Silica nanoparticles as a reusable catalyst: A straightforward route for the synthesis of thioethers, thioesters, vinyl thioethers and thio-Michael adducts under neutral reaction conditions

Article abstract of DOI:10.1039/b9nj00399a

A simple and straightforward route for the synthesis of thioethers, thioesters, vinyl thioethers and thio-Michael adducts has been demonstrated using silica nanoparticles (NPs) as a reusable catalyst via the 1,2-addition of thiols to alkenes, alkynes and alkyl/acyl halides, and the 1,4-addition of thiols to conjugated alkenes at room temperature.

Full text of DOI:10.1039/b9nj00399a

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Silica nanoparticles as a reusable catalyst: a straightforward route for
the synthesis of thioethers, thioesters, vinyl thioethers and thio-Michael
adducts under neutral reaction conditions
Subhash Banerjee,*a Jayanta Das,ab Richard P. Alvareza and
Swadeshmukul Santra*abc
Received (in Gainesville, FL, USA) 12th August 2009, Accepted 29th September 2009
First published as an Advance Article on the web 16th November 2009
DOI: 10.1039/b9nj00399a
A simple and straightforward route for the synthesis of thioethers, thioesters, vinyl thioethers and
thio-Michael adducts has been demonstrated using silica nanoparticles (NPs) as a reusable
catalyst via the 1,2-addition of thiols to alkenes, alkynes and alkyl/acyl halides, and the
1,4-addition of thiols to conjugated alkenes at room temperature.
Thioethers and thioesters play important roles in biological
and chemical processes,1 and also serve as useful building
blocks for various organosulfur compounds.2 Therefore, the
synthesis of these compounds in a ‘‘green’’ and ‘‘straightforward’’
way would be of great importance. Traditionally, these
compounds are synthesized by the addition of thiolate anions
to organic halides,3–15 alkenes and alkynes16–19 by using
different reagents and catalysts such as BuLi,3 phase transfer
catalysts,4 metal complexes,5–7 organometallic sulfides,8–10
clay materials,11 trifluoroacetic acid,12 CSF-Celite,13
Scheme 1
thiomolybdates,14 ionic liquids,15 refluxing in benzene17 and
water.18 However, most of these protocols involve the use of a
mixture. The reaction mixture was centrifuged, washed with
strong base, highly toxic and expensive catalysts, and
ethanol and the particles characterized by transmission
hazardous organic solvents. Thus, the development of a robust
electron microscopy (TEM) (Fig. 1). The average size of these
and general procedure for the synthesis of thioethers and
particles was found to be in the range 150–250 nm. These silica
thioesters via the 1,2-addition of thiols to alkyl/acyl halides,
NPs were used for the synthesis of thioethers through the 1,2-
alkenes and alkynes, and the 1,4-addition of thiols to
addition of thiols to alkenes, alkynes and alkyl halides. For the
conjugated alkenes involving a simple, non-toxic and neutral
anti-Markovnikov addition,w the alkene or alkyne was added
to a mixture of the thiol and the silica NPs, and the reaction
catalyst would be attractive to address these limitations.
Recently, we have observed the remarkable inherent catalytic
mixture stirred at room temperature until completion of the
activity20,21 of silica NPs. These NPs efficiently catalyzed the
reaction (TLC). The results are summarized in Table 1.
anti-Markovnikov addition of thiols to alkenes, leading to
A number of alkenes participated in this reaction to provide
linear thioethers. These observations prompted us to explore
linear thioethers. All the reactions were performed at room
the potential of this catalyst for other related reactions. In this
temperature to produce linear thioethers in high yield
paper, we report the application of silica NPs to the synthesis
(85–98%) after short reaction times (0.5–1.5 h). It was
of thioethers and thioesters by the 1,2-addition of thiols to
observed that the addition of thiophenol to cyclohexene was
alkyl and acyl halides, and the 1,4-addition of thiols to
unsuccessful in absence of the catalyst. The additions of thiols
conjugated alkenes. To highlight the importance of this study,
to alkenes were inconsistent when using amorphous silica as a
we also report a summary of our previous results on anti-
catalyst, and only 50% phenylsulfanylethylbenzene was
Markovnikov additions (Scheme 1).
The silica NPs were synthesized using the well known Stober
method,22 which involves the base-catalyzed condensation
w A typical experimental procedure for the anti-Markovnikov addition
of olefins to thiols (entry 6, Table 1): Styrene (104 mg, 1 mmol) was
added to a mixture of thiophenol (110 mg, 1 mmol) and silica NPs
of tetraethyl orthosilicate (TEOS) in a 1 : 1 ethanol–water
(B2–3 mg, 1 wt%) under neat conditions. The reaction mixture was
a NanoScience Technology Center, University of Central Florida,
12424 Research Parkway, Suite 400, Orlando, FL 32826, USA.
E-mail: ocsb2009@yahoo.com
stirred for 0.5 h at room temperature until completion (TLC). Extrac-
tion with ethyl acetate followed by evaporation of the solvents lead to
the crude product in an almost pure form. Purification by short
column chromatography over silica gel (hexane–ethyl acetate, 95 : 5)
provided 2-phenylsulfanylethylbenzene (209 mg, 98%) as a colorless
liquid. The product was characterized by 1H NMR and IR spectro-
scopy, and the results compared with reported data.20 This procedure
was followed for all of the reactions listed in Table 1.
b Department of Chemistry, University of Central Florida,
12424 Research Parkway, Suite 400, Orlando, FL 32826, USA
c Biomolecular Science Center, University of Central Florida,
12424 Research Parkway, Suite 400, Orlando, FL 32826, USA.
E-mail: ssantra@mail.ucf.edu
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isolated by the addition of thiophenol to styrene. The addition
of thiophenol to 1-chloromethyl-4-vinylbenzene was highly
selective in nature (entry 10, Table 1). The reactive chloro-
methyl group in the molecule remained intact, even after the
use of two equivalents of thiophenol, which could be further
functionalized.
These NPs also promoted the addition of thiols to alkynes,
leading to vinyl thioethers in high yields (85–96%) at
room temperature. The results for the addition of thiols
to alkynes are represented by entries 11–13 in Table 1.
Interestingly, we observed 100% anti-Markovnikov addition,
and no Markovnikov adducts were isolated in any case studied
herein. Alkyl, allyl and acyl halides were also thiolated by
this catalyst at room temperature to produce thioethers and
thioesters, respectively (Table 2). In a simple experimental
Fig. 1 A TEM image of the silica NPs.
Table 1 The silica NP-catalyzed anti-Markovnikov addition of thiols to alkenes and alkynes
Entry
1
Thiol
PhSH
Alkene
Product
Time/h
1.5
Yield (%)a
87
Ref.
20
2
3
PhSH
PhSH
1.5
1.0
85
88
20
20
4
EtSH
1.5
85
20
5
6
PhSH (2 equiv.)
PhSH
1.0
0.5
86
98
20
20
7
8
PhSH
PhSH
0.5
0.5
94
90
20
20
9
PhSH
PhSH
0.5
0.5
90
96
20
20
10
11
12
PhSH
PhSH
PhSH
1.0
1.0
0.5
85
85
96
20
20
20
13
a
The yield refers to those pure isolated products characterized by spectroscopic (1H NMR and IR) data.
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Table 2 The silica NP-catalyzed addition of thiols to alkyl, allyl and acyl halides
Entry
1
Thiol
PhSH
RX
Product
Time/h
20
Yield (%)a
85
Ref.
15
2
3
PhSH
PhSH
1.5
1.0
88
92
15
23
4
5
PhSH
PhSH
1.5
1.5
90
92
24
15
6
7
8
PhSH
PhSH
EtSH
1.5
1.0
2.0
89
87
85
15
15
15
9
PhSH
PhSH
PhSH
PhSH
1.0
1.5
1.5
2.0
95
90
90
85
15
15
15
15
10
11
12
MeCOCl
MeCOSPh
13
14
PhSH
PhSH
2.0
1.5
86
90
15
15
15
PhSH
1.5
90
15
a
The yield refers to those pure isolated products characterized by spectroscopic (1H NMR and IR) data.
procedure,z the alkyl or acyl halide was added to a mixture of
thiol and the silica NPs (5 wt%), and the reaction mixture was
stirred at room temperature until completion of the reaction
(TLC). The reactions of thiols with alkyl halides proceeded
faster in water in comparison to other solvents. The addition
of thiophenols to acyl halides were carried out in neat reaction
conditions. This simple procedure turned out to be applicable
to a number of substituted benzyl and allyl halides, and
we achieved 80–95% yields of thioethers within 2 h. To
investigate the nature of the addition of thiols to allylic
halides, we performed the reaction of thiophenol with crotyl
bromide. The 1,2-addition product was isolated exclusively
and no 1,4-adduct was obtained (entries 10 and 11 in Table 2).
The catalyst was found to be very effective for the synthesis of
thioesters. Both alkyl and aryl acid chlorides were converted to
their corresponding thioesters by a reaction with thiophenol in
the presence of silica NPs under neat conditions (entries 12–15,
Table 2).
z A typical experimental procedure for the 1,2-addition of thiols to
alkyl halides (entry 1, Table 2): Benzyl bromide (170 mg, 1 mmol) was
added to a mixture of thiophenol (110 mg, 1 mmol) and silica NPs
(B15 mg, 5 wt%) in water (0.5 mL). The reaction mixture was stirred
for 2.0 h at room temperature until completion of the reaction (TLC).
Extraction with ethyl acetate followed by evaporation of the solvents
lead to the crude product, which was purified by short column
chromatography over silica gel (hexane–ethyl acetate, 95 : 5) to provide
2-phenylsulfanylethylbenzene (170 mg, 85%). This procedure was
followed for all of the reactions listed in Table 2. The procedure was
also followed for the synthesis of thioesters (Table 2), but all of these
reactions were carried out under neat conditions (without water). All
of the products in Table 1, Table 2 and Table 3 are known and were
characterized from their spectroscopic (1H NMR and IR) data in
comparison with reported values (references are given in the respective
tables).
We have also tested the catalytic activity of silica NPs in
Michael additions, i.e. the 1,4-addition of thiols to conjugated
alkenes. It was observed that silica NPs efficiently catalyzed
the 1,4-addition of thiophenol to conjugated ketones,
carboxylic esters and nitriles under solvent-free conditions;
the results are summarized in Table 3. The 1,4-addition
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Table 3 The 1,4-addition of thiophenol to conjugated alkenes
Entry
1
Thiol
PhSH
Conjugated alkene
Product
Time/min
5
Yield (%)a
98
Ref.
25
5
5
5
98
86
95
2
3
PhSH
PhSH
25
25
4
PhSH
25
a
The yield refers to those pure isolated products characterized by spectroscopic (1H NMR and IR) data.
Scheme 2 A plausible reaction mechanism.
Fig. 2 The reuse of silica NPs in the synthesis of 2-phenylsulfanyl-
ethylbenzene.
This observation establishes the role of the surface groups of
the silica NPs.
reactions were very fast (5–6 min) at room temperature and no
solvents were required.
Conclusions
Finally, after each reaction, the catalyst was recovered,
washed with ethanol and dried for reuse. The catalyst was
reused seven times with minimal loss of catalytic activity.
Fig. 2 shows the variation of yield of 2-phenylsulfanylethyl-
benzene (entry 6, Table 1) with the number times the silica NPs
were recycled.
In conclusion, we have demonstrated a straightforward route
for the synthesis of thioethers, thioesters and vinyl thioethers
catalyzed by simple, neutral and stable silica NPs. The reactions
are considerably fast. This present synthesis strategy offers
several advantages, such as (1) mild reaction conditions
(room temperature), (2) high isolated yields of thioethers
and thioesters, (3) low cost, (4) the use of a non-toxic and
neutral catalyst, (5) recyclability of the catalyst, and (6)
aqueous reaction conditions. Moreover, this study demon-
strates the potential of silica NPs as a catalyst in other organic
reactions.
The silica NPs play a major role in these reactions. A
comparison of the reactivity of different reagents in the
anti-Markovnikov addition of thiophenol to styrene is pre-
sented in Table 4.
Under neutral pH conditions, a silica NP’s surface consists
of silanol groups partly in their neutral form (Si–OH) and
partly in their deprotonated (SiOꢁ) form. Here, we speculate
that SiOꢁ polarizes the SH hydrogen of thiols with the Si–OH-
promoted elimination of halide ion or acetate ion (Scheme 2).
To establish grounds for this speculation, we synthesized
vinyl silica NPs and observed that the reactivity of the catalyst
was reduced by one third compared to that of silica NPs.
Acknowledgements
This work was partly supported by the National Science
Foundation (NSF CBET-63016011 and NSF-NIRT Grant
EEC-0506560). We are also pleased to acknowledge
Dr S. Biswas for his help with the TEM.
Table 4 Comparison of results for the anti-Markovnikov addition of
thiophenol to styrene using different reagents
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306 | New J. Chem., 2010, 34, 302–306