Direct UV observation and kinetic studies of a α-alkoxy benzyloxy radical

Article abstract of DOI:10.1021/ol901215y

A α-alkoxy benzyloxy radical 3 was generated by laser flash photolysis of peroxyacetal 2, and its UV spectrum, decomposition pattern, reactivity with PPh₃, O₂, and i-PrOH, and quantum yield were explored. It was found that the radica

Full text of DOI:10.1021/ol901215y

ORGANIC
LETTERS
2
009
Vol. 11, No. 15
370-3373
Direct UV Observation and Kinetic
Studies of a r-Alkoxy Benzyloxy
Radical
3
Lu-An Chen and Kuangsen Sung*
Department of Chemistry, National Cheng Kung UniVersity, Tainan, Taiwan
kssung@mail.ncku.edu.tw
Received May 29, 2009
ABSTRACT
A r-alkoxy benzyloxy radical 3 was generated by laser flash photolysis of peroxyacetal 2, and its UV spectrum, decomposition pattern,
reactivity with PPh , O , and i-PrOH, and quantum yield were explored. It was found that the radical 3 is very unstable and highly reactive and
3
2
performs ꢀ-C-H scission much faster than ꢀ-C-O scission and H-abstraction.
•
The R-alkoxy alkoxy radicals (ROCH(O )R, 1) can be
intermediates of various reactions; the following are three
Scheme 1. Oxidation of Carbohydrates and Their Analogues,
examples. First, oxidation of ethers in air generates various
peroxyacetals. These peroxyacetals may be decomposed into
Forming R-Alkoxy Alkoxy Radicals as Intermediates
1a
the R-alkoxy alkoxy radicals 1. Some theoretical and kinetic
studies on ꢀ-scission and oxidation of 1 have been done,
1
b-d
but direct observation of the radical 1 is still absent.
Second, since the early 1960s, photodynamic therapy has
been developed for treatment of tumor cells, bacteria, and
2a
viruses by means of photosensitizer, oxygen, and light. The
photosensitization reaction generates highly reactive singlet
oxygen, which not only reacts with tumor cells, bacteria, or
viruses but also attacks biological molecules such as R-to-
(
1) (a) Carey, F. A. Organic Chemistry, 7th ed.; McGraw Hill: New
York, 2008; pp 671-672. (b) Henon, E.; Bohr, F.; Sokolowski-Gomez,
N.; Caralp, F. Phys. Chem. Chem. Phys. 2003, 5, 5431. (c) Orlando, J. J.
Phys. Chem. Chem. Phys. 2007, 9, 4189. (d) Aschmann, S. M.; Atkinson,
R. Int. J. Chem. Kinet. 1999, 31, 501.
copherol, forming the corresponding peroxyacetal, which
decomposes into the R-alkoxy alkoxy radical. To determine
out how these biological molecules are damaged, under-
standing properties of the R-alkoxy alkoxy radicals is
necessary. Third, as shown in Scheme 1, oxidation of
carbohydrates and their analogues by oxidants such as
2b
(
2) (a) Juzeniene, A.; Peng, Q.; Moan, J. Photochem. Photobiol. Sci.
2
007, 6, 1234. (b) Halliwell, B.; Gutteridge, J. M. C. Free Radicals in
Biology and Medicine, 4th ed.; Oxford University Press: New York, 2007;
pp 69-78.
10.1021/ol901215y CCC: $40.75
Published on Web 07/07/2009
 2009 American Chemical Society

(
diacetoxyiodo) benzene and iodine usually generates the
corresponding R-alkoxy alkoxy radicals, followed by frag-
3
mentation into several types of useful chemicals. However,
the R-alkoxy alkoxy radicals that were claimed as intermedi-
ates in the oxidation of carbohydrates have not yet been
identified.
Some R-alkoxy alkoxy radicals have been claimed or
assumed to be intermediates, which were formed in situ, in
the following reactions, but they were not directly observed.
Poranski, Jr. et al. used carbon-13 CIDNP to observe
conventional photolysis of tert-butyl hydroperoxide (TBHP)
4
in alcohols with the beam from a CW Hg/Xe arc source. In
this photolysis, peroxyhemiacetals were generated in situ,
followed by decomposition into carbonyl compounds pos-
sibly through R-hydroxy alkoxy radical. Wallington et al.
used modulated photolysis of Cl
or pulse radiolysis of SF /CH OCH
, whose self-reaction produced CH
followed by ꢀ-C-H scission or reacting with molecular
2
/CH
3
OCH
3 2 2
/O /N mixtures
6
3
3
/O
2
mixtures to generate
•
•
Figure 1
deoxygenated 2:1 CD
66 nm.
.
1H NMR spectra for laser flash photolysis of 2 in
CN/D O with many shots of pulse laser at
CH
3
OCH
2
O
2
3 2
OCH O ,
3
2
2
5
3
oxygen to form CH OCHO. Using high-level ab initio
calculations (CCSD(T)//MP2), Henon, et al. found that the
activation energy of ꢀ-C-H scission is around 10 kcal/mol
less than that of ꢀ-C-O scission for the decomposition of
scission was not observed. If the radical 3 undergoes
H-abstraction, the unstable hemiacetal product would follow
•
1b
2
ROCH O .
ꢀ-elimination to form benzaldehyde and n-butanol. However,
6
In this paper, we used peroxyacetal 2 as a source of
R-alkoxy benzyloxy radical 3 and explored this radical’s UV
benzaldehyde is not the reaction product, so it indicates that
the ꢀ-C-H scission rate of 3 is much faster than its
H-abstraction. On the other hand, when laser flash photolysis
3
spectrum, decomposition pattern, reactivity with PPh ,
oxygen, and isopropyl alcohol, and quantum yield. Laser
flash photolysis of 2 in deoxygenated aqueous acetonitrile
with a 266-nm pulse from a nanosecond Nd:YAG laser
generated the radical 3, which decomposed into n-butyl
benzoate through ꢀ-C-H scission (Scheme 2). Product
3
of 2 was carried out in deoxygenated CD CN without water,
not only n-butyl benzoate from ꢀ-C-H scission but also
benzaldehyde from ꢀ-C-O scission were observed in a ratio
of 3:1. Because laser flash photolysis of 2 in aqueous
acetonitrile produced a simple decomposition pattern, we did
the rest of experiment in this solvent system. Laser flash
photolysis of 2 in deoxygenated aqueous acetonitrile with
many shots of the pulse laser was also monitored by
conventional UV spectrophotometer. As shown in Figure 2,
Scheme 2. Generation of R-Alkoxy Benzyloxy Radical 3 from
Laser Flash Photolysis of 2 in Deoxygenated Aqueous
Acetonitrile, Followed by ꢀ-C-H Scission
analysis by HPLC for the laser flash photolysis of 2 in
aqueous acetonitrile showed that n-butyl benzoate was the
product, but benzaldehyde was not found. Since only a small
amount of 2 was consumed in a single shot of laser flash
Figure 2
. UV spectra for laser flash photolysis of 2 in deoxygenated
2:1 CH CN/H O with many shots of pulse laser at 266 nm.
3
2
3 2
photolysis, 2 in deoxygenated 2:1 CD CN/D O was treated
absorption at 230 nm (2: 2.3 × 10 M, ε ) 2392 cm-1
-4
with many shots of pulse laser at 266 nm and monitored by
1
-1
H NMR spectrometer. As shown in Figure 1, a series of
M
at 230 nm) kept growing as the number of shots of
pulse laser increased, generating the product of n-butyl
1
the H NMR spectra show that [2] kept decreasing and
-
1
-1
[
n-butyl benzoate] kept increasing as the number of shots
benzoate (ε ) 10,000 cm
M
at 230 nm). According to
of pulse laser increased, but benzaldehyde from ꢀ-C-O
the above results, the radical 3, generated by laser flash
Org. Lett., Vol. 11, No. 15, 2009
3371

photolysis of 2 in deoxygenated aqueous acetonitrile, follows
-C-H scission much faster than ꢀ-C-O scission and H-
abstraction. The results confirm Henon’s theoretical
transition of intramolecular charge transfer from benzene ring
10
ꢀ
to oxygen radical. The weak visible light absorption at 420
nm for the radical 3 is likely to be attributed to the charge-
transfer band. Hence, the transient we observed in Figure 3
is supposed to be the R-alkoxy benzyloxy radical 3.
Scaiano et al. reported that alkoxy radicals such as the
tert-butoxy radical, generated by laser flash photolysis in 1:2
1
b
findings that ꢀ-C-H scission is much faster than ꢀ-C-O
•
scission for the decomposition of ROCH
photodecomposition of 2 produces the in-cage radical pair,
and tert-butoxy radical. tert-Butoxy radical is known to
do H-abstraction from various H-atom donors, such as
2
O . In addition,
3
3
benzene/t-BuOO-t-Bu, can be quenched by PPh with a rate
7
9
-1 -1
toluene, Ph
2
CHOH, and i-PrOH. It is likely that tert-butoxy
constant of 1.9 × 10 M s , producing a tert-butoxy-
triphenylphosphoranyl radical with a lifetime of 900 µs and
radical performs H-abstraction from the in-cage radical 3,
enhancing ꢀ-C-H scission rate of 3. Recently, Orlando did
11
a maximum of the transient absorption spectrum at 430 nm.
atmospheric oxidation of diethyl ether and found that ꢀ-C-
Because PPh reacts very fast with alkoxy radicals at a
3
•
C(alkyl carbon) scission of CH
3
CH
2
O-CH(O )CH
3
is much
diffusion rate, we tried to use it to quench the labile radical
3. The transient generated by laser flash photolysis of 2 in
deoxygenated 66.7% acetonitrile aqueous solution can also
faster than ꢀ-C-H and ꢀ-C-O scissions because ethyl formate
1
c
is the major product. Combining the result with our
findings, one can draw the ꢀ-scission rate sequence of
R-alkoxy alkoxy radicals: ꢀ-C-C(alkyl carbon) scission >
9
-1
be quenched by PPh
3
with a rate constant of 4.0 × 10 M
-1
s , producing another transient with a maximum absorption
at around 400 nm (Figure 4). The decay rate constants of
ꢀ
-C-H scission > ꢀ-C-O scission. This ꢀ-scission rate
sequence is consistent with the results for oxidation of
carbohydrates shown in Scheme 1.
3
As shown in Figure 3, laser flash photolysis of 2 in
deoxygenated 66.7% acetonitrile aqueous solution produces
Figure 4
nm laser excitation of 2 in the presence of PPh
6.7% acetonitrile aqueous solution.
.
Transient absorption spectrum recorded 170 ns after 266-
3
in deoxygenated
6
Figure 3. Transient absorption spectrum recorded 160 ns after 266-
the transient absorption at 310 nm were found to be
proportional to [PPh ], and the correlation curve fits the
nm laser excitation of 2 in deoxygenated 66.7% acetonitrile aqueous
solution.
3
6
equation of kobs ) k
0
+ kPPh3[PPh
3
], where k
0
) 4.0 × 10
-
1
9
-1 -1
s
and kPPh3 ) 4.0 × 10 M s . The k
0
is close to the
the transient absorption spectrum with a strong absorption
maximum at around 310 nm and two weak absorption
maxima at 370 and 420 nm. The transient decay at these
maxima gives a reasonable fit to first-order kinetics with a
(
3) (a) Francisco, C. G.; Martin, C. G.; Suarez, E. J. Org. Chem. 1998,
6
3, 2099. (b) Hernandez, R.; Leon, E. I.; Moreno, P.; Suarez, E. J. Org.
Chem. 1997, 62, 8974. (c) de Armas, P.; Francisco, C. G.; Suarez, E. J. Am.
Chem. Soc. 1993, 115, 8865. (d) Francisco, C. G.; Freire, R.; Gonzalez,
C. C.; Suarez, E. Tetrahedron: Asymmetry 1997, 8, 1971.
6
-1
lifetime of 158 ns and a rate constant of 4.4 × 10 s . This
is consistent with the known results that the electronic
transition of alkoxyl radicals between the ground state and
(
4) Moniz, W. B.; Sojka, S. A.; Poranski, C. F., Jr.; Birkle, D. L. J. Am.
Chem. Soc. 1978, 100, 7940.
5) (a) Jenkin, M. E.; Hayman, G. D.; Wallington, T. J.; Hurley, M. D.;
Ball, J. C.; Nielsen, O. J.; Ellermann, T. J. Phys. Chem. 1993, 97, 11712.
b) Wallington, T. J.; Hurley, M. D.; Ball, J. C.; Straccia, A. M.; Platz, J.;
Christensen, L. K.; Sehested, J.; Nielsen, O. J. J. Phys. Chem. A 1997,
01, 5302.
6) (a) Synthetic procedure. To benzaldehyde (2 mmol) and 4 Å
molecular seives (0.5 g) in CHCl (2 mL) at rt was added TiCl (0.1 mmol,
(
8
the first excited state lies around 300 nm. In deoxygenated
(
aqueous acetonitrile, photodecomposition of 2 generates two
radicals: tert-butoxy radical and the radical 3. Scaiano et al.
reported that tert-butoxy radical has a very weak absorption
maximum at 320 nm, but it is too weak to observe for kinetic
1
(
3
4
1
3
0% in CHCl ). The mixture was stirred at rt for 1 h. Toluene solution of
TBHP (1.7 mmol) and n-butanol (1 mmol) were added into the mixture,
followed by stirring at rt condition for 2 d. The product 3 was purified by
column chromatography with silica gel as stationary phase and hexane/
EtOAc as mobile phase. (b) Ochiai, M.; Ito, T.; Takahashi, H.; Nakanishi,
A.; Toyonari, M.; Sueda, T.; Goto, S.; Shiro, M. J. Am. Chem. Soc. 1996,
118, 7716.
9
study. The other radical 3, however, has a phenyl chro-
mophore, which makes its molar absorptivity higher. In
addition, benzyloxy and cumyloxy radicals were found to
have weak visible light absorptions due to the π f π*
3372
Org. Lett., Vol. 11, No. 15, 2009

6
-1
rate constant (4.4 × 10 s ) that is associated with the
transient decay at 310 nm in the absence of PPh . The decay
of the transient absorption at 400 nm, generated by quenching
of 3 with PPh , is slower than its growth and follows first-
form benzaldehyde, which was confirmed by HPLC with an
authentic sample. The transient 3 generated by laser flash
photolysis of 2 in deoxygenated 66.7% acetonitrile aqueous
solution was quenched by various [i-PrOH]. The correlation
between the decay rate constants of the transient absorption
at 310 nm and [i-PrOH] gave the quenching rate constant
3
3
order kinetics with a lifetime of 1.7 µs. Hence, the quenching
experimental result is consistent with the assignment of the
radical 3.
6
-1 -1
(ki-PrOH) of 1.3 × 10 M s , which is consistent with the
6
-1
The transient absorption at 310 nm can also be quenched
i-PrOH quenching rate constant (ki-PrOH ) 1.8 × 10 M
-
1
7
•
by O
2
efficiently, forming n-butyl benzoate through ꢀ-C-H
quenching of other
solubility in acetonitrile and water
3 3
s ) for (CH ) CO . The H-abstraction of R-alkoxy alkoxy
scission, which is consistent with O
2
radicals might also be found in conventional photolysis of
TBHP in alcohols, in which peroxyhemiacetals were gener-
12
alkoxy radicals. The O
at 1 atm O
and 298 K is reported to be 9.1 and 1.39 × 10
M. The equilibrium between oxygen dissolved in a solvent
[O ) and molecular oxygen in the gas phase ([O ) is
temperature-dependent. Hence, the equilibrium constant
of ([O )/([O ) in 66.7% acetonitrile aqueous solution at
98 K is assumed to be 1.63 × 10 M atm . The transient
generated by laser flash photolysis of 2 in 66.7% aceto-
2
-
3
4
2
ated in situ. Decomposition of the peroxyhemiacetals into
13a
carbonyl compounds is assumed to go through R-hydroxy
alkoxy radicals, followed by (1) H-abstraction from alcohols
and (2) ꢀ-elimination.
(
]
2 s
2 g
]
1
3b
2
]
s
]
2 g
The quantum yield for the formation of 3 in laser flash
photolysis of 2 in deoxygenated 66.7% acetonitrile aqueous
solution was evaluated to be 0.027 according to the equation
-3
-1
2
3
-
•
- •
- •
nitrile aqueous solution was quenched by various [O
which was controlled by [O . The quenching rate constant
O2) for the transient absorption at 310 nm was calculated
2 s
] ,
[A450(SO4 )/A310(3)] ) [ε450(SO4 ) × Φ(SO )]/[ε310(3)
4
1
6
- •
]
2 g
× Φ(3)], which can be reformulated into [A450(SO4 )/
-
•
- •
(
k
[3]] ) [ε450(SO4 ) × Φ(SO )]/[Φ(3)]. Potassium peroxo-
4
8
-1 -1
to be 6.6 × 10 M s . It is consistent with O
2
quenching
disulfate (K S O ) was used as the chemical actinometer,
2
2
8
•
8
-1 -1 14
for ClCH
2
O (k
O
) 1.9 × 10 M s ). Similarly, reactions
and we used the solution of 2 with the same optical densities
2
of other R-alkoxy alkoxy radicals with molecular oxygen
at 266 nm as that of K S O . The formation of a sulfate
2
2
8
1
c,5
- •
also produced esters through ꢀ-C-H scission.
intensities and decay rates of oxygen-center tertiary alkoxy
radicals, such as cumyloxy radicals, tert-butoxy radical, and
aroyloxy radicals, are unaffected by molecular oxygen.
Usually,
radical (SO4 ), which was generated by laser flash pho-
-
•
tolysis of K S O , was monitored at 450 nm (ε450(SO4 ) )
2
2
-1
8
-
1
- •
16
- •
1400 M cm , Φ(SO ) ) 1.4), and A450(SO4 ) was
4
1
0,15
measured. The concentration of the transient 3 in a single
Hence, the transient, which absorbs at 310 nm and is affected
by molecular oxygen, is not tert-butoxy radical but the radical
shot of laser flash photolysis of 2 was calculated on the basis
of generated [n-butyl benzoate] in 80 shots of laser at 266
nm, which was calculated from their H NMR spectra (Figure
1
3
.
Because i-PrOH is a good H-atom donor, we used it as a
1).
quencher for the radical 3 to perform H-abstraction, produc-
ing butoxy(phenyl)methanol, followed by ꢀ-elimination to
In conclusion, the R-alkoxy benzyloxy radical 3 is very
unstable and highly reactive and performs ꢀ-C-H scission
much faster than ꢀ-C-O scission and H-abstraction.
(7) Lusztyk, J.; Kanabus-Kaminska, J. M. In CRC Handbook of Organic
Photochemistry; Scaiano, J. C., Ed.; CRC Press: Boca Raton, FL, 1989;
Vol. II, p 184.
Acknowledgment. Financial support from the National
Science Council of Taiwan (NSC 98-2113-M-006-001-MY3)
is gratefully acknowledged.
(
8) Chatgilialoglu, C. In CRC Handbook of Organic Photochemistry;
Scaiano, J. C., Ed.; CRC Press: Boca Raton, FL, 1989; Vol. II, pp 3-
1
1.
(
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Supporting Information Available: Experimental pro-
(
1
13
cedures and H and C NMR spectra and characterization
of 2 and n-butyl benzoate. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
Zgierski, M. Z.; Lusztyk, J. J. Am. Chem. Soc. 1995, 117, 2711. (c)
Baciocchi, E.; Bietti, M.; Salamone, M.; Steenken, S. J. Org. Chem. 2002,
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7, 2266.
(
11) Griller, D.; Ingold, K. U.; Patterson, L. K.; Scaiano, J. C.; Small,
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R. D., Jr. J. Am. Chem. Soc. 1979, 101, 3780.
(
(
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