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Palladium nanoparticles, stabilized by lignin, as catalyst for cross-coupling reactions in water
Accepted Manuscript Palladium nanoparticles, stabilised by lignin, as catalyst for cross-coupling re‐ actions in water Francesca Coccia, Lucia Tonucci, Nicola d’Alessandro, Primiano D’Ambrosio, Mario Bressan PII: DOI: Reference:
S0020-1693(12)00694-9 http://dx.doi.org/10.1016/j.ica.2012.12.035 ICA 15274
To appear in:
Inorganica Chimica Acta
Received Date: Revised Date: Accepted Date:
14 September 2012 19 December 2012 23 December 2012
Please cite this article as: F. Coccia, L. Tonucci, N. d’Alessandro, P. D’Ambrosio, M. Bressan, Palladium nanoparticles, stabilised by lignin, as catalyst for cross-coupling reactions in water, Inorganica Chimica Acta (2013), doi: http://dx.doi.org/10.1016/j.ica.2012.12.035
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Palladium nanoparticles, stabilised by lignin, as catalyst for crosscoupling reactions in water Francesca Cocciaa, Lucia Tonuccib, Nicola d’Alessandro c*, Primiano D’Ambrosioc and Mario Bressanc a
School of Advanced Studies in Science, University “G.d’Annunzio” of Chieti and Pescara, 65127 Pescara, Italy
b
Department of Philosophy, Human and Educational Science, University G.d’Annunzio of Chieti and Pescara, Via dei Vestini 31, I-66013 Chieti Scalo, Italy
c
Department of Engineering and Geology, University “G.d’Annunzio” of Chieti and Pescara,Viale Pindaro, 42, I-65127 Pescara, Italy
* Corresponding author; tel: xx39 0871 3555365; email: [email protected] Abstract Palladium nanoparticles of a definite shape (spherical) and dimension (8-14 and 16-20 nm) were prepared employing two water soluble lignin samples as both reducing and stabilising agent in definitely green experimental conditions, namely aqueous solution, aerobic conditions, moderate temperature, short times. The above nanoparticles were employed as catalyst for a series of carboncarbon coupling reactions carried out in water at mild conditions. Heck and Suzuki reactions were performed for several substrates, by changing the nature of halogen, the substituents at the aromatic ring, the bases employed and the temperature. Product yields were satisfactory and selectivities very good. Other two cross-coupling reactions, namely Sonogashira and Stille, were also tested: iodine derivatives showed always the best reactivity, while chlorine derivatives did not react.
Keywords: nanoparticles, cross-coupling, palladium, water media, lignin
1. Introduction Synthetic chemistry still represents an important tool to obtain derivatives of great importance for our life. Few synthetic routes can be performed also in absence of any solvents [1], whereas the largest part of organic synthetic pathways requires the presence of a solvent that, keeping into due consideration the twelve principles of “Green Chemistry” [2], should be non toxic, not expensive, and easily recyclable. In the past, chemists preferred the use of organic solvents for the necessary solubility of reagents and products, the latters often slightly or no polar at all. On the other hand, since nature dominantly prefers reactions in water media, e.g. all natural enzymatic reactions [3], the possibility to mimic nature using water as solvent in any synthetic pathway represents one of the main challenge of the chemists of the 21° century. Carbon-carbon bond construction is the basis of organic chemistry, and transition metals catalysts represent the most useful tools to obtain cross-coupling reactions in mild conditions and with high yields [4,5]. In this regard, it is important to notify that 2010 Nobel prize in Chemistry was awarded jointly to Richard F. Heck, Ei-ichi Negishi and Akira Suzuki "for palladiumcatalyzed cross couplings in organic synthesis". Palladium-catalyzed cross-coupling reactions of aryl halides for the formation of new carbon-carbon bonds have huge potential in fine organic synthesis, with particular emphasis on the pharmaceutical field [6-8]. The focus today is to make the experimental conditions more environmentally friendly, e.g. in water and aerated solutions, at moderate temperatures, and in the presence of catalysts in very small amounts. Ligand-free catalysts, like nanoparticles (NPs), can operate under conditions that are particularly green [9], by envisaging also to support such NPs on metal oxide, thus making possible an efficient re-use of catalyst without loss of activity [10,11]. We recently synthesized palladium and platinum NPs starting from the corresponding metal salts and lignin, a naturally abundant by-product from the paper industry [12], which, in our case, was used as both a stabilizing and a reducing agent [13]. Here, to synthesise Pd NPs, we used two water soluble, sulphur-containing, commercial lignins, namely lignosulfonates and Kraft lignins, both produced in huge quantities worldwide [14]. After full characterization, Pd NPs were tested as catalysts for a number of cross-coupling reactions; among them, for instance, the Heck reaction between 4-iodophenol and styrene which leads to 4-hydroxystilbene, a powerful tyrosinase inhibitor [15], with 100% yield in water solution at 100 °C. 2. Experimental 2.1. Materials
Two lignin samples were used. The Kraft lignin was purchased from Sigma-Aldrich while the lignosulfonate sample, as ammonium derivative, was a courtesy of Burgo Group S.p.A. (Tolmezzo, Italy). The lignosulfonate was obtained by cooking red pine in a calcium hydrogensulphite solution and it is highly soluble in water. Palladium chloride (PdCl2) was purchased from Strem Chemicals. The remaining reagents used in the catalytic experiments were purchased from Sigma-Aldrich. 2.2. Instruments Nuclear magnetic resonance (NMR) spectra were obtained using a Bruker Avance 300 MHz spectrometer equipped with a high resolution multinuclear probe. The 1H NMR spectra of the water solutions were run in an NMR tube (5 mm) that contained a closed co-axial capillary tube filled with a 30 mM 3-trimethylsilyl-2,2’,3,3’- tetradeutero propionic acid (sodium salt). Free induction decays (FIDs) were acquired at 22°C using a pulse sequence (Bruker-made; zgcppr) that suppresses the water signal at 4.7 ppm. 1H NMR spectra in CDCl3 solution were acquired using TMS as reference, and the standard pulse sequence (zg) was used. For the 13C NMR spectra, a proton decoupling pulse sequence (zgdc) was used. UV-vis instrument was a Jenway 6505 spectrophotometer; the spectral window range was 200 600 nm. TEM measurements were performed under vacuum by an EM 109 Zeiss microscope equipped with built-in electromagnetic objective lenses and camera (Oberkochen, Germany). XRD analyses were performed on a Miniflex II Rigaku automated power X-ray diffractometer system (Cu Ka radiation, 45 kV, 100 mA) (RINT 2500, Japan). Diffraction data were recorded using continuous scanning at 3 deg/min, step 0.010. Fourier transform infrared spectra (FT-IR) were obtained on an FT-IR spectrophotometer (Perkin Elmer 1600). The gas chromatography–mass spectroscopy (GC-MS) apparatus comprised a Thermo Scientific Focus series gas-chromatograph coupled to an ISQ mass-selective detector equipped with a split-splitless injection system (injections made in split mode) and an HP-5 MS (cross-linked 5% phenyl methyl siloxane) capillary column (30 m length, 0.25 mm diameter, 0.1 µm film thickness) using helium as carrier gas at constant pressure of 30 kPa. The acquisition parameters were: source at 250 °C, transfer line at 250 °C, 3 min of delay acquisition time at the beginning of the analysis, mass range 33 amu to 350 amu, injector temperature 250 °C, initial temperature of the analyses 60 °C (1 min), then 10 °C/min up to 250 °C (kept for 6 min), for a total acquisition time of 26 min. The sample injected was 1 µL.
A 7500A ICP quadrupolar mass spectrometer (Agilent Technologies) fitted with an ASX-510 autosampler (CETAC) was used to dose residual Pd inside the reaction products. The sample was previously digested by a microwave apparatus using nitric acid as oxidant; the eluate was then analyzed by ICP instrument comparing the result with a known concentration Pd sample. 2.3. Synthesis and characterisation of Pd NPs Lignin sample (0.06 g) was placed in 10 mL of water, then 0.01 g of PdCl2 (5.64 x 10-3 M) was added. The solution was heated at 80° C for 3 h in aerated conditions. Formation of Pd NPs was evidenced by the change of the colour of the solution (from brown to black). The samples for the UV-vis measurements were prepared by diluting 40 µL of NPs solution by addition of 140 µL of ultrapure water, then the resulting solutions were analysed by 0.1 cm quartz cuvettes (Hellma). The samples for TEM analyses were prepared by placing 5 µL of a diluted solution (ten times) of Pd NPs onto 3 mm, 300 mesh, formvar/carbon nickel grids (Agar Scientific Ltd) waiting the necessary time (24 h) for the evaporation of the solvent at room temperature. The samples for XRD analysis were prepared by evaporation of solvent of the entire NPs solution and the resulting solid powder was placed on the glass plate of the instrument. The sample for IR analysis was made on 1% (w/w) NPs power in KBr sample and the spectra were recorded between 4000 to 400 cm-1. The reaction solution of Pd NPs was used directly as catalyst in all our cross-coupling reactions. 2.4. Heck reaction In a close 25 mL flask, alkene (0.5 mmol), aryl halides (0.5 mmol), K2CO3 (1.75 mmol) and Pd NPs (0.2 mL of above NPs solution; 450/1 molar ratio reagent to catalyst) were added in 5 mL water and stirred at 100 °C for 12 h. 2.5. Suzuki reaction In a close 25 mL flask, phenylboronic acid (0.75 mmol), aryl halides (0.5 mmol), K2CO3 (1.75 mmol) and Pd NPs (0.2 mL of above NPs solution; 450/1 molar ratio reagent to catalyst) were added in 5 mL water and stirred at 70 °C for 12 h. 2.6. Sonogashira and Stille reactions Sonogashira reaction: in a close 25 mL flask, aryl alkyne (0.5 mmol), aryl halides (0.5 mmol), KOH (2 mmol) and Pd NPs (0.2 mL of above NPs solution; 450/1 molar ratio reagent to catalyst)
were added in 5 mL water and stirred at 50 °C for 4 h. In experiments in presence of copper, CuI was added at 5% of molar ratio with respect to aryl halide. Stille reaction: in a close 25 mL flask, trichloro(phenyl)stannane (0.75 mmol), aryl halides (0.5 mmol), K2CO3 (1.75 mmol) and Pd NPs (0.2 mL of above NPs solution; 450/1 molar ratio reagent to catalyst) were added in 5 mL water and stirred at 80 °C for 12 h. 2.7. Work up of cross-coupling reaction mixture After cooling to room temperature the reaction mixtures, 10 mL of brine was added and then extracted thrice with diethyl ether (15 mL x 3). The organic phase was dried over Na2SO4, filtered and concentrated to a small volume; the residue was firstly analyzed by NMR (CDCl3) and then brought to a known volume (10 mL) for the quantitative spectroscopic characterization (by GC-MS, see above for instrumental conditions). 3. Results and Discussion 3.1 Pd NPs characterisation Pd II ions were reduced to their zero-valent states in water solution at 80 °C, and under aerobic conditions in the presence of the two above-mentioned water-soluble lignins. The stable Pd NPs obtained were fully characterised by UV-vis, TEM and XRD, and their behaviours as catalysts were tested for several cross-coupling reactions i.e. Heck, Suzuki, Sonogashira and Stille. The reduction of the metal ions was followed by UV-vis, where the weak diagnostic absorbances in the visible region were used to verify the Pd NPs formation [16,17]. 1
H NMR was employed to investigate the changes in the lignin structures upon the reduction of
metal. Small amounts of acetic and formic acid and of methanol were detected in the reaction mixtures, a clear indication of partial oxidation / degradation of the polymer skeleton. On the other hand, IR spectra of lignin residues after NPs formation showed that the bands attributable to methoxyl C-O (1000-1250 cm-1) and to aromatic ring vibrations (1430 and 1510 cm-1) remained practically unchanged, while a very weak shoulder appeared at 1730 cm-1, attributable to unconjugated ketone, ester or carboxylic groups coming from the modified polymer or short chain molecules detached from the lignin skeleton. Even if in both cases we noticed some little change, we conclude that the main structure of lignins was not significantly modified. Pd NPs could be directly observed under transmission electron microscopy (TEM) as particles of spherical shape with scarce tendency to aggregate into cluster (Fig.1). Sizes, which are only slightly influenced by the amount of organic polymer used, definitely depend upon the nature of
lignins used, lignosulfonate NPs being bigger (16 – 20 nm; see ref. [13]) than Kraft lignin NPs (75% of particles having a diameter between 8 and 14 nm). The XRD analysis of NPs dried powders (Fig. 2) indicated a crystalline structure with peaks at 39.9°, 46.3°, 67.4°, 82.5° and 86.9°, values found also by other authors in Pd NPs synthesised in the presence of a variety of stabilising agents [18,19]. Peaks were slightly thinner in the case of Kraft lignin NPs, in agreement with their smaller size suggested by the TEM data. 3.2. Heck reaction The vinylation of aryl halides, mainly as iodine derivatives, is commonly called Heck reaction [20]. Palladium catalyst can be used, either in complexed or ligand-free forms. After a few years from the introduction of Heck reaction, the same discovered that the complexation of palladium by phosphine ligands increases the reactivity of aryl halides, making possible also synthetic reactions with the less expensive bromo derivatives. Another step forwards was reached when Jeffery [21] discovered the effect of quaternary ammonium salt on the reactivity of ligand-free palladium catalysts, likely related to the formation and stabilization of catalytically active palladium NPs [22]. However, the experimental conditions used are not always particularly green, since organic solvents and high temperatures are often necessary [23,24]. Our experiments were conducted at 100°C and in entirely aqueous media, with a 450:1 aryl halide to catalyst molar ratio. The commonly accepted reaction mechanism involves the critical presence of a base to facilitate the β-hydride elimination step and to speed up the regeneration of Pd0 [25,26]. Previous studies demonstrated that several bases could be successfully used, among them alkali metal carbonates (or bicarbonates), carboxylates (formates or acetates) and amines [27,28]; in the absence of a base, the presence of a quaternary ammonium salt was often required, that contributes to self-generate trialkylamines [29]. In our case, since our main challenge was to operate in green conditions, we considered only the use of alkali, carbonates and bicarbonates, and, since in the presence of NaHCO3 the reaction between iodobenzene and styrene was too slow, while with NaOH and K2CO3 it proceeded smoothly at comparable rates, we chose K2CO3 for all reactions reported in Table 1. In the presence of Kraft lignin Pd NPs, iodine derivatives reacted more efficiently than the bromine ones, while the chlorine derivatives (chlorobenzene, 4-chlorophenol and 4chloronitrobenzene; not shown in table) did not react at all. The typical reaction between iodobenzene and styrene led to a quantitative conversion, with 100% of selectivity in the coupling product (which often can be observed as a solid floating on the surface of the reaction mixture). The same reaction, conducted without Pd NPs, was completely unsuccessful. By changing the aromatic
substrate with aliphatic unsaturated derivatives, a very good reactivity was again observed: however selectivities markedly decreased, due to some secondary reactions on the reaction product, namely the oxidation of cinnamyl alcohol to cinnamaldehyde (entry 2 in Table 1) and the alkaline hydrolysis of ester derivative (entry 3 in Table 1). In the case of allyl alcohol, the reaction must be carried out in presence of large excesses of allyl alcohol, in order to avoid the formation of the diphenyl allyl alcohol (and its aldehydic counterpart) and therefore to obtain a satisfactory selectivity in the coupling product. With the aim to optimise the selectivity in the formation of cinnamyl alcohol, we performed the coupling reaction at lower temperature and for a more limited time (60 °C; 6 h): however, conversions and selectivities were noticeably reduced (a large amount of biphenyl was formed), clearly indicating that at lower temperature the coupling reaction became extremely slow. The effect of temperature was also tested for some of the reactions exhibiting quantitative conversions and 100% selectivities (entry 1 and 4 in Table 1) at 100 °C, but only in the case of 4-ethenylpyridine the reaction occurred at room temperature with acceptable 40% conversion and 100 % selectivity after 12 hours (data non in table). To understand if there is an NPs size effect on the Heck reaction, some of the experiments (entries 1, 4-9) were carried out by employing lignosulfonate Pd NPs: in the presence of iodobenzene conversions remained quantitative with good selectivities, whereas in presence of bromobenzene slightly lower conversion were observed (44% vs 50 % of Kraft lignin NPs), maintaining a comparable selectivity in the cross-coupling product. We conclude that NPs sizes probably influence the rate of the reaction, but without a macroscopic effect on the reactivity. 3.3. Suzuki reaction Suzuki-Miyaura reactions involve cross-coupling of organoboronic acids with aryl halides to form biaryls [6,7,30]. An application worthy of note is the synthesis of felbinac, a non steroidal anti-inflammatory drug [31,32]. The new tendency of such important cross-coupling reaction addresses to the use of water media and of Pd NPs catalyst [33-35]. Our experiments were conducted in plain green conditions, i.e. water solution, mild temperature (70 °C), aerobic conditions, short reaction times (12 hours or less, when specified) and with a 450:1 aryl halide to catalyst molar ratio (Table 2). In a test reaction, involving iodobenzene, and without Pd NPs, no reactivity was observed; on the other hand, with Kraft lignin Pd NPs, reactivity was found to follow the order iodo- > bromo- > chloroderivatives, with iodo- and bromobenzene converted almost quantitatively at 70 °C, although the reactions with bromobenzene were not always highly selective (for example in entry 9.a of Table 2, only a 20% of cross-coupling product was obtained, vs a 90% of conversion). At room temperature the reactivity was relatively high in
the case of iodobenzenes, where only the aminohalide was recovered unreacted, likely because of the hydrophobicity of the substrate in alkaline media, which, together with the low temperature, makes difficult the contact between substrate and catalyst. Bromobenzenes were seldom converted and the relative yields of cross-coupling products were not particularly satisfactory, reaching the higher value (25%) in the case of entry 10.a (Table 2). The finding that, in some reactions, the homocoupling and the cross-coupling reaction product coincide (biphenyl; entries 1.a, 2.a, 7.a and 8.a in Table 2), makes difficult the interpretation of reaction results since we can’t evaluate the extent of the cross-coupling reaction pathway. For this reason, we performed some additional experiments in presence of a substituted phenylboronic acid (p-hydroxymethyl-phenylboronic acid; b in Table 2). The comparable product yields obtained in the experiments between iodo- and bromobenzene with both phenylboronic acids a and b (entries 1.b, 2.b, 3.b and 4.b) strongly suggest that the homocoupling reaction pathway is not active or, if present, it is of minor importance. Accordingly (entries 1.a and 2.a), conversions and product yields are both quantitative, while the potential formation of homocoupling reaction product should require two moles of aryl halide. The effect of the nature of the added base on the cross-coupling reaction was evaluated by keeping into consideration the reaction of iodobenzene and phenylboronic acid in the presence of a number of bases, i.e. NaOH, K2CO3, NaHCO3 and Et3N (20°C, 12 hours of reaction time): only NaOH and K2CO3 exhibited 100% conversion and selectivity; with NaHCO3, only a 65 % conversion was observed, while with Et3N no reaction occurred. Among NaOH and K2CO3 we chose the more handy potassium carbonate. Regarding the substituent in the aryl halide, hydroxyl groups speeded up noticeably the coupling reaction, at least in comparison with iodobenzene (entries 3.a and 4.a vs 1.a and 2.a). The presence of amino groups led only to a partial conversion with relatively low selectivity (entry 5a), likely to be attributed to the polymerisation of the amino derivatives (indeed, after 8 hours at 70 °C, an intense blue colour was always observed); at room temperature polymerisation did not occur, but unfortunately also the coupling reaction became very slow. In order to understand the importance of the electron density on the aromatic ring of the halide, we took into consideration the reactions with 4-iodophenol in the presence of NaHCO3 (where the hydroxyl group is certainly present in its protonated form): the conversion at 70 °C was always quantitative in very short time, despite the definitely lower solubility of the reagent (additional experiment, not showed in Table 2). Our conclusion is that the electronic density on the aromatic ring has only a marginal role in the success of the reaction.
We also tested the cross-coupling reaction of iodobenzene at higher halide to catalyst ratios (900:1, 1800:1 and 3600:1, in the presence of the same concentration used in the standard reactions carried out at the 450:1 ratio). Even the lowest amounts of Pd NPs were equally efficient in converting iodobenzene to biphenyl, although at longer reaction times the product was found to partially degrade to hydroxylated biphenyls, thus strongly indicating that the 450:1 ratio was the best choice to optimize reaction time, conversion and selectivity. Also for Suzuki reaction we investigated the possible size effect of NPs. We repeated the experiments with p-hydroxymethyl phenylboronic acid employing the bigger lignosulfonate Pd NPs (70°C) and we found that iodobenzene was quantitatively transformed into the corresponding substituted biphenyl, whereas bromobenzene was totally converted, although with a 63% yield and chlorobenzene very little converted (5%), with a product yield not higher than 3%. As for the Heck reaction, we conclude that the size of NPs, at least for the range of our Pd NPs (from 10 to 20 nm), was not decisive for the reaction course. 3.4. Other cross-coupling reactions To depict in more details the catalytic behaviour of Pd NPs, we tested two other popular crosscoupling reactions: Sonogashira and Stille reactions. We chose the smaller Kraft lignin Pd NPs since their behaviour and those of lignosulfonate Pd NPs were not dramatically different. The typical Sonogashira reaction, consisting in the coupling of terminal acetylenes with unsaturated halides catalyzed by Pd–Cu [36], provides a useful method for synthesizing conjugated acetylenic compounds [37]. In our procedure, the reaction was conducted totally in water at 50° C, without added phosphine or amine ligand. The phenylhalides used were iodo-, bromo-, and chlorobenzene and 2-bromothiophene; the terminal alkyne was always phenylacetylene (Table 3). Also the influence of the added base was tested, but only KOH worked efficiently. In the presence of CuI, the reaction led exclusively to the formation of alkyne dimer, which represents the main side-reaction, effectively competitive with the Sonogashira reaction [38]. However, if the reaction is conducted in the absence of CuI, the formation of a 30% of coupling product was observed at least for iodobenzene and 2-bromothiophene (chloro- and bromobenzene did not react at all). Stille reaction is a palladium catalyzed coupling of organotin compounds with aryl or benzylhalides [39]. Its relative insensibility to most functional groups makes the Stille coupling particularly attractive for the transformations of highly functionalized molecules of pharmaceutical interest, such as dynemicin A [40] and rapamycin [41,42]. We tested the coupling of iodo- and bromobenzene, iodophenol and bromoanisole with trichloro(phenyl)stannane in water solution and in presence of K2CO3 (12 h, 80° C; Table 4). The conversions of bromoderivatives were always
lower than those of iododerivatives. Moreover, by analyzing the reactions with substituted halidederivatives (entries 3 and 4), it was possible to evaluate the relative contribution of homocoupling side-reaction to the total conversion of aryl halide. Values not higher than 5% (iodobenzene) and 10 % (bromobenzene) were observed, which demonstrated that the relative yields in the cross-coupling products were 80-85% for iodobenzene and about 50% for the less reactive bromobenzene, likely because the rate of the homocoupling side-reaction is high enough to compete with the crosscoupling one. 4. Conclusions The synthesis of catalytically active NPs in the presence of lignins bears several important advantages: i) the experimental conditions are mild, without use of any organic solvent; ii) the procedure is easy and fast; iii) the widely available and cheap lignins were used, both as reducing and stabilizing agents, thus avoiding the addition of other expensive organics. Pd NPs exhibit spherical shapes, ranging 8-14 nm (Kraft lignin) or 16-20 nm (lignosulfonate), and a remarkable stability, with the UV-vis spectra not showing any significant changes after one month under aerobic conditions at room temperature. Also the reactivity in the reaction between iodobenzene and p-hydroxymethylphenyl boronic acid, tested with a one month aged Kraft lignin NPs, did not change, compared to the reaction performed with freshly synthesised NPs. The NPs display good catalytic activities toward Suzuki and Heck reactions; also Sonogashira and Stille reactions, although with lower conversions, occur again in water alone and under mild condition. We noted a reactivity depending upon the nature of the halogen present in the aromatic ring, with chloro-derivatives reacting only in some reactions and bromo- and iododerivatives in all the examined cases, with various degree of conversions (iodo-derivatives exhibit the highest reactivity). In term of green chemistry, it is important the re-use of the catalyst. We tested the catalytic activity of the Pd NPs used in the reaction between iodobenzene and p-hydroxymethylphenyl boronic acid at 70 °C, by simply removing by filtration the reaction product (p-hydroxymethyl biphenyl) and adding new aliquots of reagents to the reaction mixtures containing the catalyst: the measured conversion was higher than 90%, with a yield of 72% of cross-coupling product. By repeating again the above procedure, a 30% conversion and a 23% yield were observed, thus indicating that Pd NPs can be used at least a couple of times. The fact that water is an excellent solvent for the Pd NPs, but not for the reagents and products, allows an easy extraction/separation procedure from the reaction mixture. Regarding a possible contamination by Pd of the cross-coupling products, ICP-MS analyses of two representative (i.e.
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[39]
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[40]
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[41]
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Table 1: Heck reaction between an unsaturated derivative and aryl halides in presence of Kraft lignin Pd NPs in aqueous alkaline conditions (K2CO3); 12 h reaction. Entry
Aryl halide
Alkene
Coupling product
T (°C)
Aryl halide conv. (%)
Coup. prod. yieds (%)
100
100
100
I
1 I
2
OH
OH
100
90
30 [a]
OH
OH
60
25
3 [b]
OH
100
80
38 [c]
O
100
100
64 [d]
100
100
100
HO
100
100
100
H2N
100
70
50 [e]
HOOC
100
100
80 [f]
100
50
30 [g]
100
50
50
I
2’
OH
I
2”
large excess O
I
3
O
O
I
4
N
N I
5 HO I
6 H2N I
7 HOOC Br
8 Br
9
H3C O
H3C O
[a]
10% cinnamaldehyde, 60% diphenylacrylaldehyde;
[b]
biphenyl is the most abundant reaction product; the reaction was stopped after 6 hours;
[c]
about 20% of biphenyl + other oxidation products coming from cinnamyl alcohol + about 5 % of the isomer coming from the addition of phenyl group to the other vinylic carbon of the alkene;
[d]
36% cinnamyl acohol;
[e]
probably polymerisation of reaction product occurs;
[f]
biphenyl was also found;
[g]
biphenyl was also present coming from the radical reaction on the bromobenzene.
Table 2: Suzuki reaction between phenylboronic acid (a) or p-hydroxymethyl phenylboronic acid (b) and aryl halides in presence of Kraft lignin Pd NPs in aqueous alkaline conditions (K2CO3). B(OH)2
B(OH)2
HOH2C
a
Entry
b
Aryl halide
1.a
Coupling product
I
2.a 3.a
I
React. time (h)
T (°C)
Aryl halide conv. (%)
Coup. prod. yieds (%)
5
70
100
100
12
20
100
100
0.5
70
100
100
2
20
100
100
12
70
70 [a]
28
12
20
0
--
12
70
100
80
12
20
15
10
12
70
90
20
12
20
90
25
12
70
100
100
12
20
84
84
12
70
95
75
12
20
20
15
12
70
10
5
12
20
18
12
HO
HO
4.a 5.a
I H2N
H2 N
6.a 7.a
Br
8.a 9.a
Br H3C O
H3C O
10.a 1.b
I CH 2OH
2.b 3.b
Br CH2OH
4.b 5.b
Cl CH2OH
6.b [a]
4-Amino-iodobenzene is scarcely soluble in strongly alkaline water solution; in addition, at 70
°C, a partial polymerisation of both reagent and coupling product occurs
Table 3: Sonogashira reaction between phenylacetylene and aryl halides in presence of Kraft lignin Pd NPs in aqueous alkaline conditions (KOH): 4 h of reaction, 50 °C.
Entry
Aryl halide
Coupling product
Coup. prod. yieds (%)
1
I
30
30
2
Br
0
0 [a]
3
Cl
0
0 [a]
30
30
4 Br S
S
[a]
Aryl halide conv. (%)
the phenylacetilene dimer is the only reaction product.
Table 4: Stille reaction between aryl halides and trichloro(phenyl)stannane in water: 12 h reaction; 80°C SnCl3
Entry
Aryl halide
Coupling product
Aryl halide conv. (%)
Coup. prod. yieds (%)
1
I
45
43
2
Br
5
5
45
40 [a]
20
9 [b]
3
I OH
HO
4
Br O CH3
H3C O
[a]
5% of biphenyl
[b]
10 % of biphenyl
Figure 1: TEM image of Kraft lignin Pd NPs (top) and statistical distribution of NPs dimensions (bottom)
Figure 2: XRD pattern of Kraft lignin Pd NPs
Palladium nanoparticles, stabilised by lignin, as catalyst for crosscoupling reactions in water We describe the synthesis and characterization of novel palladium nanoparticles formed in the presence of lignin in green conditions. They exhibited a good catalytic efficiency in several crosscoupling reactions, namely Heck, Suzuki, Sonogashira and Stille reactions, all of them carried out in entirely aqueous media.
Graphical abstract Palladium nanoparticles, stabilised by lignin, as catalyst for cross-coupling reactions in water By Francesca Coccia, Lucia Tonucci, Nicola d’Alessandro,* Primiano D’Ambrosio and Mario Bressan
Highlights •
Pd nanoparticles (NPs) were synthesised in water media, 80 C, in air and with lignin as reducing agent
•
The NPs water solution was used directly as catalyst in a series of cross-coupling reactions
•
Pd NPs display high catalytic activities toward Suzuki and Heck reactions
•
Br and I derivatives react in all the examined cases, with various degree of conversions
•
The catalytic activity of the Pd NPs changes from 90% - first use - to 72 % - second use.
S0020-1693(12)00694-9 http://dx.doi.org/10.1016/j.ica.2012.12.035 ICA 15274
To appear in:
Inorganica Chimica Acta
Received Date: Revised Date: Accepted Date:
14 September 2012 19 December 2012 23 December 2012
Please cite this article as: F. Coccia, L. Tonucci, N. d’Alessandro, P. D’Ambrosio, M. Bressan, Palladium nanoparticles, stabilised by lignin, as catalyst for cross-coupling reactions in water, Inorganica Chimica Acta (2013), doi: http://dx.doi.org/10.1016/j.ica.2012.12.035
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.
Palladium nanoparticles, stabilised by lignin, as catalyst for crosscoupling reactions in water Francesca Cocciaa, Lucia Tonuccib, Nicola d’Alessandro c*, Primiano D’Ambrosioc and Mario Bressanc a
School of Advanced Studies in Science, University “G.d’Annunzio” of Chieti and Pescara, 65127 Pescara, Italy
b
Department of Philosophy, Human and Educational Science, University G.d’Annunzio of Chieti and Pescara, Via dei Vestini 31, I-66013 Chieti Scalo, Italy
c
Department of Engineering and Geology, University “G.d’Annunzio” of Chieti and Pescara,Viale Pindaro, 42, I-65127 Pescara, Italy
* Corresponding author; tel: xx39 0871 3555365; email: [email protected] Abstract Palladium nanoparticles of a definite shape (spherical) and dimension (8-14 and 16-20 nm) were prepared employing two water soluble lignin samples as both reducing and stabilising agent in definitely green experimental conditions, namely aqueous solution, aerobic conditions, moderate temperature, short times. The above nanoparticles were employed as catalyst for a series of carboncarbon coupling reactions carried out in water at mild conditions. Heck and Suzuki reactions were performed for several substrates, by changing the nature of halogen, the substituents at the aromatic ring, the bases employed and the temperature. Product yields were satisfactory and selectivities very good. Other two cross-coupling reactions, namely Sonogashira and Stille, were also tested: iodine derivatives showed always the best reactivity, while chlorine derivatives did not react.
Keywords: nanoparticles, cross-coupling, palladium, water media, lignin
1. Introduction Synthetic chemistry still represents an important tool to obtain derivatives of great importance for our life. Few synthetic routes can be performed also in absence of any solvents [1], whereas the largest part of organic synthetic pathways requires the presence of a solvent that, keeping into due consideration the twelve principles of “Green Chemistry” [2], should be non toxic, not expensive, and easily recyclable. In the past, chemists preferred the use of organic solvents for the necessary solubility of reagents and products, the latters often slightly or no polar at all. On the other hand, since nature dominantly prefers reactions in water media, e.g. all natural enzymatic reactions [3], the possibility to mimic nature using water as solvent in any synthetic pathway represents one of the main challenge of the chemists of the 21° century. Carbon-carbon bond construction is the basis of organic chemistry, and transition metals catalysts represent the most useful tools to obtain cross-coupling reactions in mild conditions and with high yields [4,5]. In this regard, it is important to notify that 2010 Nobel prize in Chemistry was awarded jointly to Richard F. Heck, Ei-ichi Negishi and Akira Suzuki "for palladiumcatalyzed cross couplings in organic synthesis". Palladium-catalyzed cross-coupling reactions of aryl halides for the formation of new carbon-carbon bonds have huge potential in fine organic synthesis, with particular emphasis on the pharmaceutical field [6-8]. The focus today is to make the experimental conditions more environmentally friendly, e.g. in water and aerated solutions, at moderate temperatures, and in the presence of catalysts in very small amounts. Ligand-free catalysts, like nanoparticles (NPs), can operate under conditions that are particularly green [9], by envisaging also to support such NPs on metal oxide, thus making possible an efficient re-use of catalyst without loss of activity [10,11]. We recently synthesized palladium and platinum NPs starting from the corresponding metal salts and lignin, a naturally abundant by-product from the paper industry [12], which, in our case, was used as both a stabilizing and a reducing agent [13]. Here, to synthesise Pd NPs, we used two water soluble, sulphur-containing, commercial lignins, namely lignosulfonates and Kraft lignins, both produced in huge quantities worldwide [14]. After full characterization, Pd NPs were tested as catalysts for a number of cross-coupling reactions; among them, for instance, the Heck reaction between 4-iodophenol and styrene which leads to 4-hydroxystilbene, a powerful tyrosinase inhibitor [15], with 100% yield in water solution at 100 °C. 2. Experimental 2.1. Materials
Two lignin samples were used. The Kraft lignin was purchased from Sigma-Aldrich while the lignosulfonate sample, as ammonium derivative, was a courtesy of Burgo Group S.p.A. (Tolmezzo, Italy). The lignosulfonate was obtained by cooking red pine in a calcium hydrogensulphite solution and it is highly soluble in water. Palladium chloride (PdCl2) was purchased from Strem Chemicals. The remaining reagents used in the catalytic experiments were purchased from Sigma-Aldrich. 2.2. Instruments Nuclear magnetic resonance (NMR) spectra were obtained using a Bruker Avance 300 MHz spectrometer equipped with a high resolution multinuclear probe. The 1H NMR spectra of the water solutions were run in an NMR tube (5 mm) that contained a closed co-axial capillary tube filled with a 30 mM 3-trimethylsilyl-2,2’,3,3’- tetradeutero propionic acid (sodium salt). Free induction decays (FIDs) were acquired at 22°C using a pulse sequence (Bruker-made; zgcppr) that suppresses the water signal at 4.7 ppm. 1H NMR spectra in CDCl3 solution were acquired using TMS as reference, and the standard pulse sequence (zg) was used. For the 13C NMR spectra, a proton decoupling pulse sequence (zgdc) was used. UV-vis instrument was a Jenway 6505 spectrophotometer; the spectral window range was 200 600 nm. TEM measurements were performed under vacuum by an EM 109 Zeiss microscope equipped with built-in electromagnetic objective lenses and camera (Oberkochen, Germany). XRD analyses were performed on a Miniflex II Rigaku automated power X-ray diffractometer system (Cu Ka radiation, 45 kV, 100 mA) (RINT 2500, Japan). Diffraction data were recorded using continuous scanning at 3 deg/min, step 0.010. Fourier transform infrared spectra (FT-IR) were obtained on an FT-IR spectrophotometer (Perkin Elmer 1600). The gas chromatography–mass spectroscopy (GC-MS) apparatus comprised a Thermo Scientific Focus series gas-chromatograph coupled to an ISQ mass-selective detector equipped with a split-splitless injection system (injections made in split mode) and an HP-5 MS (cross-linked 5% phenyl methyl siloxane) capillary column (30 m length, 0.25 mm diameter, 0.1 µm film thickness) using helium as carrier gas at constant pressure of 30 kPa. The acquisition parameters were: source at 250 °C, transfer line at 250 °C, 3 min of delay acquisition time at the beginning of the analysis, mass range 33 amu to 350 amu, injector temperature 250 °C, initial temperature of the analyses 60 °C (1 min), then 10 °C/min up to 250 °C (kept for 6 min), for a total acquisition time of 26 min. The sample injected was 1 µL.
A 7500A ICP quadrupolar mass spectrometer (Agilent Technologies) fitted with an ASX-510 autosampler (CETAC) was used to dose residual Pd inside the reaction products. The sample was previously digested by a microwave apparatus using nitric acid as oxidant; the eluate was then analyzed by ICP instrument comparing the result with a known concentration Pd sample. 2.3. Synthesis and characterisation of Pd NPs Lignin sample (0.06 g) was placed in 10 mL of water, then 0.01 g of PdCl2 (5.64 x 10-3 M) was added. The solution was heated at 80° C for 3 h in aerated conditions. Formation of Pd NPs was evidenced by the change of the colour of the solution (from brown to black). The samples for the UV-vis measurements were prepared by diluting 40 µL of NPs solution by addition of 140 µL of ultrapure water, then the resulting solutions were analysed by 0.1 cm quartz cuvettes (Hellma). The samples for TEM analyses were prepared by placing 5 µL of a diluted solution (ten times) of Pd NPs onto 3 mm, 300 mesh, formvar/carbon nickel grids (Agar Scientific Ltd) waiting the necessary time (24 h) for the evaporation of the solvent at room temperature. The samples for XRD analysis were prepared by evaporation of solvent of the entire NPs solution and the resulting solid powder was placed on the glass plate of the instrument. The sample for IR analysis was made on 1% (w/w) NPs power in KBr sample and the spectra were recorded between 4000 to 400 cm-1. The reaction solution of Pd NPs was used directly as catalyst in all our cross-coupling reactions. 2.4. Heck reaction In a close 25 mL flask, alkene (0.5 mmol), aryl halides (0.5 mmol), K2CO3 (1.75 mmol) and Pd NPs (0.2 mL of above NPs solution; 450/1 molar ratio reagent to catalyst) were added in 5 mL water and stirred at 100 °C for 12 h. 2.5. Suzuki reaction In a close 25 mL flask, phenylboronic acid (0.75 mmol), aryl halides (0.5 mmol), K2CO3 (1.75 mmol) and Pd NPs (0.2 mL of above NPs solution; 450/1 molar ratio reagent to catalyst) were added in 5 mL water and stirred at 70 °C for 12 h. 2.6. Sonogashira and Stille reactions Sonogashira reaction: in a close 25 mL flask, aryl alkyne (0.5 mmol), aryl halides (0.5 mmol), KOH (2 mmol) and Pd NPs (0.2 mL of above NPs solution; 450/1 molar ratio reagent to catalyst)
were added in 5 mL water and stirred at 50 °C for 4 h. In experiments in presence of copper, CuI was added at 5% of molar ratio with respect to aryl halide. Stille reaction: in a close 25 mL flask, trichloro(phenyl)stannane (0.75 mmol), aryl halides (0.5 mmol), K2CO3 (1.75 mmol) and Pd NPs (0.2 mL of above NPs solution; 450/1 molar ratio reagent to catalyst) were added in 5 mL water and stirred at 80 °C for 12 h. 2.7. Work up of cross-coupling reaction mixture After cooling to room temperature the reaction mixtures, 10 mL of brine was added and then extracted thrice with diethyl ether (15 mL x 3). The organic phase was dried over Na2SO4, filtered and concentrated to a small volume; the residue was firstly analyzed by NMR (CDCl3) and then brought to a known volume (10 mL) for the quantitative spectroscopic characterization (by GC-MS, see above for instrumental conditions). 3. Results and Discussion 3.1 Pd NPs characterisation Pd II ions were reduced to their zero-valent states in water solution at 80 °C, and under aerobic conditions in the presence of the two above-mentioned water-soluble lignins. The stable Pd NPs obtained were fully characterised by UV-vis, TEM and XRD, and their behaviours as catalysts were tested for several cross-coupling reactions i.e. Heck, Suzuki, Sonogashira and Stille. The reduction of the metal ions was followed by UV-vis, where the weak diagnostic absorbances in the visible region were used to verify the Pd NPs formation [16,17]. 1
H NMR was employed to investigate the changes in the lignin structures upon the reduction of
metal. Small amounts of acetic and formic acid and of methanol were detected in the reaction mixtures, a clear indication of partial oxidation / degradation of the polymer skeleton. On the other hand, IR spectra of lignin residues after NPs formation showed that the bands attributable to methoxyl C-O (1000-1250 cm-1) and to aromatic ring vibrations (1430 and 1510 cm-1) remained practically unchanged, while a very weak shoulder appeared at 1730 cm-1, attributable to unconjugated ketone, ester or carboxylic groups coming from the modified polymer or short chain molecules detached from the lignin skeleton. Even if in both cases we noticed some little change, we conclude that the main structure of lignins was not significantly modified. Pd NPs could be directly observed under transmission electron microscopy (TEM) as particles of spherical shape with scarce tendency to aggregate into cluster (Fig.1). Sizes, which are only slightly influenced by the amount of organic polymer used, definitely depend upon the nature of
lignins used, lignosulfonate NPs being bigger (16 – 20 nm; see ref. [13]) than Kraft lignin NPs (75% of particles having a diameter between 8 and 14 nm). The XRD analysis of NPs dried powders (Fig. 2) indicated a crystalline structure with peaks at 39.9°, 46.3°, 67.4°, 82.5° and 86.9°, values found also by other authors in Pd NPs synthesised in the presence of a variety of stabilising agents [18,19]. Peaks were slightly thinner in the case of Kraft lignin NPs, in agreement with their smaller size suggested by the TEM data. 3.2. Heck reaction The vinylation of aryl halides, mainly as iodine derivatives, is commonly called Heck reaction [20]. Palladium catalyst can be used, either in complexed or ligand-free forms. After a few years from the introduction of Heck reaction, the same discovered that the complexation of palladium by phosphine ligands increases the reactivity of aryl halides, making possible also synthetic reactions with the less expensive bromo derivatives. Another step forwards was reached when Jeffery [21] discovered the effect of quaternary ammonium salt on the reactivity of ligand-free palladium catalysts, likely related to the formation and stabilization of catalytically active palladium NPs [22]. However, the experimental conditions used are not always particularly green, since organic solvents and high temperatures are often necessary [23,24]. Our experiments were conducted at 100°C and in entirely aqueous media, with a 450:1 aryl halide to catalyst molar ratio. The commonly accepted reaction mechanism involves the critical presence of a base to facilitate the β-hydride elimination step and to speed up the regeneration of Pd0 [25,26]. Previous studies demonstrated that several bases could be successfully used, among them alkali metal carbonates (or bicarbonates), carboxylates (formates or acetates) and amines [27,28]; in the absence of a base, the presence of a quaternary ammonium salt was often required, that contributes to self-generate trialkylamines [29]. In our case, since our main challenge was to operate in green conditions, we considered only the use of alkali, carbonates and bicarbonates, and, since in the presence of NaHCO3 the reaction between iodobenzene and styrene was too slow, while with NaOH and K2CO3 it proceeded smoothly at comparable rates, we chose K2CO3 for all reactions reported in Table 1. In the presence of Kraft lignin Pd NPs, iodine derivatives reacted more efficiently than the bromine ones, while the chlorine derivatives (chlorobenzene, 4-chlorophenol and 4chloronitrobenzene; not shown in table) did not react at all. The typical reaction between iodobenzene and styrene led to a quantitative conversion, with 100% of selectivity in the coupling product (which often can be observed as a solid floating on the surface of the reaction mixture). The same reaction, conducted without Pd NPs, was completely unsuccessful. By changing the aromatic
substrate with aliphatic unsaturated derivatives, a very good reactivity was again observed: however selectivities markedly decreased, due to some secondary reactions on the reaction product, namely the oxidation of cinnamyl alcohol to cinnamaldehyde (entry 2 in Table 1) and the alkaline hydrolysis of ester derivative (entry 3 in Table 1). In the case of allyl alcohol, the reaction must be carried out in presence of large excesses of allyl alcohol, in order to avoid the formation of the diphenyl allyl alcohol (and its aldehydic counterpart) and therefore to obtain a satisfactory selectivity in the coupling product. With the aim to optimise the selectivity in the formation of cinnamyl alcohol, we performed the coupling reaction at lower temperature and for a more limited time (60 °C; 6 h): however, conversions and selectivities were noticeably reduced (a large amount of biphenyl was formed), clearly indicating that at lower temperature the coupling reaction became extremely slow. The effect of temperature was also tested for some of the reactions exhibiting quantitative conversions and 100% selectivities (entry 1 and 4 in Table 1) at 100 °C, but only in the case of 4-ethenylpyridine the reaction occurred at room temperature with acceptable 40% conversion and 100 % selectivity after 12 hours (data non in table). To understand if there is an NPs size effect on the Heck reaction, some of the experiments (entries 1, 4-9) were carried out by employing lignosulfonate Pd NPs: in the presence of iodobenzene conversions remained quantitative with good selectivities, whereas in presence of bromobenzene slightly lower conversion were observed (44% vs 50 % of Kraft lignin NPs), maintaining a comparable selectivity in the cross-coupling product. We conclude that NPs sizes probably influence the rate of the reaction, but without a macroscopic effect on the reactivity. 3.3. Suzuki reaction Suzuki-Miyaura reactions involve cross-coupling of organoboronic acids with aryl halides to form biaryls [6,7,30]. An application worthy of note is the synthesis of felbinac, a non steroidal anti-inflammatory drug [31,32]. The new tendency of such important cross-coupling reaction addresses to the use of water media and of Pd NPs catalyst [33-35]. Our experiments were conducted in plain green conditions, i.e. water solution, mild temperature (70 °C), aerobic conditions, short reaction times (12 hours or less, when specified) and with a 450:1 aryl halide to catalyst molar ratio (Table 2). In a test reaction, involving iodobenzene, and without Pd NPs, no reactivity was observed; on the other hand, with Kraft lignin Pd NPs, reactivity was found to follow the order iodo- > bromo- > chloroderivatives, with iodo- and bromobenzene converted almost quantitatively at 70 °C, although the reactions with bromobenzene were not always highly selective (for example in entry 9.a of Table 2, only a 20% of cross-coupling product was obtained, vs a 90% of conversion). At room temperature the reactivity was relatively high in
the case of iodobenzenes, where only the aminohalide was recovered unreacted, likely because of the hydrophobicity of the substrate in alkaline media, which, together with the low temperature, makes difficult the contact between substrate and catalyst. Bromobenzenes were seldom converted and the relative yields of cross-coupling products were not particularly satisfactory, reaching the higher value (25%) in the case of entry 10.a (Table 2). The finding that, in some reactions, the homocoupling and the cross-coupling reaction product coincide (biphenyl; entries 1.a, 2.a, 7.a and 8.a in Table 2), makes difficult the interpretation of reaction results since we can’t evaluate the extent of the cross-coupling reaction pathway. For this reason, we performed some additional experiments in presence of a substituted phenylboronic acid (p-hydroxymethyl-phenylboronic acid; b in Table 2). The comparable product yields obtained in the experiments between iodo- and bromobenzene with both phenylboronic acids a and b (entries 1.b, 2.b, 3.b and 4.b) strongly suggest that the homocoupling reaction pathway is not active or, if present, it is of minor importance. Accordingly (entries 1.a and 2.a), conversions and product yields are both quantitative, while the potential formation of homocoupling reaction product should require two moles of aryl halide. The effect of the nature of the added base on the cross-coupling reaction was evaluated by keeping into consideration the reaction of iodobenzene and phenylboronic acid in the presence of a number of bases, i.e. NaOH, K2CO3, NaHCO3 and Et3N (20°C, 12 hours of reaction time): only NaOH and K2CO3 exhibited 100% conversion and selectivity; with NaHCO3, only a 65 % conversion was observed, while with Et3N no reaction occurred. Among NaOH and K2CO3 we chose the more handy potassium carbonate. Regarding the substituent in the aryl halide, hydroxyl groups speeded up noticeably the coupling reaction, at least in comparison with iodobenzene (entries 3.a and 4.a vs 1.a and 2.a). The presence of amino groups led only to a partial conversion with relatively low selectivity (entry 5a), likely to be attributed to the polymerisation of the amino derivatives (indeed, after 8 hours at 70 °C, an intense blue colour was always observed); at room temperature polymerisation did not occur, but unfortunately also the coupling reaction became very slow. In order to understand the importance of the electron density on the aromatic ring of the halide, we took into consideration the reactions with 4-iodophenol in the presence of NaHCO3 (where the hydroxyl group is certainly present in its protonated form): the conversion at 70 °C was always quantitative in very short time, despite the definitely lower solubility of the reagent (additional experiment, not showed in Table 2). Our conclusion is that the electronic density on the aromatic ring has only a marginal role in the success of the reaction.
We also tested the cross-coupling reaction of iodobenzene at higher halide to catalyst ratios (900:1, 1800:1 and 3600:1, in the presence of the same concentration used in the standard reactions carried out at the 450:1 ratio). Even the lowest amounts of Pd NPs were equally efficient in converting iodobenzene to biphenyl, although at longer reaction times the product was found to partially degrade to hydroxylated biphenyls, thus strongly indicating that the 450:1 ratio was the best choice to optimize reaction time, conversion and selectivity. Also for Suzuki reaction we investigated the possible size effect of NPs. We repeated the experiments with p-hydroxymethyl phenylboronic acid employing the bigger lignosulfonate Pd NPs (70°C) and we found that iodobenzene was quantitatively transformed into the corresponding substituted biphenyl, whereas bromobenzene was totally converted, although with a 63% yield and chlorobenzene very little converted (5%), with a product yield not higher than 3%. As for the Heck reaction, we conclude that the size of NPs, at least for the range of our Pd NPs (from 10 to 20 nm), was not decisive for the reaction course. 3.4. Other cross-coupling reactions To depict in more details the catalytic behaviour of Pd NPs, we tested two other popular crosscoupling reactions: Sonogashira and Stille reactions. We chose the smaller Kraft lignin Pd NPs since their behaviour and those of lignosulfonate Pd NPs were not dramatically different. The typical Sonogashira reaction, consisting in the coupling of terminal acetylenes with unsaturated halides catalyzed by Pd–Cu [36], provides a useful method for synthesizing conjugated acetylenic compounds [37]. In our procedure, the reaction was conducted totally in water at 50° C, without added phosphine or amine ligand. The phenylhalides used were iodo-, bromo-, and chlorobenzene and 2-bromothiophene; the terminal alkyne was always phenylacetylene (Table 3). Also the influence of the added base was tested, but only KOH worked efficiently. In the presence of CuI, the reaction led exclusively to the formation of alkyne dimer, which represents the main side-reaction, effectively competitive with the Sonogashira reaction [38]. However, if the reaction is conducted in the absence of CuI, the formation of a 30% of coupling product was observed at least for iodobenzene and 2-bromothiophene (chloro- and bromobenzene did not react at all). Stille reaction is a palladium catalyzed coupling of organotin compounds with aryl or benzylhalides [39]. Its relative insensibility to most functional groups makes the Stille coupling particularly attractive for the transformations of highly functionalized molecules of pharmaceutical interest, such as dynemicin A [40] and rapamycin [41,42]. We tested the coupling of iodo- and bromobenzene, iodophenol and bromoanisole with trichloro(phenyl)stannane in water solution and in presence of K2CO3 (12 h, 80° C; Table 4). The conversions of bromoderivatives were always
lower than those of iododerivatives. Moreover, by analyzing the reactions with substituted halidederivatives (entries 3 and 4), it was possible to evaluate the relative contribution of homocoupling side-reaction to the total conversion of aryl halide. Values not higher than 5% (iodobenzene) and 10 % (bromobenzene) were observed, which demonstrated that the relative yields in the cross-coupling products were 80-85% for iodobenzene and about 50% for the less reactive bromobenzene, likely because the rate of the homocoupling side-reaction is high enough to compete with the crosscoupling one. 4. Conclusions The synthesis of catalytically active NPs in the presence of lignins bears several important advantages: i) the experimental conditions are mild, without use of any organic solvent; ii) the procedure is easy and fast; iii) the widely available and cheap lignins were used, both as reducing and stabilizing agents, thus avoiding the addition of other expensive organics. Pd NPs exhibit spherical shapes, ranging 8-14 nm (Kraft lignin) or 16-20 nm (lignosulfonate), and a remarkable stability, with the UV-vis spectra not showing any significant changes after one month under aerobic conditions at room temperature. Also the reactivity in the reaction between iodobenzene and p-hydroxymethylphenyl boronic acid, tested with a one month aged Kraft lignin NPs, did not change, compared to the reaction performed with freshly synthesised NPs. The NPs display good catalytic activities toward Suzuki and Heck reactions; also Sonogashira and Stille reactions, although with lower conversions, occur again in water alone and under mild condition. We noted a reactivity depending upon the nature of the halogen present in the aromatic ring, with chloro-derivatives reacting only in some reactions and bromo- and iododerivatives in all the examined cases, with various degree of conversions (iodo-derivatives exhibit the highest reactivity). In term of green chemistry, it is important the re-use of the catalyst. We tested the catalytic activity of the Pd NPs used in the reaction between iodobenzene and p-hydroxymethylphenyl boronic acid at 70 °C, by simply removing by filtration the reaction product (p-hydroxymethyl biphenyl) and adding new aliquots of reagents to the reaction mixtures containing the catalyst: the measured conversion was higher than 90%, with a yield of 72% of cross-coupling product. By repeating again the above procedure, a 30% conversion and a 23% yield were observed, thus indicating that Pd NPs can be used at least a couple of times. The fact that water is an excellent solvent for the Pd NPs, but not for the reagents and products, allows an easy extraction/separation procedure from the reaction mixture. Regarding a possible contamination by Pd of the cross-coupling products, ICP-MS analyses of two representative (i.e.
with quantitative conversions) raw products of Heck and Suzuki reactions evidenced a Pd content always lower than 0.5%, referred to the initial amount of Pd used. Although the yields of reaction products are not always quantitative, we believe that in the future an optimization can be done by addition of some reaction mixture modifier (surfactants, cosolvents, etc.). Considering the green experimental conditions used, the selective formation of the desired reaction product, the short reaction times and the limited amounts of catalyst employed, we conclude that some of the reactions reported in the present paper could be effectively used for preparative purpose. 5. Acknowledgments We thank Dott. Antonio Baliva, IRSPS of International Research School of Planetary Sciences, Univ. “G.d'Annunzio“, V.le Pindaro, 42, 65127 Pescara, Italy, for performing the XRD analyses and Mr Domenico Bosco, Department of Biomorphological Science, Molecular Genetics Institute, CNR, Via dei Vestini, I-66013 Chieti Scalo, Italy, for performing the TEM analyses. We are grateful to “Consorzio di Ricerca per l’Innovazione Tecnologica, la Qualità e la Sicurezza degli Alimenti S.C.R.L.” (CIPE fundings 20.12.04; DM 28497) for financial support. References [1]
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Table 1: Heck reaction between an unsaturated derivative and aryl halides in presence of Kraft lignin Pd NPs in aqueous alkaline conditions (K2CO3); 12 h reaction. Entry
Aryl halide
Alkene
Coupling product
T (°C)
Aryl halide conv. (%)
Coup. prod. yieds (%)
100
100
100
I
1 I
2
OH
OH
100
90
30 [a]
OH
OH
60
25
3 [b]
OH
100
80
38 [c]
O
100
100
64 [d]
100
100
100
HO
100
100
100
H2N
100
70
50 [e]
HOOC
100
100
80 [f]
100
50
30 [g]
100
50
50
I
2’
OH
I
2”
large excess O
I
3
O
O
I
4
N
N I
5 HO I
6 H2N I
7 HOOC Br
8 Br
9
H3C O
H3C O
[a]
10% cinnamaldehyde, 60% diphenylacrylaldehyde;
[b]
biphenyl is the most abundant reaction product; the reaction was stopped after 6 hours;
[c]
about 20% of biphenyl + other oxidation products coming from cinnamyl alcohol + about 5 % of the isomer coming from the addition of phenyl group to the other vinylic carbon of the alkene;
[d]
36% cinnamyl acohol;
[e]
probably polymerisation of reaction product occurs;
[f]
biphenyl was also found;
[g]
biphenyl was also present coming from the radical reaction on the bromobenzene.
Table 2: Suzuki reaction between phenylboronic acid (a) or p-hydroxymethyl phenylboronic acid (b) and aryl halides in presence of Kraft lignin Pd NPs in aqueous alkaline conditions (K2CO3). B(OH)2
B(OH)2
HOH2C
a
Entry
b
Aryl halide
1.a
Coupling product
I
2.a 3.a
I
React. time (h)
T (°C)
Aryl halide conv. (%)
Coup. prod. yieds (%)
5
70
100
100
12
20
100
100
0.5
70
100
100
2
20
100
100
12
70
70 [a]
28
12
20
0
--
12
70
100
80
12
20
15
10
12
70
90
20
12
20
90
25
12
70
100
100
12
20
84
84
12
70
95
75
12
20
20
15
12
70
10
5
12
20
18
12
HO
HO
4.a 5.a
I H2N
H2 N
6.a 7.a
Br
8.a 9.a
Br H3C O
H3C O
10.a 1.b
I CH 2OH
2.b 3.b
Br CH2OH
4.b 5.b
Cl CH2OH
6.b [a]
4-Amino-iodobenzene is scarcely soluble in strongly alkaline water solution; in addition, at 70
°C, a partial polymerisation of both reagent and coupling product occurs
Table 3: Sonogashira reaction between phenylacetylene and aryl halides in presence of Kraft lignin Pd NPs in aqueous alkaline conditions (KOH): 4 h of reaction, 50 °C.
Entry
Aryl halide
Coupling product
Coup. prod. yieds (%)
1
I
30
30
2
Br
0
0 [a]
3
Cl
0
0 [a]
30
30
4 Br S
S
[a]
Aryl halide conv. (%)
the phenylacetilene dimer is the only reaction product.
Table 4: Stille reaction between aryl halides and trichloro(phenyl)stannane in water: 12 h reaction; 80°C SnCl3
Entry
Aryl halide
Coupling product
Aryl halide conv. (%)
Coup. prod. yieds (%)
1
I
45
43
2
Br
5
5
45
40 [a]
20
9 [b]
3
I OH
HO
4
Br O CH3
H3C O
[a]
5% of biphenyl
[b]
10 % of biphenyl
Figure 1: TEM image of Kraft lignin Pd NPs (top) and statistical distribution of NPs dimensions (bottom)
Figure 2: XRD pattern of Kraft lignin Pd NPs
Palladium nanoparticles, stabilised by lignin, as catalyst for crosscoupling reactions in water We describe the synthesis and characterization of novel palladium nanoparticles formed in the presence of lignin in green conditions. They exhibited a good catalytic efficiency in several crosscoupling reactions, namely Heck, Suzuki, Sonogashira and Stille reactions, all of them carried out in entirely aqueous media.
Graphical abstract Palladium nanoparticles, stabilised by lignin, as catalyst for cross-coupling reactions in water By Francesca Coccia, Lucia Tonucci, Nicola d’Alessandro,* Primiano D’Ambrosio and Mario Bressan
Highlights •
Pd nanoparticles (NPs) were synthesised in water media, 80 C, in air and with lignin as reducing agent
•
The NPs water solution was used directly as catalyst in a series of cross-coupling reactions
•
Pd NPs display high catalytic activities toward Suzuki and Heck reactions
•
Br and I derivatives react in all the examined cases, with various degree of conversions
•
The catalytic activity of the Pd NPs changes from 90% - first use - to 72 % - second use.