Ligand-promoted reaction on silver nanoparticles: Phosphine-promoted, silver nanoparticle-catalyzed cyclization of 2-(1-hydroxy-3-arylprop-2-ynyl) phenols

Article abstract of DOI:10.1016/j.tetlet.2010.10.065

A highly efficient annulation of 2-(1-hydroxy-3-arylprop-2-ynyl)phenols leading to the key intermediates to synthesize aurones was catalyzed by silver nanoparticles/carbon black-supported silver nanoparticles. In the presence of phosphine ligand, both the

Full text of DOI:10.1016/j.tetlet.2010.10.065

Tetrahedron Letters 51 (2010) 6722–6725
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Ligand-promoted reaction on silver nanoparticles: phosphine-promoted, silver
nanoparticle-catalyzed cyclization of 2-(1-hydroxy-3-arylprop-2-ynyl)phenols
Min Yu a, Mingdeng Lin a, Chengyan Han a, Li Zhu b, Chao-Jun Li c, , Xiaoquan Yao a,
⇑
⇑
a Department of Applied Chemistry, School of Material Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, PR China
b School of Pharmacy, Nanjing Medical University, Nanjing 210029, PR China
c Department of Chemistry, McGill University, Montreal, QC, Canada, H3A 2K6
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly efficient annulation of 2-(1-hydroxy-3-arylprop-2-ynyl)phenols leading to the key intermedi-
ates to synthesize aurones was catalyzed by silver nanoparticles/carbon black-supported silver nanopar-
ticles. In the presence of phosphine ligand, both the catalysts show excellent catalytic activities in the
reaction and give the products with good yields as well as excellent regio- and stereo-selectivities in a
water-toluene mixed solvent. Furthermore, the catalysts can be recovered and recycled effectively
several times.
Received 16 August 2010
Revised 1 October 2010
Accepted 12 October 2010
Available online 20 October 2010
Keywords:
Ó 2010 Elsevier Ltd. All rights reserved.
Silver nanoparticle
Catalytic annulation
Phosphine ligand
Aurone
In recent years, there has been a great interest in using nanopar-
ticles as catalysts in organic reactions.1 Because of their easy prepa-
ration and being relative stable in air, the nanoparticles of coinage
metals such as copper, silver, and gold were widely reported; and
there are many excellent examples on their applications as cata-
lysts.2 In contrast to the many examples of using copper or gold
nanoparticles as catalysts for organic reactions, there are only a
few reports on using silver nanoparticles (SNPs) as catalysts; and
in most of the cases SNPs worked as dehydrogenation catalysts.3
Herein, we report a novel silver nanoparticle-catalyzed cyclization
of 2-(1-hydroxy-3-arylprop-2-ynyl)phenols (1) in water, leading
to an efficient and expeditious synthesis of aurones (3),4 which have
exhibited a wide range of biological activities such as antifungal
agents, tyrosinase inhibitors, antioxidant, and others5 (Scheme 1,
route A). With the promotion of a phosphine ligand and water, silver
nanoparticles showed extremely high catalytic activities towards
the annulation of 1 in good yields as well as excellent regio- and ste-
reoselectivities. To the best of our knowledge, it is also the first
example regarding the ligand-promotion observed in silver nano-
particle-catalyzed reactions.6 Furthermore, the silver nanoparticles
could be recovered and reused effectively several times.
B).7 During our further studies on the mechanism of the reaction,
accidentally, the silver black precipitated on the stir bar, which
resulted from the decomposition of Cy3P-silver(I) complex, was
found to show a certain catalytic activity to the annulation of 1 with
the promotion of a phosphine ligand in water.8 Thus, surfactant-free
silver nanoparticle catalysts and carbon black-supported silver
nanoparticles (CSNs) catalysts were synthesized and utilized in the
cyclization of 1. The average size of silver nanoparticles is ca.
50 nm based on the TEM image.9
The annulation of 2-(1-hydroxy-3-phenylprop-2-ynyl)phenol
(1a) was selected as the prototype reaction, and some ligands
and solvents were examined (Table 1). As demonstrated in Table 1,
both SNPs and CSNs showed excellent activities at room tempera-
ture to catalyze the cyclization promoted by a phosphine ligand in
a water–toluene mixed solvent (entries 1 and 2, Table 1). Although
SNPs gave higher activities than CSNs, considering their conve-
nience in handling and storage, the latter were selected for further
investigations.10
Control experiments in entries 3 and 4 showed that phosphine
ligands can promote the cyclization effectively: in the absence of a
phosphine ligand, no reaction was observed even at 100 °C, and
most starting materials were recovered. A series of phosphine li-
gands, including both mono- and bidentate ligands, were then
screened. Among the monodentate phosphine ligands, Ph3P, Cy3P,
and tri-o-tolylphosphine showed good to excellent activities at
room temperature, and up to 95% yield of the desired product
was obtained with the addition of 10 mol % of n-Bu3P at 50 °C
(entries 2, and 5–7). It is worthy noting that bidentate phosphine
ligands such as DPPE and DPPP decreased the catalytic activities
Recently, we developed
a highly efficient alkynylation–
cyclization of terminal alkynes with salicylaldehydes generating
substituted 2,3-dihydrobenzofuran-3-ol derives (2) by using
Cy3P-silver(I) complex as the catalyst in water (Scheme 1, route
⇑
Corresponding authors. Tel.: +86 25 52112902; fax: +86 25 52112626 (X.Y.);
tel.: +1 514 3988457; fax: +1 514 3988457 (C.J.L.).
E-mail addresses: cj.li@mcgill.ca (C.-J. Li), yaoxq@nuaa.edu.cn (X. Yao).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.065

M. Yu et al. / Tetrahedron Letters 51 (2010) 6722–6725
6723
O
OH
OH
Route A
R
catalyzed
R
oxidation
R
O
annulation
O
OH
R'
2
1
3
R'
R'
BuLi
CHO
+
OH
Ag(I) complex-catlyzed
addition-cyclization
Route B
R
Ar
H
Scheme 1. The synthesis of aurones based on the cyclization of 1.
(entries 8 and 9). Considering its cost and convenience in handling,
we then chose PPh3 as the ligand. Even with a lower loading or at
low temperature, ca. 90% yields were still achieved with a pro-
longed reaction time (entries 10–12).
Considering phosphine ligands might be easily oxidized under
the reaction conditions, triphenylphosphine oxide was utilized
alone and together with SNPs, respectively (entries 22 and 23);
and no reaction was observed in either case. On the other hand,
in order to remove any possible silver ions that remained on the
surface, the SNPs catalyst was treated by NaBH4 solution before
its usage, and no obvious decrease in catalytic activity was ob-
served (entry 24).
Under the optimized reaction conditions (10 mol % of CSNs,
10 mol % of PPh3 and 10 mol % of i-Pr2NEt in water–toluene mixed
solvent),11 the scope of this transformation was examined, and the
results are summarized in Table 2. A variety of substituted 2-(1-hy-
droxy-3-arylprop-2-ynyl)phenols (2) with electron donating or
electron withdrawing functional groups were compatible under
our reaction conditions: all these reactions were completed in 1–
3 h, and good to excellent yields were obtained (entries 2–13).
The effect of water in the phosphine-promoted, CSNs/SNPs-cat-
alyzed annulation was also studied. In the absence of water, almost
no reaction was observed at room temperature with either SNPs or
CSNs as catalysts; whereas much lower yields were observed and a
longer reaction time was required even at 100 °C (entries 13–16)
Some N-donor ligands were also evaluated (entries 18–21).
Bipyridine exhibited good activity to give the desired product in
moderate yields. Noticeably, when i-Pr-Pybox was introduced, up
to 90% yield of the cyclization product was obtained in 1 h (entry
20).
In order to exclude some other factors probably leading to the
same results, several control experiments were also carried out.
Table 1
Silver nanoparticles-catalyzed cyclization of 1aa
OH
OH
OH
cat. & ligand (cat.)
base (cat.), sol.
O
1a
2a
Entry
Catalyst (mol %)
Ligand (mol %)
Base (mol %)
Solvent
Conditions
Resultb
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24d
SNPs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
SNPs (10)
SNPs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
CSNs (10)
—
Ph3P (10)
Ph3P (10)
—
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (20)
i-Pr2NEt (20)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
—
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
i-Pr2NEt (10)
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Toluene
rt, 0.5 h
rt, 1 h
rt, 1 h
92%
92%
NDc
NDc
85%
95%
83%
75%
85%
90%
92%
89%
Trace
82%
Trace
63%
7%
79%
NDc
90%
NDc
NDc
Trace
86%
—
100 °C, 1 h
rt, 1.5 h
50 °C, 1 h
rt, 0.5 h
50 °C, 2 h
50 °C, 1 h
rt, 3 h
rt, 1 h
0 °C, 3 h
rt, 1 h
100 °C, 1 h
rt, overnight
100 °C, 4 h
rt, 1 h
rt, 1 h
50 °C, 1 h
rt, 1 h
Cy3P (10)
n-Bu3P (10)
o-Tol3P (10)
dppp (10)
dppb (10)
Ph3P (5)
Ph3P (20)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
bpy (10)
Pyridine (10)
i-Pr-Pybox (10)
i-Pr-Box (10)
Ph3P@O (10)
Ph3P@O (10)
Ph3P (10)
Toluene
Toluene
Toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
Water–toluene
50 °C, 1 h
rt, overnight
rt to 60 °C, 4 h
rt, 1 h
SNPs (10)
SNPs (10)
a
Conditions: 2-(1-hydroxy-3-phenylprop-2-ynyl)phenol (0.1 mmol), CSNs (10 mol %, based on silver), SNPs (10 mol %), water (1.5 mL) and toluene (0.5 mL); all reactions
were carried out in standard Schlenk system under nitrogen.
b
Isolated yield.
Not detected.
c
d
The SNPs were treated by 0.1 mol/L of NaBH4 ethanol solution before their use.

6724
M. Yu et al. / Tetrahedron Letters 51 (2010) 6722–6725
Table 2
Table 3
Silver nanoparticle-catalyzed cyclization of 1a
Application of CSNs and SNPs as a recyclable catalyst in the cyclization of 1a and 1ba
CSNs (10 mol%)
OH
OH
OH
OH
OH
i-Pr2NEt (10 mol%) R1
Ag Cat. (10 mol%)
i-Pr2NEt (10 mol%)
Ph3P (10 mol%)
R
R1
R
Ph3P (10 mol%)
O
toluene:water = 1:3
O
OH
R2
2a-2m
Product
Toluene:water =1£º3
rt
R2
R3
1a
R = H
1b R = Br
2a-b
1a-1m
R3
Entry Catalyst Substrate
Yield (%)b and reaction time (h)
Cycle 1 Cycle 2 Cycle 3
Entry
Substrate
R1
R2
R3
Time (h)
Yield (%)b
Fresh
1
2
3
4
5
6
7
8
9
10
11
12
13
1a
1b
1c
1d
1e
1f
1g
1h
1i
H
Br
Cl
NO2
Cl
Br
t-Bu
Cl
t-Bu
H
H
H
H
H
H
H
1
2a
2b
2c
2d
2e
2f
2g
2h
2i
92
90
88
90
83
85
93
88
89
90
91
90
85
1
2
3
CSNs
CSNs
SNPs
1a
1b
1a
92 (1 h)
90 (2 h)
90 (8 h) 90 (10 h) 89 (10 h)
85 (8 h) 85 (10 h) 84 (10 h)
92 (0.5 h) 90 (8 h) 89 (10 h) 75 (10 h)
H
2
H
2
H
H
H
H
1.5
1.5
1.5
3
Cl
Br
Br
NO2
NO2
H
a
Conditions: 1a or 1b (0.1 mmol), CSNs (10 mol %), PPh3 (10 mol %), and i-Pr2NEt
(10 mol %) were mixed together and stirred in water (1.5 mL)–toluene (0.5 mL)
mixed solvent at room temperature.
H
3
b
Isolated yield.
H
2
1j
1k
1l
Cl
OMe
Me
Me
1
2
1.5
1.5
2j
H
H
H
2k
2l
2m
H
Br
Table 4
Silver particle-catalyzed cyclization of 1aa
1m
a
Conditions:
2-(1-hydroxy-3-arylprop-2-ynyl)phenols
(0.1 mmol),
CSNs
OH
OH
(10 mol %), PPh3 (10 mol %), and i-Pr2NEt (10 mol %) were mixed together and
stirred in water (1.5 mL)–toluene (0.5 mL) mixed solvent at room temperature.
cat. & ligand (cat.)
b
Isolated yield.
O
OH
base (cat.), sol.
1a
2a
No obvious substituent effect on the rate or yield of the reaction
was observed. In all these cases, no other regio- or stereoisomer
was observed.
The crude product 2a, from the cyclization reaction on an en-
larged scale following the procedure above, was separated with
toluene from water, and was then oxidized by MnO2 directly with-
out further purification. The final aurone product 3a was isolated
in 88% yield (Scheme 2).
One of the advantages of heterogeneous catalysts is their easy
separation from the reaction mixture: they can be recovered and
reused readily. We are also interested in recycling the catalysts
as well as in the catalytic activity of the annulation. Thus, the solid
catalysts were separated and recovered conveniently by centrifu-
gation from the reaction mixture, and then, new solvent, substrate,
and fresh phosphine ligand were added. Following this procedure,
CSNs, and SNPs were recycled for three times with selected sub-
strates, and the results were listed in Table 3.
With 1a as the substrate and CSNs as catalyst, an 89% yield was
still obtained in the fourth reaction without a distinct decrease
compared to the first cycle (entry 1, Table 3). It was noteworthy
mentioning here that the reaction time was prolonged in the last
three recycles. When 1b was utilized as a substrate, the same trend
was observed (entry 2). On the other hand, with non-supported
catalyst (SNPs), the last recycle resulted in a prominent decrease
in yield (entry 3).
Entry Conditions
Yieldb
92%
1
2
3
4
5
SNPs 10 mol %, Ph3P 10 mol %, i-Pr2NEt 10 mol %, water–
toluene, rt, 0.5 h
A 10 mol %, Ph3P 10 mol %, i-Pr2NEt 10 mol %, water–toluene, Trace
rt, 1.5 h
A 10 mol %, Ph3P 10 mol %, i-Pr2NEt 10 mol %, water–toluene, 85%
60 °C, 1.5 h
B 10 mol %, Ph3P 10 mol %, i-Pr2NEt 10 mol %, water–toluene, Trace
rt, 1.5 h
B 10 mol %, Ph3P 10 mol %, i-Pr2NEt 10 mol %, water–toluene, 87%
60 °C, 1.5 h
a
Conditions: 1a (0.1 mmol), catalyst (10 mol %), PPh3 (10 mol %), i-Pr2NEt
(10 mol %), water (1.5 mL) and toluene (0.5 mL).
b
Isolated yield.
Thus, in order to further understand the size-effect on the silver-par-
ticle catalyst, two kinds of silver catalysts were synthesized without
any protective agent by using NaBH4 (sample A) or aqueous hydra-
zine (sample B) as reducing agents, respectively. Their SEM images
showed that the average size is around 15 lm.
With the two kinds of silver particles prepared above as cata-
lysts and PPh3 as the ligand, the cyclization of 1a was carried out
in the water–toluene two-phase system. These larger-sized silver
particles showed much lower catalytic activities than the SNPs
catalysts (Table 4, entry 1 vs entries 2 and 4). Trace product was
observed at room temperature, while ca. 85% yields were obtained
at 60 °C with a longer reaction time (entries 3 and 5).
WesuspectedthatthedecreasedreactionrateobservedinTable3
might be due to the loss of smaller particles in the process of catalyst
recovery13 and/or the conglomeration of silver nanoparticles.3a
OH
OH
CSNs (10 mol%)
i-Pr2NEt (10 mol%)
PPh3 (10 mol%)
OH
O
MnO2, rt, 4h
Ph
O
Ph
Toluene:water=1£º3
rt, 1h
O
Ph
2a
3a
1a 3a
1a
2 mmol
(no purification)
over all yield from
to : 88%
Scheme 2. Cyclization–oxidation one-pot reaction to aurone 3a.12

M. Yu et al. / Tetrahedron Letters 51 (2010) 6722–6725
6725
6499–6510; (c) Garcia, H.; Iborra, S.; Primo, J.; Miranda, M. A. J. Org. Chem.
1986, 51, 4432–4436; (d) An, Z.-W.; Catellani, M.; Chiusoli, G. P. J. Organomet.
Chem. 1990, 397, 371–373; (e) Jong, T.-T.; Leu, S.-J. J. Chem. Soc., Perkin Trans. 1
1990, 423.
In conclusion, silver nanoparticles and carbon black-supported
silver nanoparticles were utilized as highly efficient catalysts for
the cyclization of 2-(1-hydroxy-3-arylprop-2-ynyl)phenols with
good to excellent yields as well as high regio- and stereo-selectiv-
ities. In the reaction, phosphine ligand and water proved to be the
key factors that activate the solid catalyst. Furthermore, the nano-
particle catalysts can be recovered and reused at least three times
with only decreased reaction rates. The detailed mechanism, the
effect of particle size and particle support as well as the scope of
the reaction are currently under further investigation.
5. For a review, see: Boumendjel, A. Curr. Med. Chem. 2003, 10, 2621–2630.
6. There are few examples reported about the ligand effect on coinage metal
nanoparticle-catalyzed reactions. For a recent example on a phosphine ligand-
stabilized Au(0) nanoparticle-catalyzed diboration, see: Ramirez, J.; Sanau, M.;
Fernandez, E. Angew. Chem., Int. Ed. 2008, 47, 5194–5197.
7. Yu, M.; Skouta, R.; Zhou, L.; Jiang, H.; Yao, X.; Li, C.-J. J. Org. Chem. 2009, 74,
3378–3383.
8. There was a similar example about the cyclization of alkynoic acids, which
could be catalyzed by silver metal to give furanone/pyranone with high
dilutions in DMF over a long reaction time. See: (a) Negishi, E.-I.; Kotora, M.
Tetrahedron 1997, 53, 6707–6738; (b) Ogawa, Y.; Maruno, M.; Wakamatsu, T.
Synlett 1995, 871–872; (c) Ogawa, Y.; Maruno, M.; Wakamatsu, T. Heterocycles
1995, 41, 2587–2599.
Acknowledgments
We are grateful to the financial support from National Natural
Science Foundation of China (20602018 to X.Y.), and NUAA Re-
search Funding (No. 2010169 to X.Y.).
9. Silver nanoparticles and carbon black-supported silver nanoparticles were
prepared following a reported method. See: Sun, L.; Zhang, Z.; Dang, H. Mater.
Lett. 2003, 57, 3874–3879.
10. The dry CSNs catalyst can be stored in air and remains catalytically active for at
least one month, while the catalytic activity lasts less than one week for SNPs.
The latter can be stored in ethanol for a longer time.
Supplementary data
11. Typical procedure 1 (entries 1, 2 in Table 1). 2-(1-Hydroxy-3-phenylprop-2-
ynyl)phenol (1a, 0.1 mmol), SNPs (1.1 mg, 0.01 mmol, 10 mol %) or CSNs
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.10.065.
(5.1 mg, 0.01 mmol, 10 mol %), 1.7 lL of i-Pr2NEt (0.01 mmol, 10 mol %), and
Ph3P (2.6 mg, 0.01 mmol, 10 mol %), were added into a 10-mL Schlenk tube13
with 0.5 mL toluene and 1.5 mL distilled water under nitrogen atmosphere.
The mixture was stirred at room temperature for 1 h. The reaction was stopped
and extracted with ether (3 Â 3 mL). The combined organic phase was dried
with Na2SO4 and concentrated under reduced pressure. The residue was
purified by flash column chromatography on silica gel (eluent: 20:1 hexanes/
ethyl acetate). Compound 2a was obtained in 92% yield.
References
1. For recent reviews, see: (a) Shiju, N. R.; Guliants, V. V. Appl. Catal., A 2009, 356,
1–17; (b) Somorjai, G. A.; Park, J. Y. Angew. Chem., Int. Ed. 2008, 47, 9212–9228;
(c) Gu, Y.; Li, G. Adv. Synth. Catal. 2009, 351, 817–847.
12. Typical procedure 2 (Scheme 2). Following the procedure described in typical
procedure 1, 2 mmol of 2-(1-hydroxy-3-phenylprop-2-ynyl)phenol (1a) was
added into a mixed solvent of water (6 mL) and toluene (2 mL), in the presence
2. (a) Astruc, D.; Lu, F.; Aranzaes, J. M. Angew. Chem., Int. Ed. 2005, 44, 7852–7872;
(b) Corma, A.; Garcia, H. Chem. Soc. Rev. 2008, 37, 2096–2126; (c) Ref. 1c.
3. (a) Yan, W.; Wang, R.; Xu, Z.; Xu, J.; Lin, L.; Shen, Z.; Zhou, Y. J. Mol. Catal. A:
Chem. 2006, 255, 81–85; (b) Chen, L.; Ma, D.; Pietruszka, B.; Bao, X. J. Nat. Gas
Chem. 2006, 151, 81–190; (c) Wang, S.; He, X.; Song, L.; Wang, Z. Synlett 2009,
447–450; (d) Murugadoss, A.; Goswami, P.; Paul, A.; Chattopadhyay, A. J. Mol.
Catal. A: Chem. 2009, 304, 153–158; (e) Shimizu, K.-I.; Sato, R.; Satsuma, A.
Angew. Chem., Int. Ed. 2009, 48, 3982–3986. and the references therein; (f)
Shimizu, K.-I.; Nishimura, M.; Satsuma, A. ChemCatChem 2009, 1, 497–503; (g)
Shimizu, K.-I.; Ohshima, K.; Satsuma, A. Chem. Eur. J. 2009, 15, 9977–9980.
4. A highly efficient synthetic methodology of aurones based on gold(I)-catalyzed
cyclization of 1 was reported recently, see: Harkat, H.; Blanc, A.; Weibel, J.-M.;
Pale, P. J. Org. Chem. 2008, 73, 1620–1623. Some other methods for the
synthesis of aurones, also see: (a) Imafuku, K.; Honda, M.; McOmie, J. F. W.
Synthesis 1987, 199–201; (b) Thakkar, K.; Cushman, M. J. Org. Chem. 1995, 60,
of CSNs (102 mg, 0.2 mmol, 10 mol %), 34 lL i-Pr2NEt (0.2 mmol, 10 mol %) and
Ph3P (52.4 mg, 0.2 mmol, 10 mol %). When the reaction was over, the aqueous
layer was removed together with the solid catalyst by pipette. The toluene
solution was diluted to 5 mL and cooled in an ice bath, and then MnO2
(6 mmol) was added. The mixture was stirred at room temperature for 4 h, and
then, filtered through celite. The solution was concentrated under a reduced
pressure, and the residue was purified by flash column chromatography on
silica gel (eluent: hexanes/EtOAc 40:1). Compound 3a was obtained in 88%
yield.
13. During the catalyst separation by centrifugation, we did notice that some
colloidal suspension of SNPs/CSNs was washed away together with the mixed
solvent.