One-electron oxidation of 2-(4-methoxyphenyl)-2-methylpropanoic and 1-(4-methoxyphenyl)cyclopropanecarboxylic acids in aqueous solution. The involvement of radical cations and the influence of structural effects and pH on the side-chain fragmentation reactivity

Article abstract of DOI:10.1021/jo702104j

(Chemical Equation Presented) A product and time-resolved kinetic study on the one-electron oxidation of 2-(4-methoxyphenyl)-2-methylpropanoic acid (2), 1-(4-methoxyphenyl)cyclopropanecarboxylic acid (3), and of the corresponding methyl esters (substrates 4 and 5, respectively) has been carried out in aqueous solution. With 2, no direct evidence for the formation of an intermediate radical cation 2^?+ but only of the decarboxylated 4-methoxycumyl radical has been obtained, indicating either that 2^?+ is not formed or that its decarboxylation is too fast to allow detection under the experimental conditions employed (k > 1 × 10⁷ s ^-1). With 3, oxidation leads to the formation of the corresponding radical cation 3^?+ or radical zwitterion ^-3 ^?+ depending on pH. At pH 1.0 and 6.7, 3^?+ and ^-3^?+ have been observed to undergo decarboxylation as the exclusive side-chain fragmentation pathway with rate constants k = 4.6 × 10³ and 2.3 × 10⁴ s^-1, respectively. With methyl esters 4 and 5, direct evidence for the formation of the corresponding radical cations 4^?+ and 5^?+ has been obtained. Both radical cations have been observed to display a very low reactivity and an upper limit for their decay rate constants has been determined as k < 10³ s^-1. Comparison between the one-electron oxidation reactions of 2 and 3 shows that the replacement of the C(CH₃)₂ moiety with a cyclopropyl group determines a decrease in decarboxylation rate constant of more than 3 orders of magnitude. This large difference in reactivity has been qualitatively explained in terms of three main contributions: substrate oxidation potential, stability of the carbon-centered radical formed after decarboxylation, and stereoelectronic effects. In basic solution, ^-3^?+ and 5 ^?+ have been observed to react with ^-OH in a process that is assigned to the ^-OH-induced ring-opening of the cyclopropane ring, and the corresponding second-order rate constants (k_-OH) have been obtained. With ^-3^?+, competition between decarboxylation and ^-OH-induced cyclopropane ring-opening is observed at pH ≥ 10, with the latter process that becomes the major fragmentation pathway around pH 12.

Full text of DOI:10.1021/jo702104j

One-Electron Oxidation of 2-(4-Methoxyphenyl)-2-Methylpropanoic
and 1-(4-Methoxyphenyl)cyclopropanecarboxylic Acids in Aqueous
Solution. The Involvement of Radical Cations and the Influence of
Structural Effects and pH on the Side-Chain Fragmentation
Reactivity
Massimo Bietti* and Alberto Capone
Dipartimento di Scienze e Tecnologie Chimiche, UniVersita` “Tor Vergata”, Via della Ricerca
Scientifica 1, I-00133 Rome, Italy
bietti@uniroma2.it
ReceiVed September 26, 2007
A product and time-resolved kinetic study on the one-electron oxidation of 2-(4-methoxyphenyl)-2-
methylpropanoic acid (2), 1-(4-methoxyphenyl)cyclopropanecarboxylic acid (3), and of the corresponding
methyl esters (substrates 4 and 5, respectively) has been carried out in aqueous solution. With 2, no
direct evidence for the formation of an intermediate radical cation 2•+ but only of the decarboxylated
4-methoxycumyl radical has been obtained, indicating either that 2•+ is not formed or that its
decarboxylation is too fast to allow detection under the experimental conditions employed (k > 1 × 107
s-1). With 3, oxidation leads to the formation of the corresponding radical cation 3•+ or radical zwitterion
-3•+ depending on pH. At pH 1.0 and 6.7, 3•+ and -3•+ have been observed to undergo decarboxylation
as the exclusive side-chain fragmentation pathway with rate constants k ) 4.6 × 103 and 2.3 × 104 s-1,
respectively. With methyl esters 4 and 5, direct evidence for the formation of the corresponding radical
cations 4•+ and 5•+ has been obtained. Both radical cations have been observed to display a very low
reactivity and an upper limit for their decay rate constants has been determined as k < 103 s-1. Comparison
between the one-electron oxidation reactions of 2 and 3 shows that the replacement of the C(CH3)2 moiety
with a cyclopropyl group determines a decrease in decarboxylation rate constant of more than 3 orders
of magnitude. This large difference in reactivity has been qualitatively explained in terms of three main
contributions: substrate oxidation potential, stability of the carbon-centered radical formed after
decarboxylation, and stereoelectronic effects. In basic solution, -3•+ and 5•+ have been observed to react
-
-
with OH in a process that is assigned to the OH-induced ring-opening of the cyclopropane ring, and
the corresponding second-order rate constants (k OH) have been obtained. With -3•+, competition between
-
decarboxylation and -OH-induced cyclopropane ring-opening is observed at pH g10, with the latter
process that becomes the major fragmentation pathway around pH 12.
Introduction
takes part in several chemical and biological processes,6 and is
involved in particular in important processes such as the
initiation of free radical polymerization7 and the enhancement
in the efficiency of silver halide photography (two-electron
sensitization (TES)).8,9 In the latter process, the decarboxylation
of radical zwitterions derived from relatively electron rich
arylethanoic acids such as 4-dimethylaminophenylethanoic acid,
The decarboxylation of organic radical cations is an important
reaction that has attracted considerable interest.1-5 This reaction
(1) (a) Baciocchi, E.; Del Giacco, T.; Elisei, F.; Lapi, A. J. Org. Chem.
2006, 71, 853-860. (b) Baciocchi, E.; Bietti, M.; Lanzalunga, O. J. Phys.
Org. Chem. 2006, 19, 467-478.
10.1021/jo702104j CCC: $40.75 © 2008 American Chemical Society
Published on Web 12/13/2007
618
J. Org. Chem. 2008, 73, 618-629

Oxidation of Propanoic and Cyclopropanecarboxylic Acids
SCHEME 1
SCHEME 2
its R-methyl and R-hydroxy-R-methyl derivatives, and 2,4,5-
trimethoxymandelic acid proved to be one of the most useful
reactions (Scheme 1).
Control over the decarboxylation rate constant of the inter-
mediate radical cation (or radical zwitterion) represents a key
issue for the development of these processes, and accordingly
studies aimed at the quantification of the factors that govern
this fragmentation are particularly important.
However, even though a large number of studies on the
generation and reactivity of arylalkanoic acid radical cations
have been carried out,10-21 several mechanistic aspects of these
processes are still not fully clarified. A variety of alternative
mechanistic pathways for the one-electron decarboxylative
oxidation of arylethanoic acids are described in Scheme 2.
A point that has attracted considerable attention has been that
of establishing the actual role of intermediate radical cations.
In this respect, the generally accepted mechanism for the one-
electron oxidation of arylethanoic acids involves the formation
of an aromatic radical cation (or radical zwitterion) that then
undergoes decarboxylation to give the corresponding benzyl
radical (Scheme 2, path a). However, in aqueous solution direct
evidence in this respect has been obtained only in the oxidation
of relatively electron rich substrates such as 4-dimethylami-
nophenylethanoic acid, its R-methyl and R-hydroxy-R-methyl
derivatives, 2,4,5-trimethoxymandelic acid,9 ring-dimethoxylated
phenylethanoic acids,11 and 1-naphthylethanoic acid.14a Along
this line, it cannot be excluded that the one-electron oxidation
of arylethanoic acids, characterized by higher oxidation poten-
tials, occurs following pathways b or c, i.e. bypassing radical
cation formation, as suggested recently for the one-electron
oxidation of 4-methoxyphenylethanoic acid (1).12
Moreover, also the nature of the conversion of the intermedi-
ate radical cation (or radical zwitterion) into the decarboxylated
benzyl radical has attracted considerable interest,3,13,22 since
intramolecular electron transfer (from the side-chain to the
aromatic π-system) in the radical cation (or radical zwitterion)
can be coupled to or followed by bond cleavage: in other words
decarboxylation can occur directly from the radical cation (or
radical zwitterion) or from an intermediate arylacetoxyl radical.
An additional point of interest is represented by the stability
of the decarboxylated benzyl radical, which is expected to
influence the decarboxylation rate constant.3
Along this line, in view of the importance of these processes
and in order to obtain a deeper understanding on the role of
structural effects on the one-electron oxidation of arylethanoic
acids and in particular on the possible involvement of aromatic
radical cations, we have carried out a product and time-resolved
kinetic study at different pH values on the one-electron oxidation
of 2-(4-methoxyphenyl)-2-methyl propanoic acid (2) and 1-(4-
methoxyphenyl)cyclopropanecarboxylic acid (3), two structur-
ally related substrates derived from the side-chain modification
of 4-methoxyphenylethanoic acid (1), whose structures are
displayed in Chart 1. To obtain additional information, we have
also studied the one-electron oxidation of the methyl esters of
acids 2 and 3 (substrates 4 and 5, respectively), and of 1-(4-
methoxyphenyl)cyclopropanol (6).
(2) (a) Filipiak, P.; Bartoszewicz, J.; Hug, G. L.; Kozubek, H.; Pacz-
kowski, J.; Marciniak, B. J. Photochem. Photobiol. A: Chem. 2007, 191,
167-175. (b) Filipiak, P.; Hug, G. L.; Bobrowski, K.; Marciniak, B. J.
Photochem. Photobiol. A: Chem. 2005, 172, 322-330. (c) Filipiak, P.; Hug,
G. L.; Carmichael, I.; Korzeniowska-Sobczuk, A.; Bobrowski, K.; Mar-
ciniak, B. J. Phys. Chem. A 2004, 108, 6503-6512.
(3) Gould, I. R.; Lenhard, J. R.; Farid, S. J. Phys. Chem. A 2004, 108,
10949-10956.
(4) (a) Su, Z.; Mariano, P. S.; Falvey, D. E.; Yoon, U. C.; Oh, S. W. J.
Am. Chem. Soc. 1998, 120, 10676-10686. (b) Su, Z.; Falvey, D. E.; Yoon,
U. C.; Mariano, P. S. J. Am. Chem. Soc. 1997, 119, 5261-5262.
(5) (a) Mehta, L. K.; Porssa, M.; Parrick, J.; Candeias, L. P.; Wardman,
P. J. Chem. Soc., Perkin Trans. 2 1997, 1487-1491. (b) Candeias, L. P.;
Folkes, L. K.; Dennis, M. F.; Patel, K. B.; Everett, S. A.; Stratford, M. R.
L.; Wardman, P. J. Phys. Chem. 1994, 98, 10131-10137.
(6) See for example: (a) Cleland, W. W. Acc. Chem. Res. 1999, 32,
862-868. (b) Silverman, R. B. Acc. Chem. Res. 1995, 28, 335-342. (c)
Budac, D.; Wan, P. J. Photochem. Photobiol. A: Chem. 1992, 67, 135-
166. (d) Kraeutler, B.; Jaeger, C. D.; Bard, A. J. J. Am. Chem. Soc. 1978,
100, 4903-4905.
(7) Wrzyszczyn´ski, A.; Filipiak, P.; Hug, G. L.; Marciniak, B.; Pacz-
kowski, J. Macromolecules 2000, 33, 1577-1582.
(8) Gould, I. R.; Lenhard, J. R.; Muenter, A. A.; Godleski, S. A.; Farid,
S. Pure Appl. Chem. 2001, 73, 455-458.
(9) Gould, I. R.; Lenhard, J. R.; Muenter, A. A.; Godleski, S. A.; Farid,
S. J. Am. Chem. Soc. 2000, 122, 11934-11943.
(10) Warzecha, K.-D.; Go¨rner, H.; Griesbeck, A. G. J. Phys. Chem. A
2006, 110, 3356-3363.
(11) Bietti, M.; Capone, A. J. Org. Chem. 2004, 69, 482-486.
(12) Baciocchi, E.; Bietti, M. J. Chem. Soc., Perkin Trans. 2 2002, 720-
722.
(13) Bockman, T. M.; Hubig, S. M.; Kochi, J. K. J. Org. Chem. 1997,
62, 2210-2221.
(14) (a) Steenken, S.; Warren, C. J.; Gilbert, B. C. J. Chem. Soc., Perkin
Trans. 2 1990, 335-342. (b) Gilbert, B. C.; Scarratt, C. J.; Thomas, C. B.;
Young, J. J. Chem. Soc., Perkin Trans. 2 1987, 371-380. (c) Davies, M.
J.; Gilbert, B. C.; McCleland, C. W.; Thomas, C. B.; Young, J. J. Chem.
Soc., Chem. Commun. 1984, 966-967.
CHART 1
(15) Maki, Y.; Sako, M.; Oyabu, I.; Murase, T.; Kitade, Y.; Hirota, K.
J. Chem. Soc., Chem. Commun. 1989, 1780-1782.
(16) (a) Walling, C.; El-Taliawi, G. M.; Amarnath, K. J. Am. Chem.
Soc. 1984, 106, 7573-7578. (b) Walling, C.; Camaioni, D. M. J. Org. Chem.
1978, 43, 3266-3271.
(17) (a) Jo¨nsson, L. Acta Chem. Scand. 1983, B37, 761-768. (b) Jo¨nsson,
L. Acta Chem. Scand. 1981, B35, 683-689.
(18) Taylor, E. C.; Andrade, J. G.; Rall, G. J. H.; Turchi, I. J.; Steliou,
K.; Jagdmann, G. E., Jr.; McKillop, A. J. Am. Chem. Soc. 1981, 103, 6856-
6863.
Results
(19) (a) Giordano, C.; Belli, A.; Citterio, A.; Minisci, F. J. Chem. Soc.,
Perkin Trans. 1 1981, 1574-1576. (b) Giordano, C.; Belli, A.; Citterio, A.
J. Org. Chem. 1980, 45, 345-346.
(20) Dessau, R. M.; Heiba, E. I. J. Org. Chem. 1975, 40, 3647-3649.
(21) Trahanovsky, W. S.; Cramer, J.; Brixius, D. W. J. Am. Chem. Soc.
1974, 96, 1077-1081.
Spectral Properties. Argon- or nitrogen-saturated aqueous
solutions of substrates 2-6 (0.5-2 mM) were photolyzed in
(22) Andrieux, C. P.; Gonzalez, F.; Save´ant, J.-M. J. Electroanal. Chem.
2001, 498, 171-180.
J. Org. Chem, Vol. 73, No. 2, 2008 619

Bietti and Capone
FIGURE 2. Time-resolved absorption spectrum observed after 266
nm LFP of a nitrogen-saturated aqueous solution (T ) 25 °C, pH 7.0)
containing 0.1 M K2S2O8 and 0.2 mM methyl 2-(4-methoxyphenyl)-
2-methylpropanoate (4), recorded 2.1 µs after the 8 ns, 10 mJ laser
flash.
FIGURE 1. Time-resolved absorption spectra observed after 266 nm
LFP of a nitrogen-saturated aqueous solution (T ) 25 °C, pH 1.7)
containing 0.1 M K2S2O8 and 2 mM 2-(4-methoxyphenyl)-2-methyl
propanoic acid (2), recorded at 37 (filled circles), 60 (empty circles),
140 (filled squares), and 300 ns (empty squares) after the 8 ns, 10 mJ
laser flash. Insets: (a) Time-resolved absorption spectrum observed
after 266 nm LFP of a nitrogen-saturated aqueous solution (T )
25 °C, pH 1.7) containing 0.1 M K2S2O8 recorded 90 ns after the 8 ns,
10 mJ laser flash. (b) First-order decay of absorption monitored at 450
nm. (c) Corresponding first-order buildup of absorption monitored at
290 nm, measured under argon (filled circles) and oxygen (empty
circles).
Figure 1 displays the time-resolved absorption spectra
observed after LFP of a nitrogen-saturated aqueous solution (pH
1.7) containing 2-(4-methoxyphenyl)-2-methylpropanoic acid (2)
(2.0 mM) and K2S2O8 (0.1 M).
The spectrum recorded 37 ns after the laser flash (filled
circles) shows the formation of a broad absorption band between
350 and 510 nm, characterized by a maximum at 450 nm, that,
by comparison with literature data,14a,27 and with the time-
resolved absorption spectrum of SO4•-, obtained after 266 nm
the presence of 0.1 M K2S2O8 at pH e2 and pH ∼7, employing
266 nm laser flash photolysis (LFP). Under these conditions
SO4 is formed (eq 1).14a
•-
LFP of a nitrogen-saturated aqueous solution (pH 1.7) containing
•-
0.1 M K2S2O8 (inset a), can be reasonably assigned to SO4
,
S2O82- 9hv8 2SO4
(1)
formed as described in eq 1. The decay of this band (inset b)
-•
occurs with kV(450 nm) ) 1.0 × 107 s-1 and is accompanied
by the formation of a species (kv(290 nm) ) 1.1 × 107 s-1
)
Alternatively, SO4•- was generated by pulse radiolysis (PR) of
argon-saturated aqueous solutions containing substrates 2-6
(0.2-2 mM), K2S2O8 (10 mM), and 2-methyl-2-propanol (0.1
M), according to eqs 2-4.
characterized by an absorption band in the UV region of the
spectrum extending from <290 to 340 nm (an isosbestic point
is visible at 330 nm), whose decay is accelerated by the presence
of oxygen (inset c), and in an oxygen-saturated solution occurs
with an observed rate constant kobs ) 2.2 × 106 s-1. Given that
H2O ' H+, •OH, eaq
(2)
(3)
-
the solubility of oxygen in water is reported as 1.27 × 10-3
M
at T ) 25 °C,28 a second-order rate constant for reaction of this
transient species with oxygen can be derived as k ) 1.7 × 109
•OH + CH3C(CH3)2OH f H2O + •CH2C(CH3)2OH
M-1 s-1
.
The time-resolved absorption spectrum observed after 266
nm LFP of a nitrogen-saturated aqueous solution (pH 7.0)
containing 0.1 M K2S2O8 and 0.2 mM methyl 2-(4-methox-
yphenyl)-2-methylpropanoate (4) is shown in Figure 2. Visible
are two bands, centered at 290 and 450 nm, that are very similar
to those observed previously for the radical cations of 4-meth-
oxyalkylbenzenes and 1-(4-methoxyphenyl)alkanols.24,29-31 An
identical spectrum was also obtained after PR of an argon-
saturated aqueous solution (pH 7.0) containing 10 mM K2S2O8,
0.2 mM 4, and 0.1 M 2-methyl-2-propanol. On the basis of
these observations, this species can be reasonably assigned to
the radical cation 4•+, formed by SO4•--induced one-electron
oxidation of the neutral substrate 4 as described in Scheme 3.
•-
eaq- + S2O82- f SO42- + SO4
(4)
Radiolysis of water leads to the formation of the hydroxyl
radical (•OH) and the hydrated electron (eaq-) (eq 2). The former
is scavenged by 2-methyl-2-propanol (eq 3; k ) 6 × 108 M-1
s-1),23 while eaq reacts with S2O8 leading to the formation
-
2-
of SO4 (eq 4; k ) 1.2 × 1010 M-1 s-1).23 SO4 is a strong
oxidant that is known to react with ring-methoxylated aromatic
substrates via electron transfer to yield the corresponding radical
cations with k g 5 × 109 M-1 s-1 (eq 5).24-26
•-
•-
SO4•- + ArR f SO4 - + •+ArR
(5)
2
(27) Yu, X.-Y.; Bao, Z.-C.; Barker, J. R. J. Phys. Chem. A 2004, 108,
295-308.
(28) Murov, S. L.; Carmichael, I.; Hug, G. L. Handbook of Photochem-
istry, 2nd ed.; Marcel Dekker: New York, 1993.
(29) Baciocchi, E.; Bietti, M.; Ercolani, G.; Steenken, S. Tetrahedron
2003, 59, 613-618.
(30) Baciocchi, E.; Bietti, M.; Steenken, S. Chem. Eur. J. 1999, 5, 1785-
1793.
(31) Baciocchi, E.; Bietti, M.; Manduchi, L.; Steenken, S. J. Am. Chem.
Soc. 1999, 121, 6624-6629.
(23) Buxton, G. V.; Greenstock, C. L.; Helman, W. P.; Ross, A. B. J.
Phys. Chem. Ref. Data 1988, 17, 513-886.
(24) Baciocchi, E.; Bietti, M.; Putignani, L.; Steenken, S. J. Am. Chem.
Soc. 1996, 118, 5952-5960.
(25) Neta, P.; Madhavan, V.; Zemel, H.; Fessenden, R. W. J. Am. Chem.
Soc. 1977, 99, 163-164.
(26) O’ Neill, P.; Steenken, S.; Schulte-Frohlinde, D. J. Phys. Chem.
1975, 79, 2773-2779.
620 J. Org. Chem., Vol. 73, No. 2, 2008

Oxidation of Propanoic and Cyclopropanecarboxylic Acids
SCHEME 3
SCHEME 4
FIGURE 3. Time-resolved absorption spectra observed on reaction
of SO4•- with 3 (0.5 mM) recorded after PR of argon-saturated aqueous
solutions at pH 1.7 (filled circles) and 7.1 (empty circles), containing
0.1 M 2-methyl-2-propanol and 10 mM K2S2O8, 2 µs after the 300 ns,
10 MeV electron pulse.
The time-resolved absorption spectrum observed after PR of
an argon-saturated aqueous solution containing 1-(4-methox-
yphenyl)cyclopropanecarboxylic acid (3) (0.5 mM), K2S2O8 (10
mM), and 2-methyl-2-propanol (0.1 M) at pH 1.7 (filled circles)
displayed in Figure 2 shows UV and visible absorption bands
centered at 320 and 500 nm whose decay is not affected by the
presence of oxygen. An analogous spectrum was observed after
LFP of an argon-saturated aqueous solution (pH 1.7) containing
3 (1 mM) and K2S2O8 (0.1 M) (see the Supporting Information
(SI), Figure S1).
A similar spectrum, characterized by UV and visible absorp-
tion bands centered at 300 and 500 nm, was also observed after
PR of an argon-saturated aqueous solution (pH 4.0) containing
methyl 1-(4-methoxyphenyl)cyclopropanecarboxylate (5) (0.2
mM), K2S2O8 (10 mM), and 2-methyl-2-propanol (0.1 M) (see
SI, Figure S2).
It is well-known that in organic media arylcyclopropane
radical cations are characterized by an absorption band in the
visible region of the spectrum centered between 510 and 580
nm depending on the nature of the aromatic ring substituent.32,33
Along this line, the UV and visible absorption bands described
above for the transients observed in the oxidation reactions of
substrates 3 and 5 can be reasonably assigned to the radical
cations 3•+ and 5•+, formed by one-electron oxidation of the
neutral substrates as described in Scheme 4.
By increasing the pH of the solution to ∼7, the spectrum
obtained after SO4•--induced one-electron oxidation of 3 was
similar to that obtained in acidic solution. However, as described
previously for ring-methoxylated phenylalkanoic acid radical
cations,11,34 a broadening of the radical cation visible absorption
band, accompanied by a 20 nm red-shift in its position was
observed (Figure 3, empty circles). This behavior is attributed
to the formation of the radical zwitterion -3•+ as described in
Scheme 5.35 Quite importantly, no significant spectral variation
was instead observed for 5•+ between pH 4 and 10.
SCHEME 5
0.1 M 2-methyl-2-propanol, and 10 mM K2S2O8 did not provide
evidence for the formation of an intermediate radical cation,
showing instead the fast formation of a product absorbing at λ
< 370 nm, a result that suggests that 6•+ is either not formed
under these conditions or that its rate of decay exceeds the time
resolution of the PR equipment employed. Unfortunately, 266
nm LFP experiments carried out on 6 showed the formation of
transient species derived from the direct photochemistry of the
substrate and no further LFP investigation was carried out.
Product Studies. The one-electron oxidation reactions of
substrates 2-6 were carried out in argon-saturated aqueous
•-
solution (pH 1.0 or 6.7) at T ) 25 or 50 °C, employing SO4
(generated by steady-state photolysis as described in eq 1) and/
or potassium 12-tungstocobalt(III)ate (from now on simply
indicated as Co(III)W) as the oxidant. Co(III)W is a well-known
one-electron oxidant able to convert ring-methoxylated aromatic
substrates into the corresponding radical cations via outer-sphere
electron transfer.36-38 The Co(III)W-induced oxidations were
generally carried out until complete conversion of the oxidant.
In the SO4•--induced oxidations, irradiation times were generally
chosen in such a way as to avoid complete substrate consump-
tion. After workup, the reaction mixtures were analyzed by GC,
GC-MS, and 1H NMR, and the reaction products were generally
identified by comparison with authentic samples and quantita-
1
tively determined by GC or H NMR.
With 2-(4-methoxyphenyl)-2-methylpropanoic acid (2), prod-
uct studies, carried out at both pH 1.0 and 6.7 with Co(III)W
as the oxidant, showed the exclusive formation of 2-(4-
methoxyphenyl)propan-2-ol (2a), as described in Scheme 6.
The one-electron oxidation of 1-(4-methoxyphenyl)cyclopro-
panol (6) was studied employing both PR and LFP. PR of an
argon-saturated aqueous solution (pH 5.0) containing 2 mM 6,
•-
When SO4 was used as the oxidant, the reaction of 2, at
both pH 1.0 and 6.7, showed the formation of 2a as the major
product accompanied by 4-methoxyacetophenone. The relative
amount of 4-methoxyacetophenone was observed to increase
on going from pH 1.0 to pH 6.7. The product distributions
(32) Guirado, G.; Fleming, C. N.; Lingenfelter, T. G.; Williams, M. L.;
Zuilhof, H.; Dinnocenzo, J. P. J. Am. Chem. Soc. 2004, 126, 14086-14094.
(33) Dinnocenzo, J. P.; Zuilhof, H.; Lieberman, D. R.; Simpson, T. R.;
McKechney, M. W. J. Am. Chem. Soc. 1997, 119, 994-1004.
(34) Bietti, M.; Capone, A. J. Org. Chem. 2006, 71, 5260-5267.
(35) This notation represents an oversimplification because, as compared
to the radical cations, the corresponding radical zwitterions lack the presence
of the carboxylic proton.
(36) Weinstock, I. A. Chem. ReV. 1998, 98, 113-170.
(37) Baciocchi, E.; Bietti, M.; Mattioli, M. J. Org. Chem. 1993, 58,
7106-7110.
(38) Eberson, L. J. Am. Chem. Soc. 1983, 105, 3192-3199.
J. Org. Chem, Vol. 73, No. 2, 2008 621

Bietti and Capone
TABLE 1. Product Distributions Observed in the Co(III)W and
SO4•--Induced Oxidation of 2-(4-Metoxyphenyl)-2-methylpropanoic
Acid (2), Carried out in Aqueous Solutiona
TABLE 2. Product Distributions Observed in the Co(III)W and
SO4•--Induced Oxidation of
1-(4-Methoxyphenyl)cyclopropanecarboxylic Acid (3), Carried out in
Aqueous Solutiona
recovered
substrate (2) AnC(CH3)2OHc AnCOCH3
recovered
c
entry
oxidant
pHb
(%)
(2a) (%)
(%)
substrate (3)
3a
(%)
3b
(%)
3c
(%)
entry
oxidant
pHb
(%)
1d
2d
3e
4f
Co(III)W 1.0
53
40
47
60
98
89
Co(III)W 6.7
1c
Co(III)W
Co(III)W
1.0
6.7
1.0
6.7
6.7
6.7
>95
55
90
90
70
d
45
3
1
4
•-
SO4•-
1.0
6.7
2
11
2c
•-
SO4
3e,f
4e,g
5e,h
6e,i
SO4•-
4
6
20
46
3
4
6
9
SO4•-
SO4•-
SO4
a Good to excellent mass balances (g90%) were observed in all
experiments. b pH 1.0 (HClO4 0.1 M); pH 6.7 (NaH2PO4 0.1 M, adjusted
with NaOH). c An ) 4-MeOC6H4. d [substrate] ) 5 mM, [Co(III)W] ) 5
mM, T ) 50 °C. e [substrate] ) 2.5 mM, [K2S2O8] ) 0.1 M, T ) 25 °C,
irradiation time ) 30 s. f [substrate] ) 2.5 mM, [K2S2O8] ) 0.1 M, T )
25 °C, irradiation time ) 20 s.
38
7
a Good to excellent mass balances (g85%) were observed in all
experiments. b pH 1.0 (HClO4 0.1 M); pH 6.7 (NaH2PO4 0.1 M, adjusted
with NaOH). c [substrate] ) 2.5 mM, [Co(III)W] ) 2.5 mM, T ) 50 °C.
d An almost complete recovery of the substrate was observed after 48 h
and only traces of 3a were observed. e [substrate] ) 2.5 mM, [K2S2O8] )
0.1 M, T ) 25 °C. f Irradiation time ) 60 s. g Irradiation time ) 30 s.
h Irradiation time ) 120 s. i Irradiation time ) 360 s.
SCHEME 6
SCHEME 7
SCHEME 8
TABLE 3. Product Distributions Observed in the Co(III)W and
SO4•--Induced Oxidation of 1-(4-Methoxyphenyl)cyclopropanol (6),
Carried out in Aqueous Solution (pH 6.7) at T ) 25 °Ca
recovered
substrate (6)
3a
3b
3c
entry
oxidant
(%)
(%)
(%)
(%)
1b
2c
Co(III)W
SO4
74
70
11
1
9
22
6
7
•-
a Good to excellent mass balances (g95%) were observed in all
experiments. b [substrate] ) 2 mM, [Co(III)W] ) 2 mM. c [substrate] )
1.5 mM, [K2S2O8] ) 0.1 M, irradiation time ) 40 s.
propanecarboxylate (5) were carried out in argon-saturated
aqueous solution (pH 6.7) at T ) 50 °C, employing Co(III)W
as the oxidant. Under these conditions complete recovery of
the parent compound was observed for all substrates after
reaction times g24 h. This observation clearly indicates that
methyl esters 4 and 5 are essentially unreactive under these
experimental conditions. The lack of reactivity of these sub-
strates is also evidenced by the fact that no change in color
was observed for the Co(III)W/methyl ester reaction mixtures,
whereas when the Co(III)W-induced oxidation reaction of
aromatic compounds takes place, it is always accompanied by
a color change from yellow to blue (indicative of the conversion
of Co(III)W into its reduced form Co(II)W)).37,38
observed in the one-electron oxidation reactions carried out for
substrate 2 are collected in Table 1.
The Co(III)W-induced oxidation of 1-(4-methoxyphenyl)-
cyclopropanecarboxylic acid (3) was studied at pH 1.0 and 6.7.
At pH 1.0 a very slow reaction was observed (after 48 h at T )
50 °C, >95% of the substrate was recovered from the reaction
mixture). At pH 6.7 a significantly faster reaction was observed,
showing the exclusive formation of 1-(4-methoxyphenyl)-3-
hydroxypropan-1-one (3a) as described in Scheme 7.
The SO4•--induced oxidation of 3 was studied at both pH
1.0 and 6.7. The analysis of the reaction mixture showed the
formation of 3a, 1,6-bis(4-methoxyphenyl)hexane-1,6-dione
(3b), and 4-methoxypropiophenone (3c) as described in Scheme
8 (An ) 4-MeOC6H4).
The product distributions observed in the one-electron oxida-
tion reactions carried out for 3 are collected in Table 2.
The Co(III)W-induced oxidation of 3 was also studied in
AcOH/H2O 55:45 at T ) 50 °C, in the presence of 0.5 M AcOK.
Under these conditions, the analysis of the reaction mixture
showed the formation of 3a, 1-(4-methoxyphenyl)cyclopropyl
acetate (3d), and 3c. No quantitative analysis was carried out
under these conditions.
Time-Resolved Kinetic Studies. As mentioned above, no
intermediate radical cation was detected in the time-resolved
studies carried out for 2-(4-methoxyphenyl)-2-methylpropanoic
acid (2) and 1-(4-methoxyphenyl)cyclopropanol (6). Even
though the mechanistic aspects of the one-electron oxidation
of 2 and 6 will be discussed in detail later on, it is important to
point out that with 2 the kinetic data obtained by LFP indicate
that if a radical cation is actually formed after one-electron
oxidation, its decay rate constant must exceed 1 × 107 s-1
,
whereas with 6 the kinetic data obtained by PR indicate that if
a radical cation is actually formed, its decay rate constant must
With 1-(4-methoxyphenyl)cyclopropanol (6), product studies,
exceed 1 × 106 s-1 39
.
•-
carried out at pH 6.7 with Co(III)W or SO4 as the oxidant,
The decay of the radical cation 3•+ and of the corresponding
radical zwitterion -3•+ was measured spectrophotometrically
in aqueous solution (T ) 25 °C, pH 1.7 and ∼7, respectively)
following the decrease in optical density at the corresponding
showed the formation of 3a, 3b, and 3c, i.e., of the same
products observed in the SO4•--induced oxidation of 3 described
above in Scheme 8 and Table 2. The product distributions
observed in the one-electron oxidation reactions carried out for
6 are collected in Table 3.
(39) It is important to point out that the time-resolution of the LFP
equipment used in this study (8 ns laser pulse) is significantly higher than
that of the PR equipment (300 ns electron pulse).
The one-electron oxidations of methyl 2-(4-methoxyphenyl)-
2-methylpropanoate (4) and methyl 1-(4-methoxyphenyl)cyclo-
622 J. Org. Chem., Vol. 73, No. 2, 2008

Oxidation of Propanoic and Cyclopropanecarboxylic Acids
TABLE 4. First-Order Rate Constants (k) for the Decay of
Radical Cations and Radical Zwitterions Generated after PR and/or
LFP of the Parent Substrates 3-5 in Aqueous Solution, Measured
at T ) 25 °C
TABLE 5. Second-Order Rate Constants for the -OH-Catalyzed
(k OH) Decay of Radical Zwitterion -3•+ and Radical Cation 5•+
-
Generated by PR of the Parent Substrates in Aqueous Solution,
Measured at T ) 25 °C
substrate pHa transient
generation
λdetb/nm
k/s-1
k OH
c
-
transienta
pH rangeb
(M-1 s-1
)
3
1.7
1.7
1.7
7.0
7.0
7.0
7.2
3•+
PR, SO4•-, Ar
PR, SO4•-, O2
LFP, SO4•-, N2
PR, SO4•-, Ar
LFP, SO4•-, N2
PR, SO4•-, Ar
PR, SO4•-, Ar
500
500
500
520
520
450
500
4.7 × 103
4.4 × 103
4.5 × 103
2.2 × 104
2.4 × 104
<103 c
3•+
-3•+
5•+
10.2-12.3
10.0-11.3d
7.1 × 106
3•+
5.4 × 107
-3•+
-3•+
4•+
a -3•+ and 5•+ were generated by PR (dose e5 Gy/pulse) of argon
saturated aqueous solutions containing the substrate (0.4-1.0 mM), K2S2O8
4
5
(10 mM), 2-methyl-2-propanol (0.1 M), and Na2B4O7 (1 mM). b pH range
5•+
<103 c
c Obtained from the slopes of the
-
employed for the determination of k OH
.
a pH 1.7 (adjusted with HClO4); pH ∼7 (NaH2PO4 2 mM, adjusted with
NaOH). b Monitoring wavelength. c The decay of the radical cation was
observed to be influenced by the radiation chemical dose, and only an upper
limit for the decay rate constant could be determined.
kobs vs [NaOH] plots, where kobs was obtained following the decay of
absorption at the radical cation or radical zwitterion visible absorption band
maximum (500 and 520 nm, respectively). Average of three independent
determinations. Error e10%. d The pH was limited to 11.3 because at pH
>11.5 ester hydrolysis was observed
SCHEME 9
CHART 2
FIGURE 4. Plot of kobs against concentration of NaOH for the reaction
of radical zwitterion -3•+ with -OH. From the linear regression
analysis: intercept ) 1.6 × 104 s-1, slope ) 6.9 × 106 M-1 s-1, r2 )
0.9968.
carried out for 2•+ and 3•+. The potential energy surface scans
for the internal rotations about the CAr-C (R) and C-CO2H
(â) bonds (depicted for the sake of clarity in Scheme 9 for 2
and 3, showing the situation where R ) 0° and â ) 0°)
calculated for 2•+ and 3•+ are shown in the SI, Figures S4 and
S5, respectively.
With the neutral substrates 2 and 3, the most stable
conformations were those characterized by dihedral angle values
of R ) 60°, â ) 90° and R ) 89°, â ) 180°, respectively (see
SI).
visible absorption band maximum (500 and 520 nm, respec-
tively). In both cases the decay was observed to follow first-
order kinetics, and the rate constants thus obtained are collected
in Table 4.
The decay of the radical cations 4•+ and 5•+ was measured
spectrophotometrically in aqueous solution (T ) 25 °C, pH ∼7)
following the decrease in optical density at the corresponding
visible absorption band maximum (450 and 500 nm, respec-
tively). With these radical cations the decay was observed to
be influenced by the radiation chemical dose and accordingly,
only an upper limit for their decay rate constant could be
determined. The upper limits to the rate constants thus obtained
are also collected in Table 4.
The potential energy surface calculated for 3•+ (SI, Figure
S5) is strongly influenced by the relative orientation of the
cyclopropyl and carboxylic groups. Accordingly, the most stable
conformation for 3•+ is the one where the plane of the aromatic
ring bisects the plane of the cyclopropane ring (R ) 180°, â )
0°: bisected conformation) (Chart 2, structure I).
This result is in line with the well-known conformation-
dependent donor properties of the cyclopropyl group.40,41 In this
conformation, σ-π overlap between the cyclopropane σ bonds
and the aromatic π-system is maximal and electron donation
can efficiently occur. Quite interestingly, in this conformation
By monitoring the decay of the radical zwitterion -3•+, and
of the radical cation 5•+ at the visible absorption band maximum
(520 and 500 nm, respectively) a significant increase in rate
was observed when -OH was added to the solution, and by
plotting the observed rates (kobs) vs concentration of added base,
a linear dependence was observed (Figure 4 and Figure S3,
showing the kobs vs [-OH] plots for the reactions of -3•+ and
5•+, respectively). From the slopes of these plots, the second-
order rate constants for reaction of -OH with -3•+ and 5•+ (k
-
(40) Dinnocenzo, J. P.; Mercha´n, M.; Roos, B. O.; Shaik, S.; Zuilhof,
H. J. Phys. Chem. A 1998, 102, 8979-8987.
(41) Tanko, J. M.; Li, X.; Chahma, M.; Jackson, W. F.; Spencer, J. N.
J. Am. Chem. Soc. 2007, 129, 4181-4192. Drumright, R. E.; Mas, R. H.;
Merola, J. S.; Tanko, J. M. J. Org. Chem. 1990, 55, 4098-4102.
OH) were determined. The rate constants thus obtained are
collected in Table 5.
DFT Calculations. Hybrid density functional (DFT) calcula-
tions with unrestricted MO formalism [UB3LYP/6-31G(d)] were
J. Org. Chem, Vol. 73, No. 2, 2008 623

Bietti and Capone
via an intermediate radical cation 2a•+, a process that is known
to be favored by the presence of a base.44
SCHEME 10
LFP experiments carried out at pH 1.7 did not provide any
direct evidence for the formation of an intermediate radical
cation 2•+, showing instead the initial formation of SO4•- whose
decay (occurring with an observed rate constant kV(450 nm) )
1.0 × 107 s-1) is accompanied by a corresponding buildup in
absorption in the UV region of the spectrum (kv(290 nm) ) 1.1
× 107 s-1) of a transient species (Figure 1). The decay of this
species is accelerated by oxygen occurring with a second-order
rate constant k ) 1.7 × 109 M-1 s-1, a value that is similar to
those measured previously for the reactions of carbon-centered
radicals with oxygen.45-47 On the basis of these observations
and of the results of product studies described above this
transient can be assigned to the 4-methoxycumyl radical.
Overall, these results are consistent with those obtained
previously for the one-electron oxidation of 4-metoxyphenyle-
thanoic acid (1), where no direct evidence for the formation of
an intermediate radical cation 1•+ but only of the 4-methoxy-
benzyl radical was obtained.12,14a The mechanism of the one-
electron oxidation of 2 can be thus suggested to occur according
to Scheme 11, where electron removal from 2 is coupled with
the decarboxylation reaction, directly leading to the 4-meth-
oxycumyl radical. Oxidation of this radical in the reaction
medium gives 2a.
However, even though no intermediate radical cation 2•+ was
detected in the LFP experiments, the kinetic data do not allow
the possible intermediacy of 2•+ to be excluded, because its
lifetime could be too short to allow detection under the
experimental conditions employed: in other words, the decay
of 2•+ (if actually formed) is fast compared with its rate of
formation by reaction of 2 with SO4•-, and only a lower limit
for its decarboxylation rate constant (k > 1 × 107 s-1) can be
given.48
the carboxylic group is coplanar with the aromatic ring, resulting
in efficient orbital overlap between the carbonyl π-system and
the cyclopropane σ bonds. In the alternative perpendicular
conformation (Chart 2, structure II), the cyclopropyl group is
orthogonal to the π-system and no such overlap can be achieved.
As compared to the potential energy surface calculated for
3•+, the potential energy surface calculated for 2•+ (SI, Figure
S4) appears to be relatively flat, and significantly smaller energy
differences between the alternative conformations were calcu-
lated (see SI, Scheme S1) indicating that in this case the relative
arrangement of the aromatic ring and the C(CH3)2 moiety plays
a minor role.
To obtain information on the relative stabilities of the 1-(4-
methoxyphenyl)cyclopropyl and 4-methoxycumyl radicals, DFT
calculations at the UB3LYP/6-31G(d) level of theory were also
carried out to determine the gas-phase bond dissociation
enthalpies (BDEs) of the benzylic C-H bond in 4-methoxy-
cyclopropylbenzene and 4-methoxycumene (Scheme 10).
BDEs calculated at this level of theory are sufficiently reliable
for the discussion presented herein because it has been pointed
out both that the B3LYP functional offers an attractive and
seemingly accurate alternative to the expensive conventional
ab initio methods for the computation of BDEs,42 and that,
thanks to the cancellation of errors, differences in BDEs
(∆BDEs) within a closely related family of compounds are much
more reliable than the absolute values.43 BDE values were thus
obtained from the enthalpy differences between the radicals
produced by homolitic C-H bond cleavage and the parent
substrate (BDE(R-H) ) E(R•) + E(H•) - E(R-H), where R-H
) 4-methoxycyclopropylbenzene or 4-methoxycumene). BDE
values of 99.0 and 90.1 kcal mol-1 were calculated for the
benzylic C-H bond of 4-methoxycyclopropylbenzene and
4-methoxycumene, respectively.
At least partial support to this hypothesis comes from the
observation that the second-order rate constant for reaction of
•-
SO4 with 2, derived from the rate constant measured for the
•-
decay of SO4 (kV(450 nm) ) 1.0 × 107 s-1) and the
concentration of 2 (2.0 × 10-3 M) as k ) 5.0 × 109 M-1 s-1
,
is very similar to the rate constants measured previously for
reactionofSO4•- withmonomethoxylatedbenzenederivatives,24-26
thus indicating that electron removal is very likely to occur from
the aromatic nucleus. The possibility that electron removal
occurs instead from the carboxylic (or carboxylate) function,
directly leading to an acyloxyl radical, can be discarded on the
basis of the second-order rate constants determined for the
Discussion
Product studies carried out on 2-(4-methoxyphenyl)-2-me-
thylpropanoic acid (2) showed the formation of 2-(4-methox-
yphenyl)propan-2-ol (2a) as the exclusive or predominant
reaction product as described in Scheme 6 and Table 1. This
product clearly derives from the oxidation of an intermediate
4-methoxycumyl radical formed after oxidative decarboxylation
of 2, as described previously for the one-electron oxidation of
4-methoxyphenylethanoic acid (1) in acidic aqueous solution.12,14a
Along this line, the formation of 4-methoxyacetophenone in the
SO4•--induced oxidation of 2, and the observation that the
relative amount of 4-methoxyacetophenone was observed to
increase on going from pH 1.0 to pH 6.7, can be explained in
terms of the further oxidation of the first formed alcohol 2a,
•-
reaction of SO4 with ethanoic acid at pH ∼0 and 6.8: k )
8.8 × 104 and 5.0 × 106 M-1 s-1, respectively.49,50
With methyl 2-(4-methoxyphenyl)-2-methyl propanoate (4),
direct evidence for the formation of an intermediate radical
cation 4•+ after one-electron oxidation was obtained by LFP
(44) Baciocchi, E.; Bietti, M.; Lanzalunga, O.; Steenken, S. J. Am. Chem.
Soc. 1998, 120, 11516-11517.
(45) Font-Sanchis, E.; Aliaga, C.; Cornejo, R.; Scaiano, J. C. Org. Lett.
2003, 5, 1515-1518.
(46) Scaiano, J. C.; Tanner, M.; Weir, D. J. Am. Chem. Soc. 1985, 107,
4396-4403.
(47) Maillard, B.; Ingold, K. U.; Scaiano, J. C. J. Am. Chem. Soc. 1983,
105, 5095-5099.
•-
(42) Bally, T.; Borden, W. T. In ReViews in Computational Chemistry;
Lipkowitz, K. B., Boyd, D. B., Eds.; Wiley-VCH: New York, 1999; Vol.
13, pp 1-97.
(43) Pratt, D. A.; Dilabio, G. A.; Mulder, P.; Ingold, K. U. Acc. Chem.
Res. 2004, 37, 334-340 and references cited therein.
(48) An analogous situation has been described previously for the SO4
-
induced oxidation of 4-methylphenyl- and 4-methoxyphenylethanoic acids
in aqueous solution (see ref 14a).
(49) Neta, P.; Huie, R. E.; Ross, A. B. J. Phys. Chem. Ref. Data 1988,
17, 1027-1284.
624 J. Org. Chem., Vol. 73, No. 2, 2008

Oxidation of Propanoic and Cyclopropanecarboxylic Acids
SCHEME 11
SCHEME 12
and PR, as clearly shown by the time-resolved spectrum shown
in Figure 2. 4•+ displayed a very low reactivity, evidenced by
the lack of reaction observed when 4 was reacted with Co(III)W,
and by the upper limit determined for its decay rate constant (k
< 103 s-1). With this substrate, the presence of the CO2Me group
prevents the decarboxylation reaction of the corresponding
radical cation, thus determining a dramatic depression in its
reactivity as compared to 2. Moreover, the presence of the two
methyl groups in the R position precludes the possibility of
benzylic C-H deprotonation as an alternative decay pathway
of 4•+.
With 1-(4-methoxyphenyl)cyclopropanecarboxylic acid (3),
direct evidence for the formation of an intermediate radical
cation 3•+ or radical zwitterion -3•+ after one-electron oxidation
was obtained by both LFP and PR, as clearly shown by the
time-resolved spectra displayed in Figures 3 and S1. The Co-
(III)W-induced oxidation of 3 showed, at pH 6.7, the formation
of 1-(4-methoxyphenyl)-3-hydroxypropan-1-one (3a) as the
exclusive reaction product (see Scheme 7 and Table 2). The
same product, accompanied by 1,6-bis(4-methoxyphenyl)hex-
ane-1,6-dione (3b) and 4-methoxypropiophenone (3c), was also
observed after SO4•--induced oxidation of 3 at pH 1.0 and 6.7
(see Scheme 8 and Table 2).
Two possible mechanistic pathways can in principle be
proposed in order to explain the formation of 3a from 3•+
(Scheme 12). In the mechanism described in paths a-c, the
initially formed radical cation 3•+ undergoes decarboxylation
to give the 1-(4-methoxyphenyl)cyclopropyl radical (path a).
Oxidation of this radical followed by reaction with the solvent
water gives 1-(4-methoxyphenyl)cyclopropanol (6) (path b)
whose subsequent oxidation finally leads to 3a (path c).
As it is well-known that arylcyclopropane radical cations can
undergo a facile ring-opening reaction by nucleophilic attack
at the Câ carbon of the cyclopropane ring,33,51-53 a possible
mechanistic alternative is that described in paths d-f of Scheme
12. 3•+ undergoes a water-induced ring-opening reaction to give
a stabilized benzylic radical (path d). Oxidation of this radical
followed by reaction with water gives 2,4-dihydroxy-2-(4-
(50) It is important to point out that whereas the results of an indirect
kinetic study on the Co(III)W-induced oxidation of 1 were interpreted in
terms of a rate-determining electron transfer from 1 to the relatively weak
oxidant Co(III)W, leading to the conclusion that no aromatic radical cation
(51) Wang, Y.; Tanko, J. M. J. Chem. Soc., Perkin Trans. 2 1998, 2705-
2711.
(52) Wang, Y.; Tanko, J. M. J. Am. Chem. Soc. 1997, 119, 8201-8208.
(53) Dinnocenzo, J. P.; Simpson, T. R.; Zuilhof, H.; Todd, W. P.;
Heinrich, T. J. Am. Chem. Soc. 1997, 119, 987-993.
1•+ was formed as a reaction intermediate (see reference 12), the mechanistic
•-
picture may be different with the significantly stronger oxidant SO4
.
J. Org. Chem, Vol. 73, No. 2, 2008 625

Bietti and Capone
SCHEME 13
methoxyphenyl)butanoic acid (path e) whose subsequent oxida-
tive decarboxylation finally leads to 3a (path f).
However, the latter pathway can be discarded on the basis
of the observation that methyl 1-(4-methoxyphenyl)cyclopro-
panecarboxylate (5), whose radical cation 5•+ would be expected
to display a reactivity toward ring-opening comparable to that
of 3•+, showed instead a significantly lower reactivity (see Table
4), thus indicating that water is not sufficiently reactive to
promote the nucleophilic ring-opening of the cyclopropane ring
in the radical cation.
Also the observation that the decay rate constant increases
on going from 3•+ to -3•+ is in line with a decarboxylation
reaction (path a), as described previously for the one-electron
oxidation of arylethanoic acids, where the decarboxylation rate
constants were observed to increase by at least 1 order of
magnitude on going from the radical cations to the correspond-
ing radical zwitterions.11 Last but not least, the formation of
products 3b and 3c cannot be explained in terms of the
mechanism described by paths d-f.
Concerning 4-methoxypropiophenone (3c), it is well-known
that this product can derive from the acid-catalyzed or thermal
rearrangement of 6.59 Blank experiments showed the stability
toward rearrangement of 6 at pH g3. Accordingly, the observa-
tion that in aqueous solution (pH 6.7) the Co(III)W-induced
oxidation of 3 led to the exclusive formation of 3a (Scheme 6),
whereas 3c was also observed among the reaction products when
the reaction was carried out in AcOH/H2O 55:45, indicates that
in the latter experimental conditions the acid-catalyzed rear-
rangement of 6 is operating.
On the other hand, in the one-electron oxidation of 3, 1-(4-
methoxyphenyl)cyclopropanol (6) was never detected among
the reaction products. This observation is, however, not surpris-
ing because 6 was observed to be significantly more reactive
than 3, and in particular, given that the decarboxylation rate
constants for 3•+ and -3•+ were measured as 4.6 × 103 and 2.3
× 104 s-1, respectively (from the average of the PR and LFP
data, see Table 4), the kinetic data obtained by PR indicate that
if 6•+ is actually formed, its decay rate constant must be >1 ×
106 s-1. Indirect evidence in favor of the intermediacy of 6
comes from the observation that the same products (3a, 3b, and
3c) were formed after one-electron oxidation of 3 and 6, and,
more importantly, from the observation that 1-(4-methoxyphe-
nyl)cyclopropyl acetate (3d) was detected among the reaction
products when the Co(III)W-induced oxidation of 3 was carried
out in AcOH/H2O 55:45, in the presence of AcOK. The
formation of 3d under these conditions can be explained
according to Scheme 12, path b, where oxidation of the 1-(4-
methoxyphenyl)cyclopropyl radical leads to an intermediate
1-(4-methoxyphenyl)cyclopropyl cation that can react with water
to give 6 and with acetate to give 3d. The observation that 3d
but not 6 was observed among the reaction products is in full
agreement with the previous indication that the conversion of
4-methoxybenzyl alcohol into its acetate determines a significant
decrease in side-chain fragmentation reactivity of the corre-
sponding radical cations.37 Taken together, this evidence
provides strong support to the hypothesis that the one-electron
oxidation of 3 proceeds through the mechanism described by
paths a-c in Scheme 12, via decarboxylation of a first formed
radical cation 3•+.
•-
On the other hand, the formation of 3c following SO4
-
induced oxidation of 3 at pH 6.7 (see Table 2) requires a
different explanation and additional experiments in this respect
will be necessary.
Comparison between the one-electron oxidation reactions of
2 and 3 shows that the replacement of the C(CH3)2 moiety with
a cyclopropyl group determines a decrease in decarboxylation
rate constant in the corresponding radical cations of more than
3 orders of magnitude!60 This large difference in reactivity can
be qualitatively explained in terms of three main contributions:
substrate oxidation potential, stability of the carbon-centered
radical formed after decarboxylation, and stereoelectronic ef-
fects.
It is well-known that the decarboxylation rate constants of
arylalkanoic acid radical cations are influenced by the substrate
oxidation potential.9,11 In particular, with ring dimethoxylated
phenylethanoic acid radical cations, the decarboxylation rate
constant was observed to decrease by increasing radical cation
stability.11 Clearly, an increase in radical cation stability
determines an increase in the height of the kinetic barrier for
side-chain to ring intramolecular electron transfer associated to
decarboxylation (Scheme 2) resulting in a corresponding
decrease in decarboxylation rate constant.
Quite interestingly, the data discussed above also provide
indirect evidence on the involvement of an intermediate 1-(4-
methoxyphenyl)cyclopropyl cation in this process.54
Comparison between the oxidation potentials of cyclopro-
pylbenzene and cumene clearly shows that the former compound
The formation of 1,6-bis(4-methoxyphenyl)hexane-1,6-dione
(3b) can be explained according to Scheme 13, where 6•+
undergoes ring-opening to give a radical that can either dimerize
to give 3b or become oxidized in the reaction medium finally
leading to 3a.
(55) van der Vecht, J. R.; Dirks, R. J.; Steinberg, H.; de Boer, T. J. Recl.
TraV. Chim. Pays-Bas 1977, 96, 309-312.
(56) Schleyer, P. v. R.; Bremer, M. J. Org. Chem. 1988, 53, 2362-
2364.
(57) Olah, G. A.; Liang, G.; Ledlie, D. B.; Costopoulos, M. G. J. Am.
Chem. Soc. 1977, 99, 4196-4198.
(54) The involvement of a highly reactive 1-(4-methoxyphenyl)cyclo-
propyl cation has been also proposed in the alcoholisys of 1-(4-methox-
yphenyl)cyclopropyl halides.55 In this respect, it is important to point out
that clear evidence in favor of the formation of a cyclopropyl cation has
been obtained when this species is condensed in a rigid ring system,56,57 or
when the cationic center is bound to a strongly stabilizing ferrocenyl group.58
(58) Surya Prakash, G. K.; Buchholz, H.; Prakash Reddy, V.; de Meijere,
A.; Olah, G. A. J. Am. Chem. Soc. 1992, 114, 1097-1098.
(59) DePuy, C. H.; Breitbeil, F. W.; DeBruin, K. R. J. Am. Chem. Soc.
1966, 88, 3347-3354.
(60) On the basis of the assumption that if 2•+ is actually formed after
one electron oxidation, it undergoes decarboxylation with k > 1 × 107 s-1
.
626 J. Org. Chem., Vol. 73, No. 2, 2008

Oxidation of Propanoic and Cyclopropanecarboxylic Acids
is more easily oxidizable than the latter one,61 a behavior that
can be ascribed to the well-known electron-donating properties
of the cyclopropyl group.40,41 Accordingly, it is reasonable to
propose that 3•+ will be thermodynamically more stable than
2•+, on the basis of the lower oxidation potential that can be
expected for 3 as compared to 2.66 Evidence in favor of the
electron-donating ability of the cyclopropyl group is also
provided by the analysis of the time-resolved spectra obtained
for 3•+, shown in Figures 3 and S1, that resemble the spectra
observed for arylcyclopropane radical cations,32,33,40 rather that
those observed for anisole derivatives.24,26,29-31
radical cations can be influenced by the relative orientation
between the scissile bond and the π system (stereoelectronic
effect),72-75 with the most suitable orientation for cleavage being
the one where the dihedral angle between the plane of the
aromatic ring and the plane defined by the scissile bond and
the atom of the aromatic ring to which this bond is connected
is 90°. In this conformation the scissile bond is aligned with
the π system bearing the unpaired electron, and the best orbital
overlap for bond cleavage can be achieved. Along this line, in
the most stable conformation calculated for 3•+ (Chart 2,
structure I, R ) 180°, â ) 0°), the carboxylic group is coplanar
with the plane of the aromatic ring, and no efficient overlap
between the scissile C-CO2H bond and the π system can be
achieved. To reach the most stable conformation where the
scissile bond is perpendicular to the plane of the aromatic ring
(most suitable orientation for bond cleavage: structure II, R )
90°, â ) 180°) an energy barrier of at least 4.6 kcal mol-1 has
to be overtaken (see SI, Figure S5 and Scheme S2).
On the other hand, in the most stable conformation calculated
for 2•+ (see SI, Scheme S1: structure V, R ) 130°, â ) 356°),
the scissile C-CO2H bond is very close to the most suitable
orientation for cleavage (SI, Scheme S1: structure VI, R ) 90°,
â ) 210°). In this case, moving on a relatively flat potential
energy surface, in order to reach the most suitable orientation
for C-CO2H bond cleavage an energy barrier e1.8 kcal mol-1
has to be overtaken (see SI, Figure S4). Thus, even though the
observed differences in energy are relatively small, stereoelec-
tronic requirements for decarboxylation appear to disfavor
C-CO2H bond cleavage in 3•+ as compared to 2•+.
Another important factor is represented by the stability of
the carbon-centered radical formed after decarboxylation. In this
context, Gould and Farid have clearly shown that in the
decarboxylation of radical cations of anilino biscarboxylates
characterized by comparable stabilities, the decarboxylation rate
constants were influenced by the stability of the product radical,
increasing with increasing radical stability.3 Accordingly, as a
consequence of the Hammond postulate,67 an increase in stability
of the product radical determines an increase in the reaction
exothermicity and a corresponding decrease in activation energy.
Along this line, the difference between the BDEs calculated
for 4-methoxycyclopropylbenzene and 4-methoxycumene (99.0
and 90.1 kcal mol-1, respectively, ∆BDE ) 8.9 kcal mol-1
)
allows the assessment of the relative stabilities of the 1-(4-
methoxyphenyl)cyclopropyl and 4-methoxycumyl radicals,43
indicating that the 4-metoxycumyl radical appears to be
significantly more stable that the 1-(4-methoxyphenyl)cyclo-
propyl radical,68 in line with the relatively low stability reported
for cyclopropyl radicals.69-71
In summary, when comparing the one-electron oxidation
reactions of 2 and 3, the discussion presented above clearly
indicates that the stability of the radical cation, the stability of
the carbon radical formed after decarboxylation, and stereo-
electronic requirements for fragmentation all exert their effect
in the same direction, that is by decreasing the decarboxylation
rate constant of 3•+ as compared to that of 2•+.
A final point of interest is represented by the possible role
of stereoelectronic effects in these processes. It is well-known
that the side-chain fragmentation reactivity of alkylaromatic
(61) Cyclopropyl benzene: E° ) 1.91 V (Ep ) 1.97 V: sweep rate 150
mV/s).32 Cumene: E° ) 2.17 V62,63 (Ep ) 2.27 V,64 2.32 V62: sweep rates
100 mV/s). All values are in V vs SCE in acetonitrile.
(62) Howell, J. O.; Goncalves, J. M.; Amatore, C.; Klasinc, L.;
Wightman, R. M.; Kochi, J. K. J. Am. Chem. Soc. 1984, 106, 3968-3976.
(63) In ref 62, the value of the standard oxidation potential for cumene
is given in trifluoroacetic acid (TFA) as 2.29 V vs SCE. The value of 2.17
V vs SCE in acetonitrile derives from the application of the corrective factor
previously determined for the oxidation potentials of alkylbenzenes (E°MeCN
) E°TFA - 0.12 V).65
(64) Tajima, T.; Ishii, H.; Fuchigami, T. Electrochem. Commun. 2002,
4, 589-592.
(65) Schlesener, C. J.; Amatore, C.; Kochi, J. K. J. Phys. Chem. 1986,
90, 3747-3756. Schlesener, C. J.; Amatore, C.; Kochi, J. K. J. Am. Chem.
Soc. 1984, 106, 3567-3577.
(66) Also the adiabatic ionization potentials that can be obtained on the
basis of the computed energy differences between the most stable structures
of 2•+ and 2 and of 3•+ and 3 (7.48 and 7.33 eV, respectively, see the
Supporting Information) point in this direction.
(67) Hammond, G. S. J. Am. Chem. Soc. 1955, 77, 334-338.
(68) It is, however, important to point out that this approach is based on
the assumption that 4-methoxycyclopropylbenzene and 4-methoxycumene
are characterized by the same energies. In order to validate this assumption,
we have calculated, at the UB3LYP/6-31G(d) level of theory, the energy
difference between products and reagents for the isodesmic reaction shown
below (An ) 4-MeOC6H4). The energy difference thus obtained (∆E )
-3.1 kcal mol-1) is significantly smaller than the ∆BDE of ≈9 kcal mol-1
reported above, and confirms that the 4-metoxycumyl radical is more stable
than the 1-(4-methoxyphenyl)cyclopropyl radical.
Table 5 displays the second-order rate constants for reaction
of radical zwitterion -3•+ and of the corresponding methyl ester
-
radical cation 5•+ with OH: k OH ) 7.1 × 106 and 5.4 × 107
-
M-1 s-1, respectively. At pH ∼7 -3•+ was observed to undergo
decarboxylation with k ) 2.3 × 104 s-1 (Table 4), whereas 5•+
displayed a significantly lower reactivity and only an upper limit
for its decay rate constant could be obtained (k < 103 s-1). In
5•+ the presence of the CO2Me group prevents the decarboxy-
lation reaction and, moreover, the presence of the cyclopropyl
group in the R position precludes the possibility of benzylic
C-H deprotonation as an alternative decay pathway. As
mentioned above, nucleophilic ring-opening of the cyclopropane
ring was not observed at pH ∼7, indicating that water is not
sufficiently reactive to promote this reaction. In basic solution,
-
however, a different situation was observed with k OH increasing
on going from -3•+ to 5•+. In order to explain this behavior it
is reasonable to propose that under these conditions -3•+ and
(72) Bellanova, M.; Bietti, M.; Ercolani, G.; Salamone, M. Tetrahedron
2002, 58, 5039-5044.
(73) Tolbert, L. M.; Li, Z.; Sirimanne, S. R.; VanDerveer, D. G. J. Org.
Chem. 1997, 62, 3927-3930. Tolbert, L. M.; Khanna, R. K.; Popp, A. E.;
Gelbaum, L.; Bottomley, L. A. J. Am. Chem. Soc. 1990, 112, 2373-2378.
(74) Baciocchi, E.; D’Acunzo, F.; Galli, C.; Lanzalunga, O. J. Chem.
Soc., Perkin Trans. 2 1996, 133-140. Baciocchi, E.; Mattioli, M.; Romano,
R.; Ruzziconi, R. J. Org. Chem. 1991, 56, 7154-7160.
(75) Perrott, A. L.; Arnold, D. R. Can. J. Chem. 1992, 70, 272-279.
Arnold, D. R.; Lamont, L. J.; Perrott, A. L. Can. J. Chem. 1991, 69, 225-
233.
(69) Heinrich, M. R.; Zard, S. Z. Org. Lett. 2004, 6, 4969-4972.
(70) Luo, Y.-R. Handbook of Bond Dissociation Energies in Organic
Compounds; CRC Press LLC: Boca Raton, FL, 2003.
(71) Walborsky, H. M. Tetrahedron 1981, 37, 1625-1651.
J. Org. Chem, Vol. 73, No. 2, 2008 627

Bietti and Capone
SCHEME 14
(b) Oxidations with SO4•-. Irradiations were performed employ-
ing a photochemical reactor equipped with 8 × 15 W lamps with
emission at 254 nm. The reactor was a cylindrical flask equipped
with a water cooling jacket thermostated at T ) 25 °C. Irradiation
times were generally chosen in such a way as to avoid complete
substrate consumption. In a typical experiment 20 mL of an argon-
saturated aqueous solution (pH 1.0 or 6.7) containing the substrate
(1.5-2.5 mM) and K2S2O8 (0.1 M) were irradiated for times varying
between 20 and 360 s. Blank experiments performed in the absence
of irradiation showed the formation of negligible amounts of
reaction products.
5•+ both undergo a -OH-induced ring-opening of the cyclo-
propane ring, as described in Scheme 14.
With both oxidizing systems, the reaction mixture was acidified
with 2 N HCl (only for the experiments at pH 6.7), extracted with
ethyl ether, and dried over anhydrous Na2SO4. The reaction products
were identified by GC, GC-MS, and 1H NMR, by comparison with
authentic samples. The quantitative analysis was carried out by GC
Quite interestingly, the intercept of the kobs against [NaOH]
plot for the reaction of -3•+ (1.6 × 104 s-1, see Figure 4), which
represent the rate constants for the uncatalyzed reaction of -3•+,
is very close to the decarboxylation rate constant measured for
this radical zwitterion at pH 7.0 (k ) 2.3 × 104 s-1, see Table
4). On the basis of this observation it is reasonable to propose
that at pH g10 -3•+ undergoes competition between decar-
boxylation and -OH-induced ring-opening of the cyclopropane
ring, with the latter process that becomes the major fragmenta-
tion pathway around pH 12. In this context, it has been shown
that arylcyclopropane radical cations are characterized by a
certain extent of positive charge at the Câ carbon of the
cyclopropane ring, and that nucleophilic attack generally occurs
1
or H NMR. In the GC experiments 3,4-(methylendioxy)benzyl
alcohol or 3,4-dimethoxybenzyl alcohol was used as internal
standard. In the 1H NMR experiments diphenylmethanol was used
as internal standard. Good to excellent mass balances (g85%) were
obtained in all experiments.
Time-Resolved Studies. (a) Pulse Radiolysis. The pulse radi-
olysis experiments were performed with a 10 MeV electron linear
accelerator that supplied 300 ns pulses with doses such that 1-3
µM radicals were produced. Experiments were performed at room
temperature with argon-saturated aqueous solutions containing the
substrate (0.2-2.0 mM), peroxydisulfate (10 mM), and 2-methyl-
2-propanol (0.1 M). For the experiments carried out at pH 1.7, the
pH of the solutions was adjusted with HClO4. For the experiments
carried out at pH ∼7, 2 mM Na2HPO4 was added and the pH was
adjusted with NaOH. A flow system was employed in all the
experiments. Rate constants were obtained following the decrese
in absorbance at the radical cation visible absorption maxima, by
averaging at least 8 values, and were reproducible to within 10%.
The second-order rate constants for reaction of -3•+ and 5•+ with
at this position.33,40 Along this line, the k OH values reported
above can be rationalized in terms of the effect of the aromatic
ring and of the cyclopropane ring substituent (CO2 or CO2-
Me) on the stabilization of an incipient positive charge at Câ,
and consequently on the rate constant for the -OH-induced
reaction. CO2Me is a relatively strong electron-withdrawing
group that is expected to increase the extent of positive charge
at Câ whereas the CO2- group is expected to exert a negligible
-
-
-
-
effect in this respect, in full agreement with the increase in k OH
-
OH (k OH) were obtained from the slopes of the plots of the
observed on going from radical zwitterion -3•+ to the corre-
sponding methyl ester radical cation 5•+.
observed rates (kobs) vs concentration of NaOH. For these experi-
ments argon-saturated solutions containing 0.4-1.0 mM substrate,
10 mM potassium peroxydisulfate, 0.1 M 2-methyl-2-propanol, and
In conclusion, by means of product and time-resolved kinetic
studies additional information on the role of structural effects
on the one-electron oxidation of ring-methoxylated arylethanoic
acids has been obtained. Decarboxylation was observed as the
exclusive fragmentation pathway after one-electron oxidation
of both 2-(4-methoxyphenyl)-2-methylpropanoic acid and 1-(4-
methoxyphenyl)cyclopropanecarboxylic acid; however, direct
evidence for the involvement of an intermediate radical cation
was obtained only for the latter substrate. Replacement of the
C(CH3)2 moiety with a cyclopropyl group determines a decrease
in decarboxylation rate constant of more than 3 orders of
magnitude, a behavior that has been rationalized in terms of
differences in substrate oxidation potential, stability of the
carbon-centered radical formed after decarboxylation, and
stereoelectronic requirements for fragmentation. Very interest-
ingly, with the 1-(4-methoxyphenyl)cyclopropanecarboxylic acid
radical cation, competition between decarboxylation and -OH-
induced cyclopropane ring-opening is observed above pH 10.
-
1 mM sodium tetraborate were employed. kOH values were obtained
from the average of three independent determinations and were
reproducible to within 10%.
(b) Laser Flash Photolysis. Experiments were carried out by
direct laser flash photolysis (LFP) of argon-saturated aqueous
solutions, containing the substrate (0.2-2.0 mM) and K2S2O8 (0.1
M), using the fourth harmonic (266 nm) of a Q-switched Nd:YAG
laser providing 8 ns pulses. The laser energy was adjusted to e10
mJ/pulse (output power of the laser) by the use of the appropriate
filter. The concentration of K2S2O8 was such that this species
absorbed most of the 266 nm radiation. Experiments were carried
out at T ) 25 ( 0.5 °C under magnetic stirring employing a 3 mL
Suprasil quartz cell (10 mm × 10 mm). The stability of the solutions
to the experimental conditions was checked spectrophotometrically
comparing the spectrum of the solution before irradiation with that
obtained after irradiation. Rate constants were obtained by averaging
at least 8 values and were reproducible to within 10%.
Computational Details
Hybrid DFT calculations have been carried out at the UB3LYP/
6-31G(d) level of theory, using the Gaussian 03 program package.76
All species have been fully geometry optimized in the gas phase
and the Cartesian coordinates of the global minima thus obtained
are supplied in the SI. The calculated spin-squared expectation
values ( S2 ) were, after spin annihilation, e0.751 in all cases, in
good agreement with the theoretically expected value of 0.75 for a
pure doublet state.
Experimental Section
Product Studies. (a) Oxidations with Co(III)W. A 5 mL
sample of an argon-saturated aqueous solution (pH 1.0 or 6.7)
containing equimolar amounts of the substrate and Co(III)W
(between 2 and 5 mM) was stirred at T ) 25 or 50 °C until complete
conversion of the oxidant. In the experiment carried out for 3 in
AcOH/H2O 55:45 at T ) 50 °C in the presence of 0.5 M AcOK,
a 10 mM concentration of both the substrate and Co(III)W was
employed.
The potential energy surface scans for the internal rotations about
the benzylic and the C-CO2H bonds of 2•+ and 3•+ (see SI) were
628 J. Org. Chem., Vol. 73, No. 2, 2008

Oxidation of Propanoic and Cyclopropanecarboxylic Acids
carried out in redundant internal coordinates in steps of 30°. A
geometry optimization was performed on the global minimum found
for any conformation.
Gas-phase bond dissociation enthalpies (BDEs) relative to the
benzylic C-H bond in 4-methoxycyclopropylbenzene and 4-meth-
oxycumene were also calculated by geometry optimization of the
involved species at the UB3LYP/6-31G(d) level of theory (BDE-
(R-H) ) E(R•) + E(H•) - E(R-H).
Acknowledgment. Financial support from the Ministero
dell’Istruzione dell’Universita` e della Ricerca (MIUR) is grate-
fully acknowledged. Pulse radiolysis experiments were per-
formed at the Free Radical Research Facility, Daresbury
Laboratory, Warrington, UK under the support of the European
Commission’s Transnational Access to Major Research Infra-
structures. We thank Prof. Basilio Pispisa and Prof. Lorenzo
Stella for the use and assistance in the use of LFP equipment,
and Prof. Gianfranco Ercolani for assistance in the DFT
calculations.
(76) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K.
N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.;
Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich,
S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A.
D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A.
G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian
03, Revision B.01; Gaussian, Inc.: Wallingford, CT, 2004.
Supporting Information Available: Details on the synthesis
and characterization of substrates 2 and 4-6 and of reaction
products 3a, 3b, and 3d, time-resolved absorption spectra observed
after LFP of substrate 3 and PR of substrate 5, Plot of kobs vs
[NaOH] for 5•+, optimized Cartesian coordinates and potential
energies calculated for the global minima of 2, 2•+, 3, 3•+,
4-methoxycyclopropylbenzene, 1-(4-methoxyphenyl)cyclopropyl
radical, 4-methoxycumene, and 4-methoxycumyl radical, and
Potential energy surface scans for 2•+ and 3•+, calculated at the
UB3LYP/6-31G(d) level of theory. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO702104J
J. Org. Chem, Vol. 73, No. 2, 2008 629