Reactivity and Product Analysis of a Pair of Cumyloxyl and tert-Butoxyl Radicals Generated in Photolysis of tert-Butyl Cumyl Peroxide

Article abstract of DOI:10.1021/acs.joc.0c01016

Alkoxyl radicals play important roles in various fields of chemistry. Understanding their reactivity is essential to applying their chemistry for industrial and biological purposes. Hydrogen-atom transfer and C-C β-scission reactions have been reported from alkoxyl radicals. The ratios of these two processes were investigated using cumyloxyl (CumO?) and tert-butoxyl radicals (t-BuO?), respectively. However, the products generated from the pair of radicals have not been investigated in detail. In this study, CumO? and t-BuO? were simultaneously generated from the photolysis of tert-butyl cumyl peroxide to understand the chemical behavior of the pair of radicals by analyzing the products and their distribution. Electron paramagnetic resonance and/or transient absorption spectroscopy analyses of radicals, including CumO? and t-BuO?, provide more information about the radicals generated during the photolysis of tert-butyl cumyl peroxide. Furthermore, the photoproducts of (3-(tert-butylperoxy)pentane-3-yl)benzene demonstrated that the ether products were formed in in-cage reactions. The triplet-sensitized reaction induced by acetophenone, which is produced from CumO?, clarified that the spin state did not affect the product distribution.

Full text of DOI:10.1021/acs.joc.0c01016

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Article
Reactivity and Product Analysis of a Pair of Cumyloxyl and tert-
Butoxyl Radicals Generated in Photolysis of tert-Butyl Cumyl Peroxide
Ryoko Oyama, and Manabu Abe
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01016 • Publication Date (Web): 04 Jun 2020
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Reactivity and Product Analysis of a Pair of Cumyloxyl and
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tert-Butoxyl Radicals Generated in Photolysis of tert-Butyl
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Cumyl Peroxide
Ryoko Oyamaa and Manabu Abea,b*
aDepartment of Chemistry, Graduate School of Science, Hiroshima University
1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan
bHiroshima University Research Center for Photo-Drug-Delivery Systems (HiU-P-DDS), Hiroshima
University
1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan
mabe@hiroshima-u.ac.jp
ABSTRACT:
Alkoxyl radicals play important roles in various fields of chemistry. Understanding their reactivity is
essential to applying their chemistry for industrial and biological purposes. Hydrogen atom transfer
and C–C scission reactions have been reported from alkoxyl radicals. The ratios of these two
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processes were investigated using the cumyloxyl (CumO•) and tert-butoxyl radicals (t-BuO•),
respectively. However, the products generated from the pair of radicals have not been investigated in
detail. In this study, CumO• and t-BuO• were simultaneously generated from the photolysis of tert-
butyl cumyl peroxide to understand the chemical behavior of the pair of radicals by analyzing the
products and their distribution. Electron paramagnetic resonance and/or transient absorption
spectroscopy analyses of radicals, including CumO• and t-BuO•, provide more information about the
radicals generated during the photolysis of tert-butyl cumyl peroxide. Furthermore, the photoproducts
of (3-(tert-butylperoxy)pentane-3-yl)benzene demonstrated that the ether products were formed in in-
cage reactions. The triplet-sensitized reaction induced by acetophenone, which is produced from
CumO•, clarified that the spin-state did not affect the product distribution.
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INTRODUCTION
Alkoxyl radicals play crucial roles in various fields of chemistry, such as autoxidation in chemical
industry1 and DNA damage caused by intracellular lipid peroxidation2,3. Alkoxyl radicals can be
generated through thermal decomposition4 and the Fenton reaction5 of peroxides. The photochemical
generation of alkoxyl radicals from di-tert-butyl peroxide (I)6 has been frequently used in the initiation
of radical reactions for organic synthesis. In addition, pyridinethione (II)7, pyridone (III)8, perbenzoate
(IV)9, and thiazolethione (V)10 are known as radical donors in photolysis (Figure 1).
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Figure 1. Precursors of alkoxyl radicals in photolysis
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In the 1960s, Walling et al. reported the reactivity of alkoxyl radicals and clarified that the hydrogen
atom transfer (HAT) and C–C -scission reactions occur competitively (Figure 2)11. The ratios of these
two processes were investigated using the cumyloxyl radical (CumO•, R = Ph) and the tert-butoxyl
radical (t-BuO•, R = Me).12,13 The ratio was found to be dependent on the solvent polarity, acidity, and
steric effect. The reactivity of the two processes was discussed by Yurtsever et al. using quantum
chemistry calculations,14 indicating that the most stable products from CumO• and t-BuO• are Ⅵ and
Ⅶ, respectively (Figure 3).
Figure 2. Reactivity of alkoxy radicals in hydrogen atom transfer (HAT) and C–C β-scission
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Figure 3. Products with maximum stabilities that were obtained from CumO• and t-BuO•
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●
There are few reports on the direct observation of the two alkoxyl radicals (CumO and t-BuO ) and
the investigation of reaction products12a,16. The products of the alkoxy radicals have not been clarified
in detail. In this study, we are interested not only in the products of alkoxy radicals but also in the
products derived from the pair of radicals. The products derived from the radical pair cannot be
distinguished in the photolysis of symmetrically substituted peroxides such as di-tert-butyl peroxide.
To this end, in this study, the asymmetrically substituted tert-butyl cumyl peroxide derivatives 1a and
b were selected to determine the products derived from two alkoxyl radicals and the pair of radicals
(Figure 4).
Figure 4. Photochemical decomposition of tert-butyl cumyl peroxide derivatives (1a,b) used in this
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study.
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RESULTS AND DISCUSSION
Product analysis in the photolysis of 1a. First, a UV-vis absorption spectroscopic analysis was
conducted for the synthesized compound 1a (R = Me) (Figure 5). Structured absorption bands were
observed at approximately 240–270 nm in acetonitrile. A 266 nm laser was chosen as the light source
for the photoreaction of 1a. The photoreaction of 1a (20.5 mM) was conducted using a 266 nm laser
(1 mJ/pulse, 10 Hz) in CD3CN (0.5 mL) at 25 °C under air or O2 conditions (Table 1).
Figure 5. UV-vis absorption spectrum of 1a in acetonitrile.
After 1 h of photolysis in the nuclear magnetic resonance (NMR) tube, 11 photoproducts 2-
11,11-d were detected and identified by 1H NMR analysis (Table 1). The photoproducts were derived
from the A , B , and A/B sides. The A-side products consisted of acetophenone (2), -cumyl alcohol
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(3), and methyl cumyl ether (4). Acetone (5), tert-butanol (6), and tert-butyl methyl ether (7) were
derived from the B-side products. Methanol (8), formaldehyde (9), ethane (10), methane (11), and
mono-deuterated methane; CH3D (11-d) were found to be formed from the •CH3 generated from the
-scission of the two alkoxy radicals. The chemical yields of the photoproducts and the conversion of
1a were determined using triphenylmethane as an internal standard (Table 1). The conversions of 1a
under air and O2 conditions was 70.8% and 72.2 %, respectively (entries 1 and 2). Under air conditions
([O2] = 1.9 mM, entry 1), acetophenone (2) was exclusively formed in 94.1 % of the A-side products,
together with a small amount of alcohol 3 and ether 4. The selective formation of acetone (5) was
found in 57.7% of the B-side products, together with a significant amount of the corresponding alcohol
6 (18.7%) and ether 7 (17.7%). The products 8-11 and 11-d derived from •CH3 were identified by
comparing the NMR signals of the authentic samples (Figure S2a-d). The oxygenated compounds 8
and 9 were derived from the reaction of the methyl radical with molecular oxygen.
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Under O2 conditions ([O2] = 9.1 mM, entry 2), an increase in the chemical yields of alcohols 3 and 6
and oxygenated compounds 8 and 9 were observed with the decrease in the formation of ethane (10)
and ethers 4 and 7, indicating that •CH3 generated from -scission from the alkoxy radicals escaped to
the out-of-cage space to be trapped by O2 to yield oxygenated compounds 8 and 9. The decrease in the
formation of ethers 4 and 7 also supports this mechanism. The reaction of •CH3 with O2 was computed
at UB3LYP17/6-31G(d)18 to be exothermic in the formation of methyl peroxide, ΔH298 = –31.25 kcal
mol-1, without an energy barrier (Figure 6, Figure S35). The peroxide is the precursor for methanol (8)
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and formaldehyde (9). 19, 20
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Table 1. Products and chemical yields in photolysis of 1a at 266 nm irradiationa
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conv
entry
A-side
B-side
A/B-side
/%
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d
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O2
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94.1 5.1 2.5 57.7 18.7 17.7
96.6 7.3 1.9 60.6 30.0 14.3 14.6 1.7 31.3 4.3 0.8
60.8 7.1 3.9 31.2 18.7 19.4 3.4 0.5 10.1 2.0 0.4
4.8 0.5 37.2 3.1 1.6
3b
Air
aChemical yields of the photoproducts were calculated using triphenylmethane as an internal standard.
b
Experimental error (%) is photoproduct chemical yield (%) x (± 5-8%). Triplet-sensitized
photoreaction of 1a (30 mM, Abs at 266 nm = 2.6) in the presence of acetophenone (2) (51mM, Abs
at 266 nm = 34.7).
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Figure 6. Generation and reactivity of •CH3
Detection of alkoxyl radicals, CumO•, and t-BuO•. In the product analysis mentioned above,
two types of alkoxyl radicals, CumO• and t-BuO•, were proposed to be formed in the photolysis of 1a.
The detection of the two alkoxyl radicals was conducted by laser-flash-photolysis (LFP) and electron
paramagnetic resonance (EPR) measurements. In the LFP measurements, 266 nm of light (Nd-YAG,
10 mJ/pulse, 10 ns pulse-width) was irradiated into the solution of 1a (8.5 mM, MeCN, Abs = 1.1 at
266 nm) under air conditions at ~20 °C. After laser irradiation, the generation and decay of CumO•
were detected at 485 nm15 (kdecay = 6.7×105 s-1, Figure 7), which is consistent with the reported value
of CumO•.15
Figure 7. Decay process of CumO• observed at 485 nm in the laser flash photolysis of 1a.
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In the EPR measurements, the spin-trapping method was used to analyze the short-lived radicals. A
solution of 1a and ~10 equivalents of the spin trapping reagent 5,5-dimethyl-1-pyrroline N-oxide
(DMPO) (1a: 12 mM, DMPO: 141 mM, MeCN) was prepared. After photoirradiation of the solution
in a flat quartz cell with a high-pressure Hg lamp under air at 25 °C, the typical EPR signals for
nitroxides (R2N–O•) were detected (Figure 8a, Figure S19). To obtain information on the nitroxide
structures, the spectra were compared with those observed in the photolysis of di-tert-butyl peroxide
and dicumyl peroxide in the presence of DMPO (Figure 8b,c, Figures S20,21). The EPR signals
obtained in the photolysis of 1a are consistent with the sum of the two EPR spectra obtained in the
photolysis of the two peroxides. Futhermore, the simulated spectrum of the two nitroxides derived
from the reaction of CumO• and t-BuO• with DMPO (nitroxides 12 and 13) was consistent with the
experimentally observed spectrum, which can be seen by comparing Figure 8a with 8d. The triplet
signals at g-values of 1.997, 2.006, and 2.015 with a hyperfine constant of 15.2 G were consistent with
those obtained in the photolysis of DMPO in the absence of peroxides (Figure 8e, Figure S22). MS
analysis of the product confirmed that the nitroxide signals were derived from 5,5-dimethylpyrrolidin-
2-one oxide (Figure S34).
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Figure 8. EPR spectra obtained after photolysis of 1a and DMPO. (a) DMPO and di-tert-butyl
peroxide, (b) DMPO and dicumyl peroxide, (c) simulation spectrum of sum of (b; aN = 13.50 G, a
=
H
10.75 G, aH = 1.27 G), and (c; aN = 13.42 G, aH = 11.05 G, aH = 1.28 G) (not included ＊ peaks),
and (d) spectrum obtained after photoirradiation of DMPO (e)
To obtain information about the structures detected in the photoreaction of 1a and DMPO, an MS
analysis was conducted on the photolysate (Figure 9, Figures S29-32). In addition to the mass numbers
of the two alkoxyl-radical-trapped nitroxides 12 (MS 180.15) and 13 (MS 248.17), three radical
trapping compounds 14–16 were detected, indicating that methyl, methoxyl, and hydroxyl radicals
were formed during the photolysis of 1a.
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Figure 9. Five spin adducts were detected by electrospray ionization-MS (FTMS, Positive)
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measurements.
Mechanism. The mechanism of the photochemical reaction of 1a (R = CH3) is summarized in
Scheme 1, which is proposed on the basis of the products and spectroscopic observations. After the
homolytic O–O bond cleavage of 1a, the radical pair of CumO• (A: R = CH3) and t-BuO• B is
generated, which followed by the -scission reaction that lead to the production of ketones 2 (R = CH3)
and 5, as well as •CH3 and R• (R = CH3). Moreover, HAT produces corresponding alcohols 3 (R =
CH3) and 6. The released •CH3 reacts with the alkoxyl radicals to produce ethers 4 (R = CH3) and 7.
Once the •CH3 is trapped by O2, methanol (8) and formaldehyde (9) are formed after the O–O bond
cleavage, from which methoxyl and hydroxyl radicals can be generated. The dimerization of •CH3
produces ethane (10). Methane (11) can be formed by the hydrogen atom abstract from •CH3. The
deuterated isomer is formed by deuterium-atom abstraction from CD3CN. As shown in Scheme 1, the
mechanism of the formation of products in the photolysis of 1a is reasonable based on the product and
spectroscopic analyses.
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Scheme 1. Mechanism of the photolysis of 1a,b
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There are some additional questions. The first question concerns the source of hydrogen atoms. As
judged by the bond dissociation energies21, the C–H bond dissociation energy of acetonitrile is the
lowest, indicating that the hydrogen sources are CH3CN, CDH2CN, and CD2HCN, which are
contaminated in 99%-d CDCN3. In fact, deuterated methane (11-d, CH3D) was detected by an NMR
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analysis of the photolysate (Figure S2d). Other hydrogen sources are 1a and/or photoproducts such as
acetophenone (2) because non-deuterated methane (11-d) was observed during photolysis.
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The second question concerns the difference in the chemical yields of ketones 2 and 5, which are the
products of the -scission from CumO• and t-BuO•, respectively. Thus, the chemical yield of 2 (~90%)
was significantly higher than that of 5 (~50%). This is because of the differences in the transition-state
energies in the -scissions of CumO• and t-BuO•. From the quantum chemical calculations at the
UB3LYP17/6-31G(d)18 level, the -scission energy in CumO• was found to be lower than that of t-
BuO• by ~2 kcal mol-1 due to the stabilization effect of the phenyl ring (Figure 10). Indeed, the faster
-scission in CumO• than that in t-BuO• was experimentally found to be k = 7.4×105 s-1 and 6.4×
105 s-1, respectively.12b,13e The longer-lived t-BuO• has a greater chance to abstract a hydrogen atom
and react with •CH3 to yield an alcohol (6) and ether (7), respectively. The difference in the  scission
energy between CumO• and t-BuO• is key to understanding the product distribution.
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DG298 K
computed at 298 K
in vacuum at
UB3LYP/6-31G(d)
(kcal mol-1)
13.34
DH298‡ = 14.39
DS298‡ = 0.0035
11.21
TSB side
DH298‡ = 12.45
DS298‡ = 0.0042
TSA side
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0
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-9.52
DH298‡ = 3.76
DS298‡ = 0.0446
-11.96
DH298‡ = 0.99
DS298‡ = 0.0435
Figure 10. Difference in the -scission transition energy between Aside (CumO•) and B side (t-BuO•).
The energies were calculated at the UB3LYP/6-31G(d) level of theory.
The third question is whether ether products 4 and 7 are in-cage or out-of-cage products. Because both
alkoxyl radicals can release •CH3, it is difficult to distinguish the two processes. To solve this problem,
(3-(tert-butylperoxy)pentane-3yl)benzene (1b), in which the methyl substituents are replaced by ethyl
substituents, was synthesized from 1-ethyl-1-phenylpropyl hydroperoxide (see the experimental
section) and was irradiated under similar conditions as 1a (Figure 11).
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Figure 11. Photoreaction of (3-(tert-butylperoxy)pentane-3yl)benzene (1b)
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The alkoxyl radicals 1-ethyl-1-phenylpropoxyl (EPPO•) and tert-butoxyl (t-BuO•), are generated
during the photolysis of 1b, followed by -scission reactions to produce •C2H5 and•CH3. It is possible
to understand the reaction pathway for in-cage reactions and/or out-of-cage reactions, which produce
ether products. The UV-vis absorption spectrum of 1b (Figure S15) is very similar to that of 1a. The
photoreaction of 1b was also conducted using a 266 nm laser as a light source. After the photoreaction
of 1b (20.2 mM, in CD3CN) under air at 25 °C for 1 h, the photoproducts 5-11, 17, and 21-26 were
detected by 1H NMR analysis (Table 2, Figure S4a-e). The chemical yields of the photoproducts and
the conversion yields of the photoreaction were calculated using triphenylmethane as an internal
standard for the photolysis of 1a (Table 2).
Table 2. Products and chemical yields during photolysis of 1b at 266 nm irradiationa
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aChemical yields of photoproducts were calculated using triphenylmethane as internal standard.
b
Experimental error (%) is photoproduct chemical yield (%)×(± 5-8%). The chemical yields of 23,
10-d, and 26 were not calculated due to overlap of these 1H NMR peaks.
Interestingly, alcohol and ether products 18–20 were not detected in the A-side products derived from
EPPO• (A: R = CH2CH3, Scheme 1). To understand the effect of the ethyl group on the product
selectivity, the transition-state structure of the -scission process was computed at the same level of
theory (Figure12). The Gibbs activation energy of the -scission process in EPPO• was found to be
‡
ΔG298 = 7.24 kcal/mol, which was lower than those in CumO• and t-BuO• by ~4 kcal mol-1 and ~6
kcal mol-1, respectively. Bietti et al. reported that the C–Et -scission in 2-(4-methylphenyl)-2-butoxyl
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radical was found to be 350 times faster than the C–Me -scission in 4-methylcumyloxyl radical.13d
Therefore, the -scission in EPPO• is expected to be much faster than in t-BuO•, and thus, EPPO• is
shorter than CumO• and t-BuO•. Indeed, only propiophenone (17) from the A-side was detected in the
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photolysis of 1b.
DG298 K
(kcal mol-1)
computed at 298 K
in vacuum at
UB3LYP/6-31G(d)
13.34
DH298‡ = 14.39
DS298‡ = 0.0035
7.24
TSB side
DH298‡ = 7.79
DS298‡ = 0.0019
TSA side
0
24
-9.52
DH298‡ = 3.76
DS298‡ = 0.0446
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-17.63
DH298‡ = -3.78
DS298‡ = 0.0465
Figure 12. Difference in the -scission transition energy between the A side (EPPO•) and the B side
(t-BuO•). Energies were calculated at UB3LYP/6-31G(d) level of theory.
It should be noted that tert-butyl ethyl ether (25) was more preferentially formed than tert-butyl methyl
ether (7). This observation can be explained by the in-cage reaction of the pair of radicals EPPO• and
t-BuO•. Thus, •C2H5 is released rapidly from EPPO• at the A-side owing to the fast -scission process.
Another radical in the radical pair, t-BuO•, has a greater opportunity to react with •C2H5 to yield ether
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25 than the reaction with •CH3 (Figure 13a), which is released from the -scission reaction of t-BuO•
(Figure 13b). These results suggest that the ethers at the B side in the photolysis of 1a are mainly
generated from in-cage reactions (Scheme 1).
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Figure 13. (a) In-cage reaction (b) Out-of-cage reaction
Importantly, ethylene (24) was detected during the photolysis of 1b (Figure S4c). The formation of
ethylene (24) was derived from the in-cage reaction of •C2H5, which is generated from the-scission
of EPPO•, with t-BuO• (Figure 14) because the chemical yield of tert-butanol (6) in the photolysis of
1b was higher than that in the photolysis of 1a. The mechanism of the photochemical decomposition
of 1b (R = CH2CH3) is also summarized in Scheme 1. The alkoxyl radical A (R = CH2CH3) at the A
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side releases more R• than •CH3 from the B side because the -scission transition-state energy at the
A side is lower than that of the B side. The lifetime of alkoxyl radical A (R = CH2CH3) is shorter than
that of t-BuO• (= B). The relatively high chemical yields of ethane (10) even under oxygen atmosphere
can also be explained by the in-cage reaction (Scheme 1). Thus, the methyl radicals generated by the
β-scission from CumO• and t-BuO• are coupled each other to give ethane before reacting with
molecular oxygen, although the oxygenation process is supposed to be barrierless (Figure 6).
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Figure 14. Formation of tert-butanol (6) and ethylene (24)
Effects of acetophenone on product distribution. When the photoreaction of 1a (3.7 mM in
MeCN) using a 266 nm laser was monitored by a UV-vis spectrometer, the absorption spectrum of 1a
(blue line in Figure 15) gradually changed to the red spectrum after 1 h of irradiation. The red spectrum
is consistent with the spectrum of acetophenone (2), indicating that the 266 nm light mainly excites 2
after 30 min of the photolysis of 1a. The product distribution of the acetophenone-induced
decomposition of 1a should be investigated to understand the mechanism.
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Figure 15. Time-dependent change in the absorption spectrum during the photoreaction of 1a (3.7 mM,
MeCN) using a 266 nm laser (1 mJ) under air at 25 °C. UV-vis absorption spectrum of acetophenone
(2) in MeCN.
First, the rate of the photochemical decomposition of 1a was analyzed to determine whether
acetophenone affects the decomposition efficiency of 1a (Figure 16). A solution of 1a (24.9 mM) and
benzene (99.9 mM) in CD3CN was irradiated with a 266 nm laser (1 mJ) for 7 h under air at room
temperature (~22 °C). By comparing the integration of the benzene signal with that of 1a on the 1H
NMR spectra, the rate of decomposition of 1a was determined. As shown in Figure 16a, the
decomposition of 1a, that is, the conversion (%), was monoexponentially increased to 100 % during
photolysis at 266 nm, suggesting that the decomposition rate induced by the acetophenone triplet is
similar to that of the direct decomposition of 1a. When the chemical yields of the six photoproducts 2,
5, 6, 7, 11, and 11-d were plotted against the irradiation time, mono-exponential increases of these
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products were observed with the mono-exponential decrease of 1a (Figure 16b). Based on the observed
results, the product distribution was not significantly affected by the presence of acetophenone (2).
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Figure 16. (a) Photoreaction conversion yield of 1a, (b) change in the amount of 1a and photoproducts
(2, 5, 6, 7, 11, and 11-d) (mmol) with photoirradiation time.
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The mechanism of the acetophenone-induced decomposition is the energy transfer from the triplet
acetophenone to 1a, because the triplet energy of acetophenone, at 66.2 kcal mol-1, is higher than that
of the triplet state of 1a, 24.0 kcal mol-1, which was computed at the B3LYP/6-31G(d) level of theory.
The quenching reaction of acetophenone by 1a was confirmed by LFP experiments (266 nm, Nd-YAG,
6-7 mJ/pulse, 10 ns pulse-width, Eq. 1, Figure 17). The triplet acetophenone at 320 nm, which is the
triplet-triplet absorption maximum (Figure 17a)22, was quenched by 1a with a quenching rate constant
of 1a; kq = 1.6 × 108 M-1s-1 (Figure 17b). The weak negative signal at ~420 nm is derived from the
phosphorescence of 32*,22b because the decay rate constant, kd = 1.0 × 106 s-1, was consistent with the
rise signal at 420 nm. The alkoxyl radical CumO• at 485 nm in the triplet-sensitized photolysis of 1a
was also detected under air, N2, and O2 conditions at room temperature (~23 °C) (Figure 17c).
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in μs
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Figure 17. (a) Transient absorption spectrum of acetophenone (2) (1.7 mM, Abs at 266 nm = 1.1) at
25 °C under N2. (b) Decay process of acetophenone triplet with/without 1a, which was monitored at
320 nm at room temperature under N2; (c) Decay process of CumO• generated during photolysis of
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1a (11.2 mM, Abs at 266 nm = 0.9) in the presence of large amount of acetophenone (2) (5.6 mM,
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Abs at 266 nm = 3.8) under air, N2, and O2 conditions, which were monitored at 485 nm.
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The product distribution of the acetophenone-triplet-induced decomposition of 1a was examined in
the presence of a significant excess of 2 (entry 3 in Table 1). The absorbance of acetophenone at 266
nm was 14 times higher than that of 1a. After the 266 nm laser irradiation of this mixture for 2 h, the
product distribution was roughly the same as that observed in the photolysis of 1a. This result suggests
that the photoproduct distribution of 1a is not dependent on the spin state or the singlet/triplet, whose
phenomena are consistent with those observed in Figure 16.
CONCLUSIONS
In the present study, the reactivity and chemical fate of the pair of radicals, CumO• and t-BuO• which
were simultaneously generated, were investigated in detail in the photolysis of 1a (R = CH3). The
photoproducts and their distributions were carefully analyzed by 1H NMR spectroscopy. The alkoxyl
radicals produced the corresponding ketones, alcohols, ethers, methane, ethane, methanol, and
formaldehyde in the photolysis of 1a. The product ratio was largely dependent on the substituents.
Thus, the chemical yield of acetophenone (2) from CumO• was much higher than that of acetone (5)
from t-BuO• because the -elimination reaction in CumO• is faster than that in t-BuO•. Primarily ether
product 7 was found to be formed in the pair of radicals, which was an in-cage reaction because ether
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25 preferentially formed over 7 in the photolysis of 1b (R = CH2CH3). From the laser flash photolysis,
EPR measurements, and MS analyses, the generation of the two types of alkoxyl radial intermediates
as well as the generation of radicals from the alkoxy radicals were confirmed in the photolysis of 1a.
The energy transfer from the triplet acetophenone (2) to 1a was also confirmed by analyzing the fall
process of triplet acetophenone in the presence of 1a, indicating that the photoproduct distribution of
1a is independent of the spin state of the excited state of 1a.
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EXPERIMENTAL SECTION
General Information. Materials obtained from commercial suppliers were used as received.
Otherwise noted, all reactions were performed with dry solvents under an atmosphere of nitrogen gas
in dried glassware. All workup and purification procedures were carried out with reagent grade
solvents in air. Thin-layer chromatography (TLC) analyses were performed on commercial aluminium
sheets of Merck silica gel 60F254 and visualized with ultraviolet lamp (λ = 254 nm). Purification was
done by column chromatography using silica gel (63-210 μm). NMR spectra were recorded on a
Bruker Ascend 400 to give 1H NMR (400 MHz) spectra and 13C NMR (100 MHz) spectra. Chemical
shifts for 1H NMR are expressed in parts per million (ppm) relative to tetramethylsilane (δ 0.00 ppm)
or the residual peak of CDCl3 (δ 7.26 ppm) or CD3CN (δ 1.94 ppm). Chemical shifts for 13C NMR
are expressed in ppm relative to CDCl3 (δ 77.16 ppm). Data are reported as follows: chemical shift,
multiplicity (s = singlet, d = doublet, dd = doublet of doublets, t = triplet, q = quartet, dq = doublet of
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quartets, br = broad signal, m = multiplet), coupling constant (Hz), and integration. UV-vis spectra
were recorded on a SIMADZU UV-3600 Plus spectrophotometer. Gas chromatography-mass spectra
(GC-HRMS) were conducted on an Agilent 7890A GC system equipped with a HP-5 column (0.32
mm × 0.25 μm × 30 m; Split ratio 10 : 1, inject temperature: 200˚C, column temperature program:
50˚C, 10˚C min-1 to 300˚C) using Field ionization positive (FI+; 10 kV) for separating compound 1,
methyl 1-ethyl-1-phenylpropyl ether and ethyl 1-ethyl-1-phenylpropyl ether. High-resolution mass
spectra (HRMS) were performed with a Thermo Fisher Scientific LTQ Orbitrap XL using electrospray
ionization (ESI) method. EPR spectra were recorded on a Bruker BioSpin Elexsys E500.
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Synthesis
tert-Butyl Cumyl Peroxide (1a): The compound was prepared according to a known procedure23.
Added a stirring bar to the two-necked flask, drew a vacuum with drying, and purged with nitrogen.
Trichloroacetimidate (0.21 mL, 1.17 mmol) and a solution of cumene hydroperoxide (119.5 mg, 0.79
mmol) in CH2Cl2 1 mL were added to the flask, and the flask was cooled to –20℃ (NaCl + ice water
) with stirring. Then BF3-Et2O diluted with CH2Cl2 (0.6 mL, 0.03 mmol) was dropped slowly to the
reaction mixture. When the reaction temperature reached to room temperature, a small amount of
NaHCO3 was added to the reaction mixture for quenching, and solid was removed by filtration. After
evaporating and purification with column chromatography (hexane/CH2Cl2 = 20：1, Rf = 0.28), 1a
(51 mg, 0.24 mmol, 19%) was obtained as colorless oil. 1H NMR (400 MHz, CD3CN): δ (ppm) 7.12
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(d, J = 7.1 Hz, 2H), 7.24 (dd, J = 7.5, 7.5 Hz, 2H), 7.24 (t, J = 7.3 Hz, 1H), 1.53 (s, 6H), 1.21 (s, 9H).
UV-vis (CH3CN, c = 5.5 mM): λmax (ε) = 257 (178) nm (M-1 cm-1). The spectroscopic data are
consistent with those reported in the literature24.
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Methyl cumyl ether (4): The compound was prepared according to a known procedure25. NaH
(60 wt% oil dispersion) (0.683 g, 17.1 mmol) was added to a two necked-flask and the flask was purged
with nitrogen. Then, THF (10 mL) was added to the flask and stirred over 30 min. To the mixture was
α-cumyl alcohol dissolved in THF (3 mL) was added, and then stirred over 30 min. Finally, CH3I was
added to the reaction mixture and stirred overnight. After finished the reaction, H2O (15 mL) was
added, and then the mixture was extracted with EtOAc. The organic layer was dried over MgSO4,
concentrated, and purified via silica gel column chromatography (hexane/EtOAc = 5 : 1, Rf = 0.55) to
obtain 4 (569 mg, 3.8 mmol, 79%) as colorless oil. 1H NMR (400 MHz, CD3CN): δ (ppm) 7.42 (d, J
= 7.1 Hz, 2H), 7.35 (dd, J = 7.6, 6.8 Hz, 2H), 7.25 (t, J = 7.2 Hz, 1H), 3.00 (s, 3H), 1.47 (s, 6H). UV-
vis (CH3CN, c = 6.3 mM): λmax (ε) = 257 (183) nm (M-1 cm-1). The spectroscopic data are consistent
with those reported in the literature25.
1-Ethyl-1-phenylpropanol (18): The compound was prepared according to a known procedure26.
Methyl benzoate (1.36 g, 10 mmol) and dry THF (20 mL) were added to a two-necked flask. Under
N2 atmosphere, the solution was cooled to 0℃ followed by drop-wise addition of EtMgBr (in THF,
abt. 1 M) (30 mL, 30 mmol). The mixture was stirred at room temperature overnight. The reaction
mixture was diluted with EtOAc and then, saturated aqueous NH4Cl was added. The organic phase
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was extracted with EtOAc, washed with brine, dried over Na2SO4, and concentrated in vacuo. The
product was purified by silica column chromatography (hexane/EtOAc = 50 : 1, Rf = 0.13) to afford
18 (1.44 g, 8.78 mmol, 88%). 1H NMR (400 MHz, CD3CN): δ (ppm) 7.38 (d, J = 7.2 Hz, 2H), 7.32
(dd, J = 7.7, 7.7 Hz, 2H), 7.20 (t, J = 7.9 Hz, 1H), 2.71 (br, 1H), 1.81 (dq, J = 14.4, 7.5 Hz, 2H), 1.74
(dq, J = 14.1, 7.3 Hz, 2H), 0.67 (t, J = 7.4 Hz, 6H). The spectroscopic data are consistent with those
reported in the literature26.
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1-Ethyl-1-phenylpropyl hydroperoxide: The compound was prepared according to a known
procedure27. A solution of 1-ethyl-1-phenylpropanol dissolved in methanol (5 mL) was added
dropwise to the stirred mixture of 30% H2O2 (150 mL) and 2.5% H2SO4 (15 mL). After stirring for 5
h at room temperature, the reaction mixture was extracted with CH2Cl2, washed with water, dried over
Na2SO4, and concentrated in vacuo. The hydroperoxide product was given as colorless oil (purity：
88%, 324.6 mg, 1.58 mmol, 79%). 1H NMR (400 MHz, CD3CN): δ (ppm) 8.72 (br, 1H), 7.38-7.32 (m,
4H), 7.27-7.23 (m, 1H), 1.87 (dq, J = 10.9, 6.7 Hz, 4H), 0.72 (t, J = 7.4 Hz, 6H). The spectroscopic
data are consistent with those reported in the literature27.
(3-(tert-butylperoxy)pentane-3yl)benzene (1b): The compound was prepared according to a
known procedure23. Added a stirring bar to the two-necked flask, drew a vacuum with drying, and
purged with nitrogen. Trichloroacetimidate (0.24 mL, 1.34 mmol) and a solution of hydroperoxide, 1-
ethyl-1-phenylpropyl (161.1 mg, 0.89 mmol) in CH2Cl2 1.3 mL were added to the flask, and the flask
was cooled to -20℃ (NaCl + ice water ) with stirring. Then BF3-Et2O diluted with CH2Cl2 (0.5 mL,
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0.036 mmol) was dropped slowly to the reaction mixture. When the reaction temperature reached to
room temperature, a small amount of NaHCO3 was added to the reaction mixture for quenching, and
solid was removed by filtration. After evaporating and purification with column chromatography
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(hexane, Rf = 0.50)28, 1b was obtained as colorless oil (58.6 mg, 0.25 mmol, 32%). H NMR (400
MHz, CDCl3): δ (ppm) 7.34-7.28 (m, 4H), 7.23-7.18 (m, 1H), 2.02 (dq, J = 14.0, 7.4 Hz, 2H), 1.81
(dq, J = 14.0, 7.4 Hz, 2H), 1.28 (s, 9H), 0.71 (t, J = 7.4 Hz, 6H). 13C{1H} NMR (100 MHz, CDCl3): δ
(ppm) 143.6 (C), 127.6 (CH), 126.2 (CH), 126.1 (CH), 85.9 (C), 78.4 (C), 29.3 (CH2), 26.8 (CH3), 7.8
(CH3). HRMS (FI+) m/z: [M]+ calcd for C15H24O2 236.17763; found 236.17695. UV-vis (CH3CN, c =
10.2 mM): λmax (ε) = 257 (196) nm (M-1 cm-1).
Methyl 1-ethyl-1-phenylpropyl ether (19): The compound was prepared according to a known
procedure25. NaH (60 wt% oil dispersion) (159.3 mg, 3.98 mmol) was added to a two necked-flask
and the flask was purged with nitrogen. Then, THF (2.2 mL) was added to the flask and stirred over
30 min. To the mixture was alcohol compound (188.2 mg, 1.14 mmol) dissolved in THF (1 mL) was
added, and then stirred over 30 min. Finally, CH3I (0.23 mL, 3.65 mmol) was added to the reaction
mixture and stirred overnight. After finished the reaction, H2O (3.3 mL) was added, and then the
mixture was extracted with EtOAc. The organic layer was dried over MgSO4, concentrated, and
purified via silica gel column chromatography (hexane, Rf = 0.23) to obtain 19 as colorless oil (199
mg, 1.12 mmol, 98%). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.38-7.30 (m, 4H), 7.23 (t, J = 6.9 Hz,
1H), 3.06 (s, 3H), 1.88 (dq, J = 14.7, 7.5Hz, 2H), 1.82 (dq, J = 12.9, 7.4 Hz, 2H), 0.71 (t, J = 7.4 Hz,
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