Synthesis of α,β-diketotriazoles by aerobic copper-catalyzed oxygenation with triazole as an intramolecular assisting group

Article abstract of DOI:10.1002/ejoc.201101346

The catalytic oxidation of α-ketotriazoles to α,β- diketotriazoles was performed with CuCl₂ or CuI/2,9-dimethyl-1,10- phenanthroline in air at 80 °C in good yields. Studies showed that the triazole group participates in complexation to the copper and favors oxidation. Copyright

Full text of DOI:10.1002/ejoc.201101346

FULL PAPER
DOI: 10.1002/ejoc.201101346
Synthesis of α,β-Diketotriazoles by Aerobic Copper-Catalyzed Oxygenation
with Triazole as an Intramolecular Assisting Group
Christophe Menendez,[a,b] Sylvain Gau,[a,b] Sonia Ladeira,[c] Christian Lherbet,*[a,b] and
Michel Baltas*[a,b]
Keywords: Ketotriazoles / Diketotriazoles / Copper / Oxidation / Synthesis design
The catalytic oxidation of α-ketotriazoles to α,β-diketotri-
azoles was performed with CuCl2 or CuI/2,9-dimethyl-1,10-
phenanthroline in air at 80 °C in good yields. Studies showed
that the triazole group participates in complexation to the
copper and favors oxidation.
We have recently reported the synthesis of α-ketotriazoles
and related systems as potential inhibitors of InhA, an en-
oyl-ACP reductase enzyme of the type II fatty acid synthe-
sis (FAS-II) system. During the synthesis of ketotriazole 2a
by click chemistry[15] starting from trimethylsilyl (TMS)
ynone and benzyl azide under the conditions shown in Fig-
ure 1, we discovered the presence of a side product. Mass
Introduction
1,2-Diketones have found widespread application as mo-
lecular building blocks for the synthesis of various biolo-
gically active heterocyclic compounds. Moreover, they are
versatile building blocks for the synthesis of imidazoles,[1,2]
quinoxalines,[3] triazines,[4] and other heterocycles. The 1,2-
diketone framework can be prepared by different pro-
cedures, which have been described in the literature.[5]
A
typical method is the oxidation of alkynes to α-diketones in
the presence of different catalysts.[6,7] For example, Ren et
al. have reported the oxidation of alkynes to afford 1,2-dike-
tones, which is catalyzed by PdBr2 and CuBr2.[8] Chen et
al. have used a ruthenium complex for the first catalytic
oxidation of alkenes at room temperature.[9] Another ap-
proach starts from 1,2-diols[10] with (2,2,6,6-tetramethylpip-
eridin-1-yl)oxyl as the catalyst and iodobenzene chloride as
a stoichiometric oxidant or from 1,3-diols[11] using 2-iodox-
ybenzoic acid. Moghaddam et al. have reported the aerobic
oxidation of aryl thioacetamides into the corresponding α-
keto aryl thioamides in good yields with copper(II) chloride
as a catalyst. 1,2-Diketones have also been prepared by the
oxidation of α-hydroxy ketones with copper as, for example,
copper-containing hydrotalcite[12] or the “copper(II)/cesium
carbonate system”[13] in aerobic conditions. Zhang et al.
have reported the synthesis of 1,2-diketones from 1,3-diket-
ones with FeCl3 as the catalyst and tert-butyl nitrite as the
oxidant.[14]
Figure 1. ORTEP[17] view of 2a (top) and 3a (bottom). Thermal
ellipsoids are shown at 30% probability. Hydrogen atoms are omit-
ted for clarity. Crystallographic data for 2a and 3a can be found in
the Supporting Information.
[a] CNRS, Laboratoire de Synthèse et Physico-Chimie de
Molécules d’Intérêt Biologique, SPCMIB, UMR-5068
118 Route de Narbonne, 31062 Toulouse cedex 9, France
Fax: +33-5-61556011
[b] Université de Toulouse, UPS, Laboratoire de Synthèse et
Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB,
118 route de Narbonne, 31062 Toulouse cedex 9, France
[c] Institut de Chimie de Toulouse, FR2599
118 Route de Narbonne, 31062 Toulouse, France
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101346.
Scheme 1. Side product observed during click chemistry.
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409

C. Menendez, S. Gau, S. Ladeira, C. Lherbet, M. Baltas
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spectrometric and NMR spectroscopic analysis indicated
In order to gain insight into the second transformation,
the possible oxidation of 2a to afford the 1,2-diketone 3a we initiated our investigation using 2a as the model sub-
(Scheme 1). strate to establish a general procedure for the oxidation. A
In this paper, we wish to report our investigations on series of reaction conditions were screened, and the results
a copper-dependent method to produce α,β-diketotriazoles are summarized in Table 2. The reaction was monitored by
from α-ketotriazoles in air by employing triazole as an in- TLC until the disappearance of the starting material. We
tramolecular assisting group.
first conducted the reaction with copper(II) catalysts, such
as Cu(OAc)2 and CuCl2, in the presence or absence of 1,10-
phenanthroline derivatives (Table 2, Entries 1–3).
In preliminary experiments on the reaction conditions
for the preparation of 2a, we noted that with prolonged
Results and Discussion
The starting materials were readily available from cop- reaction times, a secondary product was formed, which was
per-catalyzed alkyne–azide cycloaddition reactions.[16] They identified as the 1,2-diketone 3a. Its structure was con-
were synthesized in a one-pot procedure by the in situ de- firmed by X-ray crystallography, which showed that oxi-
protection of TMS-ynone and cyclization with different az- dation of the methylene occurred (Figure 1). To the best of
ides (Scheme 2). The results are summarized in Table 1. The our knowledge, this is the first reported synthesis of a α,β-
yields remained good regardless of the alkyl or benzyl diketotriazole framework.
groups, which bear various electron-donating or electron-
withdrawing substituents.
The best yield (55%) was obtained with CuCl2 in the
presence of 2,9-dimethyl-1,10-phenanthroline with heating
Scheme 2. Synthesis of α-ketotriazole derivatives 2a–n.
Table 1. Synthesis of triazoles.
[a] Isolated yields. [b] Published in ref.[16]
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α,β-Diketotriazoles by Aerobic Cu-Catalyzed Oxygenation
Table 2. Screening of reaction conditions for the oxidation of α-ketotriazole.
Entry
Catalyst (equiv.)
Solvent
Conditions
Yield[a] [%]
1
2
3
4
5
6
7
8
Cu(OAc)2 (0.1), 1,10-phenanthroline (0.2)
CuCl2 (0.1), 1,10-phenanthroline (0.2)
CuCl2 (0.1), 2,9-dimethyl-1,10-phenanthroline (0.2)
CuCl2 (0.1), K2CO3 (1), 2,9-dimethyl-1,10-phenanthroline (0.2) DMF
Cu(OAc)2 (0.1), Na ascorbate (0.2)
Cu(OAc)2 (0.1), Na ascorbate (0.2)
CuI (0.1)
CuI (0.1), 2,9-dimethyl-1,10-phenanthroline (0.2)
CuCl (0.1), 2,9-dimethyl-1,10-phenanthroline (0.2)
CuI (0.1), K2CO3 (1), 2,9-dimethyl-1,10-phenanthroline (0.2)
CuI (0.1), 2,9-dimethyl-1,10-phenanthroline (0.2)
CuI (0.1), O2 balloon, 2,9-dimethyl-1,10-phenanthroline (0.2)
CH3CN
CH3CN
CH3CN
reflux, 20 h
reflux, 20 h
reflux, 20 h
reflux, 2 h
r.t., 48 h
reflux, 3 h
reflux, 7 h
reflux, 2 h
reflux, 2 h
reflux, 2 h
60 °C, 2 h
reflux, 30 min
40
43
55
32
17
39
37
55
52
53
34
59
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
9
10
11
12
[a] Isolated yields.
under reflux. The reaction was less efficient in N,N-dimeth- tained in 59% yield after silica gel purification (Entry 12).
ylformamide (DMF) in the presence of K2CO3 (Entry 4). Finally, when the reaction was carried out under nitrogen,
For each reaction, side products were observed, a major no product was observed, which demonstrates that oxygen
one of which was identified as benzaldehyde.
has a direct effect on the process.
Copper(I) was also investigated and was first generated
In order to verify the generality of our method, we ex-
in the presence of copper acetate and sodium ascorbate tended it to different α-ketotriazoles with different substitu-
(NaAsc) at room temperature (Entries 5 and 6). Heating ents on the aromatic moieties (Table 3).[18] As with the re-
under reflux shortened the reaction time remarkably to 3 h sults shown in Table 2, the reaction was monitored by look-
to afford 3a in 39% yield (Entry 6). When copper iodide ing at the disappearance of the starting material by TLC.
alone was used as the CuI source, a 37% yield of 3a was Two different sources of copper, CuCl2 and CuI, were used
obtained after 7 h of heating to reflux. The introduction for comparison.
of 0.2 equiv. of 2,9-dimethyl-1,10-phenanthroline afforded a
In general, the yields for the reactions performed in the
much better yield of 3a in only 2 h with heating to reflux presence of CuI are similar or better except for Entries 7
(Entry 8). The addition of CuCl instead of CuI (Entry 9) or and 9 (Table 3). The substrate with a benzylic group that
base (Entry 10) did not improve the yield, even at a lower bears an electron-rich p-methoxy substituent seems to be
temperature (Entry 11) to avoid the formation of side prod- oxidized in a way similar to that of the parent benzylic
ucts.
group (Entry 6 compared to Entry 1). In the case of sub-
We have also performed the reaction under O2. After strates with electron-poor substituents, oxidation to the cor-
30 min of heating under reflux in acetonitrile, 3a was ob- responding 1,2-diketone is quite similar (Entries 12 and 13).
Scheme 3. Investigations on the reaction mechanism.
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Scheme 4. Possible mechanism for the oxidation reaction.
The presence of substituents in the 2-position on the aryl presence of oxygen.[20] Chiba et al. have reported the first
moiety seems to favor oxidation. Indeed, when chloro or copper-catalyzed benzylic C–H oxygenation under oxygen
methoxy substituents are present, α,β-diketones were ob- with N–H imines as intramolecular directing groups and a
tained in good yields (Entries 7, 8, 14, and 15). In all cases, proposed iminyl–CuIII intermediate.[21]
either with copper(II) or copper(I), substituted benzalde-
Taking into account the suggested mechanisms cited
hydes were observed by 1H NMR spectroscopy in the crude above, a possible mechanism is depicted in Scheme 4. The
mixtures. For example, p-methoxybenzaldehyde was ob- process is initiated by the coordination of the α-ketotria-
tained as a major byproduct in 25% yield for Entry 6 with zole, which is considered as a bidentate ligand, to CuII
copper(II) and p-nitrobenzaldehyde in 20 and 33% yield for through the triazole moiety and the oxygen atom of the
Entries 12 and 13, respectively (Table 3).
carbonyl group or its enol form. The triazole frame may act
We conducted further studies in order to gain insights as an internal directing group. The copper species is oxid-
into the mechanism (Scheme 3). First, 3a was not obtained ized with O2 to form the peroxy copper(III) species II. The
from 4, which bears a methylene group instead of a carb- benzylic moiety is converted into the peroxy copper(II) spe-
onyl group. The same result was obtained with deoxyben- cies III through a benzylic radical. This intermediate may
zoin. Under copper-mediated conditions, no trace of prod- either lead to benzaldehyde, which is obtained in low yield
uct was observed. Finally, and most interestingly, when in some cases, and triazolo acid (not observed) through the
phenylacetylpyridine 5 was used as a substrate, the corre- cleavage of the carbon–carbon bond, or deliver the α,β-di-
sponding diketone 6 was observed in 32% yield with CuI ketotriazole product as described in Tables 2 and 3.
as catalyst, which strongly suggests that nitrogen partici-
The broad synthetic utility of these α,β-diketo products
pates in the oxidation reaction through copper chelation.
was demonstrated by carrying out the subsequent synthesis
Aerobic oxidation reactions that use transition metals are of quinoxalines (Scheme 5a) or imidazoles (Scheme 5b and
receiving considerable attention, and directing group as- c). These derivatives are prevalent in a number of natural
sisted inter/intramolecular C–H functionalization is consid- products and pharmacologically active compounds.[22,23]
ered to be one of the most promising approaches for new Quinoxaline 7 was obtained in 97% yield from 4,5-dimeth-
C–C (or heteroatom) bond formation. Recently, Ohno et al. ylbenzene-1,2-diamine. Imidazoles 8 and 9 were prepared
have reported CuII-mediated oxidative intermolecular func- by known procedures (Scheme 5).[2,24] The exact structure
tionalization, which uses tetrahydropyrimidine as a direct- of 9 was determined by X-ray crystallography.
ing group for the introduction of oxygen or nitrogen at the
ortho position on the aromatic ring.[19] The results indicated
that this reaction is sensitive to the presence of electron-
withdrawing groups on the aromatic ring.
Conclusions
Zhu et al. have reported direct access to formyl-substi-
tuted imidazoles and other aromatic N-heterocycles
We have developed a new approach for the synthesis of
through an intramolecular dehydrogenerative aminooxy- α,β-diketotriazoles from α-ketotriazoles in the presence of
genation via a proposed pyridine–CuIII intermediate in the 10 mol-% copper(I) or -(II) and 20 mol-% 2,9-dimethyl-
412
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Eur. J. Org. Chem. 2012, 409–416

α,β-Diketotriazoles by Aerobic Cu-Catalyzed Oxygenation
Table 3. Synthesis of α,β-diketotriazoles from α-ketotriazoles.
Scheme 5. Application to the synthesis of quinoxaline 7 or imid-
azoles 8 and 9. Crystallographic data for 9 can be found in the
Supporting Information.
provides access to a variety of α,β-diketotriazole com-
pounds, which could be of importance in medicinal chemis-
try. The investigation of further applications of this reaction
is underway.
Experimental Section
General Information: All chemicals were obtained from Aldrich or
Acros Organics and used without further purification. NMR spec-
tra were recorded with a Bruker AC 300 spectrometer (1H and 13
C
1
NMR). H NMR spectra were recorded at 300 MHz with CDCl3
(δ = 7.26 ppm) as an internal standard. 13C NMR spectra were
recorded at 75.0 MHz and are referenced against the central line
of the CDCl3 triplet at δ = 77.0 ppm. MS data were obtained with
a ThermoQuest TSQ 7000 spectrometer, and HRMS was per-
formed with a ThermoFinnigan MAT 95 XL spectrometer by using
ESI methods. IR spectra were recorded with a Perkin–Elmer 1725.
[a] Reactions with CuCl2 were performed for 20 h and those with
CuI for 2–4 h depending on the starting material. [b] Isolated
yields.
1,10-phenanthroline under air. Our study showed the im-
portance of the triazole as an intramolecular directing
Representative Procedure for the Synthesis of TMS-Ynone Deriva-
group for the oxidation of the benzylic moiety. This method tives: These compounds were prepared according to a reported pro-
Eur. J. Org. Chem. 2012, 409–416
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413

C. Menendez, S. Gau, S. Ladeira, C. Lherbet, M. Baltas
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cedure.[25] The analytical data for the compounds synthesized were
3 H), 7.51 (t, J = 7.4 Hz, 2 H), 7.66 (tt, J = 7.5, J = 1.3 Hz, 1 H),
8.03 (d, J = 8.3 Hz, 2 H), 8.21 (s, 1 H) ppm. 13C NMR (CDCl3):
δ = 29.7, 54.7, 55.5, 100.8, 106.5, 128.3, 128.9, 130.2, 132.3, 134.9,
compared with those previously reported (1a and 1b).[25]
1-(2,4-Dichlorophenyl)-4-(trimethylsilyl)but-3-yn-2-one (1c): Yellow
135.2, 144.4, 161.5, 185.5, 191.9 ppm. IR (neat): ν = 1681, 1600,
˜
1
oil. Yield 92%. H NMR (CDCl3): δ = 0.19 (s, 9 H), 3.95 (s, 2 H),
1531, 1346 cm–1. HRMS: calcd. for C19H18N3O4 [M + H]+
352.1297; found 352.1312.
7.17 (d, J = 8.2 Hz, 1 H), 7.24 (dd, J = 8.2, J = 2.1 Hz, 1 H), 7.42
(d, J = 2.1 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = –0.9, 48.2, 100.5,
101.1, 127.2, 129.4, 130.2, 132.6, 134.1, 135.6, 182.9 ppm. HRMS:
calcd. for C13H15Cl2OSi [M]+ 285.0269; found 285.0272.
1-[1-(3,5-Dimethylbenzyl)-1H-1,2,3-triazol-4-yl]-2-phenylethane-1,2-
dione (3d): Yellow powder. M.p. 97 °C. Yields (CuCl2/CuI) 48/47%.
1H NMR (CDCl3): δ = 2.31 (s, 6 H), 6.93 (s, 2 H), 7.02 (s, 1 H),
7.50 (t, J = 7.6 Hz, 2 H), 7.65 (t, J = 7.4 Hz, 1 H), 8.00 (d, J =
7.2 Hz, 2 H), 8.18 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 21.2, 54.6,
126.2, 128.2, 128.9, 130.2, 130.9, 132.3, 133.0, 134.9, 139.2, 144.4,
1-(4-Nitrophenyl)-4-(trimethylsilyl)but-3-yn-2-one (1d): Gummy yel-
1
low solid. Yield 38%. H NMR (CDCl3): δ = 0.20 (s, 9 H), 3.96 (s,
2 H), 7.41 (d, J = 8.7 Hz, 2 H), 8.20 (d, J = 8.7 Hz, 2 H) ppm. 13C
NMR (CDCl3): δ = –1.0, 51.3, 101.2, 101.3, 123.7, 130.8, 140.1,
147.3, 182.7 ppm. HRMS: calcd. for C13H16N3OSi [M]+ 262.0899;
found 262.0883.
185.6, 192.0 ppm. IR (neat): ν = 1681, 1600, 1531, 1346 cm–1
.
˜
HRMS: calcd. for C19H18N3O2 [M]+ 320.1399; found 320.1394.
1-(1-Octyl-1H-1,2,3-triazol-4-yl)-2-phenylethane-1,2-dione (3e): Yel-
1-(2-Methoxyphenyl)-4-(trimethylsilyl)but-3-yn-2-one (1e): Yellow
1
low gel. Yields (CuCl2/CuI) 40/48%. H NMR (CDCl3): δ = 0.85
1
oil. Yield 75%. H NMR (CDCl3): δ = 0.16 (s, 9 H), 3.80 (s, 3 H),
(t, J = 6.9 Hz, 3 H), 1.29 (m, 10 H), 1.95 (m, 2 H), 4.44 (t, J =
7.26 Hz, 2 H), 7.52 (t, J = 7.4 Hz, 2 H), 7.66 (t, J = 7.4 Hz, 1 H),
8.04 (dd, J = 8.3, J = 1.3 Hz, 2 H), 8.29 (s, 1 H) ppm. 13C NMR
(CDCl3): δ = 14.0, 22.6, 26.4, 28.8, 29.0, 30.1, 31.6, 128.1, 128.9,
3.82 (s, 2 H), 6.88 (d, J = 8.2 Hz, 1 H), 6.93 (td, J = 7.4, J = 1.0 Hz,
1 H), 7.15 (dd, J = 7.4, J = 1.5 Hz, 1 H), 7.28 (td, J = 8.1, J =
1.8 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = –0.9, 46.5, 53.5, 98.5,
101.7, 110.4, 120.5, 122.2, 128.8, 131.4, 157.7, 185.4 ppm. HRMS:
calcd. for C14H19O2Si [M]+ 247.1154; found 247.1155.
130.2, 132.4, 134.9, 144.1, 185.7, 192.1 ppm. IR (neat): ν = 2928,
˜
1679, 1597, 1531, 1376 cm–1. HRMS: calcd. for C18H24N3O2 [M]+
314.1869; found 314.1877.
Representative Procedure for the Synthesis of α-Ketotriazole Deriva-
tives: To a solution of 1-trimethylsilyl-1-alkynyl ketone (1 equiv.)
and azide (1.2 equiv.) in CH3CN/H2O (4:1), was added CuCl2
(0.1 equiv.) and sodium ascorbate (0.2 equiv.) at room temperature.
The reaction mixture was warmed to 80 °C for 45–60 min. After
cooling to room temperature, H2O was added, and the mixture was
extracted with EtOAc. The organic layer was washed with brine,
dried with MgSO4, filtered, and concentrated under reduced pres-
sure. The product was purified by flash chromatography (petroleum
ether/EtOAc). The compounds 2a–e, 2g, 2i have identical analytical
data to those reported.[15]
1-(1-Benzyl-1H-1,2,3-triazol-4-yl)-2-(4-methoxyphenyl)ethanone
1
(2f): Yellow powder. M.p. 116 °C. Yield 80%. H NMR (CDCl3):
δ = 3.79 (s, 3 H), 4.38 (s, 2 H), 5.56 (s, 2 H), 6.88 (d, J = 8.7 Hz,
2 H), 7.31 (m, 4 H), 7.40 (m, 3 H), 8.01 (s, 1 H) ppm. 13C NMR
(CDCl3): δ = 45.0, 54.4, 55.1, 113.9, 125.8, 128.3, 129.0, 129.2,
130.8, 133.5, 158.5, 192.4 ppm. IR (neat): ν = 1683, 1612, 1513,
˜
1362 cm–1. HRMS: calcd. for C18H18N3O2 [M]+ 308.1399; found
308.1387.
1-(1-Benzyl-1H-1,2,3-triazol-4-yl)-2-(4-methoxyphenyl)ethane-1,2-di-
one (3f): Yellow powder. M.p. 122 °C. Yields (CuCl2/CuI) 50/58%.
1H NMR (CDCl3): δ = 3.88 (s, 6 H), 5.60 (s, 2 H), 6.96 (d, J =
9.0 Hz, 2 H), 7.33 (m, 2 H), 7.39 (m, 3 H), 8.01 (d, J = 9.0 Hz,
2 h), 8.19 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 54.5, 55.6, 114.3,
125.3, 128.3, 128.4, 129.3, 129.4, 132.8, 133.3, 144.5, 165.1, 185.6,
Representative Procedure for the Synthesis of α,β-Diketotriazole De-
rivatives: To a solution of α-ketotriazole (1 equiv.) in CH3CN
(3 mL) were added CuCl2 (0.1 equiv.) and 2,9-dimethyl-1,10-phen-
anthroline (0.2 equiv.) at room temperature. The reaction mixture
was warmed to reflux with stirring under air for 20 h. The solvent
was evaporated under reduced pressure, and the residue was dis-
solved in EtOAc. The organic layer was washed with water
(3ϫ20 mL), dried with MgSO4, and concentrated under reduced
pressure. The residue was purified by flash chromatography.
190.3 ppm. IR (neat): ν = 1681, 1597, 1513, 1322 cm–1. HRMS:
˜
calcd. for C18H16N3O3 [M]+ 322.1192; found 322.1183.
1-(1-Benzyl-1H-1,2,3-triazol-4-yl)-2-(2,4-dichlorophenyl)ethane-1,2-
dione (3g): Yellow powder. M.p. 115 °C. Yields (CuCl2/CuI) 72/
1
53%. H NMR (CDCl3): δ = 5.62 (s, 2 H), 7.34 (m, 2 H), 7.42 (m,
5 H), 7.82 (d, J = 8.3 Hz, 1 H), 8.21 (s, 1 H) ppm. 13C NMR
(CDCl3): δ = 54.6, 127.8, 128.3, 128.5, 129.3, 129.4, 130.5, 131.5,
1-(1-Benzyl-1H-1,2,3-triazol-4-yl)-2-phenylethane-1,2-dione
(3a):
Yellow solid obtained upon standing. M.p. 115 °C. Yields (CuCl2/
1
CuI) 55/55%. H NMR (CDCl3): δ = 5.61 (s, 2 H), 7.31 (m, 2 H),
133.0, 133.2, 135.0, 140.6, 143.8 ppm. IR (neat): ν = 1686, 1582,
˜
1532, 1465, 1378 cm–1. HRMS: calcd. for C17H12Cl2N3O2 [M]+
360.0300; found 360.0307.
7.41 (m, 3 H), 7.50 (t, J = 7.6 Hz, 2 H), 7.66 (t, J = 7.4 Hz, 1 H),
8.02 (d, J = 8.4 Hz, 2 H), 8.19 (s, 1 H) ppm. 13C NMR (CDCl3):
δ = 54.5, 128.4, 128.9, 129.3, 129.4, 130.2, 132.2, 133.3, 134.9,
1-[1-(3,5-Dimethoxybenzyl)-1H-1,2,3-triazol-4-yl]-2-(2,4-dichloro-
phenyl)ethane-1,2-dione (3h): Yellow gummy solid. Yield 57%. 1H
NMR (CDCl3): δ = 3.75 (s, 6 H), 5.52 (s, 2 H), 6.43 (s, 3 H), 7.38
(dd, J = 8.3, J = 1.9 Hz, 1 H), 7.42 (d, J = 1.8 Hz, 1 H), 7.79 (d,
J = 8.3 Hz, 1 H), 8.26 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 54.5,
55.4, 100.7, 106.4,127.8, 128.4, 130.4, 131.4, 132.9, 134.9, 135.2,
185.5, 191.9 ppm. IR (neat): ν = 1677, 1594, 1526 cm–1. HRMS:
˜
calcd. for C17H14N3O2 [M + H]+ 292.1086; found 292.1087.
1-[1-(4-Nitrobenzyl)-1H-1,2,3-triazol-4-yl]-2-phenylethane-1,2-dione
1
(3b): Yellow powder. M.p. 139 °C. Yields (CuCl2/CuI) 40/51%. H
NMR (CDCl3): δ = 5.74 (s, 2 H), 7.5 (m, 4 H), 7.67 (t, J = 7.4 Hz,
1 H), 8.03 (d, J = 8.5 Hz, 2 H), 8.26 (d, J = 8.6 Hz, 2 H), 8.33 (s,
1 H) ppm. 13C NMR (CDCl3): δ = 53.5, 124.5, 128.6, 129.0, 130.3,
140.5, 143.6, 161.4, 183.3, 190.9 ppm. IR (neat): ν = 1686, 1598,
˜
1465, 1357 cm–1. HRMS: calcd. for C19H16Cl2N3O4 [M]+ 420.0518;
found 420.0518.
132.2, 135.1, 140.2, 144.7, 148.4, 184.9, 191.6 ppm. IR (neat): ν =
˜
1687, 1591, 1523, 1343 cm–1. HRMS: calcd. for C17H13N4O4 [M]+
337.0937; found 337.0924.
1-[1-(4-Nitrobenzyl)-1H-1,2,3-triazol-4-yl]-2-(2,4-dichlorophenyl)eth-
anone (2i): Yellow powder. M.p. 97 °C. Yield 86 %. 1H NMR
(CDCl3): δ = 4.58 (s, 2 H), 5.70 (s, 2 H), 7.23 (d, J = 1.1 Hz, 2 H),
7.39 (s, 1 H), 7.45 (t, J = 8.6 Hz, 2 H), 8.18 (s, 1 H), 8.23 (t, J =
8.6 Hz, 2 H) ppm. 13C NMR (CDCl3): δ = 43.6, 54.5, 124.5, 126.0,
1-[1-(3,5-Dimethoxybenzyl)-1H-1,2,3-triazol-4-yl]-2-phenylethane-
1,2-dione (3c): Yellow powder. M.p. 90 °C. Yields (CuCl2/CuI) 48/
1
49%. H NMR (CDCl3): δ = 3.78 (s, 6 H), 5.51 (s, 2 H), 6.45 (m,
414
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 409–416

α,β-Diketotriazoles by Aerobic Cu-Catalyzed Oxygenation
127.2, 128.9, 129.3, 130.9, 132.8, 133.8, 135.4, 140.4, 147.8, 190.1
129.5, 131.2, 133.1, 136.8, 144.0, 151.1, 184.1, 189.8 ppm. IR
ppm. IR (neat): ν = 1693, 1603, 1524, 1347 cm–1. HRMS: calcd.
(neat): ν = 1678, 1596, 1517, 1345 cm–1. HRMS: calcd. for
˜
˜
for C17H13Cl2N4O3 [M]+ 391.0365; found 391.0371.
C17H13N4O4 [M]+ 337.0937; found 337.0926.
1-[1-(4-Nitrobenzyl)-1H-1,2,3-triazol-4-yl]-2-(2,4-dichlorophenyl)eth-
ane-1,2-dione (3i): Yellow powder. M.p. 87 °C. Yields (CuCl2/CuI)
71/58%. H NMR (CDCl3): δ = 5.76 (s, 2 H), 7.43 (dd, J = 8.3, J
1-[1-(3,5-Dimethoxybenzyl)-1H-1,2,3-triazol-4-yl]-2-(4-nitrophenyl)-
ethanone (2m): White powder. M.p. 166 °C. Yield 52%. H NMR
(CDCl3): δ = 3.76 (s, 6 H), 4.53 (s, 2 H), 5.47 (s, 2 H), 6.40 (d, J =
2.1 Hz, 2 H), 6.44 (t, J = 2.1 Hz, 1 H), 7.52 (d, J = 8.7 Hz, 2 H),
8.01 (s, 1 H), 8.16 (d, J = 8.7 Hz, 2 H) ppm. 13C NMR (CDCl3):
δ = 45.6, 54.7, 55.4, 100.6, 106.5, 123.6, 126.1, 130.8, 135.3, 141.4,
1
1
= 1.9 Hz, 1 H), 7.46 (d, J = 1.8 Hz, 1 H), 7.50 (d, J = 8.7 Hz, 2
H), 7.82 (d, J = 8.3 Hz, 1 H), 8.27 (d, J = 8.7 Hz, 2 H), 8.35 (s, 1
H) ppm. 13C NMR (CDCl3): δ = 53.5, 124.6, 128.0, 128.6, 129.0,
130.5, 131.4, 133.0, 134.9, 140.2, 140.8, 144.0, 182.9, 190.8 ppm.
147.2, 161.5, 190.5 ppm. IR (neat): ν = 1687, 1602, 1504, 1347
˜
IR (neat): ν = 1685, 1582, 1524, 1348 cm–1. HRMS: calcd. for
˜
cm–1. HRMS: calcd. for C19H18N4O5 [M]+ 383.1355; found
383.1330.
C17H11Cl2N4O4 [M]+ 405.0157; found 405.0166.
2-(2,4-Dichlorophenyl)-1-[1-(cyclohexylmethyl)-1H-1,2,3-triazol-4-
1
yl]ethanone (2j): White powder. M.p. 119 °C. Yield 63%. H NMR
1-[1-(3,5-Dimethoxybenzyl)-1H-1,2,3-triazol-4-yl]-2-(4-nitrophenyl)-
ethane-1,2-dione (3m): Yellow needles. M.p. 133 °C. Yields (CuCl2/
(CDCl3): δ = 1.04–1.92 (m, 11 H), 4.24 (d, J = 6.9 Hz, 2 H), 4.60
(s, 2 H), 7.23 (d, J = 0.9 Hz, 2 H), 7.43 (s, 1 H), 8.02 (s, 1 H) ppm.
13C NMR (CDCl3): δ = 25.4, 25.9, 30.3, 38.6, 43.5, 56.8, 126.2,
1
CuI) 49/60%. H NMR (CDCl3): δ = 3.78 (s, 6 H), 5.53 (s, 2 H),
6.45 (m, 3 H), 8.20 (d, J = 8.9 Hz, 2 H), 8.29 (s, 1 H), 8.33 (d, J =
8.8 Hz, 2 H) ppm. 13C NMR (CDCl3): δ = 54.8, 55.5, 100.7, 106.5,
124.0, 128.6, 131.2, 135.1, 136.8, 144.0, 151.1, 161.5, 184.0, 189.8
127.1, 129.3, 131.2, 132.8, 133.6, 135.5, 190.4 ppm. IR (neat): ν =
˜
2928, 1692, 1589, 1531, 1381 cm– 1 . HRMS: calcd. for
C17H20Cl2N3O [M]+ 352.0983; found 352.0985.
ppm. IR (neat): ν = 1684, 1602, 1522, 1348 cm–1. HRMS: calcd.
˜
for C19H17N4O6 [M]+ 397.1148; found 397.1143.
2-(2,4-Dichlorophenyl)-1-[1-(cyclohexylmethyl)-1H-1,2,3-triazol-4-
yl]ethane-1,2-dione (3j): Yellow powder. M.p. 121 °C. Yield 52%.
1H NMR (CDCl3): δ = 1.11 (m, 5 H), 1.66 (m, 5 H), 1.94 (m, 1
H), 4.28 (d, J = 7.2 Hz, 2 H), 7.42 (dd, J = 8.3, J = 1.9 Hz, 1 H),
7.45 (d, J = 1.9 Hz, 1 H), 7.84 (d, J = 8.3 Hz, 1 H), 8.28 (s, 1 H)
ppm. 13C NMR (CDCl3): δ = 25.3, 25.9, 30.3, 38.5, 56.9, 127.8,
128.8, 130.5, 131.6, 133.0, 135.0, 140.5, 143.3, 183.5, 191.0 ppm.
1-(1-Benzyl-1H-1,2,3-triazol-4-yl)-2-(2-methoxyphenyl)ethanone
(2n): White powder. M.p. 127 °C. Yield 86%. 1H NMR (CDCl3): δ
= 3.73 (s, 3 H), 4.44 (s, 2 H), 5.54 (s, 2 H), 6.87 (d, J = 8.2 Hz, 1
H), 6.92 (td, J = 7.4, J = 1.1 Hz, 1 H), 7.22–7.34 (m, 4 H), 7.41
(m, 3 H), 8.03 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 40.9, 54.3,
55.3, 110.4, 120.4, 123.0, 125.6, 128.3, 128.4, 129.0, 129.2, 131.4,
IR (neat): ν = 2926, 1684, 1581, 1532, 1379 cm–1. HRMS: calcd.
˜
133.7, 147.9, 157.5, 192.0 ppm. IR (neat): ν = 1692, 1602, 1528,
˜
for C17H18Cl2N3O2 [M]+ 366.0776; found 352.0759.
1495, 1358 cm–1. HRMS: calcd. for C18H18N3O2 [M]+ 308.1399;
found 308.1396.
Methyl 4-[(4-{2-(2,4-Dichlorophenyl)acetyl}-1H-1,2,3-triazol-1-yl)-
methyl]furan-3-carboxylate (2k): White powder. M.p. 108 °C. Yield
1
73%. H NMR (CDCl3): δ = 3.87 (s, 3 H), 4.54 (s, 2 H), 5.64 (s, 2
1-(1-Benzyl-1H-1,2,3-triazol-4-yl)-2-(2-methoxyphenyl)ethane-1,2-di-
one (3n): Yellow powder. M.p. 121 °C. Yield 71 %. 1H NMR
(CDCl3): δ = 3.59 (s, 3 H), 5.60 (s, 2 H), 6.93 (d, J = 8.4 Hz, 1 H),
7.10 (td, J = 7.8, J = 0.7 Hz, 1 H), 7.29–7.40 (m, 5 H), 7.58 (td, J
= 7.4, J = 1.8 Hz, 1 H), 7.97 (dd, J = 7.8, J = 1.8 Hz, 1 H), 8.12
(s, 1 H) ppm. 13C NMR (CDCl3): δ = 54.5, 55.8, 112.3, 121.3,
123.2, 127.1, 128.3, 129.2, 129.3, 130.7, 133.5, 136.5, 144.4, 160.4,
H), 6.56 (d, J = 3.5 Hz, 1 H), 7.13 (d, J = 3.5 Hz, 1 H), 7.19 (s, 2
H), 7.38 (s, 1 H), 8.22 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 43.5,
46.8, 52.1, 112.5, 118.6, 126.0, 127.0, 129.2, 131.0, 132.7, 133.6,
135.4, 145.5, 147.5, 150.1, 158.5, 190.0 ppm. IR (neat): ν = 1721,
˜
1691, 1595, 1534, 1474 cm–1. HRMS: calcd. for C17H14Cl2N3O4
[M]+ 394.0361; found 394.0355.
185.6, 192.8 ppm. IR (neat): ν = 1688, 1598, 1535, 1467, 1354 cm–1.
˜
Methyl 4-[(4-{2-(2,4-Dichlorophenyl)-2-oxoacetyl}-1H-1,2,3-triazol-
1-yl)methyl]furan-3-carboxylate (3k): Yellow gummy solid. Yield
HRMS: calcd. for C18H16N3O3 [M]+ 322.1192; found 322.1197.
1
57%. H NMR (CDCl3): δ = 3.90 (s, 3 H), 5.70 (s, 2 H), 6.62 (d,
1-[1-(3,5-Dimethoxybenzyl)-1H-1,2,3-triazol-4-yl]-2-(2-methoxy-
phenyl)ethanone (2o): Light yellow oil. Yield 74 %. 1H NMR
(CDCl3): δ = 3.73 (s, 3 H), 3.76 (s, 6 H), 4.43 (s, 2 H), 5.45 (s, 2
H), 6.41 (d, J = 2.1 Hz, 2 H), 6.44 (t, J = 2.2 Hz, 1 H), 6.87 (d, J
= 8.2 Hz, 1 H), 6.91 (td, J = 7.4, J = 1.0 Hz, 1 H), 7.19 (dd, J =
7.4, J = 1.6 Hz, 1 H), 7.25 (td, J = 8.0, J = 1.3 Hz, 1 H), 8.00 (s,
1 H) ppm. 13C NMR (CDCl3): δ = 40.9, 54.4, 55.3, 55.4, 100.6,
106.3, 110.4, 120.4, 123.0, 125.6, 128.4, 131.4, 135.7, 147.9, 157.5,
J = 3.5 Hz, 1 H), 7.16 (d, J = 3.4 Hz, 1 H), 7.42 (dd, J = 8.3, J =
1.9 Hz, 1 H), 7.45 (d, J = 1.9 Hz, 1 h), 7.82 (d, J = 8.3 Hz, 1 H),
8.43 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 46.9, 52.2, 112.9, 118.7,
127.9, 128.6, 130.5, 131.5, 133.0, 135.0, 140.6, 143.9, 145.7, 149.8,
158.5, 183.1, 190.8 ppm. IR (neat): ν = 1730, 1683, 1582, 1534,
˜
1438, 1380 cm–1. HRMS: calcd. for C17H12Cl2N3O5 [M]+ 408.0154;
found 408.0136.
1-(1-Benzyl-1H-1,2,3-triazol-4-yl)-2-(4-nitrophenyl)ethanone (2l):
White powder. M.p. 142 °C. Yield 79%. 1H NMR (CDCl3): δ =
4.53 (s, 2 H), 5.57 (s, 2 H), 7.30 (m, 2 H), 7.38 (m, 3 H), 7.52 (d, J
= 8.8 Hz, 2 H), 8.00 (s, 1 H), 8.16 (d, J = 8.8 Hz, 2 H) ppm. 13C
NMR (CDCl3): δ = 45.6, 54.6, 123.6, 126.1, 128.4, 129.4, 130.8,
161.3, 192.0 ppm. IR (neat): ν = 1687, 1610, 1529, 1465, 1322 cm–1.
˜
HRMS: calcd. for C20H22N3O4 [M]+ 368.1610; found 368.1617.
1-[1-(3,5-Dimethoxybenzyl)-1H-1,2,3-triazol-4-yl]-2-(2-methoxy-
phenyl)ethane-1,2-dione (3o): White powder. M.p. 120 °C. Yield
133.3, 141.4, 147.3, 190.6 ppm. IR (neat): ν = 1685, 1601, 1531,
˜
1
68%. H NMR (CDCl3): δ = 3.60 (s, 3 H), 3.76 (s, 6 H), 5.50 (s, 2
1510, 1341 cm–1. HRMS: calcd. for C17H15N4O3 [M]+ 323.1144;
found 323.1133.
H), 6.42 (m, 3 H), 6.92 (d, J = 8.4 Hz, 1 H), 7.09 (t, J = 7.3 Hz, 1
H), 7.57 (t, J = 7.4 Hz, 1 H), 7.96 (dd, J = 7.8, J = 1.7 Hz, 1 H),
8.13 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 54.5, 55.4, 55.8, 100.7,
106.3, 112.3, 121.5, 123.2, 127.2, 130.6, 135.5, 136.5, 144.4, 160.4,
1-(1-Benzyl-1H-1,2,3-triazol-4-yl)-2-(4-nitrophenyl)ethane-1,2-dione
1
(3l): Yellow powder. M.p. 130 °C. Yields (CuCl2/CuI) 39/63%. H
NMR (CDCl3): δ = 5.63 (s, 2 H), 7.34 (m, 2 H), 7.41 (m, 3 H),
8.19 (d, J = 9.0 Hz, 2 H), 8.28 (s, 1 H), 8.33 (d, J = 9.0 Hz, 2 H)
ppm. 13C NMR (CDCl3): δ = 54.7, 123.9, 128.4, 128.5, 129.4,
161.4, 185.6, 192.8 ppm. IR (neat): ν = 1686, 1655, 1597, 1463,
˜
1301 cm–1. HRMS: calcd. for C20H20N3O5 [M]+ 382.1403; found
382.1419.
Eur. J. Org. Chem. 2012, 409–416
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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415

C. Menendez, S. Gau, S. Ladeira, C. Lherbet, M. Baltas
FULL PAPER
1-Phenyl-2-(pyridin-2-yl)ethane-1,2-dione (6): Phenylacetylpyridine
5 was synthesized as described previously.[26] The same protocol for
α,β-diketotriazoles was then used to prepare 6. Spectroscopic data
for 6 are identical to those previously reported.[27]
[1]
[2]
X. Deng, N. S. Mani, Org. Lett. 2006, 8, 269–272.
S. E. Wolkenberg, D. D. Wisnoski, W. H. Leister, Y. Wang, Z.
Zhao, C. W. Lindsley, Org. Lett. 2004, 6, 1453.
[3]
[4]
[5]
[6]
2-(1-Benzyl-1H-1,2,3-triazol-4-yl)-6,7-dimethyl-3-phenylquinoxaline
(7): α,β-Diketotriazole (1 equiv.) and 4,5-dimethylbenzene-1,2-di-
amine (1 equiv.) were dissolved in EtOH (2 mL). The reaction mix-
ture was heated to reflux overnight, concentrated under reduced
pressure, dissolved in EtOAc, and washed with water and brine.
The residue was purified by flash chromatography to afford 7 as a
F. Rong, S. Chow, S. Yan, G. Larson, Z. Hong, J. Wu, Bioorg.
Med. Chem. Lett. 2007, 17, 1663–1666.
Z. Zhao, W. H. Leister, K. Strauss, D. D. Wisnoski, C. W.
Lindsley, Tetrahedron Lett. 2003, 44, 1123–1127.
P. Nowak, D. Malwitz, D. C. Cole, Synth. Commun. 2010, 40,
2164–2171, and references herein.
Z. Wan, C. D. Jones, D. Mitchell, J. Y. Pu, T. Y. Zhang, J. Org.
Chem. 2006, 71, 826–828.
M. Niu, H. Fu, Y. Jiang, Y. Zhao, Synthesis 2008, 2879–2882.
W. Ren, Y. Xia, S.-J. Ji, Y. Zhang, X. Wan, J. Zhao, Org. Lett.
2009, 11, 1841–1844.
S. Chen, Z. liu, E. Shi, L. Chen, W. Wie, H. Li, Y. Cheng, X.
1
light brown powder. M.p. 180 °C. Yield 91%. H NMR (CDCl3):
δ = 2.50 (s, 6 H), 5.45 (s, 2 H), 6.99 (s, 1 H), 7.16 (m, 2 H), 7.34
(m, 6 H), 7.44 (m, 2 H), 7.87 (s, 1 H), 7.98 (s, 1 H) ppm. 13C NMR
(CDCl3): δ = 20.4, 54,1, 124.3, 128.0, 128.1, 128.4, 128.7, 128.9,
129.0, 129.2, 134.2, 138.9, 140.1, 140.2, 140.9, 141.2, 143.0, 146.2,
[7]
[8]
152.4 ppm. IR (neat): ν = 2923, 1731, 1629, 1534, 1456 cm–1
.
˜
[9]
HRMS: calcd. for C25H21N5 [M]+ 392.1875; found 392.1874.
Wan, Org. Lett. 2011, 13, 2274–2277.
[10]
[11]
X.-F. Zhao, C. Zhang, Synthesis 2007, 551–557.
J. S. Yadav, S. K. Biswas, R. Srinivas, Synthesis 2006, 4237–
4241.
D. Sachdev, M. A. Naik, A. Dubey, B. G. Mishra, Catal. Com-
mun. 2010, 11, 684–688.
L. Liang, G. Rao, H.-L. Sun, J.-L. Zhang, Adv. Synth. Catal.
2010, 352, 2371–2377.
L. Huang, K. Cheng, B. Yao, Y. Xie, Y. Zhang, J. Org. Chem.
2011, 76, 5732–5737.
1-Benzyl-4-(2,4-diphenyl-1H-imidazol-5-yl)-1H-1,2,3-triazole (8):
α,β-Diketotriazole (1 equiv.), benzaldehyde (1.1 equiv.), and ammo-
nium acetate (2.5 equiv.) were dissolved in HOAc (2 mL). The reac-
tion mixture was heated to 130 °C overnight, concentrated under
reduced pressure, dissolved in EtOAc, and washed with water and
brine. The residue was purified by flash chromatography to give 8
as a yellow solid upon standing. M.p. 142 °C. Yield 91%. 1H NMR
(CDCl3): δ = 5.46 (s, 2 H), 7.19–7.39 (m, 11 H), 7.60 (dd, J = 7.7,
J = 1.3 Hz, 2 H), 7.62 (s, 1 H), 7.92 (dd, J = 7.8, J = 1.3 Hz, 2 H)
ppm. 13C NMR (CDCl3): δ = 54.2, 120.4, 125.6, 127.7, 127.8,
128.1, 128.4, 128.7, 128.9, 129.0, 129.3, 130.1, 134.3, 140.3, 146.6
[12]
[13]
[14]
[15] a) K. B. Sharpless, V. V. Fokin, L. G. Green, V. V. Rostovtsev,
Angew. Chem. 2002, 114, 2126; Angew. Chem. Int. Ed. 2002,
41, 2024–2711; b) M. Meldal, C. Christensen, C. W. Tornoe, J.
Org. Chem. 2002, 67, 3057–3064.
[16] C. Menendez, S. Gau, C. Lherbet, F. Rodriguez, M. R. Pasca,
M. Baltas, Eur. J. Med. Chem. 2011, DOI: 10.1016/
j.ejmech.2011.09.013.
ppm. IR (neat): ν = 1739, 1670, 1602, 1488, 1460 cm–1. HRMS:
˜
calcd. for C24H20N5 [M]+ 378.1719; found 378.1724.
4-[1-(4-Chlorobenzyl)-2,4-diphenyl-1H-imidazol-5-yl]-1-benzyl-1H-
1,2,3-triazole (9): α,β-Diketotriazole (1 equiv.), benzaldehyde
(1.1 equiv.), 4-chlorobenzylamine (1.1 equiv.), ammonium acetate
(2.5 equiv.), and FeCl3 (0.1 equiv.) were dissolved in EtOH (2 mL).
The reaction mixture was heated to 80 °C for 24 h, concentrated
under reduced pressure, dissolved in EtOAc, and washed with
water and brine. The residue was purified by flash chromatography
to give 9 as a white solid. M.p. 145 °C. Yield 66%. 1H NMR
(CDCl3): δ = 5.41 (s, 2 H), 5.45 (s, 2 H), 6.73 (d, J = 8.5 Hz, 2 H),
7.06 (m, 3 H), 7.09 (m, 1 H), 7.13 (s, 1 H), 7.23 (m, 3 H), 7.35 (m,
[17] ORTEP3: L. J. Farrugia, J. Appl. Crystallogr. 1997, 30, 565–
565.
[18] The same reaction was performed with 1-(1-benzyl-1H-1,2,3-
triazol-4-yl)-3-phenylpropan-1-one. The starting material was
totally recovered, even after prolonged reaction times.
[19] T. Mizuhara, S. Inuki, S. Oishi, N. Fujii, H. Ohno, Chem. Com-
mun. 2009, 3413–3415.
[20] H. Wang, Y. Wang, D. Liang, L. liu, J. Zhang, Q. Zhu, Angew.
Chem. Int. Ed. 2011, 50, 5678–5681.
[21] L. Zhang, G. Y. Ang, S. Chiba, Org. Lett. 2011, 13, 1622–1625.
[22] D. E. Frantz, L. Morency, A. Soheili, J. A. Murry, E. J. J. Gra-
bowski, R. D. Tillyer, Org. Lett. 2004, 6, 843–846 and refer-
ences therein.
[23] C. Venkatesh, B. Singh, P. K. Mahata, H. Ila, H. Junjappa,
Org. Lett. 2005, 7, 2169–2172, and references therein.
[24] M. M. Heravi, F. Derikvand, M. Haghighi, Monatsh. Chem.
2008, 139, 31–33.
3 H), 7.43 (m, 3 H), 7.55–7.63 (m, 4 H) ppm. IR (neat): ν = 1671,
˜
1599, 1491, 1454, 1396 cm–1. HRMS: calcd. for C31H25N5Cl [M]+
502.1798; found 502.1833.
CCDC-807295 (for 2a), CCDC-807296 (for 3a), and CCDC-
836436 (for 9) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
[25] Y. Yamauchi, M. Yuki, Y. Tanabe, Y. Miyake, Y. Inada, S. Ue-
mura, Y. Nishibayashi, J. Am. Chem. Soc. 2008, 130, 2908–
2909.
[26] J. Easmon, G. Pürstinger, K.-S. Thies, G. Heinisch, J. Hof-
mann, J. Med. Chem. 2006, 49, 6343–6350.
Supporting Information (see footnote on the first page of this arti-
cle): Crystallographic data for 2a, 3a, and 9, copies of NMR spec-
tra.
[27] V. Mamane, E. Aubert, Y. Fort, J. Org. Chem. 2007, 72, 7294–
7300.
Acknowledgments
Received: September 15, 2011
Published Online: November 14, 2011
The authors are grateful to the Ministère de l’Enseignement et de
la Recherche Scientifique for financial support.
416
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 409–416