Flash photolytic generation and study of p-quinone α-phenylmethide and p-quinone α,α-diphenylmethide in aqueous solution

Article abstract of DOI:10.1002/poc.767

p-Quinone α-phenylmethide (7) and p-quinone α,α- diphenylmethide (8) were generated by flash photolytic dehydration of p-hydroxy-α-phenylbenzyl alcohol (9, R₁ =Ph, R₂ = H) and p-hydroxy-α,α-diphenylbenzyl alcohol (9, R₁ = R ₂ = Ph) respectively, and rates of their decay were measured in aqueous perchloric acid and sodium hydroxide solutions and also as in acetic acid, biphosphate ion, tris(hydroxymethyl)methylammonium ion, ammonium ion and bicarbonate ion buffers. The rate profiles for the hydration of these quinone methides that these data provide show hydronium ion and hydroxide ion-catalyzed regions and also 'uncatalyzed' water reactions, with saturation of hydronium ion catalysis in dilute solution for the diphenyl-substituted substrate but only in concentrated acid solution for the less basic monophenyl substrate. Both substrates also give inverse hydronium ion isotope effects (k _H+/k_D+ <1). These results show that the hydronium ion-catalyzed reactions occur by rapid pre-equilibrium protonation of the quinone methide on its carbonyl oxygen atom followed by rate-determining capture of the benzyl-type carbocation thus formed by water. Phenyl substitution retards the rate of hydration and also reduces the acidity constant of the quinone methide conjugate acid. The molecular basis of these substituent effects is discussed. Copyright

Full text of DOI:10.1002/poc.767

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2004; 17: 579–585
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.767
Flash photolytic generation and study of p-quinone
a-phenylmethide and p-quinone a,a-diphenylmethide
,
in aqueous solutiony z
J. A. Chang, A. J. Kresge,* H.-Q. Zhan and Y. Zhu
Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada
Received 14 July 2003; revised 22 September 2003; accepted 22 September 2003
ABSTRACT: p-Quinone ꢀ-phenylmethide (7) and p-quinone ꢀ,ꢀ-diphenylmethide (8) were generated by flash
epoc
photolytic dehydration of p-hydroxy-ꢀ-phenylbenzyl alcohol (9, R1 ¼ Ph, R2 ¼ H) and p-hydroxy-ꢀ,ꢀ-diphenylben-
zyl alcohol (9, R1 ¼ R2 ¼ Ph) respectively, and rates of their decay were measured in aqueous perchloric acid and
sodium hydroxide solutions and also as in acetic acid, biphosphate ion, tris(hydroxymethyl)methylammonium ion,
ammonium ion and bicarbonate ion buffers. The rate profiles for the hydration of these quinone methides that these
data provide show hydronium ion and hydroxide ion-catalyzed regions and also ‘uncatalyzed’ water reactions, with
saturation of hydronium ion catalysis in dilute solution for the diphenyl-substituted substrate but only in concentrated
acid solution for the less basic monophenyl substrate. Both substrates also give inverse hydronium ion isotope effects
þ
þ
(kH =kD <1). These results show that the hydronium ion-catalyzed reactions occur by rapid pre-equilibrium
protonation of the quinone methide on its carbonyl oxygen atom followed by rate-determining capture of the
benzyl-type carbocation thus formed by water. Phenyl substitution retards the rate of hydration and also reduces the
acidity constant of the quinone methide conjugate acid. The molecular basis of these substituent effects is discussed.
Copyright # 2004 John Wiley & Sons, Ltd.
Additional material for this paper is available in Wiley Interscience
KEYWORDS: p-quinone ꢀ-phenylmethide; p-quinone ꢀ,ꢀ-diphenylmethide; quinone methide hydration; flash photolysis;
rate profiles; solvent isotope effects; reaction mechanisms
INTRODUCTION
quinone methide hydration reactions. In order to provide
information about these hydrations, and how their rates
depend upon quinone methide structure, we have under-
taken a detailed investigation of their kinetics and
reaction mechanisms.
Quinone methides are interesting reactive species posses-
sing both nucleophilic and electrophilic centers, which
has made them useful synthetic intermediates with wide
applications in organic chemistry.1 Quinone methides
also figure prominently in wood chemistry, playing key
roles in both lignification reactions in the plant and
delignification reactions in the paper mill.2 But perhaps
most significant of all is the pronounced activity shown
by quinone methides in biological systems: they have, for
example been implicated as the ultimate cytotoxins
responsible for the effects of agents such as antitumor
drugs, antibiotics and DNA alkylators.3 In living systems
where water is the ubiquitous medium, this biological
activity must operate against a background of wasteful
We have already reported examination of the two
parent substances, o-quinone methide, 1,4 and p-quinone
methide, 2.5 These studies showed that hydration of these
quinone methides occurs by hydronium ion-catalyzed,
uncatalyzed and hydroxide ion-catalyzed pathways. They
also revealed that hydronium ion catalysis takes place by
rapid and reversible pre-equilibrium protonation of the
quinone methide on its oxygen atom, followed by rate-
determining hydration of the carbocation ion thus formed
[Eqn (1)]:
*Correspondence to: A. J. Kresge, Department of Chemistry,
University of Toronto, Toronto, Ontario M5S 3H6, Canada.
E-mail: akresge@chem.utoronto.ca
Contract/grant sponsor: Natural Sciences and Engineering Research
Council of Canada.
yThis paper is dedicated to Professor William P. Jencks in appreciation
of his seminal contributions to physical organic chemistry.
zSelected paper part of a special issue entitled ‘Biological Applications
of Physical Organic Chemistry’.
ð1Þ
The uncatalyzed reaction, on the other hand, occurs by
simple nucleophilic attack of a water molecule on
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 579–585

580
J. A. CHANG ET AL.
the unprotonated quinone methide, with or without
simultaneous proton shuffling to avoid a zwitterionic
intermediate [Eqn (2)]:
Kinetics
Flash photolytic rate measurements were made using a
microsecond conventional flash lamp system and a na-
nosecond eximer laser system operating at ꢁ ¼ 248 nm,
which have already been described.12 Initial benzyl
alcohol substrate concentrations were of the order of
1 ꢀ 10ꢁ5 M and the temperature of all reacting solutions
was controlled at 25.0 ꢂ 0.05 ꢃC. Quinone methide decay
was monitored at ꢁ ¼ 395 nm for p-quinone ꢀ-phenyl-
methide and at ꢁ ¼ 415 nm for p-quinone ꢀ,ꢀ-diphenyl-
methide, and p-methoxybenzhydryl cation decay was
monitored at ꢁ ¼ 460 nm. The data so obtained con-
formed to the first-order rate law well, and observed
first-order rate constants were obtained by least-squares
fitting of a single exponential function.
ð2Þ
We were able also to verify the reaction mechanism of
Eqn (1) for o-quinone ꢀ-phenylmethide, 3, and o-quinone
ꢀ-(p-anisyl)methide, 4, An ¼ 4-CH3OC6H4,6 and also for
cis-, 5, and trans-5-methoxy-o-quinone ꢀ-phenylethide
6,7 by showing that acid catalysis of the hydration of
these more basic substrates becomes saturated at higher
acidities as the position of the pre-equilibrium step shifts
from unprotonated to protonated substrate.
Rates with half-lives greater than a few seconds could
not be measured in this way because the monitoring lamp
power supply was not sufficiently steady. These reactions
were therefore initiated by a single flash from the con-
vention flash photolysis system and the reacting solutions
were then quickly transferred to the cell compartment of
a Cary 2200 spectrometer where absorbance decay mea-
surements were made. The temperature of these reacting
solutions was maintained at 25.0 ꢂ 0.05 ꢃC. These data
also conformed to the first-order rate law well, and
observed first-order rate constants were again obtained
by least-squares fitting of a single exponential function.
In this paper, we report on the hydration reactions of
p-quinone ꢀ-phenylmethide, 7, and p-quinone ꢀ,ꢀ-
diphenylmethide, 8. These substances together with the
parent p-quinone methide, 2, form a series which shows
the effect of successive phenyl substitution on quinone
methide reactivity.
We generated the present quinone methides, as we4–7
and others1 had done before, by photolytic dehydration of
the corresponding substituted p-hydroxybenzyl alcohols,
9 [Eqn (3)]:
RESULTS
ð3Þ
p-Quinone a,a-diphenylmethide
Most of the reactions that we studied were fairly fast,
and we therefore used flash photolytic methods to deter-
mine their rates.
Perchloric acid solutions. Rates of decay of p-
quinone ꢀ,ꢀ-diphenylmethide were measured in aqueous
perchloric acid solutions using both H2O and D2O as the
solvent. The data so obtained are summarized in Supple-
mentary Table S1 (available in Wiley Interscience) and
are also displayed in Fig. 1.
EXPERIMENTAL
Materials
It can be seen that reaction rates increase with increas-
ing acid concentration at the lower end of the acidity
range investigated, i.e. the reaction here is acid catalyzed.
In this region, moreover, rates are slower in H2O than in
D2O, i.e. the isotope effect is inverse: kH/kD < 1. At the
higher acidity end of the range investigated, on the other
hand, acid catalysis becomes saturated, and the inverse
isotope effect becomes weaker and finally disappears.
These phenomena are consequences of the operation of
the pre-equilibrium protonation reaction mechanism
shown as Eqn (1). At low acidities, the position of the
pre-equilibrium step is over on the side of unprotonated
substrate, and protonation, i.e. acid catalysis, is required
to convert unprotonated substrate into product. The pre-
equilibrium step, moreover, transforms the relatively
loose ‘non-reacting’ O—H bonds of the hydronium ion
into tighter O—H bonds of a water molecule.13 There is
p-Hydroxy-ꢀ-phenylbenzyl alcohol (9, R1 ¼ Ph, R2 ¼ H)
was prepared by treating p-hydroxybenzaldehyde with
phenylmagnesium bromide; its melting-point and 1H
NMR spectrum were consistent with literature values.8
p-Hydroxy-ꢀ,ꢀ-diphenylbenzyl alcohol (9, R1 ¼ R2 ¼
Ph) was obtained by treating methyl p-hydroxybenzoate
with phenylmagnesium bromide; its melting-point and
1H NMR spectrum also agreed with literature values.9
p-Methoxybenzhydryl acetate was synthesized by treat-
ing p-methoxybenzhydrol10 with acetic anhydride in the
1
presence of pyridine;11 its H and 13C NMR spectra
agreed with a literature report.11
All other materials were of the best available commer-
cial grades.
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 579–585

p-QUINONE ꢀ-PHENYL- AND ꢀ,ꢀ-DIPHENYLMETHIDE
581
is nicely consistent with k ¼ 1 ꢀ 103 sꢁ1 determined for
the analogous reaction of p-methoxyphenyldiphenyl-
methyl cation with water:14
ð6Þ
and the recent report that a p-hydroxyphenyl group is
about twice as good at stabilizing aryl substituted cations
as a p-methoxyphenyl group.15 The isotope effect on the
ionization of the substrate conjugate acid determined
here, KSH/KSD ¼ 3.0, is also consistent with solvent iso-
tope effects on the ionization of other oxygen acids of
similar acid strength, e.g. KH/KD ¼ 2.8 for the ionization
of picric acid.16
Rate profile. Rates of reaction of p-quinone ꢀ,ꢀ-
diphenylmethide were also measured in aqueous sodium
hydroxide solutions and in acetic acid, biphosphate ion,
tris(hydroxymethyl)methylammonium ion, ammonium
ion and bicarbonate ion buffers. The data so obtained
are summarized in Supplementary Tables S2 and S3.
The measurements in buffers were made using series of
solutions of constant buffer ratio and constant ionic
strength (0.10 M), and therefore constant hydronium ion
concentration, but varying total buffer concentration. The
data were analyzed by least-squares fitting of the buffer
dilution expression
Figure 1. Rates of hydration of p-quinone ꢀ,ꢀ-diphenyl-
methide in H2O (*) and D2O (Á) solutions of perchloric acid
at 25 ꢃC
therefore a tightening up of isotopically substituted
bonds, and an inverse isotope effect results. At high
acidities, on the other hand, the position of the pre-
equilibrium shifts to protonated substrate, and this then
becomes the reaction’s initial state; substrate protonation
is now no longer required to convert this initial state into
product and acid catalysis becomes saturated. The initial
state now also contains a water molecule rather than a
hydronium ion and tightening up of loose hydronium ion
O—H bonds no longer takes place; the inverse isotope
effect consequently disappears.
kobs ¼ kint þ kbuff½bufferꢄ
ð7Þ
Buffer catalysis was found to be either very weak or non-
existent, and buffer catalytic coefficients, kbuff, could
consequently not be well determined. Zero buffer con-
centration intercepts, kint, on the other hand, could be
determined well. These, together with the rate constants
measured in perchloric acid and sodium hydroxide solu-
tions, are displayed as the lower rate profile of Fig. 2.
The rate law that applies to this reaction mechanism is
as follows:
kobs ¼ kw0 ½Hþꢄ=ðKSH þ ½HþꢄÞ
ð4Þ
with the rate constant for carbocation ion capture, kw0 , and
the substrate conjugate acid ionization constant, KSH
as defined by Eqn (1). Least-squares fitting of this
,
expression gave kw0 ¼ (3.87 ꢂ 0.09) ꢀ 102 sꢁ1 and KSH
¼
(1.84 ꢂ 0.05) ꢀ 10ꢁ1 M, pKSH ¼ 0.74 ꢂ 0.01, plus the
isotope effects (kw0 )H O/(kw0 )D O ¼ 1.14 ꢂ 0.04 and KSH
/
2
2
KSD ¼ 2.95 ꢂ 0.13.
At low acidities where [Hþ] ꢅKSH, Eqn (4) reduces to
kobs ¼ (kw0 /KSH)[Hþ], which shows that the hydronium
ion catalytic coefficient, defined as kH ¼ Ákobs/Á[Hþ],
þ
is equal to kw0 /KSH. Use of the least-squares results given
above for kw0 and KSH then provides kH ¼ ð2:11ꢂ
þ
0:08Þ ꢀ 103 Mꢁ1 sꢁ1 and the inverse isotope effect
þ
þ
kH =kD ¼ 0:387 ꢂ 0:022.
The rate constant determined here, kw0 ¼ 3.9 ꢀ 102 sꢁ1
,
for capture of the p-hydroxyphenyldiphenylmethyl cation
by water in aqueous solution:
Figure 2. Rate profiles for the hydration of p-quinone ꢀ,ꢀ-
diphenylmethide (*) and p-quinone ꢀ-phenylmethide (Á) in
aqueous solution at 25 ꢃC
ð5Þ
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 579–585

582
J. A. CHANG ET AL.
Hydronium ion concentrations of the buffer solutions
needed for this purpose were obtained by calculation
using buffer acid ionization constants from the literature
and activity coefficients recommended by Bates.17
It can be seen that these additional data have added an
uncatalyzed water reaction and a hydroxide ion-catalyzed
process to the rate profile of Fig. 1. The rate law that now
applies is therefore that of Eqn (4) with uncatalyzed and
hydroxide ion catalyzed terms added:
This lack of saturation of acid catalysis, coupled with a
pre-equilibrium protonation reaction mechanism, means
that hydronium ion concentrations have not yet reached
the level where they are comparable to the value of the
substrate acidity constant KSH, and this requires that
the condition [Hþ] ꢅKSH be imposed upon the rate law
Eqn (8). The result is the rate law
þ
ꢁ
ꢁ
þ
k ¼ kH ½H ꢄ þ kw þ kHO ½HO ꢄ
ð9Þ
ꢁ
k ¼ kw0 ½Hþꢄ=ðKSH þ ½HþꢄÞ þ kw þ kHO ½HO ꢄ
ð8Þ
ꢁ
with kH ¼ kw0 =KSH. Least-squares fitting of this expres-
þ
sion gave kH ¼ ð2:97 ꢂ 0:04Þ ꢀ 104 Mꢁ1 sꢁ1
,
kw ¼
Least-squares fitting of this expression gave kw0 ¼
þ
(5.12 ꢂ 0.20) ꢀ 10ꢁ2 sꢁ1 and kHO ¼ ð8:20 ꢂ 0:15Þ ꢀ
(3.92 ꢂ 0.14) ꢀ 102 sꢁ1
0:10Þ ꢀ 10ꢁ1
,
KSH ¼ (1.89 ꢂ 0.08) ꢀ 10ꢁ1 M,
ꢁ
101 Mꢁ1 sꢁ1. This value of kH is nicely consistent with
kw ¼ (3.69 ꢂ 0.11) ꢀ 10ꢁ4 sꢁ1
and
kHO ¼ ð6:48 ꢂ
þ
ꢁ
kH ¼ ð2:92 ꢂ 0:03Þ ꢀ 104 Mꢁ1 sꢁ1 obtained above in the
M
ꢁ1 sꢁ1. The first two of these values
þ
isotope effect determination. The weighted average of
þ
are nicely consistent with the results obtained by fitting
Eqn (4). Weighted averages ofꢁt1he two determinations
the two values is kH ¼ ð2:94 ꢂ 0:02Þ ꢀ 104 Mꢁ1 sꢁ1
.
give kw0 ¼ (3.89 ꢂ 0.08) ꢀ 102 s
and KSH ¼ (1.85 ꢂ
0.04) ꢀ 10ꢁ1 M, pKSH ¼ 0.73 ꢂ 0.01.
Concentrated perchloric acid solutions. In an at-
tempt to detect saturation of acid catalysis, which was not
apparent from the dilute perchloric acid data
([HClO4] ꢆ 0.1 M) represented by the upper rate profile
of Fig. 2, rates of decay of p-quinone ꢀ-phenylmethide
were also measured in concentrated perchloric acid
solutions up to 3.6 M. These data are summarized in
Supplementary Table S7. They, together with the results
obtained in dilute perchloric acid solutions, are also
displayed in Fig. 3, which uses the X0 excess acidity
scale18 in its abscissa to account for the increased
effective acidity of the concentrated acid solutions.
The line drawn in Fig. 3 is based on the dilute solution
data, where observed rate constants are linearly related to
acid concentration. Saturation of acid catalysis in the
concentrated acid solutions is clearly visible. Observed
rate constants, however, do not simply level off to a
constant value as expected for simple saturation; instead,
p-Quinone a-phenylmethide
Rate profile. Rates of decay of p-quinone ꢀ-phenyl-
methide were measured in dilute aqueous perchloric acid
solutions, again using both H2O and D2O as the solvent,
as well as in sodium hydroxide solutions and also in
acetic acid, biphosphate anion, tris(hydroxymethyl)-
methylammonium ion, ammonium ion and bicarbonate
ion buffers. These data are summarized in Supplementary
Tables S4–S6.
The measurements in buffers were again made in series
of solutions of constant buffer ratio and constant ionic
strength (0.10 M) but varying total buffer concentration,
and the data were again analyzed by least-squares fitting
of Eqn (7). Buffer catalysis was now still weak although
somewhat stronger than that found for p-quinone ꢀ,ꢀ-
diphenylmethide. This is consistent with the expectation
that the buffer base serves as a nucleophile reacting
directly with the quinone methidesubstituted methylene
group, which is less crowded in the monophenyl than in
the diphenyl substrate.
The zero buffer concentration intercepts obtained in
this way, together with the rate constants determined in
perchloric acid and sodium hydroxide solutions, were
used to construct the upper rate profile shown in Fig. 2.
This rate profile has the same general shape as that
obtained for p-quinone ꢀ,ꢀ-diphenylmethide (Fig. 2,
lower profile), except that it lacks saturation of acid
catalysis. The present quinone methide nevertheless
does react by the preequilibrium protonation mechanism
of Eqn (1), as shown by its inverse hydronium ion isotope
effect: observed rate constants in dilute DClO4–D2O
solution are linear functions of acid concentration, just
as they are in dilute HClO4–H2O solutions, and linear
Figure 3. Rates of hydration of p-quinone ꢀ-phenylmethide
in dilute (*) and concentrated (Á) perchloric acid solutions,
illustrating saturation of acid catalysis and inhibition by ion-
pair formation
þ
least-squares analysis gives kH ¼ ð2:92 ꢂ 0:03Þ ꢀ
104 Mꢁ1 sꢁ1 and kH =kD ¼ 0:408 ꢂ 0:011.
þ
þ
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 579–585

p-QUINONE ꢀ-PHENYL- AND ꢀ,ꢀ-DIPHENYLMETHIDE
583
they reach a maximum value and then decrease. This
decrease is produced by the known ability of perchlorate
ions to inhibit the rates of reaction of large delocalized
carbocations with water, an effect that has been attributed
to carbocation–perchlorate ion ion-pair formation.19 This
complication requires modification of the simple pre-
equilibrium protonation reaction scheme of Eqn (1) by
inclusion of an ion-pair formation equilibrium:
constant for capture of the carbocationic quinone methide
conjugate acid by thiocyanate ion. On the reasonable
assumption that this carbocation capture is an encounter-
controlled process, the encounter-controlled rate constant
k ¼ 5 ꢀ 109 Mꢁ1 sꢁ1 could then be assigned to kS0 CN and
K
SH could be evaluated.
Protonation of the present quinone methide produces a
carbocation, 9, that is more stable than those to which this
method of estimating KSH was previously applied,4,5 and
its capture by thiocyanate ion is consequently not an
e0ncounter-controlled process (see below). An estimate of
kSCN for 9 may nevertheless still be made by measuring
the rate constant for capture of its methoxy-substituted
analog, 10, by thiocyanate ion and then applying the
factor of two by which hydroxy-substituted cations have
recently been shown to be more stable than their meth-
oxysubstituted analogs.15
ð10Þ
The simple rate law of Eqn (4) must also be modified to
include this ion-pair equilibrium, and also to include
the activity of water, which decreases significantly over
the range of acid concentrations used, in contrast to the
situation in dilute solution where water activity remained
constant. In addition, the increased effective acidity of
concentrated acid solutions must be taken into account by
including the excess acidity function X0 and an acidity
function slope parameter m.
The rate of capture of carbocation 9 by thiocyanate ion
was determined by measuring rates of decay of p-quinone
ꢀ-phenylmethide in series of dilute aqueous sodium
thiocyanate solutions at fixed perchloric acid concentra-
tions. These data are summarized in Supplementary
Table S8.
The resulting expression:
þ
kw0 ð½H ꢄ10mX ÞAH O
0
2
kobs
¼
ð11Þ
ꢁ
þ
KSH þ ð½H ꢄ10mX Þð1 þ KIP½ClO4 ꢄÞ
0
Observed first-order rate constants obtained in this way
proved to be linear functions of thiocyanate concentra-
tion, as is illustrated in Fig. 4. The gradients of these
relationships, Ákobs/Á[SCNꢁ], were in turn linear func-
tions of acid concentration, as shown in Fig. 5, and the
gradient of that relationship then provided the rate con-
contains three independent variables: [Hþ] ( ¼ [ClO4ꢁ]),
X0 and AH O, and four parameters to be determined: kw0 ,
2
KSH, KIP and m. We attempted to evaluate these four
parameters by least-squares fitting using GrafFit Soft-
ware,20 but we were unable to obtain a unique solution
that did not vary with changes in the initial guesses of
these parameters, which were needed as input for the
calculation. A similar difficulty was encountered when
the number of parameters to be determined was reduced
from four to three by fitting of a modified form of Eqn
þ
stant kS0 CN/KSH ¼ (9.15 ꢂ 0.95) ꢀ 107 Mꢁ2 sꢁ1
.
(11) that incorporated the value of kw0 /KSH ( ¼ kH
)
determined in dilute acid solutions. Despite the fact that
we could not analyze our data quantitatively, the con-
centrated acid rate measurements are nevertheless quali-
tatively consistent with saturation of acid catalysis and
ion pair formation.
Thiocyanate ion solutions. Several of the quinone
methides that we examined before also, like the present
substrate, did not show saturation of acid-catalyzed
hydration in dilute acid solution where we could analyze
the data quantitatively.4,5 We were nonetheless able to
obtain estimates of the substrate conjugate acid ionization
constants, KSH, for these systems by determining the
acid-catalyzed rate constants for reaction of these qui-
none methides with thiocyan0ate ion. This rate constant is
equal to kS0 CN/KSH, where kSCN is the bimolecular rate
Figure 4. Relationship between thiocyanate ion concentra-
tion and observed rate constants for the decay of p-quinone
ꢀ-phenylmethide in aqueous 0.05 M perchloric acid solutions
at 25 ꢃC
Copyright # 2004 John Wiley & Sons, Ltd.
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584
J. A. CHANG ET AL.
Table 1. Effect of ꢀ-phenyl substitution on p-quinone
methide reactivitya
Number of phenyl substituents
Quantity
Noneb
One
Two
ꢁ4
ꢁ1
kw(sꢁ1
)
3.3 ꢀ 100
5.3 ꢀ 104
1.1 ꢀ 102
5.8 ꢀ 106
5.1 ꢀ 10ꢁ2
8.2 ꢀ 101
2.9 ꢀ 104
1.5 ꢀ 101
4.4 ꢀ 105
3.7 ꢀ 10
6.5 ꢀ 10
ꢁ1
ꢁ
kHO (s
þ
)
—
kH (Mꢁ1 sꢁ1
KSH(M)
)
2.1 ꢀ 103ꢁ1
3.9 ꢀ 102
1.9 ꢀ 10
kw0 (sꢁ1
)
a
Aqueous solution, 25 ꢃC, ionic strength ¼ 0.10 M.
b
From Ref. 5.
DISCUSSION
Figure 5. Relationship between perchloric acid con-
centration and slopes of plots such as that shown in
Fig. 4
The data in Table 1 show that introduction of phenyl
substituents on to the ꢀ-carbon atom of the methylene
group of p-quinone methide retards the rate of its un-
catalyzed reaction with water, kw, and also retards the rate
ꢁ
of its reaction with hydroxide ion, kHO . This must be the
The methoxy-substituted carbocation 10 was generated
by flash photolysis of the corresponding benzhydryl
acetate 11,21 and rates of its decay were measured in
dilute sodium thiocyanate solutions. These data are
summarized in Supplementary Table S9. Observed first-
order rate constants obtained in this way proved to be
linear functions of thiocyanate ion concentration, giving
the rate constant k ¼ (2.81 ꢂ 0.03) ꢀ 109 Mꢁ1 sꢁ1 for
capture of the methoxy-substituted carbocation 10 by
thiocyanate ion.
Combination of this result with the factor of two by
which hydroxy-substituted carbocations have been
shown to be more stable than their methoxy-substituted
analogs15 leads to kS0 CN ¼ 1.4 ꢀ 109 Mꢁ1 sꢁ1 as an esti-
mate of the rate constant for capture of the hydroxy-
substituted carbocation 9 by thiocyanate ion. Use of this
estimate with the relationship kS0 CN/KSH ¼ 9.15 ꢀ
107 Mꢁ2 sꢁ1 then gives KSH ¼ 15 M as the acidity constant
of oxygen-protonated p-quinone ꢀ-phenylmethide. (This
value of KSH can be no more than a rough estimate
because the factor by which hydroxy-substituted carbo-
cations are less reactive than their methoxy-substituted
analogs can be expected to vary from system to system,
and the factor of two used here is itself only a rough
result, at least in part, of a steric effect produced by
the nucleophilic role that water and hydroxide ion play in
these reactions: they add directly to the quinone methide
methylene group carbon atom, which is a reaction site that
becomes increasingly crowded with successive ꢀ-phenyl
substitution. This steric effect is apparent as well in the
weak buffer catalysis of these quinone methide reactions
noted above.
An additional factor that contributes to this phenyl
group rate retardation arises from the stabilization that ꢀ-
phenyl substituents provide to the benyzl carbocation
resonance form of the quinone methide, 12, by positive
charge delocalization, as shown in Scheme 1. This
positive charge is being neutralized in these reactions,
and such delocalization is consequently less strong in the
reactions’ transition states than in their initial states. As a
result, the initial states are stabilized more strongly than
are the transition states, and that increases the free energy
difference between initial states and transition states,
raising the free energy of activation and lowering the
reaction rate.
þ
The catalytic coefficients, kH , for hydronium ion-
catalyzed addition of water to these quinone methides
also decrease as ꢀ-phenyl groups are added, but the
ꢁ
change now is considerably less than for kw or kHO .
approximation).
0
þ
þ
This result, together with kH ð¼ kw=KSHÞ ¼ 2:94ꢀ
This is because kH is a composite constant equal to the
specific rate of reaction of the quinone methide conjugate
acid with water, kw0 , divided by0 the conjugate acid
104 Mꢁ1 sꢁ1 for reaction of p-quinone ꢀ-phenylmethide
in dilute perchloric acid solutions (see above) then gives
kw0 ¼ 4.4 ꢀ 105 sꢁ1 as the rate constant for reaction of the
hydroxy-substituted carbocation 9 with water. This is
consistent with k ¼ 2 ꢀ 106 sꢁ1 reported for the reaction
of the corresponding methoxy substituted carbocation
10 with water in a mixed acetonitrile–water solvent,21
and it provides another comparison showing hydroxy-
substituted carbocations to be slightly less reactive than
their methoxy-substituted counterparts.
ionization constant, KSH: kH ¼ kw/KSH. Both kw0 and
þ
KSH diminish as phenyl groups are added, but kw0
Scheme 1
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 579–585

p-QUINONE ꢀ-PHENYL- AND ꢀ,ꢀ-DIPHENYLMETHIDE
585
decreases somewhat more strongly than KSH, and the
Acknowledgment
þ
result is a moderate drop in kH with phenyl group
introduction.
It is interesting that phenyl group substitution has a
considerably stronger effect on k0w than on KSH. The
reactions represented by these constants:
We are grateful to the Natural Sciences and Engineering
Research Council of Canada for financial support of this
work.
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ð12Þ
ð13Þ
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.
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Supplementary material
Tables S1–S9 containing rate data are vailable in Wiley
Interscience.
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Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 579–585