Hydrogen atom abstraction reactions independent of C-H bond dissociation energies of organic substrates in water: Significance of oxidant-substrate adduct formation

Article abstract of DOI:10.1039/c3sc53002g

Detailed kinetic studies on the oxidation reactions of organic substrates such as methanol with Ru^IVO complexes as oxidants, formed electrochemically in water, have been conducted to elucidate the reaction mechanism. The rate constants of the oxidation reactions exhibited saturation behaviours relative to the substrate concentration, regardless of the oxidants and the substrates employed. This indicates the existence of a pre-equilibrium process based on the adduct formation between the Ru^IVO oxidant and the substrate. Herein, we have experimentally confirmed that the driving force of the adduct formation is the hydrogen bonding between the oxidants and alcohols even in water. In addition, we have investigated the kinetic isotope effects (KIE) on the oxidation reaction using methanol and its deuterated derivatives and as a result observed moderate KIE values for the C-H bond of methanol. We have also revealed the independency of the reaction rates from the bond dissociation enthalpies of the C-H bonds of the substrates. This independency is probably derived from the tightly condensed transition state, whose energy level is strongly controlled by the activation entropy but less sensitive to the activation enthalpy.

Full text of DOI:10.1039/c3sc53002g

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Hydrogen atom abstraction reactions independent
of C–H bond dissociation energies of organic
substrates in water: significance of oxidant–
substrate adduct formation†
Cite this: Chem. Sci., 2014, 5, 1429
Tomoya Ishizuka,a Shingo Ohzu,a Hiroaki Kotani,a Yoshihito Shiota,b
b
a
*
Kazunari Yoshizawa and Takahiko Kojima
Detailed kinetic studies on the oxidation reactions of organic substrates such as methanol with RuIV]O
complexes as oxidants, formed electrochemically in water, have been conducted to elucidate the
reaction mechanism. The rate constants of the oxidation reactions exhibited saturation behaviours
relative to the substrate concentration, regardless of the oxidants and the substrates employed. This
indicates the existence of a pre-equilibrium process based on the adduct formation between the
RuIV]O oxidant and the substrate. Herein, we have experimentally confirmed that the driving force of
the adduct formation is the hydrogen bonding between the oxidants and alcohols even in water. In
addition, we have investigated the kinetic isotope effects (KIE) on the oxidation reaction using methanol
and its deuterated derivatives and as a result observed moderate KIE values for the C–H bond of
methanol. We have also revealed the independency of the reaction rates from the bond dissociation
enthalpies of the C–H bonds of the substrates. This independency is probably derived from the tightly
condensed transition state, whose energy level is strongly controlled by the activation entropy but less
sensitive to the activation enthalpy.
Received 29th October 2013
Accepted 5th December 2013
DOI: 10.1039/c3sc53002g
www.rsc.org/chemicalscience
species.9,10 Among them, RuIV]O complexes have been inten-
sively investigated as active species in oxidation reactions.11–15
The RuIV]O complexes have been prepared in situ via proton-
Introduction
Catalytic oxidations of organic substrates with a high-valent
metal–oxo complex have been intensively investigated1–3 due to
the interest for mechanistic insights into the enzymatic oxida-
tions as observed in cytochrome P4504,5 and methane mono-
oxygenase.6,7 Beyond the biological processes, efficient catalytic
oxidation of organic compounds in aqueous solutions is one of
the most required processes in light of the development of
environmentally benign procedures to attain useful primary
and secondary products from abundant feedstocks.8
coupled electron-transfer (PCET) oxidation of the correspond-
ing RuII–aqua complexes.16,17 Detailed kinetic studies on
oxidation reactions of organic substrates have been frequently
employed as useful tools to elucidate mechanisms of the
oxidation reactions performed by metal–oxo complexes.18
Recently, the inuence of the bond dissociation enthalpy (BDE)
of the C–H bond of a substrate,19 the BDE of the O–H bond
formed for the oxo ligand of the oxidant,20 and the reduction
potential of the oxidant21 on the reaction rates of the hydrogen
abstraction reactions have been also intensively investigated.
The oxidation reactions with synthetic metal–oxo complexes
have been mainly performed in organic solvents, whereas
knowledge of those in aqueous solutions has yet to be accu-
mulated sufficiently.22 In addition, the effects of pre-equilib-
rium to form an adduct between the oxidant and a substrate on
the reactivity of metal–oxo complexes have been rarely investi-
gated,23 despite the fact that the association equilibrium
between an enzyme and the specic substrate plays very
important roles in the enzymatic reactions.24
Along this line, efficient oxidation systems have been devel-
oped with use of transition metal complexes as catalysts,
involving high-valent metal–oxo complexes as reactive
aDepartment of Chemistry, Graduate School of Pure and Applied Sciences, University of
Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8571, Japan. E-mail: kojima@chem.
tsukuba.ac.jp; Fax: +81-29-853-4323
bInstitute for Materials Chemistry and Engineering, Kyushu University, 744 Motooka,
Nishi-Ku, Fukuoka 819-0395, Japan
† Electronic supplementary information (ESI) available: Details of DFT
calculations, 1H NMR spectra of the oxidized product of 2-propanol, UV-Vis
spectral changes in the course of oxidation reactions, plots of the reaction rates
against the substrate concentrations, van't Hoff and Eyring plots, titration
curves of 19F NMR signals, and MS spectrum of the decomposed product of 2.
See DOI: 10.1039/c3sc53002g
Herein, we describe the oxidation reactions of organic
substrates such as alcohols by RuIV]O complexes (1–3)15
(Fig. 1) in water under single-turnover conditions to elucidate
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Fig. 1 Proposed structures of RuIV]O complexes, 1–3.
the reaction mechanism on the basis of detailed kinetic anal-
ysis, and to discuss the inuence of BDEs of the substrates on
the rate constants. As a consequence, we have revealed the
crucial impacts of an associative pre-equilibrium between the
substrate and the oxidant on the oxidation reactivity.
Fig. 2 Thermochemical square schemes for 1 (a) and 3 (b). The pKa
values and the redox potentials are derived from ref. 15a
and c and the redox potentials are recalculated as those relative to
NHE.
Experimental
General
Chemicals and solvents were used as received from Tokyo
Chemical Industry (TCI) Co., Wako Chemicals, or Sigma-Aldrich
Corp. unless otherwise mentioned. UV-Vis spectra were
collected on a Shimadzu UV-3600 spectrophotometer, equipped
with a temperature-controller, UNISOK UnispeKs. 1H NMR
spectra were recorded on a JEOL EX-270 spectrometer at room
temperature and the chemical shis of signals were determined
with respect to residual proton signals of deuterated solvents.
19F NMR spectra were recorded on a JEOL ECS-400 spectrometer
at room temperature and potassium uoride, whose saturated
solution in D2O was sealed into a glass capillary, was used as an
internal reference (d (19F) ¼ ꢀ125.30 ppm). Electrochemical
measurements were performed on an AUTOLAB PGSTAT12
potentiometer in Britton–Robinson (B.-R.) buffer (pH ¼ 2–12) at
room temperature. pH measurements were made using a
Horiba pH-Meter F-51.
Determination of product yields for the oxidation reactions
with 1
D2O solution containing DSS (4,4-dimethyl-4-silapentane-1-
sulfonic acid) (2.0 ꢁ 10ꢀ3 M) as an internal reference, [RuII(T-
PA)(OH2)2](PF6)215a (2.0 ꢁ 10ꢀ3 M) and (NH4)2[CeIV(NO3)6] (4.0 ꢁ
10ꢀ3 M) was charged into an NMR tube, and then a substrate
(1.0 ꢁ 10ꢀ2 M) was added to the solution and stirred at room
temperature for 1 h. The solution was analysed by 1H NMR
spectroscopy (Fig. S1, ESI†), and the quantities of the products
were estimated from the relative integrals of the 1H NMR signals
against that of the DSS signal. As results, the oxidation products
were solely propionaldehyde for 1-propanol and acetone for
2-propanol and the yields against the oxidant were estimated to
be 95% for propionaldehyde and 100% for acetone.
CD3OH was formed in situ by addition of CD3OD (deutera-
tion percentage: 99.8%) into the solution of one of the three
complexes 1–3 in B.-R. buffered H2O. The oxidation of CH3OD
was done in the solution of CH3OH in B.-R. buffered D2O
(deuteration percentage: 99.9%).
Kinetic studies on oxidation reactions with RuIV]O species
The RuIV]O species, 1, 2 and 3 (0.5 mM) were generated in B.-R.
buffer (pH 1.8) from the corresponding RuII–aqua complexes,
respectively, through a bulk electrolysis as described in the lit-
erature.15c To the solution of the RuIV]O complex generated
were added substrates (CH3OH and the deuterated derivatives,
RuIV]O complexes employed in this study and the BDE
values
The three RuIV]O complexes employed here bear pyridylamine 1-propanol, 2-propanol, 4-methylbenzyl alcohol and sodium
ligands, tris(2-pyridymethyl)amine (TPA) for 1,15a N,N-bis(2-pyr- 4-ethylbenzenesulfonate (EBS)) with various concentrations at
idylmethyl)-N-(6-carboxylato-2-pyridylmethyl)amine (6-COOꢀ-TPA) various temperatures. The reaction proles were monitored by
for 2,15b and N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine the rise of the absorption assigned to the resulting RuII–OH2
(N4Py) for 3,15c respectively. They exhibit the reduction potentials complex at 620 nm for 1, 630 nm for 2, and 440 nm for 3 to
of RuIII/IV couples at +0.75, +0.68, +0.87 V vs. SCE in B.-R. buffer at determine pseudo-rst-order rate constants (kobs/sꢀ1).27 All the
pH 1.8, respectively.15 Additionally, the pKa values for the time proles of the absorbance changes obeyed rst-order
protonation processes of the RuIII–OH complexes corresponding kinetics and the pseudo-rst-order rate constants were deter-
to 1 and 3 were determined to be 2.23 and 2.48, respectively.15,25 mined with various concentrations of the substrates (Fig. S3
Based on the reduction potentials and the pKa values, the BDEs of and S5, ESI†).
RuIII–OH for 1 and 3 were calculated with eqn (1) 16c,26 to be 82.7
The saturation behaviours of the kobs values were analysed by
using the following equation:23,28,29
and 84.7 kcal molꢀ1, respectively (Fig. 2).
BDE (kcal molꢀ1) ¼ 1.37pKa + 23.06E1/2 + 55.8
(1)
kobs ¼ kK[Sub]/(1 + K[Sub])
(2)
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where K (Mꢀ1) is the equilibrium constant for the pre-equilib- concentration of 1 was analysed with eqn (3).32 The association
rium, k (sꢀ1) is the rst-order rate constant, and [Sub] (M) is the constant (K) was
(
concentration of a substrate used. Plots of kobs vs. [Sub] were
tted by eqn (1) to determine k and K values. The k and K values
determined at various temperatures were used to provide cor-
responding Eyring and van't Hoff plots, respectively.
DdN
Dd ¼
1 þ K½1ꢂ þ K½Subꢂ
0
2K½Subꢂ0
)
n
o
1=2
ꢀ
ꢁ
2
ꢀ
1 þ K½1ꢂ þ K½Subꢂ ꢀ 4K2½1ꢂ½Subꢂ
(3)
0
0
Results and discussion
determined to be 5.0 ꢁ 102 Mꢀ1 based on the titration curve
(Fig. S7 in ESI†). As well, the spectroscopic titration for 2 was
also performed under the same conditions to observe similar
chemical shi change to that observed for 1. This result indi-
cates that the chemical shi change observed for hfp is not due
to paramagnetic contact shi but the formation of hydrogen
bonding. The binding constant for 2 was also determined to be
3.6 ꢁ 102 Mꢀ1 (Fig. S7 in ESI†) using eqn (3). This result lends
credence to the adduct formation between the RuIV]O
complexes and alcohols even in water.
In addition, we conrmed the adduct formation by DFT
calculations (Fig. 4). As initial structures for the calculations,
two initial structures, which involve a hydrogen bond formed
between the aqua ligand of 1 and the hydroxyl group of hfp,
were prepared for the calculations. The optimization of one of
the initial structures, which formed a hydrogen bond between
one of the OHs of the aqua ligand of 1 and one of the lone pairs
of the hydroxyl oxygen of hfp, was converged to a solution
(Fig. 4(a)). In contrast, the structure optimization starting with
the other initial structure, in which the hydrogen bond is
formed between the lone pair of the aqua ligand of 1 and the O–
H group of hfp, did not afford a well-converged solution
maintaining the initial hydrogen-bonded structure but gave the
structure as shown in Fig. 4(b) by changing the hydrogen-
bonding position in the course of calculations. Consequently,
the most favourable structure was suggested to be the structure
Observation of the hydrogen-bonded adduct of the RuIV]O
complex
In the kinetic analysis of oxidation reactions of organic
substrates with 1–3 as oxidants, we commonly observed satu-
ration behaviours of the pseudo-rst-order rate constants (kobs
)
with respect to the concentration of substrates at all the
temperatures examined, indicating the existence of pre-equi-
librium processes prior to the oxidations.15 The driving force for
the adduct formation in the pre-equilibrium process was
supposed to be hydrogen bonding between the lone pair of the
alcohol oxygen of the substrates and the O–H proton of the aqua
ligand of the RuIV]O complex (Fig. 3).15,30 Thus far, however, no
direct evidence has been provided to support the formation of a
hydrogen-bonded adduct between a RuIV]O complex and a
substrate. Therefore, we performed titration experiments with
the addition of the solution of 1 to that of 1,1,1,3,3,3-hexa-
uoropropan-2-ol (hfp), which was employed as an inert alcohol
against oxidation reactions,31 in water under acidic conditions.
The various amounts of [RuII(TPA)(OH2)2](PF6)2 were added to
D2O (0.6 mL), which was acidied with HClO4 to pD 1.8, and
then 2 equiv. of [RuIII(bpy)3](PF6)3 was added as an oxidant to
each solution of [RuII(TPA)(OH2)2](PF6)2. The formation of 1 was
1
conrmed with the paramagnetic H NMR spectrum.15a Subse-
quently, hfp (4 mL, 0.4 mmol) was added to each solution and the
19F NMR spectrum was measured. The 19F NMR signal due to
the CF3 groups of hfp was monitored to estimate the association
constant. The chemical shi of the C19F3 groups of hfp in D2O
(pD 1.8) was observed at d (19F) ¼ ꢀ78.67 ppm in the absence of
1. The signal of the CF3 groups exhibited downeld shis upon
increasing the concentration of 1, indicating that the alcohol
oxygen of hfp forms hydrogen bonding with the O–H proton of 1
as depicted in Scheme 1. The change of the chemical shis for
the 19F NMR signals of the CF3 groups upon increasing the
Scheme 1 The association equilibrium between 1 and hfp in water.
Fig. 3 Schematic description of the adduct structure for the pre- Fig. 4 DFT-optimized structures of the hydrogen-bonded adducts
equilibrium processes.
between 1 and hfp and the relative stabilization Gibbs energy.
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Table 2 KIE values of the MeOH oxidation with 1–3 at various
temperatures
depicted in Fig. 4(a), which involves the hydrogen bonding
described in Scheme 1. The difference in the stabilization Gibbs
energies of the two structures in Fig. 4 was estimated to be
Temperature, K
2.9 kcal molꢀ1
.
Oxidant
KIE
281
289
297
305
Kinetic analysis of methanol oxidation
1
2
3
kH/kD for CH3
kH/kD for OH
kH/kD for CH3
kH/kD for OH
kH/kD for CH3
kH/kD for OH
3.3
1.2
3.3
1.0
2.1
1.0
2.6
1.1
2.3
1.1
1.8
1.1
2.5
1.0
2.3
1.1
1.7
1.1
2.1
1.0
1.9
1.2
1.8
1.1
To investigate the reaction mechanisms of the substrate
oxidation in detail, determination of the kinetic isotope effect
(KIE) was conducted on the oxidation reactions of methanol
and the deuterated derivatives (CD3OH and CH3OD) as
substrates at various temperatures. The thermodynamic
parameters for the pre-equilibrium processes and the activation
parameters for the substrate oxidations were determined on the
basis of the van't Hoff plots for the equilibrium constants and
the Eyring plots for the rate constants (Table 1 and Fig. S4 and
S6, ESI†), respectively. The activation and the thermodynamic
parameters for the same substrate are quite similar to each
other for the three different oxidants, indicating that the reac-
tion proceeds via similar transition states for the three oxidants
in terms of potential energies and structures.
According to the activation parameters, the activation Gibbs
energy changes (DG‡) of the reactions are mainly controlled by
the activation entropy terms (DS‡) and the contributions of the
activation enthalpy terms (DH‡) to the transition states are not
so large. For instance, DH‡ ¼ 20 kJ molꢀ1 and TDS‡ ¼ ꢀ66.5 kJ
molꢀ1 were obtained for the reaction of CH3OH as the substrate
and 1 as the oxidant at 298 K. The large negative TDS‡ values
suggest that the a-C–H bond in a hydrogen-bonded alcohol in
the adduct of the pre-equilibrium process may be enforced to
direct to the oxo-ligand to undergo PCET reactions as hydrogen
atom transfer (HAT) via the formation of a tightly-condensed
transition state (vide infra).15c
deuterated substrates. As previously described,15,17 the KIE
values for the hydroxyl groups, which were determined using
CH3OH and CH3OD as substrates, were negligible for all the
three oxidants (Table 2). The activation parameters for the
oxidation reactions of CH3OH and CH3OD were almost iden-
tical in comparison with the values using the same oxidant
(Table 1). In contrast, the oxidation rate constant for CD3OH
relative to that for CH3OH showed larger KIE values (Table 2)
and the activation enthalpies for the CD3OH oxidations were
larger than those for the CH3OH oxidations. Therefore, the rate-
determining step in the oxidation reactions involves the
hydrogen abstraction from the methyl group of the
methanol.15,17
The temperature dependence of the KIE of the oxidations
with oxo-complexes 1–3 was also investigated in the tempera-
ture range of 281–305 K. The KIE values for the hydroxyl group
were maintained at ca. 1.1 in the temperature range. On the
other hand, KIE values for oxidations of CH3OH and CD3OH
with 1–3 increased with decreasing temperature (Table 2). The
KIE values for the methyl group obtained here were relatively
small (1.8–3.3 for all the temperature range measured in this
study). As for a hydrogen abstraction reaction involving a
tunnelling mechanism, it has been known to show a large kH/kD,
at least larger than 7 at room temperature.33,34 As shown in Table
2, the largest KIE value for the oxidation reactions obtained here
was 3.3, which was apparently smaller than 7, suggesting no
tunnelling effect for the reactions reported here. Typically the
magnitude of the KIE increases as the proton donor–acceptor
distance increases.35 The hydrogen donor–acceptor distances
for the oxidation reactions with 1–3 should be preliminarily
xed as appropriate for HAT from the C–H moiety of the
substrate to the metal–oxo moiety of the oxidant in the transi-
tion state (Fig. 5). Furthermore, KIE for hydrogen abstraction
reactions from the methyl group of MeOH was demonstrated to
become larger as temperature decreased, which is a normal
tendency for hydrogen abstraction reactions without tunnel-
ling, in the temperature range examined (Fig. S8, ESI†).36
In general, the KIE values were dened with the ratio of the
rate constants (kH/kD) between those for the hydrogenated and
Table
1 Thermodynamic parameters for the pre-equilibrium
processes and activation parameters for the oxidation reactions of
methanol and the deuterated derivatives, and 2-propanol with RuIV]
O complexes
a
b
Oxidant
Substrate
DH‡a
DS‡b,c
DHꢃ
DSꢃ
1
CH3OH
CD3OH
CH3OD
iPrOH
20
32
25
25
26
23
38
16
25
25
15
21
12
21
18
38
ꢀ223
ꢀ189
ꢀ203
ꢀ143
ꢀ197
ꢀ211
ꢀ169
ꢀ238
ꢀ146
ꢀ203
ꢀ237
ꢀ224
ꢀ250
ꢀ156
ꢀ225
ꢀ143
21
6.9
15
ꢀ21
ꢀ23
15
12
23
ꢀ14
ꢀ29
18
15
20
ꢀ14
ꢀ16
—
102
54
80
ꢀ40
ꢀ4.8
81
nPrOHd
CH3OH
CD3OH
CH3OD
iPrOH
2
73
108
ꢀ13
ꢀ6.8
94
nPrOHd
CH3OH
CD3OH
CH3OD
iPrOH
3
88
Dependence of the thermodynamic and kinetic parameters of
the oxidation reactions on the substrates
103
ꢀ19
ꢀ2.6
—
nPrOHd
iPrOH
Oxidation reactions of 2-propanol (iPrOH)37 with complexes 1–3
were also conducted in this work (Fig. S5 and S6, ESI†). The
values of the activation parameters for the 2-propanol
[RuIV(O)(tpy)(bpy)]2+e
a
b
c
In kJ molꢀ1
.
In J molꢀ1 Kꢀ1
.
At 298 K. d Ref. 15c. e Ref. 22.
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transition states are not so large (Table 1). For instance, DH‡ ¼
20 kJ molꢀ1 and TDS‡ ¼ ꢀ66.5 kJ molꢀ1 were obtained for the
oxidation of CH3OH by 1 at 298 K. The large negative DS‡ values
suggest that the a-C–H bond in a hydrogen-bonded alcohol in
the adduct of the pre-equilibrium process may be enforced to
direct to the oxo-ligand to undergo PCET reactions as hydrogen
atom transfer (HAT) via the formation of a tightly-organized
transition state (Fig. 5).15c
Evans–Polanyi plot for the oxidation reactions
Despite the difference in BDE values among CH3OH (96.0 kcal
molꢀ1), iPrOH (90.0 kcal molꢀ1) and nPrOH (93.7 kcal molꢀ1),42
the activation parameters (DH‡ and DS‡) are almost the same for
the oxidations of all the three substrates (Table 1). This indi-
cates that the rate constants for the oxidation reactions with
complexes 1–3 and the energy levels of the transition states are
not or, if at all, very slightly dependent on the BDEs of the C–H
Fig. 5 A proposed energy diagram of the oxidation reaction of alco-
hols with a RuIV–oxo complex having an aqua ligand.
oxidations were determined through variable-temperature bonds of the substrates. To conrm the independence of the
kinetic measurements and were compared with those for reaction rates (k) from BDEs of the substrates, as observed in
1-propanol (nPrOH) oxidations obtained in the previous reports the oxidation reactions of the three alcohols, we determined the
(Table 1).15,38 The thermodynamic parameters of the pre-equi- rate constants at 298 K with 1 as the oxidant for ve substrates
librium processes (DHꢃ and DSꢃ) were signicantly different having different BDE values (Fig. S10, ESI†); methanol (BDE ¼
between CH3OH and iPrOH, whereas those of nPrOH15 and 96.0 kcal molꢀ1), nPrOH (93.7), iPrOH (90.0), 4-methylbenzyl
iPrOH were similar (Table 1). The DHꢃ and DSꢃ values for the alcohol (87.5), and sodium 4-ethylbenzenesulfonate (EBS)
CH3OH oxidations were commonly positive, whereas those for (84.6).42 A plot of log k against BDE values of the C–H bonds to
iPrOH oxidations were negative. Thus, the adduct formation in be cleaved in the substrates showed a linear correlation (Fig. 6).
the pre-equilibrium processes for iPrOH is dominated by the In general, the linear relationship between the second-order
enthalpy term, whereas that for CH3OH is governed by the rate-constant and BDE of the substrate has been known as the
entropy term. The cause of the differences in the thermody- Bell–Evans–Polanyi (BEP) relation as expressed by eqn (4).43
namic parameters between CH3OH and iPrOH for the pre-
Ea ¼ aDHꢃ + C
(4)
equilibrium processes can be ascribed to the difference in the
solvation among the three substrates in water. iPrOH (3 ¼ 19.9)
is less polar relative to CH3OH (3 ¼ 32.7),39 and the acceptor
number of iPrOH (AN ¼ 33.8) is smaller than that of CH3OH (AN
DHꢃ ¼ BDEC–H for substrate + BDEO–H for oxidant
(5)
In most cases, oxidation reactions of C–H bonds with high-
valent metal–oxo complexes obeyed the BEP relation to give the
¼ 41.3),40 although the donor numbers are comparable (DN
¼
21.1 for iPrOH, DN ¼ 19 for CH3OH).41 Thus, CH3OH should be
strongly solvated in water, and moreover, forms strong
hydrogen bonds with water molecules, whereas iPrOH is weakly
solvated and the extent of the hydrogen bonding with water
molecules should be moderate compared with that of CH3OH.
As a result, upon formation of the adduct of CH3OH with the
oxidant, a lot of water molecules are released, that should cause
the entropy gain (Fig. 3), but the enthalpy gain by the adduct
formation through the hydrogen bonding is offset by the
enthalpy loss due to the cleavage of hydrogen bonds between
CH3OH and water molecules. On the other hand, the entropy
gains for the pre-equilibrium process of iPrOH oxidations are
not signicant because iPrOH is less-solvated, but the forma-
tion of the strong hydrogen bonds of iPrOH with the oxidant
affords the large enthalpy gain. The similarity in the parameters
of the pre-equilibrium process for nPrOH15 to those for iPrOH
can be ascribed to the similarity in the characteristics (3 ¼
20.3,39 AN ¼ 37.3 (ref. 40) and DN ¼ 21.1 (ref. 41) for nPrOH).
The activation Gibbs energy changes of the oxidation reac-
tions are mainly controlled by the activation entropy terms and
Fig. 6 A plot of the log(k/n) (n: the number of equivalent C–H
hydrogen atoms) at 298 K for the oxidation of five substrates ((a) EBS,
(b) 4-methylbenzyl alcohol, (c) iPrOH, (d) nPrOH, (e) methanol) with 1
the contributions of the activation enthalpy terms to the against BDEs of C–H bonds to be cleaved in the substrates.
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coefficient a ꢄ 0.5 and oxidation reaction of a substrate having a
larger BDE value proceeded slowly.10a,44 In sharp contrast, the
rate constants for the oxidation reactions with 1 were almost
independent of the BDE values of the substrates and the slope
of the plot in Fig. 6, that is, a, was very small at 0.08.
Conclusions
Herein, we have experimentally conrmed the formation of a
hydrogen-bonded adduct with a RuIV]O complex and an
alcohol prior to the oxidation in water for the rst time.
Furthermore, we have demonstrated the signicance of the
adduct formation in the hydrogen abstraction reaction to
promote the reactions regardless of the BDEs of the C–H bonds
to be cleaved. On the basis of the large negative activation
entropy (DS‡), the PCET reactions from the substrates to
complexes 1–3 have been proposed to proceed via tightly orga-
nized transition states. All the observations can be elucidated by
the formation of the oxidant–substrate adduct in the pre-equi-
librium process, whose structure is strictly organized by
hydrogen bonding to offer a large contribution of DS‡ to the
transition state relative to that of DH‡. This work provides a
strong basis to elucidate the reactivity of a high-valent metal–
oxo complex in oxidation reactions of organic molecules,
especially those involving oxidative C–H bond functionalization
in water.
To date, some exceptional cases have been reported where
the BEP relation was not valid.45 Tanko and co-workers have
discussed the causes of the insensitivity of the rate constants to
BDEs of C–H bonds of substrates:46 they have indicated that the
systems controlled by the activation entropy (DS‡) exhibit slight
dependence of the reaction rates on BDEs of substrates and
instead accessibility to the reaction points, orientation of the
reactants and the pathways of HAT are controlling factors for
the hydrogen abstraction processes. In our case, the energy
levels of the transition states are mainly governed by the acti-
vation entropies (Table 1), and the reaction rates were insensi-
tive to the BDE changes of the C–H bonds, since the C–H bond
of the substrate should be intact at the transition state (Fig. 5).
In addition, the orientations of the substrates in the oxidant–
substrate adducts should be xed by the hydrogen bonding
formed in the pre-equilibrium process, attaining the advanta-
geous molecular arrangements for the hydrogen abstraction.
Thompson and Meyer have reported the activation parameters
for the oxidation of iPrOH by [RuIV(O)(tpy)(bpy)]2+ (tpy ¼
2,20:60,200-terpyridine, bpy ¼ 2,20-bipyridine) in water,22 indi-
cating the large negative activation entropy (DS‡ ¼ ꢀ143 J molꢀ1
Kꢀ1 at 298 K, Table 1) similar to the cases of 1–3, suggesting the
adduct formation between the RuIV]O complex and iPrOH
prior to the oxidation in water.22 On the other hand, for the
oxidation of cumene with [RuIV(O)(h3-H+TPA)(bpy)]3+ in CH3CN,
in which no adduct formation was suggested and KIE was
determined to be 12, the contribution of the DH‡ and TDS‡
terms to DG‡ was almost identical; DH‡ ¼ 42 kJ molꢀ1 and TDS‡
¼ ꢀ39 kJ molꢀ1 at 298 K.47 Since the contribution of the entropy
term is relatively small in the latter case, the reaction rates are
dependent on the BDE to show the signicant KIE value.
Aer the formation of the entropy-controlled transition
state, the hydrogen abstraction reactions from the substrate to
the RuIV]O complex spontaneously occur to afford the corre-
sponding RuIII–OH complex and the H-abstracted radical
species of the substrate (Fig. 5),48 despite the fact that the
hydrogen abstraction process is an energetically unfavourable
(uphill) process. The intermediate state aer the hydrogen
abstraction is estimated to be energetically stable relative to the
transition state. In fact, the enthalpy changes (DHabst) to form
the radical species, which can be calculated by the difference of
the BDE values between the RuIII–OH complex and the C–H
bond of the substrate, is sufficiently small compared to the free-
energy difference of the transition state: for instance, the BDE
difference between 1 and CH3OH having the highest BDE value
among the substrates studied here was estimated to be 56 kJ
molꢀ1. Additionally, the radical species should also be more
stable than the transition state in terms of entropy, because the
restricted orientation observed at the transition state is lost
aer the hydrogen abstraction. The following reactions also
proceed smoothly led by the stability of the products, i.e., the
RuII–OH2 complex and aldehydes or ketones.
Acknowledgements
This work was supported by a Grant-in-Aid (no. 24245011) from
the Japan Society of Promotion of Science (JSPS, MEXT) of Japan
and grants from the Asahi Glass Foundation and The Mitsu-
bishi Foundation. We also thank Prof. Junji Ichikawa (Univer-
sity of Tsukuba) for his kind provision of hexauoro-2-propanol.
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