Competing solvolytic elimination and substitution reactions via very short-lived ion-pair intermediates

Article abstract of DOI:10.1039/b102869n

The solvolysis of 9-methyl-9-(2-X-2-propyl)fluorene (X = Cl, Br, or OOCCF₃) (1-X) in aqueous acetonitrile or aqueous 1,1,1-trifluoroethanol (TFE) yields the alkene, 9-methyl-9-(propen-2-yl)fluorene (2), and the alcohol, 9-methyl-9-(2-hydroxy-2-propyl)fluorene (1-OH), accompanied by a small amount of substitution product from the reaction with the organic component of the solvent mixture. The fraction of elimination product increases with decreasing fraction of water in the solvent mixture as well as by addition of general bases, which can be expressed by a Br?nsted parameter of β = 0.07 for the reaction of 1-Cl, measured with substituted acetate anions. Also, the addition of chloride ions increases the fraction of alkene. The kinetic deuterium isotope effects on the reactions of the hexadeuterated substrates vary with solvent composition in a way which is not consistent with a common carbocation intermediate which has time to choose between dehydronation and addition of a solvent water molecule. A stepwise preassociation mechanism is proposed for the elimination reaction.

Full text of DOI:10.1039/b102869n

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Competing solvolytic elimination and substitution reactions via
very short-lived ion-pair intermediates
Xiaofeng Zeng and Alf Thibblin*
2
Institute of Chemistry, University of Uppsala, P.O. Box 531, Uppsala, SE-751 21, Sweden
Received (in Cambridge, UK) 28th March 2001, Accepted 12th June 2001
First published as an Advance Article on the web 16th July 2001
The solvolysis of 9-methyl-9-(2-X-2-propyl)fluorene (X = Cl, Br, or OOCCF3) (1-X) in aqueous acetonitrile or
aqueous 1,1,1-trifluoroethanol (TFE) yields the alkene, 9-methyl-9-(propen-2-yl)fluorene (2), and the alcohol,
9-methyl-9-(2-hydroxy-2-propyl)fluorene (1-OH), accompanied by a small amount of substitution product from
the reaction with the organic component of the solvent mixture. The fraction of elimination product increases with
decreasing fraction of water in the solvent mixture as well as by addition of general bases, which can be expressed
by a Brønsted parameter of β = 0.07 for the reaction of 1-Cl, measured with substituted acetate anions. Also, the
addition of chloride ions increases the fraction of alkene. The kinetic deuterium isotope effects on the reactions
of the hexadeuterated substrates vary with solvent composition in a way which is not consistent with a common
carbocation intermediate which has time to choose between dehydronation and addition of a solvent water molecule.
A stepwise preassociation mechanism is proposed for the elimination reaction.
hydron from the carbocation intermediate. A concerted uni-
molecular pericyclic mechanism has also been proposed in
Introduction
Solvolysis reactions of substrates having a hydrogen in the β-
position generally give both substitution and 1,2-elimination
products in aqueous solvents. The alcohol product usually has
which the leaving group acts as the hydron acceptor in elimin-
ation reactions of tertiary substrates.5,7 This mechanism requires
syn stereochemistry. However, it was more recently shown that
a greater thermodynamic stability and is for that reason often
both the elimination of hydrochloric acid from a very unstable
the predominant product. There seems to be a consensus that
tertiary carbocation ion pair and the elimination of 4-nitro-
the elimination from simple tertiary substrates occurs directly
benzoic acid from a cumyl-like substrate occur by anti stereo-
through the ion pair before dissociation occurs.1–3 Accordingly,
chemistry.2
the leaving group may catalyze the carbocation by acting as a
We report here a study of the competition between elimin-
general Brønsted base. It has been reported, for example, that
ation and substitution and the kinetics of the solvolysis of the
even neutral leaving groups catalyze the alkene formation from
tertiary substrates 1-X (Scheme 2) as a function of leaving
group, solvent composition, and β-deuterium substitution. We
cumyl derivatives.4 The leaving group in simple, more unstable
carbocations, is expected to function in a similar way. Also the
have previously studied the solvolysis of the corresponding
addition of water to simple tertiary carbocation intermediates
substrate with a hydrogen instead of a methyl group at the
has been suggested to occur before dissociation (Scheme 1).5,6
9-position of the fluorene moiety (A-X, Scheme 2).8–10 It was
found that, without the presence of a strong base, the terminal
alkene and the alcohol are the predominant products. It was
proposed that the solvolysis involves irreversible rate-limiting
ionization to give a common ion-pair intermediate for the
elimination and substitution reactions. The measured kinetic
deuterium isotope effects and the small Brønsted parameters
supported this conclusion. Excluding the acidic hydrogen
makes the analysis of the reaction products somewhat easier
since only one alkene is accompanying the substitution
products (Scheme 2), and there is no isomerization of alkenes.
We have frequently employed kinetic deuterium isotope
Scheme 1
effect measurements as a probe of reaction branching through
a common intermediate, both for carbanionic11 and carbo-
The role of the chloride ion leaving group in the elimination
cationic reactions.1,8–18 However, the kinetic deuterium isotope
effect measurements do not indicate a common intermediate
for the reactions of 1-X. The mechanistic implications will be
discussed.
process is, however, not clear.2,5 Does it act as a general base
that abstracts a β-hydron from the cation, or is a water molecule
of the solvation shell the active species? It has been argued that
the chloride ion is a very weak base, much weaker than water,
and therefore, is not able to compete with water as the hydron-
abstracting base.5 In contrast, it has been proposed that
incomplete solvation of the chloride ion in the contact ion pair
makes the chloride ion a much stronger base than that implied
by the pKa of HCl.2 It is also plausible that the carbocation–
chloride ion pair is so short-lived that the elimination occurs
through a stepwise preassociation mechanism with water or
an added base already correctly positioned for abstracting a
Results
The solvolysis of 9-methyl-9-(2-X-2-propyl)fluorene (1-X,
X = Cl, Br, OOCCF3) in aqueous acetonitrile or in aqueous
2,2,2-trifluoroethanol (TFE) provides the alkene 9-methyl-
9-(propen-2-yl)fluorene (2) and the substitution products 9-
methyl-9-(2-hydroxy-2-propyl)fluorene (1-OH) along with a
1600
J. Chem. Soc., Perkin Trans. 2, 2001, 1600–1607
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b102869n

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Fig. 1 Grünwald–Winstein plot for the solvolysis of 1-Cl in aceto-
nitrile–water mixtures at 25 ЊC.
Fig. 2 Grünwald–Winstein plot for the solvolysis of 1-Br in aceto-
nitrile–water mixtures at 25 ЊC.
Scheme 2
small amount of 9-methyl-9-(2-acetamido-2-propyl)fluorene
(1-NHCOMe) or 9-methyl-9-[2-(2Ј,2Ј,2Ј-trifluoroethoxy)-2-
propyl]fluorene (1-OCH2CF3), respectively (Scheme 2). The
kinetics of the solvolysis reactions of 1-Cl and 1-OOCCF3 were
studied at 25 ЊC by a sampling high-performance liquid-
chromatography procedure. The kinetics of the reactions of
1-Br were studied by following the change in absorption at
409 nm in the presence of added 4-nitrophenolate anion (see
Experimental section). The reaction rates and product com-
positions are strongly dependent on the nature of the leaving
group and reaction media. The measured rate constants and
reaction conditions for 1-Cl, 1-Br, and 1-OOCCF3 are shown in
Tables 1, 2, and 3, respectively. The separate rate constants for
the elimination and substitution reactions were derived from
the measured product compositions. Tables 1 and 3 also give
the kinetic data for reactions in 50 vol% methanol, but, owing
to overlapping HPLC peaks for 1-OMe and 2, only rate con-
stants for the disappearance of the substrates (kobs) are
reported.
Fig. 3 Grünwald–Winstein plot for the solvolysis of 1-OOCCF3
in acetonitrile–water mixtures at 25 ЊC.
The observed product ratio of 1-Nu to 1-OH is a measure of
the competition between added nucleophile (NuϪ) and water
for the reaction with substrate and/or ion pair. The second-
order rate-constant ratios kNu/kw in Tables 1–3 were derived
from the measured product ratios according to eqn. (1).
kNu/kw = ([1-Nu]/[1-OH])([H2O]/[NuϪ])
(1)
The effect of solvent polarity has been studied by measuring
Grünwald–Winstein parameters for the reactions of 1-Cl,
1-Br, and 1-OOCCF3 in aqueous acetonitrile, as shown in
Figs. 1–3.19–21 The Y values are from reports of Bunton and
coworkers.22,23
Fig. 4 The elimination-to-substitution ratio (kE/kS) for 1-Cl as a
function of [AcOϪ] (᭹), [ClϪ] (ᮀ), and [CF3COOϪ] (᭺), respectively, at
constant ionic strength of 0.5 M, maintained with sodium perchlorate
at 25 ЊC.
Added basic salts increase the elimination-to-substitution
ratio. The effect is most significant in aqueous acetonitrile
(Table 1). There is an approximately linear dependence between
base concentration and kE/kS as shown for 1-Cl with two of the
bases, AcOϪ and CF3COOϪ (Fig. 4).
The
deuterated
substrates
9-methyl-9-[2-X-2-
(1Ј,1Ј,1Ј,3Ј,3Ј,3Ј-2H6)propyl]fluorene (X = Cl, Br, OOCCF3)
yield lower reaction rates and smaller alkene fractions. The
measured kinetic deuterium isotope effects for solvolysis of
these deuterated substrates are given in Table 4.
J. Chem. Soc., Perkin Trans. 2, 2001, 1600–1607
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Table 1 Rate constants for the reactions of 1-Cla in aqueous solvents at 25 ЊC
Solventb
Salt
106kobsc/sϪ1
106kEd/sϪ1
106(kS ϩ kNu[NuϪ])d/sϪ1
kE/kS
kNu/kw
25% MeCN
33.3% MeCN
40% MeCN
50% MeCN
60% MeCN
40% MeCN
40% MeCN
40% MeCN
40% MeCN
40% MeCN
40% MeCN
40% MeCN
40% MeCN
40% MeCN
40% MeCN
50% MeOH
50% TFE
75% TFE
50% TFE
50% TFE
50% TFE
50% TFE
50% TFE
50% TFE
None
None
None
None
1001
417
181
67.7
28.1
236
413
109
165
243
160
221
82.2
127
164
499
245
118
48.4
21.9
146
245
72
109
158
106
139
57.5
87
502
172
62
19.2
6.2
90
168
36
56
85
54
81
25.7
41
0.99
1.42
1.90
2.52
3.54
1.62
1.46
1.99
1.93
1.85
1.95
1.71
2.33
2.14
1.96
None
0.50 M NaClO4
2.66 M NaClO4
0.50 M NaCl
0.50 M NaBr
0.50 M NaI
0.50 M NaN3
0.50 M NaSCN
0.45 M NaOAc
0.45 M NaO2CCH2CN
0.45 M NaO2CCF3
None
3.4e
5.1f
108
55
470
None
None
1492
1070
2127
1893
1679
1389
1635
1910
852
674
1115
1081
951
810
920
640
396
1012
812
728
579
715
880
1.33
1.70
1.10
1.33
1.31
1.40
1.29
1.17
0.50 M NaClO4
0.50 M NaCl
0.50 M NaBr
0.45 M NaOAc
0.50 M NaN3
0.50 M NaSCN
4.9e
11f
1030
a 0.04–0.12 mM. b By volume. c kobs = kE ϩ kS ϩ kNu[NuϪ], see Scheme 2: estimated maximum error 3 %. d Estimated maximum error 6%. e Ap-
proximate since the product HPLC peak of 1-N3 overlaps partially with that of alkene 2. f The ratio is based upon the sum of the products 1-SCN
and 1-NCS.
Table 2 Rate constants for the reactions of 1-Bra in aqueous acetonitrile at 25 ЊC
Solventb
Salt
109kobsc/sϪ1
109kEd/sϪ1
109(kS ϩ kNu[NuϪ])d/sϪ1
kE/kS
kNu/kw
40% MeCN
50% MeCN
60% MeCN
70% MeCN
75% MeCN
40% MeCN
40% MeCN
40% MeCN
40% MeCN
40% MeCN
50% MeCN
40% MeCN
50% MeCN
40% MeCN
40% MeCN
50% MeCN
50% MeCN
50% MeCN
50% MeCN
50% MeCN
None
None
None
None
13.7
6.28
3.42
1.81
1.26
24.4
10.1
13.9
23.0
8.52
4.46
2.64
1.51
1.10
14.2
6.6
5.19
1.81
0.78
0.30
0.16
10.2
3.5
1.64
2.46
3.39
4.98
6.91
1.39
1.87
1.75
1.71
1.46
2.14
1.83
2.71
1.99
1.81
1.95
2.00
2.63
2.56
2.66
None
0.50 M NaClO4
0.50 M NaCl
0.50 M NaBr
0.50 M NaI
0.50 M NaSCN
0.50 M NaSCN
0.50 M NaN3
0.50 M NaN3
0.45 M NaO2CCH2CN
0.45 M NaO2CCF3
0.45 M NaO2CCF3
0.50 M NaClO4
0.50 M NaBr
0.50 M NaI
0.35M NaCl
8.85
14.5
5.05
8.5
4.8f
4.1f
1.8e
1.8e
9.91
5.36
8.15
4.39
6.61
3.88
5.86
3.19
3.30
1.48
2.29
1.20
c
a 0.04–0.12 mM. b By volume. kobs = kE ϩ kS ϩ kNu[NuϪ], see Scheme 2; estimated maximum error
3%. d Estimated maximum error
6%.
e Approximate since the product HPLC peak of 1-N3 overlaps partially with that of alkene 2. f The ratio is based upon the sum of the products 1-
SCN and 1-NCS.
and 1110 times faster than the ester in 60 vol% acetonitrile
(Tables 1–3). The reaction rates of the three substrates are
also very sensitive to the ionization power of the solvent. The
Discussion
Carbocationic transition states
The methyl substituent of the fluorene moiety has a rate-
acceleration effect. Thus, the solvolyses of 1-Cl and 1-Br are
both about seven times faster than the corresponding reactions
of A-Cl and A-Br, respectively, but the effect on the product
ratio is small (Scheme 2).8,9 The difference in reactivity of
1-X and A-X, corresponding to 1.2 kcal molϪ1, is attributable
to the increased strain in the reactant caused by the methyl
group. The strain is partially relieved in the rate-limiting ioniz-
ation step.
slopes of the Grünwald–Winstein plots for the solvolysis in
acetonitrile–water mixtures are shown in Figs. 1–3. The slopes
(mobs) of the plots for the total reaction of the different
substrates are all smaller than unity; there is a decrease in the
Grünwald–Winstein parameter in the order mobs = 0.97, 0.70,
and 0.60 for 1-Cl, 1-OOCCF3, and 1-Br, respectively. The trend
in the parameter value should reflect a difference in solvation of
the three leaving groups, which parallels the extent of charge
development on the carbon in the rate-limiting transition state.
Bentley and Roberts have found the following trend in solvation
effect with different leaving groups: Cl > Br > I.24 Accordingly,
The effect of the leaving group on the reaction rate is sub-
stantial. The bromide reacts 122 times faster than the chloride,
1602
J. Chem. Soc., Perkin Trans. 2, 2001, 1600–1607

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Table 3 Rate constants for the reactions of 1-OOCCF3 a in aqueous solvents at 25 ЊC
Solventb
Salt
106kobsc/sϪ1
106kEd/sϪ1
106(kS ϩ kNu[NuϪ])d/sϪ1
kE/kS
kNu/kw
33.3% MeCN
40% MeCN
50% MeCN
60% MeCN
40% MeCN
50% MeCN
50% MeCN
50% TFE
50% TFE
50% TFE
50% TFE
50% TFE
None
None
None
None
0.50 M NaClO4
0.32 M NaClO4
0.32 M NaCl
None
0.50 M NaClO4
0.50 M NaCl
0.50 M NaBr
0.50 M NaN3
0.50 M NaSCN
None
22.6
11.8
5.50
3.08
16.3
6.93
4.12
26.5
30.5
25.6
29.8
28.8
29.7
29.5
11.4
6.8
3.6
2.2
9.0
4.4
2.9
14.0
15.4
13.9
16.2
16.2
14.4
11.2
5.0
1.9
0.9
7.3
2.5
1.2
12.5
15.0
11.7
13.6
13.5
13.3
1.02
1.35
1.93
2.49
1.24
1.73
2.32
1.13
1.03
1.19
1.19
1.20
1.07
4.0e
50% TFE
50% MeOH
11.2f
c
a 0.04–0.12 mM. b By volume. kobs = kE ϩ kS ϩ kNu[NuϪ], see Scheme 2; estimated maximum error 3%. d Estimated maximum error 6%. e Ap-
proximate since the product HPLC peak of 1-N3 overlaps partially with that of alkene 2. f The ratio is based upon the sum of the products 1-SCN
and 1-NCS.
Table 4 Kinetic deuterium isotope effects for 1-Cl, 1-Br and 1-OOCCF3 in aqueous media at 25 ЊC
D6
D6
D6
Substrate
Solvent
kobsH/kobs
kEH/kE
kSH/kS
1-Cl
25% MeCN
40% MeCN
60% MeCN
40% MeCN, 0.50 M NaClO4
40% MeCN, 0.50 M NaCl
40% MeCN, 0.45 M NaOAc
50% TFE
40% MeCN
50% MeCN
60% MeCN
70% MeCN
33.3% MeCN
50% TFE
1.76
1.97
2.46
1.84
2.29
2.41
1.91
2.03
2.16
2.47
2.45
2.03
2.15
1.98
3.5
3.2
3.2
3.1
3.4
3.5
3.5
3.2
3.2
3.3
3.0
3.8
3.7
3.6
1.2
1.2
1.3
1.1
1.2
1.4
1.2
1.3
1.2
1.4
1.3
1.4
1.5
1.4
1-Cl
1-Cl
1-Cl
1-Cl
1-Cl
1-Cl
1-Br
1-Br
1-Br
1-Br
1-OOCCF3
1-OOCCF3
1-OOCCF3
50% TFE, 0.50 M NaClO4
different Y-parameters for different leaving groups have been
proposed.
to that for rotational relaxation of a water molecule, i.e.,
kwЈ ∼ 1 × 1011 sϪ1
.
For the separate reactions of 1-X, the following parameter
values were measured: mE = 0.85, 0.58, and 0.51 for 1-Cl, 1-
OOCCF3, and 1-Br, respectively, and mS = 1.20, 0.90, and 0.87,
respectively. A substrate parameter m close to unity is expected
for a classical SN1 reaction and reactions of SN2 type usually
exhibit m values in the range 0.25–0.35.25 However, as has been
pointed out previously,26 the value of m is not a good mech-
anistic tool for distinguishing SN1 and SN2 reactions since it has
been shown that bimolecular substitution reactions can exhibit
large values.26
Since the diffusion of a dilute nucleophile into the reaction
position is much slower, the azide-clock method for measuring
the lifetime of the intermediate does not work. The small
amounts of 1-N3, 1-SCN, and 1-NCS formed in the presence
of the strongly nucleophilic anions (e.g., discrimination ratios
of kN3/kw = 3.4 and kSCN/kw = 5.1 were measured with 1-Cl in
40 vol% acetonitrile, Table 1), should therefore originate from a
preassociation reaction mechanism and/or a “pool” mechanism
in which the nucleophiles close to the ion pair are reacting. The
measured discrimination values are similar to those measured
with the corresponding fluorene derivatives without the 9-
methyl group (A-X, Scheme 2).8,9
The effect of added salts on the kinetics is rather large
Ϫ
(Tables 1–3). Addition of the large polarizable anions ClO4
,
SCNϪ, and IϪ all give an increase in the total reaction rate. The
effects are larger in aqueous acetonitrile than in aqueous TFE.
In aqueous acetonitrile there is also a considerable rate-
depressing effect of added ClϪ and AcOϪ. All these salt effects
in mixed water–organic solvents are similar to those observed
previously,8,9,12–18,26 and could be attributed to a salt-induced
medium effect.27
The extremely small nucleophilic selectivity is also mani-
fested in the formation of a substitution product with the
acetonitrile component of the solvent. Initially, nucleophilic
attack by MeCN on the ion pair gives the nitrilium ion
؉
᎐
1-N᎐CMe with subsequent hydrolysis by water providing
᎐
the amide.28 The amide 1-NHCOMe (Scheme 2) is formed
not very much slower than the alcohol, kMeCN/kw = 0.2–0.5,
despite the large difference in nucleophilicity of acetonitrile
and water. The nucleophilicity of acetonitrile is expected to be
Substitution reactions
low because the basicity of acetonitrile in water is very low,
pKMeCNH = Ϫ10.
It has recently been proposed that simple tertiary carbocations
react with water from the surrounding solvation shell faster
than the ion pair undergoes dissociation.5,6 The tertiary carbo-
cation 1ϩ is more unstable than a simple tertiary carbocation
and the direct reaction of the undissociated ion pair 1ϩXϪ is
expected to be even more favoured relative to dissociation.
Thus, the rate-limiting process of the addition of a solvent
molecule should be the rotation of the nucleophile into a
reactive position which should have a rate constant similar
29
ϩ
The competition between elimination and substitution
Lower polarity of the solvent increases the fraction of elimin-
ation products in accord with what is usually seen in solvolytic
elimination/substitution reactions. This is illustrated by the
Grünwald–Winstein plots (Figs. 1–3) which all show mS > mE.
Obviously, the two product-forming transition states following
J. Chem. Soc., Perkin Trans. 2, 2001, 1600–1607
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Fig. 5 The elimination-to-substitution ratio (kE/kS) as a function of
vol% acetonitrile in acetonitrile–water mixtures at 25 ЊC.
Fig. 6 Brønsted plot for the dehydronation of the ion-pair inter-
mediate formed in the solvolysis of 1-Cl in 40% acetonitrile in water;
ionic strength 0.50 M, maintained with sodium perchlorate at 25 ЊC.
The pKa values refer to those in water (see ref. 39).
a postulated common ion-pair intermediate show different
sensitivities to solvent polarity, suggesting a more localised
charge on the carbon in the addition step than in the elimin-
ation step.
The effect of solvent composition on the elimination-to-
substitution ratio kE/kS is shown in Fig. 5. All three sub-
strates show a considerable increase in the product ratio with
increasing fraction of acetonitrile in the solvent. Similar
behaviour was found for the closely related substrates A-X
(Scheme 2) which do not have the 9-methyl substituent.8,9
Added basic salts increase the elimination-to-substitution
ratio. The effect is most significant in aqueous acetonitrile
(Table 1). There is an approximately linear dependence between
base concentration and kE/kS as shown for the two bases AcOϪ
and CF3COOϪ in Fig. 4.
A plausible explanation for this behaviour is that the base
abstracts a hydron from the carbocation. The assumption that
the addition of solvent to the ion pair to provide a substitution
product is not affected by the general base, implies that a
Brønsted parameter for this catalysis could be derived by
employing the slope of kE/kS versus base concentration for the
Brønsted plot. Such a plot is shown in Fig. 6 for the reactions
with substituted acetate ions. A slope of β = 0.07 is obtained,
which suggests a very early transition state with very little
hydron transfer to the hydron-abstracting base. A parameter
value of β = 0.05 has previously been reported for A-Cl.8
The more stable ion pair formed from cumyl chloride has a
Brønsted parameter of β = 0.13.14 The chloride ion, which is a
very weak base, also increases the kE/kS ratio, approximately to
the same extent as the trifluoroacetate ion. However, owing to
the low pKa, the chloride ion shows an approximately three-fold
positive deviation from the Brønsted plot (Fig. 6). Water, on the
other hand, shows a ca. 10-fold negative deviation. Consistent
with the apparent catalytic effect of chloride ions on kE/kS is the
observation that the substrate 1-Cl yields a higher kE/kS ratio
than the ester 1-OOCCF3 (Fig. 5), despite the difference in pKa
of the leaving groups.
Fig. 7 The kinetic deuterium isotope effects for 1-Cl and 1-Br as a
function of vol% acetonitrile in acetonitrile–water mixtures at 25 ЊC.
Key: kobsH/kobsD6 (᭹), kEH/kED6 (᭛), kSH/kSD6 (᭺).
Isotope effects
The measured kinetic deuterium isotope effect on the total
reaction (kobsH/kobsD6) for the reactions without added salts
(Table 4) versus the fraction of acetonitrile in the solvent is
plotted in Fig. 7. There is a significant increase in isotope effect
with increase in the fraction of the organic solvent that parallels
the increase in kE/kS (Fig. 5). The data for the two substrates
1-Cl and 1-Br are very similar and are adequately described by
a single linear regression line (Fig. 7). Added salts, which affect
kE/kS, also have a corresponding effect on kobsH/kobsD6 (Table 4).
The change in the isotope effect may be explained by a small
amount of internal return that increases slightly with increasing
fraction of the organic solvent (vide infra).
The isotope effects on the separate reactions, kE and kS,
respectively, are also very similar for the leaving groups ClϪ and
BrϪ. There is a slight decrease in kEH/kED6 and a slight increase
in kSH/kSD6, with an increasing fraction of acetonitrile in the
solvent (Fig. 7).
The question concerning the possible role of ClϪ as a general
base has recently been addressed.2,5 It was pointed out that
an important driving force of the ionization is of course the
solvation of the chloride ion but it is not expected to be
complete at the contact ion-pair stage.2 In addition to this
positive effect for chloride ion as a base, there is a low catalytic
activity of water as a hydron acceptor (Fig. 6), in accord with
what has been observed previously for E1 reactions and water-
promoted E2 reactions;8,16,17,30,31 Brønsted plots generally show
a negative deviation for water as a base of about one order of
magnitude.
It has been concluded that even substrates which solvate to
give relatively stable carbocations in mostly aqueous solution
still produce most of the alkene from the ion pair.32 Moreover,
Bunton and coworkers have found that, even in highly aqueous
solvents, added ClϪ promotes elimination from relatively stable
carbocations.33
Are the measured isotope effects consistent with a branched
mechanism with a common ion-pair intermediate for the elimin-
ation and substitution reactions (Scheme 3)? Let us analyse
Scheme 3
the isotope expressions in some detail. The mechanistic model
corresponds to the following relationships between phenom-
enological and microscopic rate constants [eqns. (2)–(4)].
The expressions for the isotope effects are given by eqns. (5)–(7).
1604
J. Chem. Soc., Perkin Trans. 2, 2001, 1600–1607

View Article Online
Preassociation mechanism
kS = k1k2/(kϪ1 ϩ k2 ϩ k3)
(2)
Scheme 4 shows various reaction paths available for alkene for-
mation. The rate constant k3 represents elimination promoted
kE = k1k3/(kϪ1 ϩ k2 ϩ k3)
(3)
(4)
kS ϩ kE = k1(k2 ϩ k3)/(kϪ1 ϩ k2 ϩ k3)
kSH/kSD6 = (k1H/k1D6)(k2H/k2D6)(kϪ1D6 ϩ
k2D6 ϩ k3D6)/(kϪ1H ϩ k2H ϩ k3
H
H
)
)
(5)
(6)
kEH/kED6 = (k1H/k1D6)(k3H/k3D6)(kϪ1D6 ϩ
k2D6 ϩ k3D6)/(kϪ1H ϩ k2H ϩ k3
Scheme 4
(kSH ϩ kEH)/(kSD6 ϩ kED6) = (k1H/k1D6)[(k2H ϩ k3H)/
(k2D6 ϩ k3D6)][(kϪ1D6 ϩ k2D6 ϩ k3D6)/(kϪ1H ϩ k2H ϩ k3H)] (7)
by the leaving group and/or by the solvent. This can occur
by rotation of the leaving group or a solvent water molecule
into a reaction position, processes with expected rate constants
Reaction branching may cause enlarged and attenuated
isotope effects as will be discussed below. Let us assume for
simplicity that internal return is negligible (kϪ1 << k2, k3). The
isotope effect on the ionization step, k1H/k1D6, is a secondary
isotope effect caused by hyperconjugative weakening of the
bonds to the six β-hydrogens. A maximum β-deuterium iso-
of ∼1 × 1011 sϪ1 35–37
A concerted pericyclic reaction is not
.
reasonable; evidence that disqualifies this mechanism has
recently been reported.2 Another possible pathway is through
preassociation of the base with the substrate, followed by ion-
ization to give the triple ion complex BϪRϩXϪ. This stepwise
preassociation route is preferred for elimination when collapse
of the triple ion complex to BϪRX is faster than BϪ diffusing
away, i.e., kϪ1Ј > kϪa. If the apparent slight catalysis by
Brønsted bases is real (and not just a specific salt effect), it must
occur by this preassociation route because the ion pair is so
short-lived that diffusion is slower than the reaction of the
intermediate with the solvent or leaving group. A water
molecule is less effective as a base than the substituted acetate
anions; the deviation from the Brønsted line is one order
of magnitude as discussed above (Fig. 6). The apparent slight
general base catalysis of β = 0.07 suggests that there is a barrier
for the dehydronation of the ion pair. Accordingly, the elimin-
ation does not occur through an enforced uncoupled concerted
mechanism.
There is no competing concerted E2 reaction with the solvent
because the much stronger base, the hydroxide ion, does
not give any bimolecular elimination. The solvent-promoted
E2 reaction is significant for the closely related, more slowly
ionizing, secondary substrates, 9-(1-X-ethyl)fluorene, which
have an acidic hydrogen in the 9-position of the fluorene
moiety.16,38
The incomplete consistency of the measured isotope effects
with the common ion-pair mechanisms of Scheme 3 suggests
that the ion pair is very unstable and does not have time to
choose between dehydronation and addition of a solvent water
molecule. This supports the conclusion that the preassociation
route is significant for the elimination reaction.
D6
tope effect of 1.15/2H, i.e., a value of kobsH/kobs < 2.31 for six
D6
deuteriums is expected.34 Also k2H/k2 is a secondary isotope
effect; the value should be close to unity. The primary isotope
effect k3H/k3D6, on the other hand, should have a substantial
value since it is a primary isotope effect which includes a small
secondary isotope effect (with an expected value >1).
It can be inferred from eqn. (6) that the isotope effect on
the elimination reaction attains a maximum value of kE
H
/
kED6 = (k1H/k1D6)(k3H/k3D6) when elimination is much slower
than substitution (k3H << k2H). The isotope effect on the sub-
stitution reaction [eqn. (5)] attains under these conditions a
maximum value of kSH/kSD6 = k1H/k1D6. On the other hand, fast
elimination, i.e. k3H >> k2H, yields a minimum elimination iso-
tope effect of kEH/kED6 = k1H/k1D6, and a minimum substitution
isotope effect given by eqn. (8),
H
kSH/kSD6 = (k1H/k1D6)(k2H/k2D6)(k3D6/k3
)
(8)
which can be approximated as kSH/kSD6 = (k1H/k1D6)(k3D6/k3H).
Branching as the cause of unusually large and unusually small
isotope effects on competing reactions has been discussed pre-
viously for carbocation 1,8–18 and carbanion reactions,11 and has
also been generalized and reviewed.1,11
Fast internal return (kϪ1 >> k2, k3) yields eqn. (9),
kEH/kED6 = (k1H/k1D6)(k3H/k3D6) (kϪ1D6/kϪ1
)
(9)
H
i.e., kEH/kED6 ≈ (k1H/k1D6)(k3H/k3D6), and kSH/kSD6 ≈ (k1H/k1D6)-
(k2H/k2D6). This has the same effect on the elimination isotope
effect as fast substitution. Thus, the observed elimination iso-
tope effect is enlarged owing to multiplication by a factor larger
than unity.
Experimental
General procedures
NMR spectra were recorded at 20 ЊC on a Varian Unity 300
1
As discussed above, a small and changing amount of internal
return has to be included in the mechanistic interpretation of
spectrometer, for H NMR at 300 MHz and for 13C NMR at
75.45 MHz. Chemical shifts were indirectly referenced to TMS
via the solvent signal (chloroform-d1, 7.26 and 77.16 ppm). The
high-performance liquid chromatography analyses were carried
out with a Hewlett-Packard 1090 liquid chromatograph
equipped with a diode-array detector on an Inertsil 5 ODS-2
(3 × 100 mm) reversed-phase column. The mobile phase was a
solution of acetonitrile in water. The reactions were studied at
constant temperature maintained with a HETO 01 PT 623
thermostat bath kept at 25.00 0.03 ЊC. A Kontron Uvicon 930
spectrophotometer equipped with an automatic cell changer
kept at constant temperature with water from the thermostat
bath was used for some of the kinetic studies. The mass
spectrometry experiments were performed on a Finnigan MAT
GCQ instrument.
D
the results (Scheme 3). The slight decrease in kEH/kE with
increasing fraction of the organic solvent component is also
consistent with this interpretation. However, the slight increase
D6
in the isotope effect kSH/kS with increasing acetonitrile frac-
tion of the solvent does not seem possible to accommodate into
the mechanism of Scheme 3. The introduction of two parallel
pathways, however, removes this inconsistency (see next
section).
Previous reported results for the closely related A-X system
showed an approximately constant ionization isotope effect
D6
kobsH/kobs and changes in the isotope effects for the separate
rate constants are in accord with irreversible ionization via a
common intermediate (Scheme 3, kϪ1 << k2, k3).8–10
J. Chem. Soc., Perkin Trans. 2, 2001, 1600–1607
1605

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Materials
temperature overnight, and then most of the solvent was
evaporated. Ether was used to extract the crude product,
followed by washing 3 times with 0.5 M HCl and then 3 times
with water and drying over magnesium sulfate. Evaporation of
the solvent gave a viscous oil. NMR and HPLC confirmed the
purity. 1H NMR (CDCl3) δ 7.74 (2 H, d, J = 7.59 Hz), 7.59 (2 H,
d, J = 7.44 Hz), 7.40 (2 H, t, J = 7.44 Hz), 7.31 (2 H, t, J = 7.59
Hz), 1.83 (3 H, s), 1.67 (6 H, s); 13C NMR (CDCl3) δ 156.0
(q, J = 41.3 Hz), 148.5, 141.2, 128.1, 127.4, 125.3, 120.0, 114.8
(q, J = 287.5 Hz), 93.2, 58.1, 21.0, 19.5; m/z 334 (Mϩ).
Merck silica gel 60 (240–400 mesh) was used for flash chromato-
graphy. Diethyl ether and tetrahydrofuran (THF) were distilled
under nitrogen from sodium and benzophenone. Methanol and
acetonitrile were of HPLC grade and 2,2,2-trifluoroethanol
(TFE) was of GC grade. All other chemicals were of reagent
grade and used without further purification.
9-Methylfluorene. Synthesised according to a literature
procedure.40
9-Methyl-9-(2-trifluoroacetoxy-2-[1Ј,1Ј,1Ј,3Ј,3Ј,3Ј-2H6]propyl)-
fluorene. Prepared according to the method above. The 2H
content of the viscous oil was measured by H NMR as >99.6
9-Methyl-9-(2-hydroxy-2-propyl)fluorene (1-OH). A solution
of n-butyllithium (7.36 ml of a 1.6 M solution in hexane) was
added to 9-methylfluorene (1.929 g) dissolved in dry THF
(52 ml) at Ϫ78 ЊC under nitrogen. The resulting red solution
was stirred for 40 min at Ϫ78 ЊC, and then dry acetone (0.8 ml)
was added. The reaction mixture was stirred for 1 h, and then
poured into a saturated NH4Cl solution. The mixture was
extracted 3 times with ether. The combined ether fractions were
washed with water 3 times to neutrality, followed by washing
with brine and drying over magnesium sulfate. After removal
of the solvent, the crude product was purified by flash chroma-
tography (silica gel) with ether–pentane as eluent. Recrystalliz-
ation twice from hexane gave pure material: mp 70–71.5 ЊC
(lit. 67–70 ЊC);41 1H NMR (CDCl3) δ 7.72 (2 H, d, J = 6.84 Hz),
7.57 (2H, d, J = 6.87 Hz), 7.25–7.41 (4 H, m), 1.74 (1 H, s), 1.63
(3 H, s), 1.06 (6 H, s).
1
atom%.
9-Methyl-9-(propen-2-yl)fluorene (2). Accidentally obtained
in an attempt to purify crude 9-methyl-9-(2-bromo-2-propyl)-
fluorene (1-Br). The bromide (0.5 g) was completely de-
composed on the column (silica gel, 70 g) to give 2 as the first
fraction using CH2Cl2–C5H12 (10 : 90) as eluent: 1H NMR
(CDCl3) δ 7.42 (2 H, m), 7.26–7.40 (6 H, m), 5.35 (1 H, s), 5.07
(1 H, t, J = 1.38 Hz), 1.57 (3 H, s), 1.07 (3 H, s); m/z 220 (Mϩ).
Kinetics and product studies
Reactions with 1-Cl and 1-OOCCF3. The reaction solutions
were prepared by mixing acetonitrile, methanol, or 2,2,2-
trifluoroethanol with water at room temperature, ca. 23 ЊC. The
reaction vessel was a 1.5 ml HPLC vial, sealed with a gas-tight
PTFE septum, which was placed in an aluminium block kept at
25 ЊC with water from the thermostat bath. The concentration
of the substrate in the reaction solution was in the range of
0.04–0.12 mM. The volume of the reaction solution was usually
1.2 ml. The reactions were initiated by fast addition of a few
microliters of the substrate dissolved in acetonitrile by means
of a syringe. At appropriate intervals, samples were analysed
using the HPLC apparatus. The reactions involving the
substrate 1-Cl were followed by monitoring the increase in
the peak area of the product 1-OH, and the rate constants
were calculated from plots of peak area versus time by means
of a nonlinear regression computer program. The rate con-
stant for the disappearance of the substrate 1-OOCCF3
was calculated from plots of substrate peak area versus time
by means of the same computer program. All product ratios
were constant throughout the reaction progress. The separate
rate constants for the elimination and substitution reactions
were derived by combination of product composition data,
obtained from the peak areas and the relative response
factors determined in separate experiments, and the observed
rate constants.
9-Methyl-9-(2-hydroxy-2-[1Ј,1Ј,1Ј,3Ј,3Ј,3Ј-2H6]propyl)fluorene.
Prepared from 9-methylfluorene and 1,1,1,3,3,3-(2H6)-acetone
(>99.5 atom% 2H, Ciba-Geigy) according to the method
described above. The 2H content of the crystalline material was
measured by 1H NMR as >99.7 atom%.
9-Methyl-9-(2-chloro-2-propyl)fluorene (1-Cl).
A solution
of 1-OH (0.56 g) in dichloromethane (43 ml) containing
anhydrous calcium chloride and lithium chloride was cooled to
0 ЊC. Dry hydrogen chloride was bubbled through the solution
for 12 h. After filtration, the solvent was removed. Recrystal-
lization from pentane several times gave pure material: mp
1
95–97 ЊC; H NMR (CDCl3) δ 7.67–7.75 (4 H, m), 7.24–7.41
(4 H, m), 1.79 (3 H, s), 1.45 (6 H, s); m/z 256, 258 (Mϩ).
9-Methyl-9-(2-chloro-2-[1Ј,1Ј,1Ј,3Ј,3Ј,3Ј-2H6]propyl)fluorene.
Prepared from the deuterated alcohol according to the method
described above. The 2H content of the crystalline material was
measured by 1H NMR as >99.5 atom%.
9-Methyl-9-(2-bromo-2-propyl)fluorene (1-Br).
A solution
of 1-OH (0.2 g) in dry dichloromethane (3 ml) was added to
2.5 ml of concentrated HBr solution saturated with ZnBr2
in a separating funnel. The mixture was shaken for 15 s and
the reaction was quenched by the addition of pentane. After
separation, the organic phase was washed 3 times with water.
After evaporation the residue was purified by repeated
recrystallization (6 times) from pentane giving the pure 1-Br:
Reactions with 1-Br. The solvolytic reactions of the bromide
in aqueous acetonitrile were too fast to be followed by the
above HPLC procedure, especially in more than 50 vol%
aqueous media. Instead, a spectrophotometric method based
on monitoring the decrease in the absorbance of added 4-
nitrophenolate anion at 409 nm was used. The reaction solu-
tions were prepared by mixing acetonitrile with water at room
temperature, ca. 23 ЊC, and a few microliters of sodium 4-
nitrophenolate in 50 vol% acetonitrile in water were added. The
reaction vessel, a 3 ml tightly stoppered UV cell, was kept
at 25 ЊC. The concentration of the substrate in the reaction
solution (2 ml) was in the range 0.04–0.12 mM, while that of
the indicator was usually 2–3 times higher. The reaction was
initiated by fast addition of a few microliters of the substrate
dissolved in CH2Cl2 by means of a syringe. The reactions were
followed for about 10 half lives. The product ratios were
obtained by HPLC analyses as described above for 1-Cl and
1-OOCCF3.
1
mp 99–101 ЊC; H NMR (CDCl3) δ 7.76 (2 H, d, J = 7.56 Hz),
7.69 (2 H, d, J = 7.44 Hz), 7.39 (2 H, t, J = 7.44 Hz), 7.28 (2 H, t,
J = 7.48 Hz), 1.83 (3 H, s), 1.67 (6 H, s); m/z 300, 302 (Mϩ).
9-Methyl-9-(2-bromo-2-[1Ј,1Ј,1Ј,3Ј,3Ј,3Ј-2H6]propyl)fluorene.
Prepared from the deuterated alcohol according to the method
described above. The 2H content of the crystalline material was
measured by 1H NMR as >99.3 atom%.
9-Methyl-9-(2-trifluoroacetoxy-2-propyl)fluorene
(1-OOC-
CF3). Alcohol 1-OH (0.4 g) was dissolved in dry dichlorometh-
ane (16 ml), and dry pyridine (2 ml) and trifluoroacetic
anhydride (1 ml) were added. The mixture was stirred at room
1606
J. Chem. Soc., Perkin Trans. 2, 2001, 1600–1607

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17 Q. Meng and A. Thibblin, J. Am. Chem. Soc., 1997, 119, 4834.
18 Q. Meng, B. Du and A. Thibblin, J. Phys. Org. Chem., 1999, 12,
116.
19 E. Grunwald and S. Winstein, J. Am. Chem. Soc., 1948, 70, 846.
20 S. Winstein, E. Grunwald and H. W. Jones, J. Am. Chem. Soc., 1951,
73, 2700.
The relative HPLC response factors for 1-OH and alkene 2
were measured from the HPLC analysis of a mixture of the
two components, prepared by weighing and dissolved in
acetonitrile. The response factors for the other products were
assumed to be the same as that of 1-OH.
The estimated errors are considered as maximum errors
derived from maximum systematic errors and random
errors. The maximum errors of the directly measured quantities
were thus allowed to propagate as systematic errors into derived
quantities, e.g., reaction rate constants.
21 A. H. Fainberg and S. Winstein, J. Am. Chem. Soc., 1956, 78, 2770.
22 C. A. Bunton, M. M. Mhala and J. R. Moffatt, J. Org. Chem., 1984,
49, 3637.
23 C. A. Bunton, M. M. Mhala and J. R. Moffatt, J. Org. Chem., 1984,
49, 3639.
24 T. W. Bentley and K. Roberts, J. Org. Chem., 1985, 50, 1985.
25 C. Reichardt, Solvents and Solvent Effects in Organic Chemistry,
VCH, Weinheim, Germany, 1988.
26 J. P. Richard and W. P. Jencks, J. Am. Chem. Soc., 1984, 106, 1383.
27 E. Grunwald and A. F. Butler, J. Am. Chem. Soc., 1960, 82, 5647;
E. F. J. Duynstee, E. Grunwald and M. L. Kaplan, J. Am. Chem.
Soc., 1960, 82, 5654.
Acknowledgements
We thank the Swedish Natural Science Research Council for
supporting this work.
28 J. Bartl, S. Steenken, H. Mayr and R. A. McClelland, J. Am. Chem.
Soc., 1990, 112, 6918 and references therein.
29 A. Gervasini and A. Auroux, J. Phys. Chem., 1993, 97, 2628.
30 J. P. Richard and W. P. Jencks, J. Am. Chem. Soc., 1984, 106, 1373.
31 A. Thibblin and W. P. Jencks, J. Am. Chem. Soc., 1979, 101, 4963.
32 A. Thibblin, J. Phys. Org. Chem., 1992, 5, 367.
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