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Nucleophilic Solvent Assistance in Soholysis
for PL 480 Grant, Agreement 02-001-0, and the National Science Foundation for Grant GP32854, in support of this work. K. Humski also expresses his thanks to the Chairperson and the Faculty of the Department of Chemistry, Indiana University, for their hospitality during his sabbatical leave.
References and Notes (1) . . K. Humski. V. Sendiiarevic, and V. J. Shiner, Jr., J. Am. Chem. Soc., 95, 7722 (1973). (2) K. Humski, V. Sendijarevic, and V. J. Shiner, Jr., Croat. Chem. Acta, 46, 93 (1974). (3) K. Humski, V. Sendijarevic, and V. J. Shiner, Jr.. J. Am. Chem. SOC.,96, 6187 (1974). 14) . , K. Humski. V.Sendiiarevic. and V. J. Shiner, Jr.. J. Am. Chem. Soc , 96, 2865 (1976). (5) P. E. Peterson and G. Allen, J. Org. Chem., 27, 1505 (1962).
( 6 ) W. Dowd, Ph.D. Thesis, indiana University, 1970. (7) R. D. Fisher, Ph.D. Thesis, Indiana University, 1971. (8) F. L. Schadt, P. v. R. Schleyer, and T. W. Bentiey, Tetrahedron Left., 2335 (1974). (9) A. Streitwieser, Jr., R. H. Jagow, R. C. Fahey, and J. Suzuki. J. Am. Chem. SOC.,80, 2326 (1958). (IO) J. 0. Stoffer and J. D. Christen, J. Am. Chem. SOC.,92, 3190 (1970). (11) R. S. Tipson, J. Org. Chem., 9, 235 (1944). (12) Details of this calculation procedure will be published elsewhere. (13) Partial double bond formation does not significantly reduce the a - d effect; fractionation factors for H vs. D at ethylenic carbon seem to be very similar to those at equivalently substituted carbonium ion centers (V. J, Shiner, Jr., "Isotope Effects in Chemical Reactions", C. J. Collins and N. S. Bowman, Ed., Van Nostrand-Reinhold,Princeton, N.J., 1970, p 107). (14) V. J. Shiner, Jr., R. D. Fisher, and W. Dowd, J. Am. Chem. SOC.,91,7748 (1969). (15) 8. L. Murr, Jr.. and V. J. Shiner, Jr., J. Am. Chem. SOC., 84, 4672 (1962). (16) M. W. Rapp, Ph.D. Thesis, indiana University, 1968. (17) H. R. Pinnick, R. C.Seib, and V. J. Shiner, Jr.. unpublished results.
Contrasting Responses in Aqueous Trifluoroethanol and Aqueous Ethanol as a Probe for Nucleophilic Solvent Assistance in Solvolysis Douglas J. Raber,*la William C. Neal, Jr.,la Michael D. Dukes,la J. Milton Harris,*lb and Dwight L. Mountlb Contribution from the Department of Chemistry, The University of South Florida, Tampa, Florida 33620, and the Department of Chemistry, The Unicersity of Alabariia in Huntscille, Huntsoille, Alabama 35807. Receiced May 4, 1978
Abstract: Aqueous trifluoroethanols are m u c h less nucleophilic solvents t h a n aqueous ethanols. As a consequence, solvolysis reactions proceeding w i t h o u t nucleophilic solvent assistance ( k , a n d k A processes) a n d solvolysis reactions proceeding w i t h nucleophilic solvent assistance ( k , processes) show t o t a l l y d i f f e r e n t responses t o changes f r o m the aqueous ethanol system t o t h e aqueous t r i f l u o r o e t h a n o l system. These contrasting responses for k , a n d for k , a n d k A processes are precisel) defined in t h e present w o r k b y e x a m i n i n g solvolyses of substrates w h i c h are r e a d i l y classified either as k , o r as k , or k ~T h. e result is a new m e t h o d for d e t e r m i n i n g the involvement of solvent nucleo'phile in solvolysis reactions.
The molecularity of the rate-determining step of a solvolysis reaction is difficult to determine because first-order kinetics are observed for both unimolecular and nucleophilically assisted bimolecular reactions (Schemes I and 11). In the present work a method for detecting the presence of nucleophilic solvent assistance in these reactions is by considering the responses of model unimolecular substrates ( k , or k A rea c t i o n ~ (Scheme )~ I ) and model bimolecular substrates ( k , reaction^)^ (Scheme 11) to changes in water concentration in aqueous trifluoroethanol ( T F E ) and aqueous ethanol (EtOH). The effects of solvent variation on solvolysis reactions can be effectively predicted by use of empirical equations which consider solvent ionizing power (Y) and solvent nucleophilicity ( N ) ,eq 1 , as the only solvent parameters.6-*
Scheme I
H
'
X
-S-
H
El
-c-c-
I + SOH
I 1OS
Scheme I1
In this equation 1 and m represent respectively substrate response to variation in solvent nucleophilicity and ionizing power, ko is the rate constant in 80% aqueous ethanol, and k is the rate constant in some other solvent of nucleophilicity N and ionizing power Y . A model unimolecular substrate should show a negligible response to solvent nucleophilicity ( I N 0) and a large response to solvent ionizing power ( m N 1); in contrast a model bimolecular substrate should show a large response to solvent nucleophilicity (1 E 1) but only a moderate response to solvent ionizing power ( m N 0.5). Aqueous T F E 0002-7863/78/1500-8137$01.00/0
S,' and aqueous ethanol are quite different solvent systems. Ethanol and water are both highly nucleophilic, but water has a much greater ionizing power; consequently, for aqueous eth-
0 1978 American Chemical Society
8138
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Journal of the American Chemical Society
70
-LO
-LO
o
60
50
1#0
/
2,o
Y Figure 1. A plot of solvent nucleophilicity ( N ) against solvent ionizing power ( Y ,based on 2-adamantyl tosylate) for aqueous ethanol and aqueous trifluoroethanol. The numbers near the points refer to the percentage of the nonaqueous component in the solvent mixtures. The data are taken from ref 6b. In all figures in this paper circles are used to designate aqueous ethanols and triangles are used to designate aqueous trifluoroethanols.
anol increasing ethanol content produces a sharp decrease in ionizing power accompanied by essentially unchanged nucleophilicity. In contrast, water is far more nucleophilic than TFE, although both solvents have high ionizing power; consequently, an increase in T F E content for aqueous T F E produces a sharp decrease in nucleophilicity accompanied by essentially unchanged ionizing power. These relationships are clearly illustrated by Figure where solvent nucleophilicity N is plotted as a function of solvent ionizing power Y. The above reasoning indicates that bimolecular and unimolecular substrates should show sharply contrasting behavior in the aqueous ethanol and aqueous T F E solvent families. For example, the solvolysis of a bimolecular substrate in an aqueous T F E medium should show a large rate response to increasing the amount of water in the medium because this component provides the nucleophilic or basic solvent assistance to which this substrate responds. However, in aqueous ethanol both components have high nucleophilicity and the small variation in rate expected with changes in solvent composition should be primarily a function of the modest changes in ionizing power. Thus to a first approximation the behavior of the bimolecular substrate should be dependent on both N a n d Y in aqueous T F E but only on Y in aqueous ethanol. In contrast the behavior of a unimolecular substrate will be independent of N in both cases. It is this different dependence on N for the two substrates in the different solvent families which provides information on the molecularity of the solvolysis reaction. The differing responses of the bimolecular and unimolecular substrates can be effectively demonstrated by examing logarithmic plots of rate constants for solvolysis in aqueous T F E and aqueous ethanol for the substrates in question as a function of the corresponding rate constants for a model unimolecular substrate. For any substrate that solvolyzes by a unimolecular mechanism (Scheme I) the plot of the rate constants against those of the model substrate should result in a single straight line for both the aqueous ethanol and aqueous T F E solvent families. However, if nucleophilic participation or elimination is important in the rate-determining step then a single line should not be adequate for correlation of the data obtained in two such different families of solvents. In the present paper we develop the method described above (henceforth described as the ethanol-TFE method) by constructing logarithmic plots for the solvolytic rate constants of well-understood substrates in aqueous T F E and aqueous ethanol as a function of the rate constants for 1 -adamantyl bromide, a model unimolecular substrate.
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Results and Discussion Definitions. Solvolysis reactions proceeding by bimolecular rate-determining steps are of two mechanistic types: S N ~ (substitution and nucleophilic bimolecular) and E2 (elimination bimolecular). The designation k , has also been used frequently to describe solvolytic processes in which there is nucleophilic solvent assistance.5 This nucleophilic solvent assistance includes nucleophilicity toward both carbon and hydrogen (Scheme 11), so both s ~ and 2 E2 mechanisms are included in the k , designation. Solvolysis reactions proceeding by unimolecular rate-determining steps are also cf two mechanistic types: S\ 1 (substitution nucleophilic unimolecular) and E l (elimination unirnolecular);l0 unimolecular ionization may also be assisted by neighboring-group participation. The designation k , has been assigned to processes in which ionization is not assisted,” and the designation k A has been assigned to those processes in which unimolecular ionization is assisted by neighboring-group p a r t i ~ i p a t i o nIt . ~ is frequently observed that neighboring group assisted ( k A ) and nucleophilic solvent assisted (k,) processes are c ~ m p e t i t i v e . ~ ~ ’ ~ Solvolyses in which there is no nucleophilic solvent assistance have also been described as “limiting” solvolyses, and include both k , and kA p r o c e s ~ e s . ~ , ~ ~ There also have been attempts to include in the mechanistic designation the cxtent to which ion pairing is i n ~ o l v e d . ’ ~ However, the method which is developed in the present work is not concerned with the identification of ion pairs, so these more informative but more complicated mechanistic labels will not be used here. Our goal is simply to determine the presence or absence of nucleophilic solvent assistance. Model Unimolecular or Limiting Substrates. For the purpose of developing the ethanol-TFE method we have examined five substrates for which there is considerable evidence that reaction occurs via rate-determining unimolecular ionization. These substrates are I-adamantyl bromide (1) and chloride
s
1.
2.
s = Hr s = c‘1
/
3
H 4
OH
i-Pr
TsO
5
(2), 2-adamantyl tosylate (3), em-2-norbornyl tosylate (4), and menthyl tosylate (5). Another substrate whch might have been included in this list is tert-butyl chloride, since it has been proposed as a model limiting s ~ b s t r a t e , but ~ , ~we ~ have excluded it on the basis of its unusual behavior in aqueous TFE.* In the following paragraph we review the evidence for the limiting nature of the solvolyses of these compounds proposed as limiting models. The solvolyses of 1-adamantyl bromide and chloride, as of most bridgehead derivatives,’ must be k , processes since it is sterically impossible for a nucleophile to approach the backside of the reaction center and elimination to form a bridgehead alkene is not energetically fea~ible.1~ The solvolyses of 2-adamantyl derivatives have been studied extenand these substrates clearly react with little or no nucleophilic solvent assistance. As with 1 -adamantyl derivatives, backside approach to the reaction center of the 2adamantyl system is sterically hindered (although not totally
Raber, Harris, et al.
1 Nucleophilic Solvent Assistance in Solvolysis
8139
Table 1. Solvolysis Rates (-log k ) for Alkyl Derivatives in Various Solvents at 25
substrate 1-adamantyl bromide
I-adamantyl chloride 2-adamantyl tosylate
exo-2-norbornyl tosylate menthyl tosylate methyl tosylate 2-propyl brosylate
IOOE
90E
80E
70E
60E
50E
97T
85T
70T
60T
50T
9.06
7.61
5.81
4.54 6.04d 6.33
5.07h
3.75 5.13d 5.64 2.03 5.32 6.29' 4.94 2.939 5.29 3.16 6.48 4.73
3.46
5.46h 3.13 7.05 5.16
4.02 5.27d 5.71 2.32 5.36 8.06' 5.68 3.459 5.77 3.50 6.28 4.86
3.64
8.19
5.14 6.36 6.70 2.80 6.18 5.41
3.97
9.37 5.35
6.29 8.12' 7.62 3.64 6.75
5.71
cyclopentyll brosylate cyclohexyl tosylate cycloheptyl brosylate 2-phenyl-1 -propyl tosylate
5.89 5.20 3.50 7.75
endo-2-norborn y I brosq late
OCO
7.23
4.84 3.14 6.12h 3.67 7.54' 5.70
3.22 6.49 2.84 5.65 3.21 7.37 5.46
5.31 4.40
6.59 4.14
5.70 2.06 5.37 7.37' 5.68 3.34 6.46 4.80
5.47 5.21 6.16' 4.55 4.88 3.02 6.50 4.57
Reference 4. a E = aqueous ethanol; T = aqueous trifluoroethanol. Ethanols are volume percent, trifluoroethanols are weight percent. P. v. R. Schleyer and R. D. Nicholas, J . Am. Chem. Soc.,83,2700 (1 961). P. v. R. Schleyer and T. W. Bentley, unpublished results. e Reference 2b. I' Reference 34a; 40 O C . 9 Estimation from rates at 30 O C (ref 34a) by multiplying by a factor of 2. Reference 6a. ' Reference 39.
6
7
I
/
3
6
-LxI K
2-my:
8
9
4
-1 - 0 BR Figure 2. The EtOH-TFE plot for (a) I-adamantyl chloride (open symbols) and (b) em-2-norbornyl tosylate (filled symbols). ."~ K
as with 1 -adamantyl) and elimination is again strongly disfavored. The importance of neighboring carbon participation in 2-adamantyl tosylate solvolysis is, as usual,2'%22 difficult to assess. This substrate does react to give minor amounts of rearranged products with the stereochemistry expected for intermediacy of a bridged intermediate,'8,20but none of the several possible i n t e r p r e t a t i ~ n sof l ~these results is consistent with nucleophilic solvent assistance. The solvolysis of exo-2norbornyl derivatives gives only exo-2-norbornyl substitution products, thus eliminating a k , mechanism which would require inversion of configuration at the reaction center.2' Again the major mechanistic uncertainty is the extent to which the unimolecular ionization is assisted by neighboring carbon.22 Menthyl tosylate ( 5 ) solvolysis is interesting in that studies of stereochemistry and @-deuteriumisotope effects indicate that it reacts by a limiting mechanism; other cyclohexyl compounds react primarily by a k , m e ~ h a n i s m . For ~ ~ nucleophilic -~~ attack on carbon or for elimination by an E2 process to be favorable for menthyl tosylate, it would be necessary for the molecule to adopt conformation 5b (Scheme 111) or possibly a twist boat c ~ n f o r m a t i o n ; however, ~ ~ - ~ ~ the experimental evidence does not support such a possibility. For example, Sunko and his co-workers studied the solvolysis of menthyl tosylate in 70% aqueous ethanol and 70% T F E and found that the products which would be expected for a solvent-assisted reaction (whether direct displacement or elimination) constitute only a small proportion of the total products.23Whether or not this ionization may be assisted by neighboring u participation is not known.
a -LOG K
6 1-KV BFi
4
Figure 3. The EtOH-TFE plot for (a) 2-adamantyl tosylate (filled symbols) and (b) menthyl tosylate (open symbols).
In Table I are presented rate constants at 25 "C in several aqueous ethanol and trifluoroethanol mixtures for the substrates considered in the present work. Rate constants at temperatures other than 25 O C and experimental errors are presented in Table 11. As would be expected on the basis of the previous discussion, logarithmic rate-rate plots for any pair of the limiting substrates presently under consideration should yield linear correlations for all solvents considered. This is easily shown by further consideration of eq 1 ; for limiting substrates I will be zero and log k for each substrate will be linearly related to the ionizing power Y . A plot of log k vs. log k for two limiting substrates must therefore be linear. Since solvent assistance and elimination must be at an absolute minimum for I-adamantyl bromide we have utilized this compound as our reference ~ t a n d a r d . ' The ~ . ~plots ~ for compounds 2-5 are shown in Figures 2 and 3, and all of the plots show good linearity. Some of the deviations from linearity exhibited in these plots are due to solvent effects on leaving-group abilities.6.28 For example, several of the substrates examined later in this study are brosylates, and brosylate/tosylate rate ratios show the following solvent dependencies: OBs/OTs = 5.0 in aqueous ethanol and 3.0 in aqueous trifluoroethanol and formic and acetic acids.28 However, plots for substrates with the same leaving group are not perfectly linear.4 There are several readily identifiable contributors to this continued nonlinearity. First, reactant solvation has been d e m ~ n s t r a t e dto~be ~ a major contributor to solvent effects on ionization processes, and this
Journal of the American Chemical Society
8140
/ 100.26 / December 20, I978
Table 11. Solvolysis Rates Determined in This Study compd cycloheptyl OBs
solvent
80% EtOH 70% EtOH 50% EtOH 97% T F E 85% T F E
menthyl OTs
70% T F E 60% T F E 80% EtOH 70% EtOH 60% EtOH 50% EtOH 97% T F E 85% T F E 70% T F E 60% T F E
methyl tosylate
50% EtOH 60% EtOH
90% EtOH cyclohexyl OTs
70% E t O H 97% T F E 85% T F E
70% T F E 50% T F E 2-phenyl-I-propyl OTs
90% E t O H 70% E t O H 60% EtOH 50% E t O H
t, O
C
50.2 30.5 25.0" 50.2 30.5 25.0° 25.0 50.2 30.5 25.0° 50.2 30.5 25.0" 25.0 25.0 95.2 75.7 25.0" 95.2 75.7 25.OU 95.2 75.7 25.00 75.7 75.7 50.2 25.0" 75.7 50.2 25.0° 75.7 50.2 25.0" 75.7 50.2 25.00 100.0 74.9 25.0" 100.0 75.0 25.0" 100.0 75.0 25.0" 75.0 50.0 25.0a 50.0 75.0 25.0" 50.0 75.0 25.0" 50.0 75.0 25.0" 50.0 75.0 25.0n 100.0 125.0 25 a 100.0 125.0 25" 100.0 125.0 25n 100.0 125.0 25 a
k , s-'
3.24 f 0.01 x 3.98 f 0.01 x 2.12 x 10-4 5.54 f 0.24 x 9.23 f 0.12 x 5.38 7.45 f 0.09 X 4.29 f 0.03 X 5.78 f 0.02 X 3 . 1 6 x 10-4 6.43 f 0.04 X 8.48 f 0.03 X 4.61 x 10-4 6.98 f 0.02 x 9.47 0 . 1 8x 1.08 f O . O 1 X 1.29 f 0.06 X 1.72 x 10-7 2.20 f 0.07 X 2.66 f 0.07 X 3.22 x 10-7 4.17 f 0.06 X 4.85 f 0.33 X 6.64 x 10-7 I .07 f 0.04 X 1.63 f 0.01 x 1.05 f 0.02 X 4.40 x I O + I .8 1 f 0.04 X 1.08 f 0.01 X 4.23 X IO-h 2.46 f 0.02x I .36 f 0.00 X 4.76 X 3.18 f 0.14X I .78 X 0.02 X 6.10 X 2.68 f 0.04 X 4.37 f 0.04 X 4.87 X IO6 2.14 % 0.02 x 3.53 f 0.04 X 3.92 X 1.04 f 0.02 x I .54 % 0.02 x 1.28 X 6.62 f 0.12 x 4.77 0.02 x 2.23 x 3.35 f 0.04 x 4.33 i 0.13 x 1.70 X 1 0-6 5.53 f 0.26 x 9.21 f 0.12 x 2.09 X 1.11 f 0.01 x 1.56 i 0.01 x 5.07 x 2.53 f 0.02 x 3.21 f 0.18 X 1.31 x 10-5 3.89 f 0.04 X 2.68 f 0.1 I x 1.77 x 10-8 1.55 0.01 x 1.22 f 0.01 x 4.21 X 2.64 f 0.03 X 1.96 f 0.04 X 8.91 X 4.49 0.05 x 2.92 f 0.12 x 2.54 x 10-7
A H * , kcal/mole
AS*,eu
20.1
-7.8
17.1
-16.1
19.2
-10.1
19.4
-8.6
26.5
-0.5
26.8
1.6
26.5
2. I
23.5
-4.3
23.9
-2.9
24.8
0.37
25.0
I .4
17.9
-22.7
17.9
-23.2
19.1 22.9
-21.5 -7.8
22.2
- 10.4
24.5
-2.4
23.0
-5.7
22.0
-7.0
22.0
-20.1
23.5
-13.5
22.9
- 14.0
21.4
- 17.0
10-3
10-3
I 0-4 IO-4
IO-4
10-4
IO-?
IO-? 1O-j 1 OW3
low4
I 0-3 10-3 I 0-3 IOw4 10-3
I O-J
I 0-3 IOTJ 10-3 10-4
I 0-4 10-5 10-5
10-4 10-5 10-4
10-4
10-3 10-4 10-
10-4 10-4
10-3
10-4 10-3
Nucleophilic Solvent Assistance in Solvolysis
Raber, Harris, et a/.
8141
Table 11 (Continued) compd
solvent
t , OC
97% T F E
75.0 100.0 25.0" 75.0 100.0 25.00 75.0 100.0 25.00 75.0 100.0 25.0"
85% T F E 70% T F E 50% T F E
k , s-l 7.53 0.06 x 5.51 f 0.29 x 5.25 x 10-7 8.25 x 7.38 f 0.02 x 3.49 x 10-7 9.20 f 0.1 I x 8.76 f.0.04 3.32 x 10-7 1.18 k 0.01 X 1.26 0.01 x 3.78 x 10-7
AS*, eu
AH*, kcal/ mole 10-5
19.8
-20.7
21.9
- 14.6
22.6
-12.5
23.8
-8.6
10-4
10-5
10-3
" Calculated from rates at other temperatures. Scheme 111; hlentli).l Tosylate Solvolysis
H
i .Pr 6 -L3G K
7 'AEThYL
CH
H 5b
5a
H
a
I
I I
I
I
8
6
4
-LOG
K l-AD1 AR
Figure 4. The EtOH-TFE plot for methyl tosylate.
process is a function of molecular size and shape,30 both of which vary somewhat for the substrates under consideration, Second, solvation of the highly polar transition states for these apparently simple ionization processes is a function both of position of the transition state on the reaction coordinate (i,e,, the extent of charge development) and, as has recently been i n d i ~ a t e d , ~also ' , ~ ~of the manner in which the developing positive charge is delocalized. A third factor contributing to the observed nonlinearity is extrapolation error which results from comparison of rates determined at different temperatures. All of these factors vary for the five limiting substrates. Thus a minimum requirement for obtaining a perfectly linear correlation for plots such as those of Figures 2 and 3 would be to match substrates having the same leaving group, similar rates and positions of the transition state on the reaction coordinate, and similar sizes and shapes; but even this degree of matching might not be sufficient. The limitation on linearity does not, however, introduce any serious problems. Plots such as those in Figures 2 and 3 are indicative of reaction having little or no involvement of solvent as nucleophile, and as long as different results are obtained with k , substrates, the ethanol-TFE method will serve to detect the presence of nucleophilic solvent assistance. Model k , Substrates. Primary substrates have been convincingly demonstrated to solvolyze by nucleophilic displacement ( S N ~processes, ) which in certain instances, such as for neopentyl derivatives, may be in competition with neighboring group assisted p r o c e ~ s e sThe . ~ ~solvolysis ~ ~ ~ of secondary derivatives is much more complicated, but simple, acyclic compounds such as 2-propyl derivatives seem clearly to react by a simple nucleophilic displacement m e ~ h a n i s m . ~ ~Conse'3 quently, methyl tosylate and 2-propyl brosylate provide non-
3
-LOG
I(
4
5 6
I
I
/
6
8 -Lot K
4
l-NYlBR
Figure 5. The EtOH-TFE plot for (a) 2-propyl brosylate (open symbols) and (b) cyclopentyl brosylate (filled symbols).
controversial examples of k , substrates. Logarithmic rate-rate plots for these two compounds (again using I-adamantjl bromide as the reference substrate) produce plots (Figures 4 and sa) in which the T F E and ethanol points are not correlated by a single straight line. This can be understood more clearly by further consideration of eq 1, which, although empirical, should be capable of predicting the solvolysis rate for any substrate reacting via a single pathway. Note that the reference substrate (l-adamantyl bromide, which cannot benefit from nucleophilic solvent assistance) must have an 1 value which is effectively zero; the rates of the reference compound therefore depend only on solvent ionizing power. In contrast, the rate of solvolysis for a k , substrate must be dependent on both solvent nucleophil-
8142
Journal of the American Chemical Society
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/
100:26
/
December 20, I978
'
4 ' -Lffi K
5
'
6 .
4 1-rn BR Figure 7. The Et014 plot for 2-phenyl-I-propyl tosylate ( 2 5 "C).
8
6
-Lffi K
7
6
5
4
3
-La K 1-m8P Figure 6. The EtOH-TFE plot for (a) cyclohexyl tosylate (open symbols) and (b) cyclohept),l bros),late (filled symbols).
Scheme IV. Discrete Pathways for k , and k~ in the Solvolysis ot 2-Phenyl-1 - p r o p y l T'osylate 16) SOH
icity and solvent ionizing power. For the aqueous ethanols the solvent nucleophilicity remains nearly constant and a linear correlation with the data for 1-adamantyl bromide is anticipated. However, the solvent nucleophilicity varies greatly for the aqueous trifluoroethanols. and inspection of Figure 1 suggests that the T F E data points for a k , substance should not fall on the same line as the aqueous ethanol points. In fact the fortuitous linearity of iV as a function of Y9.33demands that the T F E data points form a second straight line, and this is precisely the behavior observed for the model k , substrates (Figures 4 and Sa). Cyclopentyl, cyclohexyl, and cycloheptyl derivatives are also regarded as compounds which solvolyze by a k , mechanism. Shiner and his co-workers have extensively studied the stereocheniistry of elimination and substitution as well as the kinetic effects of a and p deuteria to assign the mechanism of cyclopentyl brosylate with an uncommon degree of That substitution for cyclopentyl brosylate is a k , process is indicated by the a-deuterium isotope effect ( a - d ) of 1.15 (significantly less than the maximum of 1.22 found for k , processes) and the formation of totally inverted substitution product. The elimination process is indicated to be rate determining by the observation of noncumulative @-deuterium isotope effects ((l-d).34a,35 Whether or not solvent is involved as base in this elimination process cannot be determined from Shiner's work, but this would certainly be a reasonable supposition.36 Bentley and Schleyer have also applied their measure of nucleophilic solvent assistance (see discussion below) to the solvolysis of cyclopentyl tosylatehiland have concluded that the aqueous ethanolysis of this compound is a k , process. Shiner and his co-workers have also examined the aqueous trifluoroethanolysis of cyclopentyl b r o ~ y l a t eand ~ ~ reaction by a h , process was suggested on the basis of the cy- and 8deuterium isotope effects and the formation of 16-2096 racemic trifluoroethyl ether (although the alcohol produced was 100% inverted).34CHowever, our results (Figure 5b: two distinct lines are observed) strongly suggest that solvent is involved in the rate-limiting steps of solvolysis of cyclopentyl derivatives in both solvent families; in the absence of solvent assistance it would be difficult to explain the large rate increase as the aqueous component of the T F E solvent system is increased. The solvolysis of cyclohexyl derivatives has also been extensively examined. The Schleyer probes indicate weak but definite nucleophilic solvent assistance i n solvents such as aqueous ethanols.6a Also, the acetolysis of cyclohexyl tosylate has been shown to give noncumulative p - d ' consistent ~~~ with rate-dcterniining elimination, and inverted substitution product?? consistent with a k , process. The only piece of evidence which is inconsistent with cyclohexyl solvolysis by a k ,
mechanism in nucleophilic solvents is the a-d for acetolysis of 1 22,26bwhich is of the magnitude expected for a k, process.34 However, it has been suggested that the a-d may, in some instances, fail as a satisfactory probe for the involvement of a nucleophile in the rate-determining step.'3s37,38The EtOHT F E plot for cyclohexyl brosylate (Figure 6a) is similar to that for the k , substrates discussed previously, with ethanol and T F E points lying on different lines. Cycloheptyl brosylate would be expected to be similar to the cyclopentyl and cyclohexyl derivatives, and its ethanol-TFE plot (Figure 6b) again shows the two lines observed for other k , substrates. Dissection of k , and kA Processes. Another test of the ethanol-TFE method IS provided by examination of 2-phenyl1 -propyl tosylate (6) solvolysis, a reaction known39 to proceed by competitive k , and k l processes. The relative amounts of the k, and k A processes will vary with solvent composition because of changes in solvent nucleophilicity and solvent ionizing power. As might be expected for a reaction in which the proportion of k , and k A processes varies, the ethanol-TFE plot for 6 is not linear (Figure 7). The actual values of k, and k A can be determined by means of product studies, since different products are formed in the two pathways as shown in Scheme IV. Since the reactions are not reversible, the k , / k A rate ratio corresponds to the ratio of primary to secondary products.39 Therefore % primary product kobsd (2)
)
and % secondary
product
) kobsd
(3)
The product distributions for solvolysis of 6 are reported in Table 111 together with the kinetic data calculated from eq 2
Raber, Harris, et al.
/
8143
Nucleophilic Solvent Assistance in Solvolysis
Table Ill. Products, Observed Rates, and Calculated k s and k A Constants for the Solvolysis of 2-Phenyl-I-propyl Tosylate at 125 OC % seca
% prim"
% seca
solvent
ROEt
ROEt
ROH
%prima ROH
90E 80E 70E 60E 50E 91T 85T 70T 50T
53.4 39.9 29.8 22.9 15.9 65.8
10.6 6.8 2.9 2.0 0.4
23.7
0.1 0.5
32.2 48.8 63.0 72.1 81.1 32.8 75.7 83.4 80.8
3.8 5.4 4.5 3.1 2.8 1.3 0.6 2.1 0.9
a
14.1 18.3
-log
-log ksC
kobsdb
3.57 3.27d 2.92 2.71 2.53 2.50 2.30 2.20 2.00
4.41 4.18 4.05 4.00 4.03 4.39 4.45 3.78 4.04
-log k AC 3.64 3.32 2.95 2.73 2.55 2.51 2.30 2.21 2.00
Products determined by gas chromatography. From the data in Table 11. Calculated using eq 2 and 3. Reference 39.
and 3. Rate data at 125 OC rather than 25 OC were used to minimize extrapolation'error when comparing product data (determined a t 125 "C) with the kinetic data. Ethanol-TFE plots of the derived k , and kA rate constants (Figure 8a) demonstrate that while a single line can adequately correlate all of the k A data, the same is not true for the k , process. The observation of two distinct lines for the k , process confirms the validity of our use of the ethanol-TFE method as a sensitive means of detecting nucleophilic solvent assistance. Sensitivity of the Method. Comparison of Figures 2, 3, and 8 b (typical k , and kA plots) with Figures 4-6 and 8 (typical k , plots) demonstrates that the ethanol-TFE method has utility for determination of nucleophilic solvent assistance in solvolysis reactions. Next we will consider the magnitude of solvent assistance necessary for detection by this method. Insight into this question is providcd by consideration of the Schleyer k s / k , ratio6a for estimating the magnitude of nucleophilic solvent assistance:
2*0
3,O -LE
K
4,o
5'0
t
/
-LE K
1-mBR
Figure 8. The EtOH-TFE plot of calculated k , (open symbols) and k a (filled symbols) rate constants at 125 "C.
k s / k c = [ k(ROTS)/ k (2-AdOTs)lany solvent/ [ ~ ( R O T ~ ) / ~ ( ~ - A ~ O T ~ (4) )~CF,C~~H Probably the greatest limitation of the k , / k , measure comes The basic assumptions in this ratio are that all secondary from the involvement of k l processes, because significant substrates react by limiting or near-limiting mechanisms in dispersal of positive charge occurs in these transition states, trifluoroacetic acid, that 2-adamantyl tosylate reacts by a resulting in low m values. The k J k , ratio is intended to be limiting mechanism in all solvents, and that the m values for applied only to k , systems and it is assumed, as noted above, all limiting substrates are approximately the same. The result that as nucleophilic solvent assistance is removed from these is a measure of nucleophilic solvent assistance received by a reactions (Le., as they become limiting) they will have m values substrate in a particular solvent relative to that nucleophilic close to unity. However, k A processes are limiting processes solvent assistance (approximately zero) received by the same with m values significantly less than unity. This distortion of substrate in trifluoroacetic acid. k , / k , values can be illustrated with the acetolysis of 3The lowest k , / k , ratio among the model k , substrates conmethyl-2-butyl tosylate, a known kA system.40For 2-adamsidered above is the value of 61 for cyclohexyl brosylate in 50% antyl and 3-methyl-2-butyl tosylates the nz values (based on ethanol. The 50% ethanol point for this system lies on the line 2-adamantyl Y values)6b are 1 .O and 0.70,40respectively, and defined by the other ethanol points, so we can conclude that for acetic and trifluoroacetic acids the Y values are -0.61 and the ethanol-TFE method still gives two clearly separate lines 4.57, respectively.6bSubstitution into eq 1 affords the following when nucleophilic solvent assistance is as low as a factor of dependence on m: approximately 60. There are no well-studied compounds with lower k , / k , ratios for us to use to further define the limitations 1% [kAcOH/kTFAl = -5.18m (5) of the ethanol-TFE method, but in view of the ease with which Rearrangement of eq 4 permits the k J k , relationship to be assistance of a factor of 60 is detected (Le., Figure 6a) the expressed as method must be capable of detecting assistance significantly below this limit. (For further discussion on this point, see the k,/kC = [ ~ A C O H / ~ T F A ] ~ - M ~ - ~ - B ~ / [ ~ A C O H /(~6T) F A ] Z - A ~ following paper.) It should be noted, as Schleyer has pointed out,6a that the and substitution using eq 5 affords k , / k , ratio is not a simple quantitative measure of the importance of nucleophilic solvent attack on carbon. The ratio k , / k , = 10-3.63/10-5l 8 = 35 (7) measures, as does our method, both nucleophilic solvent assistance and the solvent acting as a base to promote elimination The k J k , ratio of 35 results simply because of the differences when either of these processes is kinetically significant. For in m values, not from nucleophilic solvent assistance. The exexample, the k , / k , ratio of 28 for acetolysis of cyclohexyl perimental value of the k , / k , for this acetolysis reaction is tosylateba may be as much the result of elimination as of 41 .7.40 Obviously, little of this experimental ratio results from nucleophilic attack on carbon; there is 80% elimination for this nucleophilic solvent assistance. reaction,g5aand rate-determining elimination is indicated for A further indication of the limitations of the ethanol-TFE this reaction by the noncumulative P-d.*6 method is provided by examination of the ethanol-TFE plot
8144
Journal of the American Chemical Society I
I
I
Table IV. Statistical Criteria para meter slope intercept correlation coefficient standard deviation
1
I
6.0
5.0 -WG K
I
4.0
I-SJ’BR
Figure 9. The EtOH-TFE plot for endo-2-norbornyl brosylate
OTs 7
of endo-2-norbornyl brosylate (7)(Figure 9). There is a significant amount of evidence showing that this substrate reacts with weak nucleophilic solvent assistance4 (e.g., k,/k, = 30 for acetolysis), and indeed Figure 9 suggests that the ethanol and T F E points might best be considered to lie on slightly separate lines (although the points are adequately correlated by a single line). This correlation would seem to extend the sensitivity of the ethanol-TFE method beyond the k , / k c value of 60 cited above. This possibility is further emphasized by comparison with the data for exo-2-norbornyl tosylate (4). The latter compound has a k , / k , value of 8 for acetoly~is,~’ a value which must again result from factors other than solvent assistance since its limiting nature is well established.21%22 The k , / k , ratio of the endo isomer therefore exceeds that of the limiting exo isomer by only a factor of 4.Since both isomers react largely via the same carbocation, it might be argued that the factor of 4 should actually represent the lower limit for detection of solvent assistance by the ethanol-TFE method. However, close examination of the rate-rate plot for exo-2norbornyl tosylate (Figure 3b) reveals a close similarity to that of the endo isomer; that is, separate lines can again be drawn for the ethanol and T F E points even though a single line correlates all the data quite well. Consequently, we interpret plots such as the endo-norbornyl plot (Figure 9) as representing the limit of the ethanol-TFE method; i.e., as indicative either of no nucleophilic solvent assistance or of assistance which is too weak to be detected by this method. Statistical Evaluation. Although clear-cut choices regarding the presence or absence of solvent assistance are generally possible by qualitative examination of plots such as those in Figures 2-9, the fact that we are looking for linear plots suggests that simple statistical analysis should provide more objective criteria for making mechanistic assignments. Linear regression analysis of any set of experimental points affords four parameters (slope, intercept, correlation coefficient, and standard deviation) which can be used, and criteria may be established for each of these which will allow a mechanistic assignment. These criteria are discussed below and are summarized in Table IV. 1. Slope. I n the case of a limiting process the slopes of both the ethanol and T F E lines are expected to be the same (within experimental error), whereas for a k , process the ethanol points
/ 100.26 / December 20, I978
k, slope (E) < slope (T) int (E) < int (T) R ( E ) - R ( E t T) 2 0.30 SD ( E t T) > S D (E) and > S D (T) and L 0.20
limiting slope (E) = slope (T) int (E) = int (T) R(E) - R ( E t T) 5 0 . 0 1
+
(a) SD ( E T) < S D ( E ) and
