ε-Caprolactone manufacture via efficient coupling Baeyer-Villiger oxidation with aerobic oxidation of alcohols

Article abstract of DOI:10.1016/j.mcat.2020.110947

To avoid the use of peracids oxidant or highly concentrated hydrogen peroxide which is potentially hazardous and explosive, herein, a new route to ε-caprolactone was developed in which molecule oxygen was employed as the terminal oxidant. The commercial available N-hydroxyphthalimide and ammonium cerium nitrate were used as the key catalysts for the increased yield of ε-caprolactone. For instance, the selectivity of ε-caprolactone was obtained 92 % with 85 % conversion of cyclohexanone which was comparable to the strategies using highly concentrated hydrogen peroxide. The sacrificed alcohols were transformed into corresponding ketones which were also valuable chemicals. Furthermore, the efficiency of the alcohols was achieved to unprecedented 52 %. The Baeyer-Villiger oxidation of various other cycloalkanones was also examined. The substituent group effect on the efficiency of sacrificed alcohols was investigated in which weak electron-donating substituent induced nearly quantitative yield of ε-caprolactone. The reaction mechanism was studied with the help of electron paramagnetic resonance which indicated the existence of a radical pathway.

Full text of DOI:10.1016/j.mcat.2020.110947

MolecularCatalysis490(2020)110947
Contents lists available at ScienceDirect
Molecular Catalysis
journal homepage: www.elsevier.com/locate/mcat
ε-Caprolactone manufacture via efficient coupling Baeyer-Villiger oxidation
with aerobic oxidation of alcohols
Renfeng Dua, Haoran Yuana, Chenxuan Zhaoa, Yongtao Wanga, Jia Yaoa, Haoran Lia,b,
*
a Department of Chemistry, ZJU-NHU United R&D Center, Zhejiang University, Hangzhou 310027, P. R. China
b State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, P. R. China
A R T I C L E I N F O
A B S T R A C T
Keywords:
Baeyer-Villiger oxidation
ε-Caprolactone
Molecular oxygen
Hydrogen peroxide
Electron paramagnetic resonance
To avoid the use of peracids oxidant or highly concentrated hydrogen peroxide which is potentially hazardous
and explosive, herein, a new route to ε-caprolactone was developed in which molecule oxygen was employed as
the terminal oxidant. The commercial available N-hydroxyphthalimide and ammonium cerium nitrate were used
as the key catalysts for the increased yield of ε-caprolactone. For instance, the selectivity of ε-caprolactone was
obtained 92 % with 85 % conversion of cyclohexanone which was comparable to the strategies using highly
concentrated hydrogen peroxide. The sacrificed alcohols were transformed into corresponding ketones which
were also valuable chemicals. Furthermore, the efficiency of the alcohols was achieved to unprecedented 52 %.
The Baeyer-Villiger oxidation of various other cycloalkanones was also examined. The substituent group effect
on the efficiency of sacrificed alcohols was investigated in which weak electron-donating substituent induced
nearly quantitative yield of ε-caprolactone. The reaction mechanism was studied with the help of electron
paramagnetic resonance which indicated the existence of a radical pathway.
Introduction
H2O2 catalyzed by diphenyl diselenides, in which nearly quantitative
lactones were yielded [26]. Berkessel et al. conducted BV oxidation in
The Baeyer-Villiger (BV) oxidation is an extremely useful organic
reaction in chemical industry [1–6]. For instance, ε-caprolactone pro-
duced from cyclohexanone and organic peracids is usually adopted as
the monomer of polycaprolactone (PCL) which is an extensively used
pharmaceutical material [7]. On the other hand, the BV oxidation also
played an important role in the synthesis of various natural products
[8–12]. It is always the development trend for the chemical industry
that using safer, environmentally friendlier and cheaper oxidant [13].
In terms of the BV oxidation, the replacement of currently used peracids
oxidant is especially urgent due to the facts that the peracids was
known as hazardous (instability and shock sensitivity) and with low
atomic economy. Lots of endeavors have been paid to develop the new
oxidant for the replacement of the organic peracids [14–20]. Particu-
larly speaking, hydrogen peroxide (H2O2) has been promoted as the
potential oxidant as its only theoretical by-product is water [21,22]. In
addition, H2O2 has given several promising reaction results in the last
two decades. In 2001, BV oxidation was conducted with 35 % H2O2 and
Sn-zeolite beta as catalyst by Corma and coworkers, in which the yield
of ε-caprolactone was obtained 52 % [23,24]. Neumann et al. reported
BV oxidation with 60 % H2O2 to give corresponding lactones with
60∼88 % yield [25]. Sheldon et al. reported BV oxidation with 60 %
hexafluoroisopropanol (HFIP) and 92 % yield of ε-caprolactone was
achieved [27,28]. As disclosed by the aforementioned chemists, the
H2O2 of higher concentration generally gave an ideal oxidative per-
formance. Unfortunately, the usage of H2O2 of higher concentration is
not desirable for safety concerns [29]. Except for commercial available
H2O2, the method using it generated in situ from aerobic oxidation of
alcohols was also promoted at the mean time. Ishii et al. used N-hy-
droxyphthalimide (NHPI)/InCl3 or NHPI/p-toluenesulfonic acid (p-
TsOH) as catalysts and adopted cyclohexanol or benzhydrol as the sa-
crificed agents to conduct BV oxidation [30,31]. Our group used NHPI/
ammonium cerium nitrate (CAN) to catalyzed BV oxidation with KA oil
(mixture of cyclohexanol and cyclohexanone) as the substrate [32].
However, both the methods suffered a poor selectivity of lactones when
the conversion of substrates increased.
In this work, we present a new method to synthesize ε-caprolactone
with oxygen as the oxidant and NHPI/CAN as catalysts. The alcohols
played as the sacrificed agent whose products were also valuable in-
dustrial chemicals. The new route gave a very promising result for both
conversion and selectivity. The substituent group effect on the effi-
ciency of sacrificed alcohols was investigated, as well as the corre-
sponding radical mechanism assisted by the electron paramagnetic
⁎ Corresponding author at: Department of Chemistry, Zhejiang University, 38 Zheda road, Westlake district, Hangzhou 310027, Zhejiang province, P. R. China.
E-mail address: lihr@zju.edu.cn (H. Li).
https://doi.org/10.1016/j.mcat.2020.110947
Received 24 February 2020; Received in revised form 4 April 2020; Accepted 5 April 2020
2468-8231/©2020ElsevierB.V.Allrightsreserved.

R. Du, et al.
MolecularCatalysis490(2020)110947
resonance (EPR) spectroscopy.
Experimental
Table 1
BV oxidation of cyclohexanone to ε-caprolactone under various conditions with
BHOa.
Entry Catal.mol/%b BHO/
Conv.
Ketone/
%
Sel.
Conv.
BHO/
%
Alcohol
Material
ketone
initial
ratio
Lactone/
efficiency/
c
d
%
%
NHPI, CAN, azobisisobutyronitrile (AIBN), Galvinoxyl, TEMPO,
HFIP, trifluoroethanol (TFE), biphenyl, p-TsOH•H2O, DMPO, alcohols,
ketones and lactones were purchased from Energy Chemical.
Acetonitrile (MeCN), ethyl acetate (AcOEt), n-Butyl acetate (AcOBun),
chlorobenzene (PhCl) and benzonitrile (PhCN) were purchased from
Sinopharm Chemical Reagent Co., Ltd. All the reagents were used di-
rectly without further purification.
1
2
3
4
5
6
5
1.5
1.5
1.5
0.6
1
66
85
96
45
72
95
96
81
84
61
Trace
84
78
72
96
92
73
79
75
74
69
85
92
36
0
99
99
99
99
99
99
99
99
99
99
0
42
52
47
59
54
35
22
46
51
15
–
7.5
10
7.5
7.5
7.5
7.5
7.5
7.5
0
2
3
7
8e
9f
1.5
1.5
1.5
1.5
1.5
1.5
1.5
Aerobic oxidation
10g
11h
12i
13j
14k
0
The aerobic oxidation proceeded in a 50 mL round bottom with a
magnetic stirring bar in it. In the 1st step, certain amount of NHPI and
AIBN were mixed with certain amount of cyclohexanone and benzhy-
drol (6 mmol, 1.1 g) in AcOEt (3 mL), the flask was purged with pure
oxygen for three times by a membrane pump, after which it was heated
to 75 °C by oil bath for 22 h. In the 2nd step, the temperature of reaction
solution was lowered to 45 °C and certain amount of CAN and HFIP
(20 g, 12.5 mL) were added and stirred under oxygen for 10 h. The
reaction was analyzed by a Shimadzu gas chromatography instrument
(GC-2010) which was equipped with a capillary column (HP-1, 30 m
length, 0.25 mm diameter, 0.25 μm film) and a FID detector. Biphenyl
was used as the internal standard compound. GC-MS tests were con-
ducted with a Shimadzu GCMS-QP2010 instrument.
7.5
7.5
7.5
41
26
86
99
99
81l
23
14
51
a
General conditions, 1st step, NHPI/AIBN, BHO 6 mmol, certain amount of
cyclohexanone in AcOEt 3 mL, O2 1 atm, 75 °C, 600 rpm, 22 h; 2nd step, add
CAN and 20 g HFIP, 45 °C, continue reaction for 10 h. Reaction was monitored
by GC, biphenyl was used as internal standard compound.
b
Based on BHO amount.
Sel. Lactone%
c
= ε-caprolactone production amount / cyclohexanone
consumption amount × 100 %.
d
Alcohol efficiency/% = ε-caprolactone production amount / BHO con-
sumption amount × 100 %.
e
HFIP 15 g.
HFIP 30 g.
10 mol% NHPI, 0 mol% CAN.
0 mol% NHPI, 10 mol% CAN.
10 mol% p-TsOH•H2O was used instead of CAN.
HFIP 0 g, TFE 20 g.
Benzyl alcohol was used instead of BHO.
Conversion of benzyl alcohol.
f
g
Rearrangement of peroxide intermediate
h
i
The 1, 1′-peroxybis (cyclohexan-1-ol) was synthesized according to
previous paper [59]. The rearrangement of 1, 1′-peroxybis (cyclohexan-
1-ol) proceeded in a 25 mL single-necked flask with round bottom. The
0.05 g peroxide and 0.0017 g (4 mol%) p-TsOH•H2O were added into
5 mL degassed HFIP, and the reaction mixture was stirred intensively
with a magnetic stir bar under 25 °C. A Shimadzu high performance
liquid chromatography (HPLC) equipped with shim-pack VP-ODS C18
column (4.6 mm × 250 L, 5 μm) was used to quantify the amount of
unreacted substrate.
j
k
l
amount × 100 %) which was superior to former strategy (37 % effi-
ciency of alcohol with 55 % yield of ε-caprolactone) [30,31]. When the
amount of catalyst decreased to 5 mol% (Entry 1), the efficiency of
alcohol dramatically lowered to 42 % which was attributed to the low
conversion of substrate. On the other hand, the efficiency of alcohol
was not significantly improved with the increase of catalyst addition
(Entry 3), also, the selectivity showed obviously decrease. Based on
previous work [27,28], this result could be due to the side reaction
induced by the excessive catalyst. Next, we had examined the effect of
the ratio of alcohol and substrate on the BV oxidation (Entries 4–7). As
expected, the higher efficiency of alcohol was achieved when the ad-
dition amount of cyclohexanone increased (Entries 4–6) which leaded
to the increasing accessibility of cyclohexanone for H2O2 in situ pro-
duced from the aerobic oxidation of BHO. Unfortunately, an unwanted
reaction of cyclohexanone happened which limited the further addition
of cyclohexanone (Entry 4) [32]. When the initial concentration of
cyclohexanone was low, the efficiency of alcohol and selectivity of ε-
caprolactone were both unsatisfactory (Entry 7). This result could be
explained as the higher amount of water which was harmful to the
reaction was produced from the self-decomposition of H2O2 which
could not be timely used by the insufficient cyclohexanone. The HFIP
was chosen as the, solvent for BV oxidation. As reported by former
literatures [27,28,30–32], the HFIP was proved to be irreplaceable
(Entry 13). Furthermore, the ratio of the two solvents obviously af-
fected the result of the BV oxidation (Entries 8, 9). In terms of the
catalysts (Entries 10, 11), we had attempted the p-TsOH to catalyze the
second step which was apparently inferior compared with CAN (Entry
12). Surprisingly, as effective as BHO, benzyl alcohol showed promising
result which 86 % selectivity of ε-caprolactone was obtained with 72 %
Characterization of intermediate
The H2O2 measurement was performed according to previous paper
[60]. The EPR spectrum was recorded by a Bruker cw-EPR spectrometer
(A300) at X band. The modulation frequency was 100 KHz and power of
microwave was 2 mw. 20 μL reaction solutions was adopted at certain
time and mixed with DMPO solution (0.1 M in phosphate buffer saline)
of equivalent volume. After shaking for 5 min, the mixture was injected
into a capillary and tested at room temperature. Elemental analysis
result was obtained by Elementar Vario MICRO cube. The nuclear
magnetic resonance (NMR) tests were conducted on Bruker AVANCE III
500 instrument, 1H NMR at 500 MHz and 13C NMR at 125 MHz.
Results and discussion
BV oxidation with benzhydrol (BHO) using NHPI-mediate CAN as catalyst
For the important application in producing ε-caprolactone, we chose
cyclohexanone as the model substrate. Table 1 presents the results of
BV oxidation of cyclohexanone with BHO as the sacrificed alcohol
(Scheme 1). Under the most optimized conditions (Entry 2), the se-
lectivity of ε-caprolactone maintained 92 % with 85 % conversion of
cyclohexanone. The efficiency of alcohol was 52 % (based on the de-
finition of ε-caprolactone production amount / BHO consumption
2

R. Du, et al.
MolecularCatalysis490(2020)110947
Scheme 1. BV oxidation of cyclohexanone to ε-caprolactone
with BHO.
Table 2
Table 3
Solvent effect on the BV oxidation of cyclohexanone with BHOa.
BV oxidation of cycloalkanones to lactones with BHO using NHPI/CAN as
catalysta.
Entry
Solvent
Conv. Ketone/%
Sel. Lactone/%b
Entry Cycloalkanones
Lactones
Conv.
Cycloalkanones/
%
Sel.
1
2
3
4
5
AcOEt
AcOBun
MeCN
PhCN
PhCl
85
79
82
94
87
92
91
78
74
89
Lactones/
b
%
1
2
99
85
93
92
a
General conditions, BHO 6 mmol, cyclohexanone 4 mmol, Catal. mol
% = 7.5 mol% (based on BHO), O2 1 atm, 600 rpm, solvent 3 mL, 75 °C 22 h,
then add HFIP 20 g, 45 °C 10 h.
b
Sel. Lactone/% = ε-caprolactone production amount / cyclohexanone
consumption amount × 100 %.
3
4
85
85
97
97
transformation of the substrate (Entry 14). One other thing to note was
that none H2O2 was detected when the aerobic oxidation of BHO was
conducted with the fluorinated alcohol in presence. Thus, the strategy
was separated into two steps that fluorinated alcohol was added after
the aerobic oxidation of alcohols was completed. As for the products
achievement, the significant boiling points difference of different
components should facilitate the distillation separation.
5
86
96
The choice of solvent for the aerobic oxidation of alcohol is also
crucial not only for the aerobic oxidation of alcohols but also for the
subsequent BV oxidation. We conducted the strategy in several different
solvents (Table 2). Compared with AcOEt (Entry 1), the conversion of
substrate was slightly lower, along with a similar selectivity of ε-ca-
prolactone in AcOBun (Entry 2). Although the MeCN was reported as a
favorable solvent for H2O2 production [33], its selectivity of BV product
was significantly poor in our strategy (Entry 3). Similarly, PhCN gave
an unsatisfactory result with 74 % selectivity, although the transfor-
mation of cyclohexanone was enhanced (Entry 4). The PhCl gave an
unexpected result which 89 % selectivity of ε-caprolactone was ob-
tained while 87 % of cyclohexanone was converted (Entry 5). Former
researchers examined the PhCl as an inferior solvent because the
aerobic oxidation of alcohol (production of H2O2) proceeded slowly in
it [33]. We speculated PhCl somewhat favored the BV oxidation with
low concentration of H2O2.
Based on above results, various cycloalkanones were reacted under
similar conditions (Table 3). The cyclopentanone was the most fre-
quently used model substrate for BV reaction as the strained ring
greatly facilitated the key rearrangement process [34–36]. As can be
seen, the cyclopentanone gave 93 % selectivity of δ-valerolactone with
99 % conversion (Entry 1). We had investigated the effect of substituent
group on the substrates. The weak electron-donating methyl group
slightly improved the selectivity to 85–86 % (Entries 3–5), while the
substrate was almost quantitatively transformed into lactone under the
tertiary butyl group circumstances (Entry 6). The cycloheptanone was
also examined, which gave 69 % selectivity of oxocan-2-one while 75 %
of substrate was converted (Entry 7). Other cycloalkanones like 2-
norbornanone and adamantanone were oxidized then, which both led
to satisfactory yields (Entries 8, 9).
6
7
93
75
95
69
8
98
99
95
99
9
a
General conditions, BHO 6 mmol, cycloalkanone 4 mmol, Catal.mol
% = 7.5 mol% (based on BHO), O2 1 atm, 600 rpm, AcOEt 3 mL, 75 °C 22 h,
then add HFIP 20 g, 45 °C 10 h.
b
Sel. Lactones/% = Lactones production amount / cycloalkanones con-
sumption amount × 100 %.
Scheme 2. Substituent group effect on the efficiency of BV oxidation.
donating group like methyl group, the superior selectivity of ε-capro-
lactone was obtained along with a high conversion of substrate (Entry
2). We speculated the weak electron-donating group facilitated the
breakage of the CeH bond of alcohol which was supposed to be the rate
determining step of the oxidation reaction [37,38]. On the contrary, the
BV oxidation dramatically deteriorated when alcohol with electron-
withdraw groups was used (Entries 3–7). These results could be at-
tributed to the reluctance of the aerobic oxidation of the alcohols,
which clearly lesser substrates were oxidized under the same condi-
tions. We also conducted the alcohol effect experiment with a benzyl
alcohol series (see supplementary material, Table S1). To our surprise,
the electron-donating group did not increase the efficiency of BV oxi-
dation but induced the side reaction between H2O2 and aldehydes
Substituent group effect on the efficiency of BV oxidation
As the source of in situ H2O2, the aerobic oxidation of alcohols was
assumed to seriously affect the efficiency of the BV reaction (Scheme 2).
Table 4 showed the reaction results with different alcohols under same
conditions. When the alcohol was decorated with weak electron-
3

R. Du, et al.
MolecularCatalysis490(2020)110947
Table 4
Substituent group effect on the BV oxidation of cyclohexanone to ε-caprolactone with BHOa.
Entry
Alcohols
Conv. Ketone/%
Sel. Lactone/%b
Conv. Alcohols/%
Alcohol efficiency/%c
1
2
3
4
5
6
7
R1 = H; R2 = H
R1 = CH3; R2 = CH3
R1 = Cl; R2 = H
R1 = Cl; R2 = Cl
R1 = F; R2 = F
85
93
69
68
70
71
69
92
98
81
73
66
75
72
99
99
85
83
81
88
85
52
61
44
40
38
40
40
R1 = CF3; R2 = H
R1 = CN; R2 = CN
a
General conditions, alcohol 6 mmol, cyclohexanone 4 mmol, Catal.mol% = 7.5 mol% (based on alcohol), O2 1 atm, 600 rpm, AcOEt 3 mL, 75 °C, 22 h, HFIP 20 g,
45 °C, 10 h. Reaction was monitored by GC, biphenyl was used as internal standard compound.
b
Sel. Lactone/% = ε-caprolactone production amount / cyclohexanone consumption amount × 100 %.
Alcohol efficiency/% = ε-caprolactone production amount / alcohol consumption amount × 100 %.
c
obtained from oxidation of alcohols [39,40]. The existence of the
phenols as the by-products of the side reactions was proved by GC-MS
spectroscopy (see supplementary material, Fig. S17). However, these
side reactions would not happen when electron-withdrawing groups
were in presence.
EPR evidences for the radical mechanism of BV oxidation
Considering the unique properties of HFIP including strong hy-
drogen bond donation ability, non-nucleophilicity, and high ionizing
power [41–43], former researchers usually proposed ion involved me-
chanism for the rearrangement process of the BV oxidation [31]. To
obtain insight into the reaction mechanism, we had conducted 2, 2, 6,
6-tetramethylpiperidine-N-oxyl (TEMPO) addition experiment (Fig. 1),
in which the reaction was totally inhibited and none ε-caprolactone was
observed [44,45]. This result inferred that radical intermediates maybe
involved in the pathway. Moreover, we have conducted the inhibition
experiment with another well-known radical scavenger, Galvinoxyl
[46–48], which gave similar inhibition results and confirmed the ra-
dical nature of the mechanism.
Fig. 2. EPR spectrum of the DMPO-OOH adduct. Black line was experimental
spectrum, and red line was simulation spectrum, peaks with asterisk were as-
signed to DMPO-double adduct produced simultaneously.
The direct evidences of the presence of radical intermediates were
provided by the EPR tests with the help of spin trap technique using 5,
5-dimethyl-1-pyrroline N-oxide (DMPO) as the spin trap agent [49]. As
shown in Fig. 2, a clear signal of nitroxide of hydroperoxyl (OOH) ra-
dical-DMPO adduct was observed (g = 2.006,
aN = 14.0 G,
a
Hβ = 11.4 G, aHγ = 1.5 G) when the spin trap agent (DMPO) was
Fig. 1. TEMPO inhibition effect during the rearrangement of 1, 1′-dihydroxydicycloalkyl peroxide intermediate in HFIP.
4

R. Du, et al.
MolecularCatalysis490(2020)110947
Fig. 3. EPR spectrum of (a) the DMPO-double adduct, (b) the DMPOX species derived from DMPO-double adduct. Black line was experimental spectrum, and red line
was simulation spectrum.
Scheme 3. Proposed spin trap adducts for BV oxidation by DMPO.
added during the first step of the reaction [50]. Based on previous lit-
eratures [51–53], the OOH was most likely released from the aerobic
oxidation of the alcohol, which further abstracted a hydrogen atom and
turned into H2O2. Meanwhile, a weak triplet signal (Fig. 2, peaks with
asterisk) was also mixed within the OOH signal (g = 2.005,
hydrogen atom from the allylic position of the BHO which gave the 1-
hydroxy-1, 1-diphenylmethyl radical and NHPI. The new generated
radical was facile to react with molecular oxygen to form the peroxide
radical which tended to liberate an OOH radical and a benzophenone.
After a hydrogen atom transfer from NHPI to the OOH radical, the H2O2
for following BV oxidation was produced. As proposed by Ishii et al., we
assumed the generation of ε-caprolactone was via the 1, 1′-peroxybis
(cyclohexan-1-ol) intermediate [31]. However, as suggested by EPR
detection, the rearrangement of this intermediate also happened in a
radical mechanism. For its known high activity, the dioxirane produced
from the 1, 1′-peroxybis (cyclohexan-1-ol) instantly rearranged to ε-
caprolactone [55–58], while at the mean time a cyclohexanone was
regenerated from the cyclohexanone hydrate.
a
N = 14.4 G, aHγ = 1.5 G) which was existed as the only signal when
the addition of DMPO was carried out at the second step of the reaction
(Fig. 3 (a)). We speculated this radical species maybe the key inter-
mediate during the rearrangement of 1, 1′-peroxybis (cyclohexan-1-ol)
to ε-caprolactone. Referring to the tabulated spin trap results [50], the
triplet peaks were carefully assigned to a double adduct of DMPO
(Scheme 3). The further support for this assignment was its variation
which transferred into the DMPOX with the prolongation of the spin
trap time as shown in Fig. 3 (b) (g = 2.007, aN = 6.8 G, aH = 3.9 G
(2 H)), which was a typical derivation signal from double adduct of
DMPO as reported by former literatures (Scheme 3) [54]. Finally, we
had synthesized the possible intermediate, 1, 1′-peroxybis (cyclohexan-
1-ol), and conducted the EPR experiment in HFIP which gave similar
spin trap results as above mentioned in the second step. It was noted
that the spin traps did not show significant effect on the catalysis system
including NHPI and CAN.
Conclusions
In conclusion, we have developed an alternative route to ε-capro-
lactone using molecular oxygen as the terminal oxidant, with com-
mercial available NHPI-mediated CAN as catalyst. The produced by-
product ketones were also valuable industrial chemicals, and if
necessary, could be reduced back to the original alcohols through the
sophisticated hydrogenation reaction [61–65]. A satisfactory reaction
result (92 % selectivity of ε-caprolactone with 85 % conversion of
To summarize, the mechanism was proposed as follows (Scheme 4).
In the first place, the phthalimide-N-oxyl radical (PINO) abstracted a
5

R. Du, et al.
MolecularCatalysis490(2020)110947
Scheme 4. Proposed mechanism for BV oxidation of cyclohexanone with the aerobic oxidation of BHO.
cyclohexanone) was achieved. From the efficiency point of view, this
strategy has greatly facilitated the usage of molecular oxygen in the BV
oxidation. The investigation of substituent group effect and mechanism
helped us to gain deeper insight into the reaction. Unfortunately, the
usage of the expensive solvent (HFIP) is still the main drawback of the
in situ H2O2 strategies whose replacement with cheap solvent is un-
derway in our lab.
Wiley-VCH, Weinheim, 1999, pp. 1807–1823.
[8] M.E. Jung, L. Zeng, T. Peng, H. Zeng, Y. Le, J. Su, Total synthesis of Bao Gong Teng
A, a natural antiglaucoma compound, J. Org. Chem. 57 (1992) 3528–3530, https://
doi.org/10.1021/jo00039a005.
[9] G.R. Pettit, T.R. Kasturi, Steroids and related natural products. VIII. Synthesis of
oxasteroids, J. Org. Chem. 26 (1961) 4557–4563, https://doi.org/10.1021/
jo01069a087.
[10] E.J. Tisdale, C. Chowdhury, B.G. Vong, H. Li, E.A. Theodorakis, Regioselective
synthesis of the bridged tricyclic core of garcinia natural products via in-
tramolecular aryl acrylate cycloadditions, Org. Lett. 4 (2002) 909–912, https://doi.
org/10.1021/ol017278w.
[11] N. Tibrewal, P. Pahari, G. Wang, M.K. Kharel, C. Morris, T. Downey, Y. Hou,
T.S. Bugni, J. Rohr, Baeyer-Villiger C-C bond cleavage reaction in gilvocarcin and
jadomycin biosynthesis, J. Am. Chem. Soc. 134 (2012) 18181–18184, https://doi.
org/10.1021/ja3081154.
Declarations of interest
The authors declare no competing financial interest.
CRediT authorship contribution statement
[12] F.W.J. Demnitz, C. Philippini, R.A. Raphael, Unexpected rearrangement in the
peroxytrifluoroacetic acid-mediated Baeyer-Villiger oxidation of trans-3-hydroxy-
4,4,10-trimethyl-9-decalone forming a 7-oxabicyclo[2.2.1]heptane. Structure proof
and total synthesis of (+-)-farnesiferol-c, J. Org. Chem. 60 (1995) 5114–5120,
https://doi.org/10.1021/jo00121a032.
Renfeng Du: Investigation, Writing - original draft. Haoran Yuan:
Investigation. Chenxuan Zhao: Formal analysis. Yongtao Wang:
Formal analysis. Jia Yao: Conceptualization, Writing - review &
editing. Haoran Li: Supervision, Writing - review & editing.
[13] P.T. Anastas, J.C. Warner, Green Chemistry: Theory and Practice, Oxford University
Press, Oxford, 1998.
[14] C. Bolm, G. Schlingloff, K. Weickhardt, Use of molecular oxygen in the Baeyer-
Villiger oxidation the influence of metal catalysts, Tetrahedron Lett. 34 (1993)
3405–3408, https://doi.org/10.1016/S0040-4039(00)79167-2.
Acknowledgment
[15] M. Hamamoto, K. Nakayama, Y. Nishiyama, Y. Ishii, Oxidation of organic substrates
by a molecular oxygen/aldehyde/heteropolyoxometalate system, J. Org. Chem. 58
(1993) 6421–6425, https://doi.org/10.1021/jo00075a043.
[16] T. Yamada, K. Takahashi, K. Kato, T. Takai, S. Inoki, T. Mukaiyama, The Baeyer-
Villiger oxidation of ketones catalyzed by nickel (II) complexes with combined use
of molecular oxygen and an aldehyde, Chem. Lett. 20 (1991) 641–644, https://doi.
org/10.1246/cl.1991.641.
[17] S.I. Murahashi, Y. Oda, T. Naota, Fe2O3-catalyzed Baeyer-Villiger oxidation of
ketones with molecular oxygen in the presence of aldehydes, Tetrahedron Lett. 33
(1992) 7557–7560, https://doi.org/10.1016/S0040-4039(00)60823-7.
[18] K. Kaneda, S. Ueno, T. Imanaka, Catalysis of transition metal-functionalized hy-
drotalcites for the Baeyer-Villiger oxidation of ketones in the presence of molecular
oxygen and benzaldehyde, J. Mol. Cata. A: Chem. 102 (1995) 135–138, https://doi.
org/10.1016/1381-1169(95)00055-0.
[19] E.-Y. Jeong, M.B. Ansari, S.-E. Park, Aerobic Baeyer-Villiger oxidation of cyclic
ketones over metalloporphyrins bridged periodic mesoporous organosilica, ACS
Catal. 1 (2011) 855–863, https://doi.org/10.1021/cs200163r.
This work was supported by the National Natural Science
Foundation of China (No. 21573196), the Fundamental Research Funds
for the Central Universities, and the National High Technology
Research and Development Program (863 Program) of China (Grant No.
SS2015AA020601).
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.mcat.2020.110947.
References
[20] L. Wang, Y. Wang, R. Du, R. Dao, H. Yuan, C. Liang, J. Yao, H. Li, N-
Hydroxyphthalimide (NHPI) promoted aerobic Baeyer-Villiger oxidation in the
presence of aldehydes, ChemCatChem 10 (2018) 4947–4952, https://doi.org/10.
1002/cctc.201801165.
[21] R. Noyori, M. Aoki, Green oxidation with aqueous hydrogen peroxide, Chem.
Comm. 16 (2003) 1977–1986, https://doi.org/10.1039/B303160H.
[22] J. Piera, J.-E. Bäckvall, Catalytic oxidation of organic substrates by molecular
oxygen and hydrogen peroxide by multistep electron transfer-a biomimetic ap-
proach, Angew. Chem. Int. Ed. 47 (2008) 3506–3523, https://doi.org/10.1002/
anie.200700604.
[23] A. Corma, L.T. Nemeth, M. Renz, S. Valencia, Sn-zeolite beta as a heterogeneous
chemoselective catalyst for Baeyer-Villiger oxidations, Nature 412 (2001) 423–425,
https://doi.org/10.1038/35086546.
[24] A. Corma, M.T. Navarro, L. Nemeth, M. Renz, Sn-MCM-41-a heterogeneous selec-
tive catalyst for the Baeyer-Villiger oxidation with hydrogen peroxide, Chem.
Comm. 21 (2001) 2190–2191, https://doi.org/10.1039/b105927k.
[25] K. Neimann, R. Neumann, Activation of hydrogen peroxide: selective oxidation
reactions in perfluorinated alcohol solvents, Org. Lett. 2 (2000) 2861–2863,
https://doi.org/10.1021/ol006287m.
[1] W.B. Fisher, J.F. Van Peppen, J.L. Kroshwite, M. Home-Grant (Eds.), Kirk-Othmer
Encyclopedia of Chemical Technology, fourth ed., John Wiley and Sons, New York,
1995, pp. 851–859.
[2] A. Baeyer, V. Villiger, Einwirkung des caro’schen reagens auf ketone, Ber. Dtsch.
Chem. Ges. 32 (1899) 3625–3633, https://doi.org/10.1002/cber.189903203151.
[3] A. Baeyer, V. Villiger, Ueber die einwirkung des caro’schen reagens auf ketone, Ber.
Dtsch. Chem. Ges. 33 (1900) 858–864, https://doi.org/10.1002/cber.
190003301153.
[4] M. Renz, B. Meunier, 100 years of Baeyer-Villiger oxidations, Eur. J. Org. Chem. 4
(1999) 737–750, https://doi.org/10.1002/(SICI)1099-0690(199904)
1999:4<737::AID-EJOC737>3.0.CO;2-B.
[5] J.H. Teles, I. Hermans, G. Franz, R.A. Sheldon, Oxidation, Ullman’s Encyclopedia of
Industrial Chemistry, Wiley-VCH, Weinheim, 2015, p. 5 18.
[6] G.R. Krow, B.M. Trost (Ed.), Comprehensive Organic Synthesis, Pergamon Press,
New York, 1991, pp. 671–688.
[7] T. Michael, E.I. Musser, Ullman’s Encyclopedia Industrial Organic Chemicals,
6

R. Du, et al.
MolecularCatalysis490(2020)110947
[26] G.J. ten Brink, J.-M. Vis, I.W.C.E. Arends, R.A. Sheldon, Selenium-catalyzed oxi-
dations with aqueous hydrogen peroxide. 2. Baeyer-Villiger reactions in homo-
geneous solution, J. Org. Chem. 66 (2001) 2429–2433, https://doi.org/10.1021/
jo0057710.
[27] A. Berkessel, M.R.M. Andreae, Efficient catalytic methods for the Baeyer-Villiger
oxidation and epoxidation with hydrogen peroxide, Tetrahedron Lett. 42 (2001)
2293–2295, https://doi.org/10.1016/S0040-4039(01)00141-1.
[28] A. Berkessel, M.R.M. Andreae, H. Schmickler, J. Lex, Baeyer-Villiger oxidations
with hydrogen peroxide in fluorinated alcohols: lactone formation by a nonclassical
mechanism, Angew. Chem. Int. Ed. 41 (2002) 4481–4484, https://doi.org/10.
1002/1521-3773(20021202)41:23<4481::AID-ANIE4481>3.0.CO;2-7.
[29] For international regulations, see Regulations Concerning the International
Carriage of Dangerous Goods by Rail (RID), European Agreement Concerning the
International Carriage of Dangerous Goods by Road (ADR), and International Civil
Aviation Organization Technical Instructions for the Safe Transport of Dangerous
Goods by Air (ICAO TI).
mechanistic investigation, J. Am. Chem. Soc. 136 (2014) 16588–16593, https://
doi.org/10.1021/ja508718m.
[46] G.W. Kabalka, H.C. Brown, A. Suzuki, S. Honma, A. Arase, M. Itoh, Inhibition of the
reaction of organoboranes with. α, β-unsaturated carbonyl derivatives by
Galvinoxyl. Evidence for a free-radical chain mechanism, J. Am. Chem. Soc. 92
(1970) 710–712, https://doi.org/10.1021/ja00706a054.
[47] P.D. Bartlett, T. Funahashi, Galvinoxyl (2, 6-di-tert-butyl-α-(3, 5-di-tert-butyl-4-
oxo-2, 5-cyclohexadiene-1-ylidene)-p-tolyloxy) as a scavenger of shorter-lived free
radicals, J. Am. Chem. Soc. 84 (1962) 2596–2601, https://doi.org/10.1021/
ja00706a054.
[48] E.G. Janzan, C.A. Evans, Y. Nishi, Kinetic study of radical production in the thermal
decomposition of benzoyl peroxide by electron spin resonance spin trapping (spin
counting). Rate (and substituent effect on the rate) of spin trapping by competitive
scavenging of benzoyloxy radicals with Galvinoxyl, J. Am. Chem. Soc. 94 (1972)
8236–8238, https://doi.org/10.1021/ja00778a053.
[49] J.E. Wertz, J.R. Bolton, Electron Spin Resonance: Elementary Theory and Practical
[30] O. Fukuda, S. Sakaguchi, Y. Ishii, A new strategy for catalytic Baeyer-Villiger oxi-
dation of KA-oil with molecular oxygen using N-hydroxyphthalimide, Tetrahedron
Lett. 42 (2002) 3479–3481, https://doi.org/10.1016/S0040-4039(01)00469-5.
[31] K. Kamae, Y. Obora, Y. Ishii, Baeyer-Villiger oxidation of cycloalkanones with in
situ generated hydrogen peroxide from alcohols and molecular oxygen using NHPI
as a key catalyst, Bull. Chem. Soc. Jpn. 82 (2009) 891–895, https://doi.org/10.
1246/bcsj.82.891.
[32] R. Du, H. Yuan, J. Yao, H. Li, Oxidation of KA oil to caprolactone with molecular
oxygen using N-hydroxyphthalimide-mediated Ce(NH4)2(NO3)6 catalyst, Mol.
Catal. 467 (2019) 24–29, https://doi.org/10.1016/j.mcat.2019.01.013.
[33] T. Iwahama, S. Sakaguchi, Y. Ishii, Production of hydrogen peroxide via aerobic
oxidation of alcohols catalyzed by N-hydroxyphthalimide, Org. Process Res. Dev. 4
(2000) 94–97, https://doi.org/10.1021/op990082f.
[34] J. Fischer, W.F. Hölderich, Baeyer-Villiger-oxidation of cyclopentanone with aqu-
eous hydrogen peroxide by acid heterogeneous catalysis, Appl. Catal. A Gen. 180
(1999) 435–443, https://doi.org/10.1016/S0926-860X(98)00378-0.
[35] M.Y. Rios, E. Salazar, H.F. Olivo, Chemo-enzymatic Baeyer-Villiger oxidation of
cyclopentanone and substituted cyclopentanones, J. Mol. Cata. B: Enzy. 54 (2008)
61–66, https://doi.org/10.1016/j.molcatb.2007.12.012.
[36] S. Ueno, K. Ebitani, A. Ookubo, K. Kaneda, The active sites in the heterogeneous
Baeyer-Villiger oxidation of cyclopentanone by hydrotalcite catalysts, Appl. Surf.
Sci. 121 (1997) 366–371, https://doi.org/10.1016/S0169-4332(97)00334-6.
[37] T. Iwahama, S. Sakaguchi, Y. Nishiyama, Y. Ishii, Aerobic oxidation of alcohols to
carbonyl compounds catalyzed by N-hydroxyphthalimide (NHPI) combined with Co
(acac)3, Tetrahedron Lett. 36 (1995) 6923–6926, https://doi.org/10.1016/0040-
4039(95)01431-G.
[38] R. Liu, X. Liang, C. Dong, X. Hu, Transition-metal-free: A highly efficient catalytic
aerobic alcohol oxidation process, J. Am. Chem. Soc. 126 (2004) 4112–4113,
https://doi.org/10.1021/ja031765k.
[39] M. Matsumoto, H. Kobayashi, Y. Hotta, Intramolecular [4+2] cycloadditions of
nitrosoalkenes with olefins, J. Org. Chem. 49 (1984) 4741–4743, https://doi.org/
10.1021/jo00198a038.
[40] K. Sato, M. Hyodo, J. Takagi, M. Aoki, R. Noyori, Hydrogen peroxide oxidation of
aldehydes to carboxylic acids: An organic solvent-, halide- and metal-free proce-
dure, Tetrahedron Lett. 41 (2000) 1439–1442, https://doi.org/10.1016/S0040-
4039(99)02310-2.
[41] L. Eberson, O. Persson, M.P. Hartshorn, Detection and reactions of radical cations
generated by photolysis of aromatic compounds with tetranitromethane in 1, 1, 1,
3, 3, 3-hexafluoro-2-propanol at room temperature, Angew. Chem. Int. Ed. Engl. 34
(1995) 2268–2269, https://doi.org/10.1002/anie.199522681.
Applications, McGraw-Hill, New York, 1972.
[50] G.R. Buettner, Spin trapping: ESR parameters of spin adducts 1474 1528V, Free
Radic. Biol. Med. 3 (1987) 259–303, https://doi.org/10.1016/S0891-5849(87)
80033-3.
[51] E.G. Moskvitina, S.V. Puchkov, I.M. Borisov, A.L. Perkel, Equilibrium between the
hydroperoxyl and 1-hydroxycyclohexylperoxyl radicals-chain carriers in cyclohex-
anol oxidation with molecular oxygen, React. Kinet. Catal. Lett. 54 (2013) 538–544,
https://doi.org/10.1134/S0023158413050121.
[52] C. Chang, X. Yang, B. Long, J. Li, A water-promoted mechanism of alcohol oxidation
on a Au (111) surface: understanding the catalytic behavior of bulk gold, ACS Catal.
3 (2013) 1693–1699, https://doi.org/10.1021/cs400344r.
[53] E.G. Janzen, D.E. Nutter Jr., E.R. Davis, B.J. Blackburn, On spin trapping hydroxyl
and hydroperoxyl radicals, Can. J. Chem. 56 (1978) 2237–3342, https://doi.org/
10.1139/v78-368.
[54] K. Makino, A. Hagi, H. Ide, A. Murakami, M. Nishi, Mechanistic studies on the
formation of aminoxyl radicals from 5, 5-dimethyl-1-pyrroline-N-oxide in fenton
systems. Characterization of key precursors giving rise to background ESR signals,
Can. J. Chem. 70 (1992) 2818–2827, https://doi.org/10.1139/v92-358.
[55] O. Welz, J.D. Savee, D.L. Osborn, S.S. Vasu, C.J. Percival, D.E. Shallcross,
C.A. Taatjes, Direct kinetic measurements of Criegee intermediate (CH2OO) formed
by reaction of CH2I with O2, Science 335 (2012) 204–207, https://doi.org/10.
1126/science.1213229.
[56] Y. Tu, Z.X. Wang, Y. Shi, An efficient asymmetric epoxidation method for trans-
olefins mediated by a fructose-derived ketone, J. Am. Chem. Soc. 118 (1996)
9806–9807, https://doi.org/10.1021/ja962345g.
[57] D. Yang, M.K. Wong, Y.C. Yip, Epoxidation of olefins using methyl (trifluoromethyl)
dioxirane generated in situ, J. Org. Chem. 60 (1995) 3887–3889, https://doi.org/
10.1021/jo00117a046.
[58] W. Adam, M. Müller, F. Prechtl, Dimethyldioxirane oxidation of titanium enolates:
Diastereoselective α-hydroxylations, J. Org. Chem. 59 (1994) 2358–2364, https://
doi.org/10.1021/jo00088a015.
[59] M.S. Kharasch, G. Sosnovsky, Structure of peroxides derived from cyclohexanone
and hydrogen peroxide, J. Org. Chem. 23 (1958) 1322–1326, https://doi.org/10.
1021/jo01103a021.
[60] J. Liu, Y. Yang, N. Liu, Y. Liu, H. Huang, Z. Kang, Total photocatalysis conversion
from cyclohexane to cyclohexanone by C3N4/Au nanocomposites, Green Chem. 16
(2014) 4559–4565, https://doi.org/10.1039/C4GC01126K.
[61] A. Berkessel, T.J.S. Schubert, T.N. Müller, Hydrogenation without a transition-
metal catalyst: on the mechanism of the base-catalyzed hydrogenation of ketones, J.
Am. Chem. Soc. 124 (2002) 8693–8698, https://doi.org/10.1021/ja016152r.
[62] T. Ohkuma, M. Koizumi, J. Ikehira, T. Yokozawa, R. Noyori, Selective hydrogena-
tion of benzophenones to benzhydrols. Asymmetric synthesis of unsymmetrical
diarylmethanols, Org. Lett. 2 (2000) 659–662, https://doi.org/10.1021/
ol9904139.
[42] L. Eberson, M.P. Hartshorn, O. Persson, F. Radner, Making radical cations live
longer, Chem. Comm. 18 (1996) 2105–2112, https://doi.org/10.1039/
P29950001735.
[43] B. Elsler, A. Wiebe, D. Schollmeyer, K.M. Dyballa, R. Franke, S.R. Waldvogel,
Source of selectivity in oxidative cross-coupling of aryls by solvent effect of 1, 1, 1,
3, 3, 3-hexafluoropropan-2-ol, Chem. Eur. J. 21 (2015) 12321–12325, https://doi.
org/10.1002/chem.201501604.
[44] W.B. Liu, D.P. Schuman, Y.F. Yang, A.A. Toutov, Y. Liang, H.F.T. Klare, N. Nesnas,
M. Oestreich, D.G. Blackmond, S.C. Virgil, S. Banerjee, R.N. Zare, R.H. Grubbs,
K.N. Houk, B.M. Stoltz, Potassium tert-butoxide-catalyzed dehydrogenative C–H
silylation of heteroaromatics: a combined experimental and computational me-
chanistic study, J. Am. Chem. Soc. 139 (2017) 6867–6879, https://doi.org/10.
1021/jacs.6b13031.
[63] J. Wu, J.-X. Ji, R. Guo, C.-H. Yeung, A.S.C. Chan, Chiral
[RuCl2(dipyridylphosphane)(1,2-diamine)] catalysts: Applications in asymmetric
hydrogenation of a wide range of simple ketones, Chem. Eur. J. 9 (2003)
2963–2968, https://doi.org/10.1002/chem.200204688.
[64] K. Hattori, H. Sajiki, K. Hirota, Chemoselective control of hydrogenation among
aromatic carbonyl and benzyl alcohol derivatives using Pd/C (en) catalyst,
Tetrahedron 57 (2001) 4817–4824, https://doi.org/10.1016/S0040-4020(01)
00421-5.
[65] L.W. Gosser, D. Wilmington, Hydrogenation of a Diarylketone to a Diarylmethanol,
[45] N.D. Schley, G.C. Fu, Nickel-catalyzed Negishi arylations of propargylic bromides: a
US Patent 4302435, (1981).
7