Nitrite-containing resin as an efficient and recyclable catalyst for aerobic oxidation of oximes to carbonyl compounds

Article abstract of DOI:10.1080/00397911.2016.1211290

Using novel nitrite-containing resin as an NO source and Amberlyst-15 as cocatalyst, we developed aerobic oxidation of oximes to corresponding carbonyl compounds with molecular oxygen as a clean oxidant reagent. It was distinguished from the previous related reports, and the experimental results indicated that additional water obviously decreased the yield. This process provides a better choice for oxidative deoximation with many advantages, such as high yield, simple procedure, high catalytic performance, and recyclable catalyst.

Full text of DOI:10.1080/00397911.2016.1211290

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Nitrite Containing Resin as an Efficient and
Recyclable Catalyst for Aerobic Oxidation of
Oximes to Carbonyl Compounds
Shu Guo, Renyou Zeng & Caiye Li
To cite this article: Shu Guo, Renyou Zeng & Caiye Li (2016): Nitrite Containing Resin as an
Efficient and Recyclable Catalyst for Aerobic Oxidation of Oximes to Carbonyl Compounds,
Synthetic Communications
To link to this article: http://dx.doi.org/10.1080/00397911.2016.1211290
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Date: 28 July 2016, At: 01:18

Nitrite Containing Resin as an Efficient and Recyclable Catalyst for Aerobic
Oxidation of Oximes to Carbonyl Compounds
Shu Guo1, Renyou Zeng1, Caiye Li1
1School of Chemistry and Chemical Engineering, Hainan Normal University, Haikou,
China
Corresponding authors: Shu Guo, E-mail addresses: gslzgs@hotmail.com
Abstract
Using novel nitrite containing resin as NO source, Amberlist-15 as cocatalyst, aerobic
oxidation of oximes to corresponding carbonyl compounds with molecular oxygen as a
clean oxidant reagent was developed. It was distinguished from the previous related
reports, and the experimental result indicated that additional water obviously decreased
the yield. This process provided a better choice for oxidative deoximation with many
advantages, such as higher yield, simple procedure, high catalytic performance, and
recyclable catalyst.
GRAPHICAL ABSTRACT
1

KEYWORDS: Nitrite Containing Resin; Aerobic oxidation; Deoximation Reaction;
Recyclable catalyst
INTRODUCTION
Oximes serve as important synthetic intermediates as they are extensively used for
purification, characterization and also protection of carbonyl containing molecules.
Hence many reagents and methods have been devised for the deprotection of oximes.
There were reports that Amberlyst-15 supported nitrosonium ion as an effective oxidative
reagent was applied in cleavage of oximes to the corresponding carbonyl compounds.1
An adapted process using catalytic amounts of NaNO2 and the reuse of Amberlyst-15 as
reagent was developed to the same aerobic oxidation.2 Above two reports indicated that
the organic solvent / water as a mixed solvent would enhance the reaction rate. Herein,
we report our new approach that an aerobic oxidation system which introduced novel
FPA53 containing nitrite functional group resin (FPA53-NO2) and Amberlyst-15 as the
catalyst and molecular oxygen as the environmentally friendly oxidation for regeneration
of carbonyl compounds from oximes. However, as far as our research was concerned,
there was evidence to show that the protic solvent including water, was a
negative activator to inhibit the generation of NO2, an actual oxidizing agent for aerobic
oxidation of oximes.
EXPERIMENTAL
2

The IR spectra were determined on a Nicolet Avatar360 FTIR Spectrometer (KBr
pellets), 1HNMR and 13CNMR spectra were recorded with a Bruker AV400 (400MHz)
spectrometer. GC were performed on a GC9790 ( Zhejiang Fuli Analytical Instrument
Co., Ltd) using a capillary column of HP-5 (25m×0.32mm×0.25um). Amberlite FPA53
(weakly basic anion exchange resin, moisture holding capacity 56-64 %), Amberlyst 15
(H form, dry) resin and 732 strongly acidic cation exchange resin (the same as Amberlite
IR120 H Form resin, water content 50–55%, ion-exchange capacity: 3.2 mmol/g) were
purchased from Shanghai Aladdin Bio-Chem Technology Co., LTD and used in original
form. All solvent was freshly distilled.
Preparation Of FPA53 Containing Nitrite Functional Group ( FPA53-NO2 )
The FPA53-NO2 was prepared as follow. 5.0 g Amberlite PFA53 was added to 15 ml
alcohol, and was stirred at RT for 10 min. Then 5 g phosphoric acid (85% w/w) was
slowly added to the suspension of FPA53. After 6 h stirred, the solution was filtered out.
The resin beads were thoroughly rinsed with deionized water until given a neutral
solution by pH paper detecting. Then sodium nitrite (3.5 g, 0.05 mol ), deionized water
(15 ml ) and the treated polymer beads with phosphoric acid were introduced into a flask,
and the stirring was continued for 4 hours at 40℃. The light yellow polymer beads was
filtered and washed many times with deionized water until no yellow AgNO2
precipitation was observed by dripping 0.1 M silver nitrate aqueous solutions in the
eluent. Again sodium nitrite (3.5 g, 0.05 mol ) and deionized water (15 ml ) was added
3

and the process was repeated a second time for another 4 h at 40℃. In succession, the
resin was dried in a vacuum oven at 40℃ for 4 hours. By this time, the golden resin
beads containing nitrite functional group (FPA53-NO2) were prepared.
As a comparison, FPA53 loaded NaNO2 also was prepared in the meanwhile.
Involved procedure was in agreement with process of preparing FPA53-NO2
except for protonation of tertiary amine by phosphoric acid.
General Experimental Procedure For Deoximation To The Corresponding Carbonyl
Compounds
Oximes ( 1.0 mmol ), Amberlyst-15 ( 0.02 g ), FPA53-NO2 ( 0.02 g ) and solvent ( 1.5
mL ) were introduced into a 25 cm high and 90 mL autoclave with a glass tube inside
equipped with magnetic stirring. Then the autoclave was charged with oxygen to 0.1 MPa.
The reaction mixture was stirred at desirable temperature for special time. Progress of the
reaction was monitored by TLC or GC. After the reaction, The resin (Amberlyst-15 and
FPA53-NO2 ) were separated from the reaction mixture by filtration and was extracted
with 3 mL CH3CN (2×1.5ml). The solvent was removed under reduced pressure. The
residue was further purified by column chromatographyon silicagel (300 mesh) with
hexane / ethylacetate to give the corresponding carbonyl compounds.
RESULTS AND DISCUSSION
4

FTIR spectrum of FPA53, FPA53 loaded NaNO2 and FPA53-NO2 were collected and
given in Fig. 1. FPA53 and FPA53 loaded NaNO2 showed almost no difference
absorption peaks both in number and intensity. The similarities suggested very low
loading level of NaNO2 due to no bonding interaction between the resin and NaNO2. The
above estimate also was confirmed by measuring the capacity of FPA53 loaded NaNO2
based on nitrite content by spectrophotometer. The detected result showed loading
amount of nitrite was much lower as 6.5 mg per gram of dry resin.3 However, the
quantization to FPA53-NO2 by the same spectrophotometer was unreliable because of the
decomposition in the presence of water under acidic conditions. What should happen next
is to find a accurate and useful detection methodology to determine nitrite content of
FPA53-NO2.
From Fig. 1, the infrared absorption at about 1035 cm−1 was corresponded to C-N
stretching vibration of tertiary amine in FPA53 and FPA53 loaded NaNO2. There
was reason to assume that the blueshift of C-N stretching vibration from 1035 cm−1 to
1062 cm-1 could be attribute to convert tertiary amine into tertiary aminium salt. A broad
and weak absorption peak appeared at 2553cm-1 was likely related to N-H stretching
vibration of R3NH+. The intensity of N-O symmetric stretching of nitrate at 1268 cm−1
almost have not significantly increase in FPA53 loaded NaNO2. However, a strong
absorption peak at 1268 cm−1 showed that FPA53-NO2 had higher nitrite content and it
could be attributed to form a stronger bonding interaction between FPA53 and nitrite.
5

First, acetophenoneoxime was used as a model substrate and efficiency of a variety
of solvents and catalytic conditions were investigated. The results were listed in Table 1.
In this catalyzed system, FPA53-NO2 was served as an efficient NO source, which
was immediately oxidized by oxygen to form NO2 as an oxidant to oxidize oxime. We
found that an acidic condition could make the release of NO more effective. In this work,
Amberlist-15, a strongly acidic cation exchange resin, was arranged to provide a recycled
acidic source. The trace water of Amberlyst-15 (about 1.5% water content ) actually was
an essential composition for release a little proton which helped to establish a smooth
acid reaction environment. From Table 1, the results confirmed that the lack of
Amberlist-15 made the oxidation almost was not carried out (Table 1, entry 1). When
adding 0.01 g Amberlist-15, the desired product was obtained in 45.5% yield (Table1,
entry 2). Increasing the amount of Amberlist-15 to 0.02 g, an excellent yield of
acetophenone was obtained at 60℃ for 2 h ( 100% GC yield, Table 1, entry 3). When air
was used instead of O2, the yield decreased to 42.7% (Table1, entry 4). Shorten reaction
hours and lowing reaction temperature, obvious deteriorated results could also be
observed (Table1, entry 5-6). When CH3CN was replaced with DMF (an weakly basic
aprotic solvent), an offset in the acidity of Amberlyst-15 drastically reduced the yield of
acetophenone to 1.5% (Table1, entry 11).
6

The possible mechanism of the deoximation reaction has been described.1-2 In
the existence of molecular oxygen, NO is oxidized to NO2. The latter was deemed to be
actual oxidizing agent for oxidating oximes to the corresponding carbonyl compounds in
this reaction.4-6
In the presenting of active hydroxyl, NO could be rapidly oxidized
by oxygen to nitrosonium (NO+), which reacted with nucleophilic centers such as ROH to
produce RONO alkylnitrite,7 or reacts with water to form nitric and nitrous acids
respectively.8 Both of the process inhibited formation of NO2, and resulted in an
unexpectedly low yield (Table1, entry 7 and entry 10). The result also was
supported by other experimental evidence. From Table1, entry 9 we could find that
CH2Cl2, a aprotic solvent with a low water content make the conversion of oxime
completely. When the same amount of 732 resin (50–55% water content) was used
instead of Amberlist-15 (1.5% water content ), a significant decrease of yield was
observed because of quenching the formation of actives ingredients by containing excess
water (Table1, entry 8). It was suggested that the solvent that contain excess active
hydroxyl, such as alcohols and water or basic solvent should be excluded from this
reaction.
To evaluate the scope of this catalytic system, a variety of oxime including various
aromatic aldoximes as well as aliphatic and aromatic ketoximes were subjected to these
reaction conditions. The results were summarized in Table 2. Not only the ketoximes
bearing electron withdrawing groups (such as Cl, Br, F, Ph, NO2) on the arene ring, but
7

also bearing electron donating groups (including of H, CH3, OCH3) could easily be
almost completely converted to the corresponding ketones (Table2, entries1-7).
Meanwhile, for the sterically hindered benzophenoneoxime and 9-fluorenoneoxime,
excellent yields could also be achieved (Table 2, entries 9 and 10). Deoximation reaction
of aliphatic oximes were a bit more difficult, and normally requires longer reaction times.
After 6 h reaction time, benzylacetone oxime, DL-Camphor oxime and
1,3-diphenylacetone oxime could respectively give the corresponding ketone with gentle
yields from 32% to 83% (Table 2, entries 11-13). Unexpectedly, cyclohexanoneoxime
give the corresponding ketones in poor yields (Table 2, entry 14). It is possible that the
conjugate effect or hyper conjugation effect of the aromatic ketoximes make the
intermediate to possess higher stability than those of the aliphatic ketoximes.1, 9 Similarly,
when some aldoximes, that is, benzaldehyde oxime derivatives were subjected to the
standard reaction conditions, moderate yields ( 60%- 85%) were obtained with 4 h
reaction time (Table 2, entries 15-19). However, an aliphatic aldoxime, cinnamaldehyde
oxime only got 6% yield (Table 2, entry 21). These results might indicate that the
aldoximes are more stable than ketoximes under the reaction conditions. Moreover,
for the ketoximes or aldoximes containing active hydroxyl, it is little surprise that no
corresponding carbonyl compounds could be obtained (Table 2, entry 8 and 20).
As was mentioned earlier, NO can easily produce RONO with hydroxyl and inhibit
formation of NO2.
8

In order to check recycle ability of the resin catalyst, the catalyst recycles successive
runs were carried out as following procedures. First, in the presence of FPA53-NO2 ( 0.02
g ) and Amberlyst-15( 0.02 g ), 1 mmol acetophenoneoxime and 1.5 ml acetonitrile were
allowed to test with 1 atm molecular oxygen, at 60℃ for 2h. At the end of one oxidation
run, the autoclave was cooled down and the organic phase was removed by a pipette. The
residue was further extracted twice with acetonitrile (2×1.5 ml). The solid phase was kept
in the autoclave, and then fresh 1 mmol acetophenoneoxime and another 1.5 ml
acetonitrile was added. Subsequently, the autoclave was pressurized with 1 atm O2 again
and was heated under the same reaction conditions for the next cycle. The results of the
catalyst recycle were shown in Fig. 2.
The catalyst maintained its good level of efficiency and the yield of acetophenone
were hold above 95% even after being reused for six runs (Fig. 2). The obvious decrease
in yield could be observed in the seventh reaction cycle, indicating the catalyst owned
relatively stable activity in the recycle.
CONCLUSIONS
In conclusion, we have prepared a novel nitrite containing resin FPA53-NO2, which
was accompanied with amberlyst-15 formed a simple, efficient and reused system for
aerobic oxidation of oximes to corresponding carbonyl compounds with molecular
oxygen as a clean oxidant reagent. The method has advantages in terms of yield,
9

heterogeneous nature, green and reproducible reagents, short reaction times and easy
work-up. To this catalytic system, solvent selection is of critical importance, and the
protonic solvent, basic solvent and excess water existed in the reaction system must
be avoided.
FUNDING
We are thankful to the Natural Science Foundation of Hainan (No.214025) for their
funding in this research work.
REFERENCES
1. M. M. Lakouraj，M. Noorian，M Mokhtary, Reactive & Functional Polymers, 2006, 66,
910
2. G.-F. Zhang, X. Wen，Y. Wang，W.-M. Mao，C.-R. Ding, J. Org. Chem. 2011, 76,
4665.
3. R. Diaconu, M. Vasilov, G. Mancas, J. Preventive Med. 2001, 9, 74.
4. Y.-Z. Mao, Z.-L. Liu, L.-M. Wu, Chinese J. Chem. 2000, 18, 789.
5. S. B. Shim, K. Kim, Y. H. Kim, Tetrahedron Lett. 1987, 28, 645.
6. J. Mokhtari, M. R. Naimi-Jamal, H. Hamzeali, M. G. Dekamin, G. Kaupp. Chem.
SusChem. 2009, 2, 248.
7. S. Kaiser, P. D. Mascio, M. E. Murphy, H. Sies, Arch. Biochem. Biophys. 1990, 277,
101.
10

8. Y.-N. Lee, S. E. Schwartz, J. Phys. Chem. 1981, 85, 840.
9. H. Firouzabadi, N. Iranpoor, K. Amani, Synthetic Communication. 2004, 34, 3587.
11

Table 1. The FPA53-NO2 catalyzed deoximation reaction of acetophenoneoxime with
Amberlist-15 and molecular oxygen under different reaction conditions a
OH
O
°
1atm O2, 60 C
N
CH3
FPA53-NO2, Amberlyst-15
CH3
Entry Solvent
FPA53-NO2 (g)
0.02
Amberlist-15 (g) Time (h) Yield a (%)
1
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH2Cl2
-
2
2
2
2
1
2
2
2
2
2
2
< 1
2
0.02
0.01
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
45.5
3
0.02
100 (98 b)
42.7 c
68.7
4
0.02
5
0.02
6
0.02
53.7 d
24.9 e
41.6 f
100
7
0.02
8
0.02
9
0.02
10
11
C2H5OH
DMF
0.02
0.02
1.5
1.7
a Reaction condition: acetophenoneoxime (1 mmol, 0.137 g ), solvent (1.5 mL), O2 (1atm),
at 60℃
b Yield is based on the gas chromatography (GC) with area normalization.
c Values in parentheses is the isolated yield
12

d Air (1atm) was used instead of O2 (1atm)
e Reaction temperature is at 50℃
f 0.1 mL of water was added
g The same amount of 732 resin was used instead of Amberlist-15.
13

Table 2. The FPA53-NO2 catalyzed Aerobic deoximation reaction of Ketooximes and
Aldoximes to Carbonyl Compounds in the presence of Amberlist-15 a
Entry Substrate
Product
Time (h)
Yield b (%)
OH
N
N
1
O
2
97
Cl
Cl
OH
O
2
2
2
2
2
2
2
2
2
2
6
98
97
98
98
97
97
0
Br
Br
F
OH
N
O
3
F
OH
O
N
4
O2N
O2N
O
OH
N
N
5
OH
O
6
OH
O
N
7
MeO
MeO
HO
OH
O
N
8
HO
OH
OH
N
O
9
98
98
59
O
N
10
11
OH
O
N
14

12
6
83
O
O
N
N
OH
OH
13
14
6
6
32
19
O
OH
N
OH
O
N
15
16
17
4
4
4
60
75
73
H
H
Cl
Br
Cl
OH
H
N
O
H
Br
O
H
OH
H
N
O2N
O2N
OH
O
N
18
19
4
4
79
85
H
H
OH
H
N
O
H
MeO
MeO
HO
OH
H
O
N
20
21
4
4
0
6
H
HO
OH
O
N
H
H
a Reaction condition: oxime (1 mmol ), Amberlyst 15 (0.02 g), FPA53-NO2 (0.02 g),
acetonitrile (1.5 mL), O2 (1atm), at 60℃
b Based on isolated yield
15

Scheme 1. FPA53-NO2 and Amberlyst-15 catalyzed aerobic Deoximation
16

Scheme 2. process of preparing FPA53-NO2
17

Figure 1. FTIR spectrum of FPA53, FPA53 loaded NaNO2 and FPA53-NO2
18

Figure 2. Reuse of Resins for Deomixation of acetophenoneoxime a
19