Poly(ethylene glycol) dimethyl ether mediated oxidative scission of aromatic olefins to carbonyl compounds by molecular oxygen

Article abstract of DOI:10.1039/d1ra02007b

A simple, and practical oxidative scission of aromatic olefins to carbonyl compounds using O₂as the sole oxidant with poly(ethylene glycol) dimethyl ether as a benign solvent has been developed. A wide range of monosubstituted,gem-disubstituted, 1,2-disubstituted, trisubstituted and tetrasubstituted aromatic olefins was successfully converted into the corresponding aldehydes and ketones in excellent yields even with gram-scale reaction. Some control experiments were also conducted to support a possible reaction pathway.

Full text of DOI:10.1039/d1ra02007b

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Poly(ethylene glycol) dimethyl ether mediated
oxidative scission of aromatic olefins to carbonyl
compounds by molecular oxygen†
Cite this: RSC Adv., 2021, 11, 13848
Tao Yu,‡ Mingqing Guo,‡ Simiaomiao Wen, Rongrong Zhao, Jinlong Wang,
*
*
Yanli Sun, Qixing Liu and Haifeng Zhou
A simple, and practical oxidative scission of aromatic olefins to carbonyl compounds using O2 as the sole
oxidant with poly(ethylene glycol) dimethyl ether as a benign solvent has been developed. A wide range
of monosubstituted, gem-disubstituted, 1,2-disubstituted, trisubstituted and tetrasubstituted aromatic
olefins was successfully converted into the corresponding aldehydes and ketones in excellent yields
even with gram–scale reaction. Some control experiments were also conducted to support a possible
reaction pathway.
Received 13th March 2021
Accepted 5th April 2021
DOI: 10.1039/d1ra02007b
rsc.li/rsc-advances
olens are limited to gem-disubstituted aromatic alkenes.20
Therefore, developing a wide applicable strategy for the oxida-
Introduction
tive scission of olens to aldehydes and ketones is highly
desirable but still remains a challenge.
The selective oxidative scission of olens is a practiced trans-
formation in organic synthesis. The produced carbonyl
compounds are valuable intermediates in pharmaceuticals,
fragrances, agrochemicals and bulk chemical industries.1 The
two-step ozonolysis is the conventional method to convert
olens into carbonyl compounds (Scheme 1a).2 In recent years,
the ozone was replaced by other oxidants, such as H2O2,3
Poly(ethylene glycol) dimethyl ether (PEGDME) has been
attracting increasing interest due to its benign characteristics
involving lower cost, non-volatilization, and non-toxicity, etc.21
To continue our interest in developing environmental benign
synthetic reactions.22 Herein we report a simple and practical
oxidative scission of a wide range of monosubstituted, gem- and
1,2-disubstituted, trisubstituted, and tetrasubstituted aromatic
olens to the corresponding aldehydes and ketones by O2 with
PEGDME as a benign solvent.
8
oxone,4 TBHP,5 m-CPBA,6 KMnO4,7 PhIO/HBF4 (Scheme 1b).
However, the super stoichiometric use of expensive and toxic
oxidants leads to a large amount of resource waste and envi-
ronmental pollution.
Molecular oxygen is regarded as an ideal oxidant due to its
easy availability, cheapness, environmental benignity and good
functional-group tolerance. Recently, a series oxidative scission
of olens to carbonyl compounds with O2 as the sole oxidant,
catalysed by organocatalysts NHPI,9 AIBN,10 B2pin2,11 TEMPO,12
transitional-metal complexes Pd,13 Cu,14 Fe,15 Ni,16 CAN,17 as
well as photocatalysts18 and electrocatalysts,19 have been re-
ported (Scheme 1c). However, some shortcomings including
non-commercial available catalysts, expensive additives, inevi-
table residual transitional-metals, and excess amount of volatile
organic solvents limit their application in industry. Very
recently, although a 1,2-diethoxyethane catalysed oxidative
scission of olens to ketones by air has been achieved, the
Research Center of Green Pharmaceutical Technology and Process, Hubei Key
Laboratory of Natural Products Research and Development, College of Biological
and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002,
China. E-mail: qixingliu86@163.com; zhouhf@ctgu.edu.cn
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d1ra02007b
‡ These authors contributed equally to this work.
Scheme 1 Oxidative scission of olefins to carbonyl compounds.
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monomethyl ether (DPGMME), and dipropylene glycol dimethyl
ether (DPGDME) were screened as a solvent at 130 ꢀC for 10
hours, providing 54–94% yields (entries 7–14). Moreover, it was
found that the environmentally friendly poly(ethylene glycol)
(PEG) and poly(ethylene glycol) dimethyl ether (PEGDME) gave
96% and 99% yield, respectively (entries 15–16). Therefore,
PEGDME was demonstrated to be the best solvent. Next, the
effect of the reaction temperature was examined. The yield of 2a
remained at 99% when the reaction temperature dropped to
Results and discussion
Our studies were started with gem-diphenylethylene (1a) as
a model substrate (Table 1). When the oxidation scission of 1a
was performed in N,N-dimethylformamide (DMF), methyl tert-
butyl ether (MTBE), tetrahydrofuran (THF), 2-methyltetrahy-
drofuran (2-MeTHF) at 130 ꢀC or under reux condition with O2
as the sole oxidant, only trace amount of diphenylmethanone
(2a) was observed (entries 1–4). To our delight, the desired
product 2a was detected by HPLC with 73% yield in 1,4-dioxane
at 100 ꢀC for 10 hours (entry 5). However, when 1,4-dioxane was
replaced by morpholine, the yield decreased to 49% (entry 6). To
improve the reaction efficiency, ethylene glycol (EG), triethylene
glycol (TEG), and a series of ethers including ethylene glycol
dimethyl ether (EGDME), ethylene glycol diethyl ether (EGDEE),
diethylene glycol monomethyl ether (DEGMME), diethylene
glycol dimethyl ether (DEGDME), dipropylene glycol
ꢀ
ꢀ
110 C, but lower yield of 78% was observed at 100 C (entries
17–18). Shorter reaction time was also attempted, the results
revealed that the yield remained at 99% at 8 hours (entries 19–
20). When the reaction was performed under air atmosphere,
the yield decreased to 35% (entry 21). In addition, it was found
that the higher concentration of 1a led to lower yield of 2a
(entries 22–23). Finally, the entry 19 was regarded as the optimal
reaction conditions: 1a (0.5 mmol), PEGDME (1 mL), under O2
ꢀ
atmosphere, 110 C, and 8 hours.
With the optimized reaction conditions in hand, the scope of
various olens was investigated. As shown in Scheme 2, the
oxidative scission of gem-diphenylethylenes bearing electron-
donating group (Me, OMe) at the ortho-, meta- or para posi-
tion, of the phenyl proceeded successfully to give the corre-
sponding 2b–2g with >98% yield. In addition, the halogen
element (F, Cl, Br) substituted gem-diphenylethylenes were also
gave corresponding ketones 2h–2l in 90–99% yields. The
halogen substituents are useful entities amenable to further
transformation in organic synthesis. The gem-diphenyl-
ethylenes with meta-substituted electron-withdrawing group
CF3 gave higher yield than the ortho-substituted one (2m: 73%,
2n: 99%). The gem-diphenylethylenes with two or three
substituents on the phenyls also gave the desired products 2o–
2u in 86–99% yields. When phenyl of gem-diphenylethylene was
replaced by naphthyl, thienyl and pyridyl, the oxidative scission
also proceeded smoothly, affording the corresponding products
2v–2x in 60–95% yields. To our delighted, the substrates con-
taining uorene or thioxanthene moiety also provided the
desired ketones 2y and 2z in 87% and 85% yields. Furthermore,
the aryl-alkyl disubstituted olens like a-methylstyrene and a-
cyclopropylstyrene were also applicable to this oxidative scis-
sion. The corresponding ketones 2aa and 2ab were obtained in
99% and 93% yields.
Aldehydes are also important building blocks in ne chem-
icals. And then, we examined this oxidative scission of olens to
prepare aldehydes. As shown in Scheme 3, the mono-
substituted, 1,2-disubstituted, trisubstituted and tetrasub-
stituted aromatic olens were also subjected to this
transformation. For example, the monosubstituted aromatic
olene 1ac was cleavaged to give 4-bromobenzaldehyde (2ac) in
92% yield under standard conditions. Benzaldehyde 2ad was
obtained as the sole product in 95% yield by the oxidative
scission of 1,2-disubstituted aromatic olene 1ad. Interestingly,
the 1,4-bis(2-methylstyryl)benzene (1ae) can be cleavaged to 1,4-
phthalaldehyde (2ae) and 2-methylbenzaldehyde (2ae') in 83%
and 82% yield. When trisubstituted 1,1-diphenyl-2-(4-
bromophenyl)ethene (1af) and triphenylethylene (1ag) were
used as substrates, the corresponding products 4-
Table 1 Optimization of the reaction conditionsa,b
Entry
Solvent
Temp. (ꢀC)
t (h)
Yieldc (%)
1
2
3
4
5
6
7
8
DMF
MTBE
THF
2-MeTHF
1,4-Dioxane
Morpholine
EG
TEG
EGDME
EGDEE
DEGMME
DEGDME
DPGMME
DPGDME
PEG
PEGDME
PEGDME
PEGDME
PEGDME
PEGDME
PEGDME
PEGDME
PEGDME
130
55
66
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
8
<2%
<2%
<2%
<2%
73
49
54
85
61
90
91
93
94
94
96
99
99
78
100
130
130
130
86
9
10
11
12
13
14
15
16
17
18
19
20
21d
22e
23f
130
130
130
130
130
130
130
110
100
110
110
110
110
110
78
99
83
35
64
52
6
8
8
8
a
Abbreviation: N,N-dimethylformamide (DMF), methyl tert-butyl ether
(MTBE), tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF),
ethylene glycol (EG), triethylene glycol (TEG), ethylene glycol dimethyl
ether (EGDME), ethylene glycol diethyl ether (EGDEE), diethylene
glycol monomethyl ether (DEGMME), diethylene glycol dimethyl ether
(DEGDME), dipropylene glycol monomethyl ether (DPGMME),
dipropylene glycol dimethyl ether (DPGDME), poly(ethylene glycol)
(average Mn, 400) (PEG400), poly(ethylene glycol) dimethyl ether
b
(average Mn, 250) (PEGDME250). Reaction conditions: 1a (0.5 mmol),
c
solvent (1 mL), O2 balloon. The yields were determined by HPLC.
d
Under air atmosphere. e 1 mmol of 1a. f 5 mmol of 1a.
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Scheme 3 Scope of mono, di-, tri-, and tetrasubstituted aromatic
olefins.
optimal conditions. It means that a radical reaction pathway
might be involved. When 2,2-diphenyloxirane (3a) was used as
the starting material, the desired ketone 2a could be obtained in
99% yield, indicating that 3a might be a key intermediate of this
oxidative scission reaction.
Based on the control experiments and reported work,20
a plausible reaction pathway was proposed as shown in Scheme
5. Firstly, PEGDME was oxidized by O2 to produce a peroxyl
radical 3a0. Secondly, 3,3-diphenyl-1,2-dioxetane (1a0) was
Scheme 2 Scope of gem-disubstituted aromatic olefins. Reaction
conditions: 1 (0.5 mmol), PEGDME (1 mL), O2 balloon, 110 ꢀC, 8 hours, formed by the oxidation of gem-diphenylethylene (1a) with 3a0 as
isolated yield.
bromobenzaldehyde (2ac), benzaldehyde (2ad) and diphe-
nylmethanone (2a) were obtained in about 90% yields. Finally,
the tetraphenylethylene (1ah) was also subjected to this oxida-
tive scission, less than 5% yield was obtained even if elevating
the temperature to 150 ꢀC and extending the reaction time to 24
hours.
To understand the reaction pathway, control experiments
were conducted. As shown in Scheme 4, when the oxidative
scission of gem-diphenylethylene (1a) was carried out under N2
atmosphere, no product 2a was observed. Only a trace amount
of oxidation product 2a was detected in the presence of a radical
scavenger 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) under
Scheme 4 Control experiments.
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General procedure for oxidation scission of aromatic olen
The corresponding aromatic olen 1 (0.5 mmol), PEGDME (1
mL) were added to a 10 mL Schlenk tube. The tube was evacu-
ated and lled with oxygen three times. The mixture was stirred
at 110 ꢀC for 8 hours under O2 atmosphere using a balloon.
Aer cooling, the mixture was subjected to silica gel column
chromatography (PE : EA ¼ 15 : 1) to give the product 2.
Gram-scale oxidation scission of gem-diphenylethylene (1a)
Scheme 5 Plausible reaction pathway.
The gem-diphenylethylene (1a, 1.80 g, 10 mmol), PEGDME (20
mL) were added to a 50 mL of round-bottomed ask equipped
with a three-way jointer. The ask was then evacuated and lled
with oxygen three times. The mixture was stirred at 110 ꢀC for 10
hours under O2 atmosphere using a balloon. Aer cooling, the
mixture was subjected to silica gel column chromatography
(PE : EA ¼ 15 : 1) to give the product 2a (1.75 g, 96% yield).
an oxidant, regenerating PEGDME concurrently. And then, 1a0
is converted to the more stable key intermediate 2,2-dipheny-
loxirane (3a) with one equivalent of 1a. Finally, 3a was converted
to give the product 2a with 3a0 as an oxidant.
To further demonstrate the practicality of this oxidative
scission reaction, as shown in Scheme 6, a gram–scale reaction
of gem-diphenylethylene (1a; 1.80 g, 10 mmol) was conducted
Conflicts of interest
ꢀ
under O2 atmosphere in PEGDME at 110 C for 10 hours, the
product diphenylmethanone (2a) was isolated in 96% yield (1.75
There are no conicts to declare.
g).
Acknowledgements
This work was supported by the 111 Project (D20015) and the
Natural Science Foundation of Hubei Province of China
(2018CFB241).
Conclusions
In summary, we have developed an oxidative scission of
aromatic olens to carbonyl compounds using molecular
oxygen as the sole oxidant with PEGDME as solvent. A wide
range of monosubstituted, gem- and 1,2-disubstituted, trisub-
stituted, and tetrasubstituted aromatic olens were oxidized to
aldehydes and ketones in excellent yields. A reaction pathway
was proposed based on some control experiments. A successful
gram–scale reaction also demonstrated its practicability.
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Experimental section
General information
Unless otherwise noted, all reagents, catalysts and solvents were
purchased from commercial suppliers and used without further
purication. Column chromatography was performed with
silica gel (200–300 mesh). NMR spectra were recorded on Bruker
AVANCE III (400 MHz) spectrometers. CDCl3 was the solvent
used for the NMR analysis, with tetramethyl silane as an
internal standard. Chemical shis were reported up eld to
1
TMS (0.00 ppm) for H NMR and relative to CDCl3 (77.0 ppm)
for 13C NMR. HPLC analysis was conducted on an Agilent 1200
Series instrument with 5C18-MS-II Packed Column (4.6 mm I.D.
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Scheme 6 Gram-scale synthesis.
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13852 | RSC Adv., 2021, 11, 13848–13852
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