Kinetics of self-decomposition and hydrogen atom transfer reactions of substituted phthalimide N-oxyl radicals in acetic acid

Article abstract of DOI:10.1021/jo048418t

(Chemical Equation Presented). Kinetic data have been obtained for three distinct types of reactions of phthalimide N-oxyl radicals (PINO ^?) and N-hydroxyphthalimide (NHPI) derivatives. The first is the self-decomposition of PINO^? wh

Full text of DOI:10.1021/jo048418t

Kinetics of Self-Decomposition and Hydrogen Atom Transfer
Reactions of Substituted Phthalimide N-Oxyl Radicals in Acetic
Acid
Yang Cai, Nobuyoshi Koshino, Basudeb Saha, and James H. Espenson*
Ames Laboratory and Department of Chemistry, Iowa State University of Science and Technology,
Ames, Iowa 50011
espenson@iastate.edu
Received September 8, 2004
Kinetic data have been obtained for three distinct types of reactions of phthalimide N-oxyl radicals
(PINO•) and N-hydroxyphthalimide (NHPI) derivatives. The first is the self-decomposition of PINO•
which was found to follow second-order kinetics. In the self-decomposition of 4-methyl-N-
hydroxyphthalimide (4-Me-NHPI), H-atom abstraction competes with self-decomposition in the
presence of excess 4-Me-NHPI. The second set of reactions studied is hydrogen atom transfer from
NHPI to PINO•, e.g., PINO• + 4-Me-NHPI a NHPI + 4-Me-PINO•. The substantial KIE, kH/kD
)
11 for both forward and reverse reactions, supports the assignment of H-atom transfer rather than
stepwise electron-proton transfer. These data were correlated with the Marcus cross relation for
hydrogen-atom transfer, and good agreement between the experimental and the calculated rate
constants was obtained. The third reaction studied is hydrogen abstraction by PINO• from p-xylene
and toluene. The reaction becomes regularly slower as the ring substituent on PINO• is more electron
donating. Analysis by the Hammett equation gave F ) 1.1 and 1.8 for the reactions of PINO• with
p-xylene and toluene, respectively.
CHART 1
Introduction
N-Hydroxyphthalimide (NHPI, X ) Y ) H in Chart 1)
has gained considerable attention in organic and catalytic
chemistry.1-4 Since fascinating catalysis of NHPI with
Co(II) has been found by Ishii,1 a number of studies of
its reactivity and applications have been reported.2-4 It
is proposed that NHPI is oxidized to phthalimide N-oxyl
radical (PINO•), which is a key species in the catalytic
cycles.2 We have previously studied the kinetics for
hydrogen abstraction reactions by PINO• from methyl
arenes and other organic substrates.5,6
These reactions are characterized by large kinetic
isotope effects, and we proposed that quantum tunneling
plays an important role there. This is not without further
qualification, however, as will be taken up at the end of
the Discussion.
(1) Ishii, Y.; Iwahama, T.; Sakaguchi, S.; Nakayama, K.; Nishiyama,
Y. J. Org. Chem. 1996, 61, 4520-4526.
(2) Ishii, Y.; Sakaguchi, S.; Iwahama, T. Adv. Synth. Catal. 2001,
343, 393-427.
(3) Amorati, R.; Lucarini, M.; Mugnaini, V.; Pedulli, G. F.; Minisci,
F.; Recupero, F.; Fontana, F.; Astolfi, P.; Greci, L. J. Org. Chem. 2003,
68, 1747-1754.
(4) Arends, I. W. C. E.; Sasidharan, M.; Ku¨hnle, A.; Duda, M.; Jost,
C.; Sheldon, R. A. Tetrahedron 2002, 58, 9055-9061.
(5) Koshino, N.; Saha, B.; Espenson, J. H. J. Org. Chem. 2003, 68,
9364-9370.
(6) Koshino, N.; Cai, Y.; Espenson, J. H. J. Phys. Chem. A. 2003,
107, 4262-4267.
In this study, we present new kinetic data using ring-
substituted NHPI derivatives (Chart 1) and discuss self-
10.1021/jo048418t CCC: $30.25 © 2005 American Chemical Society
Published on Web 12/14/2004
238
J. Org. Chem. 2005, 70, 238-243

Substituted Phthalimide N-Oxyl Radicals in Acetic Acid
TABLE 1. Maximum Absorption Wavelengths and
Molar Absorptivities of Substituted PINO Radicals in
Acetic Acida
TABLE 2. Rate Constants for Self-Decomposition of
Substituted PINO Radicals in HOAc at 25 °C
X-PINO•
kd/L mol-1 s-1
X-PINO•
λmax/nm
ꢀmax/103 L mol-1 cm-1
4-Cl
4-F
4-H
4-Me
3-F
0.4
4-Cl
4-F
4-H
4-Me
3-F
394
1.38
0.7
382
1.21
0.6a
1.7b
0.8c
382b
397c
367c
1.36b
1.39d
1.32d
a Reference 5. b Net self-decomposition (see text). c At 15 °C, ref
13.
a In HOAc at 25 °C. b Reference 5. c Reference 10. d Redeter-
mined more accurately.
cals, which differ relatively little from one another. It
seems that there is no obvious correlation between
substitutents on NHPI and maximum absorption wave-
lengths or molar absorptivities.
decomposition reactions, hydrogen atom self-exchange
reactions, and hydrogen abstraction reactions from p-
xylene and toluene
Self-Decomposition of the Substituted PINO Radi-
cals. We previously studied self-decomposition reaction
of the unsubstituted PINO radical and found that the
reaction obeys second-order kinetics in glacial acetic
acid.5 The products of this reaction have been identified
as some oligomers (primarily a trimer) formed by sub-
sequent reactions of the initial disproportionation.11
Experimental Section
Materials. N-hydroxyphthalimide (NHPI) was purchased
from Aldrich and used as received. 3-Fluoro- and 4-methyl-
substituted NHPI derivatives were synthesized as previously
reported.7 4-Fluoro-NHPI, whose synthesis had not been
reported, was prepared from 4-fluorophthalic anhydride and
hydroxylamine hydrochloride by the same method7 and ob-
tained in 25% yield. It was characterized by 1H NMR spec-
troscopy in DMSO-d6: δ 7.62-7.67 (m, 1H), 7.74-7.76 (m, 1H),
7.89-7.92 (m, 1H), 10.89 (s, 1H). Glacial acetic acid (Fischer)
and acetic acid-d4 (99.5% D, CIL) were used as received. Each
PINO radical was generated by the oxidation of its NHPI
precursor with Co(III) acetate or lead tetraacetate. Cobalt(III)
solutions were prepared by passing ozone through a solution
of Co(OAc)2 in acetic acid.8 The Co(III) solutions were then
bubbled with a vigorous stream of argon to remove excess
ozone. Lead tetraacetate (Aldrich) was also used to produce
the PINO radicals for hydrogen abstraction reactions with
p-xylene and toluene.9 To study kinetic isotope effects for
hydrogen abstraction reactions, p-xylene-d10 (99+% D, Aldrich)
and toluene-d8 (99+% D, Aldrich) were used as received. Other
chemical reagents were obtained commercially and used
without purification.
General Methods. The UV/vis spectra of the PINO radicals
were recorded on a Shimadzu UV-3101 spectrophotometer. The
kinetics of self-decomposition of the PINO radicals was
monitored by using a UV/Vis spectrophotometer equipped with
a temperature-controlled cell holder. The rate constants for
reactions between X-PINO• and Y-NHPI were measured in
glacial acetic acid and acetic acid-d4 by a stopped-flow spec-
trophotometer (OLIS RSM 1000) with a temperature-con-
trolled water circulation bath. The rate constants for reactions
of the PINO radicals with p-xylene and toluene were measured
spectrophotometrically in HOAc at 25.0 ( 0.1 °C under an
argon atmosphere.
The second-order rate constant, kd, was obtained from
eq 3, where Y represents absorbance, [X-PINO•]0 the
initial concentration of the X-PINO radical, given by (Y0
- Y∞)/ꢀ. 5,12 The value of ꢀ for PINO‚ in C6H6/MeCN have
been reported to be 1.46 × 103 L mol-1 cm-1 11
;
we have
used the value in HOAc from Table 1 for the calculation
of the rate constant for sake of solvent consistency. In
any event, the values of the rate constant would be very
similar no matter which value of ꢀ were used. The
decomposition rate constants (kd) are summarized in
Table 2.
(Y0 - Y∞)
Yt ) Y∞ +
)
1 + [X-PINO]0kdt
(Y0 - Y∞)
Y∞ +
(3)
1 + (Y0 - Y∞)kdt/ꢀ
We have previously reported that the reactivity of
substituted NHPI compounds in the autoxidation of
p-xylene follows the order of 4-Me-NHPI < 3-F-NHPI <
NHPI10 and proposed that the reactivity order could be
explained by the persistence of the corresponding radical
species. As shown in Table 2, the unsubstituted PINO•
(4-H-PINO•) is much more persistent than 4-Me-PINO•.
The comparison of the stability of 3-F-PINO• with those
of 4-substituted PINO radicals cannot be straightforward
because of the temperature differences. However, the self-
decomposition of 4-Me-PINO• would be faster than 1.7
Results and Discussion
Molar Absorptivities of the Substituted PINO
Radicals. The substituted PINO radicals were generated
by the oxidation of the parent NHPI compounds with
Co(III) in HOAc. Although the PINO radicals decompose
slowly, they persist long enough for accurate UV/vis
spectra to be recorded (Figure S1, Supporting Informa-
tion). Table 1 shows the wavelengths of the absorption
maxima and the molar absorptivities of the PINO radi-
(7) Wentzel, B. B.; Donners, M. P. J.; Alsters, P. L.; Feiters, M. C.;
Nolte, R. J. M. Tetrahedron 2000, 56, 7797-7803.
(8) Lande, S. S.; Falk, C. D.; Kochi, J. K. J. Inorg. Nucl. Chem. 1971,
33, 4101-4109.
(10) Saha, B.; Koshino, N.; Espenson, J. H. J. Phys. Chem. A 2004,
108, 425-431.
(9) When Co(III) was used to generate PINO•, we obtained slightly
different rate constants of hydrogen abstraction reactions even under
an argon atmosphere. Probably, Co(II) takes part in the subsequent
reactions.
(11) Ueda, C.; Noyama, M.; Ohmori, H.; Masui, M. Chem. Pharm.
Bull. 1987, 35, 1372-1377.
(12) Espenson, J. H. Chemical Kinetics and Reaction Mechanisms,
2nd ed.; McGraw-Hill: New York, 1995.
J. Org. Chem, Vol. 70, No. 1, 2005 239

Cai et al.
s-1 in practical conditions because hydrogen abstraction
from methyl group also takes place (see below). Therefore,
the stability of the three PINO radicals would be in the
order of 4-Me-PINO• < 3-F-PINO• < PINO•, consistent
with the reactivity of the NHPIs in the catalytic cycle.
The self-decomposition reactions of nitroxyl radicals
are usually observed to follow second-order kinetics.14
However, Amorati et al. reported that the self-decomposi-
tion of PINO• obeys first-order kinetics in benzene
containing 10% CH3CN,3 which is inconsistent with our
data in HOAc and those of Masui in CH3CN.11 According
to their experimental data, the decomposition of the
PINO radical in benzene obeys the first-order kinetics,
and they proposed a fragmentation at one of the carbonyl
carbon-nitrogen bonds.3,15
tionin their experiments, the resulting acetophenone
could produce some byproducts with which PINO• may
react.
Self-Decomposition of 4-Me-PINO Radical. An
exception to the general pattern of second-order kinetics
was found for 4-Me-PINO•, which follows second-order
kinetics only at lower concentrations of 4-Me-NHPI
(<0.83 mmol L-1). Deviations from second-order kinetics
were noted at higher concentrations of 4-Me-NHPI. As
the concentration of 4-Me-NHPI increased, the absor-
bance-time data approached first-order kinetics, but
both first- and second-order terms were needed for
precise fitting. Considering the fairly high H-atom ab-
straction ability of PINO radicals, we concluded that the
4-Me-PINO radical decomposes in two parallel reac-
tions: one is the self-decomposition as expressed by eq
2, and the other is hydrogen abstraction of 4-Me-PINO•
from the methyl group on 4-Me-NHPI, eq 8.
We generated the PINO radical in benzene containing
10% CH3CN by the oxidation of NHPI with AgO (Aldrich)
and monitored the self-decomposition. The result is
shown in Figure S2a,b (Supporting Information). It seems
that the decomposition of the PINO radical is more likely
to follow second-order kinetics. We have not obtained the
accurate molar absorptivity of PINO• in benzene; how-
ever, if we suppose ꢀ382 in benzene/CH3CN is equal to ꢀ382
in HOAc, kd in benzene/CH3CN is calculated as 31 L
mol-1 s-1, which is not too far from its value in CH3CN,
In that case, the differential rate law and its integrated
form are12
d[4-Me-PINO]
24.1 L mol-1 s-1 11
Even if we hypothesize that the
.
-
)
dt
reaction follows first-order kinetics, the pseudo-first-order
rate constant is given as 1.2 × 10-3 s-1. This rate constant
is much smaller than that reported (0.1 s-1).3 The
discrepancy may arise from the procedures to generate
the PINO radical.3,5 Amorati et al. used dicumyl peroxide
to generate the PINO radical.
kd[4-Me-PINO•]2 + kH[4-Me-NHPI][4-MePINO•] (9)
Yt )
H(obs) t
kH(obs)(Y0 - Y∞)0[4-Me-PINO•]e-k
kH(obs) + kd[4-Me-PINO•]0(1 - e-k
Y∞ +
(10)
H(obs) t
)
{PhCMe2O}2
9
hv8 2PhCMe2O•
(5)
where kH is the rate constant for reaction 8 and kH(obs) is
the related pseudo-first-order rate constant in the pres-
ence of excess 4-Me-NHPI (kH(obs) ) kH[4-Me-NHPI]). The
value of [4-Me-PINO]0 is calculated from the absorbance
at 397 nm and its molar absorptivity. We determined the
rate constant for the self-decomposition (eq 2) of 4-Me-
PINO• using experimental data at the lowest 4-Me-NHPI
concentrations. Figure S3a (Supporting Information)
shows the resulting fitting, which gave kd ) 1.7 L mol-1
s-1. On the other hand, at higher concentrations of 4-Me-
NHPI (>2 mmol L-1), eq 10 was used to obtain kH(obs) by
fixing kd (1.7 L mol-1 s-1). The values of kH(obs) so obtained
were plotted against [4-Me-NHPI]0 as illustrated in
Figure 1. This procedure gave kH ) 0.080 L mol-1 s-1 at
25.0 °C as the rate constant of H-atom abstraction from
4-methyl group (reaction 8). We previously reported the
rate constants of H-atom abstraction by PINO• from toluic
acids as kPR ) 0.20 (m-toluic acid) and 0.28 (p-toluic acid)
L mol-1 s-1 under an argon atmosphere.5 The difference
of the rate constants between kH and kPR of the two toluic
The PINO radical is then generated in the following
step:
PhCMe2O• + NHPI f PhCMe2OH + PINO• (6)
However, the cumyloxyl radical might produce other
species such as acetophenone by â-scission:16
PhCMe2O• f PhCOMe + Me•
(7)
It is well-known that acetophenone is also photo-
active.17 Therefore, we postulate that during the irradia-
(13) The rate constant was measured at 15 °C, because the formation
and decomposition steps of 3-F-PINO• were comparable at 25 °C, and
thus, the kinetic trace could not be separated into its components.
(14) (a) Blackley, W. D.; Reinhard, R. R. J. Am. Chem. Soc. 1965,
87, 802-805. (b) Bowman, D. F.; Gillan, T.; Ingold, K. U. J. Am. Chem.
Soc. 1971, 93, 6555-6561.
(15) Minisci, F.; Recupero, F.; Cecchetto, A.; Gambarotti, C.; Punta,
C.; Paganelli, R. Org. Process Res. Dev. 2004, 8, 163-168.
(16) Baciocchi, E.; Bietti, M.; Salamone, M.; Steenken, S. J. Org.
Chem. 2002, 67, 2266-2270.
(17) (a) Wagner, P. J.; Truman, R. J.; Puchalski, A. E.; Wake, R. J.
Am. Chem. Soc. 1986, 108, 7727-7738. (b) Wagner, P. J.; Zhang, Y.;
Puchalski, A. E. J. Phys. Chem. 1993, 97, 13368-13374.
240 J. Org. Chem., Vol. 70, No. 1, 2005

Substituted Phthalimide N-Oxyl Radicals in Acetic Acid
FIGURE 1. Plot of kH(obs) against [4-Me-NHPI]0. kH(obs) was
obtained from eq 10 with kd fixed (1.7 L mol-1 s-1) in HOAc at
25.0 °C.
FIGURE 2. Plot of the kinetic data according to eq 13 to
evaluate kf and kr of reaction 11.
acids can be attributed to two factors. First, 4-Me-NHPI
has two carbonyl groups on the benzene ring which
withdraw more electron density, making hydrogen ab-
straction from the methyl group more difficult. Second,
the BDE of the O-H group of 4-Me-NHPI is smaller than
that of unsubstituted NHPI, which is reflected in the
equilibrium constant of reaction 11 (see below). There-
fore, it is reasonable that the rate constant of H-atom
abstraction from 4-methyl group on 4-Me-NHPI by 4-Me-
PINO• (kH) is smaller than those from methyl group on
m- or p-toluic acids by the unsubstituted PINO•.
Hydrogen Atom Transfer Reaction. The combina-
tion of NHPI with Co(OAc)2 catalyzes the autoxidation
of hydrocarbons.2 This feature is interpreted by the high
H-atom abstraction ability of the PINO radical, and we
found that quantum mechanical tunneling plays a role
in the hydrogen abstraction.5 We also proposed that the
kinetic isotope effect would be maximum when the reac-
tion is thermoneutral.6 On the basis of this interpretation,
we were interested in a pseudo self-exchange reaction
between PINO• and substituted NHPI as shown in eq 11.
From a series of experiments with varying concentra-
tions (Figure 2), each rate constant was obtained at 25.0
°C: kf ) 677 ( 24 L mol-1 s-1 and kr ) 354 ( 23 L mol-1
s-1, which means that the equilibrium constant, Keq
() kf/kr), for reaction 11 is 1.91 ( 0.10 at 25 °C. Therefore,
from eq 14, the O-H bond dissociation energy of 4-Me-
NHPI is found to be1.6 kJ mol-1 lower than that of
NHPI.18
BDE (X-NHPI) ) BDE(NHPI) - RT ln Keq (14)
We also measured rate constants for the following
pseudo-self-exchange reaction:
kf
4-F-PINO• + NHPI {k
\
} 4-F-NHPI + PINO• (15)
r
The rate constants kf and kr for reaction 15 are 651
and 241 L mol-1 s-1 in HOAc at 25.0 °C, which means
the equilibrium constant of the reaction 16 is 2.70.
Therefore, the O-H bond dissociation energy of 4-F-
PINO• is calculated to be 2.46 kJ mol-1 higher than that
of NHPI. Thus, it is confirmed that electron-withdrawing
groups on NHPI strengthen the O-H bond and electron-
donating groups weaken it.
kf
PINO• + 4-Me-NHPI {k
\
} NHPI + 4-Me-PINO• (11)
r
For reaction 11, rate constants were also measured in
acetic acid-d4 to evaluate the KIE, noting the rapid
exchange of protons (deuterons) between R2NOH and
acetic acid-d4. The rate constants of the reaction 11 in
acetic acid-d4 are kf ) 61.3 ( 2.1 L mol-1 s-1 and kr )
31.8 ( 2.0 L mol-1 s-1. Therefore, the values of KIE for
kf and kr are 11.0 and 11.1, respectively. This indicates
that reaction 11 takes place through H-atom transfer,
not electron transfer (Scheme 1). This conclusion is also
supported by the finding that the rate constants for
reaction 11 are not affected by addition of CF3COOH
(Table S1, Supporting Information).20
As described above, reaction 11 takes place through
direct H-atom transfer, and the KIEs (11.0 and 11.1) of
the rate constants in both directions are larger than the
theoretical maximum value from ground-state energy
differences (7.8).12 In previous reports, quantum mechan-
Reaction 11 is nearly thermoneutral considering the
difference in bond dissociation energies.18 Although reac-
tion 11 represents hydrogen atom transfer in a stoichio-
metric sense, there are two possible mechanisms for it:
one is hydrogen atom transfer itself (or proton coupled
electron transfer), and the other is stepwise transfer of
an electron and a proton.19 We measured rate constants
for the reaction 11 with excess 4-Me-NHPI and NHPI in
HOAc at 25 °C. Reaction 11 takes place quite rapidly,
therefore hydrogen abstraction from the 4-Me group
observed in self-decomposition of 4-Me-PINO• is negli-
gible. The reaction was safely monitored by the growth
of the absorbance at 397 nm, which is λmax for 4-Me-
PINO•. The rate constant for the reaction 11 is given by
eq 12 in the presence of excess 4-Me-NHPI and NHPI.
kobs ) kf[4-Me-NHPI] + kr[NHPI]
(12)
(18) Annunziatini, C.; Gerini, M. F.; Lanzalunga, O.; Lucarini, M.
J. Org. Chem. 2004, 69, 3431-3438.
(19) Roth, J. P.; Lovell, S.; Mayer, J. M. J. Am. Chem. Soc. 2000,
122, 5486-5498.
This equation can be rearranged to the following form:
(20) We assumed that if the reaction 11 takes place through electron
transfer via preequilibrium of proton dissociation, the rate constants
would be affected by addition of strong acid; pKa ) 0.52 (CF3COOH)
and 4.76 (CH3COOH).
kobs
kf[4-Me-PINO•]
)
+ kr
(13)
[NHPI]
[NHPI]
J. Org. Chem, Vol. 70, No. 1, 2005 241

Cai et al.
SCHEME 1. Reaction Scheme for Pseudo-Self-Exchange Reaction of PINO• and 4-Me-NHPl
TABLE 3. Rate Constants and Kinetic Isotope Effect for
the Reaction of PINO Radicals with p-Xylene in HOAc at
25 °C
p-xylene
4-X-PINO•, X )
kH/s-1
kD/s-1
kH/kD
Cl
10.6 ( 0.07
8.40 ( 0.18
5.95 ( 0.07
3.90 ( 0.04
0.426 ( 0.002
0.338 ( 0.002
0.240 ( 0.001
0.166 ( 0.002
24.9
24.9
24.8
23.5
F
Ha
CH3
a Reference 5.
experimental data and each line comes from the calcu-
lated values.
FIGURE 3. Comparison of experimental data with the
calculated values (solid lines) according to eq 16 for H-atom
transfer of the reaction 11 in HOAc at various temperatures:
308.45 K (O); 303.45 K (b); 301.05 K (]); 298.15 K ([); 294.45
K (0); 291.25 K (9); 289.75 K (4).
Hydrogen Atom Transfer between PINO• and
NHPI. This study has shown that reaction 11 takes place
through H-atom transfer with rate constants, kf ) 677
and kr ) 354 L mol-1 s-1. Therefore, one estimate the
rate constant of electron-exchange reaction between
PINO• and NHPI as being near the average of these
ical tunneling has been proposed to play an important
role in PINO radical reactions,5 such as those with
p-xylene and toluene, for which remarkably small pre-
exponential factors were found, log A ≈ 5-6. This also
implies that tunneling participates in the reactions.
Therefore, we predicted that the reaction 11 also has a
small preexponential factor (in other words, a large
negative activation entropy). The rate constants for
reaction 11 were measured at various temperatures, and
were in turn analyzed by using the following equation
with Scientist 2.0.21
values, or ca. 500 L mol-1 s-1
.
kex () kAA
PINO• + *NHPI
)8 NHPI + *PINO• (17)
A second approach to estimating kAA is based on
applying the Marcus cross relation to H-atom transfer
reactions, as has been establlished.19,22 There is enough
uncertainty in BDE(NHPI) (364-375 kJ mol-1),3,6 how-
ever, as to make this approach unreliable.
Hydrogen Abstraction by PINO Radicals from
p-Xylene. As described previously, the O-H bonds of
substituted NHPI derivatives are strengthened by elec-
tron-withdrawing groups. Therefore, the H-atom abstrac-
tion ability of PINO• substituted by electron-withdrawing
groups would be higher than those of PINO• substituted
by electron-donating groups. To confirm this issue, we
measured rate constants for H-atom abstraction by
substituted PINO radicals from p-xylene and toluene.
The obtained rate constants are shown in Table 3 and
Table S2 (Supporting Information).
In both reactions, the reactivity of substituted PINO•
follows the order 4-Me < 4-H < 4-F < 4-Cl, which
corresponds to the order of the O-H bond dissociation
energies. The first three BDEs are known, and the
ordering of 4-Cl is inferred from the Hammett-based
inductive effect of this substituent.
Alternatively, the acceleration of the rate constants by
electron withdrawing groups might be explained by a
polar effect at the transition state.
q
kBT
h
∆Sf,r
∆Hfq
kobs
)
exp
exp -
[4-Me-NHPI] +
∆Hrq
(
)
(
)
R
RT
q
kBT
h
∆Sf,r
exp
exp -
[NHPI] (16)
(
)
(
)
R
RT
In this treatment, we set the activation entropies for
kf and kr equal to one another because each direction
should have almost the same activation entropy consid-
ering its structural symmetry. As a result, the activation
parameters obtained are ∆Hfq ) 40.8 ( 1.0 kJ mol-1, ∆Hrq
) 41.9 ( 1.0 kJ mol-1, ∆Sf,r ) -55 ( 3 J K-1 mol-1; an
q
Arrhenius plot of the same data gave log A ) 9.5. This
value of log A along with the KIE indicates that tunneling
occurs but not to the extent it does in certain other
reactions of PINO•.5,6 Using the obtained activation
enthalpies and activation entropy, we compared the
experimental data with the calculated values. The result
is illustrated in Figure 3, in which the points are
(21) Micro-Math Scientific Software, Inc., Salt Lake City, UT.
242 J. Org. Chem., Vol. 70, No. 1, 2005

Substituted Phthalimide N-Oxyl Radicals in Acetic Acid
because of the two electron donating methoxy groups.
And it is well-known that the C-H BDE of benzyl alcohol
is fairly low (340 kJ mol-1). Therefore, it is understand-
able that the largest KIE was obtained with 3,6-(CH3O)2-
NHPI which has the lowest O-H BDE in the series of
Annunziatini’s experiments, where the reaction with 3,6-
(CH3O)2-NHPI is more symmetric than others with
substituted NHPIs.
Further comments on tunneling are in order. In an
earlier publication, the large KIE values were attributed
to tunneling as the major or exclusive factor.5,6 Actually,
there is now cause to reassess that view. After allowance
for a secondary KIE of 1.15 per D atom in going from sp3
to sp2 hybridization,25 the primary KIE is reduced to 19.2
at 25 °C and only 5.23 at 55 °C, the latter being a normal
isotope effect. On that basis, the tunneling effect is ca.
27% at 17 °C and 7.2% at 55 °C.
A correlation between redox potentials of the 4-sub-
stituted NHPI derivatives and σp Hammett constants has
been reported.23 We constructed plots against σp, and
obtained the reaction constants, F ) 1.1 for p-xylene and
1.8 for toluene, Figure S4a,b (Supporting Information).
We also evaluated the KIE for the reactions with
p-xylene and toluene. It is noted that the values of KIE
for the reaction in the series of the PINO radicals lie in
the narrow range of 23.5-25.7. This finding further
supports that quantum mechanical tunneling plays a role
in the hydrogen abstraction of the PINO radicals. We
have reported that H-atom abstraction reaction by PINO•
has a maximum with toluene (27.1) or benzaldehyde
(27.5).6 It is expected that a maximum value for H-atom
abstraction reaction can be obtained when the reaction
is symmetric.24 Therefore, we expected that the maximum
of KIE would shift in the reaction of 4-substituted NHPI
derivatives which have different O-H BDEs. However,
the difference of BDE of NHPI derivatives is not large
enough to see the shift. Recently, Annunziatini et al.
investigated that aerobic oxidation of benzyl alcohol by
substituted NHPIs, and found that 3,6-(CH3O)2-NHPI
has the largest KIE (19.5).18 The O-H BDE of 3,6-
(CH3O)2-NHPI is 4 kJ mol-1 smaller than that of NHPI
Acknowledgment. This research was supported by
a grant from the National Science Foundation under
Grant No. CHE-020409. Some experiments were con-
ducted with the use of the facilities of the Ames
Laboratory of the U.S. Department of Energy, which is
operated by Iowa State University of Science and
Technology under Contract No. W-7405-Eng-82.
Supporting Information Available: UV/vis spectra of
the substituted PINO radical in HOAc and plots of kinetic data
to illustrate agreement to selected mathematical forms and
to evaluate numerical parameters. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO048418T
(22) Roth, J. P.; Yoder, J. C.; Won, T.-J.; Mayer, J. M. Science 2001,
294, 2524-2526.
(23) Gorgy, K.; Lepretre, J.-C.; Saint-Aman, E.; Einhorn, C.; Ein-
horn, J.; Marcadal, C.; Pierre, J.-L. Electrochim. Acta 1998, 44, 385-
393.
(25) We are grateful to Prof. A. A. Zavitsas for calling our attention
to these issues: Zavitsas, A. A.; Seltzer, S. J. Am. Chem. Soc. 1964,
86, 3836-40. See also: Zavitsas, A. A. J. Phys. Chem. A 2002, 106,
5041-5042. Zavitsas, A. A. J. Chem. Soc., Perkin Trans. 2 1998, 499-
502. Zavitsas, A. A. J. Am. Chem. Soc. 1998, 120, 6578-6586. Zavitsas,
A. A. J. Chem. Soc., Perkin Trans. 2 1996, 391-3. Zavitsas, A. A.;
Chatgilialoglu, C. J. Am. Chem. Soc. 1995, 117, 10645-54.
(24) Bell, R. P. The Tunnel Effect in Chemistry; Chapman and
Hall: London, 1980; b) Cleland, W. W.; O’Leary, M. H.; Northrop, D.
B. Isotope Effects on Enzyme-Catalyzed Reactions; University Park
Press: Baltimore, 1977.
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