A general and efficient method for the selective synthesis of β-hydroxy sulfides and β-hydroxy sulfoxides catalyzed by gallium(III) triflate

Article abstract of DOI:10.1021/jo0700124

(Chemical Equation Presented) Gallium(III) triflate-catalyzed ring opening of epoxides affords β-hydroxy sulfides with high regioselectivity and chemoselectivity in high yields (84-97%) under solvent-free conditions. Additionally, a simple, efficient, and environmentally benign one-pot procedure for the synthesis of β-hydroxy sulfoxides in sole water has been developed for the first time. The process, promoted by a H₂O ₂-Ga(OTf)₃ system, affords β-hydroxy sulfoxides in high yields (81-94%) and high chemoselectivity without any detectable overoxidation to β-hydroxy sulfones. The catalyst could be recovered easily after the reactions and reused without evident loss of activity.

Full text of DOI:10.1021/jo0700124

The oxidation of â-hydroxy sulfides is the most straightfor-
ward method for the synthesis of â-hydroxy sulfoxides. The
selective oxidation of sulfides to sulfoxides has been a challenge
for many years. Much effort has been devoted to develop a large
number of oxidants to convert sulfides into sulfoxides.8 Aqueous
hydrogen peroxide is an ideal oxidant9 in view of an effective
oxygen content of as high as 47%, and water is the only
theoretical byproduct. These obvious advantages have spurred
the development of useful procedures for H2O2 oxidation of
sulfides.10
A General and Efficient Method for the Selective
Synthesis of â-Hydroxy Sulfides and â-Hydroxy
Sulfoxides Catalyzed by Gallium(III) Triflate
Weike Su,*,†,‡ Jiuxi Chen,‡ Huayue Wu,‡ and Can Jin†
College of Pharmaceutical Sciences, Zhejiang Key Laboratory
of Pharmaceutical Engineering, Zhejiang UniVersity of
Technology, Hangzhou 310014, China, and College of
Chemistry and Materials Science, Wenzhou UniVersity,
Wenzhou 325027, China
Although a variety of catalytic systems have been introduced
for oxidation of sulfides, however, many of these methodologies
are associated with one or more disadvantages such as relatively
long reaction time, environmentally unfriendly catalyst, low
yield, the use of volatile organic solvents, requirement of excess
reagents or catalysts, and harsh reaction conditions. For the
synthesis of â-hydroxy sulfoxides, very little attention was paid
to it.6,11 Due to the importance of these compounds in organic
synthesis, the development of environmentally benign, high-
yielding, and clean approaches for the synthesis of â-hydroxy
sulfides and â-hydroxy sulfoxides is in demand.
suweike@zjut.edu.cn
ReceiVed January 3, 2007
Metal triflates have advantages of water-tolerance, air-
stability, recoverability of the agent from water, operational
(3) (a) Polshettiwar, V.; Kaushik, M. P. Catal. Commun. 2004, 5, 515.
(b) Amantini, D.; Fringuelli, F.; Pizzo, F.; Tortoioli, S.; Vaccaro, L. Synlett
2003, 2292. (c) Fringuelli, F.; Pizzo, F.; Tortoioli, S.; Vaccaro, L. J. Org.
Chem. 2003, 68, 8248. (d) Fringuelli, F.; Pizzo, F.; Vaccaro, L. J. Org.
Chem. 2004, 69, 8780. (e) Fringuelli, F.; Pizzo, F.; Tortoioli, S.; Vaccaro,
L. J. Org. Chem. 2004, 69, 2315. (f) Fringuelli, F.; Pizzo, F.; Tortoioli, S.;
Vaccaro, L. Org. Lett. 2005, 7, 4411. (g) Fringuelli, F.; Pizzo, F.; Tortoioli,
S.; Zuccaccia, C.; Vaccaro, L. Green Chem. 2006, 2, 191. (h) Fringuelli,
F.; Pizzo, F.; Tortoioli, S.; Vaccaro, L. AdV. Synth. Catal. 2002, 344, 379
and references therein.
(4) Pironti, V.; Colonna, S. Green Chem. 2005, 7, 43.
(5) Fan, R.-H.; Hou, X.-L. J. Org. Chem. 2003, 68, 726.
(6) (a) Corey, E. J.; Clark, D. A.; Goto, G.; Marfat, A.; Mioskowski, C.;
Samuelsson, B.; Hammarstro¨m, S. J. Am. Chem. Soc. 1980, 102, 1436. (b)
Luly, J. R.; Yi, N.; Soderquist, J.; Stein, H.; Cohen, J.; Perun, T. J.; Plattner,
J. J. J. Med. Chem. 1987, 30, 1609. (c) Conchillo, A.; Camps, F.; Messeguer,
A. J. Org. Chem. 1990, 55, 1728.
Gallium(III) triflate-catalyzed ring opening of epoxides
affords â-hydroxy sulfides with high regioselectivity and
chemoselectivity in high yields (84-97%) under solvent-
free conditions. Additionally, a simple, efficient, and envi-
ronmentally benign one-pot procedure for the synthesis of
â-hydroxy sulfoxides in sole water has been developed for
the first time. The process, promoted by a H2O2-Ga(OTf)3
system, affords â-hydroxy sulfoxides in high yields (81-
94%) and high chemoselectivity without any detectable
overoxidation to â-hydroxy sulfones. The catalyst could be
recovered easily after the reactions and reused without
evident loss of activity.
(7) (a) Carren˜o, M. C.; Pe´rez-Gonza´lez, M.; Ribagorda, M.; Somoza,
AÄ .; Urbano, A. Chem. Commun. 2002, 3052. (b) Broutin, P. E.; Colobert,
F. Org. Lett. 2003, 5, 3281. (c) Pradilla, R. F.; Viso, A.; Castro, S.;
Ferna`ndez, J.; Manzano, P.; Tortosa, M. Tetrahedron 2004, 60, 8171.
(8) (a) Legros, J.; Dehli, J. R.; Bolm, C. AdV. Synth. Catal. 2005, 347,
19. (b) Matteucci, M.; Bhalay, G.; Bradley, M. Org. Lett. 2003, 5, 235. (c)
Schoumacker, S.; Hamelin, O.; Te´ti, S.; Pe´caut, J.; Fontecave, M. J. Org.
Chem. 2005, 70, 301. (d) Baciocchi, E.; Gerini, M. F.; Lapi, A. J. Org.
Chem. 2004, 69, 3586. (e) Koposov, A. Y.; Zhdankin, V. V. Synthesis 2005,
22. (f) Trevisan, V.; Signoretto, M.; Colonna, S.; Pironti, V.; Strukul, G.
Angew. Chem., Int. Ed. 2004, 43, 4097. (g) Iranpoor, N.; Firouzabadi, H.;
Pourali, A. R. Synlett 2004, 347. (h) Legros, J.; Bolm, C. Angew. Chem.,
Int. Ed. 2003, 42, 5487. (i) Karimi, B.; Ghoreishi-Nezhad, M.; Clark, J. H.
Org. Lett. 2005, 7, 625. (j) Legros, J.; Bolm, C. Chem.sEur. J. 2005, 11,
1086. (k) Sato, K.; Hyodo, M.; Aoki, M.; Zheng, X.-Q.; Noyori, R.
Tetrahedron 2001, 57, 2469. (l) Legros, J.; Bolm, C. Angew. Chem., Int.
Ed. 2004, 43, 4225. (m) Linde´n, A. A.; Johansson, M.; Hermanns, N.;
Ba¨ckvall, J.-E. J. Org. Chem. 2006, 71, 3849. (n) Qian, W.-X.; Pei, L.
Synlett 2006, 709. (o) Zeng, Q.-L.; Wang, H.-Q.; Wang, T.-J.; Cai, Y.-M.;
Weng, W.; Zhao, Y.-F. AdV. Synth. Catal. 2005, 347, 1933. (p) Mahamuni,
N. N.; Gogate, P. R.; Pandit, A. B. Ultrason. Sonochem. 2007, 14, 135. (q)
Mba, M.; Prins, L. J.; Licini, G. Org. Lett. 2007, 9, 21. (r) Firouzabadi, H.;
Iranpoor, N.; Jafari, A. A.; Riazymontazer, E. AdV. Synth. Catal. 2006, 348,
434 and references therein.
Epoxides are often used as intermediates in organic synthesis,1
and their reactions with different nucleophiles (e.g., amines,
thiols, alcohols, etc.) have been the subject of extensive studies.2
Thiolysis reaction of epoxides is the most practically and widely
used route for the synthesis of â-hydroxy sulfides. It can be
catalyzed by Lewis acid,3 microwave irradiation,4 or PBu3.5
Recently, we have studied the thiolysis reaction of epoxides in
ionic liquids without any catalyst.13d â-Hydroxy sulfides6 and
â-hydroxy sulfoxides7 are important intermediates in organic
synthesis.
† Zhejiang University of Technology.
‡ Wenzhou University.
(1) (a) Hanson, R. M. Chem. ReV. 1991, 91, 437. (b) Ghosh, A. K.; Wang,
Y. J. Org. Chem. 1999, 64, 2789. (c) Dias, L. C.; de Oliveira, L. G. Org.
Lett. 2001, 3, 3951. (d) Reddy, P. G.; Varghese, B.; Baskaran, S. Org. Lett.
2003, 5, 583. (e) Lepage, O.; Kattnig, E.; Fu¨rstner, A. J. Am. Chem. Soc.
2004, 126, 15970. (f) Darensbourg, D. J.; Mackiewicz, R. M.; Phelps, A.
L.; Billodeaux, D. R. Acc. Chem. Res. 2004, 37, 836.
(9) Sato, K.; Aoki, M.; Noyori, R. Science 1998, 281, 1646.
(2) (a) Barluenga, J.; Va´zquez-Villa, H.; Ballesteros, A.; Gonza´lez, J.
M. Org. Lett. 2002, 4, 2817. (b) Wu, J.; Xia, H.-G. Green Chem. 2005, 7,
708. (c) Garc´ıa-Delgado, N.; Reddy, K. S.; Sola`, L.; Riera, A.; Perica`s, M.
A.; Verdaguer, X. J. Org. Chem. 2005, 70, 7426. (d) Azoulay, S.; Manabe,
K.; Kobayashi, S. Org. Lett. 2005, 7, 4593.
(10) (a) See review: Kaczorowska, K.; Kolarska, Z.; Mitkab, K.;
Kowalskia, P. Tetrahedron 2005, 61, 8315. (b) Applications of Hydrogen
Peroxide and DeriVatiVes; Jones, C. W., Ed.; The Royal Society of
Chemistry, 1999. (c) Modern Oxidation Methods; Ba¨ckval, J. E., Ed.; Wiley-
VCH: Weinheim, Germany, 2004; pp 193-211.
10.1021/jo0700124 CCC: $37.00 © 2007 American Chemical Society
Published on Web 05/10/2007
4524
J. Org. Chem. 2007, 72, 4524-4527

TABLE 1. Thiolysis of Epoxides Catalyzed by Ga(OLTf)3 under Solvent-Free Conditionsa
a Reaction conditions: epoxides (5 mmol), thiophenols (5 mmol), Ga(OTf)3 (1 mol %), 30 °C. b Isolated yield. c Ratios of the two regioisomers were
determined by 1H NMR. d In the absence of Ga(OTf)3. e CH3NO2 was used as solvent. f Determined by HPLC apparatus fitted with a Chiralcel OJ-H chiral
column (iPrOH/hexane ) 1/99; flow rate ) 0.8 mL/min; detector ) 254 nm).
simplicity, strong tolerance to oxygen, nitrogen, phosphorus,
and sulfur-containing reaction substrates and functional groups.12
Recently, we have successfully applied metal triflates into
several reactions.13 In continuation of our interest in green
chemistry and Lewis acid-catalyzed organic reactions,13 we
herein developed a green, simple, and practical method for the
synthesis of â-hydroxy sulfides and â-hydroxy sulfoxides from
epoxides and thiophenols using Ga(OTf)3 as catalyst under
solvent-free or sole water conditions.
Initially, we have investigated a variety of ring-opening
reaction conditions with the model reaction.14a It seems that
nitromethane is a much better solvent (yield 84%) than all others
(11) (a) Kesavan, V.; Bonnet-Delpon, D.; Be´gue´, J. P. Tetrahedron Lett.
2000, 41, 2895. (b) Cardellicchio, C.; Omar, O. H.; Naso, F.; Capozzi, M.
A. M.; Capitellic, F.; Bertolasid, V. Tetrahedron: Asymmetry 2006, 17,
223.
(12) Kobayashi, S.; Sugiura, M.; Kitagawa, H.; Lam, W. L. Chem. ReV.
2002, 102, 2227.
J. Org. Chem, Vol. 72, No. 12, 2007 4525

TABLE 2. One-pot Synthesis of â-Hydroxy Sulfides Catalyzed by
tested [water (70%), acetonitrile (73%), nitroethane (79%), and
dichloromethane (67%)]. The best results were obtained by
carrying out the reaction at 30 °C for 30 min using 1 mol % of
Ga(OTf)3 without solvent. The product 1a was obtained in good
to excellent yields, while 1a was obtained in only low yield in
the absence of metal triflates. Metal triflates examined showed
good catalytic effects, and unexpectedly, Ga(OTf)3 was par-
ticularly effective for this ring-opening reaction. In this reaction,
Ga(OTf)3 could be reused three times without any loss of
activity. In contrast, other Lewis acids, such as InCl3,5d produce
a lower yield (53%) at the first use.
a
H2O2-Ga(OTf)3
In light of this, subsequent studies were carried out under
the optimized conditions: with 1 mol % of Ga(OTf)3 at 30 °C
under solvent-free. In all cases, Ga(OTf)3-catalyzed reactions
proceeded smoothly and gave the corresponding products in
good to excellent yield, as shown in Table 1.
The selective nucleophilic attack of thiophenols occurred
almost exclusively on the less hindered R-carbon of the oxirane
ring. Interestingly, thiolysis reaction of styrene oxide afforded
the â-addition products predominantly by attacking at the
benzylic â-carbon with electronic effects. However, when the
same reaction was performed in the absence of Ga(OTf)3, the
regioselectivity and conversions of ring-opening reactions were
unsatisfactory (entries 6 and 7).
On the other hand, it was observed that thiophenols bearing
either electron-donating or electron-withdrawing groups did not
make any difference in this reaction. The chemoselective
thiolysis in the presence of unprotected reactive functional
groups such as -OH and -NH2 (entries 4, 7, 10, and 13) also
proved to be successful. Similarly, the corresponding products
(3s-3n) from reaction of aliphatic thiols with epoxides were
obtained with high yields (entries 19-22).
Under further observation, we examined the reactivity of
heterocyclic thiols in the presence of Ga(OTf)3 (entries 10 and
14). However, the reactions gave the products (1j, 1n) in
moderate yields under solvent-free conditions due to poor
solubility of heterocyclic thiols in epoxides. Thus, the yields
showed significant improvement when the reaction was run in
CH3NO2.
Moreover, to extend the scope of this reaction, the thiolysis
of chiral epoxides [(R)-epichlorohydrin (99% ee) or (S)-
epichlorohydrin (98% ee)] was also examined using the present
protocol. It is noteworthy that optically pure epoxides were
converted into the corresponding â-hydroxy sulfides (1o, 1p)
without any racemization or inversion (entries 15 and 16).
Next, we reported one-pot synthesis of â-hydroxy sulfoxides
via ring-opening and oxidation reactions starting from epoxides
and thiophenols using H2O2 in the presence of Ga(OTf)3.
First, the efficacy of various Lewis acids was investigated in
the model reaction.14b The results showed that Ga(OTf)3 was
superior with respect to the amount of catalysts, reaction times,
and product yields. In this case, only trace product was obtained
after 24 h in the absence of Ga(OTf)3. Although the reactions
also proceeded with other metal triflates, long reaction times
were required to achieve yields comparable to those obtained
with Ga(OTf)3.
a Reaction conditions: epoxides (5 mmol), thiophenols or thiols (5 mmol),
Ga(OTf)3 (1 mol %), and 30% H2O2 (10 mmol), 30 °C. Method A:
Ga(OTf)3 and H2O2 were added simultaneously. Method B: Ga(OTf)3 was
added and stirred for 30 min without solvent, followed by addition of H2O2.
b Isolated total yield. c Oxidation of pure â-hydroxy sulfide 1h at 30 °C for
25 min. d Determined by 1H NMR analysis or HPLC. e Determined by
HPLC apparatus fitted with a C18 column (CH3OH/H2O ) 35/65, flow rate
) 1.0 mL/min; detector ) 206 nm). f Not determined.
(13) (a) Su, W.-K.; Hong, Z.; Shan, W.-G.; Zhang, X.-X. Eur. J. Org.
Chem. 2006, 2, 723. (b) Su, W.-K.; Li, J.-J.; Zheng, Z.-G.; Shen, Y.-C.
Tetrahedron Lett. 2005, 46, 6037. (c) Chen, J.-X.; Wu, H.-Y.; Zheng, Z.-
G.; Jin, C.; Zhang, X.-X.; Su, W.-K. Tetrahedron Lett. 2006, 47, 5383. (d)
Chen, J.-X.; Wu, H.-Y.; Jin, C.; Zhang, X.-X.; Xie, Y.-Y.; Su, W.-K. Green
Chem. 2006, 8, 330. (e) Yu, C.-M.; Dai, X.-P.; Su, W.-K. Synlett 2007,
646.
4526 J. Org. Chem., Vol. 72, No. 12, 2007

were obtained in the absence of Ga(OTf)3, which also further
proved that Ga(OTf)3 does play an important role in the
oxidation reaction of â-hydroxy sulfides (entries 1 and 3).
In summary, we have developed a novel catalytic approach
to the selective synthesis of â-hydroxy sulfides and â-hydroxy
sulfoxides using a recyclable gallium(III) triflate. Obviously,
the advantages of this method include (1) using a catalytic
amount of Ga(OTf)3 in high yields; (2) the catalyst could be
recovered by simple extraction and reused several times; (3)
The H2O2-Ga(OTf)3 system of catalyzed reactions is a simple
and environmentally benign procedure. Currently, studies on
the extension of this protocol are ongoing in our laboratory.
FIGURE 1. Intermolecular hydrogen bonds of 3c and 3j are indicated
by dashed lines.
Interestingly, when Bi(OTf)3 was used, diphenyldisulfide was
formed contaminated by some overoxidation product â-hydroxy
sulfone 4a. The structure of 4a was established by its X-ray
single-crystal diffraction analysis.15a Only diphenyldi-
sulfide was observed in 46% isolated yield after 12 h in the
presence of Sc(OTf)3. We supposed that it was due to oxidation
coupling of thiophenol that converted it into diphen-
yldisulfide under these conditions. However, the reaction
occurred with absolute chemoselectivity for formation of 3a
without any detectable overoxidation to 4a in the presence of
Ga(OTf)3.16 We next planned to determine the influence of
solvent on the catalytic property of the reaction of cyclohexene
oxide with thiophenol. Obviously, the presence of organic co-
solvents did not make the reaction rate faster. Therefore, we
chose to perform this reaction under sole water without any
organic co-solvents.
Experimental Section
General Procedure for the Synthesis of â-Hydroxy Sulfides
1a-1v. To a mixture of epoxides (5 mmol) and thiophenols (5
mmol) was added Ga(OTf)3 (0.05 mmol, 1 mol %). The mixture
was stirred at 30 °C for 30 min. The progress of the reaction was
monitored by TLC or HPLC. After completion of the reaction, water
was added and the product was extracted with diethyl ether (3 ×
10 mL). The organic layer was dried (MgSO4) and evaporated, and
the crude product was purified by flash chromatography (ethyl
acetate/hexane, 1:15 to 1:5) to provide the corresponding products.
The catalyst in the aqueous phase was concentrated in vacuo to
give a crystalline residue, which was finally heated at 180 °C for
48 h in vacuo to afford Ga(OTf)3 as colorless crystal. The recovered
Ga(OTf)3 could be reused in the next batch reaction.
To evaluate the scope of the catalyst’s application, various
epoxides were treated with thiophenols or thiols using H2O2 in
the presence of 1 mol % of Ga(OTf)3, and the results presented
in Table 2 indicated that H2O2-Ga(OTf)3-catalyzed one-pot
reactions proceeded smoothly and produced the corresponding
â-hydroxy sulfoxides in good to excellent yield. The corre-
sponding â-hydroxy sulfoxides were afforded efficiently when
less nucleophilic thiophenols such as p-fluorothiophenol were
used. Electron-rich thiophenols such as p-methylthiophenol
afforded the corresponding product in high yield as well (entry
2). Moreover, we also examined the reaction of aliphatic thiols
with epoxides. Similarly, the corresponding products 3l and 3m
were obtained with high yields (entries 12 and 13). On the other
hand, we investigated the diastereoisomeric ratio of â-hydroxy
sulfoxides by HPLC. Diastereoisomers of 3a were isolated
successfully by TLC; however, diastereoisomers of other
â-hydroxy sulfoxides could not be isolated. The structures of
3c15b and 3j15c (entries 3 and 10) were established by their X-ray
single-crystal diffraction analysis. As shown in Figure 1, the
formation of the strong intermolecular hydrogen bond could
greatly decrease the nucleophilicity at the sulfur atom.15
Using the H2O2-Ga(OTf)3 system, the chemoselectivity was
noteworthy. The sulfide function was highly reactive, and
various functional groups, including C-C and -OH, were
tolerable and were cleanly converted to â-hydroxy sulfoxides
without epoxidation and dehydrogenation in almost excellent
yields. Additionally, the present protocol followed an environ-
mentally benign process in which the solid products were
obtained through simple filtration in sole water media.
General Procedure for One-Pot Synthesis of â-Hydroxy
Sulfoxides 3a-3m. Method A: To a mixture of epoxides (5 mmol)
and thiophenols (5 mmol) were added Ga(OTf)3 (0.05 mmol, 1
mol %) and 1.2 mL of H2O2 (30 wt % aq solution, 10 mmol) and
stirred at 30 °C. Method B: A mixture of epoxides (5 mmol),
thiophenols (5 mmol), and Ga(OTf)3 (0.05 mmol, 1 mol %) was
stirred at 30 °C. After the ring-opening reaction was completed,
1.2 mL of H2O2 (30 wt % aq solution, 10 mmol) was added. Then
the mixture was continuously stirred at 30 °C. The progress of the
reaction was monitored by TLC or HPLC. After completion of the
reaction, the excess amount of H2O2 was destroyed by the addition
of a saturated aqueous solution of Na2SO3 to the reaction mixture.
If the products are solid, they were obtained through simple filtering
which did not need further purification. If the products are liquid,
the reaction mixture was extracted with diethyl ether (3 × 10 mL).
The organic layer was dried (MgSO4) and evaporated, and the crude
product was purified by flash chromatography to provide the
products. Selected data: 3k: oil, Rf ) 0.2 (petroleum ether/EtOAc
1
) 1:1); H NMR (300 MHz, CDCl3) δ 7.68-7.63 (m, 2H, ArH),
7.58-7.53 (m, 3H, ArH), 5.84-5.73 (m, 1H, CH2 ) CH-C),
5.00-4.90 (m, 2H, CH2 ) C), 4.32-4.30 (m, 1H, CHOH), 3.04-
2.70 (m, 3H, CH2S(O) and OH), 2.06-1.99 (m, 2H, CH2 ) CH-
CH2), 1.58-1.25 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 143.8,
138.9, 131.3, 129.4, 123.9, 68.7, 62.3, 36.9, 33.7, 29.1, 28.8, 28.6,
24.8; IR νmax 3373, 2927, 2855, 1444, 1020 (SO st) cm-1; MS (EI)
m/z 281 (M+ + 1, 85), 263 (42), 126 (100). Anal. Calcd for
C16H24O2S: C, 68.53; H, 8.63. Found: C, 68.48; H, 8.71.
Acknowledgment. We are grateful to the National Basic
Research Program (No. 2003CB114402), National Natural
Science Foundation of China (No. 20476098), Natural Science
Foundation of Zhejiang Province (No. 2002095), and Wenzhou
University Post-graduate Innovation Foundation (No. YCX0515)
for financial support.
Finally, we also investigated the oxidation reactions of pure
â-hydroxy sulfides (1h, 1i), which were prepared before. The
same results were obtained. However, the poor yields (12-14%)
Supporting Information Available: General experimental
details, X-ray crystal structure, and compound characterization data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(14) See Supporting Information: (a) Table 1; (b) Table 2.
(15) (a) CCDC-614766; (b) CCDC-614633; (c) CCDC-614765 contains
the supplementary crystallographic data, which is available free of charge
via www.ccdc.cam.ac.uk.
(16) The tR (4a) and tR (3a) showed the obvious difference in the same
conditions (see Supporting Information).
JO0700124
J. Org. Chem, Vol. 72, No. 12, 2007 4527