The role of oxygen acidity on the side-chain fragmentation of ring methoxylated benzocycloalkenol radical cations

Article abstract of DOI:10.1016/S0040-4039(03)01620-4

The reactivity of 2,2-dimethyl-5-methoxyindan-1-ol (1) and 2,2-dimethyl-6-methoxytetral-1-ol (2) radical cations has been studied both in acidic and basic solution. At pH≤4 both 1^.+ and 2^.+ undergo C_α-H deprotonation as the exclusive reaction with k=4.6×10⁴ and 3.2×10⁴ s^-1, respectively. In basic solution 1^.+ and 2^.+ behave as oxygen acids undergoing ^-OH-induced α-OH deprotonation in a diffusion controlled process (k_-OH≈10¹⁰ M^-1 s^-1). An intermediate alkoxyl radical is formed which undergoes a 1,2-hydrogen atom shift in competition with C-C β-scission (with 1^.+) or as the exclusive pathway (with 2^.+). A behavior which is interpreted in terms of the greater ease of ring-opening of a five membered ring as compared to a six-membered one.

Full text of DOI:10.1016/S0040-4039(03)01620-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6401–6404
The role of oxygen acidity on the side-chain fragmentation of
ring methoxylated benzocycloalkenol radical cations
Monica Bellanova, Massimo Bietti* and Michela Salamone
Dipartimento di Scienze e Tecnologie Chimiche, Universita` ‘Tor Vergata’, Via della Ricerca Scientifica, I-00133 Rome, Italy
Received 2 May 2003; revised 27 June 2003; accepted 27 June 2003
Abstract—The reactivity of 2,2-dimethyl-5-methoxyindan-1-ol (1) and 2,2-dimethyl-6-methoxytetral-1-ol (2) radical cations has
+
+
’
’
been studied both in acidic and basic solution. At pH54 both 1 and 2 undergo CaꢀH deprotonation as the exclusive reaction
with k=4.6×104 and 3.2×104 s−1, respectively. In basic solution 1 and 2 behave as oxygen acids undergoing −OH-induced
+
+
’
’
aꢀOH deprotonation in a diffusion controlled process (k−OH:1010 M−1 s−1). An intermediate alkoxyl radical is formed which
+
+
’
’
undergoes a 1,2-hydrogen atom shift in competition with CꢀC b-scission (with 1 ) or as the exclusive pathway (with 2 ). A
behavior which is interpreted in terms of the greater ease of ring-opening of a five membered ring as compared to a six-membered
one.
© 2003 Elsevier Ltd. All rights reserved.
We have recently shown that in acidic aqueous solution
2,2-dimethyl-5-methoxyindan-1-ol (1) radical cation
undergoes CaꢀH deprotonation as the exclusive reac-
tion and that an increase in deprotonation rate results
from the alignment between the scissile CꢀH bond and
the p-system imposed by the presence of the five-mem-
bered ring, thus providing evidence for the importance
of stereoelectronic effects in the deprotonation of alkyl-
aromatic radical cations.1 In order to obtain additional
information on this important topic, we have extended
our study to 2,2-dimethyl-6-methoxytetral-1-ol (2).2
gen acids undergoing −OH-induced a–OH deprotona-
tion leading, through the intermediacy of a radical
zwitterion, to an alkoxyl radical,4 prompted us to study
the reactivity of 1 and 2 also in basic solution, in
order to obtain information on the role of structural
effects on this peculiar mechanistic behavior.
+
’
+
’
Results and discussion
Generation of the radical cations
Radical cations 1 and 2 + were generated by oxidation
of the neutral substrates employing three different
methods: chemical oxidation with potassium 12-
tungstocobalt(III)ate (K5[CoIIIW12O40], from now on
+
’
’
+
’
Also in 2 the presence of the six-membered ring
prevents a favorable alignment between the scissile CꢀC
bond and the p-system, favoring instead that with the
CꢀH bond.3
III
−
’
simply indicated as Co W) or oxidation with SO4
generated by steady-state photolysis or by pulse
radiolysis.
Oxidations induced by CoIIIW. The CoIIIW-induced oxi-
dation of 1 at pH 3.1 has been described previously.1
+
’
2
was generated in aqueous solution at pH 3.1 (50
mM citrate buffer) under nitrogen at T=50°C by reac-
tion of the substrate (0.5–2 mM) with CoIIIW (0.5–4
mM). CoIIIW is a well-known one-electron chemical
oxidant able to oxidize methoxybenzene derivatives via
outer-sphere electron transfer.5
The recent discovery that 1-(4-methoxyphenyl)alkanol
radical cations behave as carbon acids in neutral and
acidic solution, undergoing CaꢀH deprotonation,
whereas in basic solution (pH 10) they behave as oxy-
−
+
Oxidations induced by SO4 . 1 and 2 + were generated
’
’
’
Keywords: radical cation; pulse radiolysis; deprotonation; oxygen
acidity; stereoelectronic effect; alkoxyl radical.
* Corresponding author. Fax: +39-06-72594328; e-mail: bietti@
uniroma2.it
in aqueous solution at room temperature by reaction of
the substrates with SO4 . SO4 is a strong oxidant
which is able to react with aromatic substrates via
−
−
’
’
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01620-4

6402
M. Bellano6a et al. / Tetrahedron Letters 44 (2003) 6401–6404
electron transfer to yield the corresponding radical
Basic solution (pH 10). The oxidations of 1 and 2 were
carried out employing SO4 as the oxidant. Oxidation
cations with k:109 M−1 s−1 (Eq. (1)).6
−
’
of 1 led the formation of 2,2-dimethyl-5-methoxyindan-
1-one as main product (86%) together with 4-methoxy-
2-(2-methyl-2-propenyl)benzencarbaldehyde (3) (2%),
4-methoxy-2-(2-methyl-1-propenyl)benzencarbaldehyde
(4) (2%) and 8,8-dimethyl-5-methoxybenzo[c]oxacyclo-
hexan-2-one (5) (10%) (Scheme 1).9
(1)
−
’
In the product studies, SO4 was generated by steady
state photolysis (u=254 nm) of nitrogen saturated
aqueous solutions (pH 3.1 or 10.0, citrate or borate
buffer, respectively) containing 1 or 2 (2 mM) and
K2S2O8 (0.1 M) (Eq. (2)).7
Oxidation of 2 led instead to the exclusive formation of
the corresponding ketone, 2,2-dimethyl-6-methoxy-
tetral-1-one.
(2)
Kinetic studies. These were carried out using the pulse
−
’
For kinetic studies, SO4 was instead generated by
radiolysis technique. The time-resolved absorption
pulse radiolysis of argon or oxygen saturated aqueous
solutions containing 1 or 2 (0.5–1 mM), K2S2O8 (5–10
mM) and 2-methyl-2-propanol (0.1 M) according to
Eqs. (3–5).
+
’
spectrum of 2 at pH 3.3 and room temperature
showed the characteristic UV and visible absorption
bands of anisole-type radical cations centered at 290
and 460 nm,4,6b analogous to those observed previously
+ 1
’
for 1 .
(3)
+
’
Acidic solution (pH 3.1). The decay rate of 2 was
measured spectrophotometrically following the decrease
(4)
(5)
in optical density at 460 nm. Under these conditions,
+
’
2
decays with first-order kinetics with k=3.2×104 s−1,
in a reaction which, on the basis of product analysis
results, is assigned to CꢀH deprotonation. This value is
Radiolysis of water leads to the formation of the
hydroxyl radical ( OH) and the hydrated electron (eaq)
+
’
4
−1 1
similar to that obtained for 1 , k=4.6×10 s , confir-
ming that when the CꢀH bond is forced into a confor-
mation where it is almost aligned with the p-system as
−
’
(Eq. (3)). The former is scavenged by 2-methyl-2-
propanol (Eq. (4); k=6×108 M−1 s−1),6a while e−aq reacts
+
’
+
’
in 1 and 2 , the deprotonation rate increases signifi-
cantly as compared to 1-(4-methoxyphenyl)ethanol rad-
ical cation (k=7.0×103 s−1),4 where all conformations
are instead accessible for the scissile CꢀH bond.
with the peroxydisulfate anion leading to the formation
−
of SO4 (Eq. (5); k=1.2×1010 M−1 s−1).6a
’
Product studies
Basic solution. A significant increase in rate was
observed when −OH was added to the solution. By
plotting the observed rate constants for −OH-induced
decay of the radical cations (kobs) measured at 460 nm,
against the concentration of added base, a linear depen-
dence was observed. From the slope of these plots, the
second-order rate constants for reaction of −OH with
Acidic solution (pH 3.1). The oxidation of 2 was carried
III
−
’
out employing Co W or SO4 as the oxidant, showing
in both cases the exclusive formation of 2,2-dimethyl-6-
methoxytetral-1-one, in line with the results obtained
with
1
(exclusive formation of 2,2-dimethyl-5-
methoxyindan-1-one).1 Ketone formation can be
explained on the basis of the formation and deprotona-
tion of an intermediate radical cation leading to a
carbon centered radical, which is then oxidized to the
corresponding ketone, in analogy with one-electron oxi-
dations of arylalkanols.8 Thus, under these conditions
+
’
+
and 2 (k−OH) were determined as k−OH=1.3×1010
’
1
and 1.1×1010 M−1 s−1, respectively, values which are
indicative of aꢀOH deprotonation as previously dis-
cussed for 1-(4-methoxyphenyl)alkanol radical cations,
+
+
+
+
’
’
’
’
the exclusive reaction of 1 and 2 is deprotonation
from C-1.
indicating that under these conditions 1 and 2
exhibit oxygen acidity.4
Scheme 1.

M. Bellano6a et al. / Tetrahedron Letters 44 (2003) 6401–6404
6403
Scheme 2.
fundamental requisite for the occurrence of bond cleav-
On the basis of this observation, the product distribu-
tion observed after oxidation of 1 at pH 10 can be
explained in terms of the competition between 1,2-
hydrogen atom shift and CꢀC b-scission in an interme-
diate 2,2-dimethyl-5-methoxyindanyl-1-oxyl radical (or
radical zwitterion), formed by −OH-induced aꢀOH
+
+
’
’
age. In alkaline aqueous solution 1 and 2 display
oxygen acidity undergoing aꢀOH deprotonation to give
an alkoxyl radical from which the observed products of
CꢀH and CꢀC bond cleavage can be formed. CꢀC bond
cleavage represents however a minor fragmentation
pathway for these benzocycloalkenyl-1-oxyl radicals,
which mainly undergo a 1,2-H atom shift.
+
’
deprotonation of 1
(Scheme 2). 2,2-Dimethyl-5-
methoxyindan-1-one derives from the oxidation of the
a-hydroxy indanyl radical formed after 1,2-hydrogen
atom shift, whereas products 3, 4 and 5 from the
successive reactions of the carbocation generated by
oxidation of the carbon centered radical formed after
CꢀC b-scission.
Acknowledgements
This work was carried out into the framework of the
EU project ‘Towards Efficient Oxygen Delignification’
(Contract No. QLK5-CT-1999-01277). Pulse radiolysis
experiments were performed at the Free Radical
Research Facility, Daresbury Laboratory, Warrington,
UK under the support of the European Commission’s
Transnational Access to Major Research Infrastruc-
tures. We thank Mr. Luigi Gastaldo (Helios Italquartz
s.r.l.) for providing us with a photochemical reactor.
Interestingly, the observation that 2,2-dimethyl-5-
methoxyindan-1-one is the main fragmentation product
suggests that in the intermediate 2,2-dimethyl-5-
methoxyindanyl-1-oxyl radical, the 1,2-hydrogen atom
shift occurs more rapidly than CꢀC b-scission. Along
this line, the exclusive formation of 6-methoxy-2,2-
dimethyltetral-1-one in the oxidation of 2 at pH 10
indicates that the intermediate 2,2-dimethyl-6-
methoxytetralyn-1-oxyl radical undergoes exclusive 1,2-
H atom shift.
Comparison between the results obtained after oxida-
tion of 1 and 2 at pH 10 shows that the importance of
the CꢀC bond cleavage pathway decreases on going
from the indane system to the tetralyn one, a result
which can be rationalized in terms of the greater ease of
ring opening of a cyclopentoxyl radical as compared to
a cyclohexoxyl one.10
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2. 2 was prepared by reduction of 2,2-dimethyl-6-
methoxytetral-1-one with NaBH4 in 2-propanol, purified
by column chromatography (silica gel, eluent petroleum
1
ether/ethyl acetate, 10:1) and characterized by H NMR
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1
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ralyn-1-oxyl radicals the 1,2-H atom shift occurs more
rapidly than CꢀC b-scission whereas the radical derived
from aꢀOH deprotonation of 1-(4-methoxyphenyl)-2,2-
dimethyl-1-propanol radical cation undergoes exclusive
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ring plays an important role in the competition between
these processes.
6.78–6.74 (m, 1H, ArH), l 6.63 (d, 1H, ArH), l 4.21 (d,
1H, ArCHOH), l 3.78 (s, 3H, OCH3), l 2.86–2.67 (m,
2H, ArCH2), l 1.54–1.45 (m, 2H, CH2), l 1.00 (s, 3H,
CH3), d 0.95 (s, 3H, CH3). GC–MS (e.i. 70 eV) m/z: [M+]
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the p system containing the unpaired electron is a

6404
M. Bellano6a et al. / Tetrahedron Letters 44 (2003) 6401–6404
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1
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(m, 3H, ArH), l 6.55 (s, 1H, ArCHꢁ), l 3.87 (s, 3H,
OCH3), l 1.96 (d, 3H, ꢁC(CH3)trans), l 1.68 (d, 3H,
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1
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1
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