Native silica nanoparticle catalyzed anti-Markovnikov addition of thiols to inactivated alkenes and alkynes: a new route to linear and vinyl thioethers

Article abstract of DOI:10.1016/j.tetlet.2008.10.110

A new route for the synthesis of linear and vinyl thioethers has been demonstrated using bare silica nanoparticle as catalyst at room temperature under solvent-free conditions. The catalyst can be reused up to six times without loss of catalytic activity.

Full text of DOI:10.1016/j.tetlet.2008.10.110

Tetrahedron Letters 50 (2009) 124–127
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Native silica nanoparticle catalyzed anti-Markovnikov addition of thiols to
inactivated alkenes and alkynes: a new route to linear and vinyl thioethers
Subhash Banerjee a, Jayanta Das a,b, Swadeshmukul Santra a,b,c,
*
a NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA
b Department of Chemistry, University of Central Florida, 4000 Central Florida Blvd., Orlando, FL 32826, USA
c Biomolecular Science Center, University of Central Florida, College of Medicine, 4000 Central Florida Blvd., Orlando, FL 32826, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A new route for the synthesis of linear and vinyl thioethers has been demonstrated using bare silica nano-
particle as catalyst at room temperature under solvent-free conditions. The catalyst can be reused up to
six times without loss of catalytic activity.
Received 7 October 2008
Revised 20 October 2008
Accepted 21 October 2008
Available online 25 October 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Silicananoparticle
Catalysis
Anti-Markovnikov addition
Solvent-free reaction condition
Linear and vinyl thioethers
Reuse of catalyst
Recently, the use of nanoparticulate materials in catalysis has
attracted considerable attention because of their improved effi-
ciency under mild and environmentally benign conditions in the
context of Green Chemistry.1,2 Because of enormously large and
highly reactive surface area,3 nanoparticles (NPs) exhibit some un-
ique properties in comparison to bulk materials. Among many
other NPs, silica-based NPs have been well studied because of
the following reasons: (i) silica NPs are easy to syntheses at room
temperature, (ii) NP size can be easily tuned, (iii) easy adjustment
of synthesis parameters leads to NPs with narrow size distribution
(‘monodispersed NPs’), (iv) silica NPs are stable in organic solvents,
and (v) they are environmentally friendly materials. Due to these
attractive features, silica NPs found wide-spread applications in
the synthesis of core-shell hybrid nanomaterial for catalysis of or-
ganic reactions. Dominguez-Quintero et al. synthesized nanostruc-
tured palladium materials supported on silica for the catalytic
hydrogenation of benzene, 2-hexanone, and cyclohexanone.4 The
catalytic performance of silica-coated Pt metal particles for the
competitive oxidation of methane and other higher hydrocarbons
with gaseous oxygen has been reported by Hori et al.5 Corma
and coworkers demonstrated Pd nanoparticles embedded in a por-
ous sponge-like silica as a suitable catalyst for the Suzuki–Miyaura
coupling of electron-rich aryl bromides.6 Chung and co-workers7
have applied palladium and cobalt nanoparticles immobilized on
silica for the Tsuji–Trost reaction. However, the catalytic activity
of bare silica NPs in organic transformations has not been studied
to the best of our knowledge. Here, we accidentally discovered
inherent catalytic activity of native silica NPs. This discovery
stimulated us to explore the possibility of using this very old nano-
material as catalyst to study a few very basic chemical transforma-
tions that would demonstrate its potential.
Thioethers play important roles in biological and chemical pro-
cesses8 and also serve as useful building blocks for various organo-
sulfur compounds.9 Therefore, synthesis of thioethers in ‘Green’
and ‘straight-forward’ ways would have tremendous importance.
Traditionally, they are synthesized by the addition of thiolate an-
ions to olefins. The electrophilic (i.e., ionic process) addition of
thiolate anion to olefin promotes Markovnikov addition,10 whereas
free-radical course leads to anti-Markovnikov adduct.11 Most of
the protic acids (e.g., H2SO4, HClO4, and p-TSOH) and Lewis acids
(AlCl3, BF3, TiCl4, SnCl4, ZnCl2) catalysts are reported for the elec-
trophilic additions, only a few reagents such as H-rho-zeolite12
and benzene-reflux13 are found to induce anti-Markovnikov prod-
ucts. Recently, Ranu et al.14 have reported water-promoted addi-
tion of thiols to inactivated alkenes. Some of these procedures
are associated with disadvantages such as unsatisfactory yields,
long reaction times, and use of highly carcinogenic and hazardous
organic solvent (such as benzene). Moreover, limited reports are
available that involves styrenes, possibly due to their facile poly-
merization under acidic conditions.15 The development of robust
protocol (i.e., neutral catalyst) for this transformation is thus highly
* Corresponding author. Tel.: +1 407 882 2848; fax: +1 407 882 2819.
E-mail address: ssantra@mail.ucf.edu (S. Santra).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.10.110

S. Banerjee et al. / Tetrahedron Letters 50 (2009) 124–127
125
R
+
RSH
R
RS
r.t, solvent-free
0.5-1.5 h
R = alkyl, aryl
85-98%
Scheme 1. The silica NPs-catalyzed synthesis of linear thioethers is represented.
Silica NPs were synthesized using well-established Stobar
method16 that involves basic hydrolysis and condensation reaction
of tetraethoxyorthosilane (TEOS) in ethanol/water (1:1) mixtures
at room temperature. The silica NPs were characterized by trans-
mission electron microscopic image (Fig. 1).
These silica NPs exhibited a marked influence in directing the
anti-Markovnikov addition of thiols to different alkenes (Scheme
1).
In a simple experimental procedure,21 olefin (1 mmol) was
added to a mixture of thiol (1 mmol) and silica NPs (1 wt %), and
the reaction mixture was stirred at room temperature until com-
pletion of reaction (TLC). The extraction with ethyl acetate fol-
lowed by evaporation of solvents leads to the crude product in
almost pure form. The results are summarized in Table 1. Both
Figure 1. TEM image of fresh silica NPs (before reaction).
desirable. Here, we report a simple and efficient protocol for the
synthesis of linear and vinyl thioethers via anti-Markovnikov addi-
tion of thiols to alkenes and alkynes using a recyclable native silica
nanoparticle catalyst at room temperature.
Table 1
Silica NP-catalyzed anti-Markovnikov addition of thiophenol to inactivated alkenes
R
Silica NPs
PhSH
+
PhS
R
Entry
1
Thiol
PhSH
Alkene
Product
Time (h)
1.5
Yielda (%)
87
Ref.
14
SPh
SPh
C4H9
C4H9
2
3
PhSH
PhSH
1.5
1.0
85
88
19
14
C6H13
C6H13
SPh
SEt
4
EtSH
1.5
85
14
Br
PhS
SPh
5
6
7
PhSH 2 equiv
PhSH
1.0
0.5
0.5
86
98
94
19
14
20
SPh
C6H5
C6H5
SPh
PhSH
SPh
8
9
PhSH
PhSH
PhSH
0.5
0.5
0.5
90
90
96
14
14
—
Cl
Cl
SPh
MeO
Cl
MeO
Cl
SPh
10
a
Yield refers to the pure isolated products characterized by spectroscopic (1H NMR and IR) data.

126
S. Banerjee et al. / Tetrahedron Letters 50 (2009) 124–127
the aliphatic and aromatic-substituted alkenes were made to
participate in the reaction without any difficulty. All the reactions
were made to proceed at room temperature to produce the thio-
ethers in high yield (85–98%) at shorter reaction time (0.5–1.5 h).
The addition of thiols to olefins is highly regioselective and anti-
Markovnikov in nature. It is observed that the addition of thiols
to the aromatic-substituted alkenes (Table 1, entries 6–10) is faster
than that of aliphatic one (Table 1, entries 1–6). The addition of
thiophenol to 1-chloromethyl-4-vinyl-benzene is highly selective
(Table 1, entry 10). The reactive chloromethyl group in the mole-
cule remained intact even after use of two equivalents of thiophe-
nol that can be further functionalized.
We found that only 1 wt % of catalyst was sufficient to carry out
the addition reaction. The reaction of thiophenols and olefin has
been reported to give the Friedel Crafts product;17 however, no
such side-reaction was observed in this protocol.
Encouraged by the high reactivity and effectiveness of the cata-
lyst for the anti-Markovnikov addition of thiols to inactivated ole-
fins, we attempted to study the catalytic activity of silica NPs on
the addition of thiols to inactivated alkynes. We have observed
comparable reactivity of the catalyst on the addition of thiols to al-
kynes. The addition of alkyne (e.g., phenylacetylene) to a mixture
of thiol (e.g., thiophenol) and catalyst (1 wt %) leads to vinyl thio-
ethers in high yields at room temperature (Scheme 2).
tive and it exclusively produced trans-vinyl thioether (Table 2,
entry 2); on the other hand, the catalysts reported in the litera-
ture18 were found to produce a mixture of cis and trans isomers.
However, 1:1 mixture of cis and trans isomers was isolated in
the case of hydrocarbon-substituted alkyne (Table 2, entry 1). Pos-
sibly, hydrogen bond formation between –OH group of 2-Methyl-
but-3-yn-2-ol and silica NPs triggers addition of thiophenol from
the opposite site (due to steric factor) leading to trans-isomer
which was not reflected in case of hept-1-yne. Thus, silica NPs
played an important role in the addition of thiophenol to alkynes.
The catalyst can be easily recovered from the reaction mixture
by adding organic solvents (e.g., ethyl acetate) because the catalyst
(i.e., silica NPs) is insoluble in organic solvents. The catalyst was re-
used for six times without loss of any catalytic activity (Fig. 2). To
determine the fate of the catalyst after reaction, we have done the
TEM of the recovered silica NPs. We have not found any change in
the particulate nature of the silica NPs (image is not given here).
Silica NPs play an important role in this reaction. A comparison
of reactivity of different reagents for anti-Markovnikov addition of
thiophenol to styrene in benzene is presented in Table 3.
The neat reactions without silica NPs are very slow, and we
have observed that only about 45% of the reactions were com-
pleted even after 24 h. Possibly, silica NPs (also called silanol) pro-
motes the reaction through hydrogen-bond formation with the
sulfhydryl hydrogen of the thiol with surface hydroxyl group of sil-
anol, and thus increases the nucleophilicity of the thiolate ion. Fur-
The results for the addition of thiols to alkynes are represented
in Table 2. Both the aliphatic- and aromatic-substituted alkynes
were made to participate in this addition reaction to produce the
vinyl thioethers in high yield. Here, we have also observed the
100% anti-Markovnikov addition, no Markovnikov adducts were
isolated in any case. The addition of thiophenol to a hydroxyl-
substituted alkyne, 2-Methyl-but-3-yn-2-ol, is highly stereoselec-
100
80
60
40
20
0
R1
SPh
PhSH
+
R1
r.t, no solvent
0.5-1 h
1
2
3
4
5
6
R = alkyl, aryl
98-50% = E isomer
85-96%
No. of cycles
Figure 2. The variation of yield (%) with number of recycles of the catalyst for the
Scheme 2. The silica NPs-catalyzed synthesis of vinyl thioethers is represented.
addition of PhSH to styrene is represented.
Table 2
Silica NP catalyzed anti-Markovnikov addition of thiophenol to alkynes
R1
Silica NPs
R1
PhSH
+
PhS
Entry
1
Thiol
PhSH
Alkyne
Product
Time (h)
Yielda (%)
85
Ref.
18
SPh
(E:Z = 1:1)
C5H11
1.0
1.0
C5H11
SPh
2
PhSH
85
96
18
18
HO
HO
(100% E)
SPh
3
PhSH
0.5
(E:Z = 3:2)
a
Yield refers to the pure isolated products characterized by spectroscopic (1H NMR and IR) data.

S. Banerjee et al. / Tetrahedron Letters 50 (2009) 124–127
127
Table 3
Acknowledgments
The comparison of different reagent for anti-Markovnikov of thiophenol to styrene is
represented
This work has been supported by the National Science Founda-
tion (NSF CBET-63016011and NSF-NIRT Grant EEC-056560). We
are also pleased to acknowledge Dr. S. Biswas for his help in TEM
measurement for silica NPs.
Reagent
Reaction time/condition
Yield (%)
Benzene
Neat
Silica NPs
Water
24 h/rt or 10 h/Reflux
24 h/rt
0.5 h/rt
92
30
98
90
1.5 h/rt
References and notes
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H.; Osuna, J. J. Mol. Catal. A 2003, 197, 185–191.
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7. Park, K. H.; Son, S. U.; Chung, Y. K. Org. Lett. 2002, 4, 4361–4363.
8. Cremlyn, R. J. An Introduction to Organo-Sulfur Chemistry; Wiley & Sons: New
York, 1996.
9. Peach, M. E. In Thiols as Nucleophiles, In The Chemistry of the Thiol Group; John
Wiley & Sons: London, 1979.
ArSH
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δ-
Ar
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S
δ+
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Ar
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10. Griesbaum, K. Angew. Chem., Int. Ed. 1970, 9, 273–287.
11. Curran, D. P. In Comprehensive Organic synthesis; Pergamon: New York, 1991.
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12. Kumar, P.; Pandey, R. K.; Hegde, V. R. Synlett 1999, 1921–1922.
13. Kanagasabapathy, S.; Sudalai, A.; Benicewicz, B. C. Tetrahedron Lett. 2001, 42,
3791–3794.
S
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14. Ranu, B. C.; Mandal, T. Synlett 2007, 925–928.
Ar
15. Screttas, C. G.; Michascrettas, M. J. Org. Chem. 1979, 44, 713–719.
16. Rossi, L. M.; Shi, L. F.; Quina, F. H.; Rosenzweig, Z. Langmuir 2005, 21, 4277–
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18. Silva, M. S.; Lara, R. G.; Marczewski, J. M.; Jacob, R. G.; Lenardao, E. J.; Perin, G.
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Scheme 3. The proposed mechanism for the silica NPs-catalyzed addition of thiols
to alkenes is represented.
19. Rout, L.; Sen, T. K.; Punniyamurthy, T. Angew. Chem., Int. Ed. 2007, 46, 5583–
5586.
20. Lupattelli, P.; Ruzziconi, R.; Scafato, P.; DeglInnocenti, A.; Paolobelli, A. B. Synth.
Commun. 1997, 27, 441–446.
ther, it may be speculated that addition of the thiolate anion to the
C@C bond takes place in a concerted manner with steric factors
controlling the regioselectivity leading to the anti-Markovnikov
product (Scheme 3).
21. Typical experimental procedure for the anti-Markovnikov addition of olefins to
thiols (Table 1, entry 6): Styrene (104 mg, 1 mmol) was added to a mixture of
thiophenol (110 mg, 1 mmol) and silica NP (1 wt %) in neat condition, and the
reaction mixture was stirred for 0.5 h at room temperature till completion of
reaction (TLC). The extraction with ethyl acetate followed by evaporation of
solvents leads to the crude product in almost pure form, which was purified by
short column chromatography over silica gel (hexane–ethyl acetate, 95:5) to
provide 2-phenylsulfanylethylbenzene (209 mg, 98%) as a colorless liquid. This
procedure was followed for all the reactions listed in Tables 1 and 2. Except one
(Table 1, entry 10) all the products known were characterized by spectroscopic
1H NMR and IR) data, and these data were compared with the reported values.
The unknown product (Table 1, entry 10) was characterized by IR, NMR (1H
and 13C) spectroscopic data, and elemental analysis and was given below.Table
1, entry 10: Colorless liquid. IR (Neat): 689, 736, 823, 1024, 1089, 1265, 1438,
In conclusion, we have demonstrated the use of native silica
NPs as catalyst in the anti-Markovnikov addition thiols to alkenes
and alkynes for the first time. The reactions are considerably fast
(0.5–1 h) and highly regioselective in nature. This present protocol
offers several advantages such as (1) mild reaction conditions
(room temperature), (2) high isolated yields (85–99%) of the linear
and vinyl thioethers, (3) low cost, non-toxicity and recyclability of
the catalyst, and (4) solvent-free reaction conditions, which meets
the requirements for ‘green synthesis’ over existing protocols.
Moreover, this is the first use of native silica NPs in organic synthe-
sis. Certainly, this observation provides great promise toward addi-
tional useful applications.
1479, 1514, 1582 cmÀ1 1H NMR (CDCl3, 500 MHz): d 2.96 (t, J = 7.5 Hz, 2H),
.
3.19 (t, J = 7.5 Hz, 2H), 4.60 (s, 2H), 7.22–7.24 (m, 3H), 7.34–7.40(m, 6H). 13C
NMR: d 34.9, 35.3, 46.2, 125.9 (2C), 126.2 (2C), 128.7, 129.1 (2C), 129.4 (2C),
135.7, 136.2, 140.5. Anal. Calcd for C15H15ClS: C, 68.55; H, 5.75. Found: C,
68.47; H, 5.66.