ICl/AgNO3 Co-catalyzed radical oxidation of diaryl- A nd alkylarylalkynes into 1,2-diketones

Article abstract of DOI:10.1021/acs.joc.9b01667

A novel ICl/AgNO₃ co-catalyzed radical oxidation of diaryl- A nd alkylarylalkynes into 1,2-diketones is reported. The reaction proceeded smoothly under mild conditions and generated 1,2-diketones in moderate to good yields with a good tolerance of functional groups. Furthermore, the obtained C4-(1,2-diketoaryl)isoxazoles could react smoothly with 1,2-diaminobenzene to form C4-(3-arylquinoxalin-2-yl)isoxazoles. At last, a new one-pot strategy for the synthesis of quinoxalines from 1,2-diphenylethynes and 1,2-diaminobenzene is also reported.

Full text of DOI:10.1021/acs.joc.9b01667

Article
pubs.acs.org/joc
Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX
ICl/AgNO3 Co-Catalyzed Radical Oxidation of Diaryl- and
Alkylarylalkynes into 1,2-Diketones
Wen Yang,† Yu Chen,‡,§ Yongqi Yao,† Xin Yang,† Qifu Lin,† and Dingqiao Yang*,†
†Key Laboratory of Theoretical Chemistry of Environment, Ministry of Education, School of Chemistry and Environment, South
China Normal University, Guangzhou 510006, People’s Republic of China
‡Department of Chemistry and Biochemistry, Queens College of the City University of New York, 65-30 Kissena Blvd., Queens,
New York 11367, United States
§Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, 365 Fifth Avenue, New York, New York
10016, United States
S
* Supporting Information
ABSTRACT: A novel ICl/AgNO3 co-catalyzed radical oxidation of diaryl- and alkylarylalkynes into 1,2-diketones is reported.
The reaction proceeded smoothly under mild conditions and generated 1,2-diketones in moderate to good yields with a good
tolerance of functional groups. Furthermore, the obtained C4-(1,2-diketoaryl)isoxazoles could react smoothly with 1,2-
diaminobenzene to form C4-(3-arylquinoxalin-2-yl)isoxazoles. At last, a new one-pot strategy for the synthesis of quinoxalines
from 1,2-diphenylethynes and 1,2-diaminobenzene is also reported.
diketones have been reported, there are still several drawbacks:
(a) the use of high toxic Ti(NO3)3 and harsh reaction
conditions; (b) the use of high toxic Hg(NO3)2; (c) low yield
of benzil; and (d) the use of a bimetallic reagent system
(Pd(PPh3)2Cl2/Ce(NH4)4(NO3)6) and high temperature.
Therefore, developing a mild and efficient method for the
catalytic oxidation of internal alkynes is still highly desirable.
Recently, the reactions of iodide-mediated oxidative synthesis
of 1,2-diketones have also been reported.11 The reported
methods showed that the iodide could promote the process of
oxidative synthesis of 1,2-diketones. Therefore, we try to
combine iodide and metal nitrate to co-catalyze the oxidative
synthesis of 1,2-diketones from diarylalkynes, aiming to
overcome the drawbacks of metal nitrates.
INTRODUCTION
■
1,2-Dicarbonyl derivatives are one of the most important
structural motifs, since they are not only found in many natural
products and bioactive molecules1 but also broadly serve as
useful building blocks in the construction of medicinally
relevant heterocycles,2 such as imidazoles, pyrazines, and
quinoxalines. They are also used in materials chemistry3 and as
ligands for various metal complexes.4 Therefore, numerous
methods have been developed for their synthesis. For example,
transition-metal- or metal-free-catalyzed oxidative synthesis of
1,2-diketones,5 photo-catalyzed synthesis of 1,2-diketones.6
Over the past few years, metal nitrates have been applied to
the oxidative reaction of diarylalkynes, as shown in Scheme 1.
In 1972, Taylor and co-workers reported Ti(NO3)3-catalyzed
oxidative synthesis of 1,2-diketones (Scheme 1a).7 Recently,
Jung and Deng developed a method for the oxidation of
Recently, our group successfully synthesized a series of C4-
alkynylisoxazles.12 Therefore, we chose the C4-alkynylisoxazles
as substrates to test the feasibility of our ideas.
internal alkynes to 1,2-diketones in the presence of Hg-
(NO3)2−H2O (Scheme 1b). Subsequently, Konig and Wille
8
̈
RESULTS AND DISCUSSION
■
described LiNO3-mediated and visible light photoredox-
catalyzed oxidation of phenylacetylene to benzil (Scheme
1c).9 In 2019, Thongsornkleeb and co-workers reported
Ce(NH4)4(NO3)6-promoted Pd(PPh3)2Cl2-catalyzed oxidative
synthesis of 1,2-diketones (Scheme 1d).10 Although the
methods of metal nitrate-catalyzed oxidative synthesis of 1,2-
In our initial study, 3,5-diphenyl-4-(p-tolylethynyl)isoxazole
(1a) was chosen as the model substrate to optimize the
Received: June 21, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.9b01667
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affording the targeted product 2a in 82% yield (Table 1, entry
15). Another two iodine sources, such as I2 and NIS (N-
iodosuccinimide), were also tested and provided the targeted
product 2a in moderate yields (69 and 59%, respectively).
With the optimized reaction conditions in hand (Table 1,
entry 15), the scope of ICl/AgNO3 co-catalyzed oxidation of
3,5-disubstituted-4-alkynylisoxazoles into 3,5-disubstituted-4-
(1,2-diketoaryl)isoxazoles was investigated, as shown in Table
2. First, we examined the effect of varying R1 group on the
yield, while retaining R2 as a phenyl group and R3 as a 4-CH3
group. The reaction occurred smoothly when R1 was a tert-
butyl and isopropyl group, affording the corresponding
products 2b and 2c in good yields (73 and 70%, respectively).
Subsequently, R2 groups on the effect of the reaction were also
investigated, while retaining R1 as a phenyl group and R3 as a
4-CH3 group. The results indicated that the R2 group (tert-
butyl, cyclopropyl, and n-pentyl) had no distinct effect on the
reaction, affording the corresponding products 2d−2e in good
yields (78, 71, and 75%, respectively). In addition, the
substrates (1g−1i) bearing an electron-donating group on
the C3 position of isoxazole had a better compatibility than the
electron-withdrawing group, and afforded the corresponding
targeted products 2g−2i in good yields (76, 65, and 70%,
respectively). At last, we investigated the effect of the R3 group
on the reaction, while retaining R1 = R2 = Ph. All of the
targeted products 2j, 2l−2n could be obtained in good yields
(75, 79, 78, and 60%, respectively) except 2k (50% yield).
The scope of this oxidative reaction was further expanded to
diaryl-, alkylaryl- and dialkylalkynes, as shown in Table 3. The
benzil 4a could only be obtained in 62% yield under our
optimized reaction conditions (Table 1, entry 15). To our
delight, the yield of 4a could be increased to 90% in the
presence of 0.5 equiv of ICl and 3 equiv of AgNO3 in MeCN
for 4 h under an air atmosphere at room temperature.
Subsequently, a variety of 1,2-diarylacetylenes were subjected
to the reaction. In general, symmetrical and unsymmetrical
diarylacetylenes with different substituents on the aromatic
units were found to be feasible for the reaction and could
afford the corresponding targeted products (4a−4l) in good to
excellent yields (60−90%) with a good functional group
tolerance. In addition, the results showed that substrates
bearing an electron-donating group (CH3) or an electron-
withdrawing group (F, Cl, Br, CF3, NO2, COCH3, and CN)
afforded the desired products in excellent yields. However,
substrate 3b bearing the OCH3 group only produced targeted
product 4b in 60% yield. In order to further extend the scope
of the reaction, 2-(phenylethynyl)thiophene 3m and but-1-yn-
1-ylbenzene 3n were used as the substrates, which afforded the
corresponding products (4m and 4n) in good yields (87 and
75%, respectively). However, when 3-hexyne 3o and 2-butyne
3p were applied to the reaction, no corresponding product 1,2-
diketones (4o and 4p) were observed.
Scheme 1. Previous Work and Our Work
reaction conditions. To our delight, the model reaction
proceeded smoothly and generated 1-(3,5-diphenyl-isoxazol-
4-yl)-2-p-tolylethane-1,2-dione (2a) in 69% yield in the
presence of ICl (1 equiv) and AgNO3 (3 equiv) as co-catalysts
in MeCN under an air atmosphere for 4 h at room temperature
(Table 1, entry 1). The structure of 2a was confirmed by
single-crystal X-ray crystallography.13 It should be noted that in
the absence of ICl or AgNO3, none of the targeted product was
observed even when the reaction time was 12 h and the
starting material was recovered (Table 1, entries 2−3).
Subsequently, various metal nitrates, including KNO3,
LiNO3, and Ce(NH4)2(NO3)6 were tested in the reaction.
All of them afforded the targeted product 2a with low yields
(Table 1, entries 4−6). When AgNO2 was applied, the reaction
could not proceed at all (Table 1, entry 7). Other silver salts,
such as AgOAc, AgOTf, Ag2O, and Ag2CO3, only afforded a
trace of the targeted product 2a (Table 1, entries 8−11). The
effect of the solvents on the reaction was also investigated, and
MeCN turned out to be the best choice among the tested
solvents including dimethylformamide (DMF), 1,2-dichloro-
ethane (DCE) and tetrahydrofuran (THF) (Table 1, entries 1
vs 12−14). The loading of ICl and AgNO3 in the reaction was
also optimized (Table 1, entries 15−18). The results showed
that 1 equiv of ICl and 2 equiv of AgNO3 were the best,
To further demonstrate the synthetic application of C4-(1,2-
diketoaryl)isoxazoles, C4-(3-arylquinoxalin-2-yl)isoxazoles
5a−5h could be easily obtained in 82−98% yields from C4-
(1,2-diketoaryl)isoxazoles and 1,2-diaminobenzene in MeCN
at room temperature (Scheme 2a).
With the high efficiency and mild conditions of the oxidation
reaction in our hand (conditions: 0.5 equiv of ICl, 3 equiv of
AgNO3, and MeCN, rt, in air), quinoxalines 6a−6c could be
obtained in 60−74% yields via a one-pot strategy (Scheme 2b).
To illustrate a plausible mechanism for the oxidative
reaction, several control experiments were conducted and the
B
DOI: 10.1021/acs.joc.9b01667
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Article
a
Table 1. Optimization of Reaction Conditions
b
entry
catalyst (equiv)
metal nitrate (equiv)
AgNO3 (3)
solvent
time (h)
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
ICl (1)
ICl (1)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DMF
4
69
n. r.
n. r.
5
7
20
n. r.
trace
trace
trace
trace
20
trace
7
82
12
12
12
12
12
12
12
12
12
12
12
12
12
4
AgNO3 (3)
KNO3 (3)
LiNO3 (3)
ICl (1)
ICl (1)
ICl (1)
ICl (1)
ICl (1)
ICl (1)
ICl (1)
ICl (1)
ICl (1)
ICl (1)
ICl (1)
ICl (1)
ICl (1)
ICl (0.5)
ICl (0.1)
I2 (1)
Ce(NH4)2(NO3)6 (3)
AgNO2 (3)
AgOAc (3)
AgOTf (3)
Ag2O (3)
Ag2CO3 (3)
AgNO3 (3)
AgNO3 (3)
AgNO3 (3)
AgNO3 (2)
AgNO3 (1)
AgNO3 (2)
AgNO3 (2)
AgNO3 (2)
AgNO3 (2)
DCE
THF
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
12
12
12
4
69
56
10
69
NIS (1)
4
59
a
Reaction conditions: 1a (0.125 mmol, 1.0 equiv), catalyst (0.5−1 equiv), metal nitrate (1−3 equiv), and solvent (2.5 mL), under an air
b
atmosphere at room temperature. Isolated yields.
results are summarized in Scheme 3. When 2,2,6,6-tetramethyl-
1-piperidinyloxyl and 2,6-di-tert-butyl-4-methylphenol, two
commonly used radical scavengers, were added to the reaction,
respectively, no desired product 2a was obtained in either case,
suggesting that this transformation might occur via a radical
mechanism (Scheme 3a). The oxidation of 1a under a N2
atmosphere proceeded in essentially the same manner, which
afforded 2a in 79% yield (Scheme 3b). Meanwhile, when the
model reaction proceeded in H218O, a mono 18O labeled
product was observed with a ratio of 2a/2a-mono 18O/2a-di
18O in 74:25:1 (Scheme 3c). It should be noted that the 1,2-
diketones are very active, and the oxygen of the carbonyl group
can be exchanged with the oxygen of water.5f,j,14 Therefore, it is
obvious that the sole source of the two oxygen atoms of 2a is
from AgNO3.
Based on the above results described and related in the
literature,9,11e,15 a plausible mechanism for this radical
oxidative reaction was proposed, as shown in Scheme 4.
First, ICl reacted with AgNO3 to produce a AgCl precipitation
and IONO2 A, and then IONO2 A may undergo homolytic
cleavage to yield a nitrate radical under this reaction condition.
Addition of the nitrate radical to 1a generated intermediate B.
Subsequently, intermediate B reacted with IONO2 A, iodine
radical or ICl to afford intermediate C. Intermediate C was
then attacked by the nitrate radical or IONO2 A, affording
intermediate D and a nitrogen dioxide radical, and then a
nitrogen dioxide radical left as a leaving group. Finally, the
intermediate D was attacked by another nitrate radical to
produce the desired product 2a, as well as a nitrogen dioxide
radical and IONO2 A. Further investigations on the more
detailed reaction mechanism are ongoing in our laboratory.
CONCLUSIONS
■
In summary, we have developed a mild and efficient method
for the synthesis of 1,2-diketones by ICl/AgNO3 co-catalyzed
radical oxidation of diaryl- and alkylarylalkynes. The reaction is
likely to go through a radical oxidation mechanism and a
detailed mechanistic study is underway in our laboratory. The
obtained C4-(1,2-diketoaryl)isoxazoles could be easily con-
verted into corresponding C4-(3-arylquinoxalin-2-yl)-
isoxazoles. Under the reaction conditions, quinoxalines could
be synthesized by a one-pot strategy. As the newly synthesized
C4-(1,2-diketoaryl)isoxazoles and C4-(3-arylquinoxalin-2-yl)-
isoxazoles are biologically important compounds, future studies
will be focused on evaluating the biological and pharmaceutical
activities of these compounds.
EXPERIMENTAL SECTION
■
General Information. All reactions were carried out in 10/100
mL round-bottomed flask unless otherwise indicated. Analytical thin
layer chromatography (TLC) was performed with SiliCycle normal
phase glass plates (0.25 mm, 60 Å pore size, 230−400 mesh).
Visualization was done under a 254 nm UV light source.
Materials. Unless otherwise indicated, all reagents and solvents
were purchased from commercial suppliers and used without
additional purification. Compounds 1a−1h and 1j−1n were prepared
using our previously published methods.12 Compounds 3a and 3n−
3p were commercially available and were used directly in the reaction.
Instrumentation. All 1H and 13C{1H} NMR spectra were
recorded at 600/400 MHz and 150/100 MHz, respectively, using
C
DOI: 10.1021/acs.joc.9b01667
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a
Table 2. Scope of Substrates 1a−1n
a
Reaction conditions: 1 (0.125 mmol, 1.0 equiv), ICl (1.0 equiv), AgNO3 (2.0 equiv), and MeCN (2.5 mL), under an air atmosphere at room
b
temperature. Isolated yield.
CDCl3 as the solvent. 19F NMR spectra were recorded at 564 MHz at
25 °C in CDCl3. Spectral data are reported as follows: chemical shift
(δ, ppm); multiplicity (s-singlet, d-doublet, t-triplet, q-quadruplet, and
m-multiplet); coupling constants (J, Hz) and number of protons. The
chemical shifts of all 1H and 13C{1H} NMR spectra are referenced to
the residual signal of CDCl3 (δ 7.26 ppm for the 1H NMR spectra and
δ 77.23 ppm for the 13C{1H} NMR spectra). HRMS (ion trap) were
obtained from mass spectrometry (ESI). Melting points were
recorded on an electrothermal digital melting point apparatus and
were uncorrected.
Procedure for the TLC Silica Gel Preparative Plate. In a 1.5 L
beaker, carboxymethylcellulose sodium (CMC, 8 g) and 1 L
deionized water were added. After CMC was completely dissolved
in deionized water, GF254 silica gel was added (350 g) and kept for
overnight stirring. The obtained thick slurry was spread on a glass
plate (20 cm × 20 cm). The resultant glass plate was dried and
activated by heating in an oven for 10 min at 100 °C.
Synthesis of Substrate 1i. Substrate 5-(tert-butyl)-4-((4-
methoxyphenyl)ethynyl)-3-(4-(trifluoromethyl)phenyl)isoxazole 1i
was synthesized according to the literature.12 A 10 mL two-neck
round-bottomed flask with a reflux condenser was flame-dried under a
stream of nitrogen and cooled to room temperature. 5-(tert-butyl)-4-
iodo-3-(4-(trifluoromethyl)phenyl)isoxazole (118.5 mg, 0.3 mmol,
1.0 equiv), Pd(acac)2 (4.7 mg, 5 mol %), PPh3 (7.9 mg, 10 mol %),
CuI (5.8 mg, 10 mol %), and Et2NH (43.9 mg, 2 equiv) were added,
followed by the addition of anhydrous DMF (2.5 mL). The flask was
flushed with nitrogen and the 1-ethynyl-4-methoxybenzene (1.0 M in
DMF, 2.0 equiv) was added gradually by using a syringe. The
resulting solution was allowed to stir at 60 °C in an oil bath until
completion, as monitored by TLC. After cooling to room temper-
ature, the reaction was poured into 10 mL ethyl acetate and washed
three times (3 × 10 mL) with water. The organic layers were
combined, dried with anhydrous MgSO4, and then filtered. The
filtrate was concentrated under vacuum, and the resulting residue was
purified by column chromatography on silica gel (200−300 mesh)
using ethyl acetate/petroleum ether as eluent to afford the desired
product 1i.
5-(tert-Butyl)-4-((4-methoxyphenyl)ethynyl)-3-(4-
(trifluoromethyl)phenyl)isoxazole (1i). Substrate 1i was obtained as a
colorless oil (105.4 mg, 88% yield). Rf = 0.26 on silica gel (ethyl
1
acetate/petroleum ether 1:50, v/v). H NMR (600 MHz, CDCl3): δ
8.21 (d, J = 8.2 Hz, 2H), 7.74 (d, J = 8.2 Hz, 2H), 7.41 (d, J = 8.8 Hz,
2H), 6.93−6.87 (m, 2H), 3.84 (s, 3H), 1.57 (s, 9H). 13C{1H} NMR
(150 MHz, CDCl3): δ 182.4, 161.1, 160.2, 132.8, 132.6, 131.9 (q, J =
31.5 Hz), 128.3, 125.7 (q, J = 4.5 Hz), 124.4 (q, J = 270.0 Hz), 114.9,
114.4, 97.2, 96.4, 77.6, 55.5, 34.9, 28.5. 19F NMR (564 MHz, CDCl3):
δ −62.79. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for
C23H21F3NO2, 400.1524; found, 400.1515.
General Procedure (I) for the Synthesis of Alkynes (3). To a
100 mL round-bottomed flask CuI (14.3 mg, 1.5 mol %),
Pd(PPh3)2Cl2 (70.2 mg, 2% mmol), triethylamine (15 mL), and
THF (10 mL) were added. The flask was flushed with nitrogen, and
aryl iodine (5.0 mmol, 1 equiv) was added to the stirred suspension,
followed by immediate dropwise addition of terminal alkyne (4.5
mmol). The resulting mixture was allowed to stir at room temperature
overnight. Water (10 mL) was added to the reaction mixture. The
resulting mixture was extracted with ethyl acetate (3 × 20 mL). The
organic layers were combined and dried over anhydrous MgSO4. The
solvent was removed under vacuum, and the residue was purified by
column chromatography on silica gel (200−300 mesh) using ethyl
acetate/petroleum ether as the eluent to afford the desired products 3.
1-Methoxy-4-(phenylethynyl)benzene (3b). Following general
procedure (I), substrate 3b was obtained as a yellow solid (0.66 g,
70% yield), mp 93−95 °C. Rf = 0.25 on silica gel (ethyl acetate/
D
DOI: 10.1021/acs.joc.9b01667
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a
Table 3. Scope of Oxidation of Alkynes into 1,2-Diketones
a
Reaction conditions: 3 (0.15 mmol, 1.0 equiv), ICl (0.5 equiv), AgNO3 (3.0 equiv), and MeCN (2.5 mL), under an air atmosphere at room
b
temperature. ICl (1 equiv), AgNO3 (2 equiv).
Scheme 2. Synthesis of C4-(3-Arylquinoxalin-2-yl)isoxazoles 5a−5h and Quinoxalines 6a−6c
1
petroleum ether 1:30, v/v). H NMR (600 MHz, CDCl3): δ 7.53−
7.47 (m, 4H), 7.37−7.30 (m, 3H), 6.91−6.87 (m, 2H), 3.83 (s, 3H).
The 1H NMR spectral data are in good agreement with the literature
data.16
1H NMR spectral data are in good agreement with the literature
data.17
1-Fluoro-4-(phenylethynyl)benzene (3d). Following general pro-
cedure (I), substrate 3d was obtained as a white solid (0.62 g, 70%
yield), mp 108−110 °C. Rf = 0.92 on silica gel (petroleum ether). 1H
NMR (600 MHz, CDCl3): δ 7.53−7.49 (m, 4H), 7.39−7.32 (m, 3H),
7.11−7.02 (m, 2H). The 1H NMR spectral data are in good
agreement with the literature data.17
1-Methyl-4-(phenylethynyl)benzene (3c). Following general pro-
cedure (I), substrate 3c was obtained as a white solid (0.70 g, 80%
yield), mp 70−72 °C. Rf = 0.91 on silica gel (petroleum ether). H
NMR (600 MHz, CDCl3): δ 7.55−7.53 (m, 2H), 7.45 (d, J = 8.1 Hz,
2H), 7.36−7.34 (m, 3H), 7.17 (d, J = 7.9 Hz, 2H), 2.38 (s, 3H). The
1
E
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Scheme 3. Control Experiments
Scheme 4. Plausible Mechanism
1
1-Chloro-4-(phenylethynyl)benzene (3e). Following general pro-
cedure (I), substrate 3e was obtained as a white solid (0.82 g, 85%
3H). The H NMR spectral data are in good agreement with the
literature data.19
1
yield), mp 81−83 °C. Rf = 0.89 on silica gel (petroleum ether). H
4-(Phenylethynyl)benzonitrile (3j). Following general procedure
(I), substrate 3j was obtained as a white solid (0.81 g, 88% yield), mp
105−107 °C. Rf = 0.25 on silica gel (ethyl acetate/petroleum ether
1:60, v/v). 1H NMR (600 MHz, CDCl3): δ 7.65−7.59 (m, 4H),
NMR (600 MHz, CDCl3): δ 7.54−7.51 (m, 2H), 7.50−7.47 (m, 2H),
7.40−7.35 (m, 5H). The 1H NMR spectral data are in good
agreement with the literature data.18
1
1-Bromo-4-(phenylethynyl)benzene (3f). Following general pro-
cedure (I), substrate 3f was obtained as a white solid (0.93 g, 80%
7.57−7.52 (m, 2H), 7.42−7.35 (m, 3H). The H NMR spectral data
are in good agreement with the literature data.21
1
yield), mp 83−85 °C. Rf = 0.91 on silica gel (petroleum ether). H
1,2-Bis(4-fluorophenyl)ethyne (3k). Following general procedure
(I), substrate 3k was obtained as a white solid (0.67 g, 80% yield), mp
NMR (600 MHz, CDCl3): δ 7.53−7.55 (m, 2H), 7.49−7.45 (m, 2H),
7.39−7.31 (m, 5H). The 1H NMR spectral data are in good
agreement with the literature data.19
1
91−93 °C. Rf = 0.92 on silica gel (petroleum ether). H NMR (600
1
MHz, CDCl3): δ 7.53−7.48 (m, 4H), 7.08−7.01 (m, 4H). The H
NMR spectral data are in good agreement with the literature data.22
1,2-Di-p-tolylethyne (3l). Following general procedure (I),
substrate 3l was obtained as a white solid (0.80 g, 86% yield), mp
117−119 °C. Rf = 0.91 on silica gel (petroleum ether). 1H NMR (600
MHz, CDCl3): δ 7.48−7.45 (m, 4H), 7.18 (d, J = 7.9 Hz, 4H), 2.40
1-(Phenylethynyl)-4-(trifluoromethyl)benzene (3g). Following
general procedure (I), substrate 3g was obtained as a white solid
(0.98 g, 88% yield), mp 103−105 °C. Rf = 0.95 on silica gel
1
(petroleum ether). H NMR (600 MHz, CDCl3): δ 7.63 (q, J = 8.4
1
Hz, 4H), 7.59−7.53 (m, 2H), 7.41−7.35 (m, 3H). The H NMR
spectral data are in good agreement with the literature data.18
1-Nitro-4-(phenylethynyl)benzene (3h). Following general proce-
dure (I), substrate 3h was obtained as a white solid (0.83 g, 80%
yield), mp 120−122 °C. Rf = 0.30 on silica gel (petroleum ether). 1H
NMR (600 MHz, CDCl3): δ 8.24−8.20 (m, 2H), 7.68−7.65 (m, 2H),
1
(s, 6H). The H NMR spectral data are in good agreement with the
literature data.23
2-(Phenylethynyl)thiophene (3m). Following general procedure
(I), substrate 3m was obtained as a white solid (0.58 g, 70% yield),
1
mp 52−54 °C. Rf = 0.89 on silica gel (petroleum ether). H NMR
1
7.59−7.54 (m, 2H), 7.42−7.37 (m, 3H). The H NMR spectral data
(600 MHz, CDCl3): δ 7.55−7.53 (m, 2H), 7.37−7.35 (m, 3H),
are in good agreement with the literature data.20
1
7.33−7.28 (m, 2H), 7.03 (dd, J = 5.0, 3.8 Hz, 1H). The H NMR
spectral data are in good agreement with the literature data.24
General Procedure (II) for Oxidation of C4-Alkynylisox-
azoles into C4-(1,2-Diketoaryl)isoxazoles (2). C4-alkynylisox-
azole 1 (0.125 mmol, 1 equiv) and AgNO3 (42.5 mg, 2 equiv) were
simultaneously added to a 10 mL round-bottomed flask, followed by
1-(4-(Phenylethynyl)phenyl)ethan-1-one (3i). Following general
procedure (I), substrate 3i was obtained as a white solid (0.85 g, 85%
yield), mp 97−99 °C. Rf = 0.25 on silica gel (ethyl acetate/petroleum
ether 1:60, v/v). 1H NMR (600 MHz, CDCl3): δ 7.97−7.91 (m, 2H),
7.64−7.59 (m, 2H), 7.58−7.52 (m, 2H), 7.40−7.33 (m, 3H), 2.61 (s,
F
DOI: 10.1021/acs.joc.9b01667
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
the addition of MeCN (1.5 mL). Then ICl (0.25 M MeCN, 1 equiv)
was added dropwise and the solution was allowed to stir at room
temperature for 4 h under an air atmosphere. After the reaction was
completed, the reaction was poured into 10 mL ethyl acetate and
washed three times (3 × 10 mL) with brine. The organic layers were
combined, dried with anhydrous MgSO4, and then filtered. The
filtrate was concentrated under vacuum, and the resulting residue was
purified by using a TLC silica gel preparative plate using ethyl
acetate/petroleum ether as the developing solvents to afford the
desired products 2.
27.8, 27.1, 22.3, 22.1, 14.0. HRMS (ESI-ion trap) m/z: [M + H]+
calcd for C23H24NO3, 362.1756; found, 362.1754.
1-(5-(tert-Butyl)-3-(4-methoxyphenyl)isoxazol-4-yl)-2-(p-tolyl)-
ethane-1,2-dione (2g). Following general procedure (II), product 2g
was obtained as a yellow solid (35.8 mg, 76% yield), mp 102−104 °C.
1
Rf = 0.28 on silica gel (ethyl acetate/petroleum ether 1:15, v/v). H
NMR (600 MHz, CDCl3): δ 7.56 (d, J = 8.0 Hz, 2H), 7.09 (dd, J =
15.5, 8.2 Hz, 4H), 6.50 (d, J = 8.5 Hz, 2H), 3.58 (s, 3H), 2.32 (s, 3H),
1.45 (s, 9H). 13C{1H} NMR (150 MHz, CDCl3): δ 190.4, 189.6,
185.3, 163.1, 160.9, 145.7, 130.7, 130.2, 129.4, 120.2, 113.9, 113.5,
55.3, 35.5, 27.9, 22.0. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for
C23H24NO4, 378.1705; found, 378.1703.
1-(3,5-Diphenylisoxazol-4-yl)-2-(p-tolyl)ethane-1,2-dione (2a).
Following general procedure (II), product 2a was obtained as a
yellow solid (37.7 mg, 82% yield), mp 100−102 °C. Rf = 0.30 on silica
1-(5-(tert-Butyl)-3-(4-(trifluoromethyl)phenyl)isoxazol-4-yl)-2-(p-
tolyl)ethane-1,2-dione (2h). Following general procedure (II),
product 2h was obtained as a yellow oil (33.7 mg, 65% yield). Rf =
0.30 on silica gel (ethyl acetate/petroleum ether 1:35, v/v). 1H NMR
(600 MHz, CDCl3): δ 7.58 (d, J = 7.9 Hz, 2H), 7.37−7.31 (m, 4H),
7.17 (d, J = 7.9 Hz, 2H), 2.41 (s, 3H), 1.55 (s, 9H). 13C{1H} NMR
(150 MHz, CDCl3): δ 190.5, 188.9, 185.8, 162.3, 146.4, 131.9 (q, J =
33.0 Hz), 131.6, 130.0, 129,9, 129,8 129.6, 125.3 (q, J = 4.5 Hz),
123.7 (q, J = 270.0 Hz), 113.5, 35.6, 27.9, 22.1. HRMS (ESI-ion trap)
m/z: [M + H]+ calcd for C23H21F3NO3, 416.1474; found, 416.1470.
1-(5-(tert-Butyl)-3-(4-(trifluoromethyl)phenyl)isoxazol-4-yl)-2-(4-
methoxyphenyl)ethane-1,2-dione (2i). Following general procedure
(II), product 2i was obtained as a yellow solid (37.7 mg, 70% yield),
mp 83−85 °C. Rf = 0.30 on silica gel (ethyl acetate/petroleum ether
1:15, v/v). 1H NMR (600 MHz, CDCl3): δ 7.69−7.64 (m, 2H), 7.36
(s, 4H), 6.87−6.83 (m, 2H), 3.88 (s, 3H), 1.55 (s, 9H). 13C{1H}
NMR (150 MHz, CDCl3): δ 189.3, 189.1, 185.7, 165.1, 162.3, 132.4,
131.9 (q, J = 33.0 Hz), 131.8, 125.4, 125.2 (q, J = 3.0 Hz), 123.8 (q, J
= 271.5 Hz), 114.3, 113.6, 55.8, 35.6, 27.9. 19F NMR (564 MHz,
CDCl3): δ −63.11. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for
C23H21F3NO4, 432.1423; found, 432.1421.
1
gel (ethyl acetate/petroleum ether 1:20, v/v). H NMR (600 MHz,
CDCl3): δ 7.88 (d, J = 7.9 Hz, 2H), 7.67 (d, J = 8.2 Hz, 2H), 7.50 (t, J
= 7.4 Hz, 3H), 7.41 (t, J = 7.7 Hz, 2H), 7.34 (t, J = 7.5 Hz, 1H), 7.26
(dd, J = 9.5, 5.7 Hz, 2H), 7.19 (d, J = 8.1 Hz, 2H), 2.41 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3): δ 190.1, 188.2, 175.1, 163.6,
145.9, 132.1, 130.3, 130.2, 130.1, 129.6, 129.4, 129.3, 128.8, 128.6,
127.8, 126.4, 113.7, 22.1. HRMS (ESI-ion trap) m/z: [M + H]+ calcd
for C24H18NO3, 368.1287; found, 368.1285.
1-(3-(tert-Butyl)-5-phenylisoxazol-4-yl)-2-(p-tolyl)ethane-1,2-
dione (2b). Following general procedure (II), product 2b was
obtained as a yellow solid (31.7 mg, 73% yield), mp 107−109 °C. Rf =
0.28 on silica gel (ethyl acetate/petroleum ether 1:30, v/v). 1H NMR
(600 MHz, CDCl3): δ 7.64 (d, J = 8.1 Hz, 2H), 7.30 (t, J = 8.5 Hz,
3H), 7.19 (d, J = 7.9 Hz, 2H), 7.12 (t, J = 7.6 Hz, 2H), 2.40 (s, 3H),
1.52 (s, 9H). 13C{1H} NMR (150 MHz, CDCl3): δ 190.4, 189.6,
176.7, 170.7, 145.7, 131.4, 130.6, 130.0, 129.5, 129.3, 128.5, 126.7,
113.8, 33.9, 28.4, 22.1. HRMS (ESI-ion trap) m/z: [M + H]+ calcd
for C22H22NO3, 348.1600; found, 348.1593.
1-(3-Isopropyl-5-phenylisoxazol-4-yl)-2-(p-tolyl)ethane-1,2-
dione (2c). Following general procedure (II), product 2c was
obtained as a yellow solid (28.9 mg, 70% yield), mp 108−110 °C. Rf =
0.30 on silica gel (ethyl acetate/petroleum ether 1:20, v/v). 1H NMR
(600 MHz, CDCl3): δ 7.60 (d, J = 8.2 Hz, 2H), 7.30 (dd, J = 10.5, 4.3
Hz, 3H), 7.17−7.12 (m, 4H), 3.43 (hept, J = 6.9 Hz, 1H), 2.35 (s,
3H), 1.35 (d, J = 6.9 Hz, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ
190.8, 189.3, 175.9, 169.2, 146.1, 131.6, 130.4, 130.1, 129.7, 129.4,
128.6, 126.6, 112.8, 27.1, 22.1, 21.2. HRMS (ESI-ion trap) m/z: [M +
H]+ calcd for C21H20NO3, 334.1443; found, 334.1441.
1-(3,5-Diphenylisoxazol-4-yl)-2-phenylethane-1,2-dione (2j).
Following general procedure (II), product 2j was obtained as a
yellow solid (33.1 mg, 75% yield), mp 111−113 °C. Rf = 0.29 on silica
1
gel (ethyl acetate/petroleum ether 1:20, v/v). H NMR (600 MHz,
CDCl3): δ 7.86−7.79 (m, 2H), 7.68 (dd, J = 8.2, 1.1 Hz, 2H), 7.50 (t,
J = 7.4 Hz, 1H), 7.42 (dd, J = 12.0, 4.3 Hz, 3H), 7.32 (dt, J = 15.5, 7.9
Hz, 4H), 7.25 (t, J = 7.5 Hz, 1H), 7.17 (dd, J = 8.7, 6.6 Hz, 2H).
13C{1H} NMR (150 MHz, CDCl3): δ 190.4, 188.1, 175.2, 163.6,
134.7, 132.7, 132.3, 130.4, 130.1, 129.4, 129.3, 128.9, 128.8, 128.6,
127.7, 126.4, 113.7. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for
C23H16NO3, 354.1130; found, 354.1120.
1-(5-(tert-Butyl)-3-phenylisoxazol-4-yl)-2-(p-tolyl)ethane-1,2-
dione (2d). Following general procedure (II), product 2d was
obtained as a yellow solid (33.8 mg, 78% yield), mp 102−104 °C. Rf =
0.30 on silica gel (ethyl acetate/petroleum ether 1:30, v/v). 1H NMR
(600 MHz, CDCl3): δ 7.63 (d, J = 8.2 Hz, 2H), 7.26−7.24 (m, 2H),
7.23−7.16 (m, 3H), 7.09 (t, J = 7.7 Hz, 2H), 2.41 (d, J = 7.8 Hz, 3H),
1.54 (s, 9H). 13C{1H} NMR (150 MHz, CDCl3): δ 190.2, 189.4,
185.5, 163.4, 145.8, 130.2, 130.1, 130.0, 129.5, 129.3, 128.5, 128.1,
113.4, 35.6, 27.9, 22.1. HRMS (ESI-ion trap) m/z: [M + H]+ calcd
for C22H22NO3, 348.1600; found, 348.1601.
1-(5-Cyclopropyl-3-phenylisoxazol-4-yl)-2-(p-tolyl)ethane-1,2-
dione (2e). Following general procedure (II), product 2e was
obtained as a yellow oil (29.4 mg, 71% yield). Rf = 0.28 on silica gel
(ethyl acetate/petroleum ether 1:25, v/v). 1H NMR (600 MHz,
CDCl3): δ 7.68 (d, J = 8.2 Hz, 2H), 7.35−7.31 (m, 3H), 7.24−7.19
(m, 4H), 2.72 (tt, J = 8.4, 5.0 Hz, 1H), 2.43 (s, 3H), 1.42−1.39 (m,
2H), 1.27−1.24 (m, 2H). 13C{1H} NMR (150 MHz, CDCl3): δ
191.5, 188.9, 182.1, 162.8, 146.2, 130.2, 130.2, 130.1, 129.7, 129.3,
128.4, 127.7, 113.9, 22.1, 11.3, 9.7. HRMS (ESI-ion trap) m/z: [M +
H]+ calcd for C21H18NO3, 332.1287; found, 332.1281.
1-(5-Pentyl-3-phenylisoxazol-4-yl)-2-(p-tolyl)ethane-1,2-dione
(2f). Following general procedure (II), product 2f was obtained as a
yellow oil (33.8 mg, 78% yield). Rf = 0.30 on silica gel (ethyl acetate/
petroleum ether 1:35, v/v). 1H NMR (600 MHz, CDCl3): δ 7.69 (d, J
= 8.2 Hz, 2H), 7.40−7.36 (m, 2H), 7.35−7.32 (m, 1H), 7.23 (dt, J =
13.7, 7.0 Hz, 4H), 3.07−3.03 (m, 2H), 2.42 (s, 3H), 1.79 (dt, J =
15.3, 7.6 Hz, 2H), 1.37−1.32 (m, 4H), 0.89 (t, J = 7.1 Hz, 3H).
13C{1H} NMR (150 MHz, CDCl3): δ 191.1, 188.7, 181.3, 162.5,
1-(3,5-Diphenylisoxazol-4-yl)-2-(4-fluorophenyl)ethane-1,2-
dione (2k). Following general procedure (II), product 2k was
obtained as a yellow solid (23.1 mg, 50% yield), mp 160−162 °C. Rf =
0.28 on silica gel (ethyl acetate/petroleum ether 1:25, v/v). 1H NMR
(400 MHz, CDCl3): δ 7.95−7.86 (m, 2H), 7.85−7.75 (m, 2H), 7.48
(ddd, J = 21.1, 15.1, 7.4 Hz, 5H), 7.35 (t, J = 7.4 Hz, 1H), 7.27 (t, J =
7.4 Hz, 2H), 7.08 (t, J = 8.6 Hz, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ 188.8, 187.7, 175.3, 166.7 (d, J = 257.0 Hz), 163.5, 132.8
(d, J = 10.0 Hz), 132.3, 130.4, 129.4 (d, J = 8.0 Hz), 129.2 (d, J = 3.0
Hz), 128.9, 128.6, 127.7, 126.3, 116.3, 116.1, 113.6. HRMS (ESI-ion
trap) m/z: [M + H]+ calcd for C23H15FNO3, 372.1036; found,
372.1033.
1-(3,5-Diphenylisoxazol-4-yl)-2-(m-tolyl)ethane-1,2-dione (2l).
Following general procedure (II), product 2l was obtained as a
yellow solid (36.3 mg, 79% yield), mp 98−100 °C. Rf = 0.30 on silica
1
gel (ethyl acetate/petroleum ether 1:30, v/v). H NMR (400 MHz,
CDCl3): δ 7.89 (d, J = 7.2 Hz, 2H), 7.56 (d, J = 7.6 Hz, 1H), 7.53−
7.48 (m, 4H), 7.41 (dd, J = 15.2, 7.7 Hz, 3H), 7.35 (d, J = 7.4 Hz,
1H), 7.27 (d, J = 8.1 Hz, 3H), 2.34 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 190.7, 188.1, 175.2, 163.5, 135.5, 132.2, 130.3,
130.3, 129.5, 129.4, 128.9, 128.7, 128.6, 127.3, 113.7, 21.4. HRMS
(ESI-ion trap) m/z: [M + H]+ calcd for C24H18NO3, 368.1287; found,
368.1287.
1-(3,5-Diphenylisoxazol-4-yl)-2-(4-methoxyphenyl)ethane-1,2-
dione (2m). Following general procedure (II), product 2m was
obtained as a yellow solid (37.4 mg, 78% yield), mp 90−92 °C. Rf =
146.3, 130.2, 130.1, 130.0, 129.8, 129.3, 128.4, 127.8, 113.5, 31.5,
G
DOI: 10.1021/acs.joc.9b01667
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The Journal of Organic Chemistry
Article
1
1
0.25 on silica gel (ethyl acetate/petroleum ether 1:8, v/v). H NMR
(600 MHz, CDCl3): δ 7.87 (d, J = 7.8 Hz, 2H), 7.75 (d, J = 8.8 Hz,
2H), 7.49 (dd, J = 11.3, 7.6 Hz, 3H), 7.40 (t, J = 7.7 Hz, 2H), 7.33 (d,
J = 7.2 Hz, 1H), 7.26 (t, J = 7.5 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H),
3.85 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ 188.9, 188.3,
174.9, 164.8, 163.5, 132.5, 132.1, 130.2, 129.4, 129.3, 128.8, 128.5,
127.8, 126.4, 125.8, 114.1, 55.7. HRMS (ESI-ion trap) m/z: [M +
H]+ calcd for C24H18NO4, 384.1236; found, 384.1234.
acetate/petroleum ether 1:30, v/v). H NMR (600 MHz, CDCl3): δ
7.99−7.94 (m, 2H), 7.87−7.82 (m, 2H), 7.69−7.64 (m, 3H), 7.54−
7.50 (m, 2H). 13C{1H} NMR (150 MHz, CDCl3): δ 194.1, 193.5,
135.3, 132.9, 132.6, 131.9, 131.4, 130.7, 130.2, 129.3. HRMS (ESI-ion
trap) m/z: [M − Cl]+ calcd for C14H9O2, 209.0603; found, 209.0609.
1-(4-Bromophenyl)-2-phenylethane-1,2-dione (4f). Following
general procedure (III), product 4f was obtained as a yellow solid
(33.7 mg, 78% yield), mp 85−87 °C. Rf = 0.30 on silica gel (ethyl
1
acetate/petroleum ether 1:35, v/v). H NMR (600 MHz, CDCl3): δ
1-(4-(tert-Butyl)phenyl)-2-(3,5-diphenylisoxazol-4-yl)ethane-1,2-
dione (2n). Following general procedure (II), product 2n was
obtained as a yellow solid (30.7 mg, 78% yield), mp 131−133 °C. Rf =
0.30 on silica gel (ethyl acetate/petroleum ether 1:25, v/v). 1H NMR
(400 MHz, CDCl3): δ 7.81 (d, J = 7.3 Hz, 2H), 7.61 (d, J = 8.6 Hz,
2H), 7.46−7.39 (m, 3H), 7.33 (t, J = 7.6 Hz, 4H), 7.25 (t, J = 7.4 Hz,
1H), 7.16 (t, J = 7.4 Hz, 2H), 1.25 (s, 9H). 13C{1H} NMR (100
MHz, CDCl3): δ 190.1, 188.3, 175.1, 163.5, 158.8, 132.2, 130.3,
130.2, 130.0, 129.4, 129.3, 128.8, 128.5, 127.7, 126.4, 125.8, 113.7,
35.5, 31.2. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for
C27H24NO3, 410.1756; found, 410.1754.
General Procedure (III) for Oxidation of Alkynes into 1,2-
Diketones (4). Alkynes 3 (0.15 mmol, 1 equiv) and AgNO3 (76.4
mg, 3 equiv) were simultaneously added to a 10 mL round-bottomed
flask, followed by the addition of MeCN (1.5 mL). Then ICl (0.15 M
MeCN, 0.5 equiv) was added dropwise and the solution was allowed
to stir at room temperature for 4 h under an air atmosphere. After the
reaction was completed as judged by TLC, the reaction mixture was
poured into 10 mL ethyl acetate and washed three times (3 × 10 mL)
with brine. The organic layers were combined, dried with anhydrous
MgSO4, and then filtered. The filtrate was concentrated under
vacuum, and the resulting residue was purified by using a TLC silica
gel preparative plate using ethyl acetate/petroleum ether as the
developing solvents to afford the desired products 4.
7.96 (dd, J = 8.3, 1.1 Hz, 2H), 7.94−7.90 (m, 2H), 7.69−7.65 (m,
1H), 7.54−7.47 (m, 4H). 13C{1H} NMR (150 MHz, CDCl3): δ
194.1, 193.3, 141.8, 135.3, 132.9, 131.6, 131.4, 130.2, 129.6, 129.3.
HRMS (ESI-ion trap) m/z: [M + H]+ calcd for C14H10BrO2,
288.9864; found, 288.9863.
1-Phenyl-2-(4-(trifluoromethyl)phenyl)ethane-1,2-dione (4g).
Following general procedure (III), product 4g was obtained as a
yellow solid (36.2 mg, 87% yield), mp 88−90 °C. Rf = 0.30 on silica
1
gel (ethyl acetate/petroleum ether 1:30, v/v). H NMR (600 MHz,
CDCl3): δ 8.11 (d, J = 8.2 Hz, 2H), 7.98 (dd, J = 8.2, 1.1 Hz, 2H),
7.78 (d, J = 8.3 Hz, 2H), 7.69 (t, J = 7.5 Hz, 1H), 7.54 (t, J = 7.8 Hz,
2H). 13C{1H} NMR (150 MHz, CDCl3): δ 193.7, 193.2, 136.1 (q, J =
33.0 Hz), 135.8, 135.5, 132.8, 130.4, 130.2, 129.4, 126.3 (q, J = 4.5
Hz), 123.5 (q, J = 271.5 Hz). HRMS (ESI-ion trap) m/z: [M + H]+
calcd for C15H10F3O2, 279.0633; found, 279.0633.
1-(4-Nitrophenyl)-2-phenylethane-1,2-dione (4h). Following gen-
eral procedure (III), product 4h was obtained as a yellow solid (29.8
mg, 78% yield), mp 125−127 °C. Rf = 0.26 on silica gel (ethyl
1
acetate/petroleum ether 1:15, v/v). H NMR (600 MHz, CDCl3): δ
8.37−8.32 (m, 2H), 8.19−8.14 (m, 2H), 8.02−7.95 (m, 2H), 7.71
(ddd, J = 7.8, 2.5, 1.2 Hz, 1H), 7.58−7.52 (m, 2H). 13C{1H} NMR
(150 MHz, CDCl3): δ 193.1, 192.3, 151.4, 137.5, 135.7, 132.6, 131.2,
130.3, 129.4, 124.3. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for
C14H10NO4, 256.0610; found, 256.0600.
Benzil (4a). Following general procedure (III), product 4a was
obtained as a yellow solid (28.3 mg, 90% yield), mp 93−95 °C. Rf =
0.30 on silica gel (ethyl acetate/petroleum ether 1:20, v/v). 1H NMR
(600 MHz, CDCl3): δ 7.98 (d, J = 7.6 Hz, 4H), 7.66 (t, J = 7.4 Hz,
2H), 7.51 (t, J = 7.8 Hz, 4H). 13C{1H} NMR (150 MHz, CDCl3): δ
194. 8, 135.1, 133.2, 130.1, 129.2. HRMS (ESI-ion trap) m/z: [M +
H]+ calcd for C14H11O2, 211.0759; found, 211.0755.
1-(4-Acetylphenyl)-2-phenylethane-1,2-dione (4i). Following
general procedure (III), product 4i was obtained as a yellow solid
(30.9 mg, 81% yield), mp 75−77 °C. Rf = 0.29 on silica gel (ethyl
1
acetate/petroleum ether 1:15, v/v). H NMR (600 MHz, CDCl3): δ
8.05 (s, 4H), 7.97−7.94 (m, 2H), 7.68−7.65 (m, 1H), 7.53−7.50 (m,
2H), 2.63 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ 197.5,
193.9, 193.8, 141.4, 136.1, 135.4, 132.8, 130.3, 130.1, 129.3, 128.9,
27.1. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for C16H13O3,
253.0865; found, 253.0861.
1-(4-Methoxyphenyl)-2-phenylethane-1,2-dione (4b). Following
general procedure (III), product 4b was obtained as a yellow solid
(21.6 mg, 60% yield), mp 60−62 °C. Rf = 0.27 on silica gel (ethyl
1
acetate/petroleum ether 1:15, v/v). H NMR (600 MHz, CDCl3): δ
4-(2-Oxo-2-phenylacetyl)benzonitrile (4j). Following general
procedure (III), product 4j was obtained as a yellow solid (30.6
mg, 87% yield), mp 110−112 °C. Rf = 0.29 on silica gel (ethyl
7.99−7.92 (m, 4H), 7.66−7.62 (m, 1H), 7.52−7.48 (m, 2H), 6.99−
6.96 (m, 2H), 3.88 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ
195.1, 193.4, 165.2, 134.9, 133.4, 132.6, 130.1, 129.2, 126.3, 114.6,
55.9. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for C15H13O3,
241.0865; found, 241.0864.
1
acetate/petroleum ether 1:25, v/v). H NMR (600 MHz, CDCl3): δ
8.08 (d, J = 8.2 Hz, 2H), 7.97 (d, J = 7.6 Hz, 2H), 7.81 (d, J = 8.2 Hz,
2H), 7.70 (t, J = 7.4 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H). 13C{1H} NMR
(150 MHz, CDCl3): δ 193.2, 192.6, 136.1, 135.6, 132.9, 132.6, 130.4,
130.2, 129.4, 118.1, 117.8. HRMS (ESI-ion trap) m/z: [M + H]+
calcd for C15H10NO2, 236.0712; found, 236.0711.
1-Phenyl-2-(p-tolyl)ethane-1,2-dione (4c). Following general
procedure (III), product 4c was obtained as a yellow solid (29.6
mg, 88% yield), mp 93−95 °C. Rf = 0.30 on silica gel (ethyl acetate/
1
petroleum ether 1:20, v/v). H NMR (600 MHz, CDCl3): δ 7.99−
1,2-Bis(4-fluorophenyl)ethane-1,2-dione (4k). Following general
procedure (III), product 4k was obtained as a yellow solid (31.7 mg,
86% yield), mp 118−120 °C. Rf = 0.30 on silica gel (ethyl acetate/
7.94 (m, 2H), 7.87 (d, J = 8.2 Hz, 2H), 7.64 (q, J = 7.4 Hz, 1H), 7.50
(t, J = 7.8 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 2.43 (s, 3H). 13C{1H}
NMR (150 MHz, CDCl3): δ 194.9, 194.5, 146.4, 134.9, 133.3, 130.8,
130.2, 130.1, 129.9, 129.2, 22.2. HRMS (ESI-ion trap) m/z: [M +
H]+ calcd for C15H13O2, 225.0916; found, 225.0910.
1
petroleum ether 1:40, v/v). H NMR (600 MHz, CDCl3): δ 8.05−
7.99 (m, 4H), 7.22−7.17 (m, 4H). 13C{1H} NMR (150 MHz,
CDCl3): δ 192.5, 167.1 (d, J = 258.0 Hz), 133.1 (d, J = 9.0 Hz), 129.6
(d, J = 3.0 Hz), 116.7 (d, J = 22.5 Hz). 19F NMR (564 MHz, CDCl3):
δ −100.92. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for
C14H9F2O2, 247.0571; found, 247.0570.
1-(4-Fluorophenyl)-2-phenylethane-1,2-dione (4d). Following
general procedure (III), product 4d was obtained as a yellow solid
(29.4 mg, 86% yield), mp 63−65 °C. Rf = 0.30 on silica gel (ethyl
1
acetate/petroleum ether 1:25, v/v). H NMR (600 MHz, CDCl3): δ
1,2-Di-p-tolylethane-1,2-dione (4l). Following general procedure
(III), product 4l was obtained as a yellow solid (30.0 mg, 84% yield),
mp 101−103 °C. Rf = 0.28 on silica gel (ethyl acetate/petroleum
ether 1:50, v/v). 1H NMR (600 MHz, CDCl3): δ 7.89−7.82 (m, 4H),
7.30 (dd, J = 8.5, 0.5 Hz, 4H), 2.43 (s, 6H). 13C{1H} NMR (150
MHz, CDCl3): δ 194.7, 146.3, 130.9, 130.2, 129.9, 22.1. HRMS (ESI-
ion trap) m/z: [M + H]+ calcd for C16H15O2, 239.1072; found,
239.1071.
8.04−8.00 (m, 2H), 7.97 (dd, J = 8.3, 1.1 Hz, 2H), 7.69−7.64 (m,
1H), 7.52 (t, J = 7.9 Hz, 2H), 7.22−7.16 (m, 2H). 13C{1H} NMR
(150 MHz, CDCl3): δ 194.3, 192.9, 166.6 (d, J = 255.0 Hz), 135.2,
133.1, 132.9 (d, J = 15.0 Hz), 130.1, 129.6 (d, J = 15.0 Hz), 129.3,
116.6 (d, J = 30.0 Hz). HRMS (ESI-ion trap) m/z: [M + H]+ calcd
for C14H10FO2, 229.0665; found, 229.0655.
1-(4-Chlorophenyl)-2-phenylethane-1,2-dione (4e). Following
general procedure (III), product 4e was obtained as a yellow solid
(31.8 mg, 87% yield), mp 73−75 °C. Rf = 0.30 on silica gel (ethyl
1-Phenyl-2-(thiophen-2-yl)ethane-1,2-dione (4m). Following
general procedure (III), product 4m was obtained as a yellow oil
H
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(28.1 mg, 87% yield). Rf = 0.29 on silica gel (ethyl acetate/petroleum
ether 1:50, v/v). H NMR (600 MHz, CDCl3): δ 8.04 (dd, J = 8.2,
128.9, 128.8, 128.7, 128.6, 128.1, 128.0, 127.5, 127.3, 114.2. HRMS
(ESI-ion trap) m/z: [M + H]+ calcd for C29H20N3O, 426.1606; found,
426.1606.
1
1.1 Hz, 2H), 7.84 (dd, J = 4.8, 1.0 Hz, 1H), 7.81−7.78 (m, 1H), 7.65
(dd, J = 11.7, 4.3 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.18 (dd, J = 4.8,
4.0 Hz, 1H). 13C{1H} NMR (150 MHz, CDCl3): δ 192.3, 185.8,
140.1, 137.1, 136.9, 135.1, 132.8, 130.4, 129.1, 129.0. HRMS (ESI-ion
trap) m/z: [M + H]+ calcd for C12H9O2S, 217.0323; found, 217.0320.
1-Phenylbutane-1,2-dione (4n). Following general procedure
(III), product 4n was obtained as a yellow oil (18.2 mg, 75%
yield). Rf = 0.28 on silica gel (ethyl acetate/petroleum ether 1:80, v/
4-(3-(4-Fluorophenyl)quinoxalin-2-yl)-3,5-diphenylisoxazole
(5e). Following procedure (IV), product 5e was obtained as a yellow
oil (55.8 mg, 84% yield). Rf = 0.23 on silica gel (ethyl acetate/
1
petroleum ether 1:20, v/v). H NMR (600 MHz, CDCl3): δ 8.23−
8.15 (m, 2H), 7.91−7.82 (m, 2H), 7.59 (dd, J = 5.2, 3.4 Hz, 2H),
7.43−7.38 (m, 1H), 7.37−7.28 (m, 3H), 7.18 (dd, J = 10.7, 4.9 Hz,
2H), 7.11 (dd, J = 8.2, 1.2 Hz, 2H), 7.03−6.96 (m, 2H), 6.84−6.74
(m, 2H). 13C{1H} NMR (150 MHz, CDCl3): δ 168.3, 163.2 (d, J =
249.0 Hz), 162.7, 154.0, 145.5, 141.8, 141.5, 133.8 (d, J = 3.0 Hz),
131.3, 130.9 (d, J = 7.5 Hz), 130.7 (d, J = 12.0 Hz), 129.8, 129.6,
129.5, 129.1, 128.8, 128.7, 128.0, 127.5, 127.3, 115.3 (d, J = 21.0 Hz),
114.0. 19F NMR (564 MHz, CDCl3): δ −112.01. HRMS (ESI-ion
trap) m/z: [M + H]+ calcd for C29H19FN3O, 444.1512; found,
444.1512.
1
v). H NMR (600 MHz, CDCl3): δ 7.98 (dt, J = 8.4, 1.4 Hz, 2H),
7.65−7.62 (m, 1H), 7.51−7.47 (m, 2H), 2.91 (q, J = 7.3 Hz, 2H),
1.20 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ 204.1,
192.8, 134.8, 132.2, 130.3, 129.1, 32.3, 7.0. HRMS (ESI-ion trap) m/
z: [M + H]+ calcd for C10H11O2, 163.0759; found, 163.0754.
Procedure (IV) for Synthesis of 5. C4-(1,2-Diketoaryl)-
isoxazoles 2 (0.15 mmol, 1 equiv), 1,2-diaminobenzene (0.18
mmol, 19.5 mg) and MeCN (2.5 mL) were simultaneously added
to a 10 mL round-bottomed flask. Then the solution was allowed to
stir at room temperature for 6 h under an air atmosphere. After the
reaction was completed as judged by TLC, the reaction mixture was
poured into 10 mL ethyl acetate and washed three times (3 × 10 mL)
with brine. The organic layers were combined, dried with anhydrous
MgSO4, and then filtered. The filtrate was concentrated under
vacuum, and the resulting residue was purified by using a TLC silica
gel preparative plate using ethyl acetate/petroleum ether as the
developing solvents to afford the desired products 5.
3,5-Diphenyl-4-(3-(m-tolyl)quinoxalin-2-yl)isoxazole (5f). Fol-
lowing procedure (IV), product 5f was obtained as a white solid
(61.3 mg, 93% yield). mp 167−169 °C. Rf = 0.25 on silica gel (ethyl
1
acetate/petroleum ether 1:20, v/v). H NMR (600 MHz, CDCl3): δ
8.20 (dt, J = 4.9, 2.0 Hz, 2H), 7.89−7.81 (m, 2H), 7.62−7.56 (m,
2H), 7.40 (t, J = 7.4 Hz, 1H), 7.35−7.29 (m, 3H), 7.18 (t, J = 7.8 Hz,
2H), 7.11 (dd, J = 8.1, 1.0 Hz, 2H), 7.03 (d, J = 7.6 Hz, 1H), 6.99 (t, J
= 7.5 Hz, 1H), 6.79 (d, J = 7.5 Hz, 1H), 6.70 (s, 1H), 2.12 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3): δ 168.2, 162.7, 155.4, 145.8,
141.8, 141.3, 138.1, 137.5, 131.1, 130.5, 130.4, 129.8, 129.6, 129.5,
129.4, 129.3, 128.9, 128.7, 128.6, 128.1, 127.8, 127.5, 127.3, 125.7,
114.3, 21.4. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for
C30H22N3O, 440.1763; found, 440.1763.
3,5-Diphenyl-4-(3-(p-tolyl)quinoxalin-2-yl)isoxazole (5a). Fol-
lowing procedure (IV), product 5a was obtained as a white solid
(54.1 mg, 82% yield). mp 163−165 °C. Rf = 0.25 on silica gel (ethyl
1
acetate/petroleum ether 1:20, v/v). H NMR (600 MHz, CDCl3): δ
4-(3-(4-Methoxyphenyl)quinoxalin-2-yl)-3,5-diphenylisoxazole
(5g). Following procedure (IV), product 5g was obtained as a white
solid (65.5 mg, 96% yield). mp 176−178 °C. Rf = 0.21 on silica gel
(ethyl acetate/petroleum ether 1:7, v/v). 1H NMR (600 MHz,
CDCl3): δ 8.21−8.14 (m, 2H), 7.86−7.80 (m, 2H), 7.63−7.57 (m,
2H), 7.39 (dd, J = 8.3, 6.5 Hz, 1H), 7.35−7.27 (m, 3H), 7.16 (dd, J =
10.7, 4.9 Hz, 2H), 7.12 (d, J = 7.2 Hz, 2H), 7.00 (t, J = 5.7 Hz, 2H),
6.67−6.58 (m, 2H), 3.76 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3):
δ 168.1, 162.8, 160.3, 154.7, 145.7, 141.9, 141.2, 131.0, 130.6, 130.4,
130.2, 130.1, 129.6, 129.5, 129.4, 128.9, 128.7, 128.6, 127.9, 127.5,
127.3, 114.4, 113.7, 55.5. HRMS (ESI-ion trap) m/z: [M + H]+ calcd
for C30H22N3O2, 456.1712; found, 456.1712.
8.19 (td, J = 8.1, 1.6 Hz, 2H), 7.87−7.78 (m, 2H), 7.63−7.57 (m,
2H), 7.42−7.35 (m, 1H), 7.34−7.26 (m, 3H), 7.21−7.11 (m, 4H),
6.97−6.87 (m, 4H), 2.28 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3):
δ 168.1, 162.7, 155.2, 145.7, 141.8, 141.2, 138.8, 134.7, 130.9, 130.5,
130.3, 129.6, 129.5, 129.3, 128.9, 128.8, 128.7, 128.6, 128.5, 127.9,
127.5, 127.2, 114.3, 21.3. HRMS (ESI-ion trap) m/z: [M + H]+ calcd
for C30H22N3O, 440.1763; found, 440.1761.
3-Isopropyl-5-phenyl-4-(3-(p-tolyl)quinoxalin-2-yl)isoxazole
(5b). Following procedure (IV), product 5b was obtained as a white
solid (47.6 mg, 98% yield). mp 129−131 °C. Rf = 0.25 on silica gel
(ethyl acetate/petroleum ether 1:20, v/v). 1H NMR (600 MHz,
CDCl3): δ 8.23−8.13 (m, 2H), 7.82 (pd, J = 6.9, 1.7 Hz, 2H), 7.28
(ddd, J = 8.7, 6.0, 3.0 Hz, 1H), 7.21−7.16 (m, 4H), 7.14 (d, J = 8.1
Hz, 2H), 6.96 (d, J = 7.9 Hz, 2H), 3.02 (hept, J = 6.9 Hz, 1H), 2.27
(s, 3H), 1.31 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 7.0 Hz, 3H). 13C{1H}
NMR (150 MHz, CDCl3): δ 168.5, 167.2, 154.7, 145.8, 141.8, 141.3,
139.1, 134.9, 130.8, 130.3, 130.2, 129.6, 129.3, 129.0, 128.9, 128.6,
127.7, 127.1, 113.8, 26.5, 21.5, 21.3, 21.2. HRMS (ESI-ion trap) m/z:
[M + H]+ calcd for C27H24N3O, 406.1919; found, 406.1919.
5-Cyclopropyl-3-phenyl-4-(3-(p-tolyl)quinoxalin-2-yl)isoxazole
(5c). Following procedure (IV), product 5c was obtained as a yellow
oil (50.8 mg, 84% yield). Rf = 0.26 on silica gel (ethyl acetate/
4-(3-(4-(tert-Butyl)phenyl)quinoxalin-2-yl)-3,5-diphenylisoxazole
(5h). Following procedure (IV), product 5h was obtained as a yellow
oil (68.6 mg, 95% yield). Rf = 0.30 on silica gel (ethyl acetate/
1
petroleum ether 1:25, v/v). H NMR (600 MHz, CDCl3): δ 8.23−
8.14 (m, 2H), 7.88−7.79 (m, 2H), 7.60 (d, J = 7.4 Hz, 2H), 7.39 (t, J
= 7.4 Hz, 1H), 7.34−7.27 (m, 3H), 7.14 (t, J = 7.8 Hz, 2H), 7.10 (d, J
= 8.3 Hz, 2H), 7.06 (d, J = 7.5 Hz, 2H), 6.93 (d, J = 8.3 Hz, 2H), 1.28
(s, 9H). 13C{1H} NMR (150 MHz, CDCl3): δ 168.3, 162.8, 155.1,
151.9, 145.6, 141.9, 141.3, 134.6, 130.9, 130.6, 130.3, 129.6, 129.5,
129.4, 128.9, 128.8, 128.6, 128.6, 128.0, 127.6, 127.4, 125.2, 114.4,
34.7, 31.3. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for
C33H28N3O, 482.2232; found, 482.2232.
1
petroleum ether 1:20, v/v). H NMR (600 MHz, CDCl3): δ 8.23−
8.13 (m, 2H), 7.84−7.75 (m, 2H), 7.26−7.21 (m, 1H), 7.13−7.08
(m, 2H), 7.04 (d, J = 8.1 Hz, 2H), 7.01−6.92 (m, 4H), 2.31 (s, 3H),
2.18 (ddd, J = 16.9, 8.2, 5.3 Hz, 1H), 1.12 (t, J = 124.3 Hz, 4H).
13C{1H} NMR (150 MHz, CDCl3): δ 173.2, 161.9, 154.9, 145.5,
141.7, 141.3, 138.8, 135.2, 130.6, 130.1, 129.5, 129.3, 129.2, 128.9,
128.4, 127.7, 114.4, 21.4, 8.2. HRMS (ESI-ion trap) m/z: [M + H]+
calcd for C27H22N3O, 404.1763; found, 404.1763.
Procedure (V) for Synthesis of 6. 1,2-Diarylalkynes 3 (0.15
mmol, 1 equiv) and AgNO3 (76.4 mg, 3 equiv) were simultaneously
added to a 10 mL round-bottomed flask, followed by the addition of
MeCN (1.5 mL). Then ICl (0.15 M in MeCN, 0.5 equiv) was added
dropwise and the solution was allowed to stir at room temperature for
4 h under an air atmosphere. After the reaction was completed as
judged by TLC, 1,2-diaminobenzene (0.18 mmol, 19.5 mg) was
added to the reaction mixture directly. The mixture was stirred at
room temperature for 4 h. Then the reaction mixture was poured into
10 mL ethyl acetate and washed three times (3 × 10 mL) with brine.
The organic layers were combined, dried with anhydrous MgSO4, and
then filtered. The filtrate was concentrated under vacuum, and the
resulting residue was purified by using a TLC silica gel preparative
plate using ethyl acetate/petroleum ether as the developing solvents
to afford the desired products 6.
3,5-Diphenyl-4-(3-phenylquinoxalin-2-yl)isoxazole (5d). Follow-
ing procedure (IV), product 5d was obtained as a yellow oil (61.2 mg,
96% yield). Rf = 0.20 on silica gel (ethyl acetate/petroleum ether 1:20,
v/v). 1H NMR (600 MHz, CDCl3): δ 8.20 (ddd, J = 7.5, 5.5, 1.9 Hz,
2H), 7.89−7.82 (m, 2H), 7.58 (d, J = 7.5 Hz, 2H), 7.42−7.36 (m,
1H), 7.35−7.28 (m, 3H), 7.23−7.19 (m, 1H), 7.17 (dd, J = 10.7, 4.9
Hz, 2H), 7.09 (dd, J = 15.7, 7.8 Hz, 4H), 7.00 (d, J = 8.1 Hz, 2H).
13C{1H} NMR (150 MHz, CDCl3): δ 168.2, 162.7, 155.1, 145.7,
141.9, 141.4, 137.6, 131.1, 130.6, 130.5, 129.7, 129.6, 129.4, 129.0,
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2,3-Diphenylquinoxaline (6a). Following procedure (V), product
6a was obtained as a yellow solid (41.1 mg, 73% yield). mp 119−121
°C. Rf = 0.27 on silica gel (ethyl acetate/petroleum ether 1:20, v/v).
1H NMR (600 MHz, CDCl3): δ 8.19 (dd, J = 6.4, 3.4 Hz, 2H), 7.81−
7.74 (m, 2H), 7.56−7.50 (m, 4H), 7.40−7.30 (m, 6H). 13C{1H}
NMR (150 MHz, CDCl3): δ 153.7, 141.4, 139.2, 130.2, 130.1, 129.4,
129.0, 128.5. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for
C20H15N2, 283.1235; found, 283.1230.
2,3-Bis(4-fluorophenyl)quinoxaline (6b). Following procedure
(V), product 6b was obtained as a yellow solid (47.7 mg, 65%
yield). mp 173−175 °C. Rf = 0.30 on silica gel (ethyl acetate/
petroleum ether 1:30, v/v). 1H NMR (600 MHz, CDCl3): δ 8.15 (dd,
J = 6.4, 3.4 Hz, 2H), 7.78 (dd, J = 6.4, 3.4 Hz, 2H), 7.54−7.47 (m,
4H), 7.09−7.01 (m, 4H). 13C{1H} NMR (150 MHz, CDCl3): δ 163.4
(d, J = 247.5 Hz), 152.4, 141.4, 135.2 (d, J = 4.5 Hz), 131.9 (d, J = 9.0
Hz), 130.4, 129.3, 115.7 (d, J = 21.0 Hz). 19F NMR (564 MHz,
CDCl3): δ −111.91. HRMS (ESI-ion trap) m/z: [M + H]+ calcd for
C20H12F2N2, 319.1047; found, 319.1047.
2,3-Di-p-tolylquinoxaline (6c). Following procedure (V), product
6c was obtained as a yellow solid (46.5 mg, 60% yield). mp 169−171
°C. Rf = 0.30 on silica gel (ethyl acetate/petroleum ether 1:35, v/v).
1H NMR (600 MHz, CDCl3): δ 8.16 (dd, J = 6.3, 3.4 Hz, 2H), 7.74
(dd, J = 6.4, 3.4 Hz, 2H), 7.44 (d, J = 8.1 Hz, 4H), 7.15 (d, J = 7.9 Hz,
4H), 2.37 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ 153.7,
141.4, 138.9, 136.6, 129.9, 129.8, 129.3, 129.1, 21.5. HRMS (ESI-ion
trap) m/z: [M + H]+ calcd for C22H19N2, 311.1548; found, 311.1548.
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̃
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.9b01667.
Ortíz, G.; Maldonado, J. L.; Cadenas-Pliego, G. High-Tg Functional
Aromatic Polymers. Macromolecules 2015, 48, 1026−1037.
■
S
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C10H7S)2TiCp2,[(η5-C5H5)Fe (η5-C5H4CH2S)]2TiCp2 and [η2-OC-
(Ph)C(Ph)O]TiCp2. J. Organomet. Chem. 2002, 648, 119−125.
X-ray crystal characterization data for compound 2a
(CIF)
1
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̈
13C{1H}, 19F NMR spectra (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail: yangdq@scnu.edu.cn. Phone: +86 20 31040403. Fax:
+86 20 31040403.
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ORCID
Yu Chen: 0000-0002-4696-9269
Dingqiao Yang: 0000-0002-5226-7722
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully thank the National Natural Science Foundation
of China (21172081, 21372090), the Natural Science
Foundation of Guangdong Province (S2013020013091) and
the City of Guangzhou Science and Technology Plan Projects
(201510010054) for financial support.
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