Dependence of the rate of an interfacial Diels-Alder reaction on the steric environment of the immobilized dienophile: An example of enthalpy-entropy compensation

Article abstract of DOI:10.1021/ja010740n

This paper describes a physical organic study of the relationship between the rate for an interfacial Diels-Alder reaction and the steric environment around the reacting molecules. The study used as a model reaction the cycloaddition of cyclopentadiene with a self-assembled monolayer (SAM) presenting benzoquinone groups surrounded by hydroxyl-terminated alkanethiolates. The accessibility of the quinone was varied by preparing monolayers from hydroquinone-terminated alkanethiols of different lengths [HS-(CH₂)_n-HQ, n = 6-14] and a hydroxyl-terminated alkanethiol [HS(CH₂)₁₁-OH] of constant length. Cyclic voltammetry was used to measure the rate of the reaction by monitoring the decay of the redox-active quinone. The second-order rate constant showed a modest change as the position of quinone was varied relative to the hydroxyl groups of the monolayer. For monolayers wherein the quinone groups were extended from the interface, the rate constants oscillated near 0.20 M^-1 s^-1 with an even-odd dependence on the length of the alkanethiol. For monolayers that positioned the quinone groups below the surrounding hydroxyl groups, the rate constants decreased by approximately 8-fold. Examination of the activation parameters revealed that the quinone groups that were positioned below the interface (and in a crowded environment) reacted with an enthalpy of activation that was 4 kcal/mol greater than did the quinones that were accessible at the interface. The reaction of the buried quinone, however, proceeded with an entropy of activation that was more favorable by 13 eu, and therefore with a similar free energy of activation. The combination of SAMs for preparing model interfaces and cyclic voltammetry for measuring rates provides a new opportunity for physical organic studies of interfacial reactions.

Full text of DOI:10.1021/ja010740n

Published on Web 01/11/2002
Dependence of the Rate of an Interfacial Diels-Alder Reaction
on the Steric Environment of the Immobilized Dienophile:
An Example of Enthalpy-Entropy Compensation
Youngeun Kwon and Milan Mrksich*
Contribution from the Department of Chemistry, UniVersity of Chicago, Chicago, Illinois 60637
Received March 20, 2001
Abstract: This paper describes a physical organic study of the relationship between the rate for an interfacial
Diels-Alder reaction and the steric environment around the reacting molecules. The study used as a model
reaction the cycloaddition of cyclopentadiene with a self-assembled monolayer (SAM) presenting
benzoquinone groups surrounded by hydroxyl-terminated alkanethiolates. The accessibility of the quinone
was varied by preparing monolayers from hydroquinone-terminated alkanethiols of different lengths [HS-
(CH2)n-HQ, n ) 6-14] and a hydroxyl-terminated alkanethiol [HS(CH2)11-OH] of constant length. Cyclic
voltammetry was used to measure the rate of the reaction by monitoring the decay of the redox-active
quinone. The second-order rate constant showed a modest change as the position of quinone was varied
relative to the hydroxyl groups of the monolayer. For monolayers wherein the quinone groups were extended
from the interface, the rate constants oscillated near 0.20 M-1 s-1 with an even-odd dependence on the
length of the alkanethiol. For monolayers that positioned the quinone groups below the surrounding hydroxyl
groups, the rate constants decreased by approximately 8-fold. Examination of the activation parameters
revealed that the quinone groups that were positioned below the interface (and in a crowded environment)
reacted with an enthalpy of activation that was 4 kcal/mol greater than did the quinones that were accessible
at the interface. The reaction of the buried quinone, however, proceeded with an entropy of activation that
was more favorable by 13 eu, and therefore with a similar free energy of activation. The combination of
SAMs for preparing model interfaces and cyclic voltammetry for measuring rates provides a new opportunity
for physical organic studies of interfacial reactions.
Physical organic studies of reactions that occur at the solid-
liquid interface have lagged considerably behind studies of
reactions in solution.1-4 The reasons for this difference stem
from the added complexity in developing model systems for
interfacial reactions, which require substrates that present
reactants in defined environments, and from a lack of convenient
analytical techniques that have the sensitivity and temporal
resolution necessary for measuring the rates of reactions at the
interface. The opportunities for mechanistic studies of interfacial
reactions have improved with the development of model organic
surfacessand of monolayers of alkanethiolates on gold in
particularswhich present reactants in well-defined environments
and permit wide flexibility in modifying the microenvironment
of the immobilized molecules.5 Early studies have motivated a
growing recognition that interfacial reactions can differ in
dramatic ways from the corresponding homogeneous phase reac-
tions6 and that these differences can have substantial practical
implications in sensing,7 catalysis,8 and combinatorial libraries.9
In this paper we use as a model reaction the Diels-Alder
cycloaddition of cyclopentadiene to benzoquinone immobilized
at a monolayer to investigate the dependence of the rate constant
on changes in the steric environment of the quinone.
(5) (a) Badia, A.; Lennox, R. B.; Reven, L. Acc. Chem. Res. 2000, 33, 475-
481. (b) Bain, C. D.; Whitesides, G. W.; Science 1988, 240, 62-63.
(6) (a) Bunton. C. A.; Nome, F.; Quina, F. H.; Romsted, F. S. Acc. Chem.
Res. 1991, 24, 357-364. (b) Flyxell, G. E.; Rieke, P. C.; Wood, L. L.;
Engelhard, M. H. J.; Williford, R. E.; Graff, G. L.; Campbell, A. A.; Wiacek,
R. J.; Lee, L.; Halverson, R. E. Langmuir 1996, 12, 5064-5075. (c) Zhuang,
X.; Lackritz, H.; Shen, Y. R. Chem. Phys. Lett. 1995, 246, 279-284. (d)
Ahmad, J.; Astin, B. Langmuir 1990, 6, 1797-1799. (e) Ryswyk, H. V.;
Turtle, E. D.; Watson-Clark, R.; Tanzer, T. A.; Herman, T. K.; Chong, P.
Y.; Waller, P. J.; Taurog, A. L.; Wagner, C. E. Langmuir 1996, 12, 6143-
6150. (f) Chechik, V.; Stirling, C. J. M. Langmuir 1997, 13, 6354-6356.
(7) (a) Lin, V. S. Y.; Motesharei, K.; Dancil, K. P. S.; Sailor, M. J.; Ghadiri,
M. R. Science 1997, 278, 840-843. (b) Blonder, R.; Levi, S.; Tao, G.;
Ben-Dov, I.; Willner, I. J. Am. Chem. Soc. 1997, 119, 10467-10478. (c)
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Chem. 1998, 37, 2466-2468. (c) Li, H.; Luk, Y. Y.; Mrksich, M. Langmuir
1999, 15, 4957-4959. (d) Kuramitz, H.; Sugawara, K.; Tanaka, S.
Electroanalysis 2000, 12, 1299-1303.
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* To whom correspondence should be addressed.
(1) (a) Chechik, V.; Crooks, R. M.; Stirling, C. J. M. AdV. Mater. 2000, 12,
1161-1171. (b) Schonherr, H.; Chechik, V.; Stirling, C. J. M.; Vancso, G.
J. J. Am. Chem. Soc. 2000, 119, 3679-3687. (c) Duevel, R. V.; Corn, R.
M. Anal. Chem. 1992, 64, 337-342. (d) Chechik, V.; Stirling, C. J. M.
Langmuir 1998, 14, 99-105. (e) Horton, R. C.; Herne, T. M.; Myles, D.
C. J. Am. Chem. Soc. 1997, 119, 12980-12981. (f) Booth, J.; Compton,
R. G.; Atherton, J. H. J. Phys. Chem. B 1998, 102, 3980-3985. (g) Yan,
L.; Marzolin, C.; Tefort, A.; Whitesides, G. M. Langmuir 1997, 13, 6704-
6712.
(2) O’Shaughnessy, B.; Vavylonis, D. Macromolecules 1999, 32, 1785-1796.
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481-488. (b) Templeton, A. C.; Hostetler, M. J.; Kraft, C. T.; Murray, R.
W. J. Am. Chem. Soc. 1998, 120, 1906-1911.
(4) (a) Faull, J. D.; Gupta, V. K. Langmuir 2001, 17, 1470-1476. (b) Maeda,
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806 VOL. 124, NO. 5, 2002 J. AM. CHEM. SOC.
10.1021/ja010740n CCC: $22.00 © 2002 American Chemical Society

An Example of Enthalpy−Entropy Compensation
A R T I C L E S
Figure 1. Model substrate for the interfacial Diels-Alder reaction of cyclopentadiene with an immobilized benzoquinone group. The quinone group undergoes
a reversible two-electron reduction to give the corresponding hydroquinone and therefore permits the use of cyclic voltammetry to measure the rate of the
reaction.
In previous work we described the Diels-Alder reaction of
dienes with a self-assembled monolayer (SAM) prepared from
an alkanethiol terminated in a benzoquinone group and a second
alkanethiol terminated in a hydroxyl group (Figure 1).10 In this
mixed monolayer, the density of the quinone can be controlled
(which is important to ensure that the quinones are isolated from
one another at the interface) and the choice of the second
alkanethiol defines the chemical environment surrounding the
quinone.11 The benzoquinone group was used as the dienophile
because it undergoes a reversible two-electron reduction to give
the corresponding hydroquinone and therefore permits use of
cyclic voltammetry to measure the loss of quinone on the
surface.12 This electrochemical method has the important
advantage over many spectroscopic methods in that it measures
the rate in situ and does not require the sample to be periodically
removed from solution prior to each measurement. For the
monolayer shown in Figure 1, we found that the Diels-Alder
reaction of immobilized benzoquinone with cyclopentadiene
proceeded with a second-order rate constant of kDA ) 0.22 M-1
This model system is well suited for investigating other
aspects of interfacial reactions. In this paper, we investigate the
relationship between the second-order rate constant of the
reaction and the steric environment around the benzoquinone.
Our studies reveal that the rate constant shows a modest decrease
as the quinone is positioned below the monolayer interface. A
determination of the activation parameters for two limiting
casesswhere the quinone is either freely accessible at the
interface or buried within the monolayersreveals that the buried
quinone reacts with an enthalpy of activation that is 4 kcal/mol
larger than that of the accessible quinone but that this difference
is nearly compensated by a favorable entropy of activation for
the reaction of the buried quinone.
Experimental Design
Our strategy for controlling the steric environment of the
benzoquinone group within the monolayer is illustrated in Figure
2. We prepared several mixed monolayers from an alkanethiol
terminated in the benzoquinone group and a second alkanethiol
terminated in a hydroxyl group. The accessibility of the quinone
was systematically altered by adjusting the length of the
quinone-terminated alkanethiol, while keeping a constant length
of the hydroxyl-terminated alkanethiol. When a linker of seven
methylene units is used for the benzoquinone-terminated al-
kanethiol (C7), for example, the quinone is buried within the
monolayer. With a linker of 14 methylene units (C14), the
benzoquinone group is freely accessible at the interface. In this
work, we used eight analogues of the quinone-terminated
alkanethiol, wherein the length of the alkyl groups ranged from
seven to 14 methylene units. We report the second-order rate
constants for this series of monolayers. We also report activation
parameters for the reaction to understand the mechanistic basis
for differences in reaction rates that result from the change of
steric environment around the benzoquinone. In all cases, the
quinone-terminated alkanethiolate was present at a density of
3-5% relative to total alkanethiolate. The low density of
benzoquinone isolates the reactant groups at the surface and
provides a uniform microenvironment around each group.
s-1
.
In subsequent work we investigated the reaction of cyclo-
pentadiene with monolayers that presented quinone groups that
were surrounded by methyl-terminated alkanethiolates (in place
of the hydroxyl-terminated alkanethiolates).13 The reaction of
cyclopentadiene with the immobilized quinone did not proceed
with a second-order rate constant but instead approached a
maximum rate with increasing concentrations of diene. A kinetic
analysis of this reaction was consistent with a model wherein
the diene first adsorbed to the monolayer and then underwent
reaction with the immobilized quinone. The analysis provided
both an equilibrium association constant for adsorption and a
first-order rate constant for the reaction. Further, we found that
changes in the solvent composition had an effect on the
association constant of diene for the substrate but had no effect
on the rate constant for reaction of the adsorbed diene and
immobilized quinone.14 This example illustrates one way in
which an interfacial reaction can differ dramatically from the
corresponding solution-phase reaction.
Results
(10) Yousaf, M. N.; Mrksich, M. J. Am. Chem. Soc. 1999, 121, 4286-4287.
(11) Kakiuchi, T.; Sato, K.; Iida, M.; Hobara, D.; Imabayashi, S. I.; Niki, K.
Langmuir 2000, 16, 7238-7244.
Synthesis of Benzoquinone-Terminated Alkanethiol. Each
of the benzoquinone-terminated alkanethiols was prepared by
a common route (Figure 3). The syntheses started with treatment
of the appropriate alkenyl bromides with lithiated 1,4-
dimethoxybenzene to give the alkylated hydroquinones (1a-
1i). The terminal olefins were converted to the corresponding
(12) (a) Park, H.; Oyama, M.; Shim, Y. B.; Okazaki, S. J. Electroanal. Chem.
2000, 484, 131-136. (b) Sato, Y.; Fujita, M.; Mizutani, F.; Uosaki, K. J.
Electroanal. Chem. 1996, 409, 145-154.
(13) Yousaf, M. N.; Chan, E. W. L.; Mrksich, M. Angew. Chem. 2000, 39,
1943-1946.
(14) Chan, E. W. L.; Yousaf, M. N.; Mrksich, M. J. Phys. Chem. A 2000, 104,
9315-9320.
9
J. AM. CHEM. SOC. VOL. 124, NO. 5, 2002 807

A R T I C L E S
Kwon and Mrksich
Figure 2. This work investigated the relationship between the rate constant for an interfacial Diels-Alder reaction and the steric environment about the
immobilized quinone. A series of mixed SAMs was prepared wherein the quinone group was tethered to an alkanethiolate having from 7 to 14 methylene
units and surrounded by a hydroxyl-terminated alkanethiolate of a constant length. The use of a short alkyl group (C7, left) positions the quinone within the
monolayer, while an intermediate-sized alkyl group (C11, middle) positions the quinone at the periphery of the monolayer, and a long alkyl group (C14,
right) positions the quinone in an accessible environment above the interface.
Figure 3. Synthetic route for the preparation of hydroquinone-terminated alkanethiols C6-C14. See text for an explanation.
thioacetates by treatment with thiolacetic acid and AIBN under
photolytic conditions. Both methyl ethers were efficiently
cleaved with boron tribromide to give the unprotected hydro-
quinones (3a-3i). The terminal acetyl groups were removed
by refluxing in HCl/MeOH to give the desired alkanethiols
(C6-C14). Throughout the paper, we refer to the alkanethiols
with a nomenclature that indicates the length of the alkyl chain
that separates the benzoquinone and thiol groups (C6 through
C14).
Preparation of Monolayers. Monolayers were prepared
according to standard methods.15 Gold-coated silicon substrates
were immersed in ethanolic solutions of a benzoquinone-
terminated alkanethiol and a hydroxyl-terminated alkanethiol
(in ratios of 1:12 to 2:3) for 18 h. Because the ratio of
alkanethiolates in a mixed SAM is rarely identical to the ratio
of alkanethiols in the solution from which the monolayer
assembled, we used cyclic voltammetry to independently
determine the density of the hydroquinone in the SAM.
Integration of the voltammetric wave for reduction of the
benzoquinone gave the density of quinone in the monolayer.
We found that the longer quinone-terminated alkanethiols were
incorporated in the monolayer at higher densities, but we
adjusted the solution ratios to ensure that final densities of
quinone in all monolayers were between 3% and 5%. For these
densities of quinone, all reactions proceeded to completion with
a uniform rate, which ensures that the quinone groups are indeed
isolated at the interface. When we used monolayers that
presented quinone groups at densities of 10-15%, by contrast,
the rates showed deviations (usually becoming slower) as the
reactions progressed.
Determination of Rate Constant. We used cyclic voltam-
metry to follow the rate of reaction because the quinone group
displays a reversible redox couple and the Diels-Alder adduct
is not redox-active over the potential range used here. Hence,
the rate of decay of quinone redox waves is proportional to the
rate of the Diels-Alder reaction. Cyclic scans were performed
between -400 and +600 mV at a scan rate of 25 mV/s in an
electrolyte that was equal parts of tetrahydrofuran (THF) and
water (154 mM NaCl and 3 mM phosphate, pH 7.7). We used
this solvent mixture because a protic solvent is required for the
reduction of quinone to the corresponding hydroquinone, while
the THF provides solubility for the diene.10 Equation 1 describes
the rate for this second-order reaction (in units of mol‚cm-2‚s-1),
where ΓQ is the density of quinone groups in the monolayer (in
units of mol‚cm-2) and kDA is the second-order rate constant
(M-1 s-1). Under these conditions, the oxidation of hydro-
quinone was reversible over as many as 100 scans, but when
cyclopentadiene was added to the electrolyte the voltammetric
waves for both oxidation and reduction decreased over consecu-
tive scans (Figure 4A). Figure 4B shows a representative plot
of the peak current, It, for the reduction waves as a function of
time. Because these experiments were carried out under pseudo-
first-order conditionssthe amount of diene is in large excess
over the immobilized quinonesthe apparent rate constant k′ is
(15) Bain, C. D.; Troughton, E. B.; Tao, Y. T.; Evall, J.; Whitesides, G. M.;
Nuzzo, R. G. J. Am. Chem. Soc. 1989, 111, 321-335.
9
808 J. AM. CHEM. SOC. VOL. 124, NO. 5, 2002

An Example of Enthalpy−Entropy Compensation
A R T I C L E S
Table 1. Second-Order Rate Constants for the Interfacial
Diels-Alder Reactions of Cyclopentadiene and Quinone Groups
Presented at Self-Assembled Monolayer with Methylene Linkers of
Varying Lengthsa
monolayer
kDA (M-1 s-1
)
errorb
C7
C8
C9
C10
C11
C12
C13
C14
0.010
0.027
0.035
0.135
0.219
0.175
0.209
0.188
0.001
0.004
0.004
0.015
0.021
0.016
0.024
0.008
a The labels for monolayers refer to the number of methylene units in
the quinone-terminated alkanethiols. b Errors were calculated at the 95%
confidence level.
of the reaction. For monolayers containing C7, C8, C9, and C10
alkanethiolates (which were shorter than the hydroxyl-terminated
alkanethiolate), the disappearance of quinone over the first half
of the reaction was described well by a single exponential decay
but then deviated from the exponential at longer extents of
reaction. Plots of ln [(It - If)/(I0 - If)] versus time showed an
upward deviation (the rate of reaction slowed) as the reaction
proceeded, which was likely due to a steric accumulation of
the product in the monolayer. For these cases, we fitted data
from the start of the reaction to ∼60% completion. As described
above, for each monolayer (C7-C14), we measured the pseudo-
first-order rate constant at concentrations of cyclopentadiene
ranging from 3 to 70 mM. In all cases, the first-order rate
constants (k′) were linearly related to the concentration of diene.
The resulting second-order rate constants are listed in Table 1.
C6 Rate Constant with C6 (-OH) Background. The data
presented above show that the rate constant for the Diels-Alder
reaction decreases as the quinone is positioned within the
monolayer. To verify that the changes in rate were due primarily
to changes in the relative positions of quinone and hydroxyl
background, we characterized the Diels-Alder reaction for a
monolayer prepared from a short hydroquinone-terminated
alkanethiol (C6) and mixed with a hydroxyl-terminated alkane-
thiolate that also had six methylene units. Our hypothesis was
that the Diels-Alder reaction with these monolayers should
proceed with a rate constant that was similar to that for mono-
layers having the C11 quinone mixed with 11-hydroxyundecane-
thiol (as shown in Figure 1). Reactions with this monolayer
were kinetically well-behaved and gave first-order rate constants
that increased linearly with the concentration of diene (Figure
5, inset). The second-order rate constant kDA of 0.19 M-1 s-1
was indeed similar to that for monolayer presenting the quinone
and hydroxyl groups at longer alkanethiolates.
Figure 4. (A) Consecutive cyclic voltammetric scans of a monolayer
presenting the hydroquinone group (C11) at a density of 4% mixed with
hydroxyl-terminated alkanethiolate. The scans were performed in the
presence of cyclopentadiene (24 mM) in 1:1 THF/H2O with phosphate (3
mM) and NaCl (154 mM) at a scan rate of 25 mV/s. (B) Plot of peak current
for the reduction wave versus time for the data shown in panel A. It is the
peak current at time t, I0 is the peak current for the first scan, and If is the
residual nonfaradaic current. The pseudo-first-order rate constant k′ was
obtained from the slope of a plot of ln [(It - If)/(I0 - If)] versus time. The
rate constants k′ were determined for several concentrations of diene. These
rate constants increased linearly with the concentration of diene (inset) and
gave a second-order rate constant, kDA, of 0.22 M-1 s-1
.
equal to kDA[Cp] (eq 2). The data for decay of quinone were
fitted to eq 3 to give the pseudo-first-order rate constant k′,
where It is the peak current at time t, I0 is the initial peak current,
If is the residual nonfaradaic current, and t is the reaction time
after correction for the fraction of time during which the
monolayer presents the nonreactive hydroquinone.
V ) kDA[Cp]ΓQ
V ) k′ΓQ ([Cp] . ΓQ)
ln [(It - If)/(I0 - If)] ) -k′t
(1)
(2)
(3)
We repeated this experiment with concentrations of cyclo-
pentadiene ranging from 3 to 70 mM. A plot of the pseudo-
first-order rate constants versus the concentration of cyclopen-
tadiene was linear (Figure 4B, inset). A least-squares fit of these
linear data gave the second-order rate constants kDA
.
Activation Parameters. To understand the mechanistic basis
for the rather modest changes in rate constant observed with
the series of monolayers, we measured activation parameters
for the Diels-Alder reaction of two monolayers: one in which
the benzoquinone was freely accessible (C13) and one in which
benzoquinone was partially buried within the monolayer (C9).
In both cases, the reaction rates were measured as described
above and were repeated at eight different temperatures ranging
from 0 to 40 °C. The rate constants are summarized in Table 2.
Activation parameters were determined in the normal fashion
by a least-squares fit of plots of ln (kDA/T) versus 1/T (Figure
6) by use of eq 4, where κ is the transmission coefficient (≈1,
C7-C14 Rate Constants with C11 (-OH) Background. We
repeated the analysis described above for each of the eight
monolayers prepared from one of the quinone-terminated
alkanethiols (C7-C14) and the hydroxyl-terminated alkanethiol.
In all cases, the benzoquinone groups displayed a reversible
two-electron reduction, though the positions of oxidation and
reduction waves showed a slight dependence on the distance
of quinone to the gold substrate (∼400 mV difference between
C7 and C14). For monolayers containing either C11, C12, C13,
or C14 quinones, the rate of loss of quinone (due to Diels-
Alder reaction) followed an exponential decay to completion
9
J. AM. CHEM. SOC. VOL. 124, NO. 5, 2002 809

A R T I C L E S
Kwon and Mrksich
Table 3. Comparison of the Activation Parameters for the
Interfacial Diels-Alder Reaction of Cyclopentadiene with
Monolayers That Present the Quinone Group in a Buried
Environment (C9) and an Accessible Environment (C13)
activation parameter
C9
C13
∆Gq
∆Hq
∆Sq
19.1 ( 0.4 kcal
9.8 ( 0.5 kcal
-31 ( 3 eu
18.5 ( 0.4 kcal
5.5 ( 0.4 kcal
-44 ( 3 eu
Figure 5. Plot of peak current for the reduction wave versus time for the
mixed monolayer of (mercaptohexanyl)hydroquinone (C6) and mercapto-
hexanol. It is the peak current at time t, I0 is the peak current for the first
scan, and If is the residual nonfaradaic current. The pseudo-first-order rate
constant k′ was obtained from the slope of a plot of ln((It-If)/(Io-If)) versus
time. The rate constants k′ were determined for several concentrations of
diene. These rate constants increased linearly with the concentration of diene
(inset) and gave a second-order rate constant, kDA, of 0.19 M-1 s-1
.
Table 2. Summary of Second-Order Rate Constants for the
Diels-Alder Reaction of Cyclopentadiene with Two Monolayers
Presenting Quinone Groups (C9 and C13)
C9
C13
Figure 7. Relationship between the second-order rate constants for
interfacial Diels-Alder reactions and the length of the quinone-terminated
alkanethiol (the background hydroxyl-terminated alkanethiol has a length
of 11 methylene units). The error bars were calculated with 95% confidence
level.
temp (°C)
k (M-1 s-1
)
temp (°C)
ka (M-1 s-1
)
2
7
0.009
0.020
0.027b
0.036b
0.042b
0.053b
0.080
0.106
2
0.065
0.089
0.109
0.102
0.136
0.147
0.152
0.224
6.5
10
14
18
21
25
33
12
17
22
27
32
37
as a model substrate was significant for two reasons. First, the
well-defined structure of the monolayer gives excellent control
over the steric accessibility of the quinone groups and at the
same time allows these groups to be diluted in the film so that
they are isolated and therefore each reacts with uniform kinetics.
The structural order of the monolayers and the synthetic
flexibility to adjust the environments of reactive groups is
unmatched by other model substrates for studying interfacial
reactions. Second, since the benzoquinone group is redox-active,
cyclic voltammetry could be used to monitor the rate of the
interfacial reaction. This technique has a primary advantage
compared to other analytical tools that have been used for
interfacial kinetic studies [including X-ray photoelectron spec-
troscopy, IR, and contact angle measurement] in that it provides
kinetic information in real time without causing unwanted
damage to the interface. The combination of SAMs and cyclic
voltammetry gives an excellent model system for physical
organic studies of interfacial reactions.
a Second-order rate constant determined with monolayers presenting
quinone groups at 15% density. b Average rate constant from two different
measurements.
We quantitatively measured the dependence of rate constant
for the interfacial Diels-Alder reaction on the accessibility of
the benzoquinone and found that there is a difference of about
2 kcal/mol between the largest and smallest rate constants
(Figure 7). For monolayers presenting quinone groups on
alkanethiolates that were as same length as, or longer than the
hydroxyl-terminated alkanethiolate (C11-C14), the rate con-
stants were between 0.18 and 0.22 M-1 s-1 and showed a slight
even-odd alternation with the number of methylene units in
the alkyl chains. While this finding is consistent with previous
studies that have shown a dependence of interfacial properties
on an even-odd effect, which derives from the orientation of
the terminal group at the interface, the mechanistic significance
for the more rapid reaction of vertically oriented quinone groups
is unclear.16 For monolayers presenting quinone groups on
alkanethiolates that were shorter than the hydroxyl-terminated
alkanethiolates (C7-C9), the rate constants were all near 0.03
Figure 6. Plot of ln (k/T) versus 1/T for the reaction of cyclopentadiene
with monolayers presenting quinone groups in either a crowded environment
(C9, top) or an accessible environment (C13, bottom). Values for ∆Hq and
∆Sq were calculated from the slope and the intercept of the best-fit lines to
these data.
in many cases), kb is the Boltzmann constant (1.380 × 10-23
J/K), R is the gas constant (1.987 cal/mol·K), and h is Planck’s
constant (6.626 × 10-34 J‚s); the activation parameters are listed
in Table 3.
ln (kDA/T) ) ln (κkb/h) + ∆Sq/R - ∆Hq/RT
Discussion
(4)
This paper presents a physical organic study of an interfacial
Diels-Alder reaction. The use of a self-assembled monolayer
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810 J. AM. CHEM. SOC. VOL. 124, NO. 5, 2002

An Example of Enthalpy−Entropy Compensation
A R T I C L E S
M-1 s-1, which is approximately 7-fold lower than those for
monolayers that present the quinone in an accessible environ-
ment.
quinone requires either that the transition-state complex is less
ordered or the reactants are more ordered as compared to
reaction of the accessible quinone. We favor the explanation
that the transition state is less ordered, because it is more
consistent with the larger ∆Hq that accompanies reaction of the
buried quinone. As we suggested above, the hydroxyl-terminated
alkanethiolates surrounding the buried quinone groups can
prevent optimal alignment of the two π systems, thereby relaxing
the requirement for strict alignment of the two molecules. We
must note that these explanations do not address roles that the
solute molecules near the interface can play, which could easily
dominate changes in ∆Sq. A sophisticated understanding of
interfacial solvation, however, is still lacking due to limited
experimental techniques that can assess interfacial properties,
and therefore it is not yet possible to fully interpret activation
parameters for interfacial reactions.18
It is important to recognize that although the monolayer
substrates are structurally well-ordered, they do in practice
contain defects and display conformational dynamics at the
surface, which can lead to structures that deviate from the
idealized structures commonly shown in figures. At the same
time, they are sufficiently ordered that modest changes in
structure, including changing the relative positions of reactive
groups and neighboring groups by a single methylene unit, can
have a significant influence on the reaction. To gain support
that the differences in reactivity observed in this work were
due primarily to changes in the relative position of the quinone
relative to the interface, we determined the rate constant for
reaction with a monolayer presenting quinone groups on a short
alkanethiolate (C6) and surrounded by a short hydroxyl-
terminated alkanethiolate [S(CH2)6OH]. Indeed, we found that
the rate constant was similar to that for the C11 quinone
described above. As we noted above, the reaction of monolayers
presenting the quinone group above the interface (C11-C14)
proceeded to completion with a uniform rate constant, whereas
reaction of monolayers presenting the quinone group below the
interface showed deviations in rate as the reaction progressed.
This result suggests that, for the latter case, the product exerts
a steric influence on unreacted quinone groups.
This paper describes studies of the relationship between the
rate constant for an interfacial Diels-Alder reaction and the
accessibility of the immobilized dienophile. This work used self-
assembled monolayers of alkanethiolates on gold as a model
substrate to vary the position of a benzoquinone group within
the monolayer and found a modest effect of the environment
on the rate constant for reaction. A mechanistic analysis of these
rates showed that the enthalpy of activation was strongly
dependent on the environment but was largely masked by a
compensating entropy of activation. This work is significant
because it provides an example that illustrates the importance
of steric factors in interfacial reactions. This type of steric effect,
which is due to the structure of the interface, does not have an
analogue in corresponding solution-phase reactions. The system
used in this work has the additional significance that it permits
quantitative studies of reaction kinetics at a level that has
previously only been possible with reactions that take place in
We had expected to observe a larger difference in rate
constants for monolayers that varied the position of the quinone
groups relative to the hydroxyl groups. To investigate the
mechanistic basis for the modest change in rate constant, we
determined the activation parameters for two monolayers: one
that presented the quinone above the interface (C13) and one
that positioned the quinone below the interface (C9). This
experiment showed that the enthalpies and entropies of activa-
tion were very different for the two cases and that these
differences compensated one another to give similar free
energies of activation (∆Gq). The reaction of cyclopentadiene
with the accessible quinone had an enthalpy of activation (∆Hq)
of 5.5 kcal/mol. This value is consistent with (but on the lower
end of) values found for analogous Diels-Alder reactions in
solution.17 The interfacial reaction with the buried quinone (C9)
had a ∆Hq of 9.8 kcal/mol, a value that is 4 kcal/mol higher
than that for C13. This enthalpic penalty for the buried system
is likely due to the following two reasons. First, the steric
environment imposed by the dense-packed alkanethiolates likely
prevents optimal alignment and orientation of diene with the
dienophile, leading to less overlap between the two reacting
π-systems in the transition state. Second, the approach of the
diene to the quinone group within the monolayer likely requires
that the alkanethiolates surrounding the quinones undergo
conformational changes to introduce gauche interactions. It is
also possible that the activation parameters are influenced by
changes in the local dielectric constant (which should be lower
for the buried quinone), but we would expect this effect to be
minimal because the concerted Diels-Alder reaction proceeds
with little charge separation in the transition state. In any case,
the ∼4 kcal/mol difference in ∆Hq for the two reactions, in the
event that there was no change in ∆Sq, would correspond to a
1000-fold difference in rate constants.
The entropies of activation (∆Sq) for the two monolayers,
however, differed by a magnitude that negated much of the
enthalpic penalty incurred by the buried quinone. For the
monolayer that presents the quinone above the interface (C13),
the ∆Sq was -44 eu, a value that is slightly more unfavorable
than analogous Diels-Alder reactions in solution.17 Monolayers
having the quinone group in a crowded environment (C9), by
contrast, had a ∆Sq of -31 eu, a value that is less unfavorable
than analogous solution-phase reactions. In both cases, the
negative values of ∆Sq reveal that the transition-state complexes
are more ordered than the reactants, which is due to a required
specific alignment of the π systems in the Diels-Alder reaction.
The smaller negative value of ∆Sq for reaction of the buried
quinone shows that two molecules undergo less ordering in the
transition state than they do in reaction of the accessible quinone.
This smaller absolute value of ∆Sq for reaction of the buried
(16) (a) Ge, J. J.; Honigfort, P. S.; Ho, R. M.; Wang, S. Y.; Harris, F. W.;
Cheng, S. Z. D. Macromol. Chem. Phys. 1999, 200, 31-43. (b) Sumner,
J. J.; Weber, K. S.; Hockett, L. A.; Creager, S. E. J. Phys. Chem. B 2000,
104, 7449-7454. (c) Sinniah, K.; Cheng, J.; Terrettaz, S.; Reutt-Robey, J.
E.; Miller, C. J. J. Phys. Chem. 1995, 99, 14500-14505. (d) Lee, S.; Puck,
A.; Graupe, M.; Colorado, R.; Shon, Y. S.; Lee, T. R.; Perry, S. S. Langmuir
2001, 17, 7364-7370.
(17) (a) Kumar, A. Chem. ReV. 2001, 101, 1-20. (b) Braun, R.; Schuster, F.;
Sauer, J. Tetrahedron Lett. 1986, 27, 1285-1288. (c) Sauer, J.; Sustmann,
R. Angew. Chem. 1980, 19, 779-806. (d) Wassermann, A. J. Chem. Soc.
1939, 376-381. (e) Wassermann, A. J. Chem. Soc. 1935, 828-839.
(18) (a) Eisert, M. Z. F.; Pipper, J.; Herrwerth, S.; Eck, W.; Buck, M.; Grunze,
M. Langmuir 2000, 16, 5849-5852. (b) Kim, J.; Cremer, P. S. J. Am.
Chem. Soc. 2000, 122, 12371-12372. (c) Rao, C. S.; Damodaran, S.
Langmuir 2000, 16, 9468-9477. (d) Pertsin, A. J.; Grunze, M. Langmuir
2000, 16, 8829-8841.
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J. AM. CHEM. SOC. VOL. 124, NO. 5, 2002 811

A R T I C L E S
Kwon and Mrksich
2.54 (t, J ) 7.7 Hz, 2H, -CH2Ar), 2.3 (s, 3H, -SCOCH3), 1.54 (br s,
4H, -CH2CH2SCOCH3, -CH2CH2Ar), 1.28 (br s, 14H, -(CH2)7-).
11-(2,5-Dihydroxyl)-1-(thioacetyl)undecane (3f). A solution of 2f
(3.14 g, 7.68 mmol) in methylene chloride (50 mL) was cooled to -78
°C and a solution of boron tribromide (7.26 mL, 76.8 mmol) was added.
The mixture was allowed to warm to room temperature and stirred for
2 h. The reaction was then cooled to -78 °C and quenched by addition
of diethyl ether and water. The reaction mixture was washed with water
and brine and dried over MgSO4. The organic layer was concentrated
and purified by column chromatography with 1:6 ethyl acetate/hexane
to give 2.71 g (93%) of product as a white powder: 1H NMR (CDCl3)
δ 6.6 (m, 3H, -C6H3(OH)2), 2.83 (t, J ) 7.3 Hz, 2H, -CH2SCOCH3),
2.54 (t, J ) 7.7 Hz, 2H, -CH2Ar), 2.3 (s, 3H, -SCOCH3), 1.56 (br s,
4H, -CH2CH2SCOCH3, -CH2CH2Ar), 1.27 (br s, 14H, -(CH2)7-).
11-(2,5-Dihydroxyl)-1-mercaptoundecane (4f). To a solution of
3f (2.30 g, 6 mmol) in methyl alcohol (50 mL) was added concentrated
HCl (5 mL, 60 mmol), and the mixture was then heated to reflux for
10 h. The reaction mixture was washed with water and dried over
MgSO4. The organic layer was concentrated to give a white powder,
which was purified by column chromatography with 1:3 ethyl acetate/
hexane to give 1.76 g (99%) of product as a white powder: 1H NMR
(CDCl3) δ 6.6 (m, 3H, -C6H3(OH)2), 2.9 (m, 4H, -CH2SCOCH3, -CH2-
Ar), 1.58 (br s, 4H, -CH2CH2SCOCH3, -CH2CH2Ar), 1.34 (br s, 14H,
-(CH2)7-).
Preparation of Monolayer Substrates. Substrates were prepared
by vacuum deposition titanium (100 Å) and then gold (1000 Å) onto
the silicon wafers (111, Silicon Sense) by use of a Thermionics e-GUN
evaporator. Mixed monolayers were formed by immersing the gold-
coated substrates into ethanolic solutions of hydroxyl-terminated
alkanethiol (0.6-0.92 mM) and hydroxyquinone-terminated alkanethiol
(0.4-0.08 mM, respectively) for 12-24 h. The substrates were removed
from the solution, washed with deionized water and absolute ethanol,
and dried with a stream of nitrogen gas.
Electrochemical Measurement. Cyclic voltammetry was performed
with a Bioanalytical Systems CV-50W potentiostat in an electrolyte
comprising equal parts of THF and phosphate-buffered saline solution.
The apparent pH of the electrolyte was adjusted to 7.7 with 0.1 N HCl
solution and 1 N NaOH solution. All experiments used the monolayer
as a working electrode, with a platinum wire counterelectrode and Ag/
AgCl reference electrode. Cyclic scans were performed within -400
mV ∼ +600 mV at a scan rate of 25 mV/s.
a homogeneous phase. We believe that the combination of
SAMs and cyclic voltammetry employed here will be valuable
in identifying other mechanistic factors that are unique to
interfacial reactions.
Experimental Section
Chemicals and solvents were purchased from Aldrich Chemical Co,
Pfaltz & Bauer, and Fluka. THF was distilled from sodium benzophe-
none ketyl, and CH2Cl2 was distilled from calcium hydride. Column
chromatography was performed with 70-230 mesh silica gel (Fisher
Scientific). NMR spectra were acquired on Bruker DRX 400 MHz or
DMX 500 MHz spectrometers. For electrochemistry, deionized ultra-
filtered water, tetrahydrofuran (optima grade), and absolute ethanol were
purchased from Fisher Scientific. Phosphate-buffered saline was
purchased from Gibco-BRL. Adsorbates were synthesized or purchased
from Aldrich and purified before use. Cyclopentadiene was distilled
prior to each experiment in order to remove dimer and was kept at
-20 °C as a 10 M solution in THF.
11-(2,5-Dimethoxyphenyl)-1-undecene (1f). To a solution of n-
butyllithium solution in hexanes (2.5mM, 5.8 mL, 14.5 mmol) was
added dry tetramethylethylenediamine (2.19 mL, 14.5 mmol) at room
temperature. The reaction mixture was cooled to 0 °C, and a solution
of p-dimethoxybenzene (2 g, 14.5 mmol) in THF (20 mL) was added
over a period of 30 min. The resulting pale yellow solution was stirred
for 90 min and a solution of undecenylbromide (1.9 mL, 8.66 mmol)
in THF (10 mL) was added. The colorless reaction mixture was warmed
to room temperature and stirred for 10 h. The reaction mixture was
diluted with ethyl acetate, washed with saturated NH4Cl solution, water,
and brine, and dried over MgSO4. The organic layer was concentrated
to a pale yellow oil and purified by column chromatography with 6:1
hexane/methylene chloride to afford 1.97 g (79% yield) of product as
colorless oil: 1H NMR (CDCl3) δ 6.72 (m, 3H, -C6H3(OCH3)2), 5.8
(m, 1H, -CHCH2), 4.95 (dq, J ) 2.0 and 17.1 Hz, 2H, -CHCH2), 3.77
(s, 3H, -OCH3), 3.76 (s, 3H, -OCH3), 2.57 (t, J ) 7.6 Hz, 2H, -CH2-
Ar), 2.03 (q, J ) 6.7 Hz, 2H, -CH2CHCH2), 1.58 (br s, 2H, -CH2CH2-
Ar), 0.96 (br s, 12H, -(CH2)-).
11-(2,5-Dimethoxyphenyl)-1-(thioacetyl)undecane (2f). To a solu-
tion of 1f (800 mg, 2.7 mmol) in THF (30 mL) was added thiolacetic
acid (0.49 mL, 6.95 mmol) and azobis(isobutylnitrile) (46 mg, 0.28
mmol). The reaction mixture was irradiated in a photochemical reactor
(Rayonet reactor lamp, Southern New England Ultraviolet Co., model
RPR-100) for 5 h under a nitrogen atmosphere. The reaction mixture
was concentrated and purified by column chromatography with 1:20
ethyl acetate/hexane to give 970 mg (98%) of product as a yellowish
oil: 1H NMR (CDCl3) δ 6.71 (m, 3H, -C6H3(OCH3)2), 3.75 (s, 3H,
-OCH3), 3.74 (s, 3H, -OCH3), 2.84 (t, J ) 7.4 Hz, 2H, -CH2SCOCH3),
Acknowledgment. We are grateful for support provided by
the Materials Research in Science and Engineering Center (NSF,
DMR-9808595).
JA010740N
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812 J. AM. CHEM. SOC. VOL. 124, NO. 5, 2002