Synthesis of α-Keto-1,2,3-triazoles through copper iodide catalyzed oxygenation

Article abstract of DOI:10.1002/ejoc.201301035

Benzyltriazoles have been catalytically oxidized by using CuI and tert-butyl hydroperoxide to yield phenyl(1H-1,2,3-triazol-4-yl)methanone derivatives in good yields at room temperature. Benzyltriazoles have been catalytically oxidized by using CuI and tert-butyl hydroperoxide to yield phenyl(1H-1,2,3-triazol-4-yl)methanone derivatives in good yields at room temperature. Copyright

Full text of DOI:10.1002/ejoc.201301035

FULL PAPER
DOI: 10.1002/ejoc.201301035
Synthesis of α-Keto-1,2,3-triazoles Through Copper Iodide Catalyzed
Oxygenation
Swantje Nawratil,[a,b] Maria Grypioti,[a,b] Christophe Menendez,[a,b] Sonia Mallet-Ladeira,[c]
Christian Lherbet,*[a,b] and Michel Baltas*[a,b]
Keywords: Nitrogen heterocycles / C–H activation / Oxidation / Copper / Ketones
Benzyltriazoles have been catalytically oxidized by using CuI
and tert-butyl hydroperoxide to yield phenyl(1H-1,2,3-tri-
azol-4-yl)methanone derivatives in good yields at room tem-
perature.
Ketotriazoles can be synthesized from ynones[10] through
Sharpless–Fokin cycloaddition reactions (Scheme 1)[11] as
well as by amine-catalyzed [3+2] cycloaddition reactions be-
tween carbonyl compounds and azides.[12]
Introduction
Benzylic oxidation is one of the most important and use-
ful reactions in organic chemistry.[1] The possibility of gen-
erating ketones is one of its greatest advantages because
these compounds are used as building blocks for pharma-
ceuticals and agrochemicals.[2] Therefore several methods
for benzylic oxidation have been developed during the last
few years. In 2007, Nakanishi and Bolm reported benzylic
oxidation reactions promoted by catalytic amounts of FeCl3
and tert-butyl hydroperoxide (TBHP) as oxidant in pyridine
as solvent at 80 °C,[3] Reddy and co-workers reported the
oxidation of benzylic moieties by using TBHP and potas-
sium iodide as catalyst (20 mol-%),[4] and recently, a selec-
tive oxidation of C(sp3)–H bonds to C(sp3)–O bonds in the
presence of copper catalysts bearing quinoline-imine li-
gands with peresters as oxidants was described.[5]
Scheme 1. Synthetic routes to α-ketotriazoles.
In an ongoing project aimed at developing novel anti-
tuberculosis agents, we focused on the synthesis of α-keto-
triazoles. We recently synthesized a series of benzyltriazoles
that exert biological activities against InhA (also called 2-
trans-enoyl-ACP reductase enzyme).[6,7] To create small li-
braries of families of compounds based on judiciously func-
tionalized triazole frameworks, we decided to oxidize the
benzylic moieties of these compounds. α-Ketotriazoles dis-
play various interesting biological activities and are found
as building blocks in numerous biological molecules[8] and
recently Sau and Hrdlicka used them for the synthesis of
functionalized triazole-linked DNA as promising hybridiza-
tion probes in nucleic acid chemistry and biotechnology.[9]
In this context we wish to report herein our investi-
gations on a copper-dependent method for the preparation
of α-ketotriazoles directly from benzyltriazoles by em-
ploying catalytic amounts of copper iodide in the presence
of TBHP (70% in water).
Results and Discussion
The starting materials (i.e., benzyltriazoles) are readily
available by copper-catalyzed alkyne-azide cycloaddition
(CuAAC) reaction.[11d] They were synthesized by click
chemistry using CuSO4 (0.2 equiv.) and sodium ascorbate
(0.4 equiv.). When not commercial, the alkyne precursors
were prepared in two steps from commercially available
phenethyl alcohol derivatives. First, Dess–Martin oxidation
of the corresponding alcohols followed by condensation
with the Ohira–Bestmann reagent[13] provided the desired
alkyne products in good yields.
[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
http://spcmib.ups-tlse.fr/
[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] Université de Toulouse, UPS and CNRS, ICT FR2599,
118 Route de Narbonne, 31062 Toulouse, France
The initial attempt to transform 1,4-dibenzyl-1H-1,2,3-
triazole into the ketone was performed with potassium iod-
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301035.
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α-Ketotriazoles by CuI-Catalyzed Oxygenation
ide in the presence of TBHP (70% in water) at room tem- 2 equiv. of TBHP instead of 4 equiv. (as frequently reported
perature with diphenylmethane, as described by Reddy and in the literature) only slightly modified the yield of the
co-workers.[4] An average yield of 48% was obtained after product (74 vs. 81%). Finally, TBHP alone does not pro-
several attempts (Table 1; entry 1). A control reaction was mote the reaction; the starting material was totally reco-
then performed with diphenylmethane as described pre- vered (data not shown).
viously,[4] which gave a yield similar to that published (70
These reactions also indicated that the CuI/TBHP couple
vs. 78%). Slightly higher yields were obtained when the re- is more efficient than KI/TBHP in oxidizing benzyltri-
action was conducted at reflux with KI (0.1 or 0.3 equiv.; azoles. The use of FeCl2 as catalyst in the presence of acetic
entries 3 and 4).
acid and O2 was also tested, as described by Maes and co-
With our continuing interest in developing more conve- workers;[14] only traces of the desired product were detected
nient reactions catalyzed by copper, we investigated dif- (entry 16). However, when TBHP was used as oxidant in
ferent copper sources. When copper(II) chloride was used the presence of FeCl2, the product was obtained in good
as catalyst along with TBHP and/or 2,9-dimethyl-1,10- yield (78%, entry 17). Heating the same reaction mixture at
phenanthroline, the reaction outcome showed that the pres- reflux led to the product with a slight improvement in both
ence of TBHP is vital whereas the ligand had no important the conversion (Ͼ95%) and yield (82%; entry 18).
effect on the reaction (entries 5–7). In addition, no signifi-
Finally, it is noteworthy that the reaction is completely
cant amounts of product were observed with copper chlor- chemoselective; no oxidation of the methylene group of the
ide in the presence of DDQ as oxidant (entry 8). The source N-benzyl moiety was observed.
of copper, the reaction temperature, and solvent were criti-
cal.
To evaluate the scope of the reaction, different triazoles
were tested under the standard reaction conditions. All re-
The presence of copper iodide and TBHP in MeCN at actions were conducted for 20 h at room temperature in the
reflux afforded the desired product in only 51% yield (en- presence of 10 mol-% CuI or at reflux in the presence of
try 9). Replacement of the aqueous TBHP (70 wt-% in 10 mol-% FeCl2. The catalysis was not sensitive to the na-
water) with TBHP in organic solution (5 m in decane) led ture of the substituent on the triazole. Triazole systems pos-
to a lower yield (33%; entry 10). After screening different sessing remote aromatic groups at the 1-position led to
solvents, acetonitrile proved to be the optimal solvent for good yields (entries 1–5) except in the case of the naphth-
the reaction, with CuI (0.1 equiv.) at room temperature and ylmethyl group (entry 6). In this case, the naphthyl deriva-
TBHP (4 equiv.) being the best system for oxidation (en- tive 1f was only partially soluble and the reaction took
try 14). The reaction was clean and the desired product was more time, as shown by TLC. When a mixture containing
isolated in 81% yield. Extending the reaction time did not 1,4- and 1,5-dibenzyltriazoles in a ratio of 1:4 was subjected
improve the yield (entry 15). Increasing the amount of CuI to the oxidation reaction, the same ratio of products was
to 0.2 equiv. had no effect on the yield and the use of obtained in 77% yield (entry 7), thereby revealing the ab-
Table 1. Screening of the reaction conditions for the oxidation of benzyltriazole.
Entry
Catalyst, oxidant
Solvent
Conditions
Yield[a] [%]
1
2
3
4
5
6
7
8
KI (0.1 equiv.), TBHP (4 equiv.)
KI (0.1 equiv.), TBHP (4 equiv.)
KI (0.1 equiv.), TBHP (4 equiv.)
KI (0.3 equiv.), TBHP (4 equiv.)
CuCl2 (0.1 equiv.), TBHP (4 equiv.)
CuCl2 (0.1 equiv.), 2,9-dimethyl-1,10-phenanthroline (0.2 equiv.)
CuCl2 (0.1 equiv.), TBHP (4 equiv.), 2,9-dimethyl-1,10-phenanthroline (0.2 equiv.)
CuCl2 (0.1 equiv.), DDQ (1.5 equiv.)
CuI (0.1 equiv.), TBHP (4 equiv.)
CuI (0.1 equiv.), TBHP (4 equiv.)
CuI (0.1 equiv.), TBHP (4 equiv.)
CuI (0.1 equiv.), TBHP (4 equiv.)
CuI (0.1 equiv.), TBHP (4 equiv.)
CuI (0.1 equiv.), TBHP (4 equiv.)
CuI (0.1 equiv.), TBHP (4 equiv.)
FeCl2 (0.1 equiv.), AcOH, O2 (balloon)
FeCl2 (0.1 equiv.), TBHP (4 equiv.)
FeCl2 (0.1 equiv.), TBHP (4 equiv.)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DMSO
DMF
MeOH
MeCN
MeCN
DMSO
MeCN
MeCN
r.t., 20 h
r.t., 20 h
48
70[b] (78)[c]
reflux, 20 h
reflux, 20 h
reflux, 20 h
reflux, 20 h
reflux, 20 h
reflux, 20 h
reflux, 20 h
reflux, 20 h
80 °C, 20 h
reflux, 20 h
reflux, 20 h
r.t., 20 h
49
53
25
0
23
14
51
33[d]
37
6
13
81
77
0
78
82
9
10
11
12
13
14
15
16
17
18
r.t., 44 h
100 °C, 24 h
r.t., 20 h
reflux, 20 h
[a] Isolated yields. [b] Reaction performed with diphenylmethane. [c] See ref.[4] [d] Reaction performed with TBHP in decane.
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C. Lherbet, M. Baltas et al.
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sence of regioselectivity. Triazole systems with alkyl substit- Table 2. Scope of the CuI-catalyzed oxidation of benzylic triazoles.
uents at the 1-position (entries 8–11) also afforded the oxid-
ized products in good yields.
As shown in Table 2, the reaction is not sensitive to the
electronic properties of substituents present on the phenyl
ring of the benzyltriazoles as electron-donating and -with-
drawing groups could be employed in the reaction (en-
tries 12–14). We recently disclosed a copper-mediated oxi-
dation of α-ketotriazoles to α,β-diketotriazoles with triazole
as an effective intramolecular directing group.[10] This reac-
tion was carried out with either copper chloride or iodide
as catalyst in the presence of 2,9-dimethyl-1,10-phen-
anthroline, the use of copper iodide allowing shorter reac-
tion times. By using the method we report here (i.e., CuI
and TBHP), α-ketotriazole was oxidized to α,β-diketotri-
azole in only 16% yield (entry 15).
The use of FeCl2 (0.1 equiv.) in the presence of TBHP
(4 equiv.) at reflux was also tested in the oxidation reaction;
similar (entries 1, 3, 6) or lower (entries 9, 12) yields were
obtained in comparison with CuI.
Again, no oxidation occurred on the benzylic moiety
(when present) attached to the nitrogen atom of the triazole
ring.
To gain an insight into the reaction mechanism, we also
performed this reaction on four other starting compounds
(Scheme 2). The oxidation reactions of diphenylmethane
and 2- and 3-benzylpyridines were performed for compari-
son. A slightly better yield was obtained in the case of 3-
benzylpyridine, but the difference is not sufficient to con-
firm the role of the nitrogen atom in the oxidation process.
Finally, when the corresponding alcohol of the benzyltri-
azole system was used as the starting material, the alcohol
was oxidized quantitatively to the corresponding ketone 4
(Scheme 2).
This last reaction is analogous to that reported by Sasson
and co-workers in 1998 for the oxidation of allylic and
benzylic alcohols to the respective ketones by using TBHP
in the presence of CuCl2 or CuCl under phase-transfer ca-
talysis conditions.[15] Nikolaropoulos and co-workers in
2003 proposed a multistep process with the formation of a
radical intermediate generated by the tert-butoxyl radical
and the intermediate CuII–O–O–tBu.[16] In 2007, Kirihara
et al. reported the oxidation of thiols to disulfides with
H2O2 in the presence of catalytic amounts of NaI.[17] They
suggested the oxidation of iodide to the very reactive hy-
poiodous acid (I–OH). In 2011, Wan and co-workers re-
ported the α-oxyacylation of ethers with carboxylic acids in
the presence of iodide and TBHP.[18] They proposed a radi-
cal mechanism through a I2/I– redox process. In our hands,
the presence of iodide was assessed by the typical green-
brown solution after the addition of TBHP (4 equiv.) to a
colorless solution of copper iodide in CH3CN.
The results obtained with the TBHP–CuI system in this
work can be explained by modifying the mechanisms pro-
posed by Sasson et al. and earlier by Kochi,[19] who used a
series of redox reactions to form benzylic tert-butyl perox-
ide, which decomposes to afford the ketone [Equations (a)–
(e)].
[a] Yields of isolated compounds. [b] Synthesized from the corre-
sponding α-ketotriazole. [c] Not determined.
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α-Ketotriazoles by CuI-Catalyzed Oxygenation
reported by us. Only a single, final purification step was
then necessary for the production of α-ketotriazole. The ox-
idized 5-iodotriazole 2p (characterized by 1H and 13C
NMR, IR, and mass spectrometry) was identified as a by-
product formed in 8% yield. Its structure was confirmed by
single-crystal X-ray analysis.[21] It was gratifying to find that
when a catalytic amount of CuI was used, triazole 2a was
obtained in 57% yield without any traces of 2p.
Conclusions
We have developed a catalytic copper iodide mediated
method to oxidize benzylic triazoles to ketotriazoles in
good yields. The insight gained from this method permitted
a two-step, one-pot sequence from the corresponding alk-
yne and azide to afford α-ketotriazole in a good yield,
again under catalytic copper iodide conditions. This
method represents a useful access to α-keto-1,2,3-triazoles.
Scheme 2. Further copper-catalyzed oxidation reactions.
Experimental Section
General: All chemicals were obtained from Aldrich or Acros Or-
ganics and used without further purification. NMR spectra were
recorded with a Bruker AC 300 spectrometer (1H and 13C NMR).
1H NMR spectra were recorded at 300 MHz with CDCl3 (δ =
7.26 ppm) as internal standard. 13C NMR spectra were recorded
at 75.0 MHz and resonances are referenced against the central line
of the CDCl3 triplet at δ = 77.0 ppm. Mass spectra were recorded
with a ThermoQuest TSQ 7000 spectrometer and HRMS was per-
formed with a ThermoFinnigan MAT 95 XL spectrometer using
electrospray ionization (ESI). IR spectra were recorded with a Per-
kin–Elmer 1725 spectrometer.
In the absence of copper, the tert-butoxyl radical can be
generated by an I2/I– redox process, which can create both
benzylic and tert-butoxyl radicals.[20]
In both cases (presence or absence of copper), 2 equiv.
of tBuOOH are needed to generate the tBuO· and tBuOO·
radicals.
Finally, benzoyltriazoles can be synthesized in a one-pot
strategy, as shown in Scheme 3. In this one-pot synthesis,
TBHP was added after 20 h to a stoichiometric CuI-pro-
Triazoles 1a–1o were synthesized by copper-catalyzed alkyne–azide
cycloaddition (CuAAC) reactions as described previously.[7]
Representative Procedure for the Synthesis of α-Ketotriazole Deriva-
tives:
A solution of 1,4-dibenzyl-1H-1,2,3-triazole (1.0 equiv.,
moted alkyne-azide cycloaddition reaction, as previously 0.281 mmol, 70.0 mg), tBuOOH (4.0 equiv., 1.124 mmol), and CuI
Scheme 3. One-pot synthesis of α-ketotriazole.
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657

C. Lherbet, M. Baltas et al.
FULL PAPER
or FeCl2 (0.1 equiv., 0.028 mmol) in solvent (1.0 mL) was stirred at
room temperature or reflux, respectively, for 20 h. Ethyl acetate was
added and the residue was washed with water (25 mL), extracted
with ethyl acetate (50 mL), washed with brine (30 mL), and dried
with MgSO4. When DMSO or DMF was used as solvent, the ex-
traction was carried out with diethyl ether. The solvent was re-
moved under reduced pressure and the product isolated by flash
chromatography (gradient, petroleum ether/ethyl acetate = 90:10 to
50:50). The product was obtained as a white solid.
(s, 1 H), 7.75–7.38 (m, 3 H), 4.45 (t, J = 7.2 Hz, 2 H), 2.17–1.78
(m, 2 H), 1.48–1.18 (m, 10 H), 1.05–0.69 (m, 3 H) ppm. 13C NMR
(CDCl3): δ = 185.8, 136.6, 133.3, 130.6, 128.4, 50.7, 31.7, 30.2, 29.0,
28.9, 26.4, 14.1 ppm. HRMS (DCI/CH4): calcd. for C17H24N3O
286.1919; found 286.1929.
(1-Nonyl-1H-1,2,3-triazol-4-yl)(phenyl)methanone (2i): White crys-
tals, m.p. 47.3 °C, yield 82%. IR (neat): ν = 3126, 2925, 1634, 1522,
˜
1
1240 cm–1. H NMR (CDCl3): δ = 843 (d, J = 7.1 Hz, 2 H), 8.25
(s, 1 H), 7.61 (t, J = 7.3 Hz, 1 H), 7.51 (t, J = 7.4 Hz, 2 H), 4.34
(t, J = 7.2 Hz, 2 H), 1.96 (m, 2 H), 1.25 (m, 12 H), 0.86 (t, J =
6.7 Hz, 3 H) ppm. 13C NMR (CDCl3): δ = 185.8, 148.1, 136.5,
(1-Benzyl-1H-1,2,3-triazol-4-yl)(phenyl)methanone (2a): White crys-
tals, m.p. 116.5 °C, yield 81%. IR (neat): ν = 3120, 1638, 1518,
˜
1230 cm–1. 1H NMR (CDCl3): δ = 8.47–8.35 (m, 2 H), 8.19 (s, 1 133.2, 130.6, 128.4, 128.1, 50.6, 31.8, 30.1, 29.3, 29.1, 28.9, 26.4,
H), 7.66–7.56 (m, 1 H), 7.56–7.46 (m, 2 H), 7.37 (m, 5 H), 5.61 (s,
2 H) ppm. 13C NMR (CDCl3): δ = 185.7, 136.5, 133.7, 133.3, 130.6,
129.4, 129.2, 128.4, 54.5 ppm. HRMS (DCI/CH4): calcd. for
C16H14N3O 264.1137; found 264.1138.
22.6, 14.1 ppm. HRMS (DCI/CH4): calcd. for C18H26N3O
299.1998; found 299.2002.
(1-Dodecyl-1H-1,2,3-triazol-4-yl)(phenyl)methanone (2j): White so-
lid, m.p. 49.8 °C, yield 83%. IR (neat): ν = 3127, 2921, 2849, 1633,
˜
[1-(3,5-Dimethylbenzyl)-1H-1,2,3-triazol-4-yl](phenyl)methanone 1525, 1241 cm–1. 1H NMR (CDCl3): δ = 8.44 (d, J = 7.1 Hz, 2 H),
(2b): White powder, m.p. 121.4 °C, yield 64%. IR (neat): ν = 3132,
8.26 (s, 1 H), 7.61 (t, J = 7.3 Hz, 1 H), 7.51 (t, J = 7.3 Hz, 2 H),
4.44 (t, J = 7.2 Hz, 2 H), 1.96 (m, 2 H), 1.25 (m, 18 H), 0.87 (t, J
= 6.7 Hz, 3 H) ppm. 13C NMR (CDCl3): δ = 185.8, 136.6, 133.2,
130.6, 128.3, 50.7, 31.9, 30.1, 29.5, 29.4, 29.32, 29.29, 28.9, 26.4,
22.6, 14.1 ppm. HRMS (DCI/CH4): calcd. for C21H32N3O
342.2545; found 342.2549.
˜
1632, 1519, 1234 cm–1. 1H NMR (CDCl3): δ = 8.42 (d, J = 7.1 Hz,
2 H), 8.15 (s, 1 H), 7.61 (t, J = 7.4 Hz, 1 H), 7.51 (t, J = 7.3 Hz, 2
H), 7.02 (s, 1 H), 6.94 (s, 2 H), 5.52 (s, 2 H), 2.32 (s, 6 H) ppm. 13
C
NMR (CDCl3): δ = 185.7, 148.3, 139.0, 136.5, 133.4, 133.2, 130.7,
130.5, 128.3, 128.2, 126.2, 54.4, 21.2 ppm. HRMS (DCI/CH4):
calcd. for C18H18N3O 292.1450; found 292.1450.
(5-Iodo-1-nonyl-1H-1,2,3-triazol-4-yl)(phenyl)methanone (2k): Yel-
(1-Phenethyl-1H-1,2,3-triazol-4-yl)(phenyl)methanone (2c): White
low powder, m.p. 49.8 °C, yield 84%. IR (neat): ν = 2925, 2855,
˜
crystals, m.p. 124.1 °C, yield 69%. IR (neat): ν = 3120, 1637, 1526,
1645, 1472, 1228 cm–1. 1H NMR (CDCl3): δ = 8.32 (d, J = 7.1 Hz,
2 H), 7.60 (t, J = 7.3 Hz, 1 H), 7.50 (t, J = 7.4 Hz, 2 H), 4.48 (t, J
= 7.4 Hz, 2 H), 1.96 (m, 2 H), 1.26 (m, 12 H), 0.87 (t, J = 6.7 Hz,
3 H) ppm. 13C NMR (CDCl3): δ = 185.6, 147.0, 136.6, 133.2, 130.7,
128.2, 84.5, 31.7, 29.7, 29.3, 29.1, 28.9, 26.3, 22.6, 14.0 ppm.
HRMS (DCI/CH4): calcd. for C18H25N3OI 426.1042; found
426.1056.
˜
1
1237 cm–1. H NMR (CDCl3): δ = 7.61 (t, J = 7.4 Hz, 1 H), 7.51
(t, J = 7.5 Hz, 2 H), 7.13 (d, J = 7.8 Hz, 2 H), 4.69 (t, J = 7.2 Hz,
2 H), 3.28 (t, J = 7.2 Hz, 2 H) ppm. 13C NMR (CDCl3): δ = 185.6,
136.4, 133.2, 130.5, 129.0, 128.6, 128.3, 127.3, 51.9, 36.5 ppm.
HRMS (DCI/CH4): calcd. for C17H16N3O 278.1293; found
278.1307.
[1-(4-Methoxyphenethyl)-1H-1,2,3-triazol-4-yl](phenyl)methanone (1-Benzyl-1H-1,2,3-triazol-4-yl)(3,4-dimethoxyphenyl)methanone
(2d): White crystals, m.p. 116.3 °C, yield 61%. IR (neat): ν = 3121,
(2l): White crystals, m.p. 126.0 °C, yield 83%. IR (neat): ν = 3122,
˜
˜
1
1638, 1513, 1239 cm–1. 1H NMR (CDCl3): δ = 8.37 (d, J = 7.1 Hz,
1633, 1574, 1509, 1269 cm–1. H NMR (CDCl3): δ = 8.36 (dd, J =
2 H), 7.98 (br. s, 1 H), 7.61 (t, J = 7.4 Hz, 1 H), 7.50 (t, J = 7.4 Hz, 8.5, 2.0 Hz, 1 H), 8.15 (s, 1 H), 7.98 (d, J = 2.0 Hz, 1 H), 7.39 (m,
2 H), 7.02 (d, J = 8.6 Hz, 2 H), 6.83 (d, J = 8.7 Hz, 2 H), 4.65 (t,
J = 7.1 Hz, 2 H), 3.78 (s, 3 H), 321 (t, J = 7.1 Hz, 2 H) ppm. 13C
NMR (CDCl3): δ = 185.6, 158.8, 136.6, 133.2, 130.5, 129.6, 128.3,
114.3, 55.2, 52.1, 35.6 ppm. HRMS (DCI/CH4): calcd. for
C18H18N3O2 308.1399; found 308.1405.
3 H), 7.35 (m, 2 H), 6.96 (d, J = 8.6 Hz, 1 H), 5.60 (s, 2 H), 3.97
(s, 6 H) ppm. 13C NMR (CDCl3): δ = 183.7, 153.6, 146.8, 133.7,
129.34, 129.30, 129.1, 128.4, 128.2, 126.2, 112.4, 110.1, 56.1, 56.0,
54.4 ppm. HRMS (DCI/CH4): calcd. for C18H18N3O3 324.1348;
found 324.1353.
Methyl 5-[(4-Benzoyl-1H-1,2,3-triazol-1-yl)methyl]furan-2-carb-
(1-Benzyl-1H-1,2,3-triazol-4-yl)(3-methoxyphenyl)methanone (2m):
oxylate (2e): White crystals, m.p. 118.6 °C, yield 71%. IR (neat): ν
White crystals, m.p. 92.3 °C, yield 81%. IR (neat): ν = 3134, 1639,
˜
˜
1
= 3141, 1715, 1639, 1521, 1306, 1244 cm–1. 1H NMR (CDCl3): δ =
1583, 1514, 1302, 1213 cm–1. H NMR (CDCl3): δ = 8.14 (s, 1 H),
8.39 (d, J = 7.1 Hz, 2 H), 8.35 (s, 1 H), 7.61 (t, J = 7.3 Hz, 1 H), 8.07 (d, J = 7.7 Hz, 1 H), 7.91 (dd, J = 2.4, 1.4 Hz, 1 H), 7.31–7.44
7.51 (t, J = 7.4 Hz, 2 H), 7.15 (d, J = 3.5 Hz, 1 H), 6.59 (d, J =
3.5 Hz, 1 H), 5.69 (s, 2 H), 3.89 (s, 3 H) ppm. 13C NMR (CDCl3):
δ = 185.4, 158.5, 150.3, 148.4, 145.5, 136.3, 133.3, 130.5, 128.4,
118.7, 112.5, 52.2, 46.8, 26.4 ppm. HRMS (DCI/CH4): calcd. for
C16H14N3O4 312.0984; found 312.0992.
(m, 6 H), 7.16 (dd, J = 8.2, 2.5 Hz, 1 H), 5.60 (s, 2 H), 3.87 (s, 3
H) ppm. 13C NMR (CDCl3): δ = 185.3, 159.5, 137.7, 133.6, 129.4,
129.3, 129.1, 128.4, 123.4, 120.1, 114.4, 55.4, 54.5 ppm. HRMS
(DCI/CH4): calcd. for C17H16N3O2 294.1243; found 294.1252.
(1-Benzyl-1H-1,2,3-triazol-4-yl)(3-nitrophenyl)methanone (2n):
[1-(Naphthalen-2-ylmethyl)-1H-1,2,3-triazol-4-yl](phenyl)methanone
White powder, m.p. 146.4 °C, yield 72%. IR (neat): ν = 3131, 2923,
˜
1
(2f): White crystals, m.p. 118.0 °C, yield 52%. IR (neat): ν = 3121,
1652, 1526, 1343, 1226 cm–1. H NMR (CDCl3): δ = 9.28 (s, 1 H),
˜
1
3056, 1638, 1517, 1223 cm–1. H NMR (CDCl3): δ = 8.42 (d, J =
8.85 (d, J = 7.8 Hz, 1 H), 8.46 (d, J = 8.2 Hz, 1 H), 7.72 (t, J =
8.0 Hz, 1 H), 7.42 (m, 3 H), 7.36 (m, 2 H), 5.64 (s, 2 H) ppm. 13C
NMR (CDCl3): δ = 183.1, 148.2, 147.6, 129.6, 129.44, 129.36,
128.7, 128.5, 127.4, 125.6, 54.6 ppm. HRMS (DCI/CH4): calcd. for
C16H13N4O3 309.0988; found 309.0981.
8.3 Hz, 2 H), 8.20 (s, 1 H), 7.86 (m, 4 H), 7.53 (m, 5 H), 7.40 (dd,
J = 8.5, 1.8 Hz, 1 H), 5.76 (s, 2 H) ppm. 13C NMR (CDCl3): δ =
185.6, 136.5, 133.3, 133.2, 131.0, 130.6, 129.4, 128.4, 128.0, 127.9,
127.8, 127.0, 126.9, 125.3, 54.7 ppm. HRMS (DCI/CH4): calcd. for
C20H16N3O 314.1293; found 314.1306.
(1-Benzyl-5-iodo-1H-1,2,3-triazol-4-yl)(phenyl)methanone (2p): Col-
(1-Octyl-1H-1,2,3-triazol-4-yl)(phenyl)methanone (2h): White crys-
orless crystal (crystallization: AcOEt/heptane), m.p. 114.6 °C, yield
8%. H NMR (CDCl3): δ = 8.33 (d, J = 7.1 Hz, 4 H), 7.61 (t, J =
7.3 Hz, 2 H), 7.51 (t, J = 7.4 Hz, 4 H), 7.36 (m, 10 H), 5.72 (s, 4
1
tals, m.p. 36.1 °C, yield 79%. IR (neat): ν = 3128, 2925, 2855, 1638,
˜
1
1519, 1236 cm–1. H NMR (CDCl3): δ = 8.55–8.34 (m, 2 H), 8.25
658
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Eur. J. Org. Chem. 2014, 654–659

α-Ketotriazoles by CuI-Catalyzed Oxygenation
3
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Supporting Information (see footnote on the first page of this arti-
cle): Analytical data for 1l, 1m, and 1n, X-ray structure determi-
nation of 2p, and H and 13C NMR spectra.
1
Acknowledgments
The authors are grateful to the Ministère de l’Enseignement et de
la Recherche Scientifique and the Centre National de la Recherche
Scientifique (CNRS) for financial support. They are also grateful
for support by the European Union (EU) (to S. N., M. G., Erasmus
program, Germany, Greece, respectively).
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Received: July 11, 2013
Published Online: November 26, 2013
Eur. J. Org. Chem. 2014, 654–659
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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