Highly selective hydrogenation of quinolines promoted by recyclable polymer supported palladium nanoparticles under mild conditions in aqueous medium

Accepted Manuscript Title: HIGHLY SELECTIVE HYDROGENATION OF QUINOLINES PROMOTED BY RECYCLABLE POLYMER SUPPORTED PALLADIUM NANOPARTICLES UNDER MILD CONDITIONS IN AQUEOUS MEDIUM Author: Maria Michela Dell’Anna Vito Filippo Capodiferro Matilda Mali Daniela Manno Pietro Cotugno Antonio Monopoli Piero Mastrorilli PII: DOI: Reference:

S0926-860X(14)00295-6 http://dx.doi.org/doi:10.1016/j.apcata.2014.04.041 APCATA 14814

To appear in:

Applied Catalysis A: General

Received date: Revised date: Accepted date:

4-3-2014 16-4-2014 24-4-2014

Please cite this article as: M.M. Dell’Anna, V.F. Capodiferro, M. Mali, D. Manno, P. Cotugno, A. Monopoli, P. Mastrorilli, HIGHLY SELECTIVE HYDROGENATION OF QUINOLINES PROMOTED BY RECYCLABLE POLYMER SUPPORTED PALLADIUM NANOPARTICLES UNDER MILD CONDITIONS IN AQUEOUS MEDIUM, Applied Catalysis A, General (2014), http://dx.doi.org/10.1016/j.apcata.2014.04.041 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

HIGHLY

SELECTIVE

HYDROGENATION

OF

QUINOLINES

PROMOTED

BY

RECYCLABLE POLYMER SUPPORTED PALLADIUM NANOPARTICLES UNDER MILD CONDITIONS IN AQUEOUS MEDIUM

Cotugno,e Antonio Monopoli,e Piero Mastrorillia,b

cr

ip t

Maria Michela Dell’Anna,*a Vito Filippo Capodiferro,c Matilda Mali,a Daniela Manno,d Pietro

DICATECh, Politecnico di Bari, via Orabona 4, 70125 Bari, Italy.

b

Consiglio Nazionale delle Ricerche, Istituto di Chimica dei Composti Organometallici (CNR-

us

a

ICCOM), via Orabona 4, 70125 Bari, Italy.

d

Department of Pharmacy, University of Bari “Aldo Moro”, Via Orabona, 4, 70126 Bari, Italy

an

c

Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Via

Department of Chemistry, University of Bari “Aldo Moro”, Via Orabona, 4, 70126 Bari, Italy

d

e

M

Monteroni, 73100 Lecce, Italy

Ac ce p

fax: +39 080 5963611

te

*Corresponding author: e-mail address: [email protected], tel: +39 080 5963695,

Abstract

Polymer supported palladium catalyst, obtained by copolymerization of Pd(AAEMA)2 [AAEMA− = deprotonated form of 2-(acetoacetoxy)ethyl methacrylate] with ethyl methacrylate (co-monomer) and ethylene glycol dimethacrylate (cross-linker), exhibited excellent activity and selectivity for the hydrogenation of quinolines to 1,2,3,4-tetrahydroquinolines under mild temperature (80°C) and H2 pressure (10 bar) in aqueous medium. Both the activity and selectivity could be maintained for at least nine reaction runs. No metal leaching into solution occurred during duty. TEM analyses

1    Page 1 of 24

carried out on the catalyst showed that the active species were supported palladium nanoparticles having a mean size of 4 nm, which did not aggregate with the recycles.

ip t

Keywords: water solvent, quinoline hydrogenation, polymer supported Pd nanoparticles, recyclable

cr

catalyst.

1. Introduction

us

1,2,3,4-Tetrahydroquinolines are important intermediates for the synthesis of drugs, agrochemicals, dyes, alkaloids, and many other biological active molecules [1,2,3]. Although different methods

an

have been developed for their synthesis, such as the catalytic cyclization [4,5] and the Beckman rearrangement [6], the direct catalytic hydrogenation of readily available quinolines should be the

M

best approach to access tetrahydroquinolines in terms of atom economy. However, this catalytic hydrogenation is not as trivial as the simple reduction of a C-C or a C-N double bond could be.[7]

d

In fact, quinolines are challenging substrates [8] for the following reasons: i) the aromatic rings

te

render these molecules reluctant to undergo hydrogenation; ii) the presence of the N-heterocycle

Ac ce p

often results in strong interaction with the catalyst so to poison it [9,10]; iii) the formation of strong hydrogen bonds between the substrate (at the N position) and the solvent molecule (when this is a protic molecule) may impede the interaction of the substrate with the catalyst [11], thus rendering the common hydrogenation catalytic systems, generally designed to work in methanol or ethanol, uneffective [12].

Many soluble metal catalysts based on Os [13], Ir [8,14] Ru [15,16,17] and Rh [18,19] can reduce the quinoline ring, but they are difficult to be re-used and very often they need the presence of a cocatalyst. Recently, heterogeneous catalytic systems based on noble metals [20], such as Ru [21,22], Rh [23] and Au [24] have been developed. In some cases they are vulnerable to the poisoning effect of strongly adsorbed quinolines and/or their hydrogenated derivatives. Moreover, clear drawbacks 2    Page 2 of 24

of these systems are: i) their low activity under mild reaction conditions, since almost all quinoline hydrogenation catalysts require high pressures (30÷60 bar) and temperatures (100÷150 °C), ii) the need of organic solvents (for example: toluene).

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Recently, water has been viewed as an eco-friendly alternative to common organic solvents because it is non-toxic, nonflammable, has a high heat capacity, it is cheap and renewable. In some cases,

cr

due to its high polarity, its acid–base properties and its ability of building hydrogen bonding, water may influence the reactivity and the selectivity of certain catalytic systems. However, it is known

us

that the formation of hydrogen bonds between the hydroxyl groups of the water and the quinoline

an

nitrogen may inhibit the absorption of the substrate on the surface of the catalyst, thus lowering its activity [25]. For this reason, despite the advantages in using water as the solvent, only a limited

M

number of heterogeneous catalysts have been employed for promoting the hydrogenation reactions of quinolines in water. Among them, Ru nanoparticles intercalated in hectorite were found to be

d

active in water under 30 bar H2 at 100 °C for the partial reduction of quinoline, but their

te

recyclability was really poor because of separation problem in aqueous media [26]. A water soluble Ir complex anchored onto a solid support has been used as catalyst for the hydrogenation of

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quinolines in water under 20 bar H2 at 80 °C, but it suffered from severe metal leaching [27]. Palladium nanoparticles stabilized by black wattle tannin were active and recyclable in the quinoline hydrogenation at 60÷80 °C under 20 bar H2 both in neat water [28] and in a biphasic system made by water and an immiscible organic solvent [29]. On the contrary, Pd nanoparticles grafted onto polymeric mesoporous carbon graphitic nitrides were almost inactive for the quinoline hydrogenation in water, being much more efficient catalyst in acetonitrile or toluene even under 1 atm H2 [30]. A similar behavior has been observed for Pd/MgO catalyst, active in hexane under 40 atm H2 at 150°C [31], and for the catalytic system based on hydroxyapatite supported Pd nanoparticles, for which the best solvent in terms of activity and recyclability under mild conditions was toluene [32]. 3    Page 3 of 24

With the aim to develop innovative catalytic processes that enable chemical transformations to be performed under mild and sustainable conditions with high efficiency, we decided to evaluate the catalytic activity of a polymer supported palladium catalyst (in the following Pd-pol) for the partial

ip t

hydrogenation of quinolines in water. In order to obtain a material with a uniform distribution of the catalytically active sites, the catalyst was not synthetized by classical immobilization of palladium

cr

centers onto a pre-fabricated support, but it was prepared by co-polymerization of the metalcontaining monomer [33] Pd(AAEMA)2 [AAEMA− = deprotonated form of 2-(acetoacetoxy)ethyl

us

methacrylate] with suitable co-monomer (ethyl methacrylate) and cross-linker (ethylene glycol

O

O

O

O

ethyl methacrylate

O Pd(AAEMA) 2

d

O

O

O

O

O ethylene glycol dimethacrylate hv

Pd-pol

 

te

O

O

+

O

+

Pd O

O

M

O

an

dimethacrylate) [34,35] (scheme 1).

Ac ce p

Scheme 1: synthesis of Pd-pol

Pd-pol

was

already

found

active

and

recyclable

in

several

palladium

promoted

reactions,[36,37,38,39,40,41] even under air and in water solvent [42]. The reticular and macro porous polymeric support of Pd-pol is able to immobilize and stabilize palladium nanoparticles (formed under reaction conditions by reduction of the pristine Pd(II) anchored complex), suitable for the Suzuki cross coupling of arylhalides with arylboronic acids in water [42] for the aerobic selective oxidation of benzyl alcohols in water [43], and for the reductive amination reaction under 1 atm of H2 [40]. Furthermore, its good swellability in water renders Pd-pol an ideal potential catalyst for reactions carried out in water, since the migration of the reagents to the active sites would be not hampered by the solid support. 4    Page 4 of 24

Herein we report on the ability of Pd-pol to efficiently catalyze the selective reduction of quinolines

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into tetrahydroquinolines under mild conditions in aqueous medium.

2. Experimental Section

cr

2.1 General considerations

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Tap water was de-ionized by ionic exchange resins (Millipore) before use. All other chemicals were purchased from commercial sources and used as received. Pd-pol (Pd %w = 2.3) was synthesized

an

according to literature procedure [41]. Palladium content in Pd-pol was assessed after sample mineralization by atomic absorption spectrometry using a Perkin –Elmer 3110 instrument. Catalyst

M

mineralization prior to Pd analyses was carried by microwave irradiation with an ETHOS E-

weighted sample.

d

TOUCH Milestone applicator, after addition of 12 mL HCl/HNO3 (3:1, v/v) solution to each

te

GC-MS data (EI, 70 eV) were acquired on a HP 6890 instrument using a HP-5MS crosslinked 5%

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PH ME siloxane (30.0 m × 0.25 mm × 0.25 μm) capillary column coupled with a mass spectrometer HP 5973. The products were identified by comparison of their GC-MS features with those of authentic samples. Reactions were monitored by GLC or by GC-MS analyses. GLC analysis of the products was performed using a HP 6890 instrument equipped with a FID detector and a HP-1 (Crosslinked Methyl Siloxane) capillary column (60.0 m x 0.25 mm x 1.0 μm). Conversions and yields were calculated by GLC analysis as moles of hydrogenated product per mole of starting substrate by using biphenyl as internal standard. The microstructure of the polymeric matrix embedded Pd nanoparticles was determined by TEM observations at acceleration voltage of 100 kV (Model HITACHI 7700). The samples were prepared by dispersing the powders in distilled water using an ultrasonic stirrer and then placing a 5    Page 5 of 24

drop of suspension on a pretreated copper grid, which was coated with an amorphous thin carbon film. The particle size distributions were obtained by TEM image analysis using the ImageJ

2.2. General procedure for catalytic hydrogenation of quinolines.

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software (freeware software: http://rsb.info.nih.gov/ij/).

cr

In a typical run, a 50 mL stainless steel autoclave equipped with a transducer for online pressure monitoring was charged, under air, of Pd-pol (23.2 mg, Pd: 0.5 mol %), the substrate (1.0 mmol),

us

and water (5.0 mL) or water (4.0 mL) and CH3OH (1.0 mL). The autoclave was then purged three

an

times with hydrogen, then pressurized with 10 bar H2, set on a magnetic stirrer and heated to 80°C. After the minimum time needed to reach reaction completion, the autoclave was let to reach room

M

temperature, the hydrogen was vented and the autoclave opened. The catalyst was recovered by filtration while the organic product was extracted with ethyl acetate (3 mL), the water phase was

d

washed with ethyl acetate (2 × 5 mL) and the organic layers were collected. The yields were

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2.3.Recycling experiments

te

assessed by GLC analysis of the ethyl acetate solution with the internal standard (biphenyl) method.

The catalyst recovered by filtration was washed with water, methanol, and diethyl ether and dried under high vacuum. The recovered catalyst was thus weighed and reused for a new cycle employing appropriate amounts of organic substrate and solvent, assuming that the palladium content remained unchanged with the recycles. Iteration of this procedure was continued for nine reuses of the catalyst.

3. Results and Discussion

6    Page 6 of 24

In exploratory experiments,  we selected the hydrogenation of 8-methylquinoline to the corresponding 8-methyl-1,2,3,4-tetrahydroquinoline as the model reaction to study the catalytic activity and selectivity of Pd-pol (scheme 2). The relevant results are reported in table 1.

ip t

Pd-pol (0.5 mol%) H2, solvent N

cr

N H

 

an

us

Scheme 2: Hydrogenation of 8-methylquinoline.

Table 1. Hydrogenation of 8-methylquinoline to 8-methyl-1,2,3,4-tetrahydroquinolinea

1

H2 O

2

H2 O

10

25

M

20

10

>99

1.0

3

CH3CH2OH

10

25

20

43

>99

4.3

4

CH3OH

10

25

20

52

>99

5.2

5

CH3OH/H2O (1/4)

10

25

20

40

>99

4.0

te

d

Solvent

Ac ce p

a

P (bar)b T (°C) t (h)c Conv. d Selectivityd TOF (%) (%) (h–1) 1 25 20 0 0 0

Entry

6

CH3OH/H2O (1/4)

10

80

9

>99

>99

22.2

7e

CH3OH/H2O (1/4)

10

80

16

0

0

0

8-methylquinoline (1.0 mmol), solvent (5.0 mL), Pd-pol (Pd: 0.5 mol%) under H2; b H2 pressure; c

minimum time at which the reaction stopped; d calculated by GLC analysis; e in the absence of Pdpol.

The reaction was significantly affected by different parameters, such as reaction temperature, hydrogen pressure and solvent. After the experiments summarized in Table 1, the best sustainable

7    Page 7 of 24

conditions were found to be those employed in entry 6, that is: 8-methylquinoline (1.0 mmol), Pdpol (0.5 mol% of Pd), hydrogen (10 bar) in water/methanol (4 mL/1 mL) at 80 °C for 9 h. The exploratory experiments revealed that in water at room temperature after 20 hours the

ip t

conversion into the hydrogenated product was negligible under 1 atm pressure of H2 (entry 1), confirming the reluctance of the substrate to be reduced under ambient conditions. By increasing

cr

the pressure of H2 up to 10 bar the quinoline conversion raised up to 10% in water (entry 2), 43% in ethanol (entry 3) and 53% in methanol (entry 4) after 20 hours, according to the enhanced ability of

us

the three different solvents in stabilizing the hydride intermediates [12] and in dissolving the

an

hydrogen gas and the organic substrate. The reaction performed at 25 °C under 10 bar dihydrogen in water/methanol (4/1, v/v) gave results (entry 5) similar to those obtained by using neat ethanol as

M

the solvent (entry 3). The enhanced activity of the catalytic system in water/methanol compared to neat water is probably due to the low solubility of the substrate in the latter solvent and/or in the

d

higher solubility of the dihydrogen gas in the water/methanol mixture. Since in terms of green

te

chemistry it is more convenient the use of the aqueous mixture (water/methanol, 4/1) than methanol or ethanol as the solvent, we decided to carry out the catalytic hydrogenation of 8-methylquinoline

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in water/methanol (4/1, v/v), increasing the temperature up to 80 °C in order to reach higher substrate conversion. As expected, the catalytic activity of Pd-pol was enhanced, giving quantitative 8-methyl-quinoline conversion into 8-methyl-1,2,3,4-tetrahydroquinoline after 9 hour reaction (entry 6).

The best conditions reported in entry 6 of Table 1 were applied to the same hydrogenation reaction carried out in the absence of the palladium catalyst (entry 7). No reduction of the model substrate occurred at all, even after 16 hour stirring, thus confirming that Pd-pol catalyst was essential for the desired transformation. Using the optimized reaction conditions, the activity and the scope of the catalyst was explored in the hydrogenation reaction of some quinolines and quinoxalines (Table 2). 8    Page 8 of 24

Table 2. Pd-pol-catalyzed hydrogenation of quinolines and heteroaromatic nitrogen compoundsa Substrate

Product

1 N H

9

99

us

2 N

an M

Ac ce p

N

98

8

99

8

99

8

98

H N

N

N H

16

N H

N

H 3CO

H N

te

4

98

N H

d

N

N

9

N H

3

c

99

cr

 

6

Yieldb (%)

20

N

5c

t (h)

ip t

Entry

N H

N

NH

N H

H 3CO

a

Substrate (1.0 mmol), H2O/CH3OH (4 mL/ 1 mL), Pd-pol (Pd: 0.5 mol %), 80 °C, 10 bar H2. bGLC

yields using biphenyl as the internal standard. The conversion was >99% for all substrates. c in neat water (5.0 mL). 9    Page 9 of 24

The hydrogenation of 8-methylquinoline was highly regioselective, producing the relevant 1,2,3,4tetrahydroquinoline exclusively, even after 20 hour stirring under reaction conditions (entry 1). No trace of 5,6,7,8-tetrahydroquinoline or decahydroquinoline, byproducts frequently formed under

ip t

hydrogenation catalysis [44] was observed. Reaction of quinoline (entry 2) and quinoline bearing a methyl group at the 2- and 6-positions (entry 3) proceeded successfully to give the corresponding

cr

1,2,3,4-tetrahydroquinolines, even if for the latter substrate the minimum time to reach quantitative conversion was longer (16 h) for steric hindrance [45].

us

Encouraged by these results, we applied this protocol to the regioselective hydrogenation of the

an

heterocyclic ring of two quinoxalines, important heteroaromatic nitrogen compounds used as intermediates for the synthesis of dyes, pharmaceutics and antibiotics. 5-Methylquinoxaline and 2-

M

methylquinoxaline were tested, obtaining quantitative yield in the corresponding 1,2,3,4tetrahydroquinoxaline in both cases (entries 4 and 5). It is noteworthy that for these two water

d

soluble substrates, it was possible to carry out the reaction in neat water.

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Finally, the hydrogenation of harmaline, another biologically important heteroaromatic nitrogen compound, proceeded smoothly in 8 hours giving quantitative yield in leptaflorine (entry 6).

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The reusability of Pd-pol catalyst in 8-methylquinoline hydrogenation was investigated. After the first use, the supported catalyst was recovered by simple filtration and reused in the next run after a washing workup. The recovered catalyst was successfully employed in the subsequent nine cycles with a high catalytic activity, giving the product in excellent yields (95-99%, figure 1).

10    Page 10 of 24

us

cr

ip t

Yield (%)

cycle

an

Figure 1: Recyclability of Pd-pol (0.5 mol% of Pd) in the hydrogenation of 8-methylquinoline in water/methanol (4/1, v/v) under H2 (10 bar) at 80 °C (t = 9 h). GLC yields using biphenyl as the

M

internal standard.

d

In addition, deeper stability studies were performed, repeating each run and stopping the reaction at

te

70% conversion ca. (6 h). The catalytic system confirmed the same activity with the re-cycles even at conversions less than 100% and no catalyst deactivation was observed.

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To verify whether the observed catalysis is truly heterogeneous or not, the reaction mixture was hot filtered at 40% conversion of 8-methylquinoline at 80 °C. Further stirring of the filtrate under the above reaction conditions did not yield any additional product. In addition, both this mother liquor and the filtrate obtained by removing the supported catalyst at the end of reaction (i.e. at quantitative conversion) were mineralized and analyzed by atomic absorption spectrometry that confirmed that no palladium species leached from the solid support into solutions. Furthermore, the samples of Pd-pol recovered from the two aforementioned hot filtrations (at 40% conversion and after 9 h, respectively) were mineralized and analyzed by atomic absorption spectrometry showing the same palladium content (in the range of the experimental error). The same palladium amount

11    Page 11 of 24

was also found in the catalyst recovered at the end of the ninth cycle of 8-methylquinoline hydrogenation. These results rule out any possible contribution of homogeneous catalysis by leached palladium

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species. Remarkably, the commercial Pd/C catalyst used to promote the quinoline hydrogenation under

cr

conditions (20 atm H2, 60 °C) similar to those reported in the present work was not recyclable, being completely inactive after 3 runs [28]. The different behavior of Pd/C with respect to Pd-pol

us

may be due both to the different nature of the support (that in Pd-pol case stabilizes the metal

an

nanoparticles) and/or to the different mean metal particle size.

This study was completed with the TEM characterization of Pd-pol before, after the first and the

M

ninth cycle, respectively, with the aim of ascertaining whether the reaction cycles affected the morphology and the dispersion of the palladium active species on the surface of the support.

d

TEM pictures of pristine Pd-pol and of the catalyst recovered after the first and the ninth runs, are

te

reported in Figures 2a, 2b and 2c, respectively. The pristine catalyst was constituted mainly by polymer-bound Pd(II) species (not visible in the TEM micrographs) [41], together with a low

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number density of metallic Pd nanoparticles (with diameter ranging between 1.5 and 6.5 nm, figure 2a). This nanostructure reflected the way of preparation of the pre-catalyst [46]. In fact, these nanoparticles likely formed during the thermal polymerization step of the catalyst synthetic procedure [41].

The TEM image of Pd-pol recovered after the first run (figure 2b) showed the formation of new Pd nanoparticles, now ranging from 1.5 to 8.5 nm, ascribable to the hydrogen reduction of Pd(II) supported polymer. On passing from the first to the ninth cycle (figure 2c), the mean Pd(0) nanoparticle size increased, with diameters ranging from 4.5 nm to 10.5 nm, and their size distribution appeared broader. However, the nanostructure of the catalyst was substantially maintained during the subsequent cycles and the Pd nanoparticles remained embedded into the 12    Page 12 of 24

polymer bulk. Interestingly, it has been reported that palladium(II) centers supported onto a methacrylic resin similar to Pd-pol pre-catalyst, once reduced to Pd(0), lead to nanoparticles, which in turn can increase their size (growth) or/and agglomerate (aggregation) with the time [47]. The

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aggregation process would decrease the catalytically active superficial area much more than the growth of a single nanoparticle. Remarkably, even if the Pd nanoparticles supported onto Pd-pol

cr

slightly grew with the recycles, they remained isolated from each other and did not aggregate. This

comparable to that of the catalyst re-used after the first run.

us

explains why the catalytic activity of the supported catalyst recovered after nine cycles was

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The formation of catalytically active palladium nanoparticles, stabilized by the insoluble matrix of Pd-pol and ascribable to hydrogen reduction, was observed also when Pd-pol was used as catalyst

M

for the reductive amination of carbonyl compounds carried out under 1 atm H2 in methanol [41]. The mean size of those Pd nanoparticles was slightly bigger than the one observed in the present

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te

d

work, possibly reflecting the different hydrogen pressure employed in the two studies [48].

13    Page 13 of 24

Figure 2: Transmission electron micrographs and associated size distribution (inset) of matrix polymer embedded Pd nanoparticles: (a) pristine Pd-pol; (b) Pd-pol recovered after the first run of the hydrogenation of 8-methylquinoline; (c) Pd-pol recovered after the ninth run of the

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hydrogenation of 8-methylquinoline

cr

It has been demonstrated that the reduction of polar bonds, such as C=O or C=N, with homogeneous metal complexes bearing polar ligands initiates with the heterolytic cleavage of H2 to

us

yield H− in metal hydrides and H+, and the resulting H+/H− pair preferentially transfers to the polar

an

bonds [49]. Moreover, the heterolytic cleavage of H2 (assisted by the basic support) has been substantiated in heterogeneous quinoline hydrogenation by Au dispersed onto modified TiO2 [24],

M

by Ru/MgO catalyst [50] or by Ru/poly(4-vinylpyridine) system [51]. A mechanism able to explain the high selectivity of Pd-pol system in water would thus be based on

d

an ionic pathway, involving solvent assisted heterolytic hydrogen activation promoted by the basic

te

substrate (scheme 3). This would result in protonation of the quinoline, followed by H-transfer from the metal to the adjacent carbon atom, as suggested by Crabtree and Eisenstein [8], leading to a high

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selectivity for the hydrogenation of the heterocyclic ring [52].

N H

H H O

Pd

H  

Scheme 3: solvent assisted heterolytic splitting of H2 in water 14    Page 14 of 24

Changing the reaction medium from water to an aprotic and apolar solvent is expected to decrease the selectivity and indeed experimentally such behavior is observed. In fact, carrying out the 8-

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methylquinoline hydrogenation in n-heptane at 80 °C and under 10 bar H2 resulted in both reaction rate and selectivity lower than those observed in water. In n-heptane the conversion was 63% after 9

cr

h, and the minimum time to reach the maximum conversion (83%) was 30 h. As to the selectivity, a 5% of 8-methyl-5,6,7,8-tetrahydroquinoline (despite the presence of a methyl group in 8-position)

us

and ca. 1 % of decahydroquinoline (a product never detected using water as solvent) was obtained

an

at the end of reaction.

This suggests that when an apolar and non-protic solvent is used, the ionic pathway becomes

M

unlikely. Binding of the basic nitrogen atom to the Lewis acidic Pd centers would still be preferred (scheme 4), leading to preferential reduction of the heterocyclic ring [53], being hydrogenation of

d

the  carbocyclic ring through standard H-atom transfer still possible, with formation of 5,6,7,8-

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te

tetrahydro and deca-hydro products, as experimentally observed.

N

NH

H

H

Pd

 

Scheme 4: plausible transition state for the hydrogenation of quinoline with Pd-pol in n-heptane.

15    Page 15 of 24

The reported results demonstrate that quinoline, a poison for traditional noble metal-containing hydrogenation catalysts [54], can be smoothly hydrogenated by Pd-pol catalytic system with

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activities (and selectivities) depending on the used solvent.

4. Conclusions

cr

An efficient approach is proposed for mild and clean hydrogenation of quinolines (a class of wellknown poisons for the traditional noble metal-based hydrogenation catalysts) and related

us

heteroaromatic nitrogen compounds to the corresponding tetrahydroderivatives using polymer

an

supported palladium catalyst in aqueous solvent. Of practical significance is the fact that the catalyst can be recovered at the end of the reaction and re-cycled for at least nine times with the

M

same activity and selectivity. TEM analyses showed that the active species are Pd nanoparticles with average size of 4 nm diameter, that do not aggregate with the re-uses and do not leach out in

d

solution during reaction. To the best of our knowledge, Pd-pol is the second example reported to

te

date of active palladium catalyst recyclable in aqueous solvent for the selective hydrogenation of

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quinolines and heteroaromatic nitrogen compounds under mild conditions.

Acknowledgement:

The

authors

thank

Italian

MIUR

(project

PRIN

2010-2011

n.

2010FPTBSH_001) for financial support. The TEM observations are supported by the Project 2HE (PONa3_00334).

16    Page 16 of 24

Table 1. Hydrogenation of 8-methylquinoline to 8-methyl-1,2,3,4-tetrahydroquinolinea Solvent

1

H2 O

2

H2 O

10

25

20

10

>99

3

CH3CH2OH

10

25

20

43

4

CH3OH

10

25

20

52

ip t

P (bar)b T (°C) t (h)c Conv. d Selectivityd TOF (%) (h–1) (%) 1 25 20 0 0 0

Entry

5

CH3OH/H2O (1/4)

10

25

20

40

6

CH3OH/H2O (1/4)

10

80

9

>99

7e

CH3OH/H2O (1/4)

10

80

16

4.3

>99

5.2

cr

>99

4.0

>99

22.2

0

0

us

>99

8-methylquinoline (1.0 mmol), solvent (5.0 mL), Pd-pol (Pd: 0.5 mol%) under H2; b H2 pressure; c

an

a

0

1.0

minimum time at which the reaction stopped; d calculated by GLC analysis; e in the absence of Pd-

Ac ce p

te

d

M

pol.

17    Page 17 of 24

 

Table 2. Pd-pol-catalyzed hydrogenation of quinolines and heteroaromatic nitrogen compoundsa Substrate

Product

1 N

N H

us

2 N

an d

Ac ce p

N

H 3CO

N H

99

9

98

16

98

8

99

8

99

8

98

H N

N

6

20

N H

N

5c

H N

te

4

99

N H

M

N

N

9

N H

3

c

Yieldb (%)

cr

 

t (h)

ip t

Entry

N H

N

NH

N H

H 3CO

a

Substrate (1.0 mmol), H2O/CH3OH (4 mL/ 1 mL), Pd-pol (Pd: 0.5 mol %), 80 °C, 10 bar H2. bGLC

yields using biphenyl as the internal standard. The conversion was >99% for all substrates. c in neat water (5.0 mL). 18    Page 18 of 24

Pd-pol (0.5 mol%) H2 (10 bar) H2O/CH3OH (4/1, v/v) 80 °C t=9h

N H

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N

yield = 98%

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cycle

 

 

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Graphical Abstract

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Yield (%)

20    Page 19 of 24

Highlights

• Polymer supported Pd catalyst (Pd-pol) promoted the quinoline hydrogenation • Pd-pol was active under mild conditions in aqueous medium • The catalyst could be reused at least nine times without loss of activity

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• Pd leaching did not occur

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• The in situ formed supported Pd nanoparticles were the true active species

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te

d

M

an

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21    Page 20 of 24

References                                                             

[1] R.T. Shuman, P.L. Ornstein, J.W. Paschal, P.D. Gesellchen, J. Org. Chem. 55 (1990) 738−741.

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[2] A.R. Katritzky, S. Rachwal, B. Rachwal, Tetrahedron 52 (1996) 15031−15070.

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[3] V. Sridharan, P. Suryavanshi, J.C. Menendez, Chem. Rev. 111 (2011) 7157−7259.

[4] R. Omar-Amrani, A. Thomas, E. Brenner, R. Schneider, Y. Fort, Org. Lett. 5 (2003)

us

2311−2314.

[5] T. Kubo, C. Katoh, K. Yamada, K. Okano, H. Tokuyama, T. Fukuyama, Tetrahedron 64 (2008)

an

11230−11236.

Am. Chem. Soc. 105 (1983) 2831−2843.

M

[6] K. Maruoka, T. Miyazaki, M. Ando, Y. Matsumura, S. Sakane, K. Hattori, H. Yamamoto, J.

[7] Y.-G. Zhou, Acc. Chem. Res. 40 (2007) 1357–1366.

d

[8] G. E. Dobereiner, A. Nova, N.D. Schley, N. Hazari, S.J. Miller, O. Eisenstein, R.H.J. Crabtree,

te

Am. Chem. Soc. 133 (2011) 7547-7562 and refs therein.

Ac ce p

[9] R. H. Fish, J. L. Tan, A. D. Thormodsen, J. Org. Chem. 49 (1984) 4500-4505. [10] R. H. Fish, J. L. Tan, A. D. Thormodsen, Organometallics 4 (1985) 1743-1747. [11] C. Bianchini, A. Meli, F. Vizza, Eur. J. Inorg. Chem. 2001, 43−68. [12] R.L. Augustine, Heterogeneous Catalysis for the Synthetic Chemist; Marcel Dekker: New York, 1996

[13] M. Rosales, S. Castillo, A. Gonzalez, L. Gonzalez, K. Molina, J. Navarro, I. Pacheco, H. Perez, Transition Met. Chem. 29 (2004) 221−228. [14]W. B. Wang, S.M. Lu, P.Y. Yang, X.W. Han, Y.G. Zhou, J. Am. Chem. Soc. 125 (2003) 10536−10537.

22    Page 21 of 24

                                                                                                                                                                                                     

[15] Y.-P. Sun, H.-Y. Fu, D.-l. Zhang, R.-X. Li, H. Chen, X.-J. Li, Catal. Commun. 12 (2010) 188– 192. [16] P. Frediani, V. Pistolesi, M. Frediani, L. Rosi, Inorg. Chim. Acta 359 (2006) 917–925.

ip t

[17] H. Zhou, Z. Li, Z. Wang, T. Wang, L. Xu, Y. He, Q.-H. Fan, J. Pan, L. Gu, A.S.C. Chan, Angew. Chem., Int. Ed. 47 (2008) 8464–8467.

cr

[18] C. Wang, C.Q. Li, X.F. Wu, A. Pettman, J.L. Xiao, Angew. Chem., Int. Ed. 2009, 48, 6524–

[19] G.-Y. Fan, J. Wu, Catal. Commun. 31 (2013) 81–85.

us

6528.

an

[20] D. Tabuani, O. Monticelli, A. Chincarini, C. Bianchini, F. Vizza, S. Moneti, S. Russo, Macromolecules 2003, 36, 4294-4301.

M

[21] A. Spitaleri, P. Pertici, N. Scalera, G. Vitulli, M. Hoang, T.W. Turney, M. Gleria, Inorg. Chim. Acta 352 (2003) 61–71.

d

[22] R.A. Sanchez-Delgado, N. Machalaba, N. Ng-A-Qui, Catal. Commun. 8 (2007) 2115–2118.

te

[23] M. Campanati, M. Casagrande, I. Fagiolino, M. Lenarda, L. Storaro, M. Battagliarin, A. Vaccari, J. Mol. Catal. A: Chem. 184 (2002) 267–272.

Ac ce p

[24] D. Ren, L. He, L. Yu, R.-S. Ding, Y.-M. Liu, Y. Cao, H.-Y. He, K.-N. Fan, J. Am. Chem. Soc. 134 (2012) 17592−17598.

[25] C. Bianchini,← V. Dal Santo, A. Meli, S. Moneti, M. Moreno, W. Oberhauser, R Psaro,

L. Sordelli, F. Vizza, J. Catal. 213 (2003) 47–62. [26] B. Sun, F.-A. Khan, A. Vallat, G. Suss-Fink, Applied Catal. A: Gen. 467 (2013) 310–314. [27] P. Barbaro, L. Gonsalvi, A. Guerriero, F. Liguori, Green Chem. 14 (2012) 3211−3219. [28] H. Mao, C. Chen, X. Liao, B. Shi, J. Mol. Catal. A: Chem. 341 (2011) 51–56. [29] H. Mao, J. Ma, Y. Liao, S. Zhao, X. Liao, Catal. Sci. Technol. 3 (2013) 1612-1617. 23    Page 22 of 24

                                                                                                                                                                                                     

[30] Y. Gong, P. Zhang, X. Xu, Y. Li, H. Li, Y. Wang, J. Catal. 297 (2013) 272–280 [31] R. Rahi, M. Fang, A. Ahmed, R. A. Sánchez-Delgado, Dalton Trans. 41 (2012) 14490–14497. [32] N. Hashimoto, Y. Takahashi, T. Hara, S. Shimazu, T. Mitsudome, T. Mizugaki, K.

ip t

Jitsukawa, K. Kaneda, Chem. Lett. 39 (2010) 832.

[33] M. M. Dell’Anna, G. Romanazzi, P. Mastrorilli, Curr. Org. Chem. 17 (2013) 1236–1273. 

cr

[34] M.M. Dell’Anna, P. Mastrorilli, A. Rizzuti, G.P. Suranna, C.F. Nobile, Inorg. Chim. Acta 304

us

(2000) 21–25.

[35]  M. M. Dell’Anna, P. Mastrorilli, C.F. Nobile, in: P.J.H. Scott (Ed.), Solid-Phase Organic

an

Syntheses, vol. 2, John Wiley & Sons, Inc., Hoboken, NJ, USA, 2012, pp. 79–86. [36] M. M. Dell’Anna, M. Gagliardi, P. Mastrorilli, C. F. Nobile, J. Mol. Catal. A: Chem. 158

M

(2000) 515–520.

[37] M. M. Dell’Anna, P. Mastrorilli, F. Muscio, C. F. Nobile, G. P. Suranna, Eur. J. Inorg. Chem.

d

8 (2002) 1094–1099.

te

[38] M. M. Dell’Anna, P. Mastrorilli, F. Muscio, C. F. Nobile, in: M. Anpo, M. Onaka, H.

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Yamashita (Eds.), Science and Technology in Catalysis, Elsevier, Amsterdam, 2002, pp. 133–136. [39] M. M. Dell’Anna, P. Mastrorilli, C. F. Nobile, G. P. Suranna, J. Mol. Catal. A: Chem. 201 (2003) 131–135.

[40] M. M. Dell’Anna, A. Lofu, P. Mastrorilli, V. Mucciante, C. F. Nobile, J. Organomet. Chem. 691 (2006) 131–137.

[41] M. M. Dell’Anna, P. Mastrorilli, A. Rizzuti, C. Leonelli, Appl. Catal. A: Gen. 401 (2011) 134– 140. [42]  M. M. Dell’Anna, M. Mali, P. Mastrorilli, A. Rizzuti, C. Ponzoni, C. Leonelli, J. Mol. Catal. A: Chem. 366 (2013) 186–194. 

24    Page 23 of 24

                                                                                                                                                                                                     

[43] M. M. Dell’Anna, M. Mali, P. Mastrorilli, P. Cotugno, A. Monopoli, J. Mol. Catal. A: Chem. 386 (2014) 114–119. [44] Y. Sun, H. Fu, D. Zhang, R. Li, H. Chen, X. Li, Catal. Commun. 12 (2010) 188−192.

ip t

[45] F. Fache, Synlett 15 (2004) 2827–2829.

cr

[46] S. Sarkar, E. Guibal, F. Quignard, A.K. SenGupta, J. Nanopart. Res. (2012) 14:715 doi:10.1007/s11051-011-0715-2.

us

[47] L. De Zan, D. Gasparovicova, M. Kralik, P. Centomo, M. Carraro, S. Campestrini, K. Jerabek, B. Corain, J. Mol. Catal. A: Chem. 265 (2007) 1–8.

an

[48] C. Salzemann, C. Petit, Langmuir 28 (2012) 4835−4841.

M

[49] R. M. Bullock, Chem., Eur. J. 10 (2004), 2366–2374.

[50] M. Fang, R. A. Sánchez-Delgado, J. Catal. 311 (2014) 357–368.

d

[51] M. Fang, N. Machalaba, R. A. Sánchez-Delgado, Dalton Trans. 40 (2011) 10621–10632.

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[52] We attempted to detect the characteristic vibrations associated with the Pd hydrides, by recording the IR spectrum of the catalyst recovered immediately after duty in aqueous medium.

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Unfortunately, such vibrations were not detected by IR spectroscopy, presumably because of the instability of the Pd-H species. In fact if heterolytic hydrogen activation takes place under the reaction conditions, assisted by the polymer support, it would generate very reactive hydrides on the Pd particles and protons in close proximity to each other. Once the temperature is lowered and the hydrogen pressure is released, the proton and the hydride would couple back to the thermodynamically stable hydrogen molecule, rendering unsuitable the IR measurements.  [53] E. Baralt, S.J. Smith, J. Hurwitz, I.T. Horvath, R.H. Fish, J. Am. Chem. Soc. 114 (1992) 5187– 5196. [54] S. Nishimura, Handbook of Heterogeneous Catalytic Hydrogenation for Organic Synthesis, Wiley: New York, 2001. 25    Page 24 of 24