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Nanoparticle Based on Poly(ionic liquid) as an Efficient Solid Immobilization Catalyst for Aldol Reaction and Multicomponent Reaction in water Xinjuan Li, Chunna Lv, Xianbin Jia, maoqin chen, kai wang, and Zhiguo Hu ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.6b12334 • Publication Date (Web): 14 Dec 2016 Downloaded from http://pubs.acs.org on December 20, 2016

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ACS Applied Materials & Interfaces

Nanoparticle Based on Poly(ionic liquid) as an Efficient Solid Immobilization Catalyst for Aldol Reaction and Multicomponent Reaction in Water Xinjuan Lia,*, Chunna Lva, Xianbin Jiaa, Maoqin Chenga, Kai Wanga, Zhiguo Hua,* a Henan Key Laboratory of Green Chemistry, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, P. R. China, Correspondence to: Xinjuan Li(E-mail:) [email protected] Zhiguo Hu (E-mail: [email protected])

Abstract: •

An environmentally friendly nanoparticle-supported catalyst was successfully

prepared via in situ ionic complexation between imidazolium-based polymer ionic liquid (PIL) and poly (L-prolinamide-co-MAA). The physical and chemical properties of the obtained nanoparticles were characterized by TEM, FTIR, XPS and static water contact angle experiments. The surface properties of the nanoparticle were found to significantly affect the catalytic performance. The nanoparticle with PIL outer facilitated the adsorption of reaction substrate in it. As a result, the catalytic system efficiently catalyzed the asymmetric Aldol reaction and multicomponent reaction in pure water efficiently. The catalytic system was able to be reused and recycled five times, and with no discernible loss in catalytic activity and enantioselectivity. These findings suggest that nanoparticles based on PIL may provide a new approach for preparing high performance supported catalysts for organic reactions in water. This technology also addresses issues associated with mass transfer in pure water reactions. Key words: nanoparticle, polymer ionic liquids, Aldol reaction, multicomponent reaction,

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in water. Introduction： Compared to the organic solution, the aqueous phase as a green system has a great advantage of economical and environmental. So organic reactions in aqueous have attracted people’s widespread attention recently. Though water as reaction solvent is of great significance for chemical processes, water posses several disadvantages such as low solubility of organic reactants in water,1-4 which can result in biphasic reactions and/or immiscible mixtures.5 Many methods have been proposed to solve this problem including mixing with co-solvents,6 using surfactant combined phases,7, 8 and heating the reaction mixture.9-11 However, the organic reaction in aqueous media still faces with great challenges. The immobilization of chiral catalysts have been used to address the recyclability issues associated with organic catalysts in water.12-28 Amphiphilic copolymers have been extensively studied in catalysts in water and have been shown to self-assemble into nano-micelles in water. The nano-micelle provides a hydrophobic environment which acts to lower the interfacical energy of the reaction system and promote organic reactions in water.29-34 Recently, Hansen and co-workers immobilized the Macmillan catalyst in a nanogel system via emulsion polymerization and showed that the lightly cross-linked nanogel provided a hydrophobic environment by copolymerization with the hydrophobic monomer.35 Previous work has also shown that the hairy particles grafting with amphiphilic copolymer supported L-proline, which catalyzes the asymmetric Aldol with good catalytic activity and enantioselectivity, and can also be recycled in pure


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water.31 The hydrophobic effect in the catalytic system is the main contributor to the development of supported catalysts in water. Ionic liquids (ILs) have attracted considerable attention due to favourable

•

properties such as good ionic conductivity, low vapor pressure, wide temperature range, and ability to readily dissolve many chemicals.36, 37 Polymer ionic liquids (PILs) poss unique features that belong to both polymer and counter intrinsic properties of IL with anion and cation.38 Loading ionic liquids have been used as the solvent for catalytic active centers to help loading catalyst or serve as basic catalysts.39-42 However, as we all known, the heterogeneous catalytic systems based on PIL which may be used as an efficient supported organic catalyst in water, have not been previously studied. In addition, immobilization of ILs on the solid support material has some issues such as complicated synthetic procedures and low loading of immobilized ILs.43 In the current study, a simple, green, and efficient method was used to prepare

•

the nanopartilce supported L-prolinamide catalyst based on the poly(ionic liquid) via an in

situ

ionic

complexation

(as

scheme

1).

The

surface

structure

and

hydrophobicity-hydrophilicity performance of the nanoparticles were tuned by varying the PIL reaction ratio and applying different anions. The obtained nanoparticle catalysts were characterized by FTIR, TEM, XPS and static water contact angle experiments. The influence of nanoparticle surface structure on the catalytic activity and asymmetric selectivity was investigated through Aldol and multicomponent reactions (MCRs). The chiral solid catalyst could catalyze the Aldol and multicomponent reactions (MCRs) in water efficiently, and exhibit much better



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catalytic activity and enantioselectivity than its homogeneous catalyst system. The existence of PIL outer in this catalytic reaction system was the key factor to accelerate the organic reaction in water. The nanoparticles based on PILs provide a new approach to synthesize of the high performance supported catalysts for organic reactions in water.

Scheme 1. The synthesis process of nanoparticle supported catalyst via a situ ionic complexation in alkaline organic solvent.

Experimental section Materials and reagents Methacrylicacid (>98%, MAA, Aldin, China) was purified by distillation under pressure. Azobisisobutyronitrile (>98%, AIBN, Tianjin chemical reagent co, China) was


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recrystallized in ethanol. N-styrene benzenesulfonyl-L-prolinamide was prepared using previously described methods.44 PIL preparation is described in detail in the Supporting Information, and other chemical reagents were used as-received condition. Method  1H

NMR spectra were measured on a Bruker 400 MHz NMR spectrometer. A

Thermo FLASH 1112 elemental analyzer was used to determine the elemental analysis. The IR measurements were carried out on a Fourier transform infrared spectrometer (Nicolet NEXUS). HPLC method was performed on an Agilent TM 1100. The molecular weight and molecular weight distribution (PDI=Mw/Mn) of the synthesized polymer samples were determined by gel permeation chromatography (GPC) equipped with a Waters 1515 apparatus, DMF was used as eluent, the flow rate was 1.0 mL.min-1, and polystyrene samples were used as standards. Transmission electron microscopy (TEM, JEOL-2010, 200 kV) was used to determine the number-average diameter (Dn) of the nanoparticles. Preparation of catalysts 1.1 Synthesis of N- styrene benzenesulfonyl-L- prolinamide copolymer •

The copolymer was synthesized by free radical copolymerization using the following

procedure:

MAA

(0.32

g,

4.50

mmol),

and

N-styrene

benzenesulfonyl-L-prolinamide (2.52 g, 9.0 mmol) were added into 13.5 mL DMSO in succession. The clear solution was stirred for 30 min at room temperature, and AIBN (0.02 mmol, 4.5 mg) was added. After five freeze pump thaw cycles for degassing, the sealed flask was put in a 75°C oil bath for 48 h. The resulting polymers were



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precipitated in ether, and then was dried enough under vacuum at 40°C. This process produced a yellow powder with a yield of 81.7%. 1.2 Synthesis of poly(ionic liquid) complexs (PILCs) PILC-1

was

prepared

as

follows:

PIL-1

(0.3

mmol,

0.6

g)

and

poly(L-prolinamide-co-MAA) (0.3 mmol, 0.06 g) were dissolved in 5.0 mL DMSO to form a clear solution. 50 mL of ethanol containing 0.5 wt% NH3 (prepared from 25 wt% aqueous NH3 solution) was added to a plastic tube, and placed in an ulrasonication bath. 5 mL of PIL and poly(L-prolinamide-co-MAA) mixture solution was added dropwise (2 mL/min) into the plastic tube under stirring (900 rpm) and sonication (40% sonication amplitude). Insoluble PILC particles formed immediately upon addition of the PIL and Poly(L-prolinamide-co-MAA) mixture solution, and the ultrasonication was maintained for an additional 5 min. The product was collected by centrifugation, and washed with ethanol for 4 times. The obtained product was dried at 50°C, and the yield was 73%. PILC-2 and PILC-3 based on the mole ratio of 1:2 and 2:1 for PIL-1 and poly(L-prolinamide-co-MAA) were prepared in a similar way, with yields of 67% and 59%, respectively. PILC-4

was

prepared

with

the

mole

ratio

of

2:1

for

PIL-2

and

poly(L-prolinamide-co-MAA), giving a yield of 81%. The prolinamide catalyst loadings were 0.84, 0.81, 1.38, and 0.91 mmol/g for PILC-1, PILC-2, PILC-3 and PILC-4 respectively, as determined by the elemental analysis (Supporting Information, Table S1) 1.3 PILCs as catalysts applied in direct asymmetric Aldol reaction


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PILCs (10 mol%, 0.025 mmol prolinamide content) as catalyst were added to a mixture of acetone (104 µl, 1.0 mmol) and 4-nitrobenzaldehyde (0.25 mmol, 38 mg) in corresponding 1 mL solvent. The mixture was stirred at different temperatures till the reaction completed which was monitored by TLC. The reaction mixture was isolated by centrifugation, and the poly(ionic liquid) complex (PILCs) were washed using methanol. The solid was dried under vacuum for the next cycle. The aqueous layer was extracted with EtOAc then and dehydrated with MgSO4. After evaporation of the solvent, the crude product was separated and purified by column chromatogram (petroleum ether/EtOAc=4:1, v/v) to yield the desired product. 1.4 PILCs applied in multicomponent reaction PILC-3 (10 mol%, 0.025 mmol prolinamide content) as catalyst was added to a mixture of urea (0.3 mmol, 1.2eq), benzaldehyde (0.25 mmol, 1eq) and ethyl acetoacetate (0.5 mmol, 2eq) in corresponding solvent (1 mL). The resulting mixture was put in a 25°C oil bath under stirring, during the reaction period, and the reaction was monitored by TLC. After filtration and purification with ethanol, the solid product was dried enough under pressure for subsequent characterization. PILCs (20 mol%, 0.2 mmol prolinamide content) as catalyst were added to a mixture of 2-hydroxy-1,4-naphthoquinone (1 mmol) and Aldehyde (1 mmol) in corresponding 1 mL solvent. The mixture was heated in an 80°C oil bath under stirring for 30 minutes. After the addition of 1 mmol 3-amino-5-methylpyrazole, the reaction continued to react under stirring until the reaction was completed as monitored by TLC. The resulting solid was filtered and purificatied with ethanol. The PILCs catalysts were



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then dissolved in the tetrahydrofuran, filtered, and washed by ethanol for the next cycle. The aqueous layer was then evaporated to give the product. Results and Discussion Preparation and characterization of the catalysts The chiral copolymer was prepared via free radical copolymerization, and the structure was characterized by 1H-NMR (Figure 1). The molar ratio of the different copolymers was calculated through comparing the NMR signals (δ 1.4-1.8 ppm for PMAA and prolinamide Ha+b+c+e, 6.0-9.1 ppm for L-prolinamide Hd). The ratio of MAA and L-prolinamide) was 1:1.2, the average molecular weight for the copolymer was 43,100, and PDI=1.13 (GPC analysis). DMSO

b a CH3

c

x HOOC

y

d

d

d

d

O

S O NH

O

e

a+c+e

f

HN g

b

f d g

14 13 12 11 10

9

8

7

6

5

4

3

2

1

0

ppm

Figure 1.1HNMR spectrum of poly(L-prolinamide-co-MAA) in DMSO-d6.

Poly(ionic liquid) complexes (PILCs) were prepared by a simple and efficient method. Poly(ionic liquid) and poly(L-prolinamide-co-MAA) were dissolved in DMSO and formed a homogeneous solution. As the most of the COOH units in poly(L-prolinamide-co-MAA) chains stay in a non-dissociated form, after an excess of


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ethanol was added to the solution, insoluble PILC particles formed immediately as weak complexation occurred, because MAA was tuned into a charge state at the same time. We prepared the different poly(ionic liquid) complexes by the situ ionic complexation between the poly(ionic liquid) (m) and the copolymer (n) with the different mole ratio. When the ratio (m:n) was 1:1, PILC-1 supported L-prolinamide without more functional groups appeared on the surface. With the same method, the polymer complex (PILC-2 and PILC-3, 4) were prepared with the ratios of 1:2 and 2:1 to compare and investigate the structure−function relationship of PIL with the chiral complex catalyst, as shown in Scheme 1. Due to the excess of PILs, the surface of PILC-3 and PILC-4 contained more ions. FT-IR spectra of the resulting PILCs are showed in Figure 2. The characteristic peak at 1700 cm−1 may be ascribed to C=O stretching vibration in the COOH group, which shifts to 1550 cm-1 due to conversion of COOH to COO− groups. The FT-IR results indicate that some additional characteristic peaks for example amide I band (1257 cm−1, C=O stretching) and amide II band (1625 cm−1, C-N stretching) also appeared in addition to the peaks corresponding to the PIL, which further verifies the successful complex. TEM analysis of PILC-1 (Figure 3a) showed that the complex formatted the uniform sphere structure with an average diameter (Dn) of 68 nm. The number-average diameters (Dn) of the PILC-2 and PILC-3 were determined to be 102 and 172 nm, respectively (Figure 3b and 3c). The increased particle size for PILC-3 demonstrated the successful attachment of the PILs onto the surface of nanoparticle. The TEM image of



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PILC-4 (Figure 3d) showed an averaged diameter (Dn) of 23 nm suggesting that the particles possess collapse of the aggregates due to the hydrophobic PF6-. Elemental analysis (Table S1) of PILCs showed that they have a stoichiometric composition, in accordance with the experiment ratio. The XPS spectra were used to determine the surface chemical properties of the PILCs in Figure 4. Most Cl existed in PILC-3, which may be attributed to the addition of a high ratio of PIL. The relative amount of Cl on the surface of the catalysts was calculated by the XPS data with the following results: PILC-3 (6.96%, 1.96 mmol.g−1) >PILC-2 (5.25%, 1.48 mmol.g−1) > PILC-1 (2.33%, 0.66 mmol.g−1). F and P existed in PILC-4 due to the addition of high ratio of PIL-2. The FT-IR and XPS analysis results demonstrated the presence of a variety of functional groups such as −COOH, −Cl- and −PF6- on the surface of the catalysts. 10

(a) 1681 3437

831

1203 1633

1138

(b)

750 1112

3417

(c)

1660 1625

(d)

1257

(e) (f) 0

3500

3000

2500

2000

1500

1000

500

Wavenumber(cm-1) Figure 2. Fourier transform infrared spectra (FT-IR) of (a) L- prolinamide functionalized copolymer, (b) PIL-1, (c) PILC-1, (d) PILC-2, (e) PILC-3, and (f) PILC-4.


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Figure 3. TEM images of (a) PILC-1, (b) PILC-2, (c) PILC-3, (d) PILC-4. 0

10

280000

F

C

(d)

Intensity( a.u.)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


N

31.49%

53.13%

10.33%

(a)

5.05%P

19.47%

(b)

71.57%

Cl2.33% S6.63%

17.15% 73.45% 5.25% 5.25%

(c)

15.76% 73.97% 6.96% 3.31%

0 800

700

600

500

400

300

200

100

Electron Binding Energy( eV) Figure 4. XPS spectra of (a) PILC-1, (b) PILC-2, (c) PILC-3, and (d) PILC-4.

Static water contact angle experiments were performed to evaluate the surface hydrophilicity of the complex (in Figure 5). The static water contact angles were found



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to be 64.5°, 85.2°, 79.4°, and 92.3° for PILC-1, PILC-2, PILC-3 and PILC-4, respectively. These results clearly demonstrated that PILC-3 exhibited some hydrophilic-hydrophobic property compared with PILC-1 and PILC-2. PILC-4 with PF6anion should be super hydrophobic, however, the contact angle was only 92.3°, which showed some hydrophobic performance. The reason may be attributed to the existence of the other polar groups such as amide and sulfamide groups. The above result also proved that the nanoparticles were modified with different shell structures.

Figure 5. Static water contact angle experiments of the PILCs (1) PILC-1, (2) PILC-3, (3) PILC-2, and (4) PILC-4.

Poly(ionic liquid) nanoparticle supported catalyst applied in direct asymmetric Aldol reaction •

In order to study the catalytic performance of the obtained PILCs, a

series of experiments were carried out in a Aldol reaction between 4-nitrobenzaldehyde and acetone. This same reaction has been studied for the L-prolinamide functionalized copolymers, as well as unsupported L-prolinamide monomer. The reactions were firstly carried out in DMF at 25°C, and reaction kinetics results are detailed in Figure 6a. The


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activity of PILC-1 was found to be significantly higher than the small molecule chiral catalyst and copolymer supported catalyst system. The conversion rate of PILC-1 was near 100% within 12 h at 10% catalyst loading, while the small molecule catalyst and copolymers had conversion rates of 40% and 48%, respectively. Asymmetric reactions in pure water have already attracted extensive attention because water is a cheap, safe and green media. So, we studied the catalytic activity in the green pure water system. The reaction kinetics in Figure 6b showed that the complex catalysts maintained high catalytic activity in pure water without the addition of other agents at 0°C (a lower reaction temperature improves the enantioselectivity). PIL as catalyst can catalyze the Aldol reaction in water (the conversion was 57% for 8 h). The conversion for PILC-3 was 91% and the conversion for PILC-4 was the highest (97%) (Table 1), which was higher than the conversion rate for PILC-1 and PILC-2. The results disclosed the surface structure with the PIL exposed more anions and cations affected the reaction rate. These results also suggest that PIL plays a key role in asymmetric Aldol reactions. In previous report, ILs acted as alkali catalysts in asymmetric reactions.45 In the current catalytic system, the essence of the high catalytic activity was the inherent synergistic effect between PIL and organic catalyst built into the PILC nanoparticle.



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Figure 6. The catalytic kinetic curves of a: (a) PILC-1，(b) L- prolinamide functionalized copolymer， (c) L-prolinamide monomer at 25°C in DMF. The catalytic kinetic curves of b: (a) PILC-4, (b) PILC-3, (c) PILC-2, (d) PILC-1, and (e) Lprolinamide functionalized copolymer at 0°C in water.


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Figure 7. Images of (a) 4-nitrobenzaldehyde was dispersed in water, (b) PILC-3 and 4-nitrobenzaldehyde was added in water , (c) PILC-4 and 4-nitrobenzaland dehyde was added in water, (d) 4-nitrobenzaldehyde was adding in pure PIL-1; (e) 4-nitrobenzaldehyde was dissolved in PIL-1 after 10 minutes, and (f) 4-nitrobenzaldehyde was dissolved in PIL-2 after 10 minutes. Table 1. The Aldol reaction between acetone and 4-nitrobenzaldehyde catalyzed by the different catalyst system for 8 h in water. O H

OH

catalyst 10 mol%

O

O

O2N

O 2N

Catalysts

Temperature (°C)

PIL

0

% Conversion 57

% Ee N

L-prolinamide copolymer

0

0

N

PILC-1

0

56

87

PILC-2

0

62

89

PILC-3

0

91

91

PILC-4

0

97

82

Due to incompatibility and the existing interface between the hydrophilic proline catalyst and hydrophobic reactants, asymmetric reaction always results in low yields even no product when the reaction is in pure water system. To clear the reason for their



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excellent catalytic performance of PILCs in water, the dissolved experiments for 4-nitrobenzaldehyde were carried out. Figure 7e and 7f showed that 4-nitrobenzaldehyde can fully dissolve in PIL-1 and PIL-2, but do not dissolve in water (Figure 7a). When PILC-3 or PILC-4 were added with 4-nitrobenzaldehyde in water, 4-nitrobenzaldehyde was encased in the PILCs (as seen in Figure 7b and 7c). The PIL-functionalized nanoparticle (PILC-3 and PILC-4) had good wettability with organic reactant molecules, which helped to enhance the accessibility of the active sites on the catalyst. Furthermore, PILC-4 with hydrophobic anion provided a hydrophobic nano-reaction cavity for the organic reaction.[7] Thus, the PIL-functionalized nanoparticles can promote the Aldol reaction efficiently. PILCs supported catalyst applied in multicomponent reaction Recently, L-proline was used to synthesize the heterocyclic compound such as the 2H-benzo [g] pyrazolo [3,4-b] quinoline-5,10 (4H, 11H)-dione derivatives46 and et al,47 the heterocyclic compounds synthesized by the multicomponent reaction are a very important class of organic compounds which were widely used in the fields of medicine,48-55 pesticides,56 and other materials.57 Firstly, PILC-3 was used to catalyze the simple multicomponent reaction such as the Biginelli reaction (Table 2). Interesting, the catalytic activity appeared to increase for the PILC-3 in water than it was used in the other solvent, and the reaction provided a relatively better product with 80% conversion and 40% ee. Table 2. Solvent effects on the Biginelli reactions at room temperature for 72 h.


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O

CHO O H2N

O

catalyst (10 mol%)

O

NH2

HN

NH

OEt

Ph COOEt

Entry

Catalyst

Solvent

1 2 3 4 5 6

PILC-3 PILC-3 PILC-3 PILC-3 PILC-3 PILC-3

H2O Toluene THF MeCN EtOH CH2Cl2

 Furthermore,

reactions

of

Conversion（%） Ee（%） 80 35 50 40 60 65

40 29 39 19 6 34

we also investigated the relatively complicated three-component

4-chlorobenzaldehyde

with

2-hydroxy-1,4-naphthoquinone

and

3-amino-5-4-methylpyrazole using PILCs as the catalyst. As a typical experiment, 4-chlorobenzaldehyde and 2-hydroxy-1,4-naphthoquinone were combined with PILCs as a catalyst to initiate a domino Aldol reaction. At last, the desired product was obtained via a Michael addition reaction by adding the 3-amino-5-4-methylpyrazole. PILC-3 produced the desired product in an acetonitrile, ethanol, and pure water system (Table 3). Interesting, the catalytic activity and enantioselectivity were the highest for the PILC-3 in water which provided the optimal conversion (99%) and ee value (98%) compared with other solvents (Table 3, entry 1). Multicomponent reactions (MCRs) as a powerful tool were used to synthesize heterocycles in organic synthesis and drug discovery. However, there are little published methods on the synthesis of solid loading catalyst used in the preparation of heterocycles in water. Table 3. Solvent effects on the three component reactions 4-chlorobenzaldehyde with 2-hydroxy-1,4-naphthoquinone and 3-amino-5-4-methylpyrazole at 80°C.

＊



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Entry

Catalyst

Solvent

Page 18 of 27

Reaction time

Conversion

Ee (%)

（%）

(h) 1 2

PILC-3 PILC-3

H2 O EtOH

21 21

99 85

98 40

3

PILC-3

MeCN

21

80

18

4

PILC-3

THF

21

45

36

Table 4. Comparison of the different catalyst system catalyzing the three component reactions between 4-chlorobenzaldehyde, 2-hydroxy-1,4-naphthoquinone and 3-amino-5-4-methylpyrazole at 80℃ in water.

Entry

Catalyst

Reaction time

Conversion

(h)

a

Ee (%)

（%）

1 2

PIL-1 PIL-1

3 21

0 60

Na 12

3

L-prolinamide monomer

3

25

N

4

L-prolinamide monomer

21

50

55

5


3

15

N

6


21

60

58

7

PILC-1

3

30

N

8

PILC-1

21

95

94

9

PILC-2

3

42

N

10

PILC-2

21

95

93

11

PILC-3

3

60

N

12

PILC-3

21

99

98

13

PILC-4

3

68

N

14

PILC-4

15

99

98

which means no detection.

To determine the contribution of the PIL on the catalytic properties of PILCs, three component reactions were conducted with different catalyst systems (Table 4). L-prolinamide monomer was used as the reference, which gave a 50% conversion and 55% ee value for 21 h (Table 4, entry 4). These results showed that the PILCs were more effective than the free polymer supported system and the monomer catalyst. In contrast, PILC-4 provided the highest catalytic activity and enantioselectivity (the


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conversion for PILC-4 was 68% for 3 h, 99% conversion and 98% ee for 15 h), which indicate that the hydrophobic PIL surface provided a more favorable catalytic environment in water. PIL-3 and PIL-4 displayed the excellent catalytic activity and enantioselectivity which means our design by increasing the PIL amount to adjust the catalytic properties is successful, PILC-3 and PILC-4 supported catalyst system with more IL structures can effectively catalyze three components reactions in water. The

reaction

between

2-hydroxy-1,4-naphthoquinone,

3-amino-5-4-methylpyrazole and several substituted benzaldehydes with PILC-3 as catalyst were also investigated. From these results, we found that a variety of aromatic aldehydes including p-nitrobenzaldehyde as well as m-nitrobenzaldehyde also produced the product with better conversions (above 90%) in water than in the other solvents (Table 5). In contrast, m-nitrobenzaldehyde showed better enantioselectivity in acetonitrile and water with the ee values of 90% and 99%, respectively. Furthermore, PILC-4 as catalyst was successfully used in the aqueous Aldol reaction for 5 cycles with no discemible decreases in activity and enantioselectivity. The three component reaction was also catalyzed by PILC-4 in water for 5 cycles without losing significant activity and enantioselectivity (Figure 8). Table 5. The three component reactions between different substitution in water at 80℃ with PILC-3 as catalyst.



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R1

Solvent

Reaction time (h)

Page 20 of 27

Conversion

Ee (%)

（%） p-nitrobenzaldehyde m-nitrobenzaldehyde

EtOH EtOH

21 21

75 80

5 29

p-nitrobenzaldehyde

MeCN

21

75

27

m-nitrobenzaldehyde

MeCN

21

70

90

p-nitrobenzaldehyde

H2 O

21

91

24

m-nitrobenzaldehyde

H2 O

21

90

99

Figure 8. Aldol reaction between 4-nitrobenzaldehyde and acetone was catalyzed by PILC-4 in H2O for 8 h (a) and three component reactions between 3-amino-5-4-methylpyrazole, 2-hydroxy-1,4-naphthoquinone, and 4-chlorobenzaldehyde was catalyzed by PILC-4 in H2O for 21 h in multiple cycles (b).

Conclusions •

A simple, green and efficient method for the preparation of nanoparticle

supported chiral catalyts based on PIL were described. Nanoparticles were successfully prepared via in situ ionic complexation between poly(L-prolinamide-co-MAA) and imidazolium-based PILs in alkaline organic solvent. With PIL content increasing, the chiral nanoparticle with PIL as the particle outer was obtained, which could catalyze the Aldol reaction and multicomponent reaction in pure water efficiently. The system displayed higher activity and enantioselectivity compared with their homogeneous counterparts. The reason owes to the fact that the nanoparticle with PIL outer structure


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facilitates the mass transfer of reaction substrates into the nanoparticle. Furthermore, the catalysts were easily separated and recycled. The synthetic method for nanopaticles supported catalysts is green which solves the problem associated with mass transfer in pure water reactions. Supporting Information Synthesized method of the PIL-1 (Scheme S1) and PIL-2 (Scheme S2), 1HNMR spectrum of PIL-1 in DMSO-d6 (Figure S1) and FT-IR spectrum of PIL-1 (Figure S2). the elemental analysis and catalyst loading for PILCs (Table S1), 1HNMR spectrum and HPLC messages of the different racemes (Figure S3-7). Acknowledgements This work was supported by the National Natural Science Foundation of China (No.21204019), and the Youth Backbone Teacher Foundation of Henan Normal University (No.HSDGGJS201407). References (1) Butler, R. N.; Coyne, A. G. Water: Nature’s Reaction Enforcers Comparative Effects for Organic Synthesis “In-Water” and “On-Water”. Chem. Rev. 2010, 110, 6302−6337. (2) Baldwin, J. E.; Herchen, S. R.; Schulz, G. Hydrophobic Acceleration of Diels-Alder Reactions. J. Am. Chem. Soc. 1980, 102, 7817−7818. (3) Chakraborti, A. K.; Rudrawar, S.; Jadhav, K. B.; Kaur, G.; Chankeshwara, S. V. ‘‘On Water’’ Organic Synthesis: a Highly Efficient and Clean Synthesis of 2-aryl/heteroaryl/styryl Benzothiazoles and 2-alkyl/aryl Alkyl Benzothiazolines. Green Chem. 2007, 9, 1335−1340. (4) Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb, H. C.; Sharpless, K. B. “On Water”: Unique Reactivity of Organic Compounds in Aqueous Suspension. Angew. Chem., Int. Ed. 2005, 44, 3275−3279. (5) da Silva, C. X. A.; Goncalves, V. L. C.; Mota, C. J. A. Water-tolerant Zeolite Catalyst for the Acetalisation of Glycerol. Green Chem. 2009, 11, 38−41. (6) Luque, R.; Clark, J. H. Water-tolerant Ru-Starbon® materials for the Hydrogenation of Organic Acids in Aqueous Ethanol. Catal. Commun. 2010, 11, 928−931. (7) Shrikhande, J. J.; Gawande, M. B.; Jayaram, R. V. A Catalyst-free



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

N-benzyloxycarbonylation of Amines in Aqueous Micellar Media at Room Temperature. Tetrahedron Lett. 2008, 49, 4799−4803. (8) Shrikhande, J. J.; Gawande, M. B.; Jayaram, R. V. Cross-aldol and Knoevenagel Condensation Reactions in aqueous Micellar Media. Catal. Commun. 2008, 9, 1010−1016. (9) Zhang, Z. H.; Zhang, X. N.; Mo, L. P.; Li, Y. X.; Ma, F. P. Catalyst-free Synthesis of Quinazoline Derivatives Using Low Melting Sugar–urea–salt Mixture as a Solvent. Green Chem. 2012, 14, 1502−1506. (10) Martínez, R.; Berbegal, L.; Guillena, G.; Ramón, D. J. Bio-renewable Enantioselective Aldol reaction in Natural Deep Eutectic Solvents. Green Chem. 2016, 18, 1724−1730. (11) Li, Y. L.; Chen, H.; Shi, C. L.; Shi, D. Q.; Ji, S. J. Efficient One-Pot Synthesis of Spirooxindole Derivatives Catalyzed by L-Proline in Aqueous Medium. J. Comb. Chem. 2010, 12, 231−237. (12) Pedrosa, R.; Andrés, J. M.; Gamarra, A.; Manzano, R.; Pérez-López, C. Novel Sulfonyl Polystyrene-supported Prolinamides as Catalysts for Enantioselective Aldol Reaction in Water. Tetrahedron 2013, 69, 10811−10819. (13) Gruttadauria, M.; Salvo, A. M. P.; Giacalone, F.; Agrigento, P.; Noto, R. Enhanced Activity and Stereoselectivity of Polystyrene-Supported Proline-Based Organic Catalysts for Direct Asymmetric Aldol Reaction in Water. Eur. J. Org. Chem. 2009, 2009, 5437−5444. (14) Evans, A. C.; Lu, A.; Ondeck, C.; Longbottom, D. A.; O’Reilly, R. K. Organocatalytic Tunable Amino Acid Polymers Prepared by Controlled Radical Polymerization. Macromolecules 2010, 43, 6374−6380. (15) Chandrasekhar, S.; Reddy, N. R.; Sultana, S. S.; Narsihmulu, C.; Reddy, K. V. L-Proline Catalysed Asymmetric Aldol Reactions in PEG-400 as Recyclable Medium and Transfer Aldol Reactions. Tetrahedron 2006, 62, 338−345. (16) Zamboulis, A.; Rahier, N. J.; Gehringer, M.; Cattoën, X.; Niel, G.; Bied, C.; Moreau, J. J. E.; Man, M. W. C. Silica-supported L-proline Organocatalysts for Asymmetric Aldol Reaction. Tetrahedron: Asymmetry 2009, 20, 2880−2885. (17) Doyagüez, E. G.; Calderón, F.; Sánchez, F.; Fernández-Mayoralas, A. Asymmetric Aldol Reaction Catalyzed by a Heterogenized Proline on a Mesoporous Support. The Role of the Nature of Solvents. J. Org. Chem. 2007, 72, 9353−9356. (18) Elmekawy, A. A.; Sweeney, J. B.; Brown, D. R. Efficient Synthesis of Supported Proline Catalysts for Asymmetric Aldol Reactions. Catal. Sci. Technol. 2015, 5, 690−696. (19) An, Z.; Guo,Y.; Zhao, L. W.; Li, Z.; He, J. L-Proline-Grafted Mesoporous Silica with Alternating Hydrophobic and Hydrophilic Blocks to Promote Direct Asymmetric Aldol and Knoevenagel−Michael Cascade Reactions. ACS Catal. 2014, 4, 2566−2576. (20) Khalafi-Nezhad, A.; Shahidzadeh, E. S.; Sarikhani, S.; Panahi, F. A new Silica-supported Organocatalyst Based on L-proline: An Efficient Heterogeneous Catalyst for One-pot Synthesis of Spiroindolones in Water. J. Mol. Catal. A: Chem. 2013, 379, 1−8. (21) Luo, S. Z.; Mi, X. L.; Zhang, L.; Liu, S.; Xu, H.; Cheng, J. P. Functionalized Ionic


Page 22 of 27

Page 23 of 27

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Liquids Catalyzed Direct Aldol Reactions. Tetrahedron 2007, 63, 1923−1930. (22) Chen, Z.; Li, Y.; Xie, H.; Hu, C. G.; Dong, X. Ionic Liquid-Supported Proline as Catalyst in Direct Asymmetric Aldol Reaction. Russ. J. Org. Chem. 2008, 44, 1807−1810. (23) Doyagüez, E. G.; Fernandez-Mayoralas, A. Proline-cyclodextrin Conjugates: Synthesis and Evaluation as Catalysts for Aldol Reaction in Water. Tetrahedron 2012, 68, 7345−7354. (24) Li, J.; Yang, G. X.; Qin, Y. Y.; Yang, X. R.; Cui, Y. C. Recyclable Merrifield Resin-supported Thiourea Organocatalysts Derived from L-proline for Direct Asymmetric Aldol Reaction. Tetrahedron: Asymmetry 2011, 22, 613−618. (25) Safaei-Ghomi, J.; Zahedi, S. Diastereoselective Synthesis of Isoxazolidines and Spirois oxazolidines via Catalytic 1,3-dipolar Cycloaddition Reactions in the Presence of Fe3O4-L-proline Nanoparticles as a Magnetic Organocatalyst. Tetrahedron Lett. 2016, 57, 1071−1073. (26) Kong, Y.; Tan, R.; Zhao, L. L.; Yin, D. H. L-Proline Supported on Ionic liquid-modified Magnetic Nanoparticles as a Highly Efficient and Reusable Organocatalyst for Direct Asymmetric Aldol Reaction in Water. Green Chem. 2013, 15, 2422−2433. (27) Doyagüez, E. G.; Corrales, G.; Garrido, L.; Rodríguez-Hernández, J.; Gallardo, A.; Fernández-Mayoralas, A. Linear Copolymers of Proline Methacrylate and Styrene as Catalystsfor Aldol Reactions in Water: Effect of the Copolymer Aggregationon the Enantioselectivity. Macromolecules 2011, 44, 6268−6276. (28) Wu, C.; Long, X.; Fu, X.; Wang, G.; Mirza, Z. A. Efficient Synthesis of Zirconium Poly(styrenephenylvinylphosphonate)phosphate-supported Proline as a Recyclable Catalyst for Direct Asymmetric Aldol Reactions in Water. RSC Adv. 2015, 5, 3168−3176. (29) Cotanda, P.; Lu, A.; Patterson, J. P.; Petzetakis, N.; O’Reilly, R. K. Functionalized Organocatalytic Nanoreactors: Hydrophobic Pockets for Acylation Reactions in Water. Macromolecules 2012, 45, 2377−2384. (30) Doyagüez, E. G.; Rodríguez-Hernández, J.; Corrales, G.; Fernández-Mayoralas, A.; Gallardo, A. Water-Soluble Pendant Copolymers Bearing Proline and Permethylated β-Cyclodextrin: pH-Dependent Catalytic Nanoreactors. Macromolecules 2012, 45, 7676−7683. (31) Li, X. J.; Yang, B. L.; Jia, X. B.; Chen, M. Q.; Hu, Z. G. Temperature-responsive Hairy Particle-supported Proline for Direct Asymmetric Aldol Reaction in Water. RSC Adv. 2015, 5, 89149−89156. (32) Lu, A.; Cotanda, P.; Patterson, J. P.; Longbottom, D. A.; O'Reilly, R. K. Aldol reactions catalyzed by L-proline Functionalized Polymeric Nanoreactors in Water. Chem. Commun. 2012, 48, 9699−9701. (33) Lu, A.; Smart, T. P.; Epps, T. H.; Longbottom, D. A.; O'Reilly, R. K. L-Proline Functionalized Polymers Prepared by RAFT Polymerization and Their Assemblies as Supported Organocatalysts. Macromolecules 2011, 44, 7233−7241. (34) Li, X. J.; Chen, M. Q.; Yang, B. L.; Zhang, S. L.; Jia, X. B.; Hu, Z. G. Combining RAFT Precipitation Polymerization and Surface-initiated RAFT Polymerization: an



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Efficient Approach to Prepare Hairy Particles—supported Proline. RSC Adv. 2014, 4, 43278−43285. (35) Kristensen, T. E.; Vestli, K.; Jakobsen, M. G.; Hansen, F. K.; Hansen, T. A General Approach for Preparation of Polymer-Supported Chiral Organocatalysts via Acrylic Copolymerization. J. Org. Chem. 2010, 75, 1620−1629. (36) Dong, K.; Zhang, S.; Wang, J. Understanding the Hydrogen Bonds in Ionic Liquids and Their Roles in Properties and Reactions. Chem. Commun. 2016, 52, 6744−6764. (37) Peleteiro, S.; Rivas, S.; Alonso, J. L.; Santos, V.; Parajo, J. C. Furfural Production Using Ionic Liquids: A review. Bioresour. Technol. 2016, 202, 181−191. (38) Xin, B.; Hao, J. Imidazolium-based Ionic Liquids Grafted on Solid Surfaces. Chem. Soc. Rev. 2014, 43, 7171−7187. (39) Sadeghzadeh, S. M.; Daneshfar, F. Ionic liquid immobilized on FeNi3 as Catalysts for Efficient, Green, and One-pot Synthesis of 1,3-thiazolidin-4-one. J. Mol. Liq. 2014, 199, 440−444. (40) Ni, B.; Headley, A. D. Ionic-Liquid-Supported (ILS) Catalysts for Asymmetric Organic Synthesis. Chem. Eur. J. 2010, 16, 4426−4436. (41) Kucherenko, A. S.; Siyutkin, D. E.; Maltsev, O. V.; Kochetkov, S. V.; Zlotin, S.G. Asymmetric Organocatalysis: From Proline to Highly Efficient Immobilized Organocatalysts. Russ. Chem. Bull. 2012, 61, 1313−1320. (42) Kochetkov, S. V.; Kucherenko, A. S.; Kryshtal, G. V.; Zhdankina, G. M.; Zlotin, S. G. Simple Ionic Liquid Supported C2-Symmetric Bisprolinamides as Recoverable Organocatalysts for the Asymmetric Aldol Reaction in the Presence of Water. Eur. J. Org. Chem. 2012, 2012, 7129−7134. (43) Li, H.; Bhadury, P. S.; Song, B.; Yang, S. Immobilized Functional Ionic Liquids: Efficient, Green, and Reusable Catalysts. RSC Adv. 2012, 2, 12525−12551. (44) Bakessel, A.; Koch, B.; Lex, J. Proline-Derived N-Sulfonylcarboxamides: Readily Available, Highly Enantioselective and Versatile Catalysts for Direct Aldol Reactions. Adv. Synth. Catal. 2004, 346, 1141−1146. (45) Eyckens, D. J.; Brozinski, H. L.; Delaney, J. P.; Servinis, L.; Naghashian, S.; Henderson, L. C. Ion-Tagged Prolinamide Organocatalysts for the Direct Aldol Reaction On-Water. Catal. Lett. 2015, 146, 212−219. (46) Karamthulla, S.; Pal, S.; Parvin, T.; Choudhury, L. H. L-proline Catalyzed Multicomponent Reactions: Facile Access to 2H-benzo[g]pyrazolo[3,4-b]quinoline-5,10(4H,11H)-dione Derivatives. RSC Adv. 2014, 4, 15319−15324. (47) Khalafi-Nezhad, A.; Sarikhani, S.; Shahidzadeh, E. S.; Panahi, F. L-Proline-promoted Three-component Reaction of Anilines, Aldehydes and Barbituric Acids/malononitrile: Regioselective Synthesis of 5-arylpyrimido-[4,5-b]quinoline-diones and 2-amino-4-arylquinoline-3-carbonitriles in Water. Green Chem. 2012, 14, 2876−2884. (48) Martinez-Ariza, G.; McConnell, N.; Hulme, C. One-Pot Two-Step Multicomponent Process of Indole and Other Nitrogenous Heterocycles or Amines toward α ‑ Oxo-acetamidines. Org. Lett. 2016, 18, 1864−1867 (49) Wu, Q.; Tao, J. Multicomponent Reactions, in Green Techniques for Organic


Page 24 of 27

Page 25 of 27

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Synthesis and Medicinal Chemistry (eds Zhang, W.; Cue, B. W.). John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470711828.ch18. (50) Martinez-Ariza, G.; Ayaz, M.; Roberts, S. A.; Rabanal-León, W. A.; Arratia-Pérez, R.; Hulme, C. The Synthesis of Stable, Complex Organocesium Tetramic Acids through the Ugi Reaction and Cesium-Carbonate-Promoted Cascades. Angew. Chem. Int. Ed. 2015, 54, 11672-11676. (51) Hulme, C.; Dietrich, J. Emerging molecular diversity from the intra-molecular Ugi reaction: iterative efficiency in medicinal chemistry. Mol. Diversity. 2009, 13, 195– 207. (52) Rotstein, B. H.; Zaretsky, S.; Rai, V.; Yudin, A. K. Small Heterocycles in Multicomponent Reactions. Chem. Rev. 2014, 114, 8323−8359. (53) Czechtizky, W.; Hamley, P. Small Molecule Medicinal Chemistry: Strategies and Technologies. Wiley & Sons, Inc: New Jersery, 2015, 6, 1-4. (54) Li, Y. L.; Chen, H.; Shi, C. L.; Shi, D. Q.; Ji, S. J. Efficient One-Pot Synthesis of Spirooxindole Derivatives Catalyzed by L-Proline in Aqueous Medium. J. Comb. Chem. 2010, 12, 231–237. (55) Wolin, R.; Wang, D.; Kelly, J.; Afonso, A.; James, L.; Kirschmeier, P.; McPhail, A. T. Synthesis and evaluation of Pyrazolo[3,4-b]quinoline Ribofuranosides and their Derivatives as Inhibitors of Oncogenic. Bioorg. Med. Chem.Lett. 1996, 6, 195−200. (56) Sumesh, R. V.; Muthu, M.; Almansour, A. I.; Kumar, R. S.; Arumugam, N.; Athimoolam, S.; Prabha, E. A. J. Y.; Kumar, R. R. Multicomponent Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Novel Spiro-Tethered Pyrazolo[3,4-b]quinoline Hybrid Heterocycles. ACS Comb. Sci. 2016, 18, 262−270. (57) Crenshaw, R. R.; Luke, G. M.; Siminoff, P. Interferon Inducing Activities of Derivatives of 1,3-Dimethyl-4-(3-dimet hy1aminopropylamino)-1H-pyrazolo[3,4-b]quinoline and Related Compounds. J. Med. Chem. 1976, 19, 262−275.

Nanoparticle supported prolinamide catalyst was successfully prepared based on polymer ionic liquid (PIL). The nanoparticles with PIL outer catalyze the direct



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asymmetric Aldol reaction and multicomponent reaction in pure water efficiently. The technology solves the problem associated with mass transfer in pure water reactions.


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Nanoparticle Based on Poly(Ionic Liquid) as an ... - ACS Publications

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