Nitrile hydration to amide in water: Palladium-based nanoparticles vs molecular catalyst

Article abstract of DOI:10.1016/j.molcata.2015.09.003

The catalytic performance of small Pd-nanoparticles (NPs) (2.0 nm), partially covered by chemisorbed oxygen atoms, and of Pd-acetate, both stabilized by 2,2′-bipyridine-end functionalized poly(ethyleneglycol) monomethylether was compared in the selective hydration of nitriles to amide in water under mild reaction conditions (353 K). Regardless of the nitrile substrate employed, the Pd-NP-based catalyst showed much higher normalized TON-values (i.e. refereeing to the amount of surface Pd atoms) compared to the Pd(II) macrocomplex, as far as the first catalytic run was considered. Deactivation of the Pd-NP-based catalyst was significant due to the formation of a hydroxide-water layer on the NPs' surface.

Full text of DOI:10.1016/j.molcata.2015.09.003

Accepted Manuscript
Title: Nitrile hydration to amide in water: Palladium-based
nanoparticles versus molecular catalyst
Author: W. Oberhauser Mattia Bartoli Giorgio Petrucci
Damiano Bandelli Marco Frediani Laura Capozzoli Cinzia
Cepek Sunil Bhardwaj Luca Rosi
PII:
S1381-1169(15)30078-9
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2015.09.003
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7-8-2015
1-9-2015
4-9-2015
Please cite this article as: W.Oberhauser, Mattia Bartoli, Giorgio Petrucci,
Damiano Bandelli, Marco Frediani, Laura Capozzoli, Cinzia Cepek, Sunil
Bhardwaj, Luca Rosi, Nitrile hydration to amide in water: Palladium-based
nanoparticles versus molecular catalyst, Journal of Molecular Catalysis A: Chemical
http://dx.doi.org/10.1016/j.molcata.2015.09.003
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Nitrile hydration to amide in water: Palladium-based nanoparticles
versus molecular catalyst
W. Oberhausera,*, Mattia Bartolib, Giorgio Petruccib, Damiano Bandellib, Marco Fredianib, Laura
Capozzolic, Cinzia Cepekd, Sunil Bhardwajd, Luca Rosib
a
Istituto di Chimica dei Composti Organometallici (CNR-ICCOM), Via Madonna del Piano 10,
50019 Sesto Fiorentino, Italy
b Dipartimento di Chimica, Università Degli Studi di Firenze, Via della Lastruccia 13, 50019 Sesto
Fiorentino, Italy
c
Istituto di Fisica Applicata Nello Carrara CNR, Via Madonna del Piano 10, 50019 Sesto
Fiorentino, Italy
d IOM-CNR Laboratorio TASC, Area Science Park, s.s. 14 km 163.5, Basovizza, Trieste, Italy
Corresponding author. Fax: +39 055 5225203. E-mail address: werner.oberhauser@iccom.cnr.it
1

Graphical abstract
2

Highlights
 -Selective nitrile hydration to amide in water by Pd-based catalysts.
 -Small Pd-nanoparticles (NPs) stabilized by end-functionalized poly(ethyleneglycol).
 -Higher nitrile hydration activity of Pd-NPs compared to Pd(II) macrocomplexes.
 -Deactivation of Pd-NPs by formation of a surface hydroxide layer.
ABSTRACT
The catalytic performance of small Pd-nanoparticles (NPs) (2.0 nm), partially covered by chemi-
sorbed oxygen atoms, and of Pd-acetate, both stabilized by 2,2’-bipyridine-end functionalized
poly(ethyleneglycol) monomethylether was compared in the selective hydration of nitriles to amide
in water under mild reaction conditions (353 K). Regardless of the nitrile substrate employed, the
Pd-NP-based catalyst showed much higher normalized TON-values (i.e. refereeing to the amount of
surface Pd atoms) compared to the Pd(II) macrocomplex, as far as the first catalytic run was
considered. Deactivation of the Pd-NP-based catalyst was significant due to the formation of a
hydroxide-water layer on the NPs’ surface.
Keywords: poly(ethyleneglycol); nitriles; amides; palladium; nanoparticles
3

1. Introduction
Amide bonds are fundamental for the composition of biologically active systems, since they are
the key link between amino acids in proteins. Moreover many marketed drug molecules contain
amide bonds [1-2], for instance Atorvastatin [3], a top selling drug worldwide which blocks the
production of cholesterol or Diltiazem a calcium channel blocker used for treatment of angina and
hypertension [4]. The majority of amide bond syntheses involve the use of stoichiometric amounts
of coupling reagents [5], making this approach expensive and not sustainable from an
environmental point of view. Hence atom-efficient catalytic amide bond forming reactions are
highly desired [6]. Four different types of metal-catalyzed primary amide synthesis procedures of
relevance have been described, namely: (i) the dehydrogenative coupling of primary alcohols with
ammonia in water [7-9]; (ii) the primary amide synthesis from aldoximes or aldehydes [10-11]; (iii)
the palladium-catalyzed aminocarbonylation of halide compounds either in the presence of
ammonia [12] or formamide [13] and (iv) the metal catalyzed hydration of nitriles [14] in the
homogeneous [15-16] and heterogeneous phases [17-24], with [25] and without the presence of
metal nanoparticles (NPs) [26-28]. Excellent homogenous catalysts for this latter reaction were
designed based on the concept of bifunctional catalysis, where the metal centre acts as a Lewis acid,
activating the nitrile functional group and the ligand as Brønsted base, providing the nucleophilic
hydroxide group which attacks the metal-coordinated nitrile group [16,29-31]. This latter catalytic
concept has been also applied to heterogeneously-catalyzed nitrile hydration reactions, where the
nitrile functional group is activated by the surface atoms of metal NPs and chemisorbed oxygen
atoms function as Brønsted base [32-34]. Indeed, it has been found that the percentage of the NPs’
oxygen atom coverage is a key parameter for the observed catalytic activity [17-18].
Herein we compare the catalytic performance of small Pd-NPs with that of Pd(OAc)2 (OAc =
acetate) in the hydration of nitriles to amide in water. In order to solubilize both catalysts in the
reaction medium, we stabilized both Pd-based catalysts with 2,2’-bipyridine end-functionalized
4

poly(ethyleneglycol) (PEG) monomethylether. PEG is an amphiphatic polymer and functions itself
as a unique solvent [35-36]. The high water solubility of PEG combined with its insolubility in
diethyl ether and hexane was exploited to separate the organic reaction compounds from catalyst.
2. Results and Discussion
2.1. Synthesis and characterization of catalysts
The reaction of Mesityl-PEG-OMe [37] (i.e. the mesityl functional group is an ideal leaving
group for nucleophilic substitution reactions) with 4’-methyl-(2,2’-bipyridine)-4-yl-methanol in the
presence of NaH and anhydrous DMF gave after work-up the 2,2’-bipyridine-end-functionalized
macroligand BiPy-PEG-OMe (L) as off-white powder in 75% yield (Scheme 1). The methoxy-
capped PEG gives not undesired side products during the mesitylation reaction step, whereas PEG
bearing two terminal OH-groups is prone to inter- and intramolecular nucleophilic substitution
reactions in the course of the latter reaction.
The successful binding of 4’-methyl-(2,2’-bipyridine)-4-yl to PEG through an ether functional
group was proved by 1H NMR and UV-vis spectroscopy conducted in water. The corresponding 1H
NMR spectrum showed the presence of signals assigned to the aromatic part of the 2,2’-bipyridine
ligand (Figure 1, trace a). Accordingly, the UV-vis spectrum of L showed the absorption at 282.5
nm and an absorption shoulder at 239.4 nm, while PEG does not show any absorption in this region
(Fig. 2). The reaction of L with one molequivalent of Pd(OAc)2 (OAc = acetate) in CH2Cl2 at room
temperature gave a brownish solution from which the macrocomplex [Pd(OAc)2L] (1) (Scheme 1)
l
was precipitated as brown solid with 72% yield. The H NMR spectrum (D2O) of Pd(OAc)2
coordinated to the 2,2’-bipyridine unit of the macroligand showed the expected coordination shift of
1
the 2,2’-bipyridine unit (Fig. 1, trace b vs a). In addition the presence of two H NMR singlets
centered at 1.84 and 1.97 ppm confirmed the presence of acetate hydrogen atoms and the lacking
symmetry of L. The coordination of Pd(OAc)2 to L caused also a shift of the bipyridine UV-vis
5

absorption bands to higher wavelength. Hence absorption maxima at 311, 302 (shoulder), 247.5 nm
for 1 have been observed (Fig. 2).
The reaction of a CH2Cl2 solution of 1 with hydrogen (15 bar) at room temperature for 12 h gave
a black solution, which upon solvent evaporation and successive washing of the solid obtained with
diethyl ether (2 × 5.0 mL) gave the L-stabilized Pd-NPs (2)as dark brown solid with 93% yield. An
1H NMR spectrum of the latter solid, acquired in D2O, showed a clear shift of the 1H NMR signals,
assigned to the aromatic 2,2’-bipyridine hydrogen atoms, compared to that of 1 and L (Fig. 1, trace
c vs b and a), indicating interactions of the nitrogen atoms of L with the Pd-NP surface [38]. The
pattern of the UV-vis spectrum of 2 resembles very much that of 1 with the absorption maxima
being lower compared to 1 (Fig. 2). Transmission electron microscopy (TEM) micrographs of 2
confirmed the presence of well-dispersed Pd-NPs characterized by an average particle size (dm) of
2.09 ± 0.49 nm (Fig. 3). The Pd-content, determined by induced coupled plasma-optical emission
spectroscopy (ICP-OES), was of 2.0 wt%. The corresponding Pd dispersion, calculated from
average particle size obtained from TEM analysis by using the equation drel(VS) = 3.32/FE1.23 [39]
(i.e. FE is the fraction of Pd atoms exposed to solution, drel(VS) = dVS/dat, “(dVS)” is the volume-
surface mean diameter of an assembly of particles of different sizes, and dat is the atomic diameter
of palladium (2.74 Å)) revealed to be 51%. The 2,2’-bipyridine end group of L efficiently controls
the reduction of Pd(II) to Pd(0) and the successive stabilization of the obtained Pd-NPs. In fact, the
reduction of Pd(OAc)2 in the presence of pyridine-end functionalized PEG [40] (i.e. pyridine is less
coordinating to Pd(II) and Pd(0) compared 2,2’-bipyridine) or not functionalized PEG give Pd-NPs
which is much bigger in size [41].
In accordance with TEM measurements, X-ray photo-electron spectroscopy (XPS) analysis,
conducted on isolated 2, showed the presence of Pd(0) (i.e. Pd 3d5/2 at 334.8 eV) [42] and Pd(II)
(i.e. Pd 3d5/2 at 337.1 eV) [43] in a 4:1 atom ratio (Fig. 4a). The binding energies (BE) of Pd(II)
correspond to that of chemisorbed oxygen atoms (Oads) on Pd-NPs’ surface [17].
6

2.2. Catalytic nitrile hydration reactions
1 and 2 were used to chemoselectively hydrate aromatic and aliphatic nitriles in water in the
presence of an air atmosphere to give the corresponding amide as proved by GC-MS analysis.
Pd(II) 2,2’-bipyridine complexes [44-45] (i.e. 349 K, substrate to Pd molar ratio of 383) as well as
Pd-NPs supported onto carbon [17] (i.e. 413 K, substrate to Pd molar ratio of 50) have been
employed to catalyze the nitrile hydration under completely different experimental conditions. We
compare the catalytic performance of both Pd-based catalysts at 353 K and a substrate to Pd molar
ratio of 56, using the normalized TON value (i.e. TON referred to the Pd atoms exposed to the
catalytic solution). The results of the comparative catalytic reactions are compiled in Table 1.
From the catalytic data shown in Table 1, we infer that: (i) Regardless of the substrate employed,
the Pd-NP-based catalyst showed significantly higher activity in terms of normalized TON (i.e. 1
and 2 have respectively 100% and 51% of the Pd atoms exposed to the catalytic solution. This
experimental fact holds also for the nitrile hydration with time as shown for benzonitrile (Table 1,
entries 8-12 vs 1-5). The difference in catalytic activity between both catalysts was most
pronounced in those cases where a strong substrate coordination to Pd(II) is expected, as for 2- and
4-cyanopyridine (Table 1, entry 20 vs 19 and entry 22 vs 21). (ii) The catalytic activity drop is
higher in the case of 2 compared to 1 (Table 1, entries 12-14 vs 5-7). (iii) The addition of one mole
equivalent of L to 2 had no beneficial effect on the catalyst performance over three consecutive
catalytic reactions (i.e. benzonitrile conversion dropped from 83% to 45% in the first and second
recycling experiment, respectively) (Table 1, entry 16 vs 17 and 18).
Table 1, here
7

2.3. Mechanistic investigations
2.3.1.Pd-NP-catalyzed reactions
In order to investigate the deactivation mechanism operative in Pd-NP-catalyzed nitrile hydration
reactions in water, we isolated the water soluble catalyst upon precipitation with iso-propanol and
studied the recovered catalyst by TEM, XPS, and powder X-ray diffraction (PXRD). TEM
micrographs of recovered 2 (i.e. recovered after the first catalytic run) and 2+L (i.e. recovered after
the third catalytic run) (Fig. 5) clearly showed a strong aggregation of Pd-NPs in 2 already after the
first catalytic run (Fig. 5, left). In contrast, the presence of an additional amount of macroligand L,
significantly avoided the NP-aggregation process (Fig. 5, right). This experimental fact is strongly
indicating that 2 is in equilibrium with naked Pd-NPs, generated by L dissociation from 2, and L.
Naked Pd-NPs strongly aggregate during catalysis, while free L interacts with 2, avoiding hence the
aggregation of 2 as proved by the TEM-micrograph of 2+L (Fig. 5, right). The average Pd-NP size
of recovered 2 and 2+L were of 3.5 and 4.5 nm, respectively.
XPS spectra acquired on recovered 2 and 2+L showed the presence of Pd(0) (i.e. Pd 3d5/2 at
334.2 eV) and Pd(II) (i.e. Pd 3d5/2 BE at 337.7 and 337.4 eV). The Pd 3d BE of these latter Pd(II)
species are slight shifted to higher energies compared to that observed for either PdO or Pd-NPs
covered by chemisorbed oxygen atoms [43,46] (Fig. 4, traces b and c). The shift of the BE is in
accordance with the presence of hydroxide ions on the Pd-NPs’ surface [47-48] which are stabilized
by water molecules through hydrogen bond interactions [49-51]. An increase of the Pd(II)/Pd(0)
atom ratio from 2.6:1 (i.e. 2 after the first run, Fig. 4, trace b) to 7:1 (i.e. 2+L, after the third run,
Figure 4, trace c) is indicative for a continuous coverage of Pd-NPs with a hydroxide-water layer.
By combining results obtained from catalytic reactions, TEM and XPS analyses, we propose the
following reaction steps operative in 2-catalyzed nitrile hydration in water (Scheme 2). The
activation of a water molecule is assisted by a surface chemisorbed oxygen atom (Oads), followed by
a concerted attack of the coordinated nitrile functional group [17,33-34]. Theoretical calculations
8

confirmed a notable decrease of the water-splitting activation energy when chemisorbed oxygen-
assisted [34] compared to a clean Pd surface [32] (i.e. 0.48 eV vs 1.12 eV). In order to prove the
importance of chemi-adsorbed oxygen atoms for the catalytic nitrile hydration, we carried out
analogous catalytic reactions in the presence of rigorously deaerated water and a nitrogen
atmosphere. As a result, an almost identical substrate conversion was achieved (Table 1, entry 15 vs
12).
A much lower substrate conversion in D2O compared to H2O (i.e. TON: 52 (24 h) vs 91 (24 h))
proved that the water splitting reaction is essential for the catalytic nitrile hydration. The negatively
charged nitrogen atom of the coordinated iminolate interacts through a hydrogen bond with a water
molecule. Proton transfer from water to the iminolate nitrogen atom generates coordinated iminol
and surface coordinating hydroxide unit, which is stabilized by hydrogen bonding with water
molecules. The coordinated iminol is successively released from the metal surface and isomerizes
to the thermodynamically more stable amide species. Once all surface adsorbed oxygen atoms are
converted into hydroxide groups localized on the Pd-NP surface and interconnected with water
molecules forming a hydroxide-water layer, the activation of water molecules and the coordination
of the nitrile substrate becomes much more difficult to occur. Hence the hydroxide formation on the
Pd-NP surface is a real deactivation process in 2-catalyzed nitrile hydration reactions.
2.3.2.Pd(II)-macrocomplex-catalyzed reactions
1-catalyzed nitrile hydration reactions carried out in water at 353 K were studied by operando 1H
NMR spectroscopy. The effect of coordinated acetate to Pd(II) on the catalytic reaction mechanism
was estimated by carrying out the same NMR study with [Pd(OTs)2L] (1’) which bears the weakly
coordinating tosylate (OTs) instead of acetate. Importantly, 1’ showed under the same catalytic
conditions, as reported for 1 (Table 1), comparable results (i.e. 84%, 80% (first recycle) and 79%
(second recycle)), indicating a negligible effect of the acetate anion on the overall catalytic activity.
9

In Fig. 6 is shown a sequence of 1H NMR spectra of 1 and 1’, acquired under identical experimental
conditions.
1
A comparison of the room temperature spectra of 1 and 1’ clearly showed a different H NMR
pattern for the aromatic bipyridine hydrogen atoms (Fig. 6, traces a and b), which is consistent with
the coordination of acetate to Pd(II) at room temperature. 1H NMR spectra of both latter catalysts at
353 K, which is the reaction temperature of the catalytic reactions, showed almost identical NMR
patterns (Fig. 6, traces c and d), corroborating the fast anion exchange in both latter complexes with
D2O, generating hence charged Pd(II)-water species. In the presence of the nitrile substrate (i.e.
valeronitrile) an equilibrium between Pd(II) species bearing water molecules and valeronitrile (i.e.
1H NMR signals with an asterisk) coordinating typically with the nitrogen atom is observed with
both Pd(II) catalyst precursors at 353 K (Fig. 6, traces e and f). This latter equilibrium is strongly
shifted toward the Pd-nitrile species, proving the strong coordination properties of the nitrile
functionality to Pd(II). The Pd(II)-based catalytic nitrile hydration in water as reaction medium is
sketched in Scheme 3.
The Pd(II) precursor species 1 and 1’ are activated at 353 K upon dissociation of the anion and
coordination of water molecules forming a charged Pd(II)-aqua complex (Scheme 3, step a).
1
Accordingly the H NMR spectra of the latter precatalysts showed the same NMR pattern for the
2,2’-bipyridine moiety at 353 K in D2O (Fig. 6, traces c and d).
The cationic Pd(II)-aqua complex react with the nitrile substrate leading to a Pd(II)-bis-nitrile
species which is in equilibrium with the former species (step b) as proved by the operando 1H NMR
spectra shown in Fig. 6 traces e and f. The partial substitution of nitrile by water gives the Pd(II)-
nitrile-water complex (step c), which is transformed, anion-assisted, into the Pd(II)-hydroxy-nitrile
species (step d), which is a key species of the catalytic cycle. The attack of the coordinated
hydroxide anion on the cis-coordinated nitrile is mandatory, yielding the Pd-iminolate species (step
e). A kinetic study carried out on isolated Pd(II)-OH species bearing 2,2’-bipyridine as ligand [43]
10

confirmed this latter finding. The strong coordination of hydroxide to Pd(II) slows down the
migration process. In this respect, a ligand-assisted water activation, without formation of free
hydroxide, as described for Ru(acac)2(PPh2Py)2 (acac = acetylacetonate) notably increases the
catalytic performance [29].
The protonation of the Pd-iminolate by HX (X= OAc- or OTs-) (i.e. HX is more acidic then
coordinated H2O) yields the coordinated iminol (step f), which dissociates from metal centre (step
g) and tautomerizes to the amide (step h).
3. Conclusions
2,2’bipyridine end-functionalized poly(ethyleneglycol) methylether was employed to stabilize
small Pd-nanoparticles (NPs) (2.0 nm), partially covered with chemi-adsorbed oxygen atoms, and
Pd-acetate. Both types of catalyst were used to catalyze the selective hydration of nitriles to the
corresponding amide under identical experimental conditions (i.e. reactions in water at 353 K).
Based on normalized TON values, the Pd-NP-based catalyst exhibited on one hand a much higher
catalytic activity compared to the molecular counterpart, outperforming related heterogeneous
catalysts such as Pd on carbon [17] or Ag on SiO2 [19] (i.e. reaction temperatures >403 K), reaching
TON-values observed for Au on TiO2 (i.e. reaction temperatures 333-353 K) [18]. On the other
hand, the Pd-NP-based catalyst experienced a strong deactivation during the first catalytic run,
which was rationalized with the conversion of chemisorbed oxygen atoms, which assists the water
activation step, into an hydroxide-water layer, located on the Pd-NPs’ surface. Once all
chemisorbed oxygen is converted to Pd(II) strongly coordinating hydroxide ions, the positive effect
of the oxygen-assisted water activation vanishes and a less efficient reaction mechanism similar to
that postulated for the Pd-acetate catalyst becomes operative.
11

4. Experimental
4.1. Chemicals
Poly(ethyleneglycol) monomethyl ether (Mn = 5000 gmol-1), methanesulfonyl chloride,
dichloromethane, DMF, NaH, Pd(OAc)2, p-TsOH monohydrate, n-hexane, diethyl ether, and 4’-
methyl-(2,2’-bipyridine)-4-yl-methanol were purchased from Aldrich and used as received.
4.2. Physical Measurements
1H NMR spectra were recorded on a Bruker Avance II DRX 300 spectrometer at 300.13 MHz.
Chemical shifts (δ) are reported in ppm relative to TMS.
UV-vis spectra were recorded on a Varian-Cary 4000 UV-vis spectrometer, using water
solutions with a concentration of 3 mgmL-1. The measurements were performed in a quartz cuvette
with a 10 mm optical path length.
TEM analyses were carried out on a TEM PHILIPS CM 12 instrument, equipped with an
OLYPMPUS Megaview G2 camera and using an accelerating voltage of 80 keV. Samples suitable
for the analyses were prepared by depositing a drop of a CH2Cl2 solution of the corresponding
sample on a holey film of a 300 mesh Cu grid, followed by evaporation of the solvent at room
temperature.
XPS spectra were acquired at room temperature in normal emission geometry, using a 120 mm
hemispherical electron energy analyzer (PSP) and a conventional Mg Kα1,2 (1253.6 eV) X-ray
source, with an overall experimental energy resolution of ~0.8 eV. Binding energies were calibrated
by fixing the C 1s signal stemming from atmospheric contaminants at 284.6 eV. All spectra were
normalized to the incident photon flux and analyzed by performing a nonlinear mean square fit of
the data in the binding energy range of interest, following the Levenberg-Marquardt algorithm. We
used a Shirley background [52] and reproduced the photoemission lineshape of the Pd 3d levels
using asymmetric and symmetric Doniach-Sijunich curves for Pd(0) and Pd(II), respectively [53].
GC-analyses were performed with a Shimadzu 2010 gas chromatograph equipped with a flame
ionization detector and a 30 m (0.25 mm i.d., 0.25 μm film thickness) VF-WAXms capillary
column.
GC-MS-analyses were performed with a Shimadzu QP 5000 apparatus, equipped with a 30 m
(0.32 mm i.d., 0.50 μm film thickness) CP-WAX 52 CB WCOT-fused silica column.
ICP-OES analysis was carried out on a iCAP 6200 Duo Thermofisher instrument.
12

4.3. Syntheses
4.3.1.Synthesis of L
Mesyl-PEG-OMe (5.00 g, 0.99 mmol), which was synthesized as described elsewhere [37], was
dissolved in anhydrous DMF (30.0 mL). To this solution was added 4’-methyl-(2,2’-bipyridin)-4-
yl)-methanol (2.18 g, 10.9 mmol) and NaH (2.4 g, 99.0 mmol) and the resulting suspension was
stirred at 308 K for 24 h. The resulting suspension was then filtered and to the clear solution was
added diethyl ether (200.0 mL) to precipitate the product as off-white solid which was separated by
1
filtration, dried in vacuum and used without further purification. Yield: 3.84 g, 75%. H NMR
(300.13 MHz, D2O, 294 K): δ = 2.72 (s, 3H, CH3), 3.30 (s, 3H, OCH3), 3.61 (br s, 456H,
CH2CH2O) 4.71 (s, 2H, CH2O), 7.35 (br s, 1H, ArH), 7.48 (br s, 1H, ArH), 7.88 (s, 1H, ArH), 7.98
(s, 1H, ArH), 8.44 (br s, 1H, ArH), 8.56 (br s, 1H, ArH).
4.3.2.Synthesis of 1
Pd(OAc)2 (47.0 mg, 0.120 mmol) and L ( 1.00 g, 0.190 mmol) were dissolved in anhydrous
CH2Cl2 (10.0 mL) and the resulting solution was stirred at room temperature for 3 h. Upon addition
of n-hexane (50.0 mL), the product precipitated as dark brown solid which was separated by
filtration and dried by vacuum. Yield: 0.74 g, 72%. 1H NMR (300.13 MHz, D2O, 294 K): δ = 1.84
(s, 3H, CH3CO2), 1.97 (br s, 3H, CH3CO2), 2.44 (br s, 3H, CH3), 3.26 (s, 3H, OCH3), 3.58 (br s,
456H, CH2CH2O) 4.73 (s, 2H, CH2O), 7.40 (br s, 1H, ArH), 7.51 (br s, 1H, ArH), 7.89 (s, 1H,
ArH), 7.98 (s, 1H, ArH), 8.08 (br s, 1H, ArH), 8.15 (br s, 1H, ArH).
4.3.3.Synthesis of 1’
1 (400.0 mg, 0.0729 mmol) was dissolved in CH2Cl2 (10.0 mL). To the latter solution was added
p-TsOH monohydrate (28.4 mg, 0.149 mmol), which dissolved upon reaction. After stirring the
solution for 4 h, n-hexane (10.0 mL) was added, which caused the precipitation of the product as
light brown powder, which was separated from solution by filtration and dried by vacuum. Yield:
366.3 mg, 0.0620 mmol. 1H NMR (300.13 MHz, D2O, 294 K): δ = 2.27 (s, 6H, CH3(tosylate)), 2.51
(br s, 3H, CH3), 3.29 (s, 3H, OCH3), 3.61 (br s, 456H, CH2CH2O) 4.78 (s, 2H, CH2O), 7.23 (d,
3
3J(H,H) = 6.9 Hz, 4H, ArH(tosylate)), 7.47 (br s, 1H, ArH), 7.57 (d, J(H,H) = 6.9 Hz, 5H,
ArH(tosylate) + ArH), 7.94 (br s, 1H, ArH), 8.07 (br s, 2H, ArH), 8.16 (s, 1H, ArH).
13

4.3.4.Synthesis of 2
1 (1.50 g, 0.278 mmol) was dissolved in CH2Cl2 (20.0 mL) and then transferred into a teflonated
stainless steel autoclave (75.0 mL), which was successively sealed and purged with hydrogen.
Afterward the autoclave was pressurized with hydrogen (15 bar) and the solution stirred at room
temperature for 12 h. Then the hydrogen pressure was released and the black solution concentrated
to dryness. The obtained black solid was suspended in diethyl ether (10.0 ml), filtered and dried by
vacuum at room temperature. The dark brown solid was used without further purification. Yield:
1.40g, 93%. Pd content: 2.0 wt%
4.4. Catalytic nitrile hydration in water
Catalyst (50.0 mg, 0.009 mmol of Pd) and substrate (0.50 mmol) were dissolved in water
(milliQ-grade) and transferred into a pyrex vial. The obtained suspension was stirred at 353 K in air
atmosphere for the desired time. Afterward, the obtained solution was cooled to 273 K and
extracted with diethyl ether (3 × 2.0 mL). To the unified organic phases was added toluene (50.0
μL) as internal standard. The obtained solution was objected to GC and GC-MS analysis. The
catalyst was recovered after diethyl ether extraction by precipitation with iso-propanol, filtration
and drying by vacuum at room temperature. The recovered catalyst was then used for recycling
experiments.
4.5. Variable-temperature 1H NMR spectroscopy
1 and 1’ (15.0 mg) were separately dissolved in D2O (1.3 mL). The obtained solutions were
transferred under nitrogen in 5.0 mm NMR tubes, sealed and inserted in the NMR probe, followed
1
by the acquisition of H NMR spectra at room temperature. Afterward, the samples were heated to
1
353 K, followed by the acquisition of H NMR spectra. The NMR samples were cooled to room
temperature and removed from the NMR probe. At the latter temperature was added valeronitrile
(25.0 μL) to the D2O solutions of 1 and 1’, followed by sealing the NMR tubes, inserting in the
probe and heating them to 353 K. 1H NMR spectra at the latter temperature were acquired for 6 h in
a time interval of 1 h.
14

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17

Figures with captions
Fig. 1. 1H NMR spectra acquired in D2O in the chemical shift range from 7.1 to 8.8 ppm of a) L, b)
1, and c) 2.
Fig. 2. UV-vis spectra of L, 1 and 2 acquired in water.
18

Fig. 3. TEM micrograph and histogram of 2.
Fig. 4. XPS Pd 3d spectra of a) as-synthesized 2, b) recovered 2, and c) recovered 2+L.
19

Fig. 5. TEM micrographs of recovered 2 (left), and 2+L (right).
1
Fig. 6. H NMR spectra in the chemical shift range from 9.0 to 5.0 ppm acquired in D2O at: room
temperature of a) 1, and b) 1’; at 353 K of c) 1, and d) 1’; at 353 K in the presence of valeronitrile
after 1.5 h of e) 1, and f) 1’. Asterisk denote the Pd(II)-bis nitrile complex.
20

Schemes
Scheme 1. Syntheses of L, 1, and 2.
Scheme 2. Proposed reaction steps in 2-catalyzed nitrile hydration reactions in water.
Scheme 3. Proposed catalytic cycle for Pd(II)L-based catalyst with weakly coordinating anions.
21

Table 1.Catalytic nitrile hydration in water with 1 and 2.
Entry
1
Catalyst
1
Time [h]
1
Substrate
Conversion [%]/TONa)
33/18
2
3
59/33
1
3
6
68/38
1
4
5
6b)
7c)
8
12
24
24
24
1
70/39
93/52
87/48
81/45
1
1
1
1
21/23
2
9
3
44/48
2
10
11
12
13b)
14c)
15d)
16e)
17b,e)
18c,e)
19
20
6
51/55
66/72
84/91
57/n.d.
40/n.d.
82/89
83/90
45/49
2
2
2
2
2
2
2+L
2+L
2+L
1
12
24
24
24
24
24
24
24
24
24
45/49
18/10
40/43
2
21
22
24
24
20/11
34/37
1
2
23
24
24
24
99/55
89/97
1
2
25
26
27
28
24
24
24
24
85/47
62/67
55/30
32/35
1
2
1
2
Catalytic conditions: catalyst (50.0 mg, Pd content= 9×10-3 mmol), substrate (0.50 mmol), T (353 K), H2O (2.0 mL).
a) Normalized TON defined as: mmol (substrate converted)/mmol (Pdsurface); Pdsurface = 4.6×10-3 mmol.
b) First recycle.
c) Second recycle.
d) Catalytic reaction carried out under nitrogen atmosphere.
e) Addition of L (50.0 mg, 0.01 mmol).
22