micellar charge effects upon hydrolyses of substituted benzoyl chlorides. their relation to...

Micellar Charge Effects upon Hydrolyses of SubstitutedBenzoyl Chlorides. Their Relation to Mechanism†

Clifford A. Bunton,*,‡ Nicholas D. Gillitt,‡ Marutirao M. Mhala,‡John R. Moffatt,‡ and Anatoly K. Yatsimirsky*,⊥

Department of Chemistry and Biochemistry, University of California, Santa Barbara,California, 93106, and Facultad de Quimica, Universidad Nacional Autonoma de Mexico,

Mexico City, DF 04510, Mexico

Received January 28, 2000. In Final Form: May 2, 2000

Micellar rate effects on hydrolyses of substituted benzoyl chlorides, 1, depend on headgroup charge andelectron donation or withdrawal by substituents. Micellized sodium dodecyl sulfate, SDS, inhibits hydrolyses,and first-order rate constants in the micellar pseudophase, k′M, decrease, relative to those in water, k′W,over a range of ca. 10, but in cetyl trimethylammonium chloride, CTACl, k′M/k′W > 1 for hydrolyses of1,3,5-(NO2)2 and 1, 4-NO2, and decreases steeply with electron-donating substituents in the followingsequence: 1,4-Cl ≈ 4-Br > 4-H > 4-Me > 4-OMe, over a range of >103. Cetyl trimethylammonium bromideand mesylate behave like CTACl. Fits to the Hammett equation give F ≈ 1 in SDS and F ≈ 4 in CTACl.Anionic micelles have higher interfacial polarities than cationic micelles, but micellar and solvent effectsdo not correspond because over a range of solvents, H2O to H2O-MeCN, 1:1 w/w plots of log k′W againstσ go through minima with positive F for 1, 3,5-(NO2)2, and 4-NO2 and negative for the other substrates.The micellar effects correspond to differing extents of bond-making and -breaking in the transition state.Values of k+/k- (rate constants in CTACl and SDS) decrease strongly with increasing electron donationby substituents. Micellar rate effects in hydrolyses of benzyl bromide and 4-methoxybenzyl chloride aresimilar to those with the benzoyl chlorides. Although data were analyzed by a pseudophase treatment,application of transition state theory and reported micellar surface potentials allows estimation of localcharge at the reaction center for hydrolyses of the benzoyl chlorides.

There is extensive evidence on the ability of aqueousmicelles and other association colloids to influence reactionrates and equilibria, and concentration, or depletion, ofreactants in the interfacial region have major effects onratesofbimolecular reactions.1 However, this regiondiffersfrom water as a reaction medium,2-4 which can affect ratesof spontaneous reaction. The effects depend on the transferof substrate from water to micelles, the reaction mech-anism, and properties of the interfacial region, e.g., localcharge, and polarity and water content, which are lowerthan in water. Spontaneous reactions that are acceleratedby decreases in solvent polarity, e.g., anionic decarboxy-lation and dephosphorylation, are micellar-accelerated,and most spontaneous hydrolyses that are accelerated byincreases in solvent polarity are micellar-inhibited.1d,f,g,4-6

Comparisons of kinetic solvent and micellar effects onspontaneous hydrolyses provide evidence on the structuresof interfacial regions, especially with regard to changesin the headgroups. This kinetic evidence complementsphysical evidence and that from the use of spectral, orother, probes.2,3 The polarities of the interfacial regionscan be compared with those of bulk solvents in terms ofET(30) or effective dielectric constant, which agrees withindependent evidence that these regions are partiallydepleted in water.3

Hydrolysis of methylnaphthalene-2-sulfonate followsthe SN2 mechanism and is inhibited by decreases in solventpolarity and water content and by ionic and zwitterionicsulfobetaine micelles.7 Anionic micelles of SDS inhibitreaction more than cationic and sulfobetaine micelles,showing that micellar charge, as well as polarity, isimportant. Consistently SN11d,6,8,9 reactions are stronglymicellar-inhibited, but inhibition by SDS is less than thatby cationic or sulfobetaine micelles,9 although kineticsolvent effects are qualitatively similar to those onspontaneous SN2 reactions.10 Sulfobetaine micelles are

† Part of the Special Issue “Colloid Science Matured, Four ColloidScientists Turn 60 at the Millennium”.

‡ University of California.§ Deceased.⊥ Universidad Nacional Autonoma de Mexico.(1) (a) Fendler, J. H.; Fendler, E. J. Catalysis in Micellar and

Macromolecular Systems; Academic Press: New York, 1975. (b) Fendler,J. H. Membrane-Mimetic Chemistry; Wiley-Interscience: New York,1982. (c) Martinek, K.; Yatsimirsky, A. K.; Levashov, A. V.; Berezin, I.V. In Micellization, Solubilization and Microemulsions; Mittal, K. L.,Ed.; Plenum Press, New York, 1977; Vol. 2, p 489. (d) Bunton, C. A.;Savelli, G. Adv. Phys. Org. Chem. 1986, 22, 213. (e) Bunton, C. A.;Nome, F.; Quina, F. H.; Romsted, L. S. Acc. Chem. Res. 1991, 24, 357.(f) Tascioglu, S. Tetrahedron 1996, 52, 11113. (g) Bunton, C. A. J. Mol.Liq. 1997, 72, 231. (h) Romsted, L. S.; Bunton, C. A.; Yao, J. Curr. Opin.Colloid Interface Sci. 1997, 2, 622.

(2) (a) Zachariasse, K. A.; Phuc, N. Y.; Kozankiewicz, B. J. Phys.Chem. 1981, 85, 2676. (b) Ramachandran, C.; Pyter, R. A.; Mukerjee,P. Phys. Chem. 1982, 86, 3198. (c) Novaki, L. P.; El Seoud, O. A. Phys.Chem. Chem. Phys. 1999, 1, 1957.

(3) (a) Chaudhuri, A.; Loughlin, J. A.; Romsted, L. S.; Yao, J. J. Am.Chem. Soc. 1993, 115, 8351. (b) Romsted, L. S.; Yao, J. Langmuir 1996,12, 2425 and references cited therein.

(4) Buurma, N. J.; Herranz, A.; Engberts, J. B. F. N. J. Chem. Soc.,Perkin Trans. 2 1999, 113, and references cited therein.

(5) (a) Possidonio, S.; El Seoud, O. A. J. Mol. Liq. 1999, 80, 231. (b)Possidonio, S.; Siviero, F.; El Seoud, O. A. J. Phys. Org. Chem. 1999,12, 325.

(6) (a) Bunton, C. A. In Nucleophilicity; Harris, J. M., McManus, S.P., Eds.; Advances in Chemistry Series 215; American ChemicalSociety: Washington, D. C., 1987; Chapter 29. (b) Bunton, C. A.; Mhala,M. M.; Moffatt, J. R. In Surfactants in Solution; Mittal, K. L., Bothorel,P., Eds.; Plenum Press: New York, 1986; Vol. 5, p 625.

(7) Brinchi, L.; Di Profio, R.; Germani, R.; Savelli, G.; Spreti, N.;Bunton, C. A. J. Chem. Soc., Perkin Trans. 2 1998, 361.

(8) Menger, F. M.; Yoshinaga, H.; Venkatasubban, K. S.; Das, A. R.J. Org. Chem. 1981, 46, 415.

(9) (a) Al-Lohedan, H.; Bunton, C. A.; Mhala, M. M. J. Am. Chem.Soc. 1982, 104, 6654. (b) Bunton, C. A.; Ljunggren, S. J. Chem. Soc.,Perkin Trans. 2 1984, 355.

(10) Ingold, C. K. Structure and Mechanism in Organic Chemistry,2nd ed.; Cornell University Press: Ithaca, New York, 1969; Chapter 7.

8595Langmuir 2000, 16, 8595-8603

10.1021/la000109k CCC: $19.00 © 2000 American Chemical SocietyPublished on Web 07/12/2000

formally uncharged, but they behave like cationic micellesin their effects on rates of hydrolyses and other spontane-ous reactions.6,7,9

Spontaneous solvolyses of acyl halides do not fit readilyinto the concepts of the SN1-SN2 duality of mechanismdeveloped for reactions at alkyl centers, or of the addition-elimination mechanism of deacylation.11,12 Substituenteffects, which are typically described by the value of Ffrom the Hammett equation, vary in both sign andmagnitude, depending on substituents, leaving groups,and the reaction medium. Solvents play a variety of roles,e.g., as nucleophiles, as general bases, and by interactingwith developing ionic centers. There is extensive mecha-nistic work in this area, especially in delineation of theSN1-SN2 and addition-elimination reaction paths thatwere recently critically discussed by Kevill and Wang.12

Spontaneous hydrolyses of carboxylic anhydrides, diarylcarbonates, and acyltriazoles are micellar-inhibited, but,as for SN2 hydrolysis, inhibition is greater with anionicthan with cationic, or sulfobetaine, micelles.1d,4-6,8,9a Itappears that reactions in which there is extensive nu-cleophilic intervention by water in formation of thetransition state are most inhibited by anionic micelles,probably because of development of negative charge inthe organic residue.

The situation for hydrolyses of acyl chlorides is complex,because cationic micelles accelerate hydrolyses whensubstrates contain strongly electron-withdrawing sub-stituents but otherwise micelles inhibit reactions. Hy-drolyses of aryl chloroformates and acyl chlorides areaffected similarly by aqueous micelles.1d,5,6,9a A systematicstudy of micellar and solvent effects upon these sponta-neous hydrolyses should provide evidence on both reactionmechanism and the nature of the interfacial region as areaction medium.

Micellar effects upon overall first-order rate constants,kobs, of spontaneous reaction are typically described asshown in Scheme 1.1

Substrate, S, associates with micellized surfactant(detergent), Dn, with an association constant, KS, k′W andk′M are, respectively, first-order rate constants in theaqueous and micellar pseudophases, and [Dn] is [DT] lessthe concentration of monomeric surfactant, which isassumed to be the critical micelle concentration, cmc,under the reaction conditions.13

First-order rate constants are given by

First-order rate constants of bimolecular, nonspontaneous,

reactions depend on local concentration of the addedreactant in water and micelles.1,14

Reactions are

Substrates are designated, 1,4-Z or 1,3,5-Z2, where Z )NO2, Cl, Br, H, Me, OMe. Some of the hydrolyses are toofast to be followed in water; we therefore followed themin H2O-MeCN and estimated k′W by extrapolation andalso obtained information on kinetic solvent effects. Somedata on hydrolyses of benzyl halides, 2-Z, Z ) 4-OMe, H,halide ) Cl, Br, are included for comparison.

The surfactants are typically cetyl trimethylammoniumchloride, n-C16H33NMe3Cl, CTACl, or sodium dodecylsulfate, n-C12H25OSO3Na, SDS, but we used CTABr orCTAOMs in a few experiments. (OMs ≡ O3SMe).

The pseudophase model treats water and micelles asdistinct reaction regions (Scheme 1 and eq 1). Providedthat the value of k′W is known, eq 1 can be linearized as13

which, in effect, allows extrapolation to infinite [surfac-tant] but is unsatisfactory when k′W . k′M.8

A simpler extrapolation, which does not depend on k′W,uses data at high [surfactant] where KS[Dn] . 1, giving

i.e., as 1/[Dn] f 0, k′M ) kobs.These methods give considerable weight to data at high

[surfactant] and another approach involves simulation ofthe dependence of kobs on [Dn], eq 1.

All these treatments involve the assumption that therate and equilibrium constants in eq 1 remain constantover the experimental conditions, and limitations of thetreatment are considered later in the context of hydrolysesof specific substrates.

Experimental SectionMaterials. Surfactants were materials used earlier;9 most of

the substrates were commercial samples (Aldrich) and wererecrystallized or vacuum-distilled. 4-Methoxybenzoyl chloridewas prepared from the acid and SOCl2 and vacuum-distilled,bp., 91 °C at 1 mm. 4-Methoxybenzyl chloride prepared from thealcohol and HCl in Et2O and chromatographed on SiO2 gel withelution by petroleum ether (bp. 30-60 °C), was purified byvacuum distillation, bp. 82-83 °C at 8 mm. MeCN (spectral grade)was purified as described.15 Deionized H2O was redistilled, andreactions were in dilute HCl, 10-3 M, unless specified, to eliminatereaction with adventitious base.

Kinetics. Hydrolyses were followed spectrophotometricallyfollowing the general methods described earlier,7,9 in a Beckmanspectrometer or an HP 8451A diode-array spectrometer for thefaster reactions. All reactions were at 25.0 °C. Substrate wasadded in MeCN, the reaction solution contained 0.2 vol % MeCN,and [substrate] was between 5 × 10-6 and 10-4 M, depending onthe change of absorbance during reaction and its rate. We used

(11) (a) Kivinen, A. In The Chemistry of Acyl Halides; Patai, S., Ed.;Interscience: New York, 1972; Chapter 6. (b) Talbot, R. J. E. InComprehensive Chemical Kinetics; Bamford, C. H., Tipper, C. F. H.,Eds.; Elsevier: New York, 1972;, Vol. 10, p 226.

(12) Kevill, D. N.; Wang, W. F. K. J. Chem. Soc., Perkin Trans. 21998, 2631 and references cited therein.

(13) Menger, F. M.; Portnoy, C. E. J. Am. Chem. Soc. 1967, 89, 4698.

(14) (a) Romsted, L. S. In Micellization, Solubilization and Micro-emulsions; Mittal, K. L., Ed.; Plenum Press: New York, 1977; Vol. 2,p 509. (b) Romsted, L. S. In Surfactants in Solution; Mittal K. L.,Lindman, B., Eds.; Plenum Press: New York, 1984; vol. 2, p 1015.

(15) Coetzee, J. F.; Cunningham, G. P.; McGuire, D. K.; Padnambham,G. R. Anal. Chem. 1962, 34, 1139.

Scheme 1

kobs )k′W + k′MKS[Dn]

1 + KS[Dn](1)

1(k′W - kobs)

) 1(k′W - k′M)

+ 1(k′W - k′M)KS[Dn]

(2)

kobs )k′W

KS[Dn]+ k′M (3)

8596 Langmuir, Vol. 16, No. 23, 2000 Bunton et al.

the following wavelengths (nm): benzoyl chlorides: 4-MeO, 285;4-Me, 258; 4-H and 4-Br, 245; 4-Cl and 4-NO2, 260; 3,5-(NO2)2,230; and for 4-methoxybenzyl chloride and benzyl bromide, 238and 250, respectively. All the reactions were cleanly first-order.Some values of kobs obtained from independent experiments were(5%, except for faster hydrolyses of the more reactive substrates,where values were always (10%. Substrate was injected intothe cuvette with a spring-loaded Hamilton syringe with stirring,and the HP diode-array spectrometer takes data points at 0.1 sintervals. Provided that reaction follows first-order kinetics, weobtained good agreement for relatively fast reactions, even thoughwe could only follow the latter part of the reaction. For hydrolysisof 1,4-Br in water, independent values of kobs were 0.189, 0.179,and 0.204 s-1 with 10-4 M substrate, and for hydrolysis of 1,4-Mein 0.1 M SDS, values were 0.260 and 0.240 s-1 with 2 × 10-5 Msubstrate. The agreement deteriorated for the faster reactions,but for hydrolysis of 2,4-OMe, Cl (4 × 10-5 M) values of kobs werein 0.1 M SDS, 0.456 and 0.460 s-1 and in H2O-MeCN 4:1 v/v,0.61 and 0.53 s-1.

Initially we thought that acceleration of the hydrolysis of 1,4-NO2 by CTACl might have been due to reaction with adventitiousbase, but addition of up to 0.05 M HCl did not eliminate theacceleration. Hydrolysis of 1,3,5-(NO2)2 is strongly acceleratedby dilute CTACl, and values of kobs, s-1, are 0.20, 0.27, 0.37, and0.39 in H2O, 0.001, 0.0025, and 0.005 M CTACl respectively. Thecorresponding values are 0.47 and 0.45 s-1 in 0.005 and 0.01 MCTAOMes, respectively. These hydrolyses were in 0.01 M HCl.

Fitting of Surfactant Kinetics. Linearization of eq 1 as eq213 is not useful with our most reactive substrates whosehydrolyses are too fast to be followed in water, and theextrapolation procedure gives most weight to data in relativelyconcentrated surfactant. As an alternative procedure we tookvalues of k′M and KS obtained by using eq 3, with experimentallydetermined or extrapolated values of k′W, simulated variationsof kobs in terms of eq 1 and adjusted values of k′M and KS to obtainreasonable fits. This procedure is least satisfactory when k′W .k′M because then the fits are insensitive to values of k′M and its(low) value is uncertain, but in general there is no problem indetermining the micellar charge effect on a given reaction. Thesesimulations were made with [surfactant] . cmc, and we took thecmc of CTACl and SDS as 10-3 and 7 × 10-3 M, respectively, onthe assumption that these hydrophobic organic substrates woulddecrease the cmc.16

Computers will happily provide nonlinear least-squares fits,but they are not useful in many situations, for example, if valuesof k′W, k′M, or KS are not strictly constant over a range of[surfactant]. Even if values of these parameters are constant,those of kobs in dilute surfactant are insensitive to values of k′M,

when k′W . k′M, and the parameters that control kobs are verydifferent in dilute and more concentrated surfactant. There is astrong temptation to obtain so-called “best fits” by using statisticalmethods that treat random errors, even though in treatmentsof micellar rate effects some errors are systematic rather thanrandom.

Results

Rate Constants in Water and Kinetic SolventEffects. Hydrolyses of 1,4-H, 1,4-Me, 1,4-OMe, and4-methoxybenzyl chloride, 2,4-OMe,Cl are too fast to befollowed in water by conventional methods. The first-orderrate constant for the hydrolysis of 1,4-H is 1.4 s-1 at 25.0°C,17 and for the other compounds we used a plot of logkobs against log øH2O (øH2O is the mole fraction of water) toestimate k′W. These plots are linear with greater than 50wt % H2O. We also used the Grunwald-Winstein equa-tion18 (eq 4), with literature values of Y.19 This equationfits

data with the following values of m: 0.93, 1.0, 0.93, and0.95 for 1,4-Z, Z ) Me, H, Cl, and Br, respectively, andestimated, or directly measured, values of k′W are in Table1. Values of kobs in H2O-MeCN are in Tables S1 and S2in the Supporting Informatioin. Our extrapolated valuefor hydrolysis of 1,4-H agrees with the literature value ofBentley et al. who found that eq 4 was obeyed for solvolysisin EtOH-H2O of high water content, although over anextended range of composition a better fit was obtainedby including a term for solvent nucleophilicity.17 Thereaction of 1,4-OMe could only be followed in solvents oflow water content, and our estimate of k′W ≈ 10 s-1 is veryapproximate based on eq 4. The plot of log kobs against Yfor hydrolysis of 1,4-NO2 is slightly curved with m f 0 inthe more aqueous media and m ≈ 0 for hydrolysis of 1,3,5-(NO2)2. There is also uncertainty in the value of k′W for2,4-OMe,Cl (Table 2) because extrapolations of log kobs

(16) Mukerjee, P.; Mysels, K. J. Critical Micelle Concentrations ofAqueous Surfactant Systems; National Bureau of Standards: Wash-ington, D. C., 1971.

(17) Bentley, T. W.; Carter, G. E.; Harris, H. C. J. Chem Soc., Chem.Commun. 1984, 398.

(18) (a) Fainberg, A. H.; Winstein, S. J. Am. Chem. Soc. 1956, 78,2770. (b) Bentley, T. W.; Schleyer, P. v. R. Adv. Phys. Org. Chem. 1977,14, 1.

(19) Bunton, C. A.; Mhala, M. M.; Moffatt, J. R. J. Org. Chem. 1984,49, 3637.

Table 1. Hydrolyses of Benzoyl Chlorides in Water and Ionic Micellesa

k′M, s-1 Ks, M-1

substituent k′W, s-1 CTACl SDS CTACl SDS k+/k-

3,5-(NO2)2 0.20 >0.5b 0.062 (0.060) 30 >84-NO2 0.053 0.11 (0.11)c 0.0062 (0.0065) 100 80 164-Cl 0.214 0.012 (0.011)d 0.003 (0.003)e 500 270 44-Br 0.190 0.009 (0.011) 0.0025 (0.003) 500 350 3.64-H 1.41 0.004 (0.007) 0.015 (0.02) 130 130 0.274-Me 5 0.0015 (0.002) 0.04 (0.03) 250 150 0.0384-OMe ca. 11 <0.01 (0.01) ca. 0.4 (ca. 0.3) 100 <0.03

a Values of kM in parentheses are from eq 3. b See Experimental Section for values of kobs. c Values of kobs are similar in CTACl andCTAOMes (Supporting Section). d Equation 2 gives 0.011 s-1. e Equation 2 gives 0.003 s-1.

Table 2. Hydrolyses of Benzyl Halides in Water and Ionic Micellesa

k′M, s-1 Ks, M-1

substituent k′W, s-1 CTACl SDS CTACl SDS k+/k-

2,4-H,Brb 1.56 × 10-4 9 × 10-6 (1.1 × 10-5)b 1.5 × 10-5 (1.9 × 10-5) 250 220 0.62,4-MeO,Clc 2.5-4 <0.01 (0.01) 0.12 (0.11) 300 100 <0.08a Values of kM in parentheses are from eq 3. b From data in CTABr and SDS;9a values are similar in CTABr and CTAOMes. c In CTACl

and SDS; values in CTAOMes are slightly higher than in CTACl (Supporting Information).

log k/k0 ) mY (4)

Micellar Charge Effects upon Hydrolyses Langmuir, Vol. 16, No. 23, 2000 8597

against øΗ2Ã or Y give k′W ≈ 2.5 or 4 s-1, respectively, withm ) 1.1. Values of kobs in H2O-MeCN are given asSupporting Information (Tables S1 and S2).

Micellar Rate Data. We used eq 3 to estimateapproximate values of k′M, although, for hydrolysis of 1,3,5-(NO2)2 in CTACl, reaction is too fast to be followed exceptin very dilute CTACl (Experimental Section) and we haveonly a lower limit of k′M. Extrapolation is not needed for1,4-NO2, where we reached a limiting value of kobs ) k′M,and because of the fast reaction of 1,4-OMe in SDS dataare scattered. With a few substrates values of k′W and k′Mare such that we could use eq 2.

Except as noted we fitted the rate data to eq 1; fits areshown in Figure 1, and rate and equilibrium constantsare in Table 1. Approximate values of k′W for the morereactive substrates were obtained by extrapolation (TableS2), and we allowed k′W to vary slightly in fitting micellarrate data. In general we obtained similar values of k′M byextrapolation, eq 3, and simulation, eq 1. Values of kobsare given as Supporting Information (Tables S3, S4, andS5) and in Figure 1. Values for hydrolyses of 1,4-H in SDSand 2,HBr are from ref 9a.

Limitations in the validity of eq 1 need to be considered,although they do not affect qualitative conclusions re-garding relative values of k′M in cationic and anionicmicelles. Values of k′W, k′M, and KS (eq 1) may not beconstant over an extended range of [surfactant]. Molecularweights of surfactants are such that even at moderate

concentration, e.g., 0.5 M, CTACl (MW 320) or SDS (MW288) represent significant amounts of the solution andmay affect properties of bulk water as a reaction regionby exerting an electrolyte effect on k′W or by binding waterand reducing its availability in the aqueous pseudo-phase.2c,3 These perturbations should not be highlysurfactant specific, and, to a first approximation, CTACland SDS should have similar medium effects on k′W.

Changes in micellar structure, e.g., by growth, mayaffect both k′M and KS, but micelles of CTACl and SDS donot grow rapidly in the absence of added electrolyte,although growth of micelles of CTABr could createproblems and we did not use it in most of our work.20

Our fitting of the micellar rate data gives values of KSfor most of the substrates in CTACl and SDS (Table 1).These values are subject to the approximations in thepseudophase model, but variations are as expected fromrelations between solute structures and micellar affini-ties,21 and there is a reasonably good linear free-energyrelation between binding in CTACl and SDS (Figure S1).The line in Figure S1 has a slope of 1.23 ( 0.23 from alinear regression.

(20) (a) Ikeda, S.; Hayashi, S.; Imae, T. J. Phys. Chem. 1981, 85, 106.(b) Porte, G.; Appell, J. J. Phys. Chem. 1981, 85, 2511.

(21) (a) Sepulveda, L.; Lissi, E.; Quina, F. Adv. Colloid Interface Sci.1986, 25, 7. (b) Quina, F. H.; Alonso, E. O.; Farah, J. P. S. J. Phys.Chem. 1995, 99, 11708. (c) Abraham, M. H.; Chadha, H. C.; Dixon, J.P.; Rafols, C.; Treiner, C. J. Chem. Soc., Perkin Trans. 2 1995, 887.

Figure 1. Plots of kobs, s-1 against [surfactant], M (x-axis) for benzoyl chlorides, benzyl bromide (*), and 4-methoxybenzyl chloride(**). Plots are simulated; solid and broken lines are for CTACl and SDS, respectively, except for reaction of benzyl bromide inCTABr.


We treat our data in terms of the pseudophasemodel,1,13,14 but we could alternatively disregard micellesas a distinct reaction region and apply the Bronsted-Bjerrum formalism, eq 522-24

where γS and γq are activity coefficients of substrate, S,and the transition state, respectively. Micellar incorpora-tion of substrates decreases γS similarly in CTACl andSDS (Table S1 and Figure S1) owing largely to hydrophobicinteractions, which will also exist, to some extent, in thetransition state. We would then ascribe different reac-tivities in solutions of CTACl and SDS to changes in γq,which will depend on interactions of the transition statewith the differently charged micelles, and we considerthis question later.

Substrate Structure and Micellar Rate Effects. Wecan make several generalizations regarding ionic micellareffects upon spontaneous, water-catalyzed and SN1-SN2,hydrolyses of benzoyl chlorides and other acyl and alkylderivatives: (i) except for hydrolyses of the nitro deriva-tives, 1,4-NO2 and 1,3,5-(NO2)2 and 4-nitrophenyl chloro-formate5,6,9 in cationic micelles (Figure 1 and Table 1) thereis inhibition; (ii) relative values of k′M in cationic andanionic micelles are related to electronic substituenteffects; (iii) there is no simple, direct, relationship betweensolvent and micellar effects, but both are related to thesubstituent effects.

The micellar charge effects, k+/k- (k+ and k- representvalues of k′M in cationic and anionic micelles, respectively)and values of k′M and k′W are shown in Table 1 but areonly approximate for the more labile substrates. Valuesof k+/k- increase monotonically as substituents becomeless electron-donating and k+/k- g 1 with electron-withdrawing substituents.

The limited data on hydrolyses of benzyl halides inmicelles are similar to those in hydrolyses of the benzoylchlorides. Micelles inhibit these reactions, but for hy-drolysis of 2,4-OMe,Cl k+/k- < 0.08 whereas for hydrolysisof 2,4-H,Br k+/k- ) 0.6 (CTABr and SDS). These solvolysesin polar hydroxylic solvents are typically accelerated byelectron-donating substituents, but reactions with goodnucleophiles are second-order.10,25 Solvolyses probablyfollow borderline mechanisms within the SN1-SN2 con-tinuum, with extents of bond making and breakingdepending on substituents and the reaction medium.

Mechanisms of Hydrolysis. Micellar and solventeffects on hydrolyses of the benzyl halides (Tables 2 andS2) indicate that bond breaking is dominant in the reactionof 2,4-OMe,Cl, i.e., it follows the classical SN1 mechanism,but nucleophilic attack is important in reaction of 2,4-H,Br, as in a classical SN2 mechanism.10,25 Solvolyses ofacyl halides are sometimes analyzed in terms of the SN1-SN2 duality of mechanism, and acyl cations are interme-diates in some special conditions.11,12,26 However, the SN2mechanistic model is inadequate in describing bimolecularattack at acyl centers because a tetrahedral intermediatecan form in deacylation, but the corresponding increasein covalency at the reaction center is strongly unfavorablefor nucleophilic attack on an alkyl group. We note that a

tetrahedral intermediate may be a “dead-end” species,which is not on the reaction path. However, in a concerteddeacylation there can be charge development on bothcarbonyl oxygen and the leaving group in the transitionstate, depending on the reaction medium and substratestructure.

There is strongevidence for involvementofgeneralbasesin solvolyses of acyl derivatives.12 The general base canbe a second solvent molecule, and it is difficult todemonstrate catalysis by an added general base insolvolyses of acyl halides because many bases, e.g., tertiaryamines and carboxylate ions, can also react nucleophili-cally.

Kevill and Wang explained solvent and substituenteffects on solvolyses of acyl halides in terms of a dualityof reaction paths as adapted for hydrolyses in Scheme 2,where B is typically a water molecule.12 In this mechanisticdescription initial addition is reversible and intermediate3 can form the tetrahedral intermediate 4, which readilyloses Cl-. This addition-elimination mechanism is favoredby electron-withdrawing substituents. The alternativeSN1-SN2-like mechanism should be favored by electron-donating substituents, because 5 is equivalent to a tightlysolvated acyl cation. This general description can beapplied to our hydrolyses in H2O-MeCN or in aqueousmicelles, but the steps may be concerted; i.e., there is acontinuum between an addition-elimination mechanismand one involving, in the limit, a hydrated acyl cation, 5.Such concerted hydrolyses with differing extents of bondmaking and breaking can be analyzed in terms of Jencks-More O’Ferrall free energy diagrams27 without postulatingthe existence of intermediates such as 4 or 5 (Scheme 2).

It appears that hydrolyses of the nitrobenzoyl chlorideshave transition states akin to the tetrahedral intermedi-ate, 4 (Scheme 2), with negative charge dispersed into theorganic moiety, and the developing positive charge on theattacking water molecule dispersed into the solvent. Thischarge development will be more favorable in a cationicthan in an anionic interfacial region.

Electron-donating substituents, e.g., OMe and Me,increase the extent of C-Cl bond breaking in the transitionstate, which will be akin to a solvated acyl cation (Scheme2) and will interact more favorably with anionic than withcationic headgroups. However, we do not consider thesehydrolyses to be following a classical SN1 mechanism withno nucleophilic interaction at the reaction center, becausein that event 4-methoxybenzyl chloride, which reacts bythe SN1 mechanism, should be more reactive than4-methoxybenzoyl chloride (Tables 1, 2, and S2). Thedistinction between SN1 and bimolecular, eg., SN2, sol-volyses is firm, provided that a cationic intermediate canbe identified by trapping.10,12,26 Otherwise, it is difficultto demonstrate the absence of covalent interactionsbetween solvent and the reaction center, as in limitingSN1 solvolyses, and a mechanistic continuum, with dif-

(22) Hall, D.G. J. Phys. Chem. 1987, 91, 4287.(23) Lopez-Cornejo, P. L.; Jimenez, R.; Moya, M. L.; Sanchez, F.;

Burgess, J. Langmuir 1996, 12, 4981.(24) Bunton, C. A.; Robinson, L. J. Am. Chem. Soc. 1968, 90, 5972.(25) Lowry,T.H.;Richardson,K.S. MechanismandTheory inOrganic

Chemistry, 3rd ed.; Harper and Row: New York, 1987; Chapter 4.(26) Song, B. D.; Jencks, W. P. J. Am. Chem. Soc. 1989, 111, 8470.

(27) (a) More O’Ferrall, R. A. J. Chem. Soc. B 1970, 274. (b) Jencks,W. P. Chem. Rev. 1972, 72, 705. (c) Harris, J. M.; Shafer, S. G.; Moffatt,J. R.; Becker, A. R. J. Am. Chem. Soc. 1979, 101, 3295.

Scheme 2

k )k0γSaH2O

γq

(5)


fering degrees of bond making and breaking, provides areasonable model.

Zwitterionic, sulfobetaine, micelles behave very muchlike cationic micelles in their effect on spontaneoushydrolyses at acyl, alkyl, and sulfonyl centers6,7,9a,28

consistent with similarities in their charge asymmetriesin the interfacial region.

These interactions between anionic or cationic head-groups and transition states are shown in cartoon formsin Scheme 3 where we show transition states that (i)involve significant C-Cl bond breaking, 5, or (ii) aresimilar to a tetrahedral intermediate, 3 or 4, for reactionsin the interfacial regions of cationic and anionic micelles.Counterions are omitted for clarity, although they mayaffect the interactions by changing the micellar fractionalcharge and the surface charge density, and we includeonly the nucleophilic water molecule.

Charge is shown as localized on this incoming watermolecule, although it will be dispersed into the solvent byhydrogen bonding. Micellar effects on hydrolyses of arylchloroformates,5,6,9a which involve extensive bond mak-ing,29 can also be rationalized in terms of Schemes 2 and3. These micellar-charge effects on reactivity are inaddition to rate changes due to micelles of CTACl havinglower polarities, based on ET(30) or effective dielectricconstant, than those of SDS.2

Micellar and Solvent Effects. There is some cor-respondence between solvent and micellar-charge effectsand electronic effects of substituents. For example, hy-drolyses of 1,4-OMe and 1,4-Me are much faster in anionicthan in cationic micelles and are accelerated by an increasein the water content of H2O-MeCN, whereas hydrolysisof 1,3,5-(NO2)2 is faster in cationic than in anionic micelles,but the rate is not very sensitive to the water content ofthe solvent (Figure 2 and Table S1). However, these

generalizations do not apply to hydrolyses of all thecompounds; e.g., hydrolyses of 1,4-Cl and 1,4-Br areaccelerated by an increase in the water content of thesolvent but are faster in cationic than anionic micelles(Figures 1 and 2 and Table 1). We note that our data onsolvent effects are for generally greater than 50 mol %H2O, and behaviors are different from those seen earlierwhere, with few exceptions, reactions were followed insolvents of low water content.11,12,30,31

Plots of log kobs against σ go through minima over therange of solvents studied (Figure 2) with F ≈ 3 forhydrolyses of 1,Z ) Me, H, Cl, Br, and little dependenceon solvent composition. For hydrolyses of 1,3,5-(NO2)2 and1,4-NO2, F decreases from +1.6 in 50 to ca. +0.9 in 100wt % H2O (cf. refs 12, 31, and 32). We do not include thedata for hydrolysis of 1,4-OMe in this Hammett plotbecause we cannot estimate a reliable value of kobs in H2O.If we take k′W ≈ 10 s-1 in H2O and 0.2 s-1 in 50 wt % H2Ofitting to the plot would be reasonable with the value ofσ+ ) -0.78 for the 4-OMe group,33 consistent withmesomeric electron donation.

Hydrolyses of the benzoyl chlorides are accelerated byincreasing the water content of the solvent, although theincrease is small for the nitro derivatives. The decreasedwater content in the micellar interfacial region2c,3 shouldinhibit hydrolyses, but cationic micelles accelerate hy-drolyses of the nitrobenzoyl chlorides (Figure 1 and Table1). Therefore, cationic micelles affect these hydrolyses toan extent that overcomes inhibition due to the low polarityorwater contentof cationic, butnotanionic,micelles.Whenelectron-donating groups are present, as in 1,4-OMe,cationic micelles exert an effect that reinforces theinhibition due to low polarity and water content. The valueof ET of CTACl is very similar to that of ca. 39 M H2O inMeCN,2c depending slightly on the structure of the probe.This molarity corresponds approximately to 75 wt % H2O

(28) Bunton, C. A.; Mhala, M. M.; Moffatt, J. R. J. Org. Chem. 1985,50, 4921.

(29) Kevill, D. M.; D’Souza, M. J. J. Chem. Soc., Perkin Trans. 21997, 1721 and references cited therein.

(30) (a) Brown, D. A.; Hudson, R. F. J. Chem. Soc. 1953, 3352. (b)Crunden, E. W.; Hudson, R. F. J. Chem. Soc. 1956, 501.

(31) Johnson, S. L. Adv. Phys. Org. Chem. 1967, 5, 237.(32) Fry, A. In Isotope Effects in Chemical Reactions; Collins, C. J.,

Bowman, N. S., Eds.; Van Nostrand Reinhold: New York, 1970; pp379-380, 402.

(33) Reference 25, Chapter 2.

Scheme 3a

a Symbols δ+ and δ- represent partial charges withoutnumerical significance.

Figure 2. Variations of log with in H2O and H2O-MeCN. O,0, ], 4, b, and [: H2O wt % ) 100, 90, 80, 70, 60, and 50. Somevalues of k′W are interpolated, Tables S1 and S2. A dot in anopen symbol denotes 4-Br and data points with 4-Cl in 50 wt% H2O overlap.


and for 1,4-Me and 1,4-H, and probably for 1,4-OMe,reactions are slower in this solvent by factors of ap-proximately 15 (Figure 2). However, inhibition by CTAClis much larger, by factors >3 × 102 (Table 1), owing inpart to unfavorable interactions with the cationic head-group.

Values of k+/k- (Table 1) and k′M/k′W (Table 3) are relatedto substituent electronic effects, although we cannotestimate the latter in all conditions. Plots of log(k′M/k′W)against σ illustrate the role of electronic effects (Figure3). The apparent minimum in the plot for data in SDSmay be an artifact of the uncertain value of k′W for 1,4-OMe, and we can only set limits on k′M for 1,4-OMe and1,3,5-(NO2)2 in CTACl. We show a linear relationshipbetween log(k′M/k′W) and σ for reactions in CTACl, but,unless 1,3,5-(NO2)2 is very much more reactive in CTAClthan 1,4-NO2 (Table 1 and Experimental Section) the plotwill be curved for the nitro derivatives with a lower valueof F. We see no simple way of testing this speculation forthese hydrolyses.

These comparisons show that while effects of micellesof SDS do not depend strongly on electronic effects ofsubstituents those of CTACl are very sensitive to electroniceffects. We assume that development of positive chargeat the reaction center increases as substituents becomemore electron donating. This positive charge developmentis apparently strongly disfavored by cationic head groups,which should favor development of negative charge in theorganic moiety when the transition state is similar to atetrahedral intermediate, as in hydrolyses of 1,3,5-(NO2)2and 1,4-NO2 (Scheme 2).

Substituent electronic effects as given by the (positive)value of F for hydrolyses of the nitro derivatives increaseas thepolarityorwater contentofH2O-MeCNisdecreased(Figure 2), and values of F are higher in micelles of CTAClthan in water (Figure 3). These differences are due, inpart, to differences in polarities, or effective dielectricconstants.2 However, although there are minima in plots

of log kobs against F for solvolyses of benzoyl chlorides ina variety of solvents, depending on solvents and substit-uents (Figure 3 and refs 31 and 32), there are no suchminima in hydrolyses in CTACl, and probably not in SDSmicelles (Table 1).

We know of no deviations from the qualitative gener-alization that k+/k- > 1 for spontaneous hydrolysesinvolving extensive bond making in the transition state,e.g., SN2 and addition-elimination hydrolyses, but if bondbreaking is dominant, as in SN1 hydrolyses, k+/k- < 1.This pattern is independent of kinetic solvent effects andrelative reactivities in water and micelles and is under-standable in terms of developments of charge in thetransition states, as shown in simplified forms for hy-drolyses of benzoyl chlorides (Scheme 2).

The lower polarity of cationic relative to anionic micelles2

should make k+/k- sensitive to the extent of bond breakingin the transition state, but we cannot explain our datasolely in terms of apparent polarities in the interfacialregions. Solvent and micellar effects on hydrolyses of thenitrobenzoyl chlorides and 4-nitrophenyl chloroformateare understandable only on the assumption that the chargeasymmetry in the interfacial region of a cationic micellemakes hydrolyses faster than in water, and converselythe charge asymmetry plus other interfacial properties inanionic micelles makes these hydrolyses slower than inwater.5,6,9

The gradual variation of k+/k- with substituent elec-tronic effects (Table 1) is consistent with a mechanisticcontinuum, rather than an abrupt change, although thereare minima in plots of log kobs against σ or σ+ in variousmixed solvents and in microemulsions (Figure 2 and refs12, 31, 32, 34). Fry and co-workers used 35Cl/37Cl kineticisotope effects to show that extents of bond breaking innucleophilic reactions of benzyl and benzoyl chloridesincrease with increasing electronic donation from 4-sub-stituents.32 They also saw minima in the Hammett plots.

(34) Garcia-Rio, L.; Leis, J. R. Chem. Commun. 2000, 455.

Figure 3. Variations of log(k′M/k′W) with σ in CTACl and SDS.

Table 3. Relative Rate Constants for Hydrolyses of Benzoyl Chlorides in Water and Ionic Micelles

substituent 3,5-(NO2)2 4-NO2 4-Cl 4-Br 4-H 4-Me 4-OMe

CTACl >2.5 2 0.056 0.047 0.003 5 × 10-4 <10-3

SDS 0.3 0.12 0.014 0.013 0.011 0.01 ca. 0.03


Garcia-Rio and Leis recently examined hydrolyses ofbenzoyl chlorides in water-in-oil microemulsions of Aerosol(AOT) and isooctane, and, on the assumption that therewas no reaction in the aqueous microdroplet, estimatedrate constants, k, at the interface.34 Plots of log k againstσ+ went through minma, depending on water content, W) [H2O]/[AOT], which was ascribed to a change ofmechanism from associative to dissociative due to a changeof interfacial properties.

The observation that substituent effects upon k′M/k′Ware much larger in CTACl than in SDS micelles (Table 2and Figure 3) is consistent with differences in polaritiesof the interfacial reaction region. The lower polarity ofCTACl than SDS2 reinforces the unfavorable chargeinteractions in transition states that involve extensivebond breaking, as in hydrolyses of 1,Z ) 4-H, 4-Me, and4-OMe.

The Transition State Formalism. The pseudophasetreatment analyzes micellar rate effects upon thesehydrolyses in terms of transfer free energies of substratesand values of k′W and k′M (eq 1).1 Alternately we can applythe Eyring equation,22,23 which is equivalent to eq 5, andobtain eq 6

where Kq is the (hypothetical) equilibrium constant fortransfer of the transition state between water and micelles,which gives

where + and - refer to reactions in CTACl and SDS,respectively. To a first approximation we assume that KS

-

≈ KS+ (Table 1 and Figure 1), and if we factor K+

q and K-q

into electrostatic and apolar terms, i.e.

and assume that Kapolarq is the same in CTACl and SDS,

we can relate k+/k- to the micellar surface potentials, ψ,and the apparent charge on the organic reaction centerin the transition state. On the basis of these assumptions

where ∆ψ is the sum of the absolute values of ψ for CTACland SDS and δQ is the apparent fractional charge in thetransition state.

We so not know the surface potential of an ionic micelle,although values are estimated by electrostatic treat-ments.35 Values have also been reported based on analysesof indicator equilibria, and we use them because acid-base equilibria involve differences of one charge unit.Fernandez and Fromherz estimate ψ ) +148 and -134mV for CTACl and SDS, respectively, from their model ofmicellar effects on acid-base equilibria,36 cf., ref 37, and

eq 10 gives

Values of δQ are given in Table 4. They are not verysensitive to values of ψ as shown by values in parenthesescalculated with absolute values of ψ of 100 mV andindependent of micellar charge.

This treatment is oversimplified, but it indicates thatthe observed micellar rate effects are consistent withdevelopment of fractional charge at the reaction center,depending on electronic substituent effects and theconsequent changes in extents of bond making andbreaking in the transition state. Our use of surfacepotentials estimated from acid-base equilibria is simplya convenient method of comparing apparent chargedevelopment in hydrolysis with the change of unit chargein proton transfer from indicator acid to base.

The pseudophase treatment and that based on theEyring equation are alternative ways of analyzing reac-tivities in association colloids, and the choice between themdepends largely on descriptive convenience.

Conclusions. Rate effects of aqueous micelles onhydrolyses of substituted benzoyl chlorides depend onelectronic substituent effects and micellar charge. Exceptfor hydrolyses of nitro derivatives in cationic, or sulfo-betaine, micelles, reactions are inhibited, in part becausepolarities, and water contents, of micellar interfacialregions are lower than those of bulk water.2,3 Values ofk′M/k′W in anionic micelles of SDS are modestly increasedby electron withdrawal by substituents, but the increaseis steeper for hydrolyses in cationic micelles of CTACl.Electron withdrawal strongly increases k+/k- and favorsextensive bond making in the transition state withdevelopment of negative charge in the organic moiety.The micellar effects, with fully-bound substrates, arerelated to relative extents of bond making and breakingin the transition state, the lower polarity of cationic,relative to anionic, micellar interfaces, and interactionsbetween forming ionic centers and the charge asymmetryof the interfacial regions.

Hydrolyses of 1,4-NO2 and 1,3,5-(NO2)2 are acceleratedby cationic micelles of CTACl because favorable interac-tions with the developing negative charge at the reactioncenter more than offset effects due to the lower polarityof the interfacial region, relative to water. The unfavorablecharge effects in anionic micelles of SDS contribute to theinhibition.

The opposite trend appears in the absence of stronglyelectron-withdrawing substituents. Hydrolyses of benzoylchloride and its methyl and methoxy derivatives, 1,Z,Z )4-H, 4-Me, and 4-OMe, are very strongly inhibited bycationic micelles of CTACl, because low interfacial polarityreinforces unfavorable interactions between the cationicheadgroup and the developing charge at the reactioncenter. There is relatively little inhibition of these hy-(35) (a) Gunnarsson, G.; Jonsson, B.; Wennerstrom, H. J. Phys. Chem.

1980, 84, 3114. (b) Bunton, C. A.; Moffatt, J. R. J. Phys. Chem. 1986,90, 538. (c) Bunton, C. A.; Mhala, M. M.; Moffatt, J. R. J. Phys. Chem.1989, 93, 7851. (d) Rodenas, E.; Ortega, F. J. Phys. Chem. 1987, 91,837.

(36) Fernandez, M. S.; Fromherz, P. J. Phys. Chem. 1977, 81, 1755.

(37) (a) Almgren, M.; Rydholm, R. J. Phys. Chem. 1979, 83, 360. (b)Drummond, C. J.; Grieser, F.; Healy, T. W. J. Chem. Soc., FaradayTrans. 1 1989, 85, 537 and references cited therein.

Table 4. Estimated Fractional Charge at the ReactionCenter in Hydrolyses of Benzoyl Chloridesa

substituent δQ substituent δQ

3,5-(NO2)2 >-0.2 (>-0.28) 4-H 0.13 (0.18)4-NO2 -0.25 (-0.36) 4-Me 0.29 (0.41)4-Cl -0.12 (-0.17) 4-OMe <0.31 (<0.44)4-Br -0.11 (-0.16)

log(k+

k-) ) (28258 )δQ ) 4.9δQ (10)

k′M ) k′WKq

KS(6)

k+

k- ) (K+q

K-q )(KS

-

KS+) (7)

Kq ) Kelq Kapolar

q (8)

log(k+

k-) ) log(K+q

K-q )

el

)∆ψ(δQ)

58(9)


drolyses by SDS micelles where a rate decrease due topolarity of the interfacial region is offset by the chargeeffects.

Acknowledgment. We acknowledge valuable discus-sions with Professor O. A. El Seoud made possible bysupport from the National Science Foundation and CNPq.US-Brazil Cooperative Program. A.K.Y. thanks CONA-CYT for support of a Sabbatical leave at UCSB.

Supporting Information Available: Table S1, solventeffects on hydrolyses of benzoyl chlorides in H2O-MeCN; TableS2, solvent effects on hydrolyses of methyl and methoxy deriva-tives; Table S3, hydrolyses in SDS; Table S4, hydrolyses of benzoylchlorides in CTACl; Table S5, hydrolysis of 4-methoxybenzylchloride in cationic micelles; Figure S1, relation between KS

(CTACl) and KS (SDS).

LA000109K


micellar charge effects upon hydrolyses of substituted benzoyl chlorides. their relation to...

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