Recyclable DMAP-Functionalized polymeric nanoreactors for highly efficient acylation of alcohols in aqueous systems

Article abstract of DOI:10.1016/j.polymer.2021.123660

Fabrication of highly efficient and recyclable nanoreactors via macromolecular self-assembly represents a promising strategy for green organic transformation. In this study, small-molecule catalysts 4-(N,N-dimethylamino)pyridine (DMAP) functionalized nanoreactors were constructed by self-assembly of amphiphilic block copolymers with DMAP moieties in the hydrophobic block, leading to heterogeneous catalysts with excellent dispersity in water. The key preparation route included reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(N-methyl-N-(4-pyridyl)amino)ethyl methacrylate (MAPMA) and methyl methacrylate (MMA) using poly (oligomeric (ethylene glycol) methyl ether methacrylate) (POEGMA) as a hydrophilic macromoleculer RAFT reagent. The characterization by dynamic light scattering (DLS) and transmission electron microscopy (TEM) shows that the nanoreactors possess a core-shell nanostructure with the diameter of around 110 nm. The resulting polymeric nanoreactors showed excellent catalytic activity for acylation of alcohols in water. High conversion of a variety of alcohol (>99%) and excellent product selectivity were achieved. The high catalytic efficiency of the nanoreactors may be attributed to the enhancement of the interaction between the reactant and the catalyst in the confined hydrophobic space, which simulates how enzymes usually work. Moreover, the catalyst could be easily recovered by thermos-responsive separation and reused with high activity for more than 5 cycles. This study presents an efficient approach to achieve green catalytic reactions which are normally incompatible to aqueous conditions, potentially applicable to other catalytic systems such as metal-mediated organic transformations.

Full text of DOI:10.1016/j.polymer.2021.123660

Polymer 222 (2021) 123660
Contents lists available at ScienceDirect
Polymer
journal homepage: http://www.elsevier.com/locate/polymer
Recyclable DMAP-Functionalized polymeric nanoreactors for highly
efficient acylation of alcohols in aqueous systems
,
,c,
Jiaqi Qiua 1, Fuliang Menga 1, Maolin Wanga, Jinjin Huanga, Chengzhan Wanga, Xiao Lia,
Guang Yangb, Zan Huab **, Tao Chena
,
,*
a Key Laboratory of Advanced Textile Materials & Manufacturing Technology, Ministry of Education, Eco-Dyeing and Finishing Engineering Research Center, Ministry of
Education, National Base for International Science and Technology Cooperation in Textiles and Consumer-Goods Chemistry, Zhejiang Sci-Tech University, Hangzhou,
Zhejiang, 310018, China
b Biomass Molecular Engineering Center, Department of Materials Science and Engineering, Anhui Agricultural University, Hefei, 230036, China
c Hangmo New Materials Group Co., Ltd, Tianzihu Modern Industrial Park, Anji, 313300, China
A R T I C L E I N F O
A B S T R A C T
Keywords:
Fabrication of highly efficient and recyclable nanoreactors via macromolecular self-assembly represents a
promising strategy for green organic transformation. In this study, small-molecule catalysts 4-(N,N-dimethyla-
mino)pyridine (DMAP) functionalized nanoreactors were constructed by self-assembly of amphiphilic block
copolymers with DMAP moieties in the hydrophobic block, leading to heterogeneous catalysts with excellent
dispersity in water. The key preparation route included reversible addition-fragmentation chain transfer (RAFT)
polymerization of 2-(N-methyl-N-(4-pyridyl)amino)ethyl methacrylate (MAPMA) and methyl methacrylate
(MMA) using poly (oligomeric (ethylene glycol) methyl ether methacrylate) (POEGMA) as a hydrophilic mac-
romoleculer RAFT reagent. The characterization by dynamic light scattering (DLS) and transmission electron
microscopy (TEM) shows that the nanoreactors possess a core-shell nanostructure with the diameter of around
110 nm. The resulting polymeric nanoreactors showed excellent catalytic activity for acylation of alcohols in
water. High conversion of a variety of alcohol (>99%) and excellent product selectivity were achieved. The high
catalytic efficiency of the nanoreactors may be attributed to the enhancement of the interaction between the
reactant and the catalyst in the confined hydrophobic space, which simulates how enzymes usually work.
Moreover, the catalyst could be easily recovered by thermos-responsive separation and reused with high activity
for more than 5 cycles. This study presents an efficient approach to achieve green catalytic reactions which are
normally incompatible to aqueous conditions, potentially applicable to other catalytic systems such as metal-
mediated organic transformations.
DMAP
nanoreactor
Acylation of alcohol
Aqueous catalysis
1. Introduction
hydromethyl-silylation, triphenylmethylation, Steglich rearrangement,
Staudinger synthesis of doxy lactam, to name just a few [4–10]. In
Acylation of alcohols is one of the most fundamental reactions in
organic chemistry. Common acylation catalysts include protic acids,
Lewis acids and strong-acid ion exchange resins [1,2]. Dicyclohex-
ylcarbodiimide (DCC), as a good acylation dehydrating agent, is also
used for the acylation of alcohols under the catalysis of excess acid or
organic base [3]. 4-(N,N-dimethylamino)pyridine (DMAP) as an effi-
cient small-molecule nucleophilic catalyst has widely used for a variety
of organic transformations, such as Baylis-Hillman reaction,
addition, DMAP exhibits a high catalytic activity in the acylation of
various alcohols [11–13]. Although there are lots of advantages such as
low prices and efficient catalytic activities, DMAP also exhibits highly
dermal toxicity, unfriendliness to the environment and poor recovery
performance [14,15]. Therefore, anchoring DMAP into a solid support
to avoid dissemination and facilitate catalyst recycling is very
significant.
In the past decades, many efforts have been done in this area. Various
* Corresponding author.
** Corresponding author.
E-mail addresses: z.hua@ahau.edu.cn (Z. Hua), tao.chen@zstu.edu.cn (T. Chen).
1
Equal contribution.
https://doi.org/10.1016/j.polymer.2021.123660
Received 4 January 2021; Received in revised form 10 March 2021; Accepted 14 March 2021
Available online 18 March 2021
0032-3861/© 2021 Elsevier Ltd. All rights reserved.

J. Qiu et al.
Polymer 222 (2021) 123660
supports such as inorganic ones [16], linear polymers [17], dendritic
polymers [18], microcapsule [19] and microporous organic nanotube
[20] etc. were employed for DMAP immobilization [21,22]. For
ethyl acetate and dichloromethane solution was combined and the
mixture was dried over anhydrous magnesium sulfate. Crude product
was yielded after filtering and concentrating. The desired product was
crystallized from ethyl acetate/petroleum ether in a 68% yield. The
assigned 1H NMR spectrum is shown in Figure S2. 1H NMR (400 MHz,
CDCl3): δ (ppm) 8.07 (dd, J = 5.2, 3.6 Hz 2H), 6.46 (dd, J = 5.2, 1.6 Hz
2H), 3.80 (t, J = 5.6 Hz 2H), 3.51 (t, J = 5.6 Hz 2H), 3.01 (s, 3H).
example, Zhao et al. constructed
a
thermosensitive polymer
brush-supported 4-N, N-dialkylaminopyridine catalyst on silica particles
´
and applied in the hydrolysis of an activated ester [16,23]. Frechet et al.
reported the fabrication of dendritic polymers containing 4-(dia-
lkylamino)pyridines and the effects of polymer architecture and nano-
environment on acylation reactions [24,25]. McQuade et al.
encapsulated a DMAP-containing homopolymer within microcapsules
through interfacial polymerization [26].
2.2. Preparation of 2-(N-methyl-N-(4-pyridyl)amino)ethyl methacrylate
(MAPMA)
Amphiphilic linear copolymers can form micelles by self-assembly in
aqueous media due to the thermodynamic incompatibility of hydro-
philic and hydrophobic segments [27]. The resulting micelles possessing
many desirable properties including easy preparation, good dispersion
in water phase and easy regulation of structure, have been widely used
in the fields of biology, medicine and molecular optoelectronic devices
[28–30]. Selective incorporation of catalyst functionalized monomer
into the hydrophobic segment of a polymeric micelle via copolymeri-
zation techniques offers a convenient way for the fabrication of catalytic
nanoreactors [31,32]. The compartmentalization of catalytic sites
within the hydrophobic core of the nanoreactors enables the catalysis
reaction of hydrophobic substrates in aqueous solution [33,34].
In recent years, micellar nanoreactors based on L-proline [35], chiral
imidazolinone (Macmillan catalyst) [36], 2,2,6,6-tetramethylpiperidine
nitrogen oxide (TEMPO) [37] and other organic small molecular cata-
lysts [38] have been successfully applied to various organic catalytic
reactions, realizing the effective combination of homogeneous and
heterogeneous catalysis. The researchers used the substrate concentra-
tion effect in the hydrophobic core of the nanoreactor and its high
dispersion in the water phase to realize the water-phase catalytic reac-
tion and improve the catalytic performance of the catalyst [39,40].
The synthesis of MAPMA was as follows. To a 50 mL two-neck flask, a
solution of MPAE (1.5 g, 9.86 mmol) and triethylamine (1.58 g, 15.58
mmol) in dry dichloromethane (7.5 mL) was charged under nitrogen
◦
atmosphere. The mixture was cooled to 0 C and a solution of meth-
acryloyl chloride (1.72 g, 16.47 mmol) in dry dichloromethane (4.5 mL)
was added dropwise. After that, the reaction mixture was stirred at room
temperature for 4 h and poured into an aqueous NaOH solution (2.5 M,
25 mL). The organic phase was collected and the aqueous phase was
extracted three times with chloroform. The combined organic layers
were dried over anhydrous Na2SO4 and the solvents were removed in
vacuum. The crude product was then further purified by column chro-
matography using chloroform/methanol (15:1) as the eluent, and finally
◦
dried at 45 C under vacuum to obtain a light yellow liquid in a 28%
yield. The NMR spectrum is shown in Figures S3 and S4. 1H NMR (400
MHz, CDCl3): δ (ppm) 8.21 (d, J = 6.0 Hz 2H), 6.53 (d, J = 5.6 Hz 2H),
6.03 (s, 1H), 5.55 (s, 1H), 4.32 (t, J = 6.0 Hz 2H), 3.67 (t, J = 5.6 Hz 2H),
3.02 (s, 3H), 1.89 (s, 3H). 13C NMR (100 MHz, CDCl3): δ (ppm) 167.33,
153.48, 149.95, 135.87, 126.32, 106.22, 61.50, 49.79, 37.91, 18.37.
2.3. Preparation of water-soluble macromolecular chain transfer reagent
(Macro-CTA) CEPA-P(OEGMA70
)
Additionally,
some
also
utilitized
the
macromolecular
stimuli-responsive characteristics of the nanoreactor to realize the
recycling of the catalyst [41–43].
4-Cyano-4-(ethylthiocarbonothioylthio) pentanoic acid (CEPA) was
synthesized by the procedure described in our previous reports [44,45].
Water-soluble macro-CTA was prepared by the following procedure:
CEPA (50 mg, 0.19 mmol), oligo(ethylene glycol) methyl ether meth-
acrylate (OEGMA with the average molecular weight of 300 Da) (5.7 g,
19 mmol), and AIBN (3 mg, 0.019 mmol) were added to dioxane (5 mL)
in a 25 mL ampule. The mixture was degassed by freeze-pump-thaw
cycles for 3 cycles and then refilled with N2. The polymerization was
performed at 65 ◦C for 24 h. The reaction mixture was cooled down and
then quenched by exposure to air. The crude polymer was precipitated
in cold diethyl ether to yield the desired macro-CTA as a light yellow oil.
The degree of polymerization (DP) was calculated by 1H NMR spectrum
(Figure S5).
Herein, the DMAP functional methacrylate monomer was synthe-
sized. Next, an amphiphilic copolymer was successfully prepared
through RAFT polymerization of DMAP functional monomer and MMA
using thermo-responsive CEPA-POEGMA as a hydrophilic macromo-
lecular chain transfer agent (CTA). Then recyclable core-shell type
DMAP functional micellar nanoreactors were conveniently constructed
by self-assembly in water. On one hand, the high dispersity of micelle in
water endows the catalytic reaction with the characteristic of homoge-
neous catalysis. On the other hand, the core-shell structure provides a
hydrophobic microenvironment and high catalyst concentration inside
the nanoreactors. Because of these features, the nanoreactors realized
the acylation of alcohols in aqueous solution, which is sensitive to water
and usually occurred in dry organic solvents, and demonstrated high
catalytic activity. In addition, the catalyst can be easily recycled by a
heating/centrifugation/filtration strategy based on the temperature
responsive property of nanoreactors. We believe that this facile and
efficient strategy can be extended to construct functional nanoreactors
for various kinds of catalytic applications.
2.4. Preparation of P(MAPMAx-co-MMAy)-b-P(OEGMA70
)
Taking the diblock copolymer P(MAPMA4-co-MMA30)-b-P
(OEGMA70) as an example, macro-CTA (998 mg, 0.05 mmol), methyl
methacrylate (MMA) (0.18 g, 1.8 mmol), AIBN (0.82 mg, 0.005 mmol)
and MAPMA (55 mg, 0.25 mmol) were added to DMF (4 mL) in a 25 mL
ampule. Similar procedures to the preparation of macro-CTA were
adopted for the polymerization. The mixture was degassed by freeze-
pump-thaw for 3 cycles, and then the ampule was refilled with N2.
The polymerization was performed at 65 ◦C for 12 h. The reaction
mixture was cooled down and then quenched by exposure to air, and the
crude product was purified by dialysis in deionized water for 3 days. And
then, the P(MAPMA4-co-MMA30)-b-P(OEGMA70) copolymer was ob-
tained by freeze-drying. The degree of polymerization and monomer
proportion of the copolymers were determined by the 1H NMR spec-
troscopy (Fig. S7). Block copolymer containing different proportions of
hydrophobic monomers were prepared to study the influence of the ratio
of hydrophilic/hydrophobic monomer on the morphology, LCST and
catalytic activity of the nanoreactors. Molecular weight and
2. Experimental section
2.1. Preparation of 2-(methyl-4-pyridinylamino)-ethanol (MPAE)
To a solution of (2-methylamino)-ethanol (15.0 g, 0.2 mol) in 50 mL
tert-amyl alcohol, 4-chloropyridine hydrochloride (3.0 g, 0.02 mol) and
ZnCl2 (136 mg, 1 mmol) were added. The solution was refluxed at
110 ◦C for 24 h. The solution was concentrated after the reaction
finished and then poured into a solution of hydrochloric acid (6 mol Lꢀ 1
,
30 mL). The solution was extracted three times with ethyl acetate, and
adjusted the pH of the water layer to 12–14. Then, the extraction pro-
cedure was repeated three times with dichloromethane. The obtained
2

J. Qiu et al.
Polymer 222 (2021) 123660
temperature of the aqueous solution was raised above its LCST. The
nanoreactors were separated from the water layer after the aqueous
phase was centrifuged at 10,000 g for 30 min. At last, the recovered
catalyst was used for the next run after washing with cold ether
carefully.
Table 1
The molecular characterization data of the polymers.
Sample
Mna (kg
Mnb(kg
Mwc(kg
PDIb
molꢀ 1
)
molꢀ 1
)
molꢀ 1
)
CEPA-P(OEGMA70)(P1)
P(MAPMA4-co-MMA20)-b-P
(OEGMA70)(P2)
19.96
22.75
21.34
25.07
25.18
29.08
1.18
1.16
3. Results and discussion
P(MAPMA4-co-MMA30)-b-P
(OEGMA70)(P3)
23.73
25.69
25.96
26.42
30.37
29.06
1.17
1.10
3.1. Synthesis and structural characterization of block copolymer P
(MAPMAx-co-MMAy)-b-P(OEGMA70)
P(MAPMA4-co-MMA50)-b-P
(OEGMA70)(P4)
a
Determined by 1H NMR spectroscopy (in d-chloroform, Fig. 2a, S5~S8).
Measured by SEC (using polymethyl methacrylate as the standard in THF).
Calculated from SEC data.
In this study, the successful preparation of MPAE, MAPMA and CEPA
was confirmed by the 1H NMR spectra (Fig. S1~S3). Macro-CTA CEPA-P
(OEGMA70) P1 (Mn = 19.96 kg molꢀ 1, PDI = 1.18) (Table 1) was syn-
thesized by RAFT polymerization while CEPA was employed as the
chain transfer agent. Then, an amphiphilic block copolymer incorpo-
rating DMAP analogue on the hydrophobic segment was synthesized
b
c
polydispersity were determined by gel permeation chromatography
(GPC) using THF as the eluent.
providing the low dispersity P(MAPMA-co-MMA)-b-P(OEGMA70
)
2.5. Fabrication of amphiphilic block copolymer-based DMAP
nanoreactors
diblock copolymer P2–P4 (Table 1) (Fig. 1). The successful incorpora-
tion of DMAP analogue toward the amphiphilic block copolymer was
validated by the 1H NMR and 13C NMR spectrum (Fig. S3, S4). It can be
seen that the proton signals of pyridyl ring at 6.48, 8.21 ppm were
observed, whereas the proton signals of olefin in monomer at 5.55, 6.03
ppm were not found. The diblock copolymers with different hydrophilic
and hydrophobic ratios were also obtained successfully through con-
trolling the feed ratios of the hydrophobic monomer. The proportion of
100 mg of P(MAPMAx-co-MMAy)-b-P(OEGMA70) was completely
dissolved in THF (2.0 mL). The THF solution was added to 10 mL of
deionized water using a peristaltic pump. After that, THF in the system
was removed through dialysis in deionized water. Next, dynamic light
scattering (DLS) and transmission electron microscopy (TEM) were
adopted to characterize the size and morphology of the nanoreactor.
1
MAPMA and MMA on the polymer were calculated by H NMR spec-
troscopy (Fig. 2a, S5~S8). Kinetic plot for the copolymerization of MMA
with MAPMA could be seen in Fig. 2b. The actual molecular weight was
determined by size exclusion chromatography (SEC, Fig. 2c).
2.6. General procedure of acylation of alcohols catalyzed by DMAP-
functionalized polymeric nanoreactors in aqueous systems
To a DMAP nanoreactor solution (32 mg of P(MAPMA4-co-MMA30)-
b-P(OEGMA70) in 1 mL deionized water obtained by the solvent ex-
change method, 5 mol%), alcohol (0.1 mmol), 3 equiv. of anhydride, 1.5
equiv. of auxiliary base (DIPEA) were added. The reaction solution was
vigorously stirred at room temperature. After completion of the reac-
tion, cold ether was added to extract product and residual starting ma-
terials. The product and conversion were analyzed by GC-MS. The
3.2. Measurement of the lower critical solution temperatures (LCSTs)
Temperature responsive property is one of the most important
characteristics of polymers, including POEGMA, poly(N-isopropyl
acrylamide) (PNIPAM), and so on. The block copolymers P(MAPMA-co-
MMA)-b-P(OEGMA70) are hydrophilic and highly swollen below their
LCST. However, they become hydrophobic and sharply collapse above
Fig. 1. Schematic illustration of the preparation of P(MAPMAx-co-MMAy)-b-P(OEGMA70) and the fabrication of a DMAP-containing nanoreactor.
3

J. Qiu et al.
Polymer 222 (2021) 123660
Fig. 2. (a) 1H NMR of P(MAPMA4-co-MMA20)-b-P(OEGMA70) (after purification) in CDCl3 (b) kinetics plot for the RAFT polymerization of P2 and (c) SEC traces of
macro-CTA P1 and P(MAPMA-co-MMA)-b-P(OEGMA70) diblock copolymer P2–P4.
Fig. 3. (a) Transmittance of polymer aqueous solutions as a function of temperature investigated by UV–Vis spectroscopy, (b) First derivatives of transmittances
respect to temperature plotted as a function of temperature.
their LCST. The temperature responsive characteristic offers a straight-
forward catalyst recovery method by heating to precipitate the catalyst.
To probe the suitable temperature for the recycling of the current
polymer-based catalyst, their temperature responsive performance was
investigated. The temperature responsive property of the polymers with
different monomer proportions was analyzed by UV–visible spectrom-
eter as shown in Fig. 3a. The concentration of aqueous polymer solution
was fixed to 1.0 mg mLꢀ 1, and the transmittance was measured at 500
nm. During the measurements, the polymers were heated from 50 to
80 ◦C with a heating rate of 1 ◦C minꢀ 1 (Fig. 3a). The maximum value in
4

J. Qiu et al.
Polymer 222 (2021) 123660
Fig. 4. (a) DLS distribution of nanoreactors 2–4 (N2–N4), (b) the representative autocorrelation function of nanoreator 2, (c) the TEM image and (d)histogram of
particle size distribution of N2 obtained by TEM.
the first derivative was defined as the LCST by plotting the first de-
rivatives of transmittances respect to temperature as a function of
nanoreactors 2–4 (N2–N4) ranged from 100 to 120 nm, and the size
increases with the increasing of hydrophobic chain length. In order to
further verify the successful fabrication of DMAP nanoreactors, TEM was
employed to characterize the morphology of the micelles. It can be
found that N2 through the self-assembly of P(MAPMA4-co-MMA20)-b-P
(OEGMA70) showed a spherical morphology, and the average diameter
was around 110 nm. These results were basically consistent with the
results of dynamic light scattering analysis.
◦
temperature (Fig. 3b). It can be found that the LCST of 72.5 C for P
(OEGMA70) P1 is the highest. With the increasing of the ratio of the
hydrophobic MMA, the LCST of the block polymer decreased gradually.
The LCSTs of block polymers P2–P4 are 65, 62.5 and 61 ◦C respectively.
The effect of the hydrophobic block on the LCST is basically consistent
with previous reports [44].
3.3. Preparation and characterization of DMAP analogue-containing
nanoreactor
3.4. Acylation of alcohols in water using DMAP analogue-containing
nanoreactors as catalyst
Self-assembly of amphiphilic diblock copolymers is an important
method to prepare polymeric nanostructures, which has been widely
studied [46–48]. After the preparation of P(MAPMA-co-MMA)-b-P
(OEGMA70) with the DMAP analogue in the hydrophobic chain, the
amphiphilic block copolymers were self-assembled into micelles in
deionized water (DMAP nanoreactor) by solvent exchange method
(Fig. 1). P(MAPMA-co-MMA)-b-P(OEGMA70) was dissolved in THF.
After filtration with a polytetrafluoroethylene (PTFE) type membrane
filter, the diblock copolymer was slowly dropped into the agitated
deionized water through a peristaltic pump, and then the mixture was
put into dialysis bag to remove organic solvent and make the copolymer
micellization at room temperature (T < LCST).
With the polymer-based catalytic nanoreactors in hand, the catalytic
activity of the DMAP functional nanoreactors was evaluated with the
acylation of alcohols. The acylation of paranitrobenzyl alcohol was
firstly chosen as a model reaction to optimize the reaction conditions.
Firstly, acylation reagents were screened. It could be found that octanoic
anhydride give the best result, offering more than 99% conversion of
alcohol in 1 h (Table 1, entries 1–3). Anhydride with better water sol-
ubility such as acetic anhydride and butyric anhydride provided low to
moderate conversions due to its more sensitivity to water. GC-MS
analysis confirmed that most of the excessive anhydrides was hydro-
lyzed into acid during the reaction even if 3 equivalents of acid anhy-
dride was added (Fig. S11~S22). With shortening the reaction time to
half an hour, the alcohol could not be fully converted, and around 78%
conversion was achieved (Table 1, entry 4). The addition of auxiliary
base to the reaction system was beneficial to the higher conversion rate.
Using Et3N as the auxiliary base at the same condition gave 79%
The shape, size, and distribution of the formed polymeric micelles
were next analyzed through DLS (Fig. 4a and b) and TEM (Fig. 4c and d).
Analysis of the nanoreactors by DLS were performed in water at 1.0 mg
mLꢀ 1. The results showed that average hydrodynamic diameters of
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J. Qiu et al.
Polymer 222 (2021) 123660
Table 2
Table 3
The optimization of reaction conditions for the acylation of paranitrobenzyl
Acylation of alcohols with different molecular structuresa.
alcohola.
c
Entrya
Alcohol
Time (h)
1
Conv. (%)b
99
TOF (hꢀ 1
19.8
)
Entry
Catalyst
Auxiliary
base
Anhydride
Time
(h)
Conv.
(%)b
1
1
nanoreactor
DIPEA
DIPEA
DIPEA
DIPEA
Et3N
acetic
1
34
55
99
78
79
31
75
99
64
99
2d
1
31
6.2
2
anhydride
butyric
2
nanoreactor
1
2
anhydride
octanoic
anhydride
octanoic
anhydride
octanoic
anhydride
octanoic
anhydride
octanoic
anhydride
octanoic
anhydride
octanoic
anhydride
octanoic
anhydride
3
4
1
1
99
99
19.8
19.8
3
nanoreactor
1
2
4
nanoreactor
0.5
1
2
5
6
7
0.75
075
1
99
98
99
26.4
26.1
19.8
5
nanoreactor
2
6
DMAPc
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
1
7
nanoreactor
0.5
1
3
8
nanoreactor
3
8
1
99
19.8
9
nanoreactor
0.5
1
0
4
10
nanoreactor
4
9
0.75
0.75
98
99
26.1
26.4
1
a
The reaction conditions: alcohol (0.1 mmol), acid anhydride (3 equiv.),
auxiliary base (1.5 equiv.), and nanoreactors (5 mol%) in water at room
temperature.
10
2
11
0.75
96
25.6
b
c
3
The reactant conversion based on the alcoholwas determined by GC-MS.
Use unsupported DMAP as the catalyst, and all else being the same.
12
13
0.75
0.75
98
99
26.1
26.4
4
5
conversion, which was worse than DIPEA (Table 2, entry 5). To study the
effect of nanoreactors, unsupported DMAP as the catalyst in the aqueous
phase was performed as the control experiment. Only 31% conversion of
alcohol was achieved, which couldn’t be improved even if the reaction
time was extended to 1 h (Table 2, entry 6). The high efficiency of the
DMAP functional nanoreactors may be ascribed to the micellar structure
where the core provides an ideal hydrophobic environment for the
substrate concentration and the enhancement of the interaction between
the reactant and the catalyst in aqueous solution. Similarly, nanoreactor
3 and 4 demonstrated high catalytic activities towards the acylation
reaction when the time reaches 60 min, providing excellent conversion
and selectivity (Table 2, entries 8, 10). The yield after 0.5 h for nano-
reactor 3 (75%, Table 2, entry 7) and nanoreactor 4 (64%, Table 2, entry
9) was even lower than nanoreactor 2 (78%). The content of hydro-
phobic monomer in the nanoreactor 2 to 4 increased gradually, which
led the concentration of DMAP in the nanoreactor core decreased. In
turn, the lower DMAP concentration caused the catalytic efficiency
decrease to a certain extent.
a
The reaction conditions: alcohol (0.1 mmol), octanoic anhydride (3 equiv.),
DIPEA (1.5 equiv.), and N2 (5 mol%) in water at room temperature.
b
c
The reactant conversion based on alcohols was determined by GC-MS.
Turnover frequency.
d
Use unsupported DMAP as the catalyst, and all else being the same.
group, the acylation reaction could be completely converted to the
desired acylation product in an hour (Table 3, entries 3, 4). While, the
reaction time could be shortened to only 45 min for the benzyl alcohol
with electron-donating group in the phenyl ring, which should be
attributed to the increase of nucleophilicity (Table 3, entries 5, 6). 1-
Phenylethanol and diphenyl methanol are commonly used as second-
ary alcohols. Their acylation reaction was also completed in an hour
(Table 3, entries 7, 8). The steric hindrance affects the attack of elec-
trophilic reagent to a certain degree, and then slows down the reaction.
Different aliphatic alcohols were also conveniently transformed to their
corresponding ester in near 99% conversion within 45 min due to their
relatively high nucleophilicity (Table 3, entries 9–13).
Recyclability is an important factor in the catalyst design. Nano-
reactors based on temperature responsive polymers offered a convenient
recycle strategy through a heating/centrifugation/filtration strategy.
For the recyclability of DMAP functional nanoreactor, we took the
acylation reaction of paranitrobenzyl alcohol by nanoreactor 2 as the
template reaction. The small molecules in the water were extracted with
an excess of diethyl ether after the reaction. The nanoreactor underwent
a phase separation in water when the temperature was raised above the
LCST of the block copolymer P(MAPMA4-co-MMA20)-b-P(OEGMA70) P2.
Followed by sequential centrifugation, filtration and washing with ether
thoroughly, the catalyst could be recovered effectively. Around only
8.5% weight loss of catalyst was observed by comparing with the stan-
dard curve of P(MAPMA4-co-MMA20)-b-P(OEGMA70) in UV–vis spec-
troscopy (Fig. S9). The recyclability of the catalysts was tested over a six-
3.5. Substrate scope study and the recyclability of the DMAP functional
nanoreactor
Encouraged by the above results, the generality of the acylation
using DMAP nanoreactor in aqueous system was further tested. It can be
seen from Table 3 that benzyl alcohols, secondary alcohols and aliphatic
alcohols were successfully acylated to yield the corresponding esters in
excellent conversions (>95%) in the presence of Nannoreactor 2 in
aqueous solution. For paranitrobenzyl alcohol, the acylation reaction
could be completely converted to octanoic acid paranitrobenzyl ester in
an hour (Table 3, entry 1, TOF = 19.8 hꢀ 1). While, unsupported DAMP
led to 31% conversion (Table 3, entry 2, TOF = 6.2 hꢀ 1). Obviously, the
conversion and TOF were increased when nanoreactor was adopted as
catalyst. For the benzyl alcohols with electron-withdrawing substituent
6

J. Qiu et al.
Polymer 222 (2021) 123660
derivative containing a 1,1’-binaphthyl unit: importance of the hydroxy groups,
J. Org. Chem. 82 (2017) 6846–6856.
run recycling experiment with 8.5% supplement. No marked deactiva-
tion was observed. The kinetics for each run of recycling experiment
clearly demonstrated the recovery performance of the nanoreactor
(Fig. S10).
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In conclusion, in this work we have successfully constructed recy-
clable core-shell type catalytic nanoreactors in a simple two-step pro-
cedure, through RAFT polymerization of DMAP functional monomer
and MMA using thermo-responsive POEGMA as a hydrophilic macro-
molecular chain transfer agent, followed by self-assembly in deionized
water. The obtained DMAP functionalized nanoreactors exhibit excel-
lent activity in the acylation of various alcohols in aqueous solution. Its
catalytic activity was proved much higher than that of unsupported
catalyst. The high activity could be attributed to the unique micelle
structure where the core provides an ideal hydrophobic environment for
the substrate concentration and the enhancement of the interaction
between the reactant and the catalyst. Furthermore, the catalyst could
be easily recovered by heating/centrifugation/filtration strategy based
on the temperature responsive property, and the results showed that the
catalyst remains high catalytic activity after 6 times of recovery. This
study reports a facile method to achieve green chemical transformations
in aqueous solution, which is potentially applicable to other moisture-
sensitive catalytic systems such as metal-mediated organic
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Declaration of competing interest
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The authors declare that they have no known competing financial
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Acknowledgments
The authors appreciate the financial support to this research by the
Zhejiang Provincial Natural Science Foundation of China (No.
LY17B020013) and the Fundamental Research Funds of Zhejiang Sci-
Tech University (No. 2019Q020). Z.H. acknowledges the financial sup-
port by Anhui Provincial Natural Science Foundation (2008085QE249),
and Anhui Provincial Innovation and Entrepreneurship Support Plan for
Overseas Returnees (2019LCX023).
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Appendix A. Supplementary data
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