Metalloprotein-Inspired Ruthenium Polymeric Complex: A Highly

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Metalloprotein Inspired Ruthenium Polymeric Complex: A Highly Efficient Catalyst in ppm Level for 1,3-dipolar Huisgen’s Reaction in Aqueous Medium at Room Temperature Ajay Gupta, Ramen Jamatia, Mrityunjoy Mahato, and Amarta Kumar Pal Ind. Eng. Chem. Res., Just Accepted Manuscript • DOI: 10.1021/acs.iecr.6b04863 • Publication Date (Web): 13 Feb 2017 Downloaded from http://pubs.acs.org on February 14, 2017

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Industrial & Engineering Chemistry Research

Metalloprotein Inspired Ruthenium Polymeric Complex: A Highly Efficient Catalyst in ppm Level for 1,3-dipolar Huisgen’s Reaction in Aqueous Medium at Room Temperature Ajay Gupta,a Ramen Jamatia,a Mrityunjoy Mahato,b and Amarta Kumar Pal*a a

Department of Chemistry, Centre for advanced studies, North-Eastern Hill

University, NEHU campus, Shillong-793022, India. b

Department of Basic Sciences and Social Sciences School of Technology, North-Eastern

Hill University, NEHU campus, Shillong-793022, India. Tel: +91 364 2307930 ext 2636, E-mail: [email protected], [email protected] Fax: +91 364 2550076

ABSTRACT: The metalloprotein inspired Ru complex (3) was prepared via molecular convolution

from

linear

amphiphilic

polymer

poly(N-isopropylacrylamide-co-N-

vinylimidazole) (1) and ruthenium trichloride (2). The insoluble black metalloprotein inspired Ru complex (3) efficiently promoted the 1,3-dipolar Huisgen’s reaction in aqueous medium at room temperature. The reaction process resulted highly regioselective product within a short reaction time. A very low catalytic loading of 172 mol ppm with respect to ruthenium was sufficient to drive the reaction process. The TON and TOF of the catalyst reached a high value of 5765 and 577 min-1 respectively. Further the catalyst could be easily separated by means of simple filtration and could be recycled and reused for six consecutive runs. No significant amount of leaching of the catalyst was observed. For industrial applicability, a gram scale reaction was also performed which resulted in good yield of the product. Hence the present catalytic process due to its reusability, high efficiency, high regioselectivity, short reaction time, aqueous reaction medium, room temperature stirring, high yield and good functional group tolerance makes it industrially and academically attractive. KEYWORD Metalloprotein inspired Ru complex, 1,3-dipolar Huisgen’s reaction, ppm level catalyst loading, aqueous medium, room temperature, high regioselectivity.

1

ACS Paragon Plus Environment


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1. INTRODUCTION Metalloproteins are supramolecular metal-organic hybrids of imidazole containing polypeptides promoting highly efficient enzymatic reactions.1,2 Imidazole unit of histidine are bound to the metallic species within a supramolecular array of proteins. Therefore imidazole unit is used to mimic the artificial metalloprotein. Metalloprotein inspired metal catalyst ensures high catalytic activity (in ppm level), easy reusability and stability. For the aforementioned reasons, the development of metalloprotein-inspired polymeric metal complexes is still intriguing to the supramolecular, organometallic and organic chemist as well as industrial and sustainable chemistry.3-6 Huisgen’s 1,3-dipolar cycloaddition reaction between alkyne and azide is one of the path breaking invention not only in synthetic organic chemistry but also in pharmaceuticals, and other industries etc. It is commonly known as click reaction. It provides 1,4- and 1,5disubstituted triazole which has lots of application as lubricants, dyes, corrosion inhibitors and photostabilizers.7 Therefore regioselective synthesis of 1,4- or 1,5 disubstituted triazole is still very much demanding. Till date most of the Huisgen reaction is reported by Copper catalyst.8-19 Recently Yamada and his group reported metalloprotein inspired Cu-complex and applied it in Huisgen reaction. They also reported very fewer amounts (ppm) of catalyst was required in this reaction but at the same time they used additives such as sodium ascorbate, tertiary butanol-water as the solvent and heated at 50 oC for a period of 1.5 h for successfully completion of the reaction (Scheme 1).6 Of transitions metals, ruthenium metal possesses wide scope owing to its wide expand of oxidation state and its tendency to form various coordination geometries. Also ruthenium metal has been widely used to promote various reactions such as oxidation,20 reduction,21 C-C bond formation,22 metathesis reactions,23 etc. Several reports of Ru in 1,3-dipolar Huisgen’s reaction are known to our knowledge.24 To search for better regioselective, environmental benign, and efficient protocol we synthesized metalloprotein inspired Ru-polymer for Huisgen reaction. Recently, metalloprotein inspired Ru-Complex has been employed for the selective oxidation of alcohols.25 This is a first report of ruthenium catalyzed Huisgen reaction in ppm level.

2


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Scheme 1. Previous and Present work

2. Experimental Section Melting points were determined in open capillaries and are uncorrected. IR spectra were recorded on Spectrum BX FT-IR, Perkin Elmer (υmax in cm-1) on KBr disks. 1H NMR and 13C NMR (400 MHz and 100 MHz respectively) spectra were recorded on Bruker Avance II-400 spectrometer in CDCl3 (chemical shifts in δ with TMS as internal standard). Mass spectra were recorded on Waters ZQ-4000. Transmission Electron Microscope (TEM) was recorded on JEOL JSM 100CX. Scanning electron microscope (SEM) was recorded on JSM-6360 (JEOL). Powder XRD was recorded on Bruker D8 XRD instrument SWAX. Thermogravimetric analysis (TGA) was recorded on a Perkin Elmer Precisely STA 6000 simultaneous thermal analyzer. CHN were recorded on CHN-OS analyzer (Perkin Elmer 2400, Series II). ICP-AES analysis was carried out on a ARCOS, Simultaneous ICP Spectrometer. XPS analysis was recorded on a XPS, ThermoScientific Inc. K-Alpha. 2.1. X-ray crystallography. The X-ray diffraction data were collected at 293 K with Mo Kα radiation (λ = 0.71073 Å) using Agilent Xcalibur (Eos, Gemini) diffractometer equipped with a graphite monochromator. The software used for data collection CrysAlis PRO (Agilent, 2011), data reduction CrysAlis PRO and cell refinement CrysAlis PRO. The structure were solved by direct methods and refined by full-matrix least-squares calculation using SHELXS97 and SHELXL-97. 2.2. Preparation of imidazole polymer 1. A solution of N-vinylimidazole (1 g, 10.62 mmol) and N-isopropylacrylamide (6.01 g, 53.13 mmol) in toluene (40 mL) was degassed for 30 min 3



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under N2 atmosphere. To this solution AIBN (16.4 mg, 0.1 mmol) was added and the resulting solution was further degassed for 30 min under N2 atmosphere. The solution was then heated at 70 oC for 12 h and a colourless powder precipitates out. After the time mentioned the precipitate was filtered off through a glass filter and washed with toluene (3 X 10 mL) and dried under reduced pressure to afford the imidazole polymer 1. IR (KBr): 3399, 3314, 2969, 2926, 2853, 1650, 1559, 1458, 1400, 1385, 1370, 1193, 1136, 1123, 1107, 752, 656, 644, 603 cm-1. 1H NMR (CDCl3 + DMSO-d6, 400 MHz) δ = 7.95-7.89 (m, 2H), 6.236.08 (m, 3H), 5.54-5.43 (m, 2H), 3.96-3.58 (m, 10H), 1.12-1.10 (m, 35H). 13C NMR (DMSOd6, 100 MHz) δ = 163.2, 131.2, 129.2, 128.8, 39.8, 39.7, 21.69, 21.60.

2.3. Preparation of polymeric ruthenium catalyst 3. The prepared imidazole polymer (1, 1g) was dissolved in 10 ml of CHCl3. An aqueous solution of ruthenium trichloride (2, 157 mg) was added to it. The resulting black suspension was heated at 70 oC for a period of 12 h. After the time mentioned the precipitate was filtered off, washed with water (3 X 10 ml) and CHCl3 (3 X 10 ml) on the glass filter and dried under reduced pressure to yield a black polymeric ruthenium catalyst 3. 2.4. Procedure for the synthesis of substituted triazoles (6aa-6gd). In a clean round bottom flask acetylenes (4a-g, 1.2 mmol), azides (5a-h, 1 mmol) and catalyst (3, 0.4mg) in 3 mL of H2O was stirred at room temperature for a period of 10 min. During this time period, a precipitation was observed. Then the precipitate was dissolved in CHCl3 (10 ml) and filtered. Catalyst was collected from the residue, washed with CHCl3, dried and reused for another set of reaction. The organic layer (filtrate) was then washed with water (3 X 10 ml), brine (1 X 10 ml) and dried over anhydrous sodium sulphate. The reaction mass was then concentrated under vacuum and finally purified by column chromatography using ethylacetate and hexane as the eluent to afford the pure product 6aa-6gd. 2.5. Procedure for the one pot synthesis of substituted triazoles (6aa, 6ba and 6ea). In a clean round bottom flask, acetylenes (4a, 4b and 4e, 1.2 mmol), benzylchloride (7a, 1 mmol), sodium azide (1mmol) and catalyst (3, 0.4mg) in H2O (3 mL) was stirred for 3 h at room temperature. During this time frame the product was precipitated. Then the precipitate was dissolved in CHCl3 (10 ml) and filtered. The filtrate was then washed with water (3 X 10 ml), brine (1 X 10 ml) and dried over anhydrous sodium sulphate. The reaction mass was 4


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then concentrated under vacuum and finally purified by column chromatography using ethylacetate and hexane as the eluent to afford the pure product 6aa, 6ba and 6ea.

3. RESULTS AND DISCUSSION Our investigation started with the synthesis of metalloprotein inspired ruthenium catalyst (3). It was prepared via a molecular convulation method from a linear amphiphilic polymer poly(N-isopropylacrylamide-co-N-vinylimidazole) (1) and ruthenium trichloride (2). The linear amphiphilic polymer poly(N-isopropylacrylamide-co-N-vinylimidazole) (1) was prepared according to the procedure given by Yamada et. Al.6 The prepared imidazole polymer (1, 1g) was then dissolved in 10 mL of CHCl3 and an aqueous solution of ruthenium trichloride (2, 157 mg) was added to this solution at room temperature. The resulting black suspension was then heated at 70 oC for a period of 12 h. After the time mentioned, the precipitate was filtered off on the glass filter, washed with CHCl3 (3 X 10 ml) and water (3 X 10 ml) and dried under reduced pressure (Scheme 2). The prepared Ru-catalyst (3) was hardly soluble in most organic solvents such as methanol, ethanol, chloroform, acetonitrile, acetone, DMSO, DMF etc. Scheme 2. Synthetic scheme for metalloprotein-inspired polymeric imidazole ruthenium catalyst (3)

Our synthesized ruthenium catalyst 3 was characterized by TEM, SEM, EDX, Powder XRD, ICE-AES, XPS and FT-IR. The thermal stability of the catalyst was examined by TGA 5



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analysis. The TEM (Figure 1A) image, the selected area electron diffraction (SAED) pattern (Figure 1B) along with EDX data (Figure 1C) and SEM image (Figure 1D) supports the presence of polymer supported Ru compound and in its nanoparticle form as indicated by the arrow in the respective figures. The TEM image shows the distributed spherical nanoparticle with size ̴10 nm. The EDX peak confirms the presence of Ru with ̴7-9 % (weight) which is in line with the atomic emission spectroscopic (ICP-AES) report (4.36%). There is also similar report of Ru content in another polymer supported Ru catalyst.26 The ring like SAED pattern (Figure 1B) indicate that the Ru complex material was not much crystalline rather semi-crystalline in nature which is evidenced from earlier study also.27 The low resolution SEM image (Figure 1D) is in line with the earlier report, which is much similar to the aggregate form of proteins.28

Figure 1. (A, B) TEM images and SAED pattern of the nanoparticle of Ru-polymer complex obtained from TEM. (C, D) EDX data and SEM image of the Ru-Polymer complex nanoparticle. Arrows on the images are indicating the presence of Ru and its nanoparticle/microparticle. Powder X-ray diffraction (XRD) data provide support for the structural aspect of RuComplex (Figure 2). The prominent characteristic peak observed at 21.31

0

(2θ) for plane 6


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(130) along with some other peaks shown in Table 1. The lattice spacing (d-values) and the diffraction planes (hkl) were compiled from the literature data.29,30 It has been found that the peak position were shifted little bit within ±1 or ±2 degree which may be due to the presence of polymer support in the Ru compound. The semicrystalline/amorphous like structure is evidenced from the background profile of the XRD data. In this regard it is also evident from literature that the Ru (III) complex has amorphous like characteristic compared to the other Pd (II) and Zr (IV) complex.31 Table 1. Represents the XRD peak assignment of the experimental data and their lattice spacing (hkl)

Sl

Experimental Peak

Literature Peak

Lattice Spacing

No

Position

Position

d( )

2θ (degree)

2θ (degree)

1

7.192

5.935

14.897

142

2

9.570

12.384

7.141

243

3

21.312

22.800

3.897

130

4

39.051

37.780

2.379

340

5

55.063

53.640

1.707

444

7



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Figure 2. Powder X-ray diffraction (XRD) data of the Ru-polymer complex after background correction. The inset figure is the background uncorrected XRD data. Thermal stability of the Ru complex was investigated using TGA over the temperature range 30-740 0C. The TGA data shows characteristics weight loss in roughly three steps (Figure 3A). The Ru complex was thermally stable up to a considerably higher temperature up to around 300 0C where there is a very little amount of weight loss ̴ 10%. The major weight loss taken place about 380 0C to 460 0C, representing the characteristics decomposition and degradation transition with a weight loss ̴ 97%. In last step about 460-740 0

C, there is a total weight loss ̴ 99.9%. This is in agreement with the earlier results of another

polymer supported Ru catalyst.26 Thus the characteristic weight loss in TGA data is a complementary evidence for polymer supported Ru complex. The X-ray photoelectron spectroscopic (XPS) measurement was carried out to gain insight on the presence of Ru and the interacting species present on the surface of Rucomplex (Figure 3B). The core level XP spectrum was taken in the region 280-290 eV. The characteristic peak has been deconvoluted into five components for best fitting parameter of R2 value 0.999 using Gaussian multipeak fitting technique. The characteristic peak for Ru 3d5/2 and 3d3/2 was observed at 282.2 eV and 283.9 eV respectively indicating the presence of Ru.32 Since the C1s reference peak also lies at 285 eV it overlaps with the Ru peak and somehow it reflects a little bit shifts in the deconvoluted data. The appearance of 3d5/2 peak at 282.2 eV is indicating Ru-O species in +3 oxidation state.32 The 286.5 eV peak attributed to the Ru-C species adjacent to carboxyl and 287.6 eV corresponds to the electron deficient carbon atom within the carboxyl.33 From FT-IR spectrum, peaks at 1642 and 1552 cm-1 corresponds to C=C and C=N stretching frequency of imidazole ring (Figure S.I. 1). The peaks observed at 284 and 313 cm-1 is due to the Ru-Cl stretching frequency. The absorption bands at 229 cm-1 can be attributed to Ru-N stretching frequency, which is very close to the literature report.34

A

B

8


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Figure 3. (A, B) Represents the TGA and XPS data of the Ru-polymer complex. We initiated our study for the synthesis of 1,3-dipolar Huisgen’s reaction by taking benzylazide and phenyl acetylene as the test substrates (Scheme 3). A test reaction containing the model substrates phenyl acetylene (4a, 1.2 mmol) and benzylazide (5a, 1 mmol) in water (3 mL) was performed in the absence of catalyst at room temperature. The reaction failed to generate any triazole derivative only starting materials were observed even after prolonged reaction time of 48 h. When the same reaction was performed in the presence of metalloprotein inspired Ru catalyst (0.4 mg, 172 mol ppm with respect to Ru) at room temperature, to our astonishment the reaction was completed within 10 min to furnish the desired product in 98 % yield (Table 2, entry 3). We cross checked the efficiency of our Rupolymer catalyst with the reported Cu-polymer complex.6 Accordingly the model reaction was set up with the Cu-polymer complex (0.4 mg) at room temperature for 10 min. It was observed that Cu-polymer catalyst afforded very poor yield (32 %) under this circumstances. Inspired by the present success, we decided to study the role of heating if any on the present reaction process. Upon heating up to 100 oC, it was observed that heating had no profound effect on the yield or reaction time, accounting only 98 % yield within 10 min (Table 2, entry 4). Next we decided to study the optimum concentration of catalyst needed to catalyze the said reaction. To our delight, it was observed that a very low catalytic loading of 0.4 mg (172 mol ppm with respect to Ru) was sufficient to catalyze the reaction. Further, higher catalytic loading did not furnished any significant enhancement of the product yield (Figure S.I. 2). The turn over number (TON) and turn over frequency (TOF) of the present catalyst was also calculated with respect to ruthenium and it showed very high value. The TON and TOF of the catalyst was found to be 5765 and 577 min-1 respectively. With the optimum catalyst loading in hand we next examined the best solvent system for the present catalytic process. It was observed that EtOH produced satisfactory yield of the product (85%, Table 2, entry 5). Other solvent systems such as toluene, 1,4-dioxane, THF, CHCl3, acetonitrile were also tested but were found to be inefficient for the present system (Table 2). The reaction was also investigated under neat condition but no conversion of the reactant to product was achieved only starting materials were witnessed (Table 2, entry 2). Therefore, water was found to be 9



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the solvent of choice resulting in 98 % yield of product within 10 min at room temperature (Table 2, entry 3).

Scheme 3. Model reaction

Table 2. Optimization of reaction parametera Entry

Reaction

Catalyst Solvent

condition

Time

Product

(mins)

Isolated yield (%)

1

r.t

Nil

H2O

2880

6aa

No Conversion

2

r.t

0.4 mg

Neat

10

6aa

No conversion

3

r.t

0.4 mg

H2O

10

6aa

98

4

100oC

0.4 mg

H2O

10

6aa

98

5

r.t

0.4 mg

EtOH

10

6aa

85

6

r.t

0.4 mg

Toluene

10

6aa

65

7

r.t

0.4 mg

1,4-Dioxane

10

6aa

54

8

r.t

0.4 mg

THF

10

6aa

48

9

r.t

0.4 mg

CHCl3

10

6aa

36

10

r.t

0.4 mg

Acetonitrile

10

6aa

30

a

Reaction condition: phenyl acetylene (4a, 1.2 mmol), benzylazide (5a, 1 mmol) and catalyst

in solvent (3 mL) was stirred for the time mentioned in Table 2.

After optimizing the reaction parameters, we next concentrated on the versatility of the reaction (Scheme 4). Various acetylenes (4a-g) and aryl azides containing electron donating and withdrawing substituents at o-, m-, p- position (5a-h) were investigated for the present study (Figure 4). All the reactions proceeded efficiently to produce the product in good to excellent yield (82% - 98%) within the time mentioned in Table 3. We have also examined the efficiency of the reaction with unsymmetrical internal alkyne (4g). We were delighted to 10


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see the formation of triazoles with good yields (83% & 87%). After general study it was established that the nature of substituent on alkynes or azides did not have any profound effect on the yield or time of the reaction. From the above observation we can generalize that the reaction condition is so mild that various functional groups remain un-effected under the optimized reaction condition (Scheme 4). Regioselectivity of the product is also very important for such reactions. There are several reports wherein it is established that copper catalysis gives regioselectively 1,4-disubstituted product.9,11,14,15 Whereas, in case of ruthenium catalysis, both 1,4- and 1,5-disubstituted regioisomers are formed.24a,b,d,e,g, But Liu et al reported 100% selective formation of 1,4-disubstituted triazoles using ruthenium complex.24h Similar results are encounterd in our study. Our Ruthenium polymer catalyst also afforded exclusively 1,4-disubstituted regioisomers with alkynes and azides as it evident from single crystal XRD analysis. From the XRD structure of 6ae is clear that only one regioisomer is formed that is 1,4-disubstituted triazole and not 1,5-disubstituted triazole (Figure 5).

4. Various acetylenes O O

O

4a

4b

O 4c

CHO

O

O C2H5 O

O

O C2H5 H3C O 4d

O CH3 O 4e

O O

N

4f 5. Various azides N3 N3

O

4g

N3

N3

N3

N3

N3

N3

OCH3

Br

Cl Cl

5a

CH3 5b

NO2 5c

5d

5e

5f

5g

5h

Figure 4. Substrates Scope.

11



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(6ae)

Page 12 of 21

(6dg)

Figure 5. Crystal structure for compounds 6ae (CCDC no.1438386) and 6dg (CCDC no. 1438212). Scheme 4. General scheme for the synthesis of triazole derivatives

Table 3. Synthesis of compounds 6aa-6gda Melting point

Entry

Acetylenes

Azides

Product

Yield (%)

1

4a

5a

6aa

98

124-126

2

4a

5b

6ab

96

166-168

3

4a

5c

6ac

86

146-148

4

4a

5d

6ad

98

183-185

5

4a

5e

6ae

92

76-78

6

4b

5d

6bd

97

138-140

7

4b

5e

6be

89

94-96

8

4b

5f

6bf

92

151-153

9

4c

5d

6cd

85

184-186

10

4c

5b

6cb

82

208-210

11

4d

5g

6dg

90

56-58

12

4d

5b

6db

95

45-47

13

4d

5f

6df

93

Gummy

14

4e

5a

6ea

85

34-36

15

4e

5g

6eg

92

Gummy

16

4f

5h

6fh

83

85-87

17

4b

5a

6ba

90

130-132

18

4g

5a

6ga

83

72-74

19

4g

5d

6gd

87

135-137

(oC)

12


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a

Reaction condition: acetylenes (4a-g, 1.2 mmol), azides (5a-h, 1 mmol) and catalyst (3, 0.4

mg) in H2O (3 mL) was stirred at room temperature for 10 min.

After the establishment the high catalytic activity of metalloprotein inspired Ru catalyst (3) for the 1,3-dipolar Huisgen’s reaction with acetylenes and azides, we decided to study other probability for the synthesis of substituted triazoles in one-pot by directly employing the benzyl chloride, sodium azide and acetylene under the same reaction condition (Scheme 5). The catalyst drove the reaction towards completion and afforded substituted triazoles with good yields but the reaction proceeded slowly taking long time producing lower yield c.f. above mention reaction procedure (Table 4).

Scheme 5. One-pot synthesis of triazole using catalyst 3

Table 4. Catalyst 3 driven one pot synthesis of triazolea Entry

Acetylene

Arylhalide

Time (h)

Product

Yield (%)

(R2)

a

1

4a

PhCH2

3

6aa

95

2

4b

PhCH2

3

6ba

89

3

4e

PhCH2

3

6ea

82

Reaction condition: acetylene (1.2 mmol), benzylchloride (1mmol), sodium azide (1 mmol)

and catalyst (3, 0.4 mg) in 3 mL H2O at room temperature for 3 h.

For industrial applicability a gram scale reaction was set up with our designed catalyst 3. In the present study, phenyl acetylene (4a, 12 mmol), benzylazide (5a, 10 mmol) and metalloprotein inspired Ru catalyst (4 mg) in 30 mL of H2O was stirred for a period of 10 min. After the completion of the time mentioned, the precipitated product was filtered and 13



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purified. A yield of 95 % of the product was achieved for the catalytic gram scale reaction (Scheme 6). Thus this protocol could be an efficient method for the synthesis of triazoles in industries. Scheme 6. Gram scale synthesis of triazole 6aaa N3

+ 4a

N N

6aa

5a Gram Scale reaction

a

N

Catalyst 3

2.2g, 95 %

Reaction condition: phenylacetylene (4a, 12 mmol), benzylazide (5a, 10 mmol) and catalyst

(3, 4 mg) in 30 mL H2O was stirred at room temperature for 10 min.

The catalyst recyclability is an important parameter for any green and sustainable protocol. Therefore the reusability of the catalyst was also performed. Since our catalyst 3 was very much insoluble in the most of the common organic solvent and water, so it’s separation and washing is very easy. Just simple filtration is enough for separation. On the other hand, any polar solvent can be utilized for washing. It was worthy to note that the present catalyst could be recycled and reused for six consecutive cycles without any significant loss in its catalytic activity. The reproducibility of the reaction with the standard reactions parameters was also accessed. For this study, five parallel reactions for each set under the optimum experimental condition were performed. The reproducibility was then calculated using the mean data for each set (97.8, 97.6, 97.4, 97.4, 96.8 and 96.2). The error bars are reported by means of standard deviation method shown as chart in Figure 6.

14


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Figure 6. Reproducibility chart. Furthermore, the probability of leaching of metalloprotein inspired Ru catalyst was also examined. In this particular study, the catalyst (0.4 mg) and 3 mL of H2O was stirred at room temperature for 1h. After the time mentioned, the catalyst was removed from the reaction medium by means of simple filtration. The reactants were then introduced into the reaction medium and stirred at room temperature for a further period of 30 min. The reaction however did not proceed and only the reactants were recovered. Thus the present study signifies that no significant leaching of the catalyst took place.

4. Conclusions In conclusion, a highly stable and efficient metalloprotein inspired Ru catalyst was prepared. Catalyst in ppm level was sufficient to catalyze the regioselective synthesis of triazoles in aqueous medium at room temperature. The catalyst was highly stable, being easily recovered by means of simple filtration. The catalyst could be recycled and reused for six consecutive runs. Gram scale reaction also furnished good yield within short period of time. Thus this present catalytic process is environmentally and economically viable. Acknowledgements We thank the Department of Chemistry, Sophisticated Analytical and Instrumentation Facility (SAIF) of North-Eastern Hill University, UGC for supporting this work under 15



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Special Assistance Programme (SAP) and DST-Purse programme of NEHU Shillong. We are also thankful to NEHU-Non-NET Fellowship for financial assistance, DST for financial support (sanctioned no: SERC/F/0293/2012-13), IASST-Guwahati and IIT-Bombay. References (1) Karlin, K. D.; Cruse, R. W.; Gultneh, Y.; Farooq, A.; Hayes J. C.; Zubieta, J. DioxygenCopper Reactivity. Reversible Binding of O2 and CO to a Phenoxo-Bridged Dicopper( I) Complex. J. Am. Chem. Soc. 1987, 109, 2668-2679. (2) Sadava, D.; Hillis, D. M.; Heller, H. C.; Berenbaum, M. R. Life: The Science of Biology: Evolution, Diversity and Ecology: Freeman, W.H.; Co. New York, 2009. (3) (a) Coelho, A.; Diz, P.; Caamaño, O.; Sotelo, E. Polymer-Supported 1,5,7Triazabicyclo[4.4.0]dec-5-ene as Polyvalent Ligands in the Copper-Catalyzed Huisgen 1,3Dipolar Cycloaddition. Adv. Synth. Catal. 2010, 352, 1179-1192. (b) Girard, C.; Önen, E.; Aufort, M.; Beau-viére, S.; Samson E.; Herscovici, J. Reusable Polymer-Supported Catalyst for the [3+2] Huisgen Cycloaddition in Automation Protocols. Org. Lett. 2006, 8, 1689-1692. (c) Park, I. S.; Kwon, M. S.; Kim, Y.; Lee J. S.; Park, J. Heterogeneous Copper Catalyst for the Cycloaddition of Azides and Alkynes without Additives under Ambient Conditions. Org. Lett. 2008, 10, 497-500. (d) Lipshutz, B. H.; Taft, B. R. Heterogeneous Copper-in-CharcoalCatalyzed Click Chemistry. Angew. Chem., Int. Ed. 2006, 45, 8235-8238. (e) Wang, Y.; Liu, J.; Xia, C. Insights into Supported Copper(II)-Catalyzed Azide-Alkyne Cycloaddition in Water. Adv. Synth. Catal. 2011, 353, 1534-1542. (f) Liu M.; Reiser, O. A Copper(I) Isonitrile Complex as a Heterogeneous Catalyst for Azide-Alkyne Cycloaddition in Water. Org. Lett. 2011, 13, 1102-1105. (4) (a) Yamaguchi, K.; Oishi, T.; Katayama, T.; Mizuno, N. A Supported Copper Hydroxide on Titanium Oxide as an Efficient Reusable Heterogeneous Catalyst for 1,3-Dipolar Cycloaddition of Organic Azides to Terminal Alkynes. Chem. Eur. J. 2009, 15, 1046410472. (b) Jin, T.; Yan, M.; Menggenbateer.; Minato, T.; Bao, M.; Yamamoto, Y. Nanoporous Copper Metal Catalyst in Click Chemistry:Nanoporosity-Dependent Activity without Supports and Bases. Adv. Synth. Catal. 2011, 353, 3095-3100. (5) (a) Chen, W.; Boven, G.; Challa, G. Studies on Immobilized Polymer-Bound ImidazoleCopper(I1) Complexes as Catalysts. 3. Immobilization of Copper(I1) Complexes of Poly(styrene-co-N-vinylimidazole) by Grafting on Silica and Their Catalysis of Oxidative Coupling of 2,6-Disubstituted Phenols. Macromolecules 1991, 24, 3982-3987. (b) Arai, T.; Mizukami, T.; Yanagisawa, A. Reaction Optimization Using Solid-Phase Catalysis-CD HTS:Nb-Imidazoline-Cu(I)-Catalyzed Asymmetric Benzoylation of 1,2-Diols. Org. Lett. 2007, 14, 1145-1147. (c) Arai, T.; Yokoyama N.; Yanagisawa, A. A Library of Chiral Imidazoline–Aminophenol Ligands: Discovery of an Efficient Reaction Sphere. Chem. Eur. J. 2008, 14, 2052-2059. 16


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Table of Content Metalloprotein Inspired Ruthenium Polymeric Complex: A Highly Efficient Catalyst in ppm Level for 1,3-dipolar Huisgen’s Reaction in Aqueous Medium at Room Temperature Ajay Gupta,a Ramen Jamatia,a Mrityunjoy Mahato,b and Amarta Kumar Pal*a a

Department of Chemistry, Centre for advanced studies, North-Eastern Hill

University, NEHU campus, Shillong-793022, India. b

Department of Basic Sciences and Social Sciences School of Technology, North-Eastern

Hill University, NEHU campus, Shillong-793022, India. Tel: +91 364 2307930 ext 2636, E-mail: [email protected], [email protected] Fax: +91 364 2550076 The metalloprotein inspired Ru complex was prepared and promoted in the 1, 3-dipolar Huisgen’s reaction in aqueous medium at room temperature (Click Chemistry). Low catalytic loading of 172 mol ppm w.r.t ruthenium was sufficient to drive the reaction. TON and TOF 5765 and 577 min-1.

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Metalloprotein-Inspired Ruthenium Polymeric Complex: A Highly

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