A Deoximation Method for Deprotection of Ketones and Aldhydes Using a Graphene-Oxide-Based Co-catalysts System

Article abstract of DOI:10.1002/adsc.201900202

The deoximation of a wide range of ketoximes and aldoximes to their corresponding carbonyl compounds with high yields has been achieved using graphene oxide (GO) and sodium nitrite (NaNO₂) as highly efficient catalysts and air as the green oxidant under mild conditions. The mechanism of deprotection and recycling use of catalyst were revealed in deep experiment. The carboxylic acid groups on the GO were essential for high catalytic activity. (Figure presented.).

Full text of DOI:10.1002/adsc.201900202

Title: A deoximation method for deprotection of ketones and aldhydes
using a graphene-oxide-based co-catalysts system
Authors: Qiaolin Tong, Yang Liu, Xuezhi Gao, Zhanfang Fan, Tianfu
Liu, Bo Li, Dangsheng Su, Qinghe Wang, and Maosheng
Cheng
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201900202
Link to VoR: http://dx.doi.org/10.1002/adsc.201900202

10.1002/adsc.201900202
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
A Deoximation Method for Deprotection of Ketones and
Aldhydes Using a Graphene-Oxide-Based Co-catalysts System
Qiaolin Tong†, a, Yang Liu†,*,a, Xuezhi Gaoa, Zhanfang Fana, Tianfu Liub, Bo Lib,
Dangsheng Sub,c, Qinghe Wang*,a, Maosheng Cheng*,a
a
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical
Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Institute of Metal Research, Chinese Academy of Science, Shenyang 110016, PR China.
Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian 116023, PR China.
Qiaolin Tong and Yang Liu contributed equally to this work.
b
c
†
* Corresponding authors. Email: y.liu@syphu.edu.cn (Y. Liu); qinghe-wang@163.com (Q. Wang);
mscheng@syphu.edu.cn (M. Cheng)
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. The deoximation of a wide range of ketoximes were revealed in deep experiment. The carboxylic acid
and aldoximes to their corresponding carbonyl compounds groups on the GO were essential for high catalytic activity.
with high yields has been achieved using graphene oxide
(GO) and sodium nitrite (NaNO2) as highly efficient
catalysts and air as the green oxidant under mild conditions.
The mechanism of deprotection and recycling use of catalyst
Keywords: Deoximation; Graphene oxide; Sodium nitrite;
Air; Oximes
TiO2 as a deoximation catalyst;[11] García and
coworkers reported a mixed (Fe2+ and Cu2+) double-
metal hexacyanocobaltate as a catalyst for the
Introduction
Oximes are used not only as efficient and stable conversion of oximes to carbonyl compounds;[12] and
protecting groups for carbonyls but are also Gil and coworkers discovered that a manganese
extensively applied in the purification of carbonyl nanocatalyst combined with N-hydroxyphthalimide
compounds, such as calone.[1] This strategy has also was an efficient catalytic system for the oxidation of
been applied in many total syntheses, such as the oximes.[13] In 2013, Cao et al. developed a
synthesis of erythronolide A.[2] Conversely, because deoximation catalyzed by FeCl3 and 2,2,6,6-
oximes can be synthesized from compounds that do tetramethylpiperidin-1-oxyl;[14] Karimi and coworkers
not contain carbonyl,[3] deoximation is a convenient demonstrated that the regeneration of carbonyl
method to obtain ketones and aldehydes, and the compounds from oximes could be catalyzed by coated
preparation of carvone is a classic example.[4] Hence, amorphous TiO2 that had formed periodic
deoximation is an important reaction for many mesoporous organosilicate channels;[15] and Gil and
reasons.
coworkers explored cobalt in the presence of N-
Many deoximation methods have been reported in hydroxyphthalimide as a catalyst for the aerobic
the past decade.[5,6] In 2019 and 2017, Yu et al. also oxidation of oximes to carbonyl compounds.[16] In
reported an organoselenium-catalyzed deoximation of 2011, Ding and coworkers explored NaNO2 as the
oximes to ketones or aldehydes.[4] Wang and co- catalyst and molecular oxygen as the oxidant for
workers used a sulfonic group-tethered mesoporous deoximation.[17]
poly(ionic liquid) as a deoximation catalyst.[7] In 2016,
The majority of these strategies are reasonably
Morís and coworkers demonstrated that laccases can efficient; however, some of the reported methods
catalyze the cleavage of oximes.[8] In 2015, a often
suffer from serious shortcomings.
deoximation approach using Ti-containing metal- Homogeneous catalysts are difficult to recover and
organic framework photocatalysts was reported by reuse; many of the systems require long reaction
Morsali and coworkers, and Coskun and coworkers times and are expensive; metals and metal oxides are
discovered that anhydrous Ce(IV) sulfate can serve as often required.
an oxidant for deoximation.[9] In 2014, Konwar and
Graphene is a single atomic plane of graphite,
coworkers developed a novel system for deoximation constructed with sp2-hybridized carbon atoms in a
using Cu nanoparticles;[10] Kaboudin and coworkers perfect hexagonal lattice.[18] Recently, graphene
reported the use of mesoporous C-N codoped nano- oxides (GOs) have been developed as catalysts in the
1
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10.1002/adsc.201900202
Advanced Synthesis & Catalysis
Friedel-Crafts acylation of active aromatic quantity of catalyst for this reaction. Futhermore, the
compounds,[19] Friedel-Crafts addition reaction of effects of the amount of NaNO2 in the co-catalyzed
indoles
to
α,β-unsaturated
ketones
and reaction system were investigated. When the amount
nitrostyrenes,[20] aza-Michael addition of amines and of NaNO2 was decreased from 1.5 mol% to 0.5 mol%,
electrondeficient olefins,[21] Michael addition there was no major difference in the yield of the
reactions,[22] direct alkylation reaction between desired product (Table 1, entries 21-23). However, if
styrenes and alcohols,[23] direct alkylation reaction the amount of NaNO2 was decreased to 0.2 mol%, 0.1
between iodobenzene and benzene,[24] oxidization mol% or 0.05 mol%, the yield of the desired product
reaction of benzene to phenol,[25] oxidation of tetralin decreased accordingly (Table 1, entries 24-26). Hence,
to tetralol and tetralone,[26] oxidation of cyclohexane 0.5 mol% was an optimal quantity of NaNO2 for this
to cyclohexanol, cyclohexanone, and adipic acid,[27] reaction.
ring-opening reactions,[28] dehydrogenation of
nitrogen heterocycles,[29] direct iodination of arenes
Table 1 GO-based co-catalyzed deoximation under
different reaction conditionsa.
and ketones,[30] trifluoromethylation of arenes, [31] and
other reaciotns.[32-34]
In this work, we report a highly efficient, easily
recyclable and simple method for deoximation with
good yields under mild conditions using a co-catalysts
system composed of graphene oxide (GO) prepared
by Hummers’ method,[35] sodium nitrite (NaNO2) and
air.
GO
NaNO2
(mol%)
time
temperature
(°C)
yieldb
(%)
entry
solvent
(mg)
(min)
1
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
1
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.5
0.5
0.2
0.1
0.05
EtOH
EtOH
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
40
40
40
40
40
40
40
40
40
40
40
25
40
55
25
40
55
25
40
55
25
40
55
25
40
55
40
40
40
40
40
40
40
40
40
40
40
2.3
2.5
2
3
EtOH
2.8
Results and Discussion
4
THF
2.1
5
THF
2.4
In this deoximation system, GO and NaNO2 are
utilized as the catalysts, and air as the green oxidant.
NaNO2 reacts firstly with GO to produce nitrous acid
(HNO2), which can release nitric oxide (NO). NO is
then oxidated by air catalysted by GO to produce
nitrogen dioxide (NO2), which is the active species
for the deoximation.[17,36]
6
THF
2.4
7
CH3COCH3
CH3COCH3
CH3COCH3
CH3COOEt
CH3COOEt
CH3COOEt
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
18.5
23.3
24.5
26.7
34.6
36.8
50.0
90.5
85.5
5.0
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
We chose benzophenone oxime (1a) as a model
compound to optimize the conditions for the GO-
based catalyzing deoximation. The results are listed in
Table 1. First, the effects of the solvents in the
catalyzed reaction system were investigated. The
conversion was poor when the reaction was carried
out in some common solvents, such as EtOH, THF,
CH3COCH3, and CH3COOC2H5, and all yields were
less than 40 % (Table 1, entries 1-12). However,
when CH3CN was used as the solvent in the presence
of GO (15 mg) and NaNO2 (1.0 mol%) at 25 °C for
50 minutes, we obtained the desired product in 50%
yield (Table 1, entry 13). Encouraged by these
5
25.0
68.0
97.5
97.0
96.8
97.0
97.5
94.5
92.0
80.0
10
20
25
50
20
20
20
20
20
preliminary results, we began
optimizing the
temperature of the reaction. When the temperature
was increased from 25 °C to 40 °C, the yield of the
desired product increased to more than 90% after 50 aReaction conditions: 1a (0.25 mmol), solvent (20 mL), water (0.05 mL,
minutes, but when the temperature was increased to 2.7 mmol), open-air atmosphere; bIsolated yield.
55 °C, the yield of benzophenone decreased to 85.5%
due to the increase of byproducts (Table 1, entries 13-
15). Hence, 40 °C was the optimal temperature for the
To identify which oxygen functionalities on the
reaction. Next, the amount of GO were investigated GO were principally responsible for the catalytic
for the deoximation of benzophenone oxime at 40 °C activity, several control experiments were performed.
in CH3CN. When the amount of GO was increased 1a was still chosen as the model substrate. First, a
from 1 mg to 20 mg, the yield of the desired product blank control reaction was conducted without GO and
increased and the time of the reaction decreased NaNO2, showing no product appeared (Table 2, entry
accordingly (Table 1, entries 14,16-19). However, if 1). Next, we carried out the reaction in the presence of
the amount was increased to 25 mg or 50 mg, there reduced graphene oxide (rGO) under the previously
was little difference in the yield or time (Table 1, optimized reaction conditions. As expected, a
entries 20-21). Hence, 20 mg of GO was an optimal extremely low conversion was obtained in this
2
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10.1002/adsc.201900202
Advanced Synthesis & Catalysis
1c
2d
/
60
60
40
40
--
reaction (Table 2, entry 2). This finding clearly
indicates that the oxygen functionalities on the
graphene oxide were crucial for the catalytic activity.
Next, benzoic anhydride, anthraquinone and phenol
were used in the deoximation reaction to study the
importance of anhydride, carbonyl and hydroxyl
groups for the catalytic activity. As listed in Table 2,
entries 3-5, no product benzophenone (2a) was
detected after these reactions, indicating that the
anhydride, carbonyl and hydroxyl groups on the GO
are not the active sites. We then used 50 mol%
benzoic acid to catalyze this reaction under the same
optimized conditions. After 60 minutes, only trace
product was detected (Table 2, entry 6), indicating
that GO not only reacted with NaNO2 to produce
HNO2, which can release NO, but also catalysted the
oxidation of NO to NO2 by air. If we added 0.1 mL of
triethylamine to the reaction system, no product was
observed (Table 2, entry 7). These results
demonstrated that the carboxyl moieties presenting on
the GO are responsible for its catalytic activity.
0
rGO
trace
0.5
3
4
60
60
40
40
--
--
0.5
0.5
5
60
60
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
--
trace
--
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0
6 e
7 f
GO-Et3N
Fe2O3
8 g
9 h
--
MnCl2·4H2O
CuSO4·5H2O
GO (Ar)
GO
--
10 i
11 j
12k
13l
--
7.0
--
NaNO2
--
0.5
aReaction conditions: 1a (0.25 mmol), acetonitrile (20.0 mL), 50 uL NaNO2
solution (0.025 mol/L), molecular analogue (0.38 mmol), 40 °C and open-air
atmosphere. bIsolated yield. Blank experiment: in the absence of graphene
c
oxide and NaNO2 solution (0.025 mol/L)
.
dReaction conditions: 1a (0.25
What is more, the Inductively Coupled Plasma
Mass Spectrometry (ICP-MS) was used to detect the
contents of the main heavy metal residues in the GO
during the preparation (Results: Fe 2303 mg/kg, Mn
621.20 mg/kg, Cu 23.34 mg/kg, K 1004 mg/kg, Na
277.50 mg/kg). Then, the corresponding quantity of
Fe2O3, MnCl2·4H2O and CuSO4·5H2O, which were
used individually to simulate the main heavy metal
residues in the GO system, were used to catalyze the
deoximation reaction. As listed in Table 2, entries 8-
10, no product benzophenone (2a) was detected after
these reactions, indicating that the main heavy metal
residues in the GO are not the active components.
It should be emphasized that if the reaction was
carried out under the atmosphere of argon, a low
conversion (7 %) was obtained in this reaction (Table
2, entries 11), indicating that the air was responsible
for the deoximation system. And if the reaction was
carried out in the absence of either NaNO2 or GO, no
product benzophenone (2a) was detected after these
reactions (Table 2, entries 12-13), indicating that both
GO and NaNO2 were responsible for the deoximation
system.
mmol), acetonitrile (20 mL), 50 uL NaNO2 solution (0.025 mol/L), reduced
graphene oxide (20 mg), 40 °C and open-air atmosphere; eReaction conditions:
1a (0.25 mmol), acetonitrile (20.0 mL), 50 uL NaNO2 solution (0.025
mol/L), molecular analogue (0.13 mmol), 40 °C and open-air atmosphere.
fReaction conditions: 1a (0.25 mmol), acetonitrile (20.0 mL), 50 uL NaNO2
solution (0.025 mol/L), graphene oxide (20 mg), with 0.1 mL triethylamine,
40 °C and open-air atmosphere. gReaction conditions: 1a (2.5 mmol),
acetonitrile (200 mL), 500 uL NaNO2 solution (0.025 mol/L), Fe2O3 (1.3 mg,
8.2×10-3 mmol), 40 °C and open-air atmosphere. hReaction conditions: 1a (2.5
mmol), acetonitrile (200 mL), 500 uL NaNO2 solution (0.025 mol/L),
MnCl2·4H2O (1.4 mg, 6.9×10-3 mmol), 40 °C and open-air atmosphere.
iReaction conditions: 1a (2.5 mmol), acetonitrile (200 mL), 500 uL NaNO2
solution (0.025 mol/L), CuSO4·5H2O (1.1 mg, 4.6×10-3 mmol), 40 °C and
j
open-air atmosphere. Reaction conditions: 1a (0.25 mmol), acetonitrile (20.0
mL), 50 uL NaNO2 solution (0.025 mol/L), graphene oxide (20 mg), 40 °C
k
and under the atmosphere of argon. Reaction conditions: 1a (0.25 mmol),
acetonitrile (20.0 mL), water (0.05 mL, 2.7 mmol), graphene oxide (20 mg)
,
40 °C and open-air atmosphere. lReaction conditions: 1a (0.25 mmol),
acetonitrile (20.0 mL), 50 uL NaNO2 solution (0.025 mol/L), 40 °C and
open-air atmosphere.
Based on above results and those previous studies
on deoximation,[17,36] we propose a plausible reaction
pathway as shown in Scheme 1. First, the little amout
of NaNO2 reacted with GO to produce HNO2. Then
HNO2 generated NO, which was oxidized by air
under the catalysing of GO to form NO2. The highly
active species NO2 attacked the α-carbon atom of the
oxime a, which cleaved the double bond between the
nitrogen and carbon, to produce the intermediate b.
This intermediate b can subsequently form c through
reacting with HNO2, then followed by intramolecular
cyclization to produce intermediate d. Then, d splited
into the corresponding carbonyl compound and
intermediate e. Subsequent oxidation of e, catalysed
by GO, generated HNO2, which was unstable and
releases NO, making the catalytic cycle continue.
What is more, to test the reaction pathway again,
di-p-tolylmethanone oxime was allowed to react with
18
water bearing oxygen-18 (H2 O) in the presence of
GO and the product were measured by liquid
chromatography-mass spectrometry (LC-MS). The di-
p-tolylmethanone with incorporated oxygen-18 was
not found in the MS, indicating that the water did not
participate in the reaction.
Table 2 Control experiments with different molecular
analogues as catalysta.
NaNO2
(mol%)
time
temperature
(°C)
yieldb
(%)
entry
catalyst
(min)
3
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10.1002/adsc.201900202
Advanced Synthesis & Catalysis
10
11
50
89
97
110
12
13
14
15
16
17
18
19
150
210
260
300
900
540
1500
80
96
96
89
97
87
92
85
96
Scheme 1 Possible reaction pathway for the GO-
catalyzed deoximation reaction.
A diverse group of ketoximes and aldoximes were
chosen to confirm the application scope of this
methodology. The results are presented in Table 3.
All of the substrates that were tested were converted
to the corresponding products in excellent yields
under the optimized reaction conditions. Notably, the
GO-NaNO2-Air catalyzed deoximation reaction was
affected by the electronic properties of the
substituents. We found that ketoximes and aldoximes
with electron-donating groups (such as CH3 and
OCH3) on the arene were more reactive than those
containing electron-withdrawing groups (Table 3,
entries 1-19).
20
21
120
100
94
96
Table 3 Deoximation of keto- and aldoximes to
carbonyl compounds catalyzed by GOa.
aReaction conditions: substrate (0.25 mmol), acetonitrile (20 mL), 50 uL
NaNO2 solution (0.025 mol/L), graphene oxide (20 mg), 40 °C and open-
air atmosphere; bIsolated yield;
entry
1
oximes
time(min)
20
yieldb(%)
97
This catalytic system was also applied to the
purification of some ketones and aldehydes in oily
form at room temperature while their corresponding
oximes are in solid form. The crude ketones and
aldehydes were firstly reacted with hydroxylamine
hydrochloride to produce oximes, which could be
purified by easier treatment such as recrystallization
in high purity, then the refined products can be
conversed back to corresponding ketones or
aldehydes with extremely high purity and quantity.
(Table 4).[37]
2
3
4
5
6
25
25
97
96
97
97
96
40
75
Table 4 Purification of ketones and aldehydes by
deoximation of their corresponding oximes catalyzed
by GO-NaNO2-Air system.a
120
7
8
9
150
160
40
94
95
97
entry
1
oximes
time(min)
30
yieldb(%)
purityc(%)
97
98.58
2
80
97
99.76
4
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10.1002/adsc.201900202
Advanced Synthesis & Catalysis
times were observed, as summarized in Fig. 2. After
being reused 9 times and separated from the reaction
system, the GO was again characterized by Fourier
transform infrared (FTIR) spectroscopy, Raman
spectroscopy (Raman), X-ray diffraction (XRD) and
X-ray photoelectron spectroscopy (XPS). There were
no noticeable differences in the XRD patterns
between the fresh GO and the reused GO (Fig. 3),
demonstrating that the catalyst was relatively stable
and did not aggregate during the reaction. SEM (Fig.
4) indicated that the morphology of the reused GO
was very similar to that of the starting GO. The FTIR
(Fig. 5), Raman (Fig. 6), XPS (Fig. 7) and C 1s XPS
(Fig. 8) analyses showed no obvious differences
between the reused and fresh GO, indicating that the
oxygen functionalities, degree of defect, oxygen
signal intensity and oxygen content were unchanged
by the reaction.
3
650
90
99.70
4
5
60
97
94
98.62
99.58
600
aReaction conditions: substrate (0.25 mmol), acetonitrile (20 mL), 50 uL
NaNO2 solution (0.025 mol/L), graphene oxide (20 mg), 40 °C and open-
air atmosphere; bIsolated yield; cDetermined by HPLC with areas of peak
normalization method.
We also confirmed the reproducibility of the
catalyst by using GOs from three different batches as
catalysts for the deoximation of benzophenone oxime.
The reaction profiles are shown in Fig. 1. Although
the reaction rates were different, the final conversions
to benzophenone were the same.
100
90
80
70
60
Batch 1
50
Batch 2
40
Batch 3
30
20
10
0
0
10
20
30
40
Fig. 2 Study of the catalyst recyclability for the
deoximation of benzophenone oxime (1a).
Time / min
Fig.1 Time-conversion plot for the deoximation of
benzophenone oxime (1a) by using GOs and XRD
patterns from three different batches.
Fig. 3 XRD patterns of GO used for 9 cycles (up) and
fresh GO (down).
To study the recyclability of the graphene oxide,
we chose the deoximation of 1a as a model reaction
again. The catalyst was easily recovered by
centrifugation (12000 rpm/min for 0.5 h) after the
reaction, and the supernatant was removed by
decanting. The unmodified catalyst was reused for
subsequent experiments (9 runs in total), and no
major differences in the yield or required reaction
5
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10.1002/adsc.201900202
Advanced Synthesis & Catalysis
Fig. 4 SEM spectroscopy of fresh GO (left) and GO
used for 9 cycles (right).
Fig. 5 IR spectra of fresh GO (up) and GO used for 9
cycles (down).
Fig. 8 C 1s peak in the XPS spectra of fresh GO (up) and
GO used for 9 cycles (down).
Conclusion
In summary, we developed a GO-NaNO2-Air co-
catalyst system for the deoximation reaction via an
efficient and mild procedure that is applicable for a
wide range of ketoximes and aldoximes. The
carboxylic acid groups on the GO were essential for
its catalytic activity. This system is ligand-free, stable
during the reaction, and highly reproducible, and
allows short reaction time. Besides, GO can be
recovered after the reaction and reused for additional
runs without noticeable loss of catalytic activity.
Fig. 6 Raman spectra of fresh GO (blue) and GO used
for 9 cycles (pink).
Experimental Section
Synthesis of graphene oxide[35]
In a typical experiment, graphite flakes (2.0 g), H2SO4
(20 mL), K2SO8 (2.5 g), and P2O5 (2.5 g) were mixed
in a round-bottom flask. The solution was heated to
80 ºC and stirred for 12 h. Next, after cooling to room
temperature, the solution was diluted with 300 mL of
DI water. After that, the mixture was filtered and
washed with 500 mL of DI water. The product was
dried at 60 °C under vacuum for 12 h. The pretreated
graphite powder was then stirred in concentrated
H2SO4 (50 mL) for 12 h. Afterwards, NaNO3 (1.0 g)
was added into the mixture, and then KMnO4 (10 g)
was added slowly while stirring, and an ice bath was
used to keep the temperature of the mixture below
20 °C. The mixture was then heated to 35 °C for 0.5 h
and later diluted with DI water (0.5 L) while keeping
the temperature below 40 °C. Next, the mixture was
heated to 90 °C and transferred into ambient
conditions after 15 min. After that, DI water (300 mL)
was added. Shortly afterward, 30% H2O2 (20 mL) was
gradually added to the mixture. After the oxidation
process, the mixture was filtered and washed three
times with 5 wt% HCl to remove metal ions and then
washed with large amounts of DI water. The as-
Fig. 7 XPS patterns in the XPS spectra of fresh GO
(up) and GO used for 9 cycles (down).
6
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10.1002/adsc.201900202
Advanced Synthesis & Catalysis
prepared dark-brown product was dried in an oven at TLC. After the reaction was finished, the mixture was
40 °C for 24 h to afford graphene oxide (black solid, centrifuged at 12,000 rpm for 0.5 h. The supernatant
2.6g). The dried product was dispersed in acetonitrile was concentrated under reduced pressure, and the
(1.0 mg/mL) and sonicated to obtain the exfoliated crude
product
was
purified
by
column
graphene oxide, which was used as the carbocatalyst.
chromatography on a silica gel column with n-
hexane/ethyl acetate as eluent to obtain the desired
product.
General experimental procedure for the deoximation
reaction
Experimental procedure for the deoximation reaction of
All the reactions were carried out under ambient benzophenone oxime under the atmosphere of argon
atmosphere unless otherwise specified. To a 50 mL of
three-necked flask were added oxime (0.25 mmol), 50 To a 50 mL of three-necked flask were added
μL of NaNO2 solution (0.025 mol/L) and GO (20 mg) benzophenone oxime (0.25 mmol, 50 mg), 50 μL of
in acetonitrile (20 mL). The solution was stirred at NaNO2 solution (0.025 mol/L) and GO (20 mg) in
40 °C. The reaction was monitored by TLC. After the acetonitrile (20 mL). Then the flask was purged
reaction was finished, the mixture was centrifuged at several times with argon (balloon filled). The solution
12,000 rpm for 0.5 h. Next, the supernatant was was stirred at 40 °C for 60 minutes. Then the mixture
concentrated under reduced pressure, and the crude was centrifuged at 12,000 rpm for 0.5 h. The
product was purified by column chromatography on a supernatant was concentrated under reduced pressure,
silica gel column with n-hexane/ethyl acetate as and the crude product was purified by column
eluent to obtain the desired product.
chromatography on a silica gel column with n-
hexane/ethyl acetate as eluent to obtain the desired
product.
Experimental procedure for the deoximation reaction of
benzophenone oxime in different solvents and at
different temperature
Experimental procedure for the recycling tests of GO
To a 50 mL of three-necked flask were added
benzophenone oxime (0.25 mmol, 50 mg), 50 μL of
NaNO2 solution (0.05 mol/L) and GO (15 mg) in
EtOH, THF, CH3COCH3, CH3COOC2H5 or CH3CN
(20 mL). The solution was stirred at 25 °C, 40 °C or
55 °C for 50 minutes. Then the mixture was
centrifuged at 12,000 rpm for 0.5 h. The supernatant
was concentrated under reduced pressure, and the
The reactions were carried out at ambient atmosphere.
To a 50 mL three-necked flask were added oxime
(0.25 mmol), 50 μL of NaNO2 solution (0.025 mol/L)
and GO (20 mg) in acetonitrile (20 mL). The solution
was stirred at 40 °C. The reaction was monitored by
TLC. After the reaction was finished, the mixture was
centrifuged at 12,000 rpm for 0.5 h. The supernatant
was concentrated under reduced pressure, and the
crude
product
was
purified
by
column
crude
product
was
purified
by
column
chromatography on a silica gel column with n-
hexane/ethyl acetate as eluent to obtain the desired
product.
chromatography on a silica gel column with n-
hexane/ethyl acetate as eluent to obtain the desired
product. The remaining solid was washed by
acetonitrile (2×10 mL) and reused in the following
runs.
Experimental procedure for the deoximation reaction of
benzophenone oxime with different amount of GO
To a 50 mL of three-necked flask were added
benzophenone oxime (0.25 mmol, 50 mg), 50 μL
NaNO2 solution (0.05 mol/L) and GO (1 mg, 5 mg, 10
mg, 15 mg, 20 mg, 25 mg or 50 mg) in acetonitrile
(20 mL). The solution was stirred at 40 °C. The
reaction was monitored by TLC. After the reaction
was finished, the mixture was centrifuged at 12,000
rpm for 0.5 h. The supernatant was concentrated
under reduced pressure, and the crude product was
purified by column chromatography on a silica gel
column with n-hexane/ethyl acetate as eluent to
obtain the desired product.
Acknowledgements
We gratefully acknowledge the financial support from
National Natural Science Foundation of China
(81473087, 81872752). Dr. Y. Liu wishes to express
his thanks for the support by the Program for
Liaoning Innovative Talents in University
(LR2017043) and the Career Development Support
Plan for Young and Middle-aged Teachers in
Shenyang Pharmaceutical University (ZQN2016005).
Experimental procedure for the deoximation reaction of
benzophenone oxime with different amount of NaNO2
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FULL PAPER
A deoximation method for deprotection of ketones
and aldhydes using a graphene-oxide-based co-
catalysts system
Adv. Synth. Catal. Year, Volume, Page – Page
Qiaolin Tong†, a, Yang Liu†,*,a, Xuezhi Gaoa,
Zhanfang Fana, Tianfu Liub, Bo Lib, Dangsheng
Sub,c, Qinghe Wang*,a, Maosheng Cheng*,a
9
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