Silica-supported ICl as a novel heterogeneous system for the rapid and selective oxidation of thiols to symmetrical disulfides

Article abstract of DOI:10.1080/17415993.2011.606625

ICl-SiO₂ as a new reactive system was prepared by treatment of iodine monochloride with activated silica gel in chloroform. ICl-SiO₂ in a heterogeneous system efficiently converted thiols to the corresponding disulfides under mild conditions in high yields at room temperature.[image omitted].

Full text of DOI:10.1080/17415993.2011.606625

This article was downloaded by: [McGill University Library]
On: 05 January 2013, At: 22:01
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Sulfur Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gsrp20
Silica-supported ICl as a novel
heterogeneous system for the rapid
and selective oxidation of thiols to
symmetrical disulfides
Bahador Karami a , Mahnaz Farahi a , Morteza Montazerozohori a
Masoud Nasr-Esfahani a
&
a Department of Chemistry, Yasouj University, Yasouj,
75918-74831, PO Box 353, Iran
Version of record first published: 12 Aug 2011.
To cite this article: Bahador Karami , Mahnaz Farahi , Morteza Montazerozohori & Masoud Nasr-
Esfahani (2011): Silica-supported ICl as a novel heterogeneous system for the rapid and selective
oxidation of thiols to symmetrical disulfides, Journal of Sulfur Chemistry, 32:5, 483-488
To link to this article: http://dx.doi.org/10.1080/17415993.2011.606625
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-
conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Journal of Sulfur Chemistry
Vol. 32, No. 5, October 2011, 483–488
Silica-supported ICl as a novel heterogeneous system for the
rapid and selective oxidation of thiols to symmetrical disulfides
Bahador Karami*, Mahnaz Farahi, Morteza Montazerozohori and Masoud Nasr-Esfahani
Department of Chemistry, Yasouj University, Yasouj 75918-74831, PO Box 353, Iran
(Received 17 December 2010; final version received 16 July 2011)
ICl–SiO2 as a new reactive system was prepared by treatment of iodine monochloride with activated silica
gel in chloroform. ICl–SiO2 in a heterogeneous system efficiently converted thiols to the corresponding
disulfides under mild conditions in high yields at room temperature.
Cl
I
OH OH
OH OH
SiO2
Chloroform
Reflux
SiO2
ICl
+
1
2
2, CHCl3
2RSH
RSSR
rt
R= Aryl, Alkyl
Keywords: iodine monochloride; iodination; thiols; disulfides; heterogeneous conditions
1. Introduction
In recent years, iodine monochloride (1) has been widely used for various organic transformations
such as iodination of activated aromatic substrates (1), synthesis of 6-iodo quinazoline-4(3H)-one
derivatives (2), iodination of nucleic acids in organic solvents (3), generation of electrophilic
iodine from reactions with CF3COOAg, CH3COONa or (CH3COO)2Pb (4), stereoselectiv-
ity in iodo-deboronation and chloro-deboronation of hindered alkenyl boronate esters using
either ICl–NaOMe or ICl–pyridine (5), addition to branched E-alkenes (6), synthesis of α-iodo
β-ketosulfones from the corresponding β-ketosulfones (7) and application as a volumetric reagent
(8). Iodine monochloride (1) has also been used as an iodinating agent without involving a catalyst.
It has two crystalline forms α and β that contain non-planar chains of ICl (1) molecules arranged
in a zig-zag manner (9). This compound (1) has high vapor pressure and, similar to I2 molecules,
evaporates easily. While it has been used frequently, there is some hazard while using it.
*Corresponding author. Email: karami@mail.yu.ac.ir
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
http://dx.doi.org/10.1080/17415993.2011.606625
http://www.tandfonline.com

484 B. Karami et al.
Recently, silica-supported reagents have been gaining considerable attention because of their
higher activity due to the larger surface area, high mechanical and thermal stabilities, ease of
handling, low toxicity, non-corrosivity, and ease of separation and work-up (10). On the other
hand, heterogeneous processes have been well studied recently for their prospective applications
in organic synthesis. The high efficiency of these processes is traditionally thought to be due to
the above advantages. In continuation of our studies on heterogeneous systems and solid acids
(11), herein we report a novel solid-supported reagent (2) based on iodine monochloride (1)
supported on silica gel as an efficient and mild reagent for iodination and oxidation of thiols to
the corresponding disulfides. We now report that we have supported ICl (1) on activated silica gel
(Scheme 1) to stabilize it and make it easier to use and handle.
Cl
I
OH OH
OH OH
SiO2
Chloroform
Reflux
SiO2
ICl
+
1
2
Scheme 1. Supported ICl (1) on activated silica gel.
Conversion of thiols into the related disulfides is of interest from both biological and chem-
ical points of view (12). Disulfides, especially diaryl disulfides, are very commonly used as
electrophiles in the sulfenylation of enolates and other anions (13). Oxidative S–S coupling of
thiols can be done under biological conditions in the presence of oxidants such as flavins and
cytochromes (14). In the laboratory, thiols can be oxidized to the corresponding disulfides by
several oxidants such as redox dyes (14), nitro compounds (15), diazocompounds (16), sulfox-
ides (17), halogens (18), 2-polyvinyl-pyridine/bromine complex (19), H2O2 (20), KMnO4/CuSO4
(21), DMSO/I2 (12a, 22) and sodium perborate (23) and by electrochemical methods (24). Due
to the synthetic importance of disulfides, interest in new chemical and biotic methods has been
increasing (25). Some of the methods mentioned above suffer from disadvantages such as long
reaction times, unavailability and toxicity of reagents and isolation of products. Therefore, the
introduction of readily available, safe and stable reagents for the oxidation of thiols to disulfides
is still a necessity. In continuation of our studies on the oxidation of thiols to disulfides (11c, 26),
we introduce the novel heterogeneous reagent (2) for this organic transformation.
2. Results and discussion
Silica gel-supported iodine monochloride (2) is stable as a light pink solid and can be successfully
used even after 5 months of storage. It can be prepared from the reaction of ICl (1) with activated
silica gel in refluxing chloroform for 12 h (Scheme 1).There are some reports about charge-
transfer complexes between a wide range of carbonyl compounds and ICl (1) (27) and a π-type
complex formed between ethyne and ICl (1) (28). In these charge-transfer complexes, I2 or ICl
(1) molecules use an anti-bonding σ*-orbital to accept π-electrons from aromatic molecules or
a lone pair of electrons from an n-donor molecule according to Mulliken’s theory (29). Based
on these results, we believe that iodine monochloride (1) binds to the surface of silica gel via an
interaction between the hydroxyl group of silica gel and positive iodine in ICl (1) (Scheme 1).
Unreacted ICl (1) on reacting with water produces HCl and HOI, which can be measured via
titration of the two acids with sodium hydroxide (Scheme 2) (1c, 30). Therefore, the amount of
the supported ICl (1) on silica gel can be determined.

Journal of Sulfur Chemistry 485
HCl +HOI
ICl+H2O
HCl +HOI +2NaOH
NaOI + NaCl + 2H2O
Scheme 2. Reaction of unreacted ICl (1) with water yielding HCl and HOI.
Oxidation of thiols is a common procedure for the preparation of disulfides. Therefore, after
preparation of ICl–SiO2 (2), we were interested in using it with organic solvents for in situ gener-
ation of ICl (1) to oxidize aliphatic and aromatic thiols under mild and heterogeneous conditions
(Scheme 3). Initially, different types of thiols were treated with ICl–SiO2 (2) in chloroform. The
oxidation reaction was performed under mild and heterogeneous conditions at room temperature
in good to excellent yields for a relatively short period of time (Table 1).
2, CHCl3
2RSH
RSSR
rt
R=Aryl, Alkyl
Scheme 3. Oxidation of the thiols to the corresponding disulfides.
Table 1. Oxidative coupling of thiols using silica gel-supported iodine monochloride (2) system in chloroform at room
temperature.
m.p. (◦C)
Reaction
time (min)
Yielda,b
(%)
Run
Thiols
Disulfides
Found
Literature
SH
S
S
1
2
40
40
95
92
144–146
43–44
142–145 (25a)
44–45 (25a)
SH
SH
CH
CH3
Cl
S
S
CH3
Cl
3
3
Cl
S
50
95
72–73
70–7 (25a)
S
CH SH
2
4
5
6
45
40
60
92
95
90
69–71
90–92
55–56
69–70 (25a)
91–93 (25a)
55–57 (25a)
CH2S
SCH2
Br
Br
S
S
SH
SH
S
S
Br
N
N
N
N
N
N
N
N
7
8
9
SH
70
50
70
90
85
88
133–135
177–179
202–204
134–136 (26b)
177–180 (26b)
202–204 (26b)
S
S
N
N
N
S
N
S
SH
S
S
S
S
S
N
N
N
SH
N
H
N
H
N
H
10
11
12
CH3(CH2)3CH2SH
CH3(CH2)6CH2SH
CH3(CH2)3SH
(CH3(CH2)3CH2S)2
(CH3(CH2)6CH2S)2
(CH3(CH2)3S)2
45
45
45
90
90
92
Oil (26b)
Oil (26b)
Oil (25a)
13
45
92
Oil (25a)
SH
S S
Notes: aRefers to isolated yields.
bIdentified by MS and 1H- and 13C-NMR spectroscopy.

486 B. Karami et al.
As shown in Table 1, compounds in Entries 1, 2 and 4 have two positions for iodination
because of the presence of an active aromatic ring, but the results showed that only S–S coupling
occurred (Scheme 3). These results highlight the chemoselectivity of our method (or this reagent)
in oxidation of thiols.
To examine the effect of the solvents, the oxidation of 4-methylthiophenol was performed
in different solvents. The observations showed that oxidations in nucleophilic solvents such as
methanol, ethanol, acetonitrile and ether were not complete. We suggest that these solvents com-
petitively react with the ICl (1) reagent and that large amounts of reagent are needed. Both
chloroformanddichloromethaneweregoodsolventsunderthereactionconditions, butchloroform
was better because of the good solubility of starting materials and products.
The oxidation reactions are heterogeneous because thiols are soluble in chloroform, whereas
reagent (2) is not soluble in it. Hence, oxidation presumably occurs at the surface of the heteroge-
neous reagent (2) via a slow controlled in situ release of a small amount of ICl (1). Consequently,
this new supported system effectively acts as an ICl source. Therefore, we proposed the following
mechanisms based on previously reported results about the applications of ICl (1) (Scheme 4)
(1–9, 31).
..
RSI+HCl
RSSR
RISH+
Cl
..
-HI
RSH+RSI
Scheme 4. Suggested mechanism of the oxidation of thiols.
3. Conclusion
In conclusion, in this work, we have prepared a reactive and heterogeneous reagent for the oxi-
dation of thiols to disulfides. This new system is equivalent to iodine monochloride but more
stable and easier to use and handle. In addition, we suggest that this reagent could be used for the
iodination of a wide variety of organic compounds. Therefore, its other applications are currently
under study in our laboratory.
4. Experimental
4.1. General
Chemicals were purchased from Aldrich, Fluka and Merck chemical companies and were freshly
used after purification by standard procedures. The products were isolated and identified by
comparison of their physical and spectral data with those given in the literature (25, 26). IR
1
spectra were recorded on FT-IR JASCO-680 using KBr disks and the H-NMR spectra were
obtained on a Brucker instrument 300 MHz model as CDCl3 solutions, and the chemical shifts
are expressed in δ with Me4Si (TMS) as the internal standard.
4.2. Activation of silica gel
Chromatography-grade silica gel (10 g, 70–230 mesh) was heated in an electric furnace at 400◦C
for 4 h. Then, it was cooled to room temperature to obtain activated silica gel (9.12 g).

Journal of Sulfur Chemistry 487
4.3. Preparation of silica-supported ICl (2)
To a stirred solution of iodine monochloride (1) (0.487 g, 3 mmol) in 10 ml of chloroform, activated
silica gel (9.12 g) was added and the mixture was refluxed for 12 h. Then, it was cooled to room
temperature and the mixture was filtered and washed three times with 10 ml of chloroform to
remove unreacted ICl (1). Then, the filtrate was dried to yield silica-supported ICl (2) (9.485 g),
which contained 0.365 g (2.247 mmol) of supported ICl (1). This amount was in agreement with
that obtained from the titration of unreacted ICl (1) with 0.1 M NaOH solution (1c, 30).
4.4. General procedure for oxidation of thiols to the corresponding disulfides
To a solution of 1 mmol thiols in 10 ml of chloroform at room temperature, 4.2 g (1 mmol) of
silica gel-supported iodine monochloride (2) was added. The reaction mixture was stirred for
40–70 min. Completion of the oxidation reaction was followed by TLC (n-hexane: ethyl acetate).
After completion of the reaction, the reaction mixture was filtered and then the residue was washed
with chloroform (10 ml). Chloroform was removed under water bath and simple distillation and
disulfides were obtained as pure products.
4.5. Typical procedure for oxidation of 4-methylthiophenol (Entry 2, Table 1)
To a solution of 1 mmol (0.1242 g) 4-methylthiophenol in 10 ml of chloroform at room tempera-
ture, 2 mmol (4.2 g) silica gel-supported iodine monochloride (2) was added. The reaction mixture
was stirred for 40 min. Completion of oxidation reaction was followed by TLC (n-hexane: ethyl
acetate, 9:1). After completion of the reaction, the reaction mixture was filtered and then the
residue was washed with chloroform (10 ml). Chloroform was removed under water bath and
simple distillation and 4,4-dimethyl diphenyl disulfide was obtained as white crystals, 0.2266 g
(92%); m.p. 45–47◦C [Lit (25a, 26b). 44–45◦C]. 1H-NMR (400 MHz, CDCl3): δ (ppm): 7.50 (d,
4H, J = 8 Hz), 7.20 (d, 4H, J = 8 Hz), 2.46 (S, 6H, 2CH3). MS (m/z): (70 eV): 246 (M+).
Acknowledgements
The authors acknowledge the Yasouj University, Yasouj, Iran, for the partial support provided for this work.
References
(1) (a) Emmanuvel, L.; Shukla, R.K.; Sudalai, A.; Gurunath, S.; Sivaram, S. Tetrahedron Lett. 2006, 47, 4793–4796; (b)
Sharma, S.; Deshmukh, A.R.A.S.; Singh, P. Catal. Lett. 1996, 40, 257–263; (c) Chaikovskii, V.K.; Filimonov, V.D.
Russ. J. Org. Chem. 2001, 37, 1130–1133; (d) Sokolovskaya, S.V.; Moldovanova, L.K. Khim. Geterotsikl. Soedin.
1984, 5, 616–618; (e) Chiappe, C.; Pieraccini, D. Arkivoc 2002, xi, 249–255; (f) Chaikovskii, V.K.; Kharlova, T.S.;
Filimonov, V.D. Russ. Chem. Bull. 1999, 48, 1291–1294.
(2) Sayyed, M.A.; Mokle, S.S.; Vibhute, Y.B. Arkivoc 2006, xi, 221–226.
(3) Ascoli, F.; Kahan, F.M. J. Biochem. 1968, 241, 428–434.
(4) Filimonov, V.D.; Krasnokutskaya, E.A.; Lesina, Y.A. Russ. J. Org. Chem. 2003, 39, 875–880.
(5) Lightfoot, A.P.; Steven, T.J.R.; Whiting, A. Tetrahedron Lett. 2004, 45, 8557–8561.
(6) (a) Jiang, W.; Weber, W.P. Polym. Bull. 1989, 21, 427–432; (b) Nazarenko, T.I.; Deev, L.E.; Ponomarev, V.G.;
Pashkevich, K.I. Izv. Akad. Nauk. SSSR, Ser. Khim. (Rus). 1989, 12, 2869.
(7) Suryakiran, N.; Reddy, T.S.; Suresh, V.; Lakshman, M.; Venkateswarlu,Y. Tetrahedron Lett. 2006, 47, 4319–4323.
(8) Singh, B.; Kashyap, G.P. Fresenius’J. Anal. Chem. 1958, 162, 357–360.
(9) Leung, H.C.; Anderson, A. Can. J. Chem. 1974, 52, 1081–1085.
(10) (a) Khan, A.T.; Choudhury, L.H.; Ghosh, S. J. Mol. Catal. A: Chem. 2006, 255, 230–235; (b) Jacob, R.G.; Dutra,
L.G.; Radatz, C.S.; Mendes, S.R.; Perin, G.; Lenardão, E.J. Tetrahedron Lett. 2009, 50, 1495–1497; (c) Perin, G.;
Álvaro, G.; Westphal, E.; Viana, L.H.; Jacob, R.G.; Lenardão, E.J.; D’Oca, M.G.M. Fuel 2008, 87, 2838–2841; (d)
Jacob, R.G.; Silva, M.S.; Mendes, S.R.; Borges, E.L.; Lenardo, E.J.; Perin, G. Synth. Commun. 2009, 39, 2747–2762.

488 B. Karami et al.
(11) (a) Karami, B.; Montazerozohori, M. Molecules 2006, 11, 720–725; (b) Karami, B.; Montazerozohori, M.; Karim-
ipour, G.R.; Habibi, M.H. Bull. Korean. Chem. Soc. 2005, 26, 1431–1433; (c) Karami, B.; Montazerozohori, M.;
Habibi, M.H. Phosphorus, Sulfur Silicon Relat. Elem. 2006, 181, 2825–2831; (d) Karami, B.; Montazerozohori, M.;
Habibi, M.H. Bull. Korean Chem. Soc. 2005, 26, 1125–1128; (e) Karami, B.; Montazerozohori, M.; Habibi, M.H.;
Zolfigol, M.A. Heterocycl. Commun. 2005, 11, 513–516; (f) Montazerozohori, M.; Karami, B. Helv. Chim. Acta.
2006, 89, 2922–2926; (g) Heydari, A.; Larijani, H.; Emami, J.; Karami, B. Tetrahedron Lett. 2000, 41, 2471–2473;
(h) Damavandi, J.; Zolfigol, M.A.; Karami, B. Synth. Commun. 2001, 31, 3183–3187; (i) Niknam, K.; Karami, B.;
Zolfigol, M.A. Catal. Commun. 2007, 8, 1427–1430.
(12) (a) Drabowicz, J.; Mikolajczyk, M. Synthesis 1980, 32–34; (b) Jocelyn, P.C. Biochemistry of the SH Group;Academic
Press: NewYork, London, 1972; (c) Wolman,Y. Protection of the Thiol Group. In The Chemistry of the Thiol Groups;
Patai, S., Ed.; John Wiley & Sons: London, 1974; pp 669–684; (d) Bodanszky, M. Principles of Peptide Synthesis;
Springer-Verlag: Berlin, 1984; Chapter 4.
(13) (a)Trost, B.; Salzmann, T.N. J. Am. Chem. Soc. 1973, 95, 6840–6842; (b) Seebach, D.;Teschner, M. Tetrahedron Lett.
1973, 14, 5113–5116; (c) Zoretic, P.A.; Soja, P. J. Org. Chem. 1976, 41, 3587–3589; (d) Gassman, P.G.; Balchunis,
R.J. J. Org. Chem. 1977, 42, 3236–3240.
(14) Kharasch, N.; Arora, A.S. Phosphorus, Sulfur Silicon Relat. Elem. 1976, 2, 155–162.
(15) Riordan, J.F.; Sokovsky, M.; Vallee, B.L. J. Am. Chem. Soc. 1966, 88, 4104–4105.
(16) Kosower, E.M.; Kosower, N.S. Nature 1969, 224, 117–120.
(17) (a) Wallace, T.T. J. Am. Chem. Soc. 1964, 86, 2018–2021; (b) Wallace, T.T.; Wein, H.A. Chem. Ind. (London), 1966,
1558.
(18) Small, D.L.; Bailey, J.H.; Cavallito, G.J. J. Am. Chem. Soc. 1947, 69, 1711–1712.
(19) Chistensen, W.L.; Heacock, D.J. Synthesis 1978, 50–51.
(20) Evans, B.J.; Doi, J.T.; Musker, W.K. J. Org. Chem. 1990, 55, 2337–2344.
(21) Noureldin, N.A.; Caldwell, M.; Hendry, J.; Lee, D.G. Synthesis 1998, 1587–1589.
(22) (a) Aida, T.; Akasaka, T.; Furukawa, N.; Oae, S. Bull. Chem. Soc. Jpn. 1976, 49, 1441–1442; (b) Fristad, W.E.;
Peterson, J.R. Synth. Commun. 1985, 15, 1–5.
(23) Mckillop, A.; Koyuncu, D. Tetrahedron Lett. 1990, 31, 5007–5010.
(24) Leite, S.L.S.; Pardini, V.L.; Viertler, H. Synth. Commun. 1990, 20, 393–397.
(25) (a) Khodaei, M.M.; Mohammadpoor-Baltork, I.; Nikoofar, K. Bull. Korean Chem. Soc. 2003, 24, 885–886; (b)
Kudryavtseva, E.V.; Sidorova, M.V.; Ovchinnikov, M.V.; Besfpalova, Z.D. J. Peptide Sci. 2000, 6, 208–216; (c)
Hajipour, A.R.; Ruoho, A.E. Phosphorus, Sulfur Silicon Relat. Elem. 2003, 178, 1277–1281; (d) Ghammamy, S.;
Tajbakhsh, M. J. Sulfur Chem. 2005, 26, 145–148; (e) Hashemi, M.; Ghafuri, H.; Karimi-Jaberi, Z. J. Sulfur Chem.
2006, 27, 165–167; (f) Hajipour, A.R.; Safaie, S.; Ruoho, A.E. J. Sulfur Chem. 2006, 27, 441–444; (g) Shaabani,
A.; Rahmati, A.; Farhangi, E. J. Sulfur Chem. 2006, 27, 287–291; (h) Silveira, C.C.; Mendes, S.R. Tetrahedron Lett.
2007, 48, 7469–7471; (i) Lenardão, E.J.; Lara, R.G.; Silva, M.S.; Jacob, R.G.; Perin, G. Tetrahedron Lett. 2007,
48, 7668–7670; (j) Trurow, S.; Pereira, V.A.; Martinez, D.M.; Alves, D.; Perin, G.; Jacob, R.G.; Lenardão, E.J.
Tetrahedron Lett. 2011, 52, 640–643; (k) Singh, D.; Galetto, F.Z.; Soares, L.C.; Rodrigues, O.E.D.; Braga, A.L. Eur.
J. Org. Chem. 2010, 14, 2661–2665.
(26) (a) Karami, B.; Montazerozohori, M.; Moghadam, M.; Habibi, M.H.; Niknam, K. Turk. J. Chem. 2005, 29, 539–546;
(b) Karami, B.; Montazerozohoria, M.; Habibi, M.H. Molecules 2005, 10, 1358–1363; (c) Karami, B.; Montazero-
zohoria, M.; Habibi, M.H. J. Chem. Res. 2006, 490–492; (d) Montazerozohori, M.; Karami, B.; Azizi, M. Arkivoc
2007, i, 99–104; (e) Montazerozohori, M.; Joohari, S.; Karami, B.; Haghighat, N. Molecules 2007, 12, 694–702.
(27) Lasabhi, A.M.; Boub, W.; Essffar, M.; Alcami, M.; Yanez, M.; Abboud, J.L.M. New. J. Chem. 2001, 25, 509–517.
(28) Davey, J.B.; Legon, A.C. Phys. Chem. Chem. Phys. 1999, 1, 3721–3726.
(29) Tang, L.T.; Wei, Y.; Wang, Y.; Hu, S.W.; Liu, X.Q.; Chu, T.W.; Wang, X.Y. J. Mol. Struct. 2004, 686, 25–30.
(30) Helmkamp, R.W.; Goodland, R.L.; Bale, W.F.; Spar, I.L.; Mutschler, L.E. Cancer Res. 1960, 20, 1495–1500.
(31) Akdag, A.; Webb, T.; Worely, S.D. Tetrahedron Lett. 2006, 47, 3509–3510.