Aerobic oxygenation of phenylboronic acid promoted by thiol derivatives under gold-free conditions: A warning against gold nanoparticle catalysis

Article abstract of DOI:10.1016/j.tetlet.2012.08.142

Oxygenation of phenylboronic acid to phenol is promoted by thiol derivatives such as 2-aminothiophenol under aerobic conditions in water without metal catalyst. A plausible mechanism involves autoxidation of thiol to generate hydrogen peroxide in situ, which converts phenylboronic acid into phenol under basic conditions. Since thiols are often utilized as protective ligands for gold nanoparticles (AuNPs), this result is a warning that excess thiols and free thiols liberated from the Au surface could participate in aerobic oxidations catalyzed by thiol-protected AuNPs.

Full text of DOI:10.1016/j.tetlet.2012.08.142

Tetrahedron Letters 53 (2012) 6104–6106
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Aerobic oxygenation of phenylboronic acid promoted by thiol derivatives
under gold-free conditions: a warning against gold nanoparticle catalysis
Patcharin Kaewmati a,b, Ekasith Somsook a, , Raghu Nath Dhital b, Hidehiro Sakurai b,c
⇑
a NANOCAST Laboratory, Center for Catalysis, Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Mahidol University, 272 Thung Phaya Thai,
Rama VI Rd., Ratchathewi, Bangkok 10400, Thailand
b Department of Functional Molecular Science, School of Physical Sciences, The Graduate University of Advanced Studies (SOKENDAI), Myodaiji, Okazaki 444-8787, Japan
c Research Center for Molecular Scale Nanoscience, Institute for Molecular Science, Myodaiji, Okazaki 444-8787, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 May 2012
Revised 18 August 2012
Accepted 31 August 2012
Available online 8 September 2012
Oxygenation of phenylboronic acid to phenol is promoted by thiol derivatives such as 2-aminothiophenol
under aerobic conditions in water without metal catalyst. A plausible mechanism involves autoxidation
of thiol to generate hydrogen peroxide in situ, which converts phenylboronic acid into phenol under basic
conditions. Since thiols are often utilized as protective ligands for gold nanoparticles (AuNPs), this result
is a warning that excess thiols and free thiols liberated from the Au surface could participate in aerobic
oxidations catalyzed by thiol-protected AuNPs.
Keywords:
Ó 2012 Elsevier Ltd. All rights reserved.
Aerobic oxygenation
Gold nanoparticle catalysis
Phenol
Gold nanoparticles (AuNPs) are of significant interest in cataly-
sis due to their high catalytic activities especially for aerobic oxida-
tion under mild conditions.1–4 Since the catalytic activity of AuNPs
is highly dependent on their size, controlling the size of AuNPs is
an important issue.5–7 The ability of thiols for tight binding on
the surface of gold has been utilized for many applications includ-
ing self-assembled monolayer (SAM) preparation and size- and
shape-controlled synthesis of AuNPs at the atomic level.8–11 On
the other hand, due to the strong affinity, thiols mostly work as a
poison to inhibit the catalytic activity of the gold surface. Hence
pretreatment such as annealing is usually required for making a
catalyst from the thiol-protected AuNPs.12 However, several re-
ports demonstrated the catalytic reaction by thiol-protected AuNPs
or oxidation of thiols to the corresponding disulfides catalyzed by
AuNPs.13–15 These results have the potential to solve the dilemma
between the size-control and the catalytic activity. Among them,
poly(2-aminothiophenol) (PATP)-protected gold was reported to
catalyze the Suzuki–Miyaura coupling.16
AuNPs/PATP were prepared according to the reported method16
by redox reactions of HAuCl4ꢀ3H2O and 2-aminothiophenol in 1 M
HCl solutions. For this work, two different molar ratios of gold(III)
to 2-aminothiophenol (1:1 and 1:100) were prepared. Transmis-
sion electron microscopy (TEM) images of the AuNPs/PATP, as
shown in Figure 1, show that the sizes of the nanoparticles are
approximately 1–3 nm for both ratios of HAuCl4 and 2-
aminothiophenol.
First, we attempted a Suzuki–Miyaura coupling using AuNPs/
PATP. However, we failed to achieve cross-coupling reaction be-
tween phenylboronic acid (1) and several aryl halides including
chlorobenzene, bromobenzene, and 4-chlorobenzoic acid. These
results surprised us as AuNPs are well known to catalyze the
homocoupling of 117,20–25; therefore at the very least biphenyl
(2), the homocoupling product, should have been observed even
though cross-coupling did not take place. Therefore we shifted
our focus to the homocoupling of 1 and the results are shown in
Table 1.
In the course of our studies on AuNPs stabilized by redox-active
polymers and their catalytic activities,17 we also investigated the
reactions using AuNPs/PATP and related catalysts and found that,
unexpectedly, aerobic oxygenation of phenylboronic acid18,19 was
promoted by thiols under gold-free conditions.
All the reactions were carried out in the presence of 300 mol %
of K2CO3 at 80 °C in water under air for 24 h. In order to exclude
the possibility of external poisoning of the catalyst, the reaction
was performed in the presence of 2 atom% of AuNPs/PVP [PVP =
poly(N-vinyl-2-pyrrolidone)], which has been reported to afford
2 and phenol (3), the oxygenated product, in 72% and 23% yields,
respectively.20 At 80 °C, the yields of 2 and 3 were 74% and 26%,
respectively, in good accordance with the previous result (entry
1). Next, the catalyst was changed to AuNPs/PATP (1:2 molar ra-
tio) which gave only a trace amount of 2 and 3 as detected by GC
⇑
Corresponding author. Tel.: +66 2 201 5123; fax: +66 2 354 7151.
E-mail addresses: scess@mahidol.ac.th, ekasith.som@mahidol.ac.th (E. Som-
sook).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.08.142

P. Kaewmati et al. / Tetrahedron Letters 53 (2012) 6104–6106
6105
Figure 1. TEM images of gold nanoparticles stabilized by PATP at different molar ratios of HAuCl4 to 2-aminothiophenol (a) 1:1 and (b) 1:100.
Table 1
Conversion of phenylboronic acid in the presence of AuNPs and/or a thiola
Table 2
Oxidation of phenylboronic acid to phenol in the presence of thiola
Entry
Reagents
Yield (%)
Entry
Thiol
Temp (°C)
Times (h)
Yieldb (%)
2
3
1b
2e
3e
4e
5e
6e
7e
AuNPs/PVP (2 atom%)c,d
74
26
Trace
15
72
68
1
2
3
4
5
6
7
8
2-Aminothiophenol
2-Aminothiophenol
2-Aminothiophenol
2-Aminothiophenol
2-Aminothiophenol
2-Aminothiophenol
2-Aminothiophenol
2-Aminothiophenol
3-Aminothiophenol
3-Aminothiophenol
4-Aminothiophenol
4-Aminothiophenol
Thiophenol
80
80
80
80
80
60
40
28
80
80
80
80
80
80
80
80
80
24
12
6.5
12c
12d
12
12
12
12
6.5
12
6.5
12
12
12
12
12
>99
>99
77
86
39
73
37
21
>99
65
>99
55
87
74
96
AuNPs/PATP (1:2)(3 atom%)c,f
AuNPs/PATP(1:100)(3 atom%)c,g
AuNPs/PVP (2 atom%)c + PATP (100 mol %)h
PATP (100 mol %)i
Trace
Trace
Trace
Trace
Trace
Trace
2-Aminothiophenol (100 mol %)j
2-Aminothiophenol (200 mol %)k
84
>99
a
General reaction condition: phenylboronic acid (0.25 mmol), K2CO3
9
(0.75 mmol), H2O (15 mL), 80 °C, 24 h.
10
11
12
13
14
15
16
17
Analyzed by 1H NMR spectroscopy with 1,4-dioxane as internal standard.
b
c
Percentage of gold atoms.
AuNPs/PVP (0.5 mM, 10 mL).
Analyzed by GC with hexadecane as internal standard.
d
e
2-Fluorothiophenol
2-Methoxythiophenol
2-Mercaptophenol
Cysteine
f
HAuCl4ꢀ3H2O (0.0075 mmol), PATP (derived from 2-aminothiophenol)
(0.015 mmol).
72
58
g
HAuCl4ꢀ3H2O (0.0075 mmol), PATP (0.75 mmol).
h
AuNPs/PVP (0.5 mM, 10 mL), PATP (0.25 mmol).
a
i
General reaction condition: phenylboronic acid (0.25 mmol), K2CO3
(0.75 mmol), H2O (15 mL), 80 °C, 24 h.
PATP (0.25 mmol).
0.25 mmol.
0.50 mmol.
j
b
k
Analyzed by GC with hexadecane as internal standard.
K2CO3 (200 mol %).
K2CO3 (100 mol %).
c
d
(entry 2), while increasing the amount of PATP (1:100 molar ra-
tio) yielded 15% of 3 with a trace amount of 2 (entry 3). These re-
sults indicated that the strong interaction of PATP with the Au
surface changes the catalytic activity. Due to the weak interaction
of PVP with the Au surface, matrix exchange proceeded by adding
another matrix having strong AuNPs coordination ability. The
reaction was carried out in the presence of AuNPs/PVP in a stoi-
chiometric amount (per thiol unit) of PATP in order to elucidate
the matrix effect. As a result, 2 was not obtained, but the yield
of 3 increased to 72% (entry 4). There are two possible explana-
tions for the non-formation of 2. First, the catalyst AuNPs/PATP it-
self might be involved in oxygenation of the C–B bond selectively
(i.e. is inactive toward the homocoupling), and the catalyst gener-
ated in situ under the conditions in entry 4 shows somewhat bet-
ter activity than the isolated AuNPs/PATP in entry 3. Second, PATP
might deactivate Au via strong coordination and the residual free
thiol unit promotes the reaction. To check the second possibility,
the reaction was performed in the absence of the Au catalyst, that
is, only 100 mol % of PATP was added, giving 3 in 68% yield with-
out the formation of 2 (entry 5). Hence, the gold catalyst itself
does not participate in the oxygenation reaction but it was of
interest whether the redox activity of PATP played an important
role in this oxidation reaction. Thus, 2-aminothiophenol, a mono-
mer of PATP, was tested and it was found that in the presence of
100 mol % of 2-aminothiophenol the yield of 3 increased to 84%
(entry 6), and quantitative conversion was achieved by adding
200 mol % of 2-aminothiophenol (entry 7). It should be noted that
2,20-diaminodiphenyl disulfide was obtained as a co-product. Fi-
nally, we concluded that aerobic oxygenation of phenylboronic
acid was promoted by 2-aminothiophenol without an Au catalyst.
Further reaction optimization was investigated for the transfor-
mation of phenylboronic acid into phenol as shown in Table 2. A
thiol (200 mol %) was used in all reactions. First, reaction time
was monitored as shown in entries 1–3 to find that oxygenation
was complete within 12 h. Next, the amount of base was screened.
On decreasing the amount of K2CO3 from 200 to 100 mol %, the
yield decreased from 86% to 39% (entries 4 and 5), therefore the
optimum amount of base was determined to be 300 mol %. The
reaction temperature was also monitored as shown in entries 6–

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P. Kaewmati et al. / Tetrahedron Letters 53 (2012) 6104–6106
from O2. Since an excess amount of thiol is often used in the prep-
aration of thiol-protected AuNPs and free thiols are usually found
and also liberated even from the Au surface, it should be consid-
ered that the free thiols could also promote the aerobic oxidation
reaction.
Acknowledgments
Scheme 1.
Financial support by the Research Development and Engineer-
ing (RD&E) fund through the National Nanotechnology Center
(NANOTEC), the National Science and Technology Development
Agency (NSTDA) (Project No. NN-B-22-FN3-15-52-16), Center for
Innovation in Chemistry (PERCH-CIC), and the Office of the Higher
Education Commission and Mahidol University under the National
Research University Initiative are acknowledged.
8. Although the reaction proceeded even at room temperature
(28 °C, 12 h, 21% yield entry 8), the higher temperature was more
convenient to complete the reaction in a shorter time. Also of
interest was the structural demand of the thiol reagent, in
particular, the role of the amino group at the ortho-position for
the chelating effect. Thus thiol reagents were screened under the
optimized conditions. As shown in entries 9 and 11, the regioisom-
ers, 3-aminothiophenol and 4-aminothiophenol, also promoted the
oxygenation smoothly to afford phenol, quantitatively. When the
reactions were terminated after 6.5 h, the yields of 3 were 65%
and 55% yields, respectively, and slightly lower than those of the
2-aminothiophenol reactions (entries 3, 10, and 12), suggesting
some chelating/substituent effect. The yields of 3 were slightly
decreased in the case of thiophenol, 2-fluorothiophenol, and
2-methoxythiophenol (entries 13–15). Since the above thiols
showed poorer solubility in water which probably resulted in the
lower yield, water-soluble thiols such as 2-mercaptophenol and
cysteine were chosen, however these gave lower yields (72% and
58%, respectively) (entries 16–17). To summarize these optimiza-
tion studies, it was found that most of the thiol compounds
generally promoted the aerobic oxygenation of phenylboronic acid
in aqueous basic solution. Among them, 2-aminothiophenol
exhibited superior reactivity.
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