Temperature responsive polymer-supported TEMPO: An efficient and recoverable catalyst for the selective oxidation of alcohols

Article abstract of DOI:10.1016/j.tetlet.2018.12.051

This study aimed to combine the advantages of homogeneous catalysis and heterogeneous catalysis by immobilizing TEMPO into a water-soluble temperature responsive polymer. The supported TEMPO was water soluble and displayed excellent activity in the selective oxidation of alcohols below the LCST and can be easily recovered.

Full text of DOI:10.1016/j.tetlet.2018.12.051

Accepted Manuscript
Temperature Responsive Polymer-Supported TEMPO: An Efficient and Re-
coverable Catalyst for the Selective Oxidation of Alcohols
Tao Chen, Zhenkai Xu, Lei Zhou, Laiyu Hua, Shuo Zhang, Jiping Wang
PII:
S0040-4039(18)31502-8
https://doi.org/10.1016/j.tetlet.2018.12.051
TETL 50514
DOI:
Reference:
Tetrahedron Letters
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Revised Date:
Accepted Date:
15 October 2018
12 December 2018
21 December 2018
Please cite this article as: Chen, T., Xu, Z., Zhou, L., Hua, L., Zhang, S., Wang, J., Temperature Responsive Polymer-
Supported TEMPO: An Efficient and Recoverable Catalyst for the Selective Oxidation of Alcohols, Tetrahedron
Letters (2018), doi: https://doi.org/10.1016/j.tetlet.2018.12.051
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Tetrahedron Letters
Temperature Responsive Polymer-Supported TEMPO: An Efficient and Recoverable
Catalyst for the Selective Oxidation of Alcohols
Tao Chen*a,b, Zhenkai Xua, Lei Zhoua, Laiyu Huaa, Shuo Zhanga and Jiping Wang*a,b
a College of Materials and Textiles, Zhejiang Sci-Tech University, Hanghzou City, Zhejiang Province, P. R. China 310018.
b Key Laboratory of Advanced Textile Materials & Manufacturing Technology, Ministry of Education, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, P. R.
China 310018
Graphical Abstract
The advantages of homogeneous catalysis and heterogeneous catalysis were combined by immobilizing TEMPO into a
temperature responsive polymer.
Leave this area blank for abstract
info.
Temperature Responsive
Polymer-Supported TEMPO:
An Efficient and Recoverable
Catalyst for the Selective
Oxidation of Alcohols
Tao Chen*a,b, Zhenkai Xua, Lei Zhoua, Laiyu Huaa, Shuo Zhanga and Jiping Wang*a,b
Highlights:



The advantages of homogeneous catalysis and heterogeneous catalysis were combined.
The catalyst system was highly efficient to the selective oxidation of alcohols.
Temperature responsive polymer was developed as a TEMPO support.
* Email: tao.chen@zstu.edu.cn, jpwang@zstu.edu.cn; Fax: +86 (0)571 8684 3666; Tel: +86 (0)571 8684 3779

2
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
This study aimed to combine the advantages of homogeneous catalysis and heterogeneous
catalysis by immobilizing TEMPO into a water-soluble temperature responsive polymer. The
supported TEMPO was water soluble and displayed excellent activity in the selective oxidation
of alcohols below the LCST and can be easily recovered.
Available online
@2018 Elsevier Ltd. All rights reserved
.
Keywords:
temperature responsive polymer
homogeneous catalysis
selective oxidation
Introduction
homogeneous and heterogeneous catalysis for selective oxidation
of alcohols is still highly desirable. Temperature responsive
polymer, due to the hydrophilic effect of the hydrophilic group
and the hydrophobic effect of the alkyl group, exhibits the Lower
Critical Solution Temperature (LCST) in water [31]. When the
temperature is lower than its LCST, the polymer form hydrogen
bonds with water molecules make the polymer water soluble.
When the temperature is higher than its LCST, it tends to form
intramolecular hydrogen bonds, resulting in phase separation
from water [3233-35]. The unique characteristic of temperature
responsive polymer make it can act an excellent carrier for
catalyst immobilization [ 36 - 39 ]. Poly(oligo(ethylene glycol)
methacrylate) as a kind of temperature responsive polymer has
been widely studied [ 40 , 41 ]. The LCST of copolymer of
di(ethylene glycol) methyl ether methacrylate (MEO2MA) and
oligo(ethylene glycol) methyl ether methacrylate (OEGMA) can
be tuned by adjusting the ratio of two monomers in the
copolymer [42]. Herein, we report the synthesis of temperature
The selective oxidation of alcohols into the corresponding
aldehyde or ketone represents one of the most important
transformations in organic synthesis and total synthesis of natural
products [1,2]. These reactions are typically achieved with the
use of stoichiomeric amounts of high-valence transition-metal
salts or organic-based oxidants that generate relatively large
amounts of hazardous wastes [ 3 - 6 ]. The development of
environmentally friendly procedures for the organic reactions is
always an important goal of chemists [7-11]. In this regards,
stable nitroxyl radical 2,2,6,6-tetramethylpiperidine-1-oxyl
(TEMPO) was developed as an organic catalyst for the selective
oxidation of alcohols, and displayed excellent catalytic
performance [12-16]. Although low catalyst loading are required,
product isolation and catalyst recovery remain key issues with
this system. To overcome these issues, immobilization of
TEMPO as heterogeneous catalysts adopting different solid
supports such as microporous organic nanotube networks [17],
magnetic core-shell nanoparticle [18], silica [19-20], SBA-15
[21], cross-linked polystyrene [22,23], Ionic liquid [24] etc. have
been reported. However, the activity and selectivity of the
catalysts are often reduced if they are fixed onto insoluble solid
or carriers with poor dispersibility [25].
responsive
polymer
P(MEO2MA-co-OEGMA)-supported
TEMPO, its catalytic activity and recovery in the selective
oxidation of alcohols.
Activated ester-amine chemistry as a post-polymerization
modification method was introduced in functional polymer
synthesis even before the advent of click chemistry [43]. In our
initial study, we tried to synthesize temperature responsive
copolymer with a terminal activated ester group by RAFT
polymerization using NHS-CEPA as a RAFT reagent. NHS-
CEPA was prepared by slightly modifying the literature method
(Scheme 1) [44]. To achieve a carrier with a suitable LCST, we
used feeding ratios of MEO2MA and OEGMA in 3:1, 2:1, 5:3,
The combination of the advantages of homogeneous and
heterogeneous catalysis, so that the catalyst has the
characteristics of homogeneous catalyst during the reaction
process, and can be recycled as a heterogeneous catalyst after
reaction, is of great significance [ 26 ]. Consequently, PEG-
supported TEMPO catalysts with excellent solubility in reaction
media have been developed, which displayed excellent catalytic
activities and can be recovered by solvent-induced precipitation
[27-30]. Developing new carrier to combine the advantages of
Table 1. Data of the P(MEO2MA-co-OEGMA) Polymers
Feeding Ratio
LCSTc
a
b
Sample
Mn
Mn
PDI
(nMEO2MA: nOEGMA
)
(oC)
NHS-P(MEO2MA48-co-OEGMA14) (1a)
NHS-P(MEO2MA45-co-OEGMA19) (1b)
NHS-P(MEO2MA42-co-OEGMA19) (1c)
NHS-P(MEO2MA35-co-OEGMA27) (1d)
NHS-P(OEGMA65) (1e)
3:1
2:1
5:3
1:1
0:1
11900
12400
11500
13000
14300
13595
14530
13966
15048
19860
1.134
1.168
1.130
1.128
1.217
43 (40)
47.5
49
55.5 (53)
72.5 (71.5)
aMeasured by GPC (in THF).
bMeasured by 1H NMR (in CDCl3, Fig. S3)
cTemperature at the maximum of |△S/△T| (Fig. S4), LCST of TEMPO-P(MEO2MA-co-OEGMA in parentheses.

a
120
100
80
1a
1b
1c
1d
1e
b
2a
1a
2d
1d
2e
1e
100
50
0
60
40
20
0
-20
35 40 45 50 55 60 65 70 75 80 85
30
40
50
60
70
80
Temperature (℃)
Temperature (℃)
Fig. 1. The percent transmittance of copolymer versus temperature (a) copolymers NHS-P(MEO2MA-co-OEGMA) 1a~1e; (b)
copolymers TEMPO-P(MEO2MA-co-OEGMA) 2a, 2d and 2e (compared with the corresponding copolymers 1a, 1d and 1e).
1:1, and 0:1 to synthesize the copolymers and the samples were
marked as 1a~1e (Scheme 2).
the successful introduction of a relative hydrophobic TEMPO to
the end group of the temperature responsive polymers (Fig. 1b),
which is consistent with our expectations. Among copolymers 2a,
2d and 2e, the LCST of copolymer 2a was 40 oC, which not only
facilitate the homogeneous catalysis at room temperature or
lower temperature, but also the catalyst recovery at acceptable
high temperature. Therefore, copolymer 2a was the catalyst of
choice.
The molecular weight and MW/Mn (PDI) of the synthesized
NHS-P(MEO2MA-co-OEGMA) were measured by Gel
Permeation Chromatography (GPC). The detail information of
was summarized in Table 1. It can be seen that NHS-
P(MEO2MA-co-OEGMA) have uniform distributions (PDI<1.22)
and their molecular weights ranged from 11.5 KDa to 14.3 KDa.
After the successful preparation of the catalyst, we examined
its catalytic activity in the selective oxidation of alcohols. The
oxidation of benzyl alcohol was selected as a model reaction to
optimize the reaction conditions using copolymer 2a as a catalyst.
To our delight, 1.0 mol% copolymer 2a could efficient catalyze
the reaction in water/DCM biphasic media at 0 oC using a slightly
excess of buffered aqueous NaClO (1.25 mol equiv., pH = 9.1) as
the terminal oxidant and NaBr (1.25 mol%) as the co-catalyst,
S
CN
O
OH
N
S
CN
DCC, rt
O
O
O
S
S
N
+
S
S
COOH
O
O
CEPA
NHS
NHS-CEPA
Scheme 1 Synthesis of NHS-CEPA.
S
CN
O
O
S
S
O
N
n
O
m
O
O
AIBN, NHS-CEPA
dioxane, 65 ℃ , 6 h
O
O
O
+
O
O
O
O 4-5
OEGMA
O 2-3
O 2-3
O 4-5
affording nearly complete conversion to benzaldehyde (Table 2,
entry 1).
MEO2MA
NHS-P(MEO2MA-co-OEGMA)
Scheme 2 Synthesis of NHS-P(MEO2MA-co-OEGMA).
Encouraged by the results, we next investigated the catalyzed
selective oxidations of a variety of alcohols under the optimized
conditions. The results were summarized in Table 2. Benzyl
alcohols containing either electron-withdrawing group (NO2-, Br-)
or electron-donating group (CH3O-, CH3-) were readily selective
oxidated to the corresponding aldehydes in almost quantitative
yields within 1 hour, as found in the case of unsubstituted benzyl
alcohol (Table 2, entries 2-5). It is worth noting that the system
also has excellent catalytic activities for different types of
aromatic alcohols including 1-phenylethanol, 2-phenylethanol, 1-
naphthalenemethanol and diphenylmethanol. Both primary and
secondary alcohols were highly efficiently oxidized to their
corresponding carbonyl compounds (Table 2, entries 6-8, 12). In
addition, fatty alcohols that are more difficult to selectively
oxidize than aromatic alcohols were also efficiently converted.
GC-MS yields were consistently high for straight-chain and less
steric alcohol (Table 2, entry 9, 10). To our delight, the sterically
hindered 2-adamantanol were also oxidized in high yield (Table 2,
entry 13), and sulfur-containing benzyl alcohol also could be
efficiently selective oxidized to corresponding aldehyde keeping
the methylthio group untouched.
The LCSTs of the copolymers were measured using UV-vis
spectrometer (Fig. 1). Where, the LCST was defined as the
temperature at the derivation absolute value (|△S/△T|) of the
curve of transmittance versus temperature (Fig. S4). We found
that the LCST of NHS-P(MEO2MA-co-OEGMA) gradually
decreases as the proportion of MEO2MA increases, which could
be well explained by less hydrogen bond between polymer chain
and water formed with the increasing of MEO2MA segments.
TEMPO was introduced into the terminal of the polymers by
the facile reaction of the activated ester of NHS-P(MEO2MA-co-
OEGMA) with 4-amino-TEMPO (Scheme 3). We found through
its 1H NMR that the characteristic peak of NHS in NHS-
P(MEO2MA-co-OEGMA) in 2.85 ppm disappeared completely
after the reaction , and the characteristic triplet signal of TEMPO
appeared in Electron Spin Resonance (ESR) spectra (Fig. 2) [45-
46].
These observation indicated that TEMPO was successfully
loaded into the temperature responsive polymers and NHS group
of NHS-P(MEO2MA-co-OEGMA) was completely replaced by
TEMPO.
Ease of separation and reusability are extremely important for
polymer-supported catalyst. The recyclability of TEMPO-
P(MEO2MA48-co-OEGMA14) was investigated using benzyl
alcohol as substrate under the optimized reaction conditions.
After the completion of the reaction, cold diethyl ether was added
to extract the product. The remaining aqueous phase appeared as
a light-yellow transparent homogeneous solution. Heating the
H
N
S
CN
S
CN
O
O
S
S
O
N
n
O
m
S
S
O
n
O
m
N
O
O
TEA,rt,N
O
2
O
O
O
O
O
H2
N
N O
2-3
4-5
2-3
4-5
O
O
O
O
NHS-P(MEO MA-co-OEGMA)
TEMPO-P(MEO MA-co-OEGMA)
2
2
o
residual aqueous solution to 60 C (>LCST) resulted in phase
Scheme 3 Synthesis of TEMPO-P(MEO2MA-co-OEGMA).
Compared to NHS-P(MEO2MA-co-OEGMA), the LCST of
separation of the temperature responsive polymer-supported
TEMPO from water. Subsequently, the muddy aqueous solution
was carefully centrifugated offering the viscous oil in the bottom
of the bottle, and then the upper aqueous solution was dumped to
o
TEMPO-P(MEO2MA-co-OEGMA) decreased 1~3 C owning to

4
Tetrahedron
Yieldb
(%)
entry
alcohol
product
Time
OH
CHO
1
1 h
>99
>99
>99
>99
>99
>99
>99
OH
O N
2
3460
3480
3500
3520
3540
2
3
4
5
6
7
1 h
O N
2
CHO
Magnetic field (G)
OH
Br
1 h
Br
CHO
Fig. 2 ESR spectra of TEMPO-P(MEO2MA-co-
OEGMA)
OH
H3CO
30 min
1 h
H3CO
H3C
CHO
recover the catalyst (Fig. 3). The loss of catalyst weight was
around 3.7% (Fig. S5) each run being observed, which may
attributed mainly to the mechanical loss during the recovery. The
loss of catalyst may be reduced through optimization of the
heating/centrifugation method. After thoroughly washing with
cold diethyl ether, the recovered catalyst was used in the next run
directly without further purification, and almost consistent
activity was obtained for 6 consecutive cycles although the
catalyst loading decreased to a certain degree (Fig. 4).
OH
H C
3
CHO
1 h
OH
O
OH
CHO
1 h
8
9
1 h
>99
>99
OH
OH
CHO
CHO
30 min
OH
CHO
10
11
1 h
1 h
>99
>99 (94)
CHO
OH
O
OH
12
13
1 h
>99 (96)
OH
O
1 h
97 (91)
Table 2. Oxidation of Alcohols with Different Substratesa
99
99
99
99
99
99
100
OH
92
CHO
S
S
14
30 min
>99 (92)
OH
R2
O
NaClO, 0 ¡æ, NaBr, H2O/DCM
R1
R1
R2
TEMPO-P(MEO2MA-co-OEGMA)
50
aReaction condition: alcohol (0.8 mmol), TEMPO-P(MEO2MA-co-OEGMA)
(1.0 mol%), NaBr (1.25 mol %) in CH2Cl2 (2 mL), aq NaClO (2 mL), at 0 oC,
pH = 9.1.
0
1
2
3
4
5
6
7
Cycle index
b GC-MS yields, and isolated yields in parenthesis.
Fig. 4 Catalytic performance of the recycled TEMPO-
P(MEO2MA48-co-OEGMA14).
Conclusions
In conclusion, we have successfully immobilized TEMPO on
temperature responsive polymer resulting in a high efficient and
recyclable catalyst for the selective oxidation of alcohols in
o
biphasic solvent media at 0 C. Under the optimized reaction
conditions, the catalyst system was highly efficient to the
selective oxidation of a variety of substrates including the benzyl
alcohols with electron-donating or electron-withdrawing group,
1-naphthalenemethanol, diphenylmethanol and sterically
hindered fatty alcohols. Importantly, the catalyst can be easily
recovered by heating/centrifugation of the polymer aqueous
solution, and reused at least six reaction cycles without loss of
catalytic activity. Investigation of the developed TEMPO system
Fig. 3 Before and after heating/centrifugation.

for selective oxidation of alcohols in halogen-free conditions is in
progress in our laboratories.
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The authors would like to thank Zhejiang Provincial Natural
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