Supported Gold Nanoparticles-Catalyzed Microwave-Assisted Hydration of Nitriles to Amides under Base-Free Conditions

Article abstract of DOI:10.1002/adsc.201600199

Polystyrene-supported gold (Au@PS) nanoparticles were synthesized by the reduction deposition approach and well characterized by UV-visible, XRD, TEM, SAED, EDX, and XPS studies. The Au@PS was applied as catalyst for the hydration of nitriles to amides in water under microwave irradiation. Several functionalized aromatic, heterocyclic and aliphatic nitriles were found to be active for synthesis of the corresponding amides where no activation of water by base, ligand and support is needed. Easy recovery, negligible leaching and recyclability for up to eight runs are added advantages of the catalyst under water-mediated reaction conditions. (Figure presented.).

Full text of DOI:10.1002/adsc.201600199

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DOI: 10.1002/adsc.201600199
Supported Gold Nanoparticles-Catalyzed Microwave-Assisted Hy-
dration of Nitriles to Amides under Base-Free Conditions
Sandeep Kumar,a,b Saurabh Sharma,a,b and Pralay Dasa,b,*
a
Natural Product Chemistry & Process Development, CSIR – Institute of Himalayan Bioresource Technology, Palampur –
176061, H.P., India
Fax : (+91)-1894-230-433; e-mail: pdas@ihbt.res.in or pdas_nbu@yahoo.com
Academy of Scientific & Innovative Research (AcSIR), New Delhi, India
b
Received: February 17, 2016; Revised: June 25, 2016; Published online: && &&, 0000
IHBT communication No. 4006.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201600199.
Abstract: Polystyrene-supported gold (Au@PS)
nanoparticles were synthesized by the reduction
deposition approach and well characterized by UV-
visible, XRD, TEM, SAED, EDX, and XPS studies.
The Au@PS was applied as catalyst for the hydra-
tion of nitriles to amides in water under microwave
irradiation. Several functionalized aromatic, hetero-
cyclic and aliphatic nitriles were found to be active
for synthesis of the corresponding amides where no
activation of water by base, ligand and support is
needed. Easy recovery, negligible leaching and recy-
clability for up to eight runs are added advantages
of the catalyst under water-mediated reaction con-
ditions.
The heterogeneous catalysts consisting mainly of
ruthenium as metal[6f–h] solved the limitations associat-
ed with homogeneous catalysts. But the application of
gold catalysts in the hydration reaction has been
rarely reported. Ramon et al. reported use of the ho-
mogeneous NHC-Au(I) complex for the first time in
the hydration of nitriles to amides under microwave
irradiation at 1408C using water as cosolvent.[7] The
only heterogeneous gold catalyst reported for the hy-
dration of nitriles to amides is gold NPs supported
over TiO2 where the support itself acts as basic site
for activation of water molecules.[8] Recently the base
and oxide support-catalyzed selective hydration of ni-
triles to amide was reported.[9] But so far the base-
and ligand-free hydrations of nitrile under heteroge-
neous gold catalyst has not yet been reported. In con-
tinuation of our work on the development of hetero-
geneous transition metal NPs as catalysts, and their
applications in various organic transformations,[10]
herein we report the efficient hydration of nitriles to
amides by well characterized Au@PS NPs as catalyst
in ligand- and base-free conditions, under microwave
Keywords: amide synthesis; heterogeneous cata-
lysts; hydration; supported gold nanoparticles;
water
The hydration of nitriles is a most economical, atom irradiation in water.
efficient and green synthetic approach for the produc-
The Au@PS catalyst was synthesized by following
tion of valuable amide molecules having importance a reduction-deposition approach using Amberlite
as chemical intermediates in the pharmaceutical and IRA 900 chloride form resin as polystyrene surface
chemical industry.[1] Traditional methods involving (PS) and HAuCl4·3H2O as metal salt precursor. The
acid and base catalysts have limitations such as forma- ClÀ counter anions of the polystyrene support (PS)
À
tion of over hydrolysis products along with generation were partially exchanged with BH4 ions giving PS-
À
of waste while the enzyme-catalyzed reactions need BH4À (Supporting Information). The treatment of PS-
purification and handling of sensitive enzymes.[2] In BH4 thus obtained with HAuCl4·3H2O in DMF at
this context, metal-catalyzed hydrations have revolu- 1008C afforded the purple-coloured Au@PS catalyst.
tionized the area in terms of activity, selectivity and Reduction of the metal salt and simultaneous deposi-
atom efficiency of the process. Different homogene- tion was monitored by UV-visible spectroscopic stud-
ous transition metal catalysts of rhodium,[3] palladi- ies (Figure 1). The disappearance of the peak at
um,[4] platinum[5] and ruthenium[6a–e] have been em- 320 nm[11] and simultaneous purple colour of the cata-
ployed for this purpose that are efficient when used lyst was confirmation of reduction as well as deposi-
in conjunction with ligands and are non-recyclable. tion on the polymer. An insight into Au@PS was
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Figure 1. a: HAuCl4·3H2O in DMF; b: spectra of solution+
NaBH4 exchanged polymer after 5 min; c: solution after
complete deposition over the polystyrene surface.
done for crystal structure determination of the gold
NPs by a powder X-ray diffraction (p-XRD) study
(Figure 2). The p-XRD pattern showed distinct reflec-
tions at 38.28, 44.33, 64.76 and 77.84 which are as-
signed to the (111), (200), (220) and (311) planes of
Au having an fcc arrangement in accordance with the
diffraction standard (JCPDS-04-0784).[12]
Figure 3. a: TEM image at 20 nm; b: TEM image at 5 nm;
c: HR-TEM image of a single crystal showing fringe spac-
ing; d: FFT diffractogram of c; e: SAED; f: EDX spectra;
g: particles size distribution as calculated from a of Au@PS.
The morphology of the synthesized catalyst was
studied by transmission electron microscopy (TEM).
The low field TEM analysis of Au@PS (Figure 3a, b) was further performed for crystal structure determina-
revealed that the gold NPs were impregnated into the tion. Figure 3c shows an HR-TEM image of the single
polymer matrix with a maximum number of particles crystal of gold NPs with two different fringe spacings
sized between 4–6 nm (Figure 3g). The high resolution of 0.24 and 0.21 nm, these are assigned to spacing be-
transmission electron microscopy (HR-TEM) analysis tween (111) and (200) planes of the face centred
cubic (fcc) arrangement of gold. The FFT image of
Au@PS single crystals also shows diffraction spots
corresponding to an fcc arrangement of gold NPs
(Figure 3d). The four distinct Debye–Sherrer rings
(Figure 3e) with d-spacings of 2.44, 2.10, 1.49, and
1.24 ꢁ were observed in the selected area electron
diffraction (SAED) pattern of Au@PS. The different
rings are indexed (111), (200), (220) and (311) based
on d-spacing values. The observed planes in the
SAED pattern were the same as observed in the p-
XRD pattern of the Au@PS. The presence of metallic
gold particles was further confirmed by energy disper-
sive X-ray (EDX) analysis of the Au@PS that showed
characteristic peaks at 9.71 and 2.12 keV due to La
and M transitions in the spectrum (Figure 3f). The X-
Figure 2. X-ray diffraction (XRD) pattern of Au@PS.
ray photoelectron spectroscopy (XPS) measurements
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were used to determine the oxidation state of gold. catalyst.[7] The hydration reaction with commercially
The spectral peak corresponding to binding energy available heterogeneous Au-TiO2 and Au-Al2O3 cata-
84.6 eV and 88.2 eV for the 4f shell corresponds to lysts gave 14 and 12% isolated yield of the desired
gold NPs (Supporting Information).
product (Table 1, entries 16 and 17) and the reason
In order to optimize the reaction conditions for the may be the lower stability of the catalyst under water-
hydration of nitriles to amides, the effect of different mediated conditions, that resulted in poor reactivity.
catalyst concentrations, temperatures, solvents and re-
Finally, the conditions Au@PS (2 mol%) at 1308C
action times was investigated on p-bromobenzonitrile (80 psi, 100 W), using water as solvent for 1 h of mi-
1a selected as a model substrate. Delightfully the crowave irradiation was found to be standard to get
Au@PS (2 mol%) at 1308C (80 psi, 100 W), using the best result of the product.
water as solvent for 1 h microwave irradiation gave
The versatility of the present protocol for different
the desired product in 90% yield and no carboxyla- substituents on the benzonitrile was tested. The ben-
tion product due to over hydrolysis was observed zonitrile 2a was smoothly hydrated to benzamide in
(Table 1, entries 1–5). The reaction under convention- good yield while those with electron-rich substituents
al conditions yielded no product (Table 1, entry 6) like OMe and Me, 3a and 4a gave lower conversion
while the metal salt precursor HAuCl4·3H2O yielded than did electron-deficient (NO2, COCH3 and CF3)
50% of the desired product (Table 1, entry 9). No re- substituted benzonitriles 5a–8a (Table 2, entries 1–7)
action was observed using only PS (Table 1, enteries and the reason may be that attack of the nucleophilic
11 and 12) and different protic as well as aprotic sol- water molecule on the less electrophilic carbon of the
vents (Table 1, enteries 13–15). The Au@PS is compa- nitrile moiety is the rate-determining step that gets
ratively more active, easy to handle and highly recy- slower for electron-rich substrates. The formyl and
clable than the reported homogeneous NHC-Au(I) mercaptomethyl group at para position 9a and 10a
were well tolerated under the reaction conditions
giving the corresponding amides 9b and 10b in good
Table 1. Optimization of the reaction conditions for hydra-
yield (Table 2, entries 8 and 9). The halo-substituted
benzonitriles 11a–15a smoothly yielded the corre-
sponding amides 11b–15b without any dehalogenation
product. Selective hydration of benzodinitriles 16a
and 17a was observed to yield mono amides 16b and
17b in 75 and 74% yield, respectively, even with an in-
crease in time up to 90 min. The hydration of the
scarcely reported biphenylcarbonitrile 18a with high
hydrophobicity was achieved using ethanol as co-sol-
vent in good yield. Interestingly, the a,b-unsaturated
cinnamonitrile 19a also participated in the reaction
and gave 19b in 82% yield.
tion of 4-bromobenzonitrile.[a]
The versatility of the method was further extended
using aromatic heterocyclic nitriles such as thiophene-
carbonitrile, 3-cyanopyridine and 4-cyanopyridine
20a–22a and yielded thiophenecarboxamide, nicotin-
AHCTUNGTREGaNNUN mide and isonicotinamide 20b–22b, in 87–92% yields
(Table 3). The substituent at the nicotinamide 23a had
no effect on the hydration as the desired product 23b
was obtained in good yield. 4-Cyanoindole 24a was
also efficiently converted to the desirable product 24b
in good yield. The aliphatic nitriles containing hetero-
cyclic molecules such as thiophene-2-acetonitrile 25a
and thiophene-3-acetonitrile 26a were also found to
be suitable reactants under the reaction conditions.
The phenylacetonitrile 27a produced the correspond-
ing amide 27b in good yield while the less active phe-
nylpropionitrile 28a was slowly hydrated to give
a moderate yield of the corresponding amide in 2 h.
The low molecular weight propionitrile 29a also gave
the corresponding amide 29b in moderate yield
(45%) proving the catalytic activation of less active
nitriles.
[a]
Conditions: 1a (100 mg), solvent (7 mL).
Isolated yield; selectivity (1b) >99%; nr=no reaction.
Reaction under conventional heating for 3 h.
For 45 min.
[b]
[c]
[d]
[e]
Used after washing with acetone and drying.
[f]
À
PS was BH4 exchanged, neutralized and dried.
[g]
Commercial catalysts.
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Table 2. Au@PS-catalyzed hydration of substituted nitriles under microwave irradiation.[a]
[a]
Reaction conditions: organonitrile 2a–19a (100 mg), water (7 mL) and Au@PS (2 mol% Au); isolated yields.
Selectivities >99%.
[b]
The methodology was also extended to the large- The recyclability experiments of Au@PS were con-
scale application for the hydration of 4-chlorobenzo- ducted by using 4-cyanopyridine as test substrate.
nitile 12a and 4-cyanopyridine 22a at 5 mmol scale After completion of reaction, the product was extract-
under microwave irradiation. The desired products ed using ethyl acetate. The catalyst was filtered and
12b and 22b were obtained in 80 and 85% isolated dried under reduced pressure after washing with ace-
yield, respectively (Scheme 1 and the Supporting In- tone. The recovered catalyst was repeatedly used for
formation).
the same reaction. The catalyst showed negligible loss
The mechanism is likely to follow the activation of of activity up to eight runs (Figure 4). A gradual de-
the nitrile moiety through interaction of the nitrogen crease in the activity of Au@PS was observed during
atom with the metal catalyst and water activated the recycling experiment (decreased yield up to 14%
under the catalyst-assisted microwave conditions.[7] in eight cycle). The ICP-AES analysis of the reaction
mixtures revealed negligible leaching <1 ppm of gold
metal from the catalytic surface (Supporting Informa-
tion). The TEM analysis of the Au@PS was per-
formed after six runs. The gold NPs were found to be
dispersed in the solid matrix that showed negligible
leaching of catalyst into the reaction mixture (Fig-
ure 5a). Interestingly the size of nanoparticles was ob-
Scheme 1. Hydration of nitriles at the 5 mmol scale.
served to be higher than the fresh Au@PS catalyst
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Table 3. Au@PS-catalyzed hydration of heterocyclic and ali-
phatic nitriles.[a]
Figure 4. Recyclability of Au@PS in the hydration reaction.
Figure 5. a: TEM analysis; b: histogram of Au@PS after six
runs.
Experimental Section
General Procedure
4-Bromobenzonitrile (100 mg, 0.55 mmol), water (7.0 mL)
and Au@PS (460 mg, 2 mol% Au) were taken in an oven-
dried reaction tube equipped with a snap cap. The reaction
mixture was then irradiated in a microwave apparatus at
1308C (100 W, 80 psi) for 1 hour. After cooling to ambient
temperature in the microwave cavity the reaction mixture
was extracted with ethyl acetate and dried under reduced
pressure. The reaction mixture after washing with hexane
yielded 4-bromobenzamide 1b as white solid; yield: 98 mg
(90%).
[a]
Reaction conditions: substituted organonitrile 20a–29a
(100 mg), water (7 mL) and Au@PS (2 mol% Au); isolat-
ed yields.
Selectivities >99%.
[b]
that accounts for the Ostwald ripening (Figure 5b)
and hence gradual decrease in the activity during re-
cyclability.
Acknowledgements
In conclusion, we have developed the polystyrene-
stabilized gold (Au@PS) NPs as air/moisture stable
heterogeneous catalyst that efficiently catalyzed the
base-free hydration of wide range of nitriles to their
corresponding amides in water under microwave irra-
diation. The catalyst was easily recovered and reused
up to eight times without any activation and no signif-
icant loss of catalytic activity was observed.
We are grateful to the Director CSIR-IHBT for providing the
necessary facilities during the course of the work. We thank
Dr. G. Saini and AIRF, JNU–New Delhi, India and Biotech-
nology Division, CSIR-IHBT for the TEM analysis; and
SAIF, PU-Chandigarh, for XRD analysis. We thank CSIR,
New Delhi, for financial support as part of XII Five Year
Plan programme under the title ORIGIN (CSC-0108). S.K
and S.S thank CSIR and UGC, New Delhi for awarding fel-
lowships.
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Supported Gold Nanoparticles-Catalyzed Microwave-
Assisted Hydration of Nitriles to Amides under Base-Free
Conditions
7
Adv. Synth. Catal. 2016, 358, 1 – 7
Sandeep Kumar, Saurabh Sharma, Pralay Das*
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