Solvolytic Reactions in Fluorinated Alcohols. Role of Nucleophilic and Other Solvation Effects

Article abstract of DOI:10.1021/jo980109d

Rate constants and products for solvolyses of chlorodiphenylmethane (Ph₂CHCl) and p-methoxybenzyl chloride in 2,2,2-trifluoroethanol (TFE)/water and TFE/ethanol are reported, along with additional kinetic data for solvolyses of tert-butyl and other alkyl halides (RX) in 97% w/w TFE/water and in 97% w/w hexafluoropropan-2-ol/water (HFIP). Results are discussed in terms of the solvent ionizing power (Y) and the solvent nucleophilicity (N), and contributions from other solvation effects are considered. Comparisons with other S_N1 solvolyses show that solvolyses of Ph₂CHCl in TFE mixtures are unexpectedly fast, but product ratios are unexceptional. An additional solvation effect influences solvolyses leading to delocalized cations, and a delocalized cationic transition state for concerted elimination may explain the recent results of Takeuchi et al., (J. Org. Chem. 1997, 62, 4904) without the need to postulate additional specific solvation effects for adamantyl systems, such as Bronsted-base solvation of α- and β-hydrogen atoms; concerted elimination may occur because simple tertiary alkyl cations are too unstable to form in predominantly aqueous media. Iodide/bromide and bromide/chloride rate ratios are very similar for 1-adamantyl halides and corresponding solvolyses of tert-butyl halides; these ratios decrease in the order aq EtOH > TFE > HFIP, as expected for an electrophilic solvation effect (this effect can readily be incorporated into Y values). From kinetic data for a series of tertiary alkyl chlorides in 97% TFE/water, it is shown that the susceptibility of rates of solvolyses of RCl to N decreases with an increase in steric hindrance or with an increase in charge stabilization. Also, the small kinetic solvent isotope effects for typical solvolyses (e.g., methyl tosylate) indicate that nucleophilic attack lags behind heterolysis of the C-X bond.

Full text of DOI:10.1021/jo980109d

4654
J . Org. Chem. 1998, 63, 4654-4659
Solvolytic Rea ction s in F lu or in a ted Alcoh ols. Role of Nu cleop h ilic
a n d Oth er Solva tion Effects
T. William Bentley,* Gareth Llewellyn, and Zoon Ha Ryu1
Department of Chemistry, University of Wales, Swansea, Singleton Park, Swansea SA2 8PP, Wales, U.K.
Received J anuary 21, 1998
Rate constants and products for solvolyses of chlorodiphenylmethane (Ph2CHCl) and p-methoxy-
benzyl chloride in 2,2,2-trifluoroethanol (TFE)/water and TFE/ethanol are reported, along with
additional kinetic data for solvolyses of tert-butyl and other alkyl halides (RX) in 97% w/w TFE/
water and in 97% w/w hexafluoropropan-2-ol/water (HFIP). Results are discussed in terms of the
solvent ionizing power (Y) and the solvent nucleophilicity (N), and contributions from other solvation
effects are considered. Comparisons with other SN1 solvolyses show that solvolyses of Ph2CHCl in
TFE mixtures are unexpectedly fast, but product ratios are unexceptional. An additional solvation
effect influences solvolyses leading to delocalized cations, and a delocalized cationic transition state
for concerted elimination may explain the recent results of Takeuchi et al., (J . Org. Chem. 1997,
62, 4904) without the need to postulate additional specific solvation effects for adamantyl systems,
such as Bronsted-base solvation of R- and â-hydrogen atoms; concerted elimination may occur
because simple tertiary alkyl cations are too unstable to form in predominantly aqueous media.
Iodide/bromide and bromide/chloride rate ratios are very similar for 1-adamantyl halides and
corresponding solvolyses of tert-butyl halides; these ratios decrease in the order aq EtOH > TFE
> HFIP, as expected for an electrophilic solvation effect (this effect can readily be incorporated
into Y values). From kinetic data for a series of tertiary alkyl chlorides in 97% TFE/water, it is
shown that the susceptibility of rates of solvolyses of RCl to N decreases with an increase in steric
hindrance or with an increase in charge stabilization. Also, the small kinetic solvent isotope effects
for typical solvolyses (e.g., methyl tosylate) indicate that nucleophilic attack lags behind heterolysis
of the C-X bond.
Rates of reactions of short-lived carbocations (e.g., Ph2-
having the same leaving group (a wide range of suitable
YX values is now available).5 In correlations of rate data
for other solvolyses, a high dependence of solvolytic
reactivity on YX and a low dependence on N is taken as
evidence for a solvolytically generated carbocation inter-
mediate, so l (eq 1) is negligible, and there is a linear
correlation with YX.6
CH+) with solvents are several orders of magnitude less
in fluorinated alcohols such as 2,2,2-trifluoroethanol
(TFE) and hexafluoropropan-2-ol (HFIP) than in the more
nucleophilic aqueous media.2 Also, solvolytic reactions
in fluorinated alcohols lead to less nucleophilically sol-
vated cationic intermediates, showing products due to
rearrangement, hydride shift, and elimination (i.e., greater
carbocation character).3 Solvent nucleophilicity (N) is one
of the two main factors influencing the rates of solvolytic
reactions, and the extended Grunwald-Winstein equa-
tion (1) accounts explicitly for the dependence of the
In fluorinated alcohols, substrates for which l > 0
usually react less rapidly than expected from an mY
correlation (i.e., a downward deviation in a plot of log k
vs Y/ N as in eq 1), and a value of l can be obtained from
eq 1. Additional solvation effects might be expected for
substrates containing additional functional groups (e.g.,
hydrogen bonding to oxygen in substrates leading to
carbocations having R-carbonyl6c or â-carbonyl6d groups),
but surprisingly, solvolyses in fluorinated alcohols of
substrates leading to delocalized cationic intermediates
have been found to occur more rapidly than expected from
an mY correlation (i.e., an upward deviation).7 We now
report further investigations of this phenomenon, and we
report additional kinetic data on solvolyses of tert-butyl
log(k/ko)RX ) lN + mY + c
(1)
logarithms of solvolysis rate constants (k) on N and on
the solvent ionizing power (Y); l is the sensitivity of the
substrate RX to changes in N, m is the sensitivity to Y,
c is a residual intercept term (usually close to zero), and
ko refers to solvolyses in 80% v/v ethanol/water.4
Adamantyl substrates are now considered to be more
suitable as model substrates than tert-butyl chloride to
define Y scales (by definition m ) 1 and l ) 0 for the
model substrate); to try to minimize complications due
to solvation of the leaving group (X), it is now usual to
select Y values based on solvolyses of adamantyl-X
(5) Bentley, T. W.; Llewellyn, G. Prog. Phys. Org. Chem. 1990, 17,
121.
(6) (a) Allen, A. D.; Sumonja, M.; Tidwell, T. T. J . Am. Chem. Soc.
1997, 119, 2371. (b) Creary, X.; Zhu, C.; J iang, Z. J . Am. Chem. Soc.
1996, 118, 12331. (c) Takeuchi, K.; Ohga, Y.; Yoshida, M.; Ikai, K.;
Shibata, T.; Kato, M.; Tsugeno, A. J . Org. Chem. 1997, 62, 5696. (d)
Yoshida, M.; Takeuchi, K. J . Org. Chem. 1993, 58, 2566.
(7) (a) Shimizu, M.; Osajima, E.; Tsuno, Y. Bull. Chem. Soc., J pn.
1991, 64, 1145. (b) Shimizu, M.; Kinoshita, C.; Osajima, E.; Hayakawa,
F.; Tsuno, Y. Bull. Chem. Soc., J pn. 1991, 64, 3280. (c) Stoelting, D.
T.; Shiner, V. J ., J r. J . Am. Chem. Soc. 1993, 115, 1695. (d) Fujio, M.;
Saeki, Y.; Nakamoto, K.; Kim, S. H.; Rappoport, Z. Bull. Chem. Soc.
J pn. 1996, 69, 751.
(1) Present address: Dong Eui University, Pusan, Korea.
(2) McClelland, R. A. Tetrahedron 1996, 52, 6823.
(3) Bentley, T. W. Advances in Chemistry Series; American Chemical
Society: Washington, DC, 1987; Vol. 215, Chapter 18.
(4) (a) Winstein, S.; Grunwald, E.; J ones, H. W. J . Am. Chem. Soc.
1951, 73, 2700. (b) Schadt, F. L.; Bentley, T. W.; Schleyer, P. v. R. J .
Am. Chem. Soc. 1976, 98, 7667.
S0022-3263(98)00109-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/11/1998

Solvolytic Reactions in Fluorinated Alcohols
J . Org. Chem., Vol. 63, No. 14, 1998 4655
Ta ble 1. Ra te Con sta n ts (k/s-1) for Solvolyses of
Ch lor od ip h en ylm eth a n e (1) a t 25 °Ca
Ta ble 3. P r od u ct Selectivities (S) for Solvolyses of
Ch lor od ip h en ylm eth a n e (1) a n d p-Meth oxyben zyl
Ch lor id e (2) in Tr iflu or oeth a n ol Solven t Mixtu r es a t
25 °Ca
k/s-1
solvent
composition trifluoroethanol/ethanolb trifluoroethanol/waterc
selectivitiesb
97
90
80
70
60
50
40
20
0
1.28d
solvent composition
[TFE]/[H2O]
1
2
(4.01 ( 0.06) × 10-1
(1.28 ( 0.06) × 10-1
(4.14 ( 0.07) × 10-2
(1.56 ( 0.01) × 10-2
(5.59 ( 0.02) × 10-3
(2.24 ( 0.03) × 10-3
(3.37 ( 0.10) × 10-4
5.34 × 10-5 h
1.33e,f
97 TFE-H2Oc
5.82
1.62
0.72
0.21d
0.27
0.30
0.36d
1.53g
90
0.40d (0.39)e
0.44
80
70
60
50
40
30
20
10
0.42
0.27
0.18
0.12
0.077
0.045
0.020
7.21j
3.20j
1.87j
1.20j
0.53j
0.20j
0.39
0.46
0.43f
0.50f
0.49g
0.34g
0.52
0.56f
0.54f
0.46g
0.29g
0.14h
0.040d
0.052
0.060
0.068
0.072
0.067
a
Determined conductometrically at least in duplicate; typically
injected 10 µL of 10% (v/v) substrate in dry acetonitrile into the
kinetics apparatus, fitted with a turbostirrer, and containing 5
mL of solvent mixtures (see also ref 10a); errors shown are
90 TFE-EtOHi
0.031d
0.035
0.039
0.041
0.047
80
70
60
40
20
c
standard deviations. bPercent v/v trifluoroethanol/ethanol. Per-
cent w/w trifluoroethanol/water. dLit.10b 1.05 (see also Table 4).
f
eInjected 10 µL of 3% (v/v) substrate in dry acetonitrile. Calculated
from data at lower temperatures; k ) (4.03 ( 0.40) × 10-2 and
(1.20 ( 0.01) × 10-1 s-1 at -10.0 and 0.0 °C; ∆Hq ) 15.1 kcal
mol-1, ∆Sq ) -7.5 cal mol-1 K-1 gData from ref 10b. hData from
.
a
Determined after 10 half-lives by response-calibrated HPLC
at least in duplicate for each of two independent samples; typical
error (2%; 10 µL of 10% (v/v) substrates in dry acetonitrile was
injected into a sample tube containing 5 mL of trifluoroethanol
ref 10c.
Ta ble 2. Ra te Con sta n ts (k/s-1) for Solvolyses of
p-Meth oxyben zyl Ch lor id e (2) in Tr iflu or oeth a n ol
Mixtu r es a t 25 °Ca
c
mixtures. bCalculated from eq 2. Weight percent. dAdded 2,6-
e
lutidine (2× excess) into the stock solution. Not containing 2,6-
f
lutidine. Injected 10 µL of 3% (v/v) substrate. gInjected 10 µL of
k/s-1
solvent
1% (v/v) substrate. hInjected 3× 10 µL of 0.2% (v/v) substrate.
composition trifluoroethanol/ethanolb trifluoroethanol/waterc,d
j
iVolume percent. Molar ratio of TFE/ethanol, and S defined by
97
90
80
70
60
50
40
30
20
0
(1.94 ( 0.04) × 10-1 d
(2.07 ( 0.01) × 10-1 e,f
(2.73 ( 0.04) × 10-1 f,g
(3.32 ( 0.09) × 10-1 f
(4.53 ( 0.03) × 10-1 f
(6.29 ( 0.25) × 10-1 f
(9.01 ( 0.13) × 10-1 h
(1.73 ( 0.15)h
replacing [ROH] and [water] by [ROEt] and [EtOH] in eq 2.
(6.72 ( 0.16) × 10-2
(2.67 ( 0.01) × 10-2
(9.46 ( 0.02) × 10-3
(3.71 ( 0.17) × 10-3
(1.42 ( 0.01) × 10-3
(5.75 ( 0.11) × 10-4
S ) [ROCH2CF3]/[ROH] × [water]/[TFE] (2)
Additional kinetic data in 97% w/w TFE/water are
given in Table 4 and in HFIP/water are given in Table
5. Recent work on kinetic solvent isotope effects in
MeOH(D) is supplemented with additional data for
solvolyses of methyl tosylate in Table 6.
(1.01 ( 0.01) × 10-4
1.67 × 10-5 i
a-c As for Table 1. dData from ref 11a. ek ) (5.72 ( 0.02) × 10-3
,
(1.82 ( 0.04) × 10-2 and (2.07 ( 0.01) × 10-1 s-1 at -10.0, 0.0,
and 25.0 °C, respectively; ∆Hq ) 15.4 kcal mol-1, ∆Sq ) -10.0 cal
Discu ssion
mol-1 K-1. Injected 10 µL of 3% (v/v) substrate in dry acetonitrile
f
Although TFE/water mixtures and ethanol/water mix-
tures differ in nucleophilicity, the YCl values of 2.83 for
97% TFE/water (97T) and of 2.75 for 40% v/v EtOH/water
(40E) are so similar that the solvolysis rate ratio k40E /k97T
gives a useful indication of the susceptibility of the rate
of solvolysis of an alkyl halide (RCl) to solvent nucleo-
philicity (N).5 It is recognized that ethanol/water mix-
tures are nonideal solvents,14 but 80% ethanol/water is
the chosen standard for Y plots, and comparisons of rate
constants in 50% methanol/water (YCl ) 2.70) with those
for 97T would be expected to give similar rate ratios to
into the kinetic apparatus. gk ) (2.22 ( 0.02) × 10-2 and (2.73 (
0.04) × 10-1 at 0 and 25 °C; ∆Hq) 15.7 kcal mol-1 and ∆Sq
)
-8.5 cal mol-1 K-1
.
hInjected 10 µL of 1% (v/v) substrate in dry
i
acetonitrile. Data from ref 11b.
halides and of other acyclic tertiary substrates, of rel-
evance to recent reports from other research groups.8,9
Resu lts
Rate constants for solvolyses in TFE/ethanol and TFE/
water of chlorodiphenylmethane (1) are given in Table 1
and of p-methoxybenzyl chloride (2) are given in Table
2. Solvolyses of substrate (RCl) gave a mixture of
trifluoroethyl ether (ROCH2CF3) and either alcohol (ROH)
or ethyl ether (ROEt), and molar concentrations of
products in TFE/water are expressed as selectivities (S,
eq 2) in Table 3 (an analogous equation was used for TFE/
ethanol mixtures).
k40E /k97T
.
The k40E /k97T ratio is 0.83 for 1-adamantyl chloride, so
when the ratio is significantly lower (corresponding to a
negative l value), a breakdown of the interpretation based
(10) (a) Bentley, T. W.; J ones, R. O. J . Chem. Soc., Perkin Trans. 2
1993, 2351. (b) Bunton, C. A.; Mhala, M. M.; Moffatt, J . R. J . Org.
Chem. 1984, 49, 3639. (c) Nishida, S. J . Org. Chem. 1967, 32, 2695.
(11) (a) Bentley, T. W.; Koo, I. S.; Norman, S. J . J . Org. Chem. 1991,
56, 1604. (b) da Roza, D. A.; Andrews, L. J .; Keefer, R. M. J . Am. Chem.
Soc. 1973, 95, 7003.
(12) (a) Shiner, V. J ., J r.; Dowd, W.; Fisher, R. D.; Hartshorn, S. R.;
Kessick, M. A.; Milakofsky, L.; Rapp, M. W. J . Am. Chem. Soc. 1969,
91, 4838. (b) Scott, F. L. Chem. Ind (London) 1959, 224.
(13) (a) Bentley, T. W.; Bowen, C. T.; Parker, W.; Watt, C. I. F. J .
Chem. Soc., Perkin Trans. 2, 1980, 1244. (b) Carter, G. E. Ph.D. Thesis,
University of Wales, Swansea, 1982.
(8) (a) Takeuchi, K.; Ohga, Y.; Ushino, T.; Takasuka, M. J . Org.
Chem. 1997, 62, 4904. (b) Takeuchi, K.; Ohga, Y.; Ushino, T.;
Takasuka, M. J . Phys. Org. Chem. 1996, 9, 777. (c) Liu, K.-T.; Hou,
S.-J .; Tsao, M.-L. J . Org. Chem. 1998, 63, 1360.
(9) (a) Richard, J . P.; J agannadham, V.; Amyes, T. L.; Mishima, M.;
Tsuno, Y. J . Am. Chem. Soc. 1994, 116, 6706. (b) Toteva, M. M.;
Richard, J . P. J . Am. Chem. Soc. 1996, 118, 11434.
(14) Luton, P. R.; Whiting, M. C. J . Chem. Soc., Perkin Trans. 2
1979, 507.

4656 J . Org. Chem., Vol. 63, No. 14, 1998
Bentley et al.
Ta ble 4. Ra te Con sta n ts (k/s-1) for Solvolyses of 1, 3-6,
a n d ter t-Bu tyl Ha lid es in 97% w /w
Sch em e 1. Va lu es of Solvolysis Ra te Ra tios in 40%
Eth a n ol/Wa ter Com p a r ed w ith 97%
Tr iflu or oeth a n ol/Wa ter a
Tr iflu or oeth a n ol/Wa ter a t 25 °Ca
∆Hq/kcal
∆Sq/cal
RX
T/°C
k/s-1
mol-1
mol-1 K-1
t-BuCl
25.0b
39.9b
(1.42 ( 0.02) × 10-4
19.8
-10
(7.32 ( 0.04) × 10-4
t-BuBr 25.0c,d (2.66 ( 0.01) × 10-3
t-BuI
1
25.0
25.0e
10.0
0.0
(3.23 ( 0.03) × 10-3
1.28 ( 0.07
(3.45 ( 0.04) × 10-1
(1.31 ( 0.01) × 10-1
6.73 × 10-4
14.2
-10.5
3
4
5
6
25.0f
25.0
25.0
25.0
(4.90 ( 0.05) × 10-4
(1.05 ( 0.01) × 10-1
(4.71 ( 0.01) × 10-2
a
Determined conductometrically in duplicate except where
stated otherwise; errors shown are average deviations. bLit.12a
k
) 1.32 × 10-4; also at 25.0 °C, k ) (1.35 ( 0.03) × 10-4 and at
49.7 °C, k ) (1.86 ( 0.08) × 10-3 s-1; ∆Hq ) 19.7, ∆Sq ) -10
(determined by T.W.B. in earlier work at Princeton). cTriplicate
a
measurement of rate constant. dFor 97% v/v TFE/water, k ) 2.88
Data from Table 4 and refs 10b, 11, and 15.
× 10-3 s-1 (ref 12b). Lit.10b k ) 1.05 s-1
.
fFrom ref 12a.
e
Ta ble 5. Ra te Con sta n ts (k/s-1) for Solvolyses of
ter t-Bu tyl Ha lid es (t-Bu X) a n d 1-Ch lor o-1-p h en yleth a n e
(3) in 97% w /w Hexa flu or op r op a n -2-ol/Wa ter a
∆Hq/kcal
∆Sq/cal
RX
T/°C
k/s-1
mol-1
mol-1 K-1
t-BuCl
25.0b
1.5
(2.55 ( 0.02) × 10-3
(2.05 ( 0.02) × 10-4
(1.77 ( 0.10) × 10-2
(1.08 ( 0.02) × 10-2
(7.0 ( 0.3) × 10-4
(2.00 ( 0.5) × 10-1
(4.75 ( 0.3) × 10-2
17
-14
t-BuBr
t-BuI
25.0c
25.0
(16.2)d
17
(-11.7)d
-10
-0.1e
25.0f
10.0f
3
14
-13
0.02f (2.00 ( 0.5) × 10-2
As for Table 1. bOther literature values in the range (2.45-
a
2.69) × 10-3 s-1 (ref 13a). Triplicate measurement of rate
c
constant. dActivation parameters from ref 14a (also k ) 2.2 ×
10-2 s-1). Five measurements of rate constant. Initial rate con-
e
f
stants determined by Carter (ref 13b).
Ta ble 6. Kin etic Solven t Isotop e Effect (KSIE) for
Solvolyses of Meth yl Tosyla te in Meth a n ol a t 49.8 °Ca
F igu r e 1. Plot of logarithms of rate constants for solvolyses
of chlorodiphenylmethane (1) vs rates for p-methoxybenzyl
chloride (2); kinetic data from Tables 1 and 2 and refs 11a
and 17.
rate constants/s-1
MeOH
MeOD
KSIE
(1.185 ( 0.015) × 10-5
(1.065 ( 0.015) × 10-5
1.11 ( 0.03
aDetermined conductometrically in duplicate.
some of the most marked effects, and a plot (Figure 1) of
logarithms of rate constants for solvolyses of Ph2CHCl
vs corresponding data for p-methoxybenzyl chloride
shows a dispersion (ca. 3-fold in rate) into separate lines
for ethanol/water and TFE/ethanol mixtures, and Ph2-
CHCl is relatively more reactive in TFE-rich media.
Dispersion is apparent even when log(k/k0) is 0 (i.e., 40%
TFE/ethanol), so deviations are not restricted to TFE-
rich media.
on eq 1 is apparent. Of the values of k40E /k97T in Scheme
1, only the value of 0.18 for Ph2CHCl is substantially less
than 0.83 (so in this case the upward deviation is 4-fold);
larger upward deviations in HFIP are probable, but
solvolyses of Ph2CHCl in HFIP were too fast to measure.10b
From our data for solvolyses of 1-chloro-1-phenylethane
(3) in 97% HFIP (Table 5), we calculate an upward
deviation of only 2-fold from the extended correlation line
for aqueous ethanol vs YCl (additional data from ref 15b);
in contrast, TFE gives a downward deviation (Scheme
1).
Although the precision of many YX correlations is
reduced when the positive charge generated during
solvolyses can be delocalized onto aromatic rings or onto
other π-electron systems adjacent to the reaction site, the
effects are often small.7d,15c,16 Solvolyses of Ph2CHCl show
Solvolysis rate data indicate that TFE does seem to
be relatively more effective than ethanol at solvating
delocalized cations7c (e.g., in solvolyses of benzylic
substrates7a,b or of substrates undergoing rearrangement
- k∆ solvolyses7c,d). Our results for 1 and 2 (Scheme 1)
provide additional examples of benzylic substrates having
k40E/k97T ratios < 0.8.
(15) (a) Fainberg, A. H.; Winstein, S. J . Am. Chem. Soc. 1956, 78,
2770. (b) Fainberg, A. H.; Winstein, S. J . Am. Chem. Soc. 1957, 79,
1597. (c) Bentley, T. W.; Dau-Schmidt, J . P.; Llewellyn, G.; Mayr, H.
J . Org. Chem. 1992, 57, 2387.
(16) (a) Liu, K. T.; Sheu, H. C. J . Org. Chem. 1991, 56, 3021. (b)
Oh, H. K.; Kown, Y. B.; Koh, H. J .; Lee, I. New J . Chem. 1996, 20,
579. (c) Kevill, D. N.; Ismail, N. HJ .; D’Souza, M. J . J . Org. Chem.
1994, 59, 6303.

Solvolytic Reactions in Fluorinated Alcohols
J . Org. Chem., Vol. 63, No. 14, 1998 4657
The environment at the reaction site can be probed
from product selectivities (Table 3); the expected order
of nucleophilic attack (EtOH > water > TFE18) is most
prominent in TFE-rich solutions, consistent with greater
selectivity for a longer-lived cation.9b Also, the less
reactive2 diphenylmethyl cation is slightly more selective
than the p-methoxybenzyl cation, and continuing this
trend, solvolyses of adamantyl substrates are virtually
unselective.18 As selectivities are lowest for solvolyses
of Ph2CHCl in TFE-rich mixtures, preferential cation
solvation by TFE (if any) does not appear to improve the
prospects for nucleophilic attack by TFE. Overall, the S
values (Table 3) are approximately constant, so there is
no evidence from product studies for a greater concentra-
tion of TFE at the reaction site.
Ethanol/water selectivities (S) for solvolyses of 1 and
2 are typically 2-4,11a,18 whereas the ratio of selectivities
(STFE/water/STFE/ethanol) is 6-10 (Table 3). Also, the STFE/water
values of 0.2-0.5 (Table 3) are much larger than the rate
ratios of 10-3 obtained from direct measurements of the
rates of nucleophilic attack on carbocations by TFE in
TFE compared with attack by water in acetonitrile/
water.2 Hence, TFE appears to suppress nucleophilic
attack by both water and ethanol, and the effect is larger
for water, so both S values and k40E/k97T ratios may be
affected by TFE in the second or third solvation shell; a
further complication is that water and ethanol may act
as general bases during nucleophilic attack on carboca-
tions.17 Consequently, deductions from S values in
binary or ternary mixtures require due caution.
The highest value of k40E /k97T (Scheme 1) is 11 for
t-BuCl. An increase in steric hindrance (e.g., 4) reduces
the k40E /k97T ratio, as reported recently;8b,8c presumably,
a more hindered substrate is less able to benefit from
nucleophilic solvent assistance, so the k40E /k97T ratio and
hence the l values (eq 1) are reduced. Our results also
show that an increase in charge stabilization by conjuga-
tion with a double bond (e.g., 5) or a triple bond (e.g., 6)
also reduces the k40E /k97T ratio; these ratios may slightly
underestimate nucleophilic solvent assistance because
the cationic intermediates from solvolyses of 5 and 6 are
delocalized, but trends are consistent with the expecta-
tion that formation of a more stable cation will require
less nucleophilic assistance.
A k40E/k97T ratio of only 0.1 was reported recently for
solvolyses of the more hindered tertiary chloride (7).8a
In addition to a negative l value (eq 1), an m value of
only 0.54 ( 0.06 was obtained and the product was
almost exclusively elimination (>98% in TFE); the sol-
volysis rates can be correlated if the N term in eq 1 is
replaced by the charge delocalization parameter (I),16c,19
and it appears that the cationic transition state has a
delocalized positive charge, consistent with the concerted
unimolecular elimination recently proposed for solvolyses
of 8 in largely aqueous solutions.9b,20
recent work.2,9b Identification of initial products is
complicated by the possibility of addition of HX to alkene;
also, it is difficult to distinguish between the trapping of
“free” carbocations by nucleophiles and the reactions of
nucleophiles by preassociation mechanisms.9b Estimates,
based on rate-equilibrium extrapolations, of the lifetime
of the tert-butyl cation in water at 25 °C are ca. 10-10
s.23 However, a 1000-fold shorter lifetime in 50% v/v
TFE/water for the cation derived from 8 has recently been
estimated,9b and an even shorter lifetime would then be
expected for the tert-butyl cation in water (tert-butyl is a
less hindered substrate and the absence of TFE will
further reduce lifetimes). The following rate-rate ex-
trapolation indicates that the lifetime of the tert-butyl
cation in water is less than the time required for a bond
vibration (10-13 s).
Direct measurements2 of the rates of reactions of Ph2-
CH+ with solvent are as follows: aqueous acetonitrile (1.3
× 109 s-1), TFE (3.2 × 106 s-1), and HFIP (ca. 1.1 × 101
s-1).2 A typical rate ratio for kwater/kTFE is 103 (seven
values2), and for kTFE/kHFIP is >104 (three values2); so a
kwater/kHFIP ratio of >107 is expected; the cumyl cation
(PhC(CH3)2+) reacts with HFIP with a rate constant of 9
× 103 s-1,2 which can be extrapolated to >9 × 1010 s-1 in
water. Hence, even this phenyl-stabilized cation may
have a lifetime of only ca. 10-11 s in water. A 104
correction factor for replacement of Ph by Me can be
obtained directly from experimental data for rates of
attack by HFIP on PhCHCH3+, which reacts >104 times
faster than attack on Ph2CH+;2 hence, a “lifetime” of ca.
10-15 s is estimated for the tert-butyl cation in water.
Even allowing an uncertainty of 102 in the above calcula-
tion, it appears that the tert-butyl cation may be too
unstable to exist as an intermediate in highly aqueous
(TFE-free) media, so both elimination and substitution
may be enforced concerted reactions.24
The importance of hydrogen bonding to the departing
leaving group during solvolyses (electrophilic assistance)
is well established.9a,25 An alkyl iodide would be expected
to hydrogen bond less strongly than an alkyl chloride to
a hydrogen bond donor solvent such as a fluorinated
alcohol. Rate ratios for solvolyses of 1-adamantyl (1-Ad)
and tert-butyl halides (e.g., iodides/bromides and bromides/
chlorides, see Table 7) follow the order 80% ethanol/water
> TFE > HFIP, in line with the order of increasing R
values of the solvents.27 Allowance is made for this
relatively small effect (ca. 5-fold) in the YX values for the
The nature of the intermediate (if any) in solvolyses
of simple aliphatic tertiary substrates is of long-standing
interest,9 and older evidence22 has been undermined by
(17) Bentley, T. W.; Ryu, Z. H. J . Chem. Soc., Perkin Trans. 2 1994,
761.
(18) Ta-Shma, R.; Rappoport, Z. Adv. Phys. Org. Chem. 1992, 27,
239.
(19) Kevill, D. N.; D’Souza, M. J . Tetrahedron Lett., 1998, 39, 3973.
(20) The large deuterium isotope effect for chloride-initiated dehy-
drochlorination of tert-butyl chloride in acetonitrile is consistent with
a bimolecular mechanism.21
(22) (a) Bunton, C. A.; Nayak, B. J . Chem. Soc. 1959, 3854. (b)
Swain, C. G.; Scott, C. B.; Lohmann, K H. J . Am. Chem. Soc. 1953,
75, 136.
(23) McClelland, R. A.; Kanagasabapathy, V. M.; Banait, N. S.;
Steenken, S. J . Am. Chem. Soc. 1989, 111, 3966.
(24) J encks, W. P. Chem. Rev. 1972, 72, 705.
(25) (a) Bentley, T. W.; Schleyer, P. v. R. Adv. Phys. Org. Chem.
1976, 14, 1. (b) Dvorko, G. F.; Ponomarev, N. E. Russ. J . Gen. Chem.
1995, 65, 111.
(21) Kevill, D. N.; Dorsey, J . E. J . Org. Chem. 1969, 34, 1985.

4658 J . Org. Chem., Vol. 63, No. 14, 1998
Bentley et al.
a higher sensitivity to nucleophilicity,31 it was not
expected that the mechanism of solvolysis was compa-
rable. Recent work on solvolyses of 9 and related
compounds32 indicates the possibility of a concerted
substitution mechanism, with a kinetic solvent isotope
effect (MeOH/ MeOD) of 2.3.33 We have confirmed (Table
6) that SN2 solvolyses of methyl tosylate give a small
MeOH/MeOD rate ratio (1.1), as expected from earlier
work on H2O/D2O;34,35 SN1 solvolyses of Ph2CHCl also
show a small MeOH/MeOD rate ratio of 1.1.36 The
kinetic solvent isotope effect has been noted as a disap-
pointing criterium of the mechanism,37 but in a recent
study of an SN2(P) solvolysis of (PhO)2POCl, we found
an l value (eq 1) of ca. 1.8 and a (MeOH/MeOD) rate ratio
as high as 3.1.38 Perhaps the small solvent isotope effects
in typical SN2 solvolyses indicate an early transition
state, with nucleophilic assistance lagging behind depar-
ture of the leaving group, as recently re-emphasized in
the case of neighboring group participation.39
Ta ble 7. Iod id e/Br om id e (I/Br ) a n d Br om id e/Ch lor id e
(Br /Cl) Ra te Ra tios for Solvolyses of 1-Ad a m a n tyl a n d
ter t-Bu tyl Ha lid es a t 25 °C
I/Br
Br/Cl
solvent
1-Ada
t-Bu
1-Adb
t-Bub
80% ethanol
97% TFE
97% HFIP
2.1
1.0
0.4
2.6c
1.2d
0.6e
35
18
9
39
22
9
a
Data from ref 26a. bData from ref 26b. cKinetic data for t-BuI
from ref 26c and for t-BuBr from ref 26d. dData from Table 4. eData
from Table 5.
various leaving groups.5 As the rate ratio 1-AdI/1-AdBr
varies from 3.7 in ethanol to 1.3 in water,26 there is
probably a small dependence of I/Br rate ratios on solvent
polarity even in the absence of a specific electrophilic
effect due to fluorinated alcohols.
Although most of the I/Br and Br/Cl rate ratios are
slightly greater for solvolyses of tert-butyl halides than
1-adamantyl halides (Table 7), the differences are very
small; these results provide important evidence that
solvolysis rates are not significantly affected by differ-
ences in the susceptibility of tert-butyl and 1-adamantyl
substrates to electrophilic assistance28 (i.e., rates of
reactions of substrates having saturated alkyl groups can
be correlated adequately using eq 1). An almost directly
contrary viewpoint was developed from solvatochromic
measures of solvent effects by a “double difference”
method, in which solvolysis rates in methanol, ethanol,
TFE, and HFIP led to estimates of the sensitivity (a) of
substrates to electrophilic solvent assistance (separated
from the sensitivity to solvent dipolarity, π*).29 Surpris-
ingly, it was found that a was significantly higher for
solvolyses of 1-AdCl (a ) 6.5) than for BuCl (a ) 4.1). As
solvolyses of 1-AdI had an a value of 5.4 (for 1-AdBr, a
) 6.0),29 this treatment leads to the very surprising
conclusion that changes in the leaving group lead to
smaller changes in a than changes in the alkyl group.
Con clu sion s
The rates of SN1 solvolytic reactions of a substrate (RX)
5
depend on the solvent ionizing power (Y or YX ), which
includes contributions from electrostatic and electrophilic
solvation of the developing anion (X-). Relative rates of
solvolyses of 1-adamantyl or tert-butyl substrates having
different halide leaving groups are influenced by solvent
electrophilicity, but solvolyses of substrates having satu-
rated alkyl groups (e.g., 1-adamantyl and tert-butyl)
respond very similarly to changes in solvent electrophi-
licity (Table 7). Solvolyses leading to delocalized cations,
which may be formed by neighboring group participation
or by charge delocalization onto adjacent π-electrons,
show unusual effects in that rates of solvolyses in
fluorinated alcohols may be faster than expected from
an mY plot for aqueous ethanols, and this effect is in the
opposite direction from that due to solvent nucleophilic-
ity. A delocalized cationic transition state for concerted
elimination may explain the recent results for 7, without
the need to postulate additional specific solvation effects
for adamantyl systems, such as Bronsted-base solvation
of R- and â-hydrogen atoms.8a As would be expected,
increases in steric hindrance or in cation-stabilization
lead to decreases in susceptibility to solvent nucleophi-
licity (Scheme 1).
A major advantage of eq 1 over solvatochromic methods
(based on π*, R, and â29) is that fewer adjustable
parameters are required. Applications of eq 1 to correlate
solvolysis rates require a suitable Y scale, and the YX
scales based on 1-adamantyl solvolyses are employed
widely.5 No additional parameters are needed for many
SN1 solvolyses, but considerable attention is currently
being given to improve the precision of correlations for
solvolyses occurring via delocalized cationic transition
states;15c,16,30 either a wider range of Y scales or an extra
adjustable parameter will be required.
Exp er im en ta l Section
Ch em ica ls. Chlorides 4-6 were available from previous
work;15c chlorodiphenylmethane (1),17p-methoxybenzyl chloride
chloride (2),11a and tert-butyl bromide13a were obtained as
reported earlier; 1-chloro-1-phenylethane (3) was prepared and
purified by standard methods;13b tert-butyl iodide was first
washed with aqueous sodium metabisulfite and was freshly
The range of l values (eq 1) was originally expected to
lie between 0 and 1.4b Although compounds such as
p-nitrobenzoyl chloride (9) have long been known to have
(31) Swain, C. G.; Mosely, R. B.; Bown, D. E. J . Am. Chem. Soc.
1955, 77, 3731.
(32) Song, B. D.; J encks, W. P. J . Am. Chem. Soc. 1989, 111, 8470.
(33) Koo, I. S.; Lee, I.; Oh, J .; Yang, K.; Bentley, T. W. J . Phys. Org.
Chem. 1993, 6, 223.
(34) Robertson, R. E. Prog. Phys. Org. Chem. 1963, 4, 213.
(35) Kurz, J . L.; Lee, J .; Love, M. E.; Rhodes, S. J . Am. Chem. Soc.
1986, 108, 2960.
(26) (a) Bentley, T. W.; Carter, G. E.; Roberts, K. J . Org. Chem. 1984,
49, 5183. (b) Bentley, T. W.; Carter, G. E. J . Am. Chem. Soc. 1982,
104, 5741. (c) Shorter, J .; Hinshelwood, C. J . Chem. Soc. 1949, 2412.
(d) Fainberg, A. H.; Winstein, S. J . Am. Chem. Soc. 1957, 79, 1602.
(27) Cativiela, C.; Garcia, J . I.; Gil, J .; Martinez, R. M.; Mayoral, J .
A.; Salvatella, L.; Urieta, J . S.; Mainar, A. M.; Abraham, M. H. J .
Chem. Soc., Perkin Trans. 2 1997, 653.
(28) Bentley, T. W.; Roberts, K. J . Chem. Soc., Perkin Trans. 2 1989,
1055.
(29) Doherty, R. M.; Abraham, M. H.; Harris, J . M.; Taft, R. W.;
Kamlet, M. J . J . Org. Chem. 1986, 51, 4872.
(36) Chang, S.; Koh, H. J .; Lee, B.-S.; Lee, I. J . Org. Chem. 1995,
60, 7760.
(37) Albery, W. J .; Kreevoy, M. M. Adv. Phys. Org. Chem. 1978, 16,
87.
(30) (a) Kevill, D. N.; D’Souza, M. J . J . Chem. Soc., Perkin Trans. 2
1997, 257. (b) Liu, K.-T.; Chin, C.-P.; Lin. Y.-S.; Tsao, M.-L. J . Chem.
Res., Synop. 1997, 18. (c) Liu, K.-T. J . Chem. Soc., Perkin Trans. 2
1996, 327.
(38) Bentley, T. W.; Ebdon, D.; Llewellyn, G.; Abduljaber, M. H.;
Miller, B.; Kevill, D. N. J . Chem. Soc., Dalton Trans. 1997, 3819.
(39) Schreiner, P. R.; Schleyer, P. v. R.; Schaefer, H. F. J . Org. Chem.
1997, 62, 4216.

Solvolytic Reactions in Fluorinated Alcohols
J . Org. Chem., Vol. 63, No. 14, 1998 4659
distilled to remove traces of iodine, which may catalyze
solvolyses;40 methyl tosylate was a commercial sample (BDH).
P r od u ct Stu d ies. Product ratios were obtained using the
same techniques and equipment as described previously.17
Kin etics. MeOD was Aldrich (>99.5+ %D), and other
solvents were prepared as described previously.26a,b Kinetic
data were obtained by our standard procedures.41
Ack n ow led gm en t. We are grateful to the EPSRC
(U.K.) for equipment grants for HPLC, to Dong Eui
University for additional financial support, and to D.
N. Kevill for helpful discussions.
(40) Cox, B. G.; Maskill, H. J . Chem. Soc., Perkin Trans. 2 1983,
1901.
(41) Bentley, T. W.; Carter, G. E.; Harris, H. C. J . Chem. Soc., Perkin
Trans. 2 1985, 983.
J O980109D