Palladium on Carbon-Catalyzed synthesis of benzil derivatives from 1,2-Diarylalkynes with DMSO and molecular oxygen as dual oxidants

Article abstract of DOI:10.1002/adsc.201000173

A palladium on carbon (Pd/C)-catalyzed synthetic method for the preparation of benzil derivatives from 1,2-diarylalkynes has been established using dimethyl sulfoxide (DMSO) and molecular oxygen as dual oxidants. Regardless of the electrical nature of the functional groups on the aromatic rings, 1,2-diarylalkynes were oxidized to the corresponding benzil derivatives in high to excellent yields. Furthermore, the oxidation could efficiently be catalyzed by both the dry and wet types of Pd/C under atmospheric conditions.

Full text of DOI:10.1002/adsc.201000173

COMMUNICATIONS
DOI: 10.1002/adsc.201000173
Palladium on Carbon-Catalyzed Synthesis of Benzil Derivatives
from 1,2-Diarylalkynes with DMSO and Molecular Oxygen as
Dual Oxidants
Shigeki Mori,a Masato Takubo,a Takayoshi Yanase,a Tomohiro Maegawa,a,b
Yasunari Monguchi,a and Hironao Sajikia,*
a
Laboratory of Organic Chemistry, Department of Organic and Medicinal Chemistry, Gifu Pharmaceutical University,
1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
Fax : (+81) 58-230-8109; e-mail: sajiki@gifu-pu.ac.jp
Current address: Graduate School of Pharmaceutical Sciences, Osaka University 1–6 Yamada-oka, Suita, Osaka 565-0871,
b
Japan
Received: March 5, 2010; Revised: May 18, 2010; Published online: June 30, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000173.
Abstract: A palladium on carbon (Pd/C)-catalyzed
synthetic method for the preparation of benzil de-
rivatives from 1,2-diarylalkynes has been estab-
lished using dimethyl sulfoxide (DMSO) and molec-
ular oxygen as dual oxidants. Regardless of the
electrical nature of the functional groups on the
and iodine reagents, such as N-iodosuccinimide[13] or
orthoperiodic acid,[14] has been essential for such reac-
tions. These reagents or methods have several draw-
backs, such as high toxicity and environmental
burden, requirement of special equipments, low cost
performance, and/or low yields. Dimethyl sulfoxide
(DMSO), an inexpensive and widely used chemical,
has been employed as an oxidant of the acid-,[15] N-
bromosuccinimide-[16] or iodine-mediated[17] oxidation
of 1,2-diarylalkynes. Although homogeneous transi-
tion metals, such as palladium(II) chloride[18] or iron-
aroACHTUNGTRENNUNGmatic rings, 1,2-diarylalkynes were oxidized to
the corresponding benzil derivatives in high to ex-
cellent yields. Furthermore, the oxidation could effi-
ciently be catalyzed by both the dry and wet types
of Pd/C under atmospheric conditions.
AHCTUNGTRENNUNG
(III) bromide,[19] have been reported to catalyze this
Keywords: alkynes; benzil; heterogeneous catalysis;
molecular oxygen; oxidation
transformation,[20,21] the use of a heterogeneous metal
catalyst should be an attractive alternative due to its
recoverability, reusability, and residual metal-free
properties. Although palladium on carbon (Pd/C), a
versatile heterogeneous catalyst for hydrogenation,
has already been used for benzil synthesis, the
Benzil derivatives are valuable compounds, which are method showed a narrow substrate applicability (only
found as a substructure of natural products,[1] and are two examples) and required the use of homogeneous
utilized as corrosion inhibitors of mild steel[2] and copper salts as a co-catalyst.[22] Our first attempt at
photosensitive agents in photocurable coatings.[3] the Pd/C-catalyzed oxidation of diphenylacetylene
Much interest has recently focused on the benzil de- (1a) was performed in DMSO under an oxygen at-
rivatives due to their potent activity as carboxylester- mosphere without any other additives and afforded
ase (CE) inhibitors.[4] Moreover, a variety of biologi- the corresponding benzil (2a) in 6% yield (Table 1,
cally active heterocyclic compounds, such as imida- entry 1). Although rhodium, ruthenium, iridium, gold,
zoles, triazines, and quinoxalines, can be synthesized and nickel on carbon displayed no catalyst activity
from benzil derivatives.[5] Several methods have been (entries 2–6), platinum on carbon (Pt/C) delivered an
developed for the synthesis of benzil derivatives.[6] improved yield (12% yield, entry 7).
The oxidation of 1,2-diarylalkynes, which are easily
Further investigations using Pd/C or Pt/C as the
prepared by the Sonogashira coupling between arylal- catalyst candidate were carried out to improve the re-
kynes and aryl halides,[7] is the most straightforward action efficiency (Table 2). Elevation of the reaction
process. The use of a stoichiometric amount of chro- temperature to 1208C dramatically increased the
mium[8] or manganese oxidants,[9] ozonolysis,[1a] the yields of 2a (entries 2 and 5). Using 10 mol% of 10%
sulfur trioxide-dioxane complex,[10] dioxiranes,[11,12] Pd/C, 2a was obtained in 92% yield, while no increase
1630
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1630 – 1634

Palladium on Carbon-Catalyzed Synthesis of Benzil Derivatives from 1,2-Diarylalkynes
Table 1. Evaluation of activated carbon-supported transition
Table 3. Determination of the role of DMSO and oxygen.[a]
metal catalysts.
Entry
Catalyst
Solvent
Gas
Ratio [%][b]
1a:2a
Entry
Catalyst
Yield [%][a]
1
2
3
4
5
6
7
10% Pd/C
10% Rh/C
10% Ru/C
10% Ir/C
10% Au/C
10% Ni/C
10% Pt/C
6
0
0
0
0
0
12
1
2
3
4
10% Pd/C
10% Pd/C
10% Pd/C
10% Pd/C
10% Pd(II)/C
10% Pd(II)/C
10% Pd(II)/C
10% Pd(0)/C
10% Pd(II)/C
10% Pd(0)/C
DMSO
toluene
DMA
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
O2
O2
O2
Ar
Ar
Ar
Ar
Ar
O2
O2
0:100
100:0
97:3
71:29
41:59
57:43
0:100
98:2
5
6[c]
7[d]
8
[a]
Isolated yield.
9
10
0:100
0:100
[a]
Table 2. Investigation of reaction temperature and catalyst
amount.
Diphenylacetylene (0.5 mmol), DMSO (0.5 mL), and cat-
alyst (10 mol%) were used unless otherwise noted.
The yield was determined by 1H NMR analysis.
DMSO (3 mL) was used.
[b]
[c]
[d]
DMSO (3 mL) and 10% Pd(II)/C (100 mol%) were used.
increase of DMSO in volume rather decreased the
yield of 2a (entries 5 vs. 6). These results suggest that
DMSO is the stoichiometric oxidant and molecular
oxygen serves to oxidize Pd(0) to the active Pd(II)
species. A plausible pathway for the benzil synthesis
is depicted in Figure 1. A Pd(II)-p-complex (A) is
formed with alkynes, facilitating the reaction with
Entry
Catalyst
Amount
[mol%]
Temp.
[8C]
Yield
[%][a]
G
1
2
3
4
5
6
10% Pt/C
5
5
10
5
5
80
12
79
77
6
66
92
120
120
80
120
120
10% Pd/C
10
[a]
Isolated yield.
in the yield was observed in the case of using 10
mol% of 10% Pt/C (entries 3 and 6). Therefore, 10%
Pd/C was chosen as the optimal catalyst for this reac-
tion.
Molecular oxygen and DMSO are two possible oxi-
dants for the present reaction system. The oxidation
hardly proceeded in toluene or N,N-dimethylacet-
ACHTUNGTRENNUNGamide (DMA) as the solvent (Table 3, entries 2 and
3) and was strongly suppressed under an argon atmos-
phere even in DMSO (entry 4). The yield of 2a in-
creased on the use of 10% Pd(II)/C instead of regular
10% Pd/C (entry 5), although the reaction hardly
took place with 10% Pd(0)/C[23] (entry 8). On the
other hand, the quantitative formation of 2a was ob-
served under an oxygen atmosphere regardless of the
oxidation state of the palladium (entries 1, 9, and 10).
Furthermore, the oxidation of 1a using 1 equivalent of
10% Pd(II)/C in an increased amount of DMSO
(3 mL) lead to a quantitative formation of 2a even
under an argon atmosphere (entry 7), while only an ly.
Figure 1. Proposed catalytic cycle involving Pd(II) exclusive-
Adv. Synth. Catal. 2010, 352, 1630 – 1634
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1631

Shigeki Mori et al.
COMMUNICATIONS
DMSO.[18,19] The nucleophilic addition of DMSO to A
followed by the loss of dimethyl sulfide and the addi-
tion of another molecule of DMSO would afford a
ketoalcohol intermediate (B), which would proceed
to the corresponding benzil derivatives together with
the palladium(II) species and a molecule of dimethyl
sulfide. An alternative Wacker-type pathway, which
generates palladium(0) in place of palladium(II) spe-
cies via the formation of a vinylpalladium(II) complex
(C), is not the prevailing reaction as is evidenced by
catalytic turnover in the Pd(II) experiments in the ab-
sence of oxygen (Figure 2).
To demonstrate the scope and limitations of this
method, a series of 1,2-diarylalkynes (1a–k) was sub-
jected to the optimized reaction conditions (10 mol%
of 10% Pd/C in DMSO at 1208C under an oxygen at-
Figure 2. Proposed catalytic cycle involving a Pd(0) inter-
mediate.
Table 4. Oxidation of various 1,2-diaryalkynes (1) to benzil derivatives (2) under the optimized conditions.
Entry
1
Substrate 1
Product 2
Yield [%][a]
92
1a
1b
1c
2a
2b
2c
2
3
74
85
4
1d
2d
98
5
6
7
1e
1f
1g
2e
2f
2g
61
84
49
1632
asc.wiley-vch.de
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1630 – 1634

Palladium on Carbon-Catalyzed Synthesis of Benzil Derivatives from 1,2-Diarylalkynes
Table 4. (Continued)
Entry
Substrate 1
Product 2
Yield [%][a]
41
8
1h
1i
2h
2i
9
62
74
10
11
1j
2j
1k
1a
2k
2a
83
84
12[b]
[a]
Isolated yield.
[b]
The reaction was performed in an air atmosphere using the wet-type 10% Pd/C (10 mol%).
mosphere, Table 4). The methyl- or methoxy-substi- entry 1, Table 4). Therefore, fresh 10% Pd/C should
tuted 1,2-diarylalkynes (1b–d) were transformed into be used for the present oxidation.
the corresponding benzil derivatives (2b–d) in excel-
In conclusion, we have established a Pd/C-catalyzed
lent yields (entries 2–4). The oxidation of the alkyne environmentally benign process for the oxidation of
possessing a methoxy group at the o-position on the various 1,2-diarylalkynes to the corresponding benzil
aromatic ring (1e) afforded 2e in a slightly lower derivatives using DMSO and molecular oxygen as
yield, presumably due to the difficult formation of the dual oxidizing agents.[25] The present reaction effi-
palladium-p complex (Figure 1) by the steric hin- ciently proceeded without any additives and the less
drance around the triple bond or unexpected benzo- pyrophoric wet-type of Pd/C was also applicable. The
furan formation (entry 5).[24] The introduction of an present method is expected to provide a practical pro-
electron-withdrawing cyano or nitro group on an aro- cess for industry.
matic ring (1g or 1h) suppressed the oxidation, result-
ing in moderate yields of the corresponding benzil de-
rivatives (entries 7 and 8). The diphenylacetylenes
bearing both electron-donating and electron-with-
Experimental Section
drawing groups on each benzene ring, 1i and 1j, un-
General Procedure for the Oxidation of
derwent the oxidation to give 2i and 2j in good yields,
Diphenylacetylene (1a)
respectively (entries 9 and 10). The smooth oxidation
A mixture of 1a (89.1 mg, 0.50 mmol), 10% Pd/C (53.2 mg,
0.05 mmol), and DMSO (0.5 mL), was stirred under an
oxygen (balloon) atmosphere at 1208C using the Chemista-
tion personal organic synthesizer (EYELA, Tokyo) for 24 h.
The mixture was cooled to room temperature, diluted with
EtOAc (10 mL) and H2O (10 mL), and then passed through
a membrane filter (Millipore, Millex-LH, 0.45 mm). The sep-
arated organic layer was washed successively with water (2ꢁ
10 mL) and brine (20 mL), then dried over anhydrous
Na2SO4, filtered, and concentrated under vacuum. The resi-
of the 4,4’-dimethoxydiphenylacetylene (1k) was also
achieved (entry 11). Furthermore, it was found that
the wet-type 10% Pd/C containing approximately
50% by weight of water, a preferred catalyst for in-
dustrial scale processes due to its lower ignition
hazard, also efficiently catalyzed the present reaction
(entry 12).
The reuse of Pd/C for the oxidation of 1a to 2a was
next investigated. However, the yield was significantly
reduced to 30% in the second run (compare with due was purified by silica gel column chromatography using
Adv. Synth. Catal. 2010, 352, 1630 – 1634
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1633

Shigeki Mori et al.
COMMUNICATIONS
n-hexane/EtOAc (20/1) as the eluent to give benzil (2a) as a
colorless solid; yield: 96.7 mg (92%).
[11] R. Curci, M. Fiorentino, C. Fusco, R. Mello, F. P. Ballis-
treri, S. Failla, G. A. Tomaselli, Tetrahedron 1992, 33,
7929–7932.
[12] A variety of a-keto-imides was prepared by the oxida-
tion of carbon-carbon triple bonds of ynamides using
dimethyldioxirane or a combination of ruthenium(II)
oxide and sodium metaperiodate, see: Z. F. Al-Rashid,
W. L. Johnson, R. O. Hsung, Y. Wei, P.-Y. Yao, R. Liu,
K. Zhao, J. Org. Chem. 2008, 73, 8780–8784.
[13] M. Niu, H. Fu, Y. Jiang, Y. Zhao, Synthesis 2008, 2879–
2882.
Acknowledgements
We sincerely thank the N.E. Chemcat Corporation for the
kind gift of the catalysts.
[14] G. Gebeyehu, E. McNelis, J. Org. Chem. 1980, 45,
4280–4283.
[15] a) S. Dayan, I. Ben-David, S. Rozen, J. Org. Chem.
2000, 65, 8816–8818; b) Z. H. Wan, C. D. Jones, D.
Mitchell, J. Y. Pu, T. Y. Zhang, J. Org. Chem. 2006, 71,
826–828.
[16] S. Wolfe, W. R. Pilgrim, T. F. Garrard, P. Chamberlain,
Can. J. Chem. 1971, 49, 1099–1105.
[17] M. S. Yusubov, V. D. Filimonov, Synthesis 1991, 131–
132.
References
[1] a) L. Re, B. Maurer, G. Ohloff, Helv. Chim. Acta 1973,
56, 1882–1894; b) M. D. Rozwadowska, M. Chrzanow-
ska, Tetrahedron 1985, 41, 2885–2890; c) W. Mahabu-
sarakam, S. Deachathai, S. Phongpaichit, C. Jansakul,
W. C. Taylor, Phytochemistry 2004, 65, 1185–1191.
[2] B. I. Ita, O. E. Offiong, Mater. Chem. Phys. 2001, 70,
330–335.
[3] Matsushita Electric Industrial Co. Ltd. Jpn. Kokai
Tokkyo Koho 1981, 203, 8198; Chem. Abstr. 1981, 95,
188163u.
[18] M. S. Yusubov, V. D. Filimonov, Synth. Commun. 1994,
24, 2119–2122.
[19] A. Giraud, O. Provot, J.-F. Peyrat, M. Alami, J.-D.
[4] a) T. Harada, Y. Nakagawa, R. M. Wadkins, P. M.
Potter, C. E. Wheelock, Bioorg. Med. Chem. 2009, 17,
149–164; b) C. C. Edwards, J. L. Hyatt, L. Tsurkan, F.
Bai, C. Fraga, C. L. Morton, E. L. Howard-Williams,
P. M. Potter, M. R. Redinbo, J. Mol. Biol. 2005, 352,
165–177; c) R. M. Wadkins, J. L. Hyatt, X. Wei, K. J. P.
Yoon, M. Wierdl, C. C. Edwards, C. L. Morton, J. C.
Obenauer, K. Damodaran, P. Beroza, M. K. Danks,
P. M. Potter, J. Med. Chem. 2005, 48, 2906–2915.
[5] W. D. Shipe, F. Yang, Z. Zhao, S. E. Wolkenberg, M. B.
Nolt, C. W. Lindsley, Heterocycles 2006, 70, 655–689.
[6] a) N. Kise, N. Ueda, Bull. Chem. Soc. Jpn. 2001, 74,
755; b) A. R. Katritzky, D. Z. Zhang, K. Kirichenko, J.
Org. Chem. 2005, 70, 3271–3274, and references cited
therein.
[7] a) H. Doucet, J. C. Hierso, Angew. Chem. 2007, 119,
850–888; Angew. Chem. Int. Ed. 2007, 46, 834–871;
b) C. Rafael, N. Carmen, Chem. Rev. 2007, 107, 874–
922.
[8] a) H. Firouzabadi, A. R. Sardarian, H. Moosavipour,
G. M. Afshari, Synthesis 1986, 285–288; b) B. Rihter, J.
Masnovi, J. Chem. Soc. Chem. Commun. 1988, 35–37.
[9] a) D. G. Lee, V. S. Chang, Synthesis 1978, 462; b) N. S.
Srinvasan, D. G. Lee, J. Org. Chem. 1979, 44, 1574;
c) D. G. Lee, V. S. Chang, J. Org. Chem. 1979, 44,
2726–2730.
Brion, Tetrahedron 2006, 62, 7667–7673.
[20] The combined use of palladium(II) bromide and cop-
per(II) bromide as the homogeneous transition metal
catalysts under an oxygen atmosphere effectively oxi-
dized alkynes to the corresponding benzil derivatives in
the presence of water as the oxygen source, see: W.
Ren, Y. Xia, S.-J. Ji, Y. Zhang, X. Wan, J. Zhao, Org.
Lett. 2009, 11, 1841–1844.
[21] A copper-catalyzed oxidative amidation-diketonization
of aniline derivatives with alkynes in the presence of
water and oxygen leading to a-keto-amides was recent-
ly reported, see: C. Zhang, N. Jiao, J. Am. Chem. Soc.
2010, 132, 28–29.
[22] M. S. Yusubov, E. A. Krasnokutskaya, V. P. Vasilyeva,
V. D. Filimonov, K.-W. Chi, Bull. Korean Chem. Soc.
1995, 16, 86–88.
[23] It should be noted that regular Pd/C typically includes
a small amount of the Pd(II) species. Since Pd(0)/C is
prepared under more reductive conditions, it mostly
consisted of the Pd(0) species.
[24] a) D. Yue, T. Yao, R. C. Larock, J. Org. Chem. 2005,
70, 10292–10296; b) J. Oppenheimer, W. L. Johnson,
M. R. Tracey, R. P. Hsung, P.-Y. Yao, R. Liu, K. Zhao,
Org. Lett. 2007, 9, 2361–2364.
[25] The protocol is currently limited to the synthesis of
benzil derivatives. When one or two aryl groups of di-
[10] V. O. Rogatchov, V. D. Filimonov, M. S. Yusubov, Syn-
thesis 2001, 1001–1003.
ACHTUNGTRENNUNG
1634
asc.wiley-vch.de
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1630 – 1634