Base-catalyzed C-H deprotonation of 4-methoxybenzyl alcohol radical cations in water: Evidence for a carbon-to-oxygen 1,2-H-shift mechanism

Full text of DOI:10.1021/ja970259q

4078
J. Am. Chem. Soc. 1997, 119, 4078-4079
age of the C-C bond according to eq 1. In contrast, the decay
of 2•+ leads to the R-hydroxybenzyl type radical 3• (λmax at 300
nm), Via cleavage of the C-H bond (eq 2). In agreement with
the pulse radiolysis results, steady state γ-irradiation of 1 and
2 gave 4-methoxybenzaldehyde and 4-methoxyacetophenone,
Base-Catalyzed C-H Deprotonation of
4-Methoxybenzyl Alcohol Radical Cations in
Water: Evidence for a Carbon-to-Oxygen
1,2-H-Shift Mechanism
respectively, the latter deriving from oxidation of 3•, in the
Enrico Baciocchi,*,1a Massimo Bietti,1b and
Steen Steenken*,1b
2- 5
presence of S2O8
.
The rate constants of reactions 1 and 2 in water, measured
by the decrease of the 450 nm absorption of the radical cation,6
turned out to be 1.8 × 105 and 3.7 × 104 s-1, respectively; i.e.,
the C-C bond cleavage (of 1•+) is ca. 5 times faster than the
deprotonation reaction (of 2•+). With both 1•+ and 2•+, the
decay rates were found to increase in the presence of OH-
(Figure 1), whereby the rate constants for the OH--catalyzed
process are almost identical (k ≈ 5 × 109 M-1 s-1) for the two
radical cations. At first sight, this is a very surprising result in
view of the fact that with 1•+ the base catalysis can only involve
the O-H bond whereas with 2•+ the C-H bond is expected to
be involved.
Dipartimento di Chimica, UniVersita´ La Sapienza
Piazzale A. Moro 5, I-00185 Roma, Italy
Max-Planck-Institut fu¨r Strahlenchemie
D-45413 Mu¨lheim, Germany
ReceiVed January 27, 1997
Fragmentation reactions of radical cations, and particularly
those involving C-H and C-C bond cleavage, are attracting
continuous interest due to their many practical and theoretical
implications.2 In this research area, we recently reported that,
in aqueous solution, the cleavage of a C-C bond in alkyl-
aromatic radical cations is assisted by the presence of an R-OH
group.3 Base catalysis was observed, and a hydrogen-bonded
transition state was suggested. In an effort to throw more light
on this phenomenon, we have now discovered that an R-OH
group can assist as well the cleavage of a C-H bond (C-H
deprotonation). The results of our study, which permit more
general conclusions to be drawn on the nature of the R-OH
group assistance in fragmentation reactions of radical cations,
are presented herewith.
To gain further information on this phenomenon, we also
studied the radical cations 4•+ and 5•+, where the only possible
fragmentation reaction is C-H deprotonation, as described in
eqs 3 and 4 and as experimentally observed.7
The starting point was the similar effect of OH- on the
fragmentation reactions of the radical cations 1•+ and 2•+, the
former of which involves the cleavage of the C-C bond (eq 1,
B symbolizes a base) and the latter one, however, that of the
C-H bond (eq 2).
The kinetic study of these reactions showed that in the
absence of NaOH the rate of deprotonation of 4•+ (7.5 × 104
s-1) is similar to that of 5•+ (1.0 × 105 s-1), as expected since
the OH and OMe R-substituents should exhibit very similar
electronic effects. However, the OH--catalyzed reaction is
drastically different for the two compounds as clearly visible
from the slopes of the corresponding plots in Figure 1. The
OH--catalyzed deprotonation of 4•+ (squares) is 27 times faster
than that of 5•+ (triangles) (5.4 × 109 Vs 2.0 × 108 M-1 s-1),
although with 4•+ and 5•+ the same bond is (finally) broken.
Even more interestingly, the second-order rate constant for the
OH--catalyzed decay of 4•+ is almost identical with those for
the case of 1•+ and 2•+, as indicated above. These values (5 ×
109 M-1 s-1) are characteristic for reaction of OH- with protons
bonded to a heteroatom such as oxygen.8 The kinetic isotope
effect was also studied, using 4-MeOC6H4-CD2OH and
-CD2OMe instead of 4 and 5. With the radical cation from
the alcohol (-CD2OH), the rate constant for reaction with OH-
was 5.3 × 109 M-1 s-1, i.e., the same as that from the
The two radical cations were generated in H2O from 1 or 2
using SO4•-, and their reactions were studied by the pulse
radiolysis technique, as previously described.3 Both radical
cations showed the characteristic absorption bands centered
around 290 and 450 nm.4 It was observed that 1•+ decayed to
form 4-methoxybenzaldehyde (absorption at 285 nm) by cleav-
(1) (a) Universita´ La Sapienza. (b) Max-Planck-Institut.
(2) For some of the most recent papers on the subject see: Anne, A.;
Fraoua, S.; Moiroux, J.; Save´ant, J.-M. J. Am. Chem. Soc. 1996, 118, 3938-
3945. Gaillard, E. R.; Whitten, D. G. Acc. Chem. Res. 1996, 29, 292-297.
Burton, R. D.; Bartberger, M. D.; Zhang, Y.; Eyler, J. R.; Schanze, K. S.
J. Am. Chem. Soc. 1996, 118, 5655-5664. Maslak, P.; Chapman, W. H.
Jr. J. Org. Chem. 1996, 61, 2647-2656. de Lijser, H. J. P.; Arnold, D. R.
J. Phys. Chem. 1996, 100, 3996-4010. Anne, A.; Fraoua, S.; Hapiot, P.;
Moiroux, J.; Save´ant, J.-M. J. Am. Chem. Soc. 1995, 117, 7412-7421.
Maslak, P.; Chapman, W. H. Jr.; Vallombroso, T. M. Jr.; Watson, B. A. J.
Am. Chem. Soc. 1995, 117, 12380-12389. Baciocchi, E.; Del Giacco, T.;
Elisei, F. J. Am. Chem. Soc. 1993, 115, 12290-12295. Anne, A.; Hapiot,
P.; Moiroux, J.; Neta, P.; Save´ant, J.-M. J. Am. Chem. Soc. 1992, 114,
4694-4700. Steenken, S.; McClelland, R. A. J. Am. Chem. Soc. 1989, 111,
4967-4973.
(5) Irradiations were carried out on argon-saturated aqueous solutions
containing the substrate, K2S2O8 (substrate/oxidant ratio g2), and 0.2 M
2-methyl-2-propanol at room temperature, using a 60Co γ-source at dose
rates of 0.3-0.9 Gy s-1, for the time necessary to obtain a 40% conversion
with respect to peroxydisulfate. Products were identified and quantitatively
determined by HPLC (comparison with authentic samples).
(6) Experiments were carried out at 25 °C by pulse-irradiating argon-
saturated aqueous solutions containing the substrate, peroxydisulfate, and
2-methyl-2-propanol. For the kinetic study of the radical cation decay, the
ionic strength of the solution was buffered with 0.5 M Na2SO4, and 1 mM
Na2HPO4 was added to avoid undesired pH changes upon irradiation. The
decay followed first-order kinetics. Second-order rate constants for the base-
induced process were obtained from the slope of the plots of kobs Vs [NaOH].
(7) The two radical cations were generated from 4 and 5, respectively,
and their decay kinetically studied as described in ref 6. In both cases, the
decay of the radical cation, monitored at 450 nm, produced the correspond-
ing carbon-centered radical (absorption at about 300 nm), as described in
eqs 3 and 4.
(3) Baciocchi, E.; Bietti, M.; Putignani, L.; Steenken, S. J. Am. Chem.
Soc. 1996, 118, 5952-5960.
(4) O’Neill, P.; Steenken, S.; Schulte-Frohlinde, D. J. Phys. Chem. 1975,
79, 2773-2779.
(8) Eigen, M. Angew. Chem. 1963, 75, 489-508.
S0002-7863(97)00259-X CCC: $14.00 © 1997 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 119, No. 17, 1997 4079
the â-fragmentation reaction, so it is not surprising that no
spectral evidence was found for the presence of the benzyloxyl
radical (λmax around 560 nm).12
The mechanism discussed above nicely accounts for the
experimental facts, particularly the kinetic isotope effect data,
presented in this paper. In this case it is perfectly understandable
that the rate constants for catalysis concerning the radical cations
1•+, 2•+, and 4•+ and its deuterated analogue are practically the
same: accordingly, very similar pKa and intramolecular electron
transfer energies are foreseeable for these species.13
Figure 1. Effect of [OH-] on the rate of decay of 1•+ (open circles),
2•+ (full circles), 4•+ (squares), and 5•+ (triangles).
Possibly, the mechanism of Scheme 1 holds only for reactions
with OH- (or bases of similar or greater strength); different
mechanisms might operate with weaker bases. For example,
in water, C-C bond cleavage in 1•+ might be assisted by
hydrogen bond formation as previously suggested,3 without
involving complete OH deprotonation. For 2•+ and 4•+ in the
absence of OH-, direct attack to the C-H bond might occur,
in agreement with the observation that, under these conditions,
2•+ and 4•+ decay with a rate similar to that of 5•+, whose
deprotonation can only involve the cleavage of the C-H bond.14
On the other hand, in an alkylaromatic radical cation, the kinetic
acidity of a â-C-H bond is expected to be significantly higher
than that of a γ-O-H bond since only the former bond can
interact with the SOMO of the radical cation which resides on
the aromatic ring. Thus, it is reasonable that, in the presence
of so weak a base as water, the deprotonation of the radical
cation mainly involves the C-H bond. In the presence of the
strong base OH-, however, OH deprotonation becomes pre-
dominant and the mechanism changes to that of Scheme 1.
Scheme 1
nondeuterated compound, which means that k(H)/k(D) ) 1.0,
whereas for the ether (-CD2OMe), k(H)/k(D) was determined
to be 1.8.
In conclusion, we have presented data indicating that the
OH--induced deprotonation of R-hydroxy-substituted alkyl-
aromatic radical cations in water to form the corresponding
carbon radical does not involve the direct attack of the base at
the C-H bond, as generally believed. We suggest that in the
first step the base deprotonates the R-OH bond to produce a
benzyloxyl radical, either directly or via a radical zwitterion
which then undergoes an intramolecular (side chain to nucleus)
electron transfer. The resulting benzyloxyl radical is then
converted into the carbon radical by a 1,2-hydrogen atom shift,
this reaction constituting the R-deprotonation.
These observations clearly indicate that the OH--catalyzed
decays of the radical cations 1•+, 2•+, and 4•+, all of which bear
an OH group on the R-carbon, have a fundamental mechanistic
feature in common, independent of whether C-C or C-H bond
cleavage eventually occurs. It is reasonable to assume and
supported by the high rate constant of 5 × 109 M-1 s-1 that
this common mechanistic feature involves the interaction of the
base with the R-OH group, as detailed in Scheme 1.
The first step is deprotonation at the OH group, leading to a
radical zwitterion (step a). In the second step the radical
zwitterion undergoes an intramolecular electron transfer, forming
a benzyloxyl radical (step b), analogous to that for the
intramolecular electron transfer converting a 4-methoxybenzoate
radical zwitterion into a benzoyloxyl radical.9 The reorganiza-
tion energy needed for this process could be quite high. An
alternative is that the conversion of the radical cation into the
benzyloxyl radical takes place in a single step. In other words,
deprotonation and intramolecular electron transfer may be
concerted (step c).
The fate of the benzyloxyl radical depends on the nature of
R, as illustrated in Scheme 1. When, as in 1•+ (R ) tBu), R
can give rise to a stabilized carbon radical such as tBu•, a
â-fragmentation reaction follows, and 4-methoxybenzaldehyde
is formed.10 This pathway is energetically less feasible when
R is H or Me, (4•+ and 2•+). In these cases we suggest that the
benzyloxyl radical is converted into the observed R-hydroxy
carbon radical Via a 1,2-hydrogen atom shift, a process which
is well documented for alkoxyl radicals in aqueous solution.11
Such a shift is expected to be very fast, and the same holds for
Acknowledgment. The contribution of the European Union (Con-
tract CEE ERBSC1-CT91-0750) is gratefully acknowledged. E.B.
thanks the Italian Ministry for University and Technological Research
(MURST) and the Consiglio Nazionale delle Ricerche (CNR) for
financial support. M.B. thanks the CNR for a short-term research
fellowship.
JA970259Q
(11) Gilbert, B. C.; Laue, H. A. H.; Norman, R. O. C.; Sealy, R. C. J.
Chem. Soc., Perkin Trans. 2 1976, 1040-1044. Dobbs, A. J.; Gilbert, B.
C.; Laue, H. A. H.; Norman, R. O. C. J. Chem. Soc., Perkin Trans. 2 1976,
1044-1047. Gilbert, B. C.; Holmes, R. G. G.; Laue, H. A. H.; Norman, R.
O. C. J. Chem. Soc., Perkin Trans. 2 1976, 1047-1052. The 1,2-H shift
can also be promoted by alcoholic solvents; see: Elford, P. E.; Roberts, B.
P. J. Chem. Soc., Perkin Trans. 2 1996, 2247-2256.
(12) Avila, D. V.; Ingold, K. U.; Di Nardo, A. A.; Zerbetto, F.; Zgierski,
M. Z.; Lusztyk, J. J. Am. Chem. Soc. 1995, 117, 2711-2718.
(13) It is evident that the observed catalytic effect of OH- (taking into
account that the k value of 5 × 109 M-1 s-1 indicates interaction with the
OH group) cannot be explained solely on the basis of the formation of a
zwitterion (i.e., without intramolecular electron transfer occurring, giving
the benzyloxyl radical) which then undergoes (2•+ and 4•+) C-H bond
cleavage, since the conversion of the OH function into the less electron-
withdrawing O- function would decrease the acidity of the radical cation,
leading to a negatiVe catalytic effect, in contrast to the experimental
observation.
(9) Ashworth, B.; Gilbert, B. C.; Holmes, R. G. G.; Norman, R. O. C.
J. Chem. Soc., Perkin Trans. 2 1978, 951-956.
(10) Ingold, K. U. In Free Radicals, Kochi, J. K., Ed.; Wiley: New
York, 1973; Vol. 1, pp 99-102.
(14) It should be noted that, for this comparison, the values reported in
the text for 4•+ and 5•+ have to be divided by 2 (statistical correction).