Synthesis of tetrasubstituted unsymmetrical 1,4-enediones via copper-promoted autotandem catalysis and air as the oxidant

Article abstract of DOI:10.1021/jo400564f

An efficient procedure has been developed for the preparation of tetrasubstituted unsymmetrical 1,4-enediones via copper-promoted autotandem catalysis and air as the oxidant. Various N-nucleophiles are compatible with this reaction, such as morpholine, pi

Full text of DOI:10.1021/jo400564f

Article
pubs.acs.org/joc
Synthesis of Tetrasubstituted Unsymmetrical 1,4-Enediones via
Copper-Promoted Autotandem Catalysis and Air As the Oxidant
Yan Yang, Fan Ni, Wen-Ming Shu, Shang-Bo Yu, Meng Gao, and An-Xin Wu*
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, P. R.
China
S
* Supporting Information
ABSTRACT: An efficient procedure has been developed for the
preparation of tetrasubstituted unsymmetrical 1,4-enediones via copper-
promoted autotandem catalysis and air as the oxidant. Various N-
nucleophiles are compatible with this reaction, such as morpholine,
piperidine, pyrrolidine, arylamines, pyrazole, imidazole, benzimidazole, and
benzotriazole. This reaction also has significant advantages in easily
available substrates, atom economy, bond-forming efficiency, and environ-
mental benignity.
utilization efficiency and bring about significant benefits in
environmental and economic terms. Another important
strategy for sustainable chemistry is utilizing the “green” natural
resources as reagents. For example, air as a “green” natural
oxidant has extraordinary advantages in great abundance and
environmentally benign. Thus, using air as the oxidant has
emerged as a hot topic in synthetic chemistry.13
Inspired by the excellent sustainable synthetic methods based
on autotandem strategy or air as the oxidant, we wish to
develop a “green” synthetic method which could efficiently
combine their advantages. Recently, we have developed an
efficient method for the synthesis of 4H-pyrido[1,2-a]-
pyrimidin-4-ones via autotandem strategy.14 In this reaction,
tetrasubstituted 1,4-enediones were proved to be the key
reaction intermediates. Considering it is highly desirable to
develop an efficient and green synthetic method for preparation
of tetrasubstituted unsymmetrical 1,4-enediones, we would like
to report herein a general method for their efficient synthesis
via autotandem strategy and air as the oxidant (Scheme 1).
INTRODUCTION
■
The 1,4-enedione scaffold not only exists in many natural
products and pharmaceutical compounds (Figure 1)1 but also is
well-known as a versatile building block for the synthesis of
various heterocyles such as furans, pyrroles, thiophenes,
pyrazines, hydantoins, isoxazoles, and indolizines.2 Thus, the
development of efficient synthetic methods for 1,4-enediones
has attracted much attention of chemists. To date, several
methods have been established for their synthesis, such as
oxidation of furans3 or α,β-enones,4 oxidative coupling
reactions,5 oxidative rearrangement of 2-alkynyl alcohols,6
nucleophilic addition to dibenzoylacetylenes,7 Stille coupling,8
Wittig reaction,9 and other synthetic methods.10 However, as
far as we know, there was no general method in the literature
has been reported for the synthesis of tetrasubstituted
unsymmetrical 1,4-enediones, which have potentially broad
applications in pharmaceutical industry.
A significant goal of sustainable chemistry is maximizing
reaction efficiency and minimizing chemical wastes.11 One of
the important strategies to achieve this goal is an “auto-tandem
catalysis” strategy, which involves two or more mechanistically
different transformations promoted by a single catalyst.12 It is
noteworthy that this strategy could greatly improve the catalyst
Received: March 18, 2013
© XXXX American Chemical Society
A
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Figure 1. Natural products and pharmaceutical compounds containing 1,4-enedione motifs.
Scheme 1. Proposed Reaction Route
(−OMe) substituents all reacted efficiently to afford the
desired products in excellent yields (Table 2, entries 1−3; 89−
91%). However, a lower yield was obtained with strong
electron-withdrawing (−NO2) R1 substituent (entry 4; 62%).
To our satisfaction, good yields were obtained with sterically
hindered (1-naphthyl, 2-naphthyl), halogenated (−Cl, −Br,
−F) and heteroaryl R1 substituents (entries 5−11; 82−88%).
As to R2 or R3 substituents, the reaction proceeded well with
good to excellent yields for alkyloxy groups (OMe, OEt),
electron-neutral (−H), electron-donating (−OMe), electron-
withdrawing (−NO2), and halogenated (−F, −Cl) aryl
substituents (entries 12−16, 89%−93%). To our delight, the
structures of 3ka and (E)-3pa were further clearly confirmed by
X-ray diffraction (Figure 2).15
RESULTS AND DISCUSSION
■
We began the optimization process by using 1,4-enedione 1a
and pyrazole 2a as model substrates. To our delight, the desired
product 3aa was obtained in 79% yield when the reaction was
conducted in DMF with 0.05 equiv of Cu(OAc)2·H2O as
catalyst under air at 80 °C (Table 1, entry 1). Further
increasing the catalyst loading to 0.1 equiv, the yield was
improved to 84% (entry 2). We then screened different
solvents, and found that DMSO showed the best result and the
yield increased to 91% (entries 3−8). When the reaction was
carried out at lower or higher temperature (60 or 100 °C),
decreased yields were obtained (entries 9 and 10). We also
screened various copper catalysts, but no better results were
obtained (entries 11−18).
To further investigate the reactivity and stability of 1,4-
enediones 1 toward N-nucleophiles with strong basicity, we
chose morpholine 2b as a model substrate, which is a much
stronger base than pyrazole 2a. For R1 substituents, electron-
neutral (−H, −Me) and sterically hindered (1-naphthyl, 2-
naphthyl) substituents could smoothly afford the desired
products in good yields (Table 3, entries 1−4; 72−88%).
Fortunately, the structure of 3bb was further confirmed by X-
With this optimized result in hand, the generality of this
reaction was then explored. On the basis of our previously
reported cross-coupling reaction of 1,3-dicarbonyl compounds
and methyl ketones, a series of trisubstituted 1,4-enediones 1
were prepared.5a As shown in Table 2, the scope of 1,4-
enediones 1 was first examined with pyrazole 2a under the
optimized reaction conditions. As to R1 substituents, substrates
with electron-neutral (−H, −Me) and electron-donating
B
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a
heteroaryl (2-furyl, 3-thienyl) R1 substituents (entries 5−9;
76−85%).
Table 1. Optimization of the Reaction Condition
We next explored the scope of N-nucleophiles with 1,4-
enedione 1a as a model substrate (Table 4). For anilines,
moderate to good yields were obtained with electron-neutral
(−H), electron-donating (−OMe), electron-withdrawing
(−CN), halogenated (−I), and sterically hindered (2-naphthyl)
substituents (Table 4, 52%−79%; 3ac−ag). To our delight, N-
methylaniline and 6-methylpyridin-2-amine could also afford
their corresponding products in good yields (70−78%; 3ah−
ai). For aliphatic N-nucleophiles, good yields were obtained
with piperidine and pyrrolidine (72%−76%; 3aj−ak). For
aromatic N-heterocyles, high yields were obtained with
imidazole, benzimidazole, and benzotriazole (73%−87%; 3al−
an). Fortunately, the structures of 3ac, 3ai, 3aj, 3ak, 3am, and
3an were clearly confirmed by X-ray diffraction (Figure 2).15
To provide insight into the mechanism, a control experiment
was performed (Scheme 2). When the reaction of 1,4-enedione
1a and pyrazole 2a was conducted without Cu(OAc)2·H2O,
only aza-Michael addition product 4 was obtained in 49% yield
after 3 h, which could be further oxidized to product 3aa in
99% yield with Cu(OAc)2·H2O (0.1 equiv) as catalyst under
air. When the reaction of 1,4-enedione 1a and pyrazole 2a was
conducted with Cu(OAc)2·H2O (0.1 equiv) under argon, a
mixture of products 3aa (10%) and 4 (55%) were obtained.
Compared with the previous results that product 3aa could be
obtained in 91% yield directly from 1a and 2a (Table 2, entry
1), a possible reaction mechanism is proposed in Scheme 3
with 1,4-enedione 1a and pyrazole 2a as an example. Initially,
the pyrazole 2a underwent aza-Michael addition with 1a to
form intermediate A under copper catalysis,16 which could
afford the product 3aa by copper catalyzed aerobic oxidative
dehydrogenation (Scheme 3).17 Because the reaction was
conducted under air atmosphere, the formed Cu(I) species in
this reaction could be oxidized to Cu(II) by air, so that the
reaction can be catalytic in copper catalyst with air as terminal
oxidant.
b
entry
catalyst (equiv)
solvent
DMF
temp (°C) yield (%)
1
Cu(OAc)2·H2O (0.05)
Cu(OAc)2·H2O (0.1)
Cu(OAc)2·H2O (0.1)
Cu(OAc)2·H2O (0.1)
Cu(OAc)2·H2O (0.1)
Cu(OAc)2·H2O (0.1)
Cu(OAc)2·H2O (0.1)
Cu(OAc)2·H2O (0.1)
Cu(OAc)2·H2O (0.1)
Cu(OAc)2·H2O (0.1)
CuBr2 (0.1)
80
80
80
80
78
80
80
80
60
100
80
80
80
80
80
80
80
80
79
84
91
83
47
72
36
82
79
85
48
47
86
43
83
75
76
82
2
DMF
3
DMSO
CH3CN
C2H5OH
CH3NO2
AcOH
4
5
6
7
8
1,4-dioxane
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
9
10
11
12
13
14
15
16
17
18
CuCl2 (0.1)
CuSO4 (0.1)
CuO (0.1)
Cu2O (0.1)
CuCl (0.1)
CuBr (0.1)
CuI (0.1)
a
Reaction conditions: 1a (0.5 mmol), 2a (0.55 mmol), solvent (2.5
mL), cat. (0.025 or 0.05 mmol), air (1 atm), 3 h. Isolated yields.
b
Table 2. Scope of Unsymmetrical 1,4-Enediones 1 with
a
Pyrazole 2a
CONCLUSION
b
■
entry
1
R1
R2
R3
Ph
3
yield (%)
In conclusion, we have developed a practical and efficient
protocol for the synthesis of tetrasubstituted unsymmetrical
1,4-enediones via copper-catalyzed tandem aza-Michael addi-
tion/aerobic oxidative dehydrogenation. This reaction has
significant advantages in that it uses air as the oxidant and
has a wide substrate scope and mild reaction conditions.
1
1a
1b
1c
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3aa
3ba
3ca
3da
3ea
3fa
91
90
89
62
85
88
83
84
82
87
86
93
90
89
92
91
2
4-Me-Ph
4-OMe-Ph
4-NO2−Ph
1-naphthyl
2-naphthyl
4-Cl-Ph
4-Br-Ph
4-F-Ph
2-furyl
3-thienyl
Ph
Ph
3
Ph
4
Ph
5
Ph
6
Ph
7
1g
1h
1i
Ph
3ga
3ha
3ia
EXPERIMENTAL SECTION
8
Ph
■
9
Ph
1. General Methods. All reagents were purchased from
commercial suppliers and used without further purification. 1,4-
Enediones 1 were prepared according to our previous reports.5a IR
spectra were recorded on an infrared spectrometer as KBr pellets with
10
11
1j
Ph
3ja
1k
1l
Ph
3ka
3la
c
12
OEt
OEt
OEt
OMe
OMe
1
absorption in cm−1. H spectra were recorded in CDCl3 on 400/600
c
13
1m
1n
1o
1p
Ph
4-OMe-Ph
4-NO2−Ph
4-Cl-Ph
3ma
3na
3oa
3pa
MHz NMR spectrometers and resonances (δ) are given in ppm
relative to tetramethylsilane. Data are reported as follows: chemical
shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, bs
= broad singlet), coupling constants (Hz), and integration. 13C spectra
were recorded in CDCl3 on 100/150 MHz spectrometers and
resonances (δ) are given in ppm relative to the center line of a triplet
at 77.0 ppm of chloroform-d. HRMS were obtained by a Fourier
transform ion cyclotron resonance (FTICR) mass spectrometry.
Melting points were determined without correction. The structures of
3ka, (E)-3pa, 3pa, 3bb, 3ac, 3ai, 3aj, 3ak, 3am, and 3an were
confirmed by X-ray diffraction. Column chromatography was
performed on silica gel (200−300 mesh).
c
14
c
Ph
15
Ph
c
16
Ph
4-F-Ph
a
Reaction was carried out using 1 (1.0 mmol), 2a (1.1 mmol), and
Cu(OAc)2·H2O (0.1 mmol) in 5 mL of DMSO at 80 °C under air (1
atm). Isolated yields. A mixture of E/Z-isomers was obtained.
b
c
ray diffraction (Figure 2).15 It is noteworthy that good yields
were also obtained with halogenated (−Cl, −Br, −F) and
C
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Figure 2. X-ray structures of compound 3.
chromatography on silica gel (eluent: CH2Cl2/petroleum ether = 5:1)
to afford a white solid 3aa (370 mg, 91%).
Table 3. Scope of Unsymmetrical 1,4-Enediones 1 with
Morpholine 2b
a
3. Experimental Procedure for Preparation of 4 from 1,4-
Enedione 1a and Pyrazole 2a without Copper Catalyst. A
mixture of 2-benzoyl-1,4-diphenylbut-2-ene-1,4-dione 1a (340 mg, 1.0
mmol) and pyrazole 2a (75 mg, 1.1 mmol) in 5 mL of DMSO was
stirred at 80 °C for 3 h under air (1 atm). After the reaction
completed, the mixture was diluted with water and extracted with
CH2Cl2 (3 × 30 mL), and the combined organic extracts were then
washed with brine. After drying over Na2SO4 and concentration under
reduced pressure, the crude product was purified by column
chromatography on silica gel (eluent: CH2Cl2/petroleum ether =
5:1) to afford a white solid 4 (200 mg, 49%).
4. Experimental Procedure for Preparation of 3aa from
Compound 4. A mixture of 2-benzoyl-1,4-diphenyl-3-(1H-pyrazol-1-
yl)butane-1,4-dione 4 (102 mg, 0.25 mmol) and Cu(OAc)2·H2O (5
mg, 0.025 mmol) in 3 mL of DMSO was stirred at 80 °C for 2 h under
air. After the reaction was complete, the mixture was diluted with
water and extracted with CH2Cl2 (3 × 30 mL), and the combined
organic extracts were then washed with brine. After drying over
Na2SO4 and evaporation, the crude product was purified by column
chromatography on silica gel (eluent: CH2Cl2/petroleum ether = 5:1)
to afford a white solid 3aa (101 mg, 99% yield).
b
entry
1
R1
3
yield (%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
Ph
3ab
3bb
3cb
3db
3eb
3fb
86
88
78
72
76
79
81
85
78
4-Me-Ph
1-naphthyl
2-naphthyl
4-Cl-Ph
4-Br-Ph
4-F-Ph
1g
1h
1i
3gb
3hb
3ib
2-furyl
3-thienyl
a
Reaction was carried out using 1 (1.0 mmol), 2b (1.1 mmol) and
Cu(OAc)2·H2O (0.1 mmol) in 5 mL DMSO at 80 °C under air.
b
Isolated yields.
5. Experimental Procedure for Reaction of 1,4-Enedione 1a
and Pyrazole 2a under Argon. A mixture of 2-benzoyl-1,4-
diphenylbut-2-ene-1,4-dione 1a (340 mg, 1.0 mmol), pyrazole 2a (75
mg, 1.1 mmol), and Cu(OAc)2·H2O (20 mg, 0.1 mmol) in 5 mL of
DMSO was stirred at 80 °C for 3 h under argon. After the reaction
completed, the mixture was diluted with water and extracted with
CH2Cl2 (3 × 30 mL), and the combined organic extracts were then
washed with brine. After drying over Na2SO4 and concentration under
reduced pressure, the crude product was purified by column
chromatography on silica gel (eluent: CH2Cl2/petroleum ether =
5:1) to afford an inseparable mixture of 3aa and 4 (265 mg). The
molar ratio of 3aa/4 was determined by 1H NMR and was found to be
2. General Experimental Procedures for Preparation of
Tetrasubstituted 1,4-Enediones 3 from 1,4-Enediones 1 and N-
Nucleophiles 2 (3aa as an Example). A mixture of 2-benzoyl-1,4-
diphenylbut-2-ene-1,4-dione 1a (340 mg, 1.0 mmol), pyrazole 2a (75
mg, 1.1 mmol), and Cu(OAc)2·H2O (20 mg, 0.1 mmol) in 5 mL of
DMSO was stirred at 80 °C for 3 h under air (1 atm). After the
reaction completed, the mixture was diluted with water and extracted
with CH2Cl2 (3 × 30 mL), and the combined organic extracts were
then washed with brine. After drying over Na2SO4 and concentration
under reduced pressure, the crude product was purified by column
D
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a
Table 4. Scope of Different N-Nucleophiles 2
a
Reaction was carried out using 1a (1.0 mmol), 2 (1.1 mmol), and Cu(OAc)2·H2O (0.1 mmol) in 5 mL of DMSO at 80 °C under air (1 atm).
Cu(OAc)2·H2O (0.2 mmol) was used. 2 (2.5 mmol) and Cu(OAc)2·H2O (0.2 mmol) were used. Cu(OAc)2·H2O (0.2 mmol) was used at 100
b
c
d
°C.
15:85. Their respective yields were thus calculated to be 3aa (41 mg,
10%) and 4 (224 mg, 55%).
109.3, 55.5; IR (KBr) 1660, 1598, 1258, 1175 cm−1; HRMS (ESI) m/z
[M + H]+ calcd for C27H21N2O4 437.1496, found 437.1497.
Spectroscopic Data. 2-Benzoyl-1,4-diphenyl-3-(1H-pyrazol-1-
yl)but-2-ene-1,4-dione (3aa): yield 91% (370 mg); white solid; mp
123.4−124.3 °C; 1H NMR (CDCl3, 400 MHz) δ 7.99 (d, J = 6.8 Hz,
2H), 7.81−7.79 (m, 4H), 7.55−7.49 (m, 2H), 7.45−7.36 (m, 7H),
7.28 (t, J = 8.4 Hz, 2H), 6.18 (t, J = 2.0 Hz, 1H); 13C NMR (CDCl3,
100 MHz) δ 191.9, 191.7, 189.1, 143.3, 142.9, 136.6 136.2, 135.3,
134.1, 133.7, 133.4, 130.6, 129.4, 129.1, 129.0, 128.8, 128.7, 128.4,
109.4; IR (KBr) 1675, 1647, 1265 cm−1; HRMS (ESI) m/z [M + H]+
calcd for C26H19N2O3 407.1390, found 407.1394.
2-Benzoyl-4-(4-nitrophenyl)-1-phenyl-3-(1H-pyrazol-1-yl)but-2-
ene-1,4-dione (3da): yield 62% (280 mg); white solid; mp 167.3−
1
168.2 °C; H NMR (CDCl3, 600 MHz) δ 8.25 (d, J = 7.8 Hz, 2H),
8.00−7.96 (m, 4H), 7.78 (d, J = 7.8 Hz, 2H), 7.56 (t, J = 7.2 Hz, 1H),
7.49−7.42 (m, 5H), 7.32 (t, J = 7.2 Hz, 2H), 6.22 (bs, 1H); 13C NMR
(CDCl3, 100 MHz) δ 191.6, 191.5, 187.5, 150.4, 143.5, 143.3, 139.8,
136.1, 135.6, 134.2, 133.8, 130.6, 129.8, 129.2, 129.0, 128.6, 124.0,
110.0; IR (KBr) 1677, 1654, 1599, 1527, 1349, 1255 cm−1; HRMS
(ESI) m/z [M + H]+ calcd for C26H18N3O5 452.1241, found 452.1239.
2-Benzoyl-4-(naphthalen-1-yl)-1-phenyl-3-(1H-pyrazol-1-yl)but-
2-ene-1,4-dione (3ea): yield 85% (388 mg); light yellow solid; mp
2-Benzoyl-1-phenyl-3-(1H-pyrazol-1-yl)-4-(p-tolyl)but-2-ene-1,4-
dione (3ba): yield 90% (378 mg); white solid; mp 127.6−128.3 °C;
1H NMR (CDCl3, 600 MHz) δ 7.99 (d, J = 7.8 Hz, 2H), 7.81 (d, J =
1
134.9−136.2 °C; H NMR (CDCl3, 600 MHz) δ 8.72 (d, J = 8.4 Hz,
1H), 8.03−8.00 (m, 3H), 7.96 (d, J = 7.8 Hz, 1H), 7.82 (d, J = 8.4 Hz,
1H), 7.77 (d, J = 7.8 Hz, 2H), 7.59 (t, J = 7.8 Hz, 1H), 7.54−7.50 (m,
2H), 7.42−7.37 (m, 6H), 7.26−7.23 (m, 2H), 6.14 (bs, 1H); 13C
NMR (CDCl3, 100 MHz) δ 191.8, 191.6, 190.7, 143.6, 142.6, 136.4,
136.0, 134.8, 133.7, 133.5, 132.2, 131.8, 130.7, 130.6, 129.3, 129.0,
128.8, 128.7, 128.4, 126.8, 125.2, 124.2, 109.1; IR (KBr) 1672, 1645,
1597, 1245 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C30H21N2O3
457.1547, found 457.1548.
2-Benzoyl-4-(naphthalen-2-yl)-1-phenyl-3-(1H-pyrazol-1-yl)but-
2-ene-1,4-dione (3fa): yield 88% (402 mg); light yellow solid; mp
139.5−141.0 °C; 1H NMR (CDCl3, 600 MHz) δ 8.33 (s, 1H), 8.03 (d,
J = 7.8 Hz, 2H), 7.87−7.80 (m, 6H), 7.59 (t, J = 7.8 Hz, 1H), 7.52 (t, J
= 7.2 Hz, 2H), 7.43−7.39 (m, 5H), 7.27−7.25 (m, 2H), 6.18 (bs, 1H);
13C NMR (CDCl3, 100 MHz) δ 192.0, 191.7, 189.1, 143.6, 142.9,
7.8 Hz, 2H), 7.70 (d, J = 7.2 Hz, 2H), 7.51 (t, J = 7.8 Hz, 1H), 7.45−
7.37 (m, 5H), 7.29 (t, J = 7.8 Hz, 2H), 7.19 (d, J = 7.8 Hz, 2H), 6.18
(bs, 1H), 2.37 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 192.0, 191.7,
188.7, 145.5, 143.5, 142.8, 136.5, 136.2, 133.6, 133.4, 133.2, 132.7,
130.5, 129.5, 129.33, 129.27, 128.9, 128.7, 128.3, 109.4, 21.8; IR (KBr)
1668, 1652, 1601, 1263 cm−1; HRMS (ESI) m/z [M + H]+ calcd for
C27H21N2O3 421.1547, found 421.1549.
2-Benzoyl-4-(4-methoxyphenyl)-1-phenyl-3-(1H-pyrazol-1-yl)-
but-2-ene-1,4-dione (3ca): yield 89% (388 mg); light yellow solid;
1
mp 104.9−106.3 °C; H NMR (CDCl3, 600 MHz) δ 7.99 (d, J = 7.8
Hz, 2H), 7.82 (d, J = 7.8 Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.50 (t, J =
7.2 Hz, 1H), 7.45−7.38 (m, 5H), 7.29 (t, J = 7.8 Hz, 2H), 6.86 (d, J =
8.4 Hz, 2H), 6.19 (bs, 1H), 3.83 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 192.0, 191.8, 187.6, 164.4, 143.4, 142.8, 136.5, 136.2, 133.5,
133.4, 133.0, 131.7, 130.5, 129.4, 128.9, 128.7, 128.33, 128.27, 114.1,
136.5, 136.1, 135.9, 133.7, 133.4, 132.6, 132.2, 131.8, 130.6, 129.8,
E
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Scheme 2. Control Experiment
Scheme 3. Proposed Reaction Mechanism
129.3, 129.2, 128.92, 128.86, 128.7, 128.4, 127.7, 127.0, 123.8, 109.5;
IR (KBr) 1655, 1279 cm−1; HRMS (ESI) m/z [M + H]+ calcd for
C30H21N2O3 457.1547, found 457.1547.
(t, J = 7.2 Hz, 2H), 7.07 (t, J = 7.8 Hz, 2H), 6.21 (bs, 1H); 13C NMR
(CDCl3, 100 MHz) δ 191.8, 191.7, 187.6, 167.4, 164.8, 143.4, 143.1,
136.4, 135.9, 133.8, 133.6, 131.9, 131.8, 131.7, 130.5, 129.3, 128.9,
128.8, 128.4, 116.3, 116.1, 109.6; IR (KBr) 1670, 1644, 1618, 1597,
1264, 1240 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C26H18FN2O3
425.1296, found 425.1297.
2-Benzoyl-4-(4-chlorophenyl)-1-phenyl-3-(1H-pyrazol-1-yl)but-2-
ene-1,4-dione (3ga): yield 83% (366 mg); white solid; mp 115.1−
1
116.4 °C; H NMR (CDCl3, 600 MHz) δ 7.98 (d, J = 7.8 Hz, 2H),
7.80 (d, J = 7.8 Hz, 2H), 7.73 (d, J = 7.8 Hz, 2H), 7.51 (t, J = 7.2 Hz,
1H), 7.45−7.35 (m, 7H), 7.29 (t, J = 7.2 Hz, 2H), 6.19 (bs, 1H); 13C
NMR (CDCl3, 100 MHz) δ 191.7, 191.6, 187.9, 143.3, 143.1, 140.7,
136.3, 135.9, 133.8, 133.6, 133.5, 130.5, 130.4, 129.3, 129.2, 128.9,
128.8, 128.5, 109.6; IR (KBr) 1674, 1655, 1586, 1280, 1257 cm−1;
HRMS (ESI) m/z [M + H]+ calcd for C26H18ClN2O3 441.1001, found
441.1001.
2-Benzoyl-4-(furan-2-yl)-1-phenyl-3-(1H-pyrazol-1-yl)but-2-ene-
1,4-dione (3ja): yield 87% (345 mg); white solid; mp 133.1−134.0
°C; 1H NMR (CDCl3, 600 MHz) δ 7.98 (d, J = 7.8 Hz, 2H), 7.89 (d, J
= 7.8 Hz, 2H), 7.54−7.47 (m, 5H), 7.40 (t, J = 7.2 Hz, 2H), 7.34 (t, J
= 7.2 Hz, 2H), 6.87 (bs, 1H), 6.47 (bs, 1H), 6.29 (bs, 1H); 13C NMR
(CDCl3, 100 MHz) δ 191.7, 191.3, 175.5, 151.1, 148.3, 140.5, 136.3,
135.7, 135.6, 133.8, 133.6, 129.3, 129.1, 128.7, 128.4, 121.0, 113.0; IR
(KBr) 1649, 1599, 1455, 1393, 1281 cm−1; HRMS (ESI) m/z [M +
H]+ calcd for C24H17N2O4 397.1183, found 397.1183.
2-Benzoyl-4-(4-bromophenyl)-1-phenyl-3-(1H-pyrazol-1-yl)but-2-
ene-1,4-dione (3ha): yield 84% (408 mg); white solid; mp 140.0−
1
141.8 °C; H NMR (CDCl3, 600 MHz) δ 7.98 (d, J = 7.2 Hz, 2H),
2-Benzoyl-1-phenyl-3-(1H-pyrazol-1-yl)-4-(thiophene-3-yl)but-2-
ene-1,4-dione (3ka): yield 86% (355 mg); white solid; mp 78.0−80.1
°C; 1H NMR (CDCl3, 600 MHz) δ 7.97 (d, J = 7.8 Hz, 2H), 7.87 (d, J
= 7.2 Hz, 2H), 7.77 (s, 1H), 7.52−7.46 (m, 4H), 7.40 (t, J = 7.8 Hz,
2H), 7.32 (t, J = 7.8 Hz, 2H), 7.26−7.23 (m, 1H), 6.25 (bs, 1H), 5.30
(bs, 1H); 13C NMR (CDCl3, 100 MHz) δ 191.8, 191.5, 182.1, 142.2,
139.9, 136.3, 135.8, 135.2, 135.1, 133.7, 133.6, 129.4, 129.0, 128.7,
128.4, 126.9, 126.8; IR (KBr) 1651, 1597, 1601, 1417, 1252 cm−1;
HRMS (ESI) m/z [M + H]+ calcd for C24H17N2O3S 413.0954, found
413.0956.
7.79 (d, J = 7.8 Hz, 2H), 7.66 (d, J = 7.8 Hz, 2H), 7.55−7.51 (m, 3H),
7.47−7.38 (m, 5H), 7.31 (t, J = 7.8 Hz, 2H), 6.20 (bs, 1H); 13C NMR
(CDCl3, 100 MHz) δ 191.8, 191.6, 188.2, 143.4, 143.2, 136.3, 135.9,
134.0, 133.9, 133.6, 132.2, 130.4, 129.6, 129.3, 128.9, 128.8, 128.5,
109.7; IR (KBr) 1677, 1642, 1585, 1261 cm−1; HRMS (ESI) m/z [M
+ H]+ calcd for C26H18BrN2O3 485.0495, found 485.0495.
2-Benzoyl-4-(4-fluorophenyl)-1-phenyl-3-(1H-pyrazol-1-yl)but-2-
ene-1,4-dione (3ia): yield 82% (348 mg); white solid; mp 114.2−
1
116.4 °C; H NMR (CDCl3, 600 MHz) δ 7.98 (d, J = 7.2 Hz, 2H),
7.84−7.80 (m, 4H), 7.52 (t, J = 7.2 Hz, 1H), 7.47−7.39 (m, 5H), 7.30
F
dx.doi.org/10.1021/jo400564f | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Ethyl 2-benzoyl-4-oxo-4-phenyl-3-(1H-pyrazol-1-yl)but-2-enoate
(3la): yield 93% (348 mg); white solid; (E:Z = 53:47). (E)-Isomer:
white solid (yield 42%, recrystallized from ethanol/hexane); mp
140.1−142.4 °C; 1H NMR (CDCl3, 600 MHz) δ 8.07 (d, J = 7.8 Hz,
2H), 8.02 (d, J = 7.8 Hz, 2H), 7.64 (t, J = 7.2 Hz, 1H), 7.58−7.51 (m,
3H), 7.47−7.45 (m, 3H), 7.38 (bs, 1H), 6.24 (bs, 1H), 4.05−4.02 (m,
2H), 0.97 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 191.1,
189.0, 163.8, 144.5, 143.5, 136.6, 135.0, 134.4, 133.3, 130.2, 129.1,
128.9, 128.7, 128.6, 118.7, 109.6, 61.9, 13.5; IR (KBr) 1710, 1681,
1624, 1245 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C22H19N2O4
375.1339, found 375.1339.
Ethyl 2-(4-methoxybenzoyl)-4-oxo-4-phenyl-3-(1H-pyrazol-1-yl)-
but-2-enoate (3ma): yield 90% (364 mg); (E:Z = 47:53); white solid;
mp 87.6−89.9 °C; 1H NMR (CDCl3, 600 MHz) δ 8.04 (d, J = 7.8 Hz,
2H), 8.00 (d, J = 7.8 Hz, 2H), 7.84 (d, J = 7.8 Hz, 2H), 7.78 (d, J = 8.4
Hz, 2H), 7.70 (bs, 1H), 7.62 (t, J = 7.8 Hz, 2H), 7.52−7.49 (m, 4H),
7.44 (bs, 1H), 7.37 (t, J = 7.2 Hz, 2H), 6.94 (d, J = 7.8 Hz, 2H), 6.87
(d, J = 8.4 Hz, 2H), 6.40 (bs, 1H), 6.24 (bs, 1H), 4.25−4.22 (m, 2H),
4.06−4.02 (m, 2H), 3.86 (s, 3H), 3.85 (s, 3H), 1.15 (t, J = 7.2 Hz,
3H), 0.98 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 189.7,
189.1, 188.9, 188.5, 164.5, 163.9, 163.8, 144.4, 143.6, 143.4, 142.8,
135.1, 135.0, 134.2, 134.0, 131.3, 131.1, 130.5, 130.2, 129.5, 129.4,
129.0, 128.8, 128.6, 127.2, 119.0, 113.9, 113.7, 109.4, 109.1, 62.0, 61.8,
55.4, 13.7, 13.4; IR (KBr) 1708, 1600, 1255 cm−1; HRMS (ESI) m/z
[M + H]+ calcd for C23H21N2O5 405.1445, found 405.1446.
Ethyl 2-(4-nitrobenzoyl)-4-oxo-4-phenyl-3-(1H-pyrazol-1-yl)but-
2-enoate (3na): yield 89% (373 mg); white solid; (E:Z = 87:13);
(E)-isomer: white solid (yield 70%, recrystallized from ethanol/
hexane); mp 140.6−141.8 °C; 1H NMR (CDCl3, 600 MHz) δ 8.32 (d,
J = 8.4 Hz, 2H), 8.17 (d, J = 7.8 Hz, 2H), 8.07 (d, J = 7.8 Hz, 2H),
7.68 (t, J = 7.8 Hz, 1H), 7.56 (t, J = 7.8 Hz, 2H), 7.45 (bs, 1H), 7.33
(bs, 1H), 6.28 (bs, 1H), 4.07−4.03 (m, 2H), 0.98 (t, J = 7.2 Hz, 3H);
13C NMR (CDCl3, 100 MHz) δ 189.0, 188.7, 163.4, 150.1, 144.9,
143.8, 141.7, 134.9, 134.7, 130.3, 129.5, 129.3, 129.0, 123.8, 117.0,
110.1, 62.2, 13.5; IR (KBr) 1717, 1684, 1613, 1526, 1244, 1195 cm−1;
HRMS (ESI) m/z [M + H]+ calcd for C22H18N3O6: 420.1190; found:
420.1192.
Methyl 2-(4-chlorobenzoyl)-4-oxo-4-phenyl-3-(1H-pyrazol-1-yl)-
but-2-enoate (3oa). Yield 92% (363 mg); white solid; (E:Z =
63:37). (E)-Isomer: white solid (yield 49%, recrystallized from
ethanol/hexane); mp 165.7−167.4 °C; 1H NMR (CDCl3, 600
MHz) δ 8.05 (d, J = 7.8 Hz, 2H), 7.95 (d, J = 7.8 Hz, 2H), 7.66 (t,
J = 7.8 Hz, 1H), 7.53 (t, J = 7.8 Hz, 2H), 7.47 (bs, 1H), 7.44 (d, J = 7.2
Hz, 2H), 7.36 (bs, 1H), 6.26 (bs, 1H), 3.58 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 189.7, 189.0, 164.2, 145.0, 143.7, 139.7, 135.1,
134.7, 134.6, 130.2, 130.1, 129.2, 129.0, 128.9, 117.3, 109.8, 52.9; IR
(KBr) 1716, 1681, 1622, 1250 cm−1; HRMS (ESI) m/z [M + H]+
calcd for C21H16ClN2O4 395.0793, found 395.0796.
Methyl 2-(4-fluorobenzoyl)-4-oxo-4-phenyl-3-(1H-pyrazol-1-yl)-
but-2-enoate (3pa): yield 91% (344 mg); white solid; (E:Z =
71:29). (E)-Isomer: white solid (yield 56%, recrystallized from
ethanol/hexane); mp 148.4−149.5 °C; 1H NMR (CDCl3, 600
MHz) δ 8.06−8.03 (m, 4H), 7.65 (t, J = 7.2 Hz, 1H), 7.53 (t, J =
7.2 Hz, 2H), 7.48 (bs, 1H), 7.37 (bs, 1H), 7.13 (t, J = 8.4 Hz, 2H),
6.26 (bs, 1H), 3.59 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 189.4,
189.0, 167.0, 164.5, 164.3, 145.0 143.7, 134.7, 134.6, 133.1, 131.4,
131.3, 130.3, 129.2, 128.9, 117.5, 116.0, 115.8, 109.8, 52.8; IR (KBr)
1715, 1683, 1624, 1598, 1247 cm−1; HRMS (ESI) m/z [M + H]+ calcd
for C21H16FN2O4 379.1089, found 379.1090.
100 MHz) δ 194.4, 165.6, 145.0, 133.7, 131.6, 129.4, 128.8, 128.7,
127.8, 65.9, 51.7, 21.7,; IR (KBr) 1599, 1508, 1294, 1261 cm−1;
HRMS (ESI) m/z [M + H]+ calcd for C28H26NO4 440.1856, found
440.1855.
2-Benzoyl-3-morpholino-4-(naphthalen-1-yl)-1-phenylbut-2-
ene-1,4-dione (3cb): yield 78% (371 mg); yellow solid; mp 194.1−
1
195.5 °C; H NMR (CDCl3, 400 MHz) δ 9.06 (d, J = 8.8 Hz, 1H),
8.12 (d, J = 6.0 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.0 Hz,
1H), 7.67 (t, J = 7.2 Hz, 2H), 7.54−7.48 (m, 3H), 7.26−7.17 (m, 8H),
3.76 (bs, 4H), 3.35 (bs, 4H); 13C NMR (CDCl3, 100 MHz) δ 194.0,
168.9, 134.7, 133.9, 132.7, 130.8, 128.9, 128.4, 128.0, 126.8, 126.2,
123.9, 66.2, 52.5; IR (KBr) 1595, 1569, 1507, 1285, 1240 cm−1;
HRMS (ESI) m/z [M + H]+ calcd for C31H26NO4 476.1856, found
476.1855.
2-Benzoyl-3-morpholino-4-(naphthalen-2-yl)-1-phenylbut-2-
ene-1,4-dione (3db): yield 72% (342 mg); yellow solid; mp 168.0−
169.4 °C; 1H NMR (CDCl3, 400 MHz) δ 8.65 (s, 1H), 8.11 (d, J = 8.4
Hz, 1H), 7.99 (d, J = 7.6 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.81 (d, J
= 7.6 Hz, 1H), 7.56−7.12 (m, 12H), 3.67 (bs, 4H), 3.25 (bs, 4H); 13C
NMR (CDCl3, 100 MHz) δ 194.3, 165.6, 135.8, 132.2, 130.6, 129.6,
128.9, 128.8, 127.9, 127.7, 126.9, 123.9, 66.0, 51.8; IR (KBr) 1595,
1572, 1506, 1263, 1237 cm−1; HRMS (ESI) m/z [M + H]+ calcd for
C31H26NO4 476.1856, found: 476.1854.
2-Benzoyl-4-(4-chlorophenyl)-3-morpholino-1-phenylbut-2-ene-
1,4-dione (3eb): yield 76% (349 mg); yellow solid; mp 105.1−106.9
1
°C; H NMR (CDCl3, 400 MHz) δ 8.01 (d, J = 7.6 Hz, 2H), 7.45−
7.16 (m, 12H), 3.68 (bs, 4H), 3.22 (bs, 4H); 13C NMR (CDCl3, 100
MHz) δ 194.1, 164.8, 140.2, 139.7, 134.5, 132.2, 129.8, 129.2, 128.9,
128.1, 114.6, 66.0, 51.9; IR (KBr) 1513, 1249 cm−1; HRMS (ESI) m/z
[M + H]+ calcd for C27H23ClNO4 460.1310, found 460.1309.
2-Benzoyl-4-(4-bromophenyl)-3-morpholino-1-phenylbut-2-ene-
1,4-dione (3fb): yield 79% (397 mg); yellow solid; mp 111.3−113.3
1
°C; H NMR (CDCl3, 600 MHz) δ 7.96 (d, J = 7.8 Hz, 2H), 7.68−
7.07 (m, 12H), 3.67 (bs, 4H), 3.19 (bs, 4H); 13C NMR (CDCl3, 100
MHz) δ 194.2, 191.5, 164.8, 139.8, 134.8, 132.1, 130.0, 129.2, 128.0,
114.6, 65.9, 51.7; IR (KBr) 1584, 1513, 1250 cm−1; HRMS (ESI) m/z
[M + H]+ calcd for C27H23BrNO4 504.0805, found 504.0803.
2-Benzoyl-4-(4-fluorophenyl)-3-morpholino-1-phenylbut-2-ene-
1,4-dione (3gb): yield 81% (359 mg); yellow solid; mp 158.7−160.2
1
°C; H NMR (CDCl3, 400 MHz) δ 8.14−8.10 (m, 2H), 7.45−7.11
(m, 12H), 3.68 (m, 4H), 3.21 (m, 4H); 13C NMR (CDCl3, 100 MHz)
δ 194.3, 167.3, 164.7, 139.9, 132.6, 131.4, 131.3, 128.8, 128.7, 128.0,
116.2, 116.0, 114.7, 66.0, 51.8; IR (KBr) 1595, 1507, 1246 cm−1;
HRMS (ESI) m/z [M + H]+ calcd for C27H23FNO4 444.1606, found
444.1605.
2-Benzoyl-4-(furan-2-yl)-3-morpholino-1-phenylbut-2-ene-1,4-
dione (3hb): yield 85% (353 mg); yellow solid; mp 192.9−194.6 °C;
1H NMR (CDCl3, 400 MHz) δ 7.59−7.17 (m, 12H), 6.50 (bs, 1H),
3.71 (m, 4H), 3.17 (m, 4H); 13C NMR (CDCl3, 100 MHz) δ 194.4,
179.7, 163.4, 152.2, 147.7, 139.9, 131.6, 128.7, 127.9, 119.8, 115.4,
112.6, 66.0, 51.8; IR (KBr) 1665, 1506, 1453, 1289, 1234 cm−1;
HRMS (ESI) m/z [M + H]+ calcd for C25H22NO5 416.1492, found
416.1492.
2-Benzoyl-3-morpholino-1-phenyl-4-(thiophene-3-yl)but-2-ene-
1,4-dione (3ib): yield 78% (336 mg); yellow solid; mp 207.9−208.6
°C; 1H NMR (CDCl3, 400 MHz) δ 8.30 (s, 1H), 7.61−7.53 (m, 5H),
7.31−7.14 (m, 7H), 3.73 (bs, 4H), 3.23 (bs, 4H); 13C NMR (CDCl3,
100 MHz) δ 194.3, 165.9, 141.2, 139.9, 134.0, 131.9, 128.9, 128.0,
127.2, 126.9, 114.6, 66.1, 51.9; IR (KBr) 1668, 1505, 1252 cm−1;
HRMS (ESI) m/z [M + H]+ calcd for C25H22NO4S 432.1264, found
432.1263.
2-Benzoyl-3-morpholino-1,4-diphenylbut-2-ene-1,4-dione (3ab):
1
yield 86% (366 mg); yellow solid; mp 199.5−200.2 °C; H NMR
2-Benzoyl-1,4-diphenyl-3-(phenylamino)but-2-ene-1,4-dione
1
(CDCl3, 400 MHz) δ 8.08 (d, J = 7.6 Hz, 2H), 7.56−7.13 (m, 13H),
3.66 (bs, 4H), 3.21 (bs, 4H); 13C NMR (CDCl3, 100 MHz) δ 194.3,
192.6, 165.5, 140.1, 136.1, 133.9, 131.5, 128.8, 127.9, 114.6, 65.9, 51.8;
IR (KBr) 1630, 1593, 1505, 1413, 1259, 1120 cm−1; HRMS (ESI) m/z
[M + H]+ calcd for C27H24NO4 426.1700, found 426.1699.
(3ac): yield 78% (336 mg); Yellow solid; mp 180.2−181.1 °C; H
NMR (CDCl3, 400 MHz) δ 13.36 (s, 1H), 7.88 (d, J = 7.6 Hz, 2H),
7.51−7.45 (m, 6H), 7.36 (t, J = 7.6 Hz, 2H), 7.17−7.05 (m, 10H); 13C
NMR (CDCl3, 100 MHz) δ 196.1, 195.0, 190.8, 164.7, 141.3, 140.1,
136.6, 135.4, 133.8, 131.5, 130.9, 129.10, 129.07, 128.7, 128.5, 128.1,
127.8, 127.6, 127.1, 124.8, 110.7; IR (KBr) 1532, 1598 cm−1; HRMS
(ESI) m/z [M + H]+ calcd for C29H22NO3 432.1594, found 432.1595.
2-Benzoyl-3-((4-methoxyphenyl)amino)-1,4-diphenylbut-2-ene-
1,4-dione (3ad): yield 79% (365 mg); yellow solid; mp 179.8−181.3
2-Benzoyl-3-morpholino-1-phenyl-4-(p-tolyl)but-2-ene-1,4-dione
1
(3bb): yYield 88% (386 mg); yellow solid; mp 114.3−116.8 °C; H
NMR (CDCl3, 400 MHz) δ 7.99 (d, J = 7.6 Hz, 2H), 7.50−7.12 (m,
12H), 3.66 (bs, 4H), 3.20 (m, 4H), 2,36 (s, 3H); 13C NMR (CDCl3,
G
dx.doi.org/10.1021/jo400564f | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
°C; 1H NMR (CDCl3, 600 MHz) δ 13.26 (s, 1H), 7.89 (d, J = 7.8 Hz,
2H), 7.49−7.47 (m, 3H), 7.44 (d, J = 7.8 Hz, 2H), 7.38 (t, J = 7.8 Hz,
2H), 7.16−7.15 (m, 2H), 7.10 (t, J = 7.2 Hz, 2H), 7.07−7.03 (m, 4H),
6.68 (d, J = 8.4 Hz, 2H), 3.70 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
196.1, 195.0, 190.9, 165.6, 158.4, 141.3, 140.2, 135.3, 133.8, 131.4,
130.8, 129.1, 128.7, 128.5, 128.2, 127.8, 127.6, 126.6, 114.1, 55.3; IR
(KBr) 1540, 1512, 1250 cm−1; HRMS (ESI) m/z [M + H]+ calcd for
C30H24NO4 462.1700, found 462.1700.
NMR (CDCl3, 400 MHz) δ 8.00 (d, J = 7.6 Hz, 2H), 7.86 (d, J = 8.0
Hz, 2H), 7.70 (d, J = 7.6 Hz, 2H), 7.54−7.27 (m, 10H), 6.96 (bs, 2H);
13C NMR (CDCl3, 100 MHz) δ 191.5, 190.6, 189.0, 138.6, 135.8,
134.8, 134.4, 133.9, 129.32, 129.29, 129.1, 129.0, 128.9, 128.6; IR
(KBr) 1670, 1650, 1596, 1319, 1269 cm−1; HRMS (ESI) m/z [M +
H]+ calcd for C26H19N2O3 407.1390, found 407.1389.
2-(1H-Benzo[d][1,2,3]triazol-1-yl)-3-benzoyl-1,4-diphenylbut-2-
ene-1,4-dione (3am): yield 73% (334 mg); yellow solid; mp 197.2−
198.4 °C; 1H NMR (CDCl3, 400 MHz) δ 7.97−7.78 (bs, 7H), 7.52−
7.26 (m, 12H); 13C NMR (CDCl3, 100 MHz) δ 191.0, 190.8, 188.7,
145.9, 141.6, 138.8, 136.0, 135.3, 134.7, 134.5, 134.1, 133.9, 132.1,
129.5, 129.3, 129.1, 128.91, 128.86, 128.7, 128.5, 124.9, 120.4, 110.0;
IR (KBr) 1671, 1651, 1594, 1450, 1318, 1285, 1257 cm−1; HRMS
(ESI) m/z [M + H]+ calcd for C29H20N3O3 458.1499, found 458.1503.
2-(1H-Benzo[d]imidazol-1-yl)-3-benzoyl-1,4-diphenylbut-2-ene-
1,4-dione (3an): yield 81% (369 mg); yellow solid; mp 206.5−208.3
4-((3-Benzoyl-1,4-dioxo-1,4-diphenylbut-2-en-2-yl)amino)-
benzonitrile (3ae): yield 52% (237 mg); yellow solid; mp 229.3−
1
230.7 °C; H NMR (CDCl3, 400 MHz) δ 13.41 (s, 1H), 7.92−7.90
(m, 2H) 7.54−7.38 (m, 9H), 7.22−7.17 (m, 4H), 7.14−7.07 (m, 4H);
13C NMR (CDCl3, 100 MHz) δ 196.4, 194.7, 162.3, 141.0, 140.7,
139.6, 135.1, 134.5, 133.3, 132.0, 131.4, 129.10, 129.06, 128.6, 128.1,
128.0, 127.9, 124.0, 117.9, 112.4, 110.0; IR (KBr) 2224, 1549, 1277
cm−1; HRMS (ESI) m/z [M + H]+ calcd for C30H21N2O3 457.1547,
found 457.1545.
1
°C; H NMR (CDCl3, 400 MHz) δ 7.96−7.27 (m, 5H), 7.72 (d, J =
7.2 Hz, 2H), 7.58 (d, J = 6.4 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 7.45 (t,
J = 7.6 Hz, 1H), 7.39−7.35 (m, 4H), 7.30−7.18 (m, 6H); 13C NMR
(CDCl3, 100 MHz) δ 191.6, 190.9, 189.7, 141.8, 141.3, 139.4, 135.9,
134.7, 134.6, 134.5, 134.4, 134.1, 129.3, 129.0, 128.9, 128.85, 128.76,
124.9, 123.9, 120.5, 111.1; IR (KBr) 1667, 1647, 1594, 1493, 1450,
1311, 1287, 1257 cm−1; HRMS (ESI) m/z [M + H]+ calcd for
C30H21N2O3 457.1547, found 457.1546.
2-Benzoyl-1,4-diphenyl-3-(1H-pyrazol-1-yl)butane-1,4-dione (4):
yield 49% (200 mg); white solid; mp 132.2−133.9 °C; 1H NMR
(CDCl3, 600 MHz) δ 7.95 (d, J = 7.8 Hz, 2H), 7.90 (d, J = 7.8 Hz,
2H), 7.84 (d, J = 8.4 Hz, 2H), 7.51−7.49 (m, 4H), 7.40−7.33 (m,
6H), 7.30 (s, 1H), 6.95 (d, J = 10.2 Hz, 1H), 6.74 (d, J = 10.2 Hz, 1H),
5.99 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 194.6, 192.5, 191.7,
141.1, 135.9, 135.6, 134.6, 133.9, 133.6, 130.7, 128.7, 128.6, 128.5,
106.8, 66.1, 57.6; IR (KBr) 1688, 1596, 1448, 1278 cm−1; MS (EI, 70
ev) m/z 408.39.
2-Benzoyl-3-((4-iodophenyl)amino)-1,4-diphenylbut-2-ene-1,4-
dione (3af): yield 68% (379 mg); yellow solid; mp 206.9−208.5 °C;
1H NMR (CDCl3, 400 MHz) δ 13.31 (s, 1H), 7.90 (d, J = 7.2 Hz,
2H), 7.49−7.37 (m, 9H) 7.16−7.04 (m, 6H), 6.85 (d, J = 7.2 Hz, 2H);
13C NMR (CDCl3, 100 MHz) δ 196.3, 194.9, 190.7, 164.0, 141.1,
140.0, 138.3, 136.5, 135.3, 134.2, 131.7, 131.1, 129.1, 128.9, 128.6,
128.2, 127.9, 127.7, 126.3, 91.9; IR (KBr) 1527, 1274 cm−1; HRMS
(ESI) m/z [M + H]+ calcd for C29H21INO3 558.0561, found 558.0558.
2-Benzoyl-3-(naphthalen-2-ylamino)-1,4-diphenylbut-2-ene-1,4-
dione (3ag): yield 74% (356 mg); yellow solid; mp 176.0−176.8 °C;
1H NMR (CDCl3, 400 MHz) δ 13.56 (s, 1H), 7.91 (d, J = 7.6 Hz,
2H), 7.69−7.46 (m, 8H), 7.40−7.38 (m, 3H), 7.30 (t, J = 7.6 Hz, 2H),
7.24−7.05 (m, 7H); 13C NMR (CDCl3, 100 MHz) δ 196.1, 195.0,
190.4, 164.6, 141.2, 140.0, 135.4, 134.0, 133.8, 133.0, 131.6, 131.0,
129.23, 129.15, 128.7, 128.5, 128.2, 127.9, 127.71, 127.68, 127.5,
126.8, 126.4, 122.9, 122.7, 110.9; IR (KBr) 1535, 1272 cm−1; HRMS
(ESI) m/z [M + H]+ calcd for C33H24NO3 482.1751, found 482.1750.
2-Benzoyl-3-(methyl(phenyl)amino)-1,4-diphenylbut-2-ene-1,4-
dione (3ah): yield 78% (347 mg); yellow solid; mp 172.9−173.7 °C;
1H NMR (CDCl3, 400 MHz) δ 7.90 (d, J = 7.2 Hz, 2H), 7.69 (bs,
ASSOCIATED CONTENT
* Supporting Information
NMR spectra of products. This material is available free of
charge via the Internet at http://pubs.acs.org.
■
S
2H), 7.51−7.44 (m, 3H), 7.38−7.00 (m, 13H), 3.20 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 195.0, 193.6, 192.7, 163.4, 144.3, 140.0,
136.6, 133.0, 132.3, 131.2, 129.0, 128.9, 128.6, 128.4, 128.2, 127.7,
126.9, 125.5, 119.1, 44.8; IR (KBr) 1615, 1502, 1245 cm−1; HRMS
(ESI) m/z [M + H]+ calcd for C30H24NO3 446.1751, found 446.1749.
2-Benzoyl-3-((6-methylpyridin-2-yl)amino)-1,4-diphenylbut-2-
ene-1,4-dione (3ai): yield 70% (312 mg); yellow solid; mp 178.6−
AUTHOR INFORMATION
Corresponding Author
*E-mail: chwuax@mail.ccnu.edu.cn.
■
Notes
1
179.5 °C; H NMR (CDCl3, 400 MHz) δ 13.56 (s, 1H), 8.00 (d, J =
The authors declare no competing financial interest.
7.2 Hz, 2H), 7.51−7.39 (s, 8H), 7.18 (t, J = 7.2 Hz, 2H), 7.12−7.05
(m, 4H), 6.82 (d, J = 8.0 Hz, 1H), 6.70 (d, J = 7.6 Hz, 1H), 1.92 (s,
3H); 13C NMR (CDCl3, 100 MHz) δ 196.4, 195.3, 159.7, 157.0,
148.4, 141.2, 140.2, 138.7, 137.8, 132.3, 131.8, 131.1, 129.1, 128.3,
127.94, 127.86, 127.7, 119.3, 113.1, 110.0, 22.2; IR (KBr) 1534, 1265
cm−1; HRMS (ESI) m/z [M + H]+ calcd for C29H23N2O3 447.1703,
found 447.1702.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(Grant Nos. 21032001 and 21272085). We also thank Dr.
Chuanqi Zhou for his help in performing HRMS analysis and
Dr. Xianggao Meng for performing X-ray diffraction analysis.
2-Benzoyl-1,4-diphenyl-3-(piperidin-1-yl)but-2-ene-1,4-dione
1
(3aj): yield 76% (322 mg); yellow solid; mp 163.9−165.5 °C; H
REFERENCES
■
NMR (CDCl3, 400 MHz) δ 8.09−8.08 (m, 2H), 7.55−7.45 (m, 7H),
7.21−7.12 (m, 6H), 3.21 (bs, 4H), 1.59 (bs, 6H); 13C NMR (CDCl3,
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128.7, 128.5, 127.8, 114.0, 53.0, 25.5, 22.7; IR (KBr) 1503, 1321, 1247
cm−1; HRMS (ESI) m/z [M + H]+ calcd for C28H26NO3 424.1907,
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I
dx.doi.org/10.1021/jo400564f | J. Org. Chem. XXXX, XXX, XXX−XXX