9,J = 7 Hz, 4 H, 2 OCHzCHa), 4.61 (8, 4 H, 2ArCHzC&), shown in Figure 2. TLC analyses employed Aldrich precoated 4.61 (s,4 H, 2ArCHN+),7.45 (d, J = 8 Hz), 7.85 (E), 8.13 (d, J polymer silicagelplateswith fluorescentindicator. Microanalyw = 8 Hz). The latter three resonances are 2H each, aromatic were performed by Robertson Laboratory, Madison, NJ, or protons. Quantitative Technologies, Whitehouse, NJ. CTACl was obAnal. Calcd for CzzHlsBrIzNO4: C, 37.6; H, 3.73; I, 36.2. tained from Eastman and purified by recrystallization from Found C, 37.5; H, 3.91; I, 36.0. methanol/ether. CTABr was a product of Sigma and was N-Ethyl-N-methyl-N,N-bis(3-carboethoxy-4-iodo)ben~ recrystallized 3 times from methanovether. Other commercially lammonium bromide, 7 (R= Et). This material was obtained available solvents and reagents were reagent grade and were used from 5 and amine 6 (R = Et) by stirring in dry THF in a sealed as received. Carius tube at 80 OC for 3 days. Removal of solvent and Syntheses. Duplex iodosobenzoate reagents 4-OH (see recryetallization from CHCWether (3X) gave 76% of 7 (R= Et), Scheme I) were all prepared by similar reactions. Therefore, we mp 164-166 OC (dec). NMFt (6, CDCb): 1.40 (t,J = 7 Hz,6 H, describe the synthesis of the octyl derivative in detail but present 20CHzCH3), 1.60 (t, J = 7 Hz, 3 H, N+CHzCHs), 3.09 (8, 3 H, only the salient properties of its Me, Et, and Bu analogues. N-n-Octyl-N-methyl-N-(3-carboethoxy-4-iodo)benzyl- MeNH+), 3.32 (9,J = 7 Hz, 2 H, N+CHzCHs), 4.39 (9, J = 7 Hz, 4 H, ~OCHZCH~), 5.15 (ABq,J = 13 Hz, 4 H, 2ArCH2N+), 7.59 amine, 6 (R= Oct). 5-(Bromomethyl)-2-iodobenzoicacidethyl (d, J = 8 Hz, 2 H), 7.83 (8, 1H), 8.02 (d, J = 8 Hz, 2H). The latter ester, SZ3 (1.5 g, 4.1 mmol), and 0.54 g (3.9 mmol) of N-methylthree resonances are 2H each, aromatic protons. n-octylamine were dissolved in 15 mL of dry THF, sealed in a Anal. Calcd for CBHlsBrIzNO,: C, 38.6; H, 3.94; N, 1.96. screw-top Carius tube, and stirred magnetically at 80 OC for 88 Found C, 38.4; H, 3.96; N, 1.93. h. The reaction solution was cooled, concentrated on the rotary N-Butyl-N-methyl-N,N-bis( 3-carbomethoxy-4-iodo)benevaporator, and added to 20 mL of 10% aqueous NaHC03. The zylammonium bromide, 7 (R = Bu). This compound was mixture was extracted with 3 X 25 mL of ether, washed with obtained from 6 (methyl ester) and amine 6 (R = Bu)by s t i r r i i water, and the organic phase was dried over MgS04. Evaporation in dry THF in a sealed Carius tube at 80-90 OC for 4 days.Removal of ether gave 6 (R= Oct) as a brown oil, 1.4 g (3.3 mmol, 83%). of solvent and recrystallization from CHCWether (2X) gave 33% NMR (6, CDCb): 0.86 (t,J = 5 Hz, Oct-CHa), 1.24-1.47 (m, 15 of 7 (R = Bu), mp 108-110 OC (dec). NMR (6, CDCb): 1.00 (t, H, (CH& + OCHzCHa), 2.16 (8, 3 H, NCHs), 2.33 (t, J = 7 Hz, J = 7 Hz,3 H, (CH2)3 CHd, 1.3-1.5 (m, 2 H, CH~CHS),1.9-2.1 (CHz)&HzN), 3.43 (8,2 H, ArCHzN), 4.37 (9,J = 7 Hz, OCHz), (m, 2 H, CH~CHZCH~), 3.11 (br "sn, 5 H, MeN+ + N+CH&sH7), 7.12 (dd, J = 8,2 Hz), 7.68 (d, J = 2 Hz), 7.88 (d, J = 8 Hz). The 3.93 (s,6 H, 20CHs), 5.20 (ABq,J = 13 Hz, 4H,2ArCH*N+),7.63 latter three resonances are 1H each, aromatic protons.% N-n-Octyl-N-methyl-N,N-bis(3-carboethoxy-4-iodo)ben- (d, J = 7 Hz,2 H), 7.84 (e, 2 H), 8.07 (d, J = 7 Hz, 2 H). The latter three resonances are 2H each, aromatic. zylammonium bromide, 7 (R = Oct). Without purification, Anal. Calcd for CzaHdrIzNO4: C, 38.6; H, 3.94; N, 1.96. amine 6 (1.4 g, 3.3 mmol) and 1.27 g (3.4 mmol) of bromo Found C, 38.7; H, 3.98; N, 1.93. compound 5 were dissolved in 15 mL of dry THF and stirred Iodosobenzoates 4-OH (R = Me, Et, Bu). These were magnetically in a sealed Carius tube for 8 days at 90 "C. After prepared analogously to the octyl compound which is described cooling, removal of THF gave an oil that was crystallized from in detail above. Oxidation times at 25 OC were as follows: R CHCldether and then recrystallized 3 times from the same Me, 4 h; R = Et, 3 days; R = Bu, 4 days. Iodometric titrationsm solvent. We obtained 630 mg (0.79 mmol, 24%) of title gave 96-107% of 1 4 (2 equiv) activity. The E t derivative was ammonium salt,7 (R = Oct), mp 87-90 OC (dec). NMR (6, CDCh) further purified by precipitation from water-THF, followed by 0.85 (t, J = 4 Hz, 3 H, Oct-CHs), 1.24-1.44 (m, 18 H, (CH2)6 + washing (3x1 with THF. Centrifugation was used to obtain the ~ O C H Z C H3.10 ~ ) , (m, 5 H, MeN+ + (CHz)&HzN+),4.25 (9,J = 7 Hz, 4 H, 2 OCHZCHd, 3.10 (m, 5 H, MeN+ + (CHZ)~CHZN+), precipitate in each instance. Vacuum dried 4-OH (R= Et) had mp 165-170 OC (dec) and NMR (6, DzO + DMSO-&): 1.42 (t, 4.25 (9, J = 7 Hz, 4 H, 20CHzCH3), 5.19 (ABq,J = 13 Hz, 4 H, J = 6.4 Hz,3 H, CHzCHs), 2.92 (8, 3 H, MeN+), 3.15-3.35 (m, 2 2ArCHzN+),7.62 (d, J = 8 Hz), 7.81 (s),8.03 (d, J = 8 Hz). The H, N+CHzCHa),4.71 (ABq,J 13 Hz, 4 H, 2ArCHzN+),7.91 (d, latter three resonances are 2H each, aromatic protons. J = 8 Hz, 2 H), 8.09 (d, J = 8 Hz, 2 H), 8.21 (s,2H). The latter H, 5.04; N, 1.75. Anal. Calcd for C ~ H ~ B r I z N OC,~ 43.5; : three resonances are aromatic protons. Found: C, 43.9; H, 5.05; N, 1.74. Kinetics. Reactions were followed on a Gilford Model 250 N-n-Octyl-N-methyl-N,N-bis(3-carboxy-4-iodoso)benzyspectrophotometer coupled to Gilford Model 6051 or Goen lammonium bromide, 4-OH (R = Oct). Ammonium salt 7 Servocor 120recorders. Constant temperature circulatingbaths (160 mg, 0.20 mmol) was added to 1.0 mL of acetic acid. Then maintained reaction temperatures at 25 & 0.5 OC. AU buffera 1mL of 32 w t 7% peracetic acid was added dropwise at 0 OC, and were prepared from steam-distilled water (distilled, U.S.P., the resulting mixture was stirred at 25 OC for 2 days. Next, 15 Electrified Water Co., East Orange, NJ). Rate constants were mL of water was added and the solvent was removed by rotary obtained from computer-generated correlations of log(A, - At) evaporation. These operations were repeated 5 times. Lyowith time for the appearance of p-nitrophenoxide ion at 400 or philization gave 151 mg (0.195 mmol, 97%) of white solid 4-OH 450 nm (excess substrate). Conditions for all of the kinetic runs (R = Oct) that displayed 96% of 1 4 activity (2 equiv) upon are described under Results and also in Tables I and 11,where iodometric titration.% rate constants are tabulated. The rate constants also appear The iodosobenzoate could be further purified by recrystalligraphically in Figure 3. Kinetic runs were generally followed to zation from warm aqueous acetonitrile, followedby precipitation 90% completion (exceptin cases of excesssubstrate), and showed with THF, centrifugation, and washing with THF and ether. good first kinetics (r > 0.9991, with rate constant reproducibility of &&lo%. (34) Both 1 and 3 (R = Et) are -11-12 times more reactive toward PNPDPP than 4 (R = Oct) in identical or closely related MEs.aO31 (35) Amines 6 (R = Me, Et, Bu) were prepared analogously; sealed Acknowledgment. W e thank Professor A. Yacynych tube reaction times were as follows: 5 + dimethylamine in EtOH, 60 OC for helpful discussions. We are grateful to the U.S.Army for 16 h; 5 + N-ethyl-N-methylamine in THF,80 "C for 1 day; 5 + N-nResearch Office and to Army CRDEC (with coordination butyl-N-methylamine in THF,80-90 "C for 2 days. Yields were 90by Dr. H. D. Durst) for financial support. 100%.

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