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17 Electrophilic Interference in Methods for Estimating Nucleophilic Assistance in Solvolyses

Downloaded by FUDAN UNIV on February 5, 2017 | http://pubs.acs.org Publication Date: July 1, 1987 | doi: 10.1021/ba-1987-0215.ch017

J. Milton Harris1, Samuel P. McManus1, M. R. Sedaghat-Herati1, N. Neamati -Mazraeh1, M. J. Kamlet2, R. M. Doherty2, R. W. Taft3, and M. H. Abraham4 1 Department of Chemistry, University of Alabama, Huntsville, AL 35899 Naval Surface Weapons Center, White Oak Laboratory, Silver Spring, MD 20910 Department of Chemistry, University of California, Irvine, CA 92717 Department of Chemistry, University of Surrey, Guildford, Surrey, GU2 5XH, England

2

3

4

Methods for estimating the extent of nucleophilic solvent assistance (NSA)

in solvolyses generally ignore electrophilic solvent assistance

(ESA), or they assume that variation in ESA covaries with solvent ionizing power during solvent variation.

In the present work, we

argue that these assumptions are incorrect and that they lead to overestimation of NSA. The solvatochromic equation is applied to the solvolyses of tert-butyl chloride, 1-adamantyl chloride, and a mustard derivative

to permit estimation of the sensitivity of these sub-

strates to ESA. The results show that ESA can vary dramatically even when the leaving group is unchanged. Finally, we examine a recent failure of the EtOH-TFE NSA

(trifluoroethanol) approach for estimating

and conclude that failure is due to the unusually high sensitivity

of the model compound, 1-adamantyl chloride, to ESA.

SOLVOLYTIC

DISPLACEMENT REACTIONS can be affected by solvents in

several ways, including nucleophilic solvent assistance (NSA) and elec trophilic solvent assistance (ESA). NSA can be defined as electron donation from solvent to the developing positive dipole of a reacting C - X bond, and E S A can be defined as electron acceptance by the solvent from the leaving group, I.

Library 1155 16th St., N.W. Washinfton. D.C 20036 Harris and McManus; Nucleophilicity Advances in Chemistry; American Chemical Society: Washington, DC, 1987.


248

NUCLEOPHL IC IT IY

Several methods are available for estimating the extent of N S A in solvolyses (1-6). Generally, either these methods ignore E S A or they assume that variation in E S A is minor during solvent variation or that E S A covaries with solvent ionizing power during solvent variation. The goal of this paper is to demonstrate that these assumptions regarding E S A lead to overestimation of NSA. To illustrate this point, we will examine the ethanol-trifluoroethanol ( E t O H - T F E ) method of Raber et al. (3). The E t O H - T F E method is based on the observation that plots of log k for solvolytic substrates against 1adamantyl chloride or bromide (1-AdCl or 1-AdBr) in a series of aqueous ethanols and T F E s fall into two general types, one type in which the plot is linear and a second type in which the plot is nonlinear. In the second case, the T F E points are found below the line defined by the aqueous ethanols (Figure 1). According to the Raber et al. interpretation, 1-AdCl solvolysis provides a measure of solvent ionizing power and solvent electrophilicity. The linear plot is then interpreted as being the result of the substrate in question reacting without N S A , as does the 1-adamantyl model. In the nonlinear plot, then, the conclusion is that nonlinearity results because the substrate in question has N S A acting as an additional factor that is not modeled by 1-AdCl. The T F E points appear to be "too slow" because NSA is absent in this weakly nucleophilic solvent. Thus, Figure 1 is considered to be evidence that the mustard compound C H S C H C H C 1 , II, reacts with N S A in solvents such as aqueous ethanol. However, other experimental methods show that H does not receive NSA (6). For example, the hydrolysis products of deuterium-labeled II are completely scrambled as would be expected for reaction through the sulfonium ion. We contend that the E t O H - T F E method fails in this case because it ignores ESA. Specifically, failure results because of large differences in the suscep tibility of the substrate (II) and 1-AdCl to solvent electrophilicity. In other words, the T F E points fall below the ethanol line because 1-AdCl is receiv ing additional E S A in the more highly electrophilic T F E and not because NSA is absent in reaction of the mustard. This same assumption of the E t O H - T F E method, that rate of reaction of 1-AdCl (or any single substrate) can provide a combined measure of solvent ionizing power and solvent electrophilicity, is made in several other methods for measuring N S A (7). Our position is that this general assumption is incorrect. 3

2

2

Solvatochromic Method To investigate the possibility of variable E S A , we have used the sol vatochromic method of Kamlet and co-workers (7-10). According to this approach, a solvent-dependent phenomenon (in this case log solvolysis rate k) is a function of four solvent properties: solvent hydrogen-bond donor ability or electrophilicity, a; solvent hydrogen-bond acceptor ability or nu-

Harris and McManus; Nucleophilicity Advances in Chemistry; American Chemical Society: Washington, DC, 1987.

17.

HARRIS ET AL.

249 Estimating Nucleophilic Assistance in Solvolyses

-2

• 50T 50Ε / % 50A d 60Ε · / -3

•

70T

I Ψ97Ί

-


log kj,

/ · 70A

-4

/ 95E

ι

ι

0

2

-5 -2

log k

r e l

4

1-AdCl

Figure 1. A typical nonlinear EtOH-TFE plot. Here the substrate indicated to react with NSA is CH SCH CH Cl, II (6). Rates are in reciprocal seconds and are relative rates for 1-adamantyl chloride. In solvent abbreviations, for example, 97T represents 97% aqueous trifluoroethanol, 95E represents 95% aqueous ethanol, and 70A represents 70% aqueous acetone, and so on. 3

2

2

cleophilicity, β; solvent dipolarity-polarizability, π * ; and a measure of the cavity term b . 2

H

log k = log k + aa + b$ 0

+ STT* + hb /l00 2

H

Three of the four solvent parameters (the exception being the cavity term) have been empirically determined from several quite different experi ments. These averaged values of the parameters have proven to be useful for predicting a diverse collection of phenomena ranging from solubility to toxicity to chromatographic retention times (8-10). The fourth parameter


(1)

250

NUCLEOPHL IC IT IY

2

(δ ) is the Hildebrand solubility parameter, which is calculated from the molar heat of vaporization. The coefficients of the independent variables are understood in the present case to represent the sensitivity of the rate to the associated variables. We first applied the solvatochromic equation (SCE) to solvolysis of tertbutyl chloride (f-BuCl) to determine if the method could give a reasonable result for this much-studied reaction (7). Abraham et al. (11) had previously attempted correlation of these rates with the S C E without the cavity term, but as Bentley and Carter (12) have noted, an unsatisfactory result was achieved (7). First, T F E and hexafluoroisopropyl alcohol (HFIP) did not fit the correlation. Second, no rate dependence on solvent nucleophilicity β was found, despite other works indicating a weak dependence on this param eter (12, 13). Also, different correlations were observed for hydroxylic and nonhydroxylic solvents; Bentley considered this finding to indicate that the dehydrohalogenation transition state (in nonhydroxylic solvents) and the solvolysis transition state (in hydroxylic solvents) were significantly different and thus concluded that the two types of reactions should not be included in the same correlation. Our decision to attempt correlation of f-BuCl rates with the S C E was based on the availability of an expanded data set (21 versus 15 solvents) and a recent appreciation that the cavity term should be included in the S C E (14). Application of the four-parameter S C E , equation 1, to correlation of the full 21-solvent data set gives an excellent correlation that removes the objections to the previous study (r = 0.9973 and sd = 0.24) (7):


Η

l o g * = - 1 4 . 5 8 + 0.488^/100 + 5.09 ττ* + 4.17α + 0.71β

(2)

Points for T F E and HFIP, as well as hydroxylic and nonhydroxylic solvents, fit the correlation nicely. Also, a weak, but statistically significant, depen dency on solvent nucleophilicity β exists. Also noteworthy is the large dependence of the reaction rate on solvent electrophilicity. These results indicate that application of the S C E to reaction rates is legitimate. We are currently applying further kinetic tests to the S C E to determine the range of its applicability to kinetic phenomena. One such test, for example, is to determine the sensitivity of reaction rate of sulfonium salt solvolysis to solvent electrophilicity (i.e. its a value). Because the leaving group is neutral in this case, such a reaction would be expected to have a very weak dependence on electrophilicity. Variable Electrophilicity and Failure of the EtOH-TFE

Method

If we assume that the S C E can be used to correlate kinetic processes, then a means of testing our earlier conclusions regarding failure of the E t O H - T F E method is provided. According to our proposal, a nonlinear E t O H - T F E plot


17.

HARRIS ET AL.

Estimating Nucleophilic Assistance in Solvolyses

251

can result from enhanced E S A for 1-AdCl and from N S A for the test sub strate. Examining the E t O H - T F E plot for f-BuCl provides an illustration of these two factors. Figure 2 shows the typical nonlinear E t O H - T F E plot that had pre viously been assumed to be typical for a k substrate reacting with NSA. In this case of f-BuCl solvolysis, however, we can use equation 1 to calculate the magnitude of N S A for i - B u C l to see if this assistance will account for the nonlinearity. A n example is for 40% ethanol and 97% T F E . According to the original assumption of Raber et al. (3), these two solvents differ only in nucleophilicity because the rate for 1-AdCl is unchanged. Thus, the differ ence in rates of approximately 1 log unit in these two solvents would, according to this assumption, result from the &β term for f-BuCl (b = 0 for 1AdCl). We estimate that β for 40% ethanol is very unlikely to be higher than 0.5, and because b = 0.71, only 0.4 log unit can be attributed to N S A for tB u C l solvolysis. According to our proposal, the remaining 0.6 log unit results from enhanced sensitivity to electrophilicity (the a value) on the part of 1AdCl. To look at the nonlinearity as resulting from E S A to 1-AdCl, we can compare the difference in rates (1.4 log units) between 60% ethanol and 97%


s

• H.0 10E · • 20E 2

3

2 log k

I

30Ε ·

40E ^ I

· 50E

•

97HF

r e l

50E · t-BuCl

J· 1

™

1 ·

*

60E 0

•

80E

T

—

J 97T

• 70E

1

I

«

ι

0

1

2

1 3 log k

1

1

4

5

1-AdCl

Figure 2. Correlation of logarithms of solvolysis rates for 1-adamantyl chloride versus tert-butyl chloride at 25 °C (7). Ε represents ethanol, Τ represents trifluoroethanol, and HF represents hexafluoro-2-propanol.


252

NUCLEOPHL IC IT IY

T F E (Figure 2). Assuming that the β value for 60% ethanol is 0.5, we calculate (from &β) that 0.4 log unit of the 1.4 log units results from N S A to teri-butyl. Thus, we see that E S A must account for 1 log unit, and because the difference in α values for 60% E t O H and T F E is 0.5, we calculate (Δα)(Δα) = E S A

(3)

(Δα)(0.5) = 1.0


Δα

=2

Because the a value for f-BuCl equals 4.17, this analysis indicates that the a value for 1-AdCl must be approximately 6. Accurate determination of the a for 1-AdCl requires solution of the full S C E equation. Unfortunately, this solution is difficult to accomplish because determining rates in weakly nucleophilic, nonhydroxylic solvents is a com plex matter. A n example is the study of Kevill and Kim (15) on the solvolysis of 1-adamantyl arenesulfonates in acetonitrile. These workers found that the reaction proceeded to give an early equilibrium between the reactant and the nitrilium ion formed by acetonitrile acting as nucleophile. So that the equilibrium could be removed and good kinetics obtained, trapping of the cation with azide ion to give a tetrazole product was necessary. Presumably, other solvolyses of 1-Ad derivatives in other weakly nucleophilic solvents would be similarly complex. Having rates in these nonhydroxylic solvents is critical if the complete equation is to be solved because of colinearity between certain of the independent variables in hydroxylic solvents. To circumvent this problem, and to permit estimation of a values for substrates such as 1-AdCl, we have developed "the method of double differ ences" or M O D D . This approach is based on the observation that the differences in b and π* values for the two pairs of solvents ethanol-methanol and T F E - H F I P are quite similar and that the differences between the differences for the pairs (i.e., the double differences) are therefore quite small: Δ τ τ * _ = 0.06, Δ τ τ * _ = 0.08, ΔΔττ* = - 0 . 0 2 , Δ Δ δ ^ / 1 0 0 = - 0 . 0 5 , Δ Δ α = 0.55, and Δ Δ β = - 0 . 1 5 . If the dipolarity-polarizability and cavity terms are assumed to be negligible, then the rate difference for these pairs can be reduced to 2

H

Τ Ρ Ε

Η Ρ Ι Ρ

ΔΔ log k = a(0.55) +

Ε ι Ο Η

Μ β Ο Η

fo(-0.15)

(4)

Because b is 0 for 1-AdCl, the equation in this case is further simplified: ΔΔ log k = 0.55a

(5)

Substituting the proper values for the rates gives an a for 1-AdCl of 6.47. Applying the M O D D equation, equation 4, to f-BuCl solvolysis gives an α of


17.

HARRIS ET AL.

Estimating Nucleophilic Assistance in Solvolyses

253

4.29, which is close to the actual value of 4.17 obtained from solution of the full S C E . The a value from the M O D D of 6.47 is consistent with the value of 6 calculated previously from the E t O H - T F E plot for f-BuCl where the plot nonlinearity was assumed to result from a combination of NSA for f-BuCl and E S A for 1-AdCl. A consistent picture emerges from these preliminary re sults: further support is provided for the conclusion that the S C E is suitable for treating kinetic results, and apparently the E t O H - T F E method for detecting N S A overestimates the importance of nucleophilicity by ignoring variations in substrate susceptibility to E S A .


Electrophilicity and Mustard Solvolysis To return to the earlier question of failure of the E t O H - T F E method for solvolysis of II, we can apply the M O D D to determine the α value for reaction of this compound; again, an α value much smaller than the value of 6 for 1-AdCl should be found. Examination of Figure 1 shows that a 2 log unit difference between 60% ethanol and 97% T F E exists. Because b = 0 for mustard, all this difference must come from differences in α values. Applica tion of equation 3 gives (Δα)(Δα) = E S A = 2, (Δα)(0.5) = 2, and Δα = 4 or a = 2. Application of the M O D D , equation 5, gives an a value of 1.6 for II. Again, reasonable agreement exists between the a value necessary to account for the nonlinearity of the E t O H - T F E plot and the a value calcu lated by the approximate M O D D approach derived from the S C E . n

Acknowledgments The work at the University of Alabama was supported by The Army Research Office (DAAG29-82-K-0181). R. M . Doherty and M . J. Kamlet received support from the Naval Surface Weapons Center Foundational Research Program.

Literature Cited 1. Bentley, T. W.; Schleyer, P. v. R. Adv. Phys. Org. Chem. 1977, 14, 1. 2. Harris, J. M . Prog. Phys. Org. Chem. 1974, 11, 89. 3. Raber, D. J.; Neal, W. C., Jr.; Dukes, M . D.; Harris, J. M . ; Mount, D. L. J. Am. Chem. Soc. 1978, 100, 8137. 4. Harris, J. M . ; McManus, S. P. J. Am. Chem. Soc. 1974, 96, 4693. 4. Streitwieser, A., Jr. Solvolytic Displacement Reactions; McGraw-Hill: New York, 1962. 6. McManus, S. P.; Neamati-Mazraeh, N . ; Hovanes, Β. Α.; Harris, J. M . J. Am. Chem. Soc. 1985, 107, 3393. 7. Harris, J. M . ; Taft, R. W.; Abraham, M . H . ; Doherty, R. M . ; Kamlet, M . J. J. Chem. Soc., Perkin Trans. 2, in press.


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8. Kamlet, M. J.; Abboud, J. L. M.; Taft, R. W. Prog. Phys. Org. Chem. 1981, 14, 485. 9. Taft, R. W.; Abraham, M. H.; Doherty, R. M.; Kamlet, M. J. Nature (London) 1985, 313, 384. 10. Taft, R. W.; Abraham, M. H.; Doherty, R. M.; Kamlet, M. J. J. Am. Chem. Soc. 1985, 107, 3105. 11. Abraham, M. H.; Taft, R. W.; Kamlet, M. J. J. Org. Chem. 1981, 46, 3053. 12. Bentley, T. W.; Carter, G. Ε. J. Org. Chem. 1983, 48, 579. 13. Kevill, D. N.; Kamil, W. Α.; Anderson, S. W. Tetrahedron Lett. 1982, 23, 4635. 14. Kamlet, M. J.; Doherty, R. M.; Abraham, M. H.; Taft, R. W.; Harris, J. M. J. Chem. Soc., Perkin Trans. 2, in press. 15. Kevill, D. N.; Kim. C. B. J. Org. Chem. 1974, 39, 3085.


RECEIVED for review November 19, 1985. A C C E P T E D June 30, 1986.


Electrophilic Interference in Methods for Estimating ... - ACS Publications

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