2246
BARLOW AND ZAUGQ
J. Org. Chern., Vol. 37, No. 14, 1972
Specific Solvent Effects. VI. The Effect of Solvent Variation on the Sedimentation Behavior of Sodio Diethyl n-Butylmalonate G. H. BARLOW AND H. E. ZAUGG* Research Division, Abbott Laboratories, North Chicago, Illinois 60064 Received January 31, 1978 A sedimentation study has been made of the sodio derivative of diethyl n-butylmalonate. In benzene it exists as a polymer of molecular weight 11,400 and appears to be monodispersed. In l12-dimethoxyethane (DME) it is monomeric a t least up to 0.28 M concentrations. The results strongly indicate the formation of micelles with different critical micelle concentrations (CMC) in mixed solvent. There is a linear relationship between the ChIC and the DME content in appropriate solvent mixtures. The behavior in DIME-cyclohexane mixtures is the same as in DME-benzene. However, dimethylformamide is more effective and tetrahydrofuran is less efficient than DME in raising the CMC in benzene mixtures. These relative activities are explained in terms of specific cation solvation. There is no correlation between the dispersity of the sodium enolate and its rate of alkylation previously measured. Therefore, it is concluded that the solvated monomeric ion pair in equilibrium with the micellar system is, relatively, a kinetically insignificant species.
Previous reports' described the marked acceleration by certain additives of the rate of alkylation of the sodium enolate of diethyl n-butylmalonate with n-butyl halides in benzene solution. It was established that the acceleration arises entirely from an alteration in the ground state of the sodio derivative, and not from an effect on either the alkyl halide or the transition state. Results further suggested that this effect is produced by a specific solvation of the cation acting to dissociate the large ion pair aggregate (mol wt >10,000) of the sodio derivative known to exist in benzene solutions. Later work12however, revealed that no rate maxima were achieved even at the highest attainable concentrations of several effective additives. This meant that, if the suggested dispersal mechanism is the only one operating, some unreactive aggregate must be present under all solvent conditions employed. This appeared, a priori, to be rather unlikely because rate maxima were not achieved even in neat solvents as polar as dimethylformamide (DMF) or dimethyl sulfoxide. The most direct approach to the problem was plainly the examination of the sedimentation behavior of this sodium enolate in benzene alone and in the presence of increasing concentrations of selected additives. Accordingly, for the present work, 1,2-dimethoxyethane (DME) was chosen as the additive for extensive study. I n addition, two others were selected for investigation in less detail: DAIF because it is more effective and tetrahydrofuran (THF) because it is less effective than DME in accelerating the alkylation reaction.
E analytical ultracentrifuge equipped with photoelectric scanning optics. It is interesting to note that this system could not have been studied without several recent advances in instrumentation. In these solvent systems the sodio derivative has such a low refractive index increment, dnldc, that it is impossible to study by light-scattering methods, or by any method requiring Schlieren or interference optics. The need for scanning absorption optics is obvious. The system was also unstable using the standard aluminum-filled Epon centerpieces, but fortunately the Kel-F coated centerpieces became available a t the beginning of this study. Experiments were made using wavelengths ranging from 365 to 290 nm depending on concentration. The equilibrium molecular weights were calculated from the equation
where R = gas constant, T = absolute temperature, B = partial specific volume, p = dengity of the solution, c = concentration and is proportional to the deflections of the recorder, r = distance from the center of rotation, and w = angular velocity. In velocity experiments, sedimentation coefficients were evaluated from a linear least-squares fit of the logarithm of the radial position plotted against time. This radial position was taken as the half-height of the plateau of the tracings. All sedimentation coefficientswere normalized to benzene a t 20'. Partial Specific Volume.-The partial specific volume was calculated from densities measured in a precision density meterO6mG The value in the various solvent mixtures varied between 0.83 and 0.89 ml/g. Viscosity Studies.-Viscosity determinations were made in Cannon-Ubbelohde semimicro dilution viscometers, size 60. The flow times were of the order of 200 sec. All determinations were made in a thermostated water bath at 25"
Results Experimental Section Materials.-All reagents used were of the purity specified in the following paper.3 Stock solutions of the sodio derivatives also were prepared as indicated therein. These solutions were drawn into Hamilton gas-tight syringes of appropriate capacity (1, 2.5, or 5 ml), and solvent dilutions (when necessary) were carried out in the syringes (mixing was effected with a bubble of dry nitrogen). Sedimentation Studies.-Ultracentrifuge cells (double sector Kel-F coated aluminum centerpieces) were dried for several days in a nitrogen atmosphere over phosphorus pentoxide. Immediately before use the reference side of the cell was filled with solvent and the other side was rinsed twice with the test solution before final filling. All analyses were made on a Spinco Model (1) H. E. Zaugg, B. W. Horrom, and S. Borgwardt, J . Amer. Chem. Soc.1 82, 2895, 2903 (1960) : parts I and I1 in the series, "Specific Solvent Effects." (2) H . E. Zaugg, ibid., 83, 837 ( l e a l ) , part IV. (3) H. E. Zaugg, J. F. Ratajczyk, J. E. Leonard, and A. D. Schaefer, J . Oru. Chem., 57, 2249 (1972).
Sedimentation equilibrium experiments in benzene were performed at 26,000 rpm and at concentrations of sodio derivative ranging from 0.072 to 0.015 M . The typical plot for equilibrium, i.e., In c os. r 2 , in all cases gave a linear response, indicating a monodispersed system. The extrapolated molecular weight at infinite dilution is 11,400 (Figure 1). The results of sedimentation velocity experiments in the same solvent are shown in Figure 2. At very low concentrations there is a marked increase in the sedimentation coefficient with an SO equal to 1.68. These (4) H. K. Schachman, L. Gropper, S. Hanlon, and F. Putney, Arch. Bzochem. Bzophys., 99, 175 (1962); K . Lamers, F. Putney, J. Z. Skinberg, and H. K . Schachman, zbzd., 103, 379 (1963). (5) Model OM2C purchased from A. Parr, Graz, Austria. (6) H. Stabinger, H. Leopold, and 0. Kratky, Monalsh. Chem., 98, 436 (1967).
J. Org. Chem., Vol. S?’, No. 14, 197.2
SPECIFIC SOLVENT EFFECTS.VI
0
1
.01
1
1
”
’
.05 CONC, MOLEI/LIIER
”
1
10
,025
.05
2247
1
CONC, MOLES/LITER
Figure 1.-Concentration dependence of sedimentation equilibrium molecular weight, The value a t infinite dilution is 11,400.
Figure 2.-Concentration dependence of the sedimentation coefficient and intrinsic viscosity. 0 = sedimentation, 0 = intrinsic viscosity.
results are consistent with thosc obtained in the scdimentation analyses of polyclcctrolytes. That this phenomenon is due to a chargc effect is verified by an increase in Ss0,CsHefrom 0.78 to 1.58 at 0.048 Ill and an increase in apparent molecular weight from 9400 to 11,400 in the prescncc of sodium hcxylene glycol monoborate7 (NaHG1\1), scrving as a solublc small clcctrolyte to quench charge effects. Calculations of the frictional ratio, f / j O , * with and without salt gave values of 1.11 and 1.24, respectively, which are values consistent with a sphcrical shape. Intrinsic viscosity determinations (Figure 2) gavc results consistent with thc sedimentation data, showing a marked concentration dependence of the rcsults. When the solvcnt is changed from bcnzene to D N E a completely diff erent sedimentation picture is obtained. Attempted equilibrium analyses with concentrations from 0.04 to 0.28 M failed to show a concentration distribution, indicating the absence of polymeric material. Sedimentation velocity studies a t 63,000 rpm failed to show a sedimenting boundary confirming the results of the equilibrium method. In fact, long time velocity experimcnts eventually showed typical equilibrium-like distributions and calculations of molecular weight gave values of 320 at 0.28 M , 274 a t 0.14 41,318 at 0.0s M , and 270 a t 0.07 M . All of these values are consistent with that of the monomer (molwt, 238). Various mixtures of benzene and DIME were employed to determine whether a correlation could be found between the per cent DIME added and the amount of polymer present. Initial determinations at concentration of DME greater than 50% and a sodio concentration of 0.06 M showed no boundary formation, indicating absence of polymer. When these patterns were calculated as equilibrium results they gave values for molecular weight consistent with monomer. On the other hand, a t lower concentrations of DME and the same concentratiori of sodio derivative a change occurred in the amount of sedimentable material. The lower the concentration of DME the less the amount of monomer. This can be seen experimentally as an increase in nonsedimentable material a t the meniscus as the per cent DME increases. A typical result is shown in Figure 3. A log-log plot of the concentration at the meniscus us. .DME concentration gives a straight line with a slope approximating unity (Figure 4). Studies also were made with three other solvent systems at 0.05 to 0.06 M concentrations of sodio deriva-
tive: T H F and DBSF in bcnzene and DR4E in cyclohexane. In every instance the salt was rcndercd completcly monomeric well before the medium consisted cntirely of the additive. Thc approximate concentrations of additive where this occurrcd in bcnzene werc DRlF, 3-5%; DIME, 50%; and THF, 70%. The variation in mcniscus concentration of thc totally monomeric state among the four systcms reflects thc cxperimental inability cxactly to rcproducc salt conccntrations in the four runs. It is intercsting, however, that extrapolation of thc DME-cyclohcxanc line to the much higher apparent concentration of tho DME-bcnzenc experimcnt gives nearly thc samc solvcnt composition (50:50) for thc break point. A series of velocity runs also wcrc madc at a constant D l I E concentration (15%) and variablc sodio conccntration. Thc results, plottcd as thc per ccnt scdimcntable material, are shown in Figure 5 . As can bc scen, a distinct break in the curvc occurs a t a sodio conccntration of 0.013 Ill. Abovc this valuc the amount of polymer increases rapidly. Attempts a t equilibrium runs at this conccntration of DME wcrc not reproduciblc and studies of concentration at thrcc ccll positions us. time showed that thcrc is no timc at which an equilibrium cxists. There is no obvious cxplanation for this phcnomcnon. To ensure that therc was no prcssurc cffcct from thc ultracentrifuge, an experiment was conductcd in which the meniscus concentration was studied as a function of speed at constant u2t. At all spccds the mcniscus concentration was identical, indicating no significant pressure effect.
(7) Purchased from U.S. Borax Research Corp. (8) T. Svedberg and K. 0. Pedersen, “The Ultracentrifuge,’’ Johnson Reprint Corp., New York, N. Y., 1969,p 40.
Discussion The results in benzcnc showing a monodispcrscd molecular system are surprising. It indicatcs that this system is not of a typical synthetic polymer type, generally characterized by a high degrcc of polydispcrsity. Confirmation of the monodispersity was obtaincd when molccular weight distribution calculations by the method of Scholtes also showed only onc molecular species present. While our calculations by this method can be questioned (it requires the use of a 8 solvcnt and benzene is obviously not a 0 solvcnt, as sccn in Figure 2 ) , the finding of only onc molccular species seems uncquivocal. Indeed, in a monodispcrsed system in a non-8 solvent, the only discrepancy appears to be a value for molecular weight which is lowcr than that mcasurcd under conditions for which corrections can bc madc for nonideality . (8) T. G.Scholte, J . Polym. Sci., Part A-6, 6 , 111 (1968).
2248
BARLOW AND ZAUGG
J . Org. Chem., Val. 37,No. 14, 19Ye
Figure 3.-Photoelectric scans of sodio derivative with varying amounts of 1)ME added. From left to nght, 20% ])ME, 15% DME, and 5% DME in benzene. Scans are a t 315 nm, scan time of 30 sec with a photomultiplier slit of 0.14. Scans are a t 128 min after reaching speed of 68,000 rpm (336,0008).
I
I
P-
P 50Y LI
5
25-
," / 0.5
1.0
Log
1.5
Z THF, DME
2.0
I
or DMF
.01
.03 .04 .05 CONC, MOLES/LITER
.02
.Ob
Figure 4.-Log-log plot of meniscus concentration in arbitrary units from the iilt,raeentrifuge scan us. per eenradditive: 0 , THF in benzene; A, 1)NE in benzene; 0, 1)311< in cyclohexane; 0, DMF in benzene. (Meniscus concentration is proportional to monomer content.)
Figure 5.--lleterrnination of per cent sedimentable component sodio concentration a t 15% 1)RIE. Per cent sedimentable component = (plateauconcentration - meniscus concentration)/ plateau concentration.
The most favorahlc intcrprctation of our results thcn would appear to bc that of micellc formation. This is consistent with the fact t,hat the systcm is monodispersed and also with the size of the polymcr, about 4050 monomcric units. The observation of micelles of this typc in nonpolar organic solvents is not new. Ekwall'o and I'eri'' bavc both obscrved thc occurrence of such structures and have pointed out the invcrse nature of these micelles, in which the hydrophobic moiety is on thc outsidc and the chargc is locatcd in the inside of the structure. We would suggest then that the critical micelle concentration (CMC) in benzene is at very low conccntrations and that thc amount of frce monomer is very small. We were unable to test this hypothesis since spectral interference by bcnzene restricted the minimum concentration at which determinations could be made. I n cyclohexane, however, two runs at 0.01 and 0.005 M salt concentration both gave values for a ChIC of 0.003 M. In DME \vc would then postulate that either no micelle can exist or that thc CAIC for this solvent is higher than 0.2s A t , which is the highest concentration studied. Thcsc two postulates would lead naturally to the conccpt that in mixtures of DhlE and benzcne there
would be a relationship between DME content and ChfC. This interpretation of our findings is confirmed in two ways. At 0.06 M sodio derivative concentration and varying DME concentrations onc gets a linear correlation with meniscus concentration (CMC) until at approximately 50% DME a break occurs. This means that at 50% DME the critical micelle concentration is approximately 0.06 M . Also, at a constant DRlE concentration of 15% and varying the concentration of sodio derivative, the amount of sedimentable material increases sharply past 0.013 M . Again, this indicates a CRfC of 0.013 AI at 15% DME. Thus, it has been possible to demonstrate a C1\IC by varying the concentration of either solvent or solute. The data of Figure 4 clearly suggest that the mechanism of format.ion of the monomeric ion pair involves specific solvation by the additivc and is not a bulk solvent cffect. In the first place, T H F and DME are quite different in action even though their hulk properties havc been found to be remarkably similar.'* Secondly, the order of effectivenessof the threc additives, DMF > DRlE > THIO, is the same as that for their efficiency in specifically solvating alkali cations, suggesting that in-
(IO) P.Ekwdl, J . Colloid Inlcrluc. Sci., 29. 16 (1969) (11) 3. B. Pari. (kid.. 29, 6 (1969).
us.
(12) C. Carvajal. K. Soc., 81, 5548 (1965).
J. Tblle, J. h i d , and M. Szwaro. J . Amsr. Cham.
J. Org. Chem., Vol. $7, No. 14, 1972
SPECIFIC SOLVENTEFFECTS.VI1 creasing the effective size of the cation by specific solvation inhibits the tendency .to form micelles. I n a spherical inverse micelle of this type, it is obvious that the cations must be small relative to the anions to permit them to be encapsulated in a lipophilic anionic shell. It is interesting that, of many benzene-soluble electrolytes studied by Kraus,13 only those with a large lipophilic ion and a relatively small counterion showed a particular tendency to agglomerate to form aggregates of high association number. Finally, the results of the present work provide a clear answer to the problem posed in the introductory paragraph. There is no quantitative correlation between the alkylation rate and the disperisty of the (13) C. A. Kraus, J . Chem. Educ., 35, 330 (1958); J . Phys. Chem., 60, 129 (1966).
2249
sodium enolate. Sedimentation studies were conducted a t salt concentrations equal to or higher than the rate measurements.l s 2 Yet a t additive concentrations providing 100% monomer at these salt concentrations no rate maxima are 0b~erved.l~Indeed, no significant discontinuities in log-log plots of rate vs. solvent composition are observable for the three additives studied in the present work. From these observations it can be concluded that the solvated monomeric ion pair that is in equilibrium with the micellar system is a kinetically insignificant species compared to some others that must be present in these solvent systems.
Registry No.-Sodio 93-7.
diethyl n-butylmalonate, 22600-
(14) See Figure 1 of ref 2, or Figure 1 of ref 3.
Specific Solvent Effects. VII. Ion-Pair Processes in the Alkylation of Alkali Enolates H. E. ZAUGG,* JEAN F. RATAJCZYK, J. E. LEONARD, AND ANND. SCHAEFER Organic Chemistry Department, Research Division, Abbott Laboratories, North Chicago, Illinois 60064 Received January 31, 1978 The observed lack of a common-ion rate depression for the alkylation of sodio diethyl n-butylmalonate in D M F shows that at the substrate concentrations used (-lo-’ M ) this reaction is an ion-pair process. Proton magnetic resonance studies have been added to previous uv studies to confirm the strong tendency of malonate ions to form tight ion pairs with alkali cations, even in DMF. The kinetic and sedimentation properties of this sys-, tem in binary solvent mixtures can be reconciled by postulating that, in THF, DME, and DMF (and their mixtures with benzene or cyclohexane), the reactive species is an ion pair more highly solvated than the one shown to be in equilibrium with the micellar system (cf. preceding paper). However, the kinetic behavior in the presence of the powerful alkali cation solvator, dicyclohexyl-18-crown-6 polyether, indicates that, in this case, the monosolvated ion pair is the reactive species.
I n the preceding study1 it was found that, in certain mixtures of benzene with three aprotic solvents (S = THF, DME, or DMF), sodio diethyl n-butylmalonate (A-Naf) consists of at least three species in equilibrium.
1
2
3
I n benzene the micelle 1 is the predominant form. I n the pure solvent, S, the solvated ion pair 3 and prcsumably other monomeric forms derived from it are the only detectable species. Results also indicated that specific cation solvation by the additive accounts for the equilibrium shift from 1 to 3. Because of the absence of a quantitative correlation between the increase in concentration of 3 and the previously measured2 acceleration in the rate of alkylation of A-Na+ under identical conditions of solvent variation, the relative kinetic insignificance of 3 was a necessary conclusion. Therefore, other species derivable from 3 must be the reactive forms accounting for the observed rate acceleration. Only two general possibilities remain: more effectively solvated (and more reactive) ion pairs,3and “free” anions (A-), (1) P a r t VI: G. H. Barlow and H. E. Zaugg, J . O r g . Chem., ST, 2246 (1972). (2) H. E. Zaugg. J . Amer. Chern. Soc., 8S, 837 (1961). (3) The concept of multiple ion pairs has become firmly grounded in the chemical literature relating t o the behavior both of carbonium ions4 and of carbanions.’ (4) A. Streitwieser, Jr., “Solvolytic Displacement Reactions,” McGrawHill, New York, N. Y., 1962, pp 167-171.
Previous work6 demonstrated the lack of a correlation between dielectric constant (and dipole moment) of the additive and its effect on the alkylation rate. Although this would tend to exclude the “free” anion, A-, as a kinetically important species, a more direct experimental test of this conclusion is included in the present work: a probe of the effect of added salts (both Na+ and Li+) on the rate of alkylation of A-Na+ in DMF. Because these experiments were conducted at fairly high salt concentrations, their validity was tested using identical conditions in the alkylation of sodio-3-phenyl-2-benzofuranone. Ultraviolet spectral studies7 have shown that the capacity of this enolate to form ion pairs in dilute DRIF solutions is distinctly inferior to that of enolates structurally similar to malonate. To show that this difference in ion pairing ability extends to the more concentrated solutions used in the rate studies, the effect of dilution on the nmr spectra of the lithium and sodium salts of both diethyl malonate and 3-phenyl-2-benzofuranone were compared in the present work. Also, to support the validity of this method, alkali salts of two phenolate ions, differing widely in ion pairing capacity, were compared. Finally, to examine further the question of more effectively solvated ion pairs as the kinetically important species in the sodiomalonate alkylation, four more (5) T. E. (1966): M . (6) H. E. (7) H. E.
ZIogen-Esch and J. Smid, J . Amer. Chem. Soc., 88, 307, 318 Srivarc, Science, 170 (3953), 23 (1970). Zaugg, J . Amer. Chem. SOC.,8’2, 2903 (1960). Zaugg and A. D. Schaefer, ibid., 87, 1857 (1965).
