Direct C2-arylation ofN-acyl pyrroles with aryl halides under palladium catalysis

Article abstract of DOI:10.1039/d0ob02579h

C2-arylation ofN-acyl pyrroles with aryl halides is developed for the first time using Pd(PPh₃)₄as a catalyst in combination with Ag₂CO₃under air, which allowed the application of a good compatibility catalytic system. This protocol provides a straightforward method for the preparation of valuable arylated pyrroles in moderate to good yields under the standard conditions with good substrate tolerance. Interestingly, whileN-benzoyl pyrroles reacted well, the use of substrates with a thiophene or furan ring indicated that the thiophene and furan rings are more reactive than pyrrole for the present catalytic system.

Full text of DOI:10.1039/d0ob02579h

Organic &
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PAPER
Direct C2-arylation of N-acyl pyrroles with aryl
halides under palladium catalysis†
Weiqiang Chen,a Hui-Jing Li,*a,b Yun-Fei Chenga and Yan-Chao Wu
Cite this: Org. Biomol. Chem., 2021,
19, 1555
a
*
C2-arylation of N-acyl pyrroles with aryl halides is developed for the first time using Pd(PPh3)4 as a catalyst
in combination with Ag2CO3 under air, which allowed the application of a good compatibility catalytic
system. This protocol provides a straightforward method for the preparation of valuable arylated pyrroles
in moderate to good yields under the standard conditions with good substrate tolerance. Interestingly,
while N-benzoyl pyrroles reacted well, the use of substrates with a thiophene or furan ring indicated that
the thiophene and furan rings are more reactive than pyrrole for the present catalytic system.
Received 27th December 2020,
Accepted 21st January 2021
DOI: 10.1039/d0ob02579h
rsc.li/obc
lyzed pyrrole arylation methods usually focused on electron-
rich pyrroles, without touching relatively electron-deficient
Introduction
Arylated pyrroles are important compounds in chemical N-acyl pyrroles. However, N-acyl pyrroles are versatile motifs in
research with applications ranging from materials science to natural products15 and biomolecules (Fig. 1).16 Various N-acyl
pharmaceutical chemistry.1–3 Owing to the widespread appli- pyrroles are required because their applications are increasing,
cations of arylated pyrroles, it is desirable to develop new and which makes the development of synthesis methods for their
more convenient synthesis methods.4 On the other hand, over derivation a high priority. In contrast to electron-rich pyrroles,
the past few decades, the area of transition-metal-catalyzed
direct arylation through cleavage of C–H bonds, followed by its
functionalization into a C–X bond, has received considerable
attention as a potentially applicable and powerful approach for
its synthetic applications in organic synthesis.5 Among the
transition metals catalyzing C–H arylation, palladium catalysts
have significantly contributed to direct C–H arylation reactions
due to their high activities and excellent tolerance of sub-
strates.6 Ohta reported the Pd-catalyzed arylation of heteroar-
enes through C–H bond activation,7 which was subsequently
used for the synthesis of arylated heteroarenes by other
groups.8–10 In particular, the Pd-catalyzed direct C2-arylation
of pyrroles by C–H bond activation using aryl halides is a topic
of ongoing interest in recent years. Bailey, Gryko, and
Jafarpour developed a Pd-catalyzed C2-arylation of N–H, N–Me,
N–Ph, and N–Bn pyrroles with aryl iodides (Scheme 1a and
b).11,12 Shortly afterwards, Langer reported a Pd-catalyzed bis-
arylation of N–Me pyrroles by using tetrabutyl-ammonium
acetate as an ionic solvent (Scheme 1c).13 Recently, Chung
developed an aqueous Pd-catalyzed bis-arylation of electron-
rich pyrroles with aryl iodides (Scheme 1d).14 These Pd-cata-
aWeihai Marine Organism & Medical Technology Research Institute, Harbin Institute
of Technology, Weihai 264209, P.R. China. E-mail: ycwu@iccas.ac.cn
bWeihai Huiankang Biotechnology Co., Ltd, Weihai 264200, P. R. China
†Electronic supplementary information (ESI) available: Experimental pro-
cedures, characterization data, and copies of NMR spectra. See DOI: 10.1039/
d0ob02579h
Scheme 1 Pd-Catalyzed direct C2-arylation of pyrroles with aryl
halides.
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Table 1 Optimization of reaction conditions for 3aa a
Entry
[Pd] Cat.
Additive
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
AgOAc
AgOTf
Ag2CO3
AgNO3
Ag3PO4
AgF
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DCE
29
12
41
33
23
17
31
<5
62
29
26
54
82
18
20
0
<5
<5
66
39
21
54
39
23
79
0
AgBF4
AgNTf2
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
K2CO3
Cu(OAc)2
PhI(OAc)2
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
9
PdCl2(PPh3)2
PdCl2(CH3CN)2
Pd(TFA)2
10
11
12
13
14
15
16
17
18
19c
20d
21
22
23
24
25e
26f
Fig. 1 N-Acyl pyrrole moieties in bioactive molecules.
PdCl2(dppp)
Pd(PPh3)4
Pd2 (dba)3
Pd (dba)2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
N-acyl pyrroles are relatively inert substrates due to their elec-
tron-withdrawing N-acyl group. Thus, alternative strategies
should be considered, such as the use of the N-acyl moiety for
Pd-catalyzed arylation of N-acyl pyrroles. It is worth noting that
the coordination of an effective chelating group to the Pd cata-
lyst could enhance reactivity and induce regioselectivity.9a,17 In
this context, we report here our research on Pd-catalyzed direct
C2-arylation of N-acyl pyrroles with aryl halides (Scheme 1e).
Dioxane
CH3CN
DMF
Toluene
Toluene
a General conditions: [Pd] Cat. (0.01 mmol), additive (0.20 mmol),
N-acyl pyrrole (1a, 0.20 mmol), and iodobenzene (2a, 0.30 mmol) in
toluene (2.0 mL) at 120 °C for 24 h under air. b Isolated yields. c Run at
110 °C. d Run at 90 °C. e [Pd] Cat. (0.01 mmol), additive (0.20 mmol),
N-acyl pyrrole (1a, 0.20 mmol), and bromobenzene (0.30 mmol) in
toluene (2.0 mL) at 120 °C for 24 h under air. f [Pd] Cat. (0.01 mmol),
additive (0.20 mmol), N-acyl pyrrole (1a, 0.20 mmol), and chloroben-
zene (0.30 mmol) in toluene (2.0 mL) at 120 °C for 24 h under air.
Results and discussion
We commenced our investigation by examining a reaction of
phenyl(1H-pyrrol-1-yl)methanone (1a) with iodobenzene (2a)
in the presence of a palladium catalyst, and the reaction was
performed under an atmosphere of air, with no special precau-
tions taken to exclude moisture. The representative results are
summarized in Table 1. Based on the study of the Pd/Ag
system in a previous report,18 substrates 1a and 2a were firstly equiv., 1.00 equiv., and 1.25 equiv. and the reaction was
reacted in the presence of Pd(OAc)2 (0.05 equiv.) and different carried out according to the general conditions. The relation-
silver salts (1.00 equiv.) in toluene at 120 °C for 24 h under air ship between the dosages of Ag2CO3 and the yields of 3aa is
(entries 1–8). When Ag2CO3 was used as the additive (entry 3), presented in Fig. 2. No further increase in the yield of 3aa was
C2-arylation product 3aa was obtained in a higher yield than observed when the loading of Ag2CO3 exceeded 1.0 equiv.
those using other silver salts. Subsequently, various palladium Furthermore, photographs of each equivalent reaction solution
catalysts were tested in combination with Ag2CO3 under other- are also presented in Fig. 2; the formation of a silver mirror
wise identical conditions. The C2-arylation product 3aa was indicated that oxidation was involved. Other solvents such as
obtained in low yield with the use of PdCl2(CH3CN)2, Pd(TFA)2, dichloroethane, dioxane, CH3CN, and DMF were also investi-
Pd2(dba)3, and Pd(dba)2 as the catalysts (entries 10, 11, 14, and gated but none gave better yields than toluene (entries 21–24),
15). Palladium catalysts PdCl2(PPh3)2, PdCl2(dppp) and Pd indicating that toluene likely stabilizes palladium-ligated phos-
(PPh3)4 improved the yields of 3aa to 62%, 54% and 82%, phine species within the catalytic cycle. To sum up, the
respectively, under otherwise similar reaction conditions optimal reaction conditions [Pd(PPh3)4 (0.05 equiv.), Ag2CO3
(entries 9, 12, and 13). Furthermore, other additives such as (1.00 equiv.), toluene, air, 120 °C, 24 h] were chosen in our
K2CO3, Cu(OAc)2 and PhI(OAc)2 inhibited the reaction (entries investigations because they led to the best yield (entries 1–24).
16–18). When the reaction was carried out at 110 °C and We attempted to extend our arylation protocol to aryl bromides
90 °C, the yields of 3aa were decreased to 66% and 39%, and chlorides. The C2-arylation product 3aa was obtained in
respectively (entries 19 and 20). Later, the dosage of Ag2CO3 79% yield when bromobenzene was used instead of iodoben-
was changed to 0.10 equiv., 0.25 equiv., 0.50 equiv., 0.75 zene (2a) (entry 25). However, when chlorobenzene was reacted
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Table 2 Direct C2-arylation reaction of N-acyl pyrroles with aryl iodidesa,b
Fig. 2 The relationship between the dosage of Ag2CO3 and the yield of
3aa.
with phenyl(1H-pyrrol-1-yl)methanone (1a), trace biphenyl was
obtained and the starting material (1a) was recovered, indicat-
ing that the reaction conditions were not suitable for the sub-
strates of aryl chlorides (entry 26). Besides, we used the pre-
vious reaction conditions from ref. 11b and 14 for
N-benzoylpyrroles, and no desired product was obtained under
these conditions.
a General conditions: Pd(PPh3)4 (0.01 mmol), Ag2CO3 (0.20 mmol),
N-acyl pyrrole (1, 0.20 mmol), and aryl iodide (2, 0.30 mmol) in
toluene (2.0 mL) at 120 °C for 24 h under air. b Isolated yields.
After establishing the optimal reaction conditions, we inves-
tigated the substrate scope using various N-acyl pyrroles 1 and
aryl iodides 2, and the representative results are summarized
in Table 2. Firstly, we examined the substituent effect of aryl
iodides 2 with 1a as a partner. The aryl iodides 2b–d bearing
electron-donating groups delivered the desired C2-arylation
products 3ab–ad in moderate to good yields. Similar results
could be obtained for aryl iodides 2e–i with electron-withdraw-
ing groups under the standard conditions. To our delight,
when aryl iodide 2j bearing an electron-donating group and an
electron-withdrawing group was used in the reaction, the
corresponding product 3aj was isolated in a yield of 73%. The
corresponding products 3ak and 3al were obtained in 79% and
75% yields when phenyl(1H-pyrrol-1-yl)methanone (1a) was
reacted with aryl iodides 2k and 2l bearing –F or –Cl groups.
Next, a variety of N-acyl pyrroles 1 were investigated, and the
results showed that the N-acyl pyrroles bearing both electron-
withdrawing and electron-donating substituents at different
positions could react smoothly with iodobenzene (2a) to afford
the corresponding C2-arylation products 3ba–ea in good
yields. N-Acyl pyrroles 1f bearing a naphthyl group proceeded
well under the standard conditions to generate the desired
product 3fa in 73% yield. We were pleased that cyclohexyl(1H-
pyrrol-1-yl)methanone (1g) was a well-tolerated substrate to
afford the desired C2-arylation product 3ga in 61% yield, indi-
cating the great synthetic value of our arylation protocol.
Table 3 Direct C2-arylation reaction of N-acyl pyrrole 1a with aryl
bromidesa,b
a General conditions: Pd(PPh3)4 (0.01 mmol), Ag2CO3 (0.20 mmol),
N-acyl pyrrole (1, 0.20 mmol), and aryl bromide (2, 0.30 mmol) in
toluene (2.0 mL) at 120 °C for 24 h under air. b Isolated yields.
It is known that aryl bromides are often cheaper than aryl of our methodology to several aryl bromides and the results
iodides because they represent industrial products that are pre- are presented in Table 3. When phenyl(1H-pyrrol-1-yl)metha-
pared on a large scale. Therefore, we studied the applicability none (1a) was reacted with aryl bromides 4a and 4b, the
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desired C2-arylation products 5aa and 5ab were obtained in
moderate yields under the optimized reaction conditions. The
aryl bromides 4c and 4d bearing a naphthyl group or a quino-
line group reacted well under the standard conditions to gene-
rate the desired products 5ac and 5ad in 75% and 81% yields,
respectively. The aryl bromides 4e and 4f were also well-toler-
ated and afforded the desired C2-arylation products 5ae and
5af in good yields, respectively. However, when aryl bromide
4g bearing a methylol group was used in the reaction, the
desired C2-arylation product was not observed. Instead, the
C2-arylation product 5ag′ was obtained in 75% yield
(Scheme 2a). A similar result was observed with the use of
aryl bromide 4h instead of aryl bromide 4g (Schemes 2b
and 2a).19
Phenylboronic acid (6), sodium benzenesulfinate (7), diphe-
nyliodonium triflate (8) and benzenesulfonyl chloride (9) were
also investigated instead of aryl halides, and the results are
shown in Scheme 3. The treatment of phenyl(1H-pyrrol-1-yl)
methanone (1a) with 6 and 9 under the standard conditions
did not give the C2-arylation product 3aa. Instead, 7 and 8
could react with 1a to afford the corresponding C2-arylation
product 3aa in 29% and 54% yields, respectively.
Scheme 3 Direct N-acyl pyrrole C2-arylation reactions using phenyl-
boronic acid (6), sodium benzenesulfinate (7), diphenyliodonium triflate
(8) and benzenesulfonyl chloride (9) as the substrates.
To demonstrate the utility of our direct C2-arylation, (1H-
indol-1-yl)(phenyl)methanone (10) was used in the reaction
with aryl bromide 4h under the standard conditions to afford
the desired C2-arylation product 11 in 73% yield (Scheme 4).
Compound 11 is a very important bioactive molecule, which
could be used as a liver X-receptor (LXR) agonist.20
Thiophene- and furan-containing N-acyl pyrroles 1h and 1i
have also been investigated, and they were converted into the
C2-arylation products 12 and 13 at the C2-position of the thio-
furan and furan rings in moderate yields under the standard
reaction conditions, respectively (Scheme 5a and b), indicating
that thiophene and furan rings are more reactive than pyrrole
for the present catalytic system.
Scheme 4 Synthetic application to a bioactive molecule.
To obtain a better understanding of this reaction, several
verification experiments were carried out and are illustrated in
Scheme 6. The control experiment demonstrated that both a
Pd catalyst and an Ag additive were essential to this system,
and no product was observed in the absence of Pd(PPh3)4 or
Scheme 5 Direct C2-arylation reaction of substrates with a thiophene
or furan ring.
Ag2CO3 (Scheme 6a and b). When 1-benzyl-1H-pyrrole (14) was
reacted with iodobenzene (2a) under the standard conditions,
the C2-arylation product was obtained in 54% yield
(Scheme 6c). At this stage, the palladium-directing ability of
the acyl group on the pyrrole C–H bond activation/functionali-
zation remains to be addressed.
Scheme 2 Direct C2-arylation reaction of N-acyl pyrrole 1a with aryl
bromides 4g and 4h.
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Hz. NMR data of known compounds is in agreement with lit-
erature values. Multiplicities are reported as follows: singlet
(s), doublet (d), doublet of doublets (dd), triplet (t), quartet
(q), and multiplet (m).
General procedure for the synthesis of N-acyl pyrroles21
Acyl chloride (10.0 mmol) was added dropwise to a stirred
solution of pyrrole (0.85 g, 12.7 mmol), triethylamine (1.30 g,
12.8 mmol) and DMAP (122 mg, 1.0 mmol) in dry dichloro-
methane (15 mL) at 0 °C. The solution was allowed to warm to
room temperature and stirred till the end of the reaction. The
reaction mixture was then diluted with Et2O, washed with 1 M
HCl (15 mL), saturated aqueous NaHCO3 (15 mL) and brine
(15 mL), dried over Na2SO4 and filtered. The volatiles were
removed in vacuo, and the residue was subjected to flash
column chromatography to give the N-acyl pyrroles.
Scheme 6 Verification experiments.
Procedure for the synthesis of aryl iodide 2d 22
Into a two-necked flask, equipped with a distillation apparatus
in one neck and a stopcock in the other, were added benzene-
1,2,4-triol (315 mg, 2.50 mmol), pyridinium p-toluenesulfonate
(0.05 mg, 0.002 mmol), and anhydrous toluene (25 mL), and
the mixture was stirred and heated to 110 °C. To the mixture
was added 2,2-dimethoxypropane (0.45 mL, 3.65 mmol) por-
tionwise. Then, the mixture was continued to stir for 2 h. After
cooling down, the solvent was removed under reduced
pressure, and the residue was purified by flash chromato-
graphy to give 2,2-dimethylbenzo[d][1,3]dioxol-5-ol as a color-
less oil.
2,2-Dimethylbenzo[d][1,3]dioxol-5-ol (500 mg, 3.00 mmol),
potassium carbonate (621 mg, 4.50 mmol), and N,N-dimethyl-
formamide (5 mL) were added to a round-bottom flask, and
the mixture was stirred at room temperature. To the mixture
was added iodomethane (511 mg, 3.54 mmol) portionwise.
Then, the mixture was stirred till the end of the reaction. The
reaction mixture was then diluted with H2O (20 mL), extracted
with EtOAc (3 × 20 mL), washed with brine (20 mL), dried over
Na2SO4 and filtered. The volatiles were removed in vacuo, and
the residue was subjected to flash column chromatography to
Conclusions
In summary, we have developed an efficient strategy for the
direct C2-arylation reaction of N-acyl pyrroles with aryl halides
under palladium catalysis. The use of an air-stable silver salt
along with a common palladium catalyst as a high-efficiency
catalytic system allowed the arylation of substrates with widely
available aryl halides. This protocol provides a straightforward
method for the preparation of valuable arylated pyrroles, a
structural motif for applications ranging from materials
science to pharmaceutical chemistry. N-Benzoyl pyrroles
reacted well under the standard conditions, while substrates
with a thiophene or furan ring showed that thiophene and
furan are more reactive than pyrrole for the present catalytic
system. Expansion of the derived methodology for direct aryla-
tion of other cross-coupling partners is under investigation.
Experimental
General information
All reactions were carried out under an atmosphere of air give 5-methoxy-2,2-dimethylbenzo[d][1,3]dioxole as a yellowish
except noted. Dichloromethane and toluene were distilled oil.
prior to use under
a
nitrogen atmosphere. Silica gel
5-Methoxy-2,2-dimethylbenzo[d][1,3]dioxole
(350
mg,
(200–300 mesh) was used for flash chromatography. The N-acyl 1.54 mmol), N-iodosuccinimide (480 mg, 2.13 mmol), bismuth
pyrroles were prepared according to the literature procedures.1 trifluoromethylsulfonate (125 mg, 0.19 mmol), and acetonitrile
Formyl chloride, aryl iodides, aryl bromides, and other (5 mL) were added into a round-bottom flask, and the mixture
reagents were purchased from commercial sources and used was stirred at room temperature for 30 min. The reaction
directly. High-resolution mass spectra (HRMS) were recorded mixture was then diluted with saturated NaS2O4 (20 mL),
by using an Electrothermal LTQ-Orbitrap mass spectrometer. extracted with EtOAc (3 × 10 mL), washed with brine (20 mL),
Melting points were measured by using
a
Gongyi dried over Na2SO4 and filtered. The volatiles were removed in
X-5 microscopy digital melting point apparatus and are uncor- vacuo, and the residue was subjected to flash column chrom-
1
1
rected. H and 13C-NMR spectra were recorded with a Bruker atography to give aryl iodide 2d as a yellowish solid. H NMR
Avance III 400 MHz NMR spectrometer with CDCl3 as solvent. (400 MHz, CDCl3) δ (ppm): 7.07 (s, 1H), 6.44 (s, 1H), 3.79 (s,
The chemical shifts are reported in ppm relative to CDCl3 (δ = 3H), 1.65 (s, 6H). 13C NMR (100 MHz, CDCl3) δ (ppm): 153.2,
1
7.26) for H NMR and relative to the central CDCl3 resonance 148.7, 142.4, 119.1, 117.5, 95.1, 72.0, 57.3, 25.7. HRMS (ESI) m/
(δ = 77.0) for 13C NMR. Coupling constants (J) are quoted in z: calcd for C10H11INaO3 [M + Na]+: 328.9645, found 328.9650.
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General procedure for the direct oxidative coupling between
N-acyl pyrroles and aryl halides
1H), 6.79 (s, 1H), 6.31 (d, J = 2.4 Hz, 2H), 6.23 (s, 1H), 3.46 (s,
3H), 1.68 (s, 6H). 13C NMR (100 MHz, CDCl3) δ (ppm): 168.9,
150.4, 147.6, 141.0, 133.4, 132.4, 132.3, 130.4, 127.9, 122.9,
A Schlenk reaction tube equipped with a magnetic stir bar was 118.2, 114.1, 113.7, 110.4, 109.3, 94.1, 55.6, 25.7. HRMS (ESI)
charged with Pd(PPh3)4 (0.05 equiv., 0.01 mmol), Ag2CO3 (1.0 m/z: calcd for C21H19NNaO4 [M + Na]+: 372.1206, found
equiv., 0.20 mmol), N-acyl pyrroles 1 (1.0 equiv., 0.20 mmol) 372.1209.
and aryl halides 2 (1.5 equiv., 0.30 mmol) in toluene (2.0 mL).
Ethyl 3-(1-benzoyl-1H-pyrrol-2-yl)benzoate (3ae). The syn-
The tube was sealed under air and heated to 120 °C with stir- thesis was carried out according to the general procedure, and
ring for 24 h. After cooling down, the solvent was removed compound 3ae was obtained in 76% yield as a yellow oil after
under reduced pressure, and the residue was purified by flash purification by silica gel column chromatography. 1H NMR
4
chromatography (ethyl acetate/petroleum ether mixtures).
(400 MHz, CDCl3) δ (ppm): 8.01 (t, J = 1.6 Hz, 1H), 7.89 (d, J
3
Phenyl(2-phenyl-1H-pyrrol-1-yl)methanone (3aa). The syn- = 8.0 Hz, 1H), 7.78 (d, 3J = 7.2 Hz, 2H), 7.54 (t, 3J = 7.4 Hz, 1H),
3
3
thesis was carried out according to the general procedure, and 7.47–7.39 (m, 3H), 7.33 (t, J = 7.8 Hz, 1H), 7.11 (dd, J = 3.2
compound 3aa was obtained in 82% yield as a colorless oil Hz, 4J = 1.6 Hz, 1H), 6.51 (dd, 3J = 3.2 Hz, 4J = 1.6 Hz, 1H), 6.33
after purification by silica gel column chromatography. 1H (t, 3J = 3.2 Hz, 1H), 4.36 (q, 3J = 7.2 Hz, 2H), 1.37 (t, 3J = 7.2 Hz,
NMR (400 MHz, CDCl3) δ (ppm): 7.80 (d, J = 7.2 Hz, 2H), 7.55 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 168.5, 166.2, 135.2,
3
3
3
3
(t, J = 7.6 Hz, 1H), 7.43 (t, J = 7.8 Hz, 2H), 7.31 (t, J = 6.2 Hz, 133.4, 133.1, 133.0, 132.3, 130.3, 129.0, 128.3, 127.9, 125.0,
3H), 7.24–7.20 (m, 2H), 7.10 (dd, J = 3.2 Hz, J = 1.6 Hz, 1H), 115.5, 111.2, 60.9, 14.2. HRMS (ESI) m/z: calcd for
6.47 (t, 3J = 4.8 Hz, 1H), 6.33 (t, 3J = 3.4 Hz, 1H). 13C NMR C20H17NNaO3 [M + Na]+: 342.1101, found 342.1105.
3
4
(100 MHz, CDCl3) δ (ppm): 168.7, 136.4, 133.3, 133.1, 132.9,
3-(1-Benzoyl-1H-pyrrol-2-yl)benzonitrile (3af). The synthesis
130.4, 128.3, 128.0, 126.9, 124.7, 114.9, 111.1. HRMS (ESI) m/z: was carried out according to the general procedure, and com-
calcd for C17H13NNaO [M + Na]+: 270.0889, found 270.0887. pound 3af was obtained in 79% yield as a yellow oil after puri-
These spectral data correspond to previously reported data.23
Phenyl(2-(m-tolyl)-1H-pyrrol-1-yl)methanone (3ab). The syn- (400 MHz, CDCl3) δ (ppm): 7.80 (d, J = 7.2 Hz, 2H), 7.63–7.59
thesis was carried out according to the general procedure, and (m, 2H), 7.54–7.46 (m, 4H), 7.38 (t, 3J = 7.8 Hz, 1H), 7.10 (dd, 3J
fication by silica gel column chromatography. 1H NMR
3
4
3
compound 3ab was obtained in 71% yield as a colorless oil = 3.2 Hz, J = 1.6 Hz, 1H), 6.51–6.50 (m, 1H), 6.33 (t, J = 3.2
after purification by silica gel column chromatography. 1H Hz, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm): 168.3, 134.4,
3
NMR (400 MHz, CDCl3) δ (ppm): 7.79 (d, J = 6.8 Hz, 2H), 7.55 133.9, 133.3, 132.8, 132.2, 131.3, 130.3, 130.2, 128.7, 128.6,
3
3
(t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.17–7.09 (m, 4H), 125.8, 118.6, 116.3, 112.2, 111.4. HRMS (ESI) m/z: calcd for
7.03 (d, J = 7.2 Hz, 1H), 6.45 (dd, J = 3.2 Hz, J = 1.6 Hz, 1H), C18H12N2NaO [M + Na]+: 295.0842, found 295.0839.
3
3
4
6.32 (t, 3J = 3.2 Hz, 1H), 2.31 (s, 3H). 13C NMR (100 MHz,
1-(4-(1-Benzoyl-1H-pyrrol-2-yl)phenyl)ethan-1-one (3ag). Th
CDCl3) δ (ppm): 168.7, 137.5, 136.5, 133.4, 132.9, 132.8, 130.3, synthesis was carried out according to the general procedure,
128.7, 128.3, 127.9, 127.7, 125.1, 124.5, 114.7, 111.0, 21.3. and compound 3ag was obtained in 73% yield as a colorless
1
HRMS (ESI) m/z: calcd for C18H15NNaO [M + Na]+: 284.1046, oil after purification by silica gel column chromatography. H
3
found 284.1050.
NMR (400 MHz, CDCl3) δ (ppm): 7.88 (d, J = 8.4 Hz, 2H), 7.82
(2-(2-Methoxyphenyl)-1H-pyrrol-1-yl)(phenyl)methanone (3ac). (d, 3J = 7.2 Hz, 2H), 7.59 (t, 3J = 7.6 Hz, 1H), 7.46 (t, 3J = 7.8 Hz,
The synthesis was carried out according to the general pro- 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.10 (dd, J = 3.2 Hz, J = 1.6 Hz,
cedure, and compound 3ac was obtained in 69% yield as a yel- 1H), 6.57 (dd, J = 3.2 Hz, J = 1.6 Hz, 1H), 6.33 (t, J = 3.4 Hz,
lowish solid after purification by silica gel column chromato- 1H), 2.57 (s, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 197.5,
graphy. Mp 104–105 °C. H NMR (400 MHz, CDCl3) δ (ppm): 168.5, 137.7, 135.3, 135.2, 133.3, 133.0, 130.4, 128.5, 128.2,
3
3
4
3
4
3
1
3
3
7.76 (d, J = 7.2 Hz, 2H), 7.51 (t, J = 7.4 Hz, 1H), 7.42–7.36 (m, 127.8, 125.9, 116.3, 111.5, 26.5. HRMS (ESI) m/z: calcd for
3H), 7.23–7.19 (m, 1H), 7.08 (dd, J = 3.2 Hz, J = 1.6 Hz, 1H), C19H15NNaO2 [M + Na]+: 312.0995, found 312.0999.
3
4
3
3
3
6.97 (t, J = 7.4 Hz, 1H), 6.67 (d, J = 8.0 Hz, 1H), 6.38 (dd, J =
(2-(3-Nitrophenyl)-1H-pyrrol-1-yl)(phenyl)methanone (3ah).
4
3
3.2 Hz, J = 1.6 Hz, 1H), 6.32 (t, J = 3.2 Hz, 1H), 3.53 (s, 3H). The synthesis was carried out according to the general pro-
13C NMR (100 MHz, CDCl3) δ (ppm): 168.8, 155.3, 133.2, 132.5, cedure, and compound 3ah was obtained in 83% yield as a yel-
132.3, 130.4, 129.6, 128.8, 127.9, 123.3, 122.8, 120.7, 114.3, lowish oil after purification by silica gel column chromato-
1
110.5, 110.2, 54.8. HRMS (ESI) m/z: calcd for C18H15NNaO2 [M graphy. H NMR (400 MHz, CDCl3) δ (ppm): 8.18 (s, 1H), 8.08
+ Na]+: 300.0995, found 300.0991. These spectral data corres- (d, 3J = 8.4 Hz, 1H), 7.81 (d, 3J = 7.6 Hz, 2H), 7.60 (t, 3J = 8.6 Hz,
pond to previously reported data.23
2H), 7.49–7.43 (m, 3H), 7.13 (dd, J = 3.2 Hz, J = 1.6 Hz, 1H),
3
4
3
4
3
(2-(6-Methoxy-2,2-dimethylbenzo[d][1,3]dioxol-5-yl)-1H-pyrrol-1- 6.57 (dd, J = 3.2 Hz, J = 1.6 Hz, 1H), 6.35 (t, J = 3.4 Hz, 1H).
yl)(phenyl)methanone (3ad). The synthesis was carried out 13C NMR (100 MHz, CDCl3) δ (ppm): 168.4, 147.9, 134.8, 133.9,
according to the general procedure, and compound 3ad was 133.8, 133.3, 132.8, 130.3, 128.8, 128.6, 125.9, 122.8, 121.6,
obtained in 61% yield as a white solid after purification by 116.7, 111.5. HRMS (ESI) m/z: calcd for C17H12N2NaO3 [M +
silica gel column chromatography. Mp 128–130 °C. 1H NMR Na]+: 315.0740, found 315.0736.
(400 MHz, CDCl3) δ (ppm): 7.75 (d, 3J = 7.2 Hz, 2H), 7.53 (t,
(2-(4-(Methylsulfonyl)phenyl)-1H-pyrrol-1-yl)(phenyl)metha-
3J = 7.4 Hz, 1H), 7.41 (t, J = 7.6 Hz, 2H), 7.06 (t, J = 2.6 Hz, none (3ai). The synthesis was carried out according to the
3
3
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general procedure, and compound 3ai was obtained in 81% 1H), 6.90 (d, J = 8.8 Hz, 2H), 6.45 (dd, J = 3.2 Hz, J = 1.6 Hz,
3
yield as a yellowish oil after purification by silica gel column 1H), 6.30 (t, J = 3.2 Hz, 1H), 3.86 (s, 3H). 13C NMR (100 MHz,
1
chromatography. H NMR (400 MHz, CDCl3) δ (ppm): 7.83 (t, CDCl3) δ (ppm): 168.2, 163.6, 136.3, 133.1, 132.9, 128.0, 127.9,
3J = 7.6 Hz, 4H), 7.61 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6 Hz, 126.8, 125.5, 124.7, 114.3, 113.7, 110.7, 55.5. HRMS (ESI) m/z:
3
3
4H), 7.11 (dd, 3J = 3.2 Hz, 4J = 1.2 Hz, 1H), 6.58 (dd, 3J = 3.2 Hz, calcd for C18H15NNaO2 [M + Na]+: 300.0995, found 300.0991.
4J = 1.6 Hz, 1H), 6.34 (t, 3J = 3.2 Hz, 1H), 3.03 (s, 3H). 13C NMR
(3-Nitrophenyl)(2-phenyl-1H-pyrrol-1-yl)methanone (3ca).
(100 MHz, CDCl3) δ (ppm): 168.4, 138.5, 138.3, 134.4, 133.4, The synthesis was carried out according to the general pro-
132.7, 130.4, 128.6, 128.4, 127.2, 126.3, 117.1, 111.6, 44.5. cedure, and compound 3ca was obtained in 77% yield as a
HRMS (ESI) m/z: calcd for C18H15NNaO3S [M + Na]+: 348.0665, yellow oil after purification by silica gel column chromato-
found 348.0669.
graphy. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.92–7.90 (m, 1H),
3
(2-(4-Methoxy-2-nitrophenyl)-1H-pyrrol-1-yl)(phenyl)metha- 7.74–7.72 (m, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.36–7.33 (m, 3H),
3
4
none (3aj). The synthesis was carried out according to the 7.25–7.22 (m, 4H), 6.66 (dd, J = 3.6 Hz, J = 1.6 Hz, 1H), 6.13
general procedure, and compound 3aj was obtained in 73% (t, 3J = 3.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm): 166.3,
yield as a yellow oil after purification by silica gel column 150.0, 137.6, 135.8, 133.0, 131.6, 128.9, 128.5, 128.4, 127.7,
1
chromatography. H NMR (400 MHz, CDCl3) δ (ppm): 7.75 (d, 127.4, 125.4, 123.5, 116.2, 112.3. HRMS (ESI) m/z: calcd for
3J = 7.6 Hz, 2H), 7.62 (d, J = 2.8 Hz, 1H), 7.58 (t, J = 7.4 Hz, C17H12N2NaO3 [M + Na]+: 315.0740, found 315.0745.
3
3
1H), 7.46 (t, 3J = 8.6 Hz, 3H), 7.20–7.17 (m, 1H), 6.99 (d, 4J = 1.6
(3-Fluorophenyl)(2-phenyl-1H-pyrrol-1-yl)methanone (3da).
Hz, 1H), 6.34 (s, 1H), 6.30 (t, J = 3.2 Hz, 1H), 3.90 (s, 3H). 13C The synthesis was carried out according to the general pro-
NMR (100 MHz, CDCl3) δ (ppm): 168.6, 159.5, 148.3, 133.7, cedure, and compound 3da was obtained in 75% yield as a
133.1, 132.5, 130.8, 130.1, 128.3, 124.5, 121.7, 119.5, 115.5, yellow oil after purification by silica gel column chromato-
111.1, 109.4, 55.9. HRMS (ESI) m/z: calcd for C18H14N2NaO4 [M graphy. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.56–7.53 (m, 1H),
3
+ Na]+: 345.0846, found 345.0843.
7.47–7.44 (m, 1H), 7.39–7.36 (m, 1H), 7.29–7.25 (m, 5H), 7.22
3
3
4
(2-(4-Fluorophenyl)-1H-pyrrol-1-yl)(phenyl)methanone (3ak). (d, J = 3.6 Hz, 1H), 7.10 (dd, J = 3.2 Hz, J = 1.6 Hz, 1H), 6.45
The synthesis was carried out according to the general pro- (dd, J = 3.2 Hz, J = 1.6 Hz, 1H), 6.34 (t, J = 3.2 Hz, 1H). 13C
cedure, and compound 3ak was obtained in 79% yield as a NMR (100 MHz, CDCl3) δ (ppm): 167.5, 162.2 (d, J = 247.1 Hz),
colorless oil after purification by silica gel column chromato- 136.4, 135.5 (d, J = 6.9 Hz), 132.9, 130.1 (d, J = 7.9 Hz), 128.1,
3
4
3
1
3
graphy. H NMR (400 MHz, CDCl3) δ (ppm): 7.77 (d, J = 7.2 127.1, 126.1 (d, J = 3.0 Hz), 124.4, 120.0 (d, J = 21.2 Hz), 117.4
Hz, 2H), 7.57 (t, 3J = 7.6 Hz, 1H), 7.43 (t, 3J = 7.6 Hz, 2H), (d, J = 23.2 Hz), 115.2, 111.6. 19F NMR (400 MHz, CDCl3): δ
3
4
7.28–7.25 (m, 2H), 7.07 (dd, J = 3.2 Hz, J = 1.6 Hz, 1H), 6.96 (ppm): −111.4. HRMS (ESI) m/z: calcd for C17H12FNNaO [M +
3
3
4
(t, J = 8.6 Hz, 2H), 6.41 (dd, J = 3.2 Hz, J = 1.6 Hz, 1H), 6.30 Na]+: 288.0795, found 288.0799.
(t, 3J = 3.2 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm): 168.7,
(4-Chlorophenyl)(2-phenyl-1H-pyrrol-1-yl)methanone (3ea).
161.9 (d, J = 245.0 Hz), 135.3, 133.3, 133.0, 130.3, 129.7 (d, J = The synthesis was carried out according to the general pro-
8.0 Hz), 129.3 (d, J = 3.5 Hz), 128.4, 124.7, 115.1, 114.9 (d, J = cedure, and compound 3ea was obtained in 78% yield as a
6.5 Hz), 111.1. 19F NMR (400 MHz, CDCl3): δ (ppm): −115.1. colorless oil after purification by silica gel column chromato-
1
3
HRMS (ESI) m/z: calcd for C17H12FNNaO [M + Na]+: 288.0795, graphy. H NMR (400 MHz, CDCl3) δ (ppm): 7.73 (d, J = 8.4
3
found 288.0791. These spectral data correspond to previously Hz, 2H), 7.40 (d, J = 8.8 Hz, 2H), 7.33–7.26 (m, 5H), 7.10 (dd,
reported data.24
3J = 3.2 Hz, J = 1.6 Hz, 1H), 6.48–6.47 (m, 1H), 6.36 (t, J = 3.4
4
3
(2-(2-Chlorophenyl)-1H-pyrrol-1-yl)(phenyl)methanone (3al). Hz, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm): 167.7, 139.4,
The synthesis was carried out according to the general pro- 136.4, 132.9, 131.8, 131.7, 128.7, 128.1, 128.0, 127.1, 124.4,
cedure, and compound 3al was obtained in 75% yield as a yel- 115.0, 111.5. HRMS (ESI) m/z: calcd for C17H12ClNNaO [M +
lowish solid after purification by silica gel column chromato- Na]+: 304.0500, found 304.0504.
1
graphy. Mp 101–102 °C. H NMR (400 MHz, CDCl3) δ (ppm):
Naphthalen-2-yl(2-phenyl-1H-pyrrol-1-yl)methanone (3fa).
7.79 (d, J = 8.0 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.43 (t, J = The synthesis was carried out according to the general pro-
3
3
3
3
7.4 Hz, 3H), 7.33–7.28 (m, 2H), 7.25–7.20 (m, 1H), 7.08 (dd, J cedure, and compound 3fa was obtained in 73% yield as a
= 3.2 Hz, 4J = 1.6 Hz, 1H), 6.41 (dd, 3J = 3.2 Hz, 4J = 1.6 Hz, 1H), colorless oil after purification by silica gel column chromato-
6.34 (t, J = 3.2 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm): graphy. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.31 (s, 1H),
3
3
3
168.3, 133.4, 133.0, 132.7, 132.5, 131.3, 130.4, 129.3, 128.8, 7.92–7.87 (m, 4H), 7.62 (t, J = 7.0 Hz, 1H), 7.56 (t, J = 7.6 Hz,
128.2, 126.6, 124.0, 115.8, 110.9. HRMS (ESI) m/z: calcd for 1H), 7.34 (d, 3J = 7.2 Hz, 2H), 7.24 (t, 3J = 7.6 Hz, 2H), 7.16 (t, 3J
C17H12ClNNaO [M + Na]+: 304.0500, found 304.0503. These = 7.4 Hz, 2H), 6.50–6.49 (m, 1H), 6.34 (t, J = 3.2 Hz, 1H). 13C
3
spectral data correspond to previously reported data.24
NMR (100 MHz, CDCl3) δ (ppm): 168.8, 136.6, 135.3, 133.1,
(4-Methoxyphenyl)(2-phenyl-1H-pyrrol-1-yl)methanone (3ba). 132.1, 132.0, 130.5, 129.3, 128.7, 128.4, 128.0, 127.9, 127.8,
The synthesis was carried out according to the general pro- 127.0, 126.9, 125.9, 124.9, 114.8, 111.1. HRMS (ESI) m/z: calcd
cedure, and compound 3ba was obtained in 70% yield as a for C21H15NNaO [M + Na]+: 320.1046, found 320.1050.
colorless oil after purification by silica gel column chromato-
Cyclohexyl(2-phenyl-1H-pyrrol-1-yl)methanone (3ga). The
1
3
graphy. H NMR (400 MHz, CDCl3) δ (ppm): 7.79 (d, J = 8.8 synthesis was carried out according to the general procedure,
3
4
Hz, 2H), 7.30–7.24 (m, 5H), 7.08 (dd, J = 3.2 Hz, J = 1.6 Hz, and compound 3ga was obtained in 61% yield as a colorless
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oil after purification by silica gel column chromatography. H (t, 3J = 7.4 Hz, 1H), 7.39 (t, 3J = 7.8 Hz, 2H), 7.23 (d, 3J = 8.4 Hz,
NMR (400 MHz, CDCl3) δ (ppm): 7.36–7.31 (m, 5H), 7.29 (dd, 1H), 7.12 (dd, 3J = 3.2 Hz, 4J = 1.6 Hz, 1H), 6.55 (dd, 3J = 3.2 Hz,
3J = 3.2 Hz, J = 1.6 Hz, 1H), 6.28 (t, J = 3.2 Hz, 1H), 6.26 (dd, 4J = 1.6 Hz, 1H), 6.34 (t, 3J = 3.2 Hz, 1H), 2.71 (s, 3H). 13C NMR
3J = 3.2 Hz, 4J = 1.6 Hz, 1H), 2.79–2.72 (m, 1H), 1.87 (d, 3J = (100 MHz, CDCl3) δ (ppm): 168.7, 158.8, 146.8, 136.1, 135.7,
13.6 Hz, 2H), 1.76 (d, 3J = 13.2 Hz, 2H), 1.66–1.62 (m, 1H), 133.2, 133.0, 130.5, 130.3, 130.0, 128.4, 128.1, 126.1, 125.8,
1.23–1.08 (m, 5H). 13C NMR (100 MHz, CDCl3) δ (ppm): 175.6, 125.1, 122.2, 115.7, 111.3, 25.2. HRMS (ESI) m/z: calcd for
135.1, 134.3, 128.7, 127.9, 127.4, 121.4, 115.3, 111.3, 44.3, 29.5, C21H16N2NaO [M + Na]+: 335.1155, found 335.1160.
4
3
25.6, 25.5. HRMS (ESI) m/z: calcd for C17H19NNaO [M + Na]+:
276.1359, found 276.1363.
(2-(Dibenzo[b,d]thiophen-4-yl)-1H-pyrrol-1-yl)(phenyl)metha-
none (5ae). The synthesis was carried out according to the
Phenyl(2-(3-vinylphenyl)-1H-pyrrol-1-yl)methanone (5aa). general procedure, and compound 5ae was obtained in 62%
The synthesis was carried out according to the general pro- yield as a colorless oil after purification by silica gel column
cedure, and compound 5aa was obtained in 54% yield as a chromatography. 1H NMR (400 MHz, CDCl3)
colorless oil after purification by silica gel column chromato- 8.12–8.10 (m, 1H), 8.01 (d, J = 7.6 Hz, 1H), 7.80–7.75 (m, 3H),
δ (ppm):
3
1
3
3
3
graphy. H NMR (400 MHz, CDCl3) δ (ppm): 7.77 (d, J = 7.2, 7.47–7.42 (m, 3H), 7.38 (t, J = 7.6 Hz, 1H), 7.32 (t, J = 7.4 Hz,
3
3
3
4
3
2H), 7.53 (t, J = 7.4 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H), 7.32 (s, 3H), 7.23 (dd, J = 3.2 Hz, J = 1.6 Hz, 1H), 6.72 ((dd, J = 3.2
1H), 7.24–7.21 (m, 2H), 7.17 (t, J = 7.4 Hz, 1H), 7.10 (dd, J = Hz, 4J = 1.6 Hz, 1H), 6.43 (t, 3J = 3.4 Hz, 1H). 13C NMR
3
3
4
3
3.2 Hz, J = 1.6 Hz, 1H), 6.69–6.62 (m, 1H), 6.46 (dd, J = 3.2 (100 MHz, CDCl3) δ (ppm): 168.4, 139.4, 139.3, 135.8, 135.7,
4
3
3
Hz, J = 1.6 Hz, 1H), 6.32 (t, J = 3.2 Hz, 1H), 5.69 (d, J = 17.6 133.6, 133.1, 132.8, 130.2, 128.7, 128.1, 127.4, 126.7, 124.5,
Hz, 1H), 5.22 (d, 3J = 10.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) 124.4, 124.3, 122.7, 121.7, 120.4, 115.6, 111.3. HRMS (ESI) m/z:
δ (ppm): 168.8, 137.3, 136.6, 136.2, 133.4, 133.3, 132.9, 130.3, calcd for C23H15NNaOS [M + Na]+: 376.0767, found 376.0773.
128.3, 128.1, 127.6, 126.0, 124.8, 124.7, 115.0, 114.0, 111.1.
5-(1-Benzoyl-1H-pyrrol-2-yl)picolinaldehyde (5af). The syn-
HRMS (ESI) m/z: calcd for C19H15NNaO [M + Na]+: 296.1046, thesis carried out according to the general procedure, and
found 296.1051.
Phenyl(2-(thiophen-3-yl)-1H-pyrrol-1-yl)methanone
The synthesis was carried out according to the general pro- (400 MHz, CDCl3) δ (ppm): 10.03 (s, 1H), 8.76 (d, J = 2.0 Hz,
cedure, and compound 5ab was obtained in 51% yield as a 1H), 7.87 (d, 3J = 8.4 Hz, 1H), 7.82 (d, 3J = 7.6 Hz, 2H),
compound 5af was obtained in 73% yield as a yellow oil after
(5ab). purification by silica gel column chromatography. 1H NMR
4
3
3
yellow oil after purification by silica gel column chromato- 7.76–7.73 (m, 1H), 7.62 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.6 Hz,
1
3
3
graphy. H NMR (400 MHz, CDCl3) δ (ppm): 7.76 (d, J = 7.6 2H), 7.16–7.15 (m, 1H), 6.65–6.64 (m, 1H), 6.38 (t, J = 3.4 Hz,
Hz, 2H), 7.56 (t, 3J = 7.4 Hz, 1H), 7.43 (t, 3J = 7.8 Hz, 2H), 1H). 13C NMR (100 MHz, CDCl3) δ (ppm): 192.9, 168.2, 150.6,
7.22–7.18 (m, 2H), 7.05–7.04 (m, 1H), 7.03–7.01 (m, 1H), 6.45 148.7, 135.6, 133.5, 133.2, 132.5, 131.7, 130.3, 128.7, 126.9,
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(dd, J = 3.2 Hz, J = 1.6 Hz, 1H), 6.29 (t, J = 3.4 Hz, 1H). 13C 121.0, 117.8, 111.9. HRMS (ESI) m/z: calcd for C17H12N2NaO2
NMR (100 MHz, CDCl3) δ (ppm): 168.8, 133.5, 133.4, 132.9, [M + Na]+: 299.0791, found299.0796.
131.3, 130.3, 128.3, 128.1, 124.8, 124.2, 122.1, 114.7, 111.0.
2-(1-Benzoyl-1H-pyrrol-2-yl)benzaldehyde (5ag′). The syn-
HRMS (ESI) m/z: calcd for C15H11NNaOS [M + Na]+: 276.0454, thesis was carried out according to the general procedure, and
found 276.0451.
compound 5ag′ was obtained in 75% yield as a yellow oil after
(2-(Naphthalen-1-yl)-1H-pyrrol-1-yl)(phenyl)methanone (5ac). purification by silica gel column chromatography. 1H NMR
3
The synthesis was carried out according to the general pro- (400 MHz, CDCl3) δ (ppm): 10.08 (s, 1H), 7.92 (dd, J = 3.6 Hz,
cedure, and compound 5ac was obtained in 75% yield as a 4J = 0.8 Hz, 1H), 7.80 (d, J = 6.8 Hz, 2H), 7.61–7.56 (m, 2H),
3
3
3
3
yellow solid after purification by silica gel column chromato- 7.48 (t, J = 7.6 Hz, 3H), 7.42 (d, J = 8.0 Hz, 1H), 7.13 (dd, J =
1
4
3
4
graphy. Mp 133–134 °C. H NMR (400 MHz, CDCl3) δ (ppm): 3.2 Hz, J = 1.6 Hz, 1H), 6.43 (dd, J = 3.2 Hz, J = 1.6 Hz, 1H),
3
3
3
3
7.84 (t, J = 4.6, 1H), 7.79 (t, J = 4.8 Hz, 1H), 7.73 (d, J = 7.6 6.39 (t, J = 3.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm):
3
Hz, 1H), 7.60 (d, J = 7.2 Hz, 2H), 7.43–7.36 (m, 5H), 7.27 (dd, 191.9, 168.3, 136.0, 134.4, 133.2, 133.1, 132.9, 131.6, 131.3,
4
3
3J = 3.2 Hz, J = 1.6 Hz, 1H), 7.23 (t, J = 7.8 Hz, 2H), 6.52 (dd, 130.2, 129.4, 128.4, 128.0, 124.8, 117.8, 111.2. HRMS (ESI) m/z:
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3
3J = 3.2 Hz, J = 1.6 Hz, 1H), 6.45 (t, J = 3.2 Hz, 1H). 13C NMR calcd for C18H13NNaO2 [M + Na]+: 298.0838, found 298.0833.
(100 MHz, CDCl3) δ (ppm): 168.5, 133.6, 133.3, 133.3, 132.5, 3-(4-(1-Benzoyl-1H-indol-2-yl)phenyl)propanenitrile (11). The
132.3, 131.4, 129.8, 128.2, 128.0, 127.9, 127.8, 126.3, 125.6, synthesis was carried out according to the general procedure,
125.2, 125.0, 123.7, 116.1, 111.2. HRMS (ESI) m/z: calcd for and compound 11 was obtained in 73% yield as a colorless oil
C21H15NNaO [M + Na]+: 320.1046, found 320.1051. These spec- after purification by silica gel column chromatography.
tral data correspond to previously reported data.23
1H NMR (400 MHz, CDCl3) δ (ppm): 7.65–7.61 (m, 4H), 7.42 (t,
3
(2-(2-Methylquinolin-5-yl)-1H-pyrrol-1-yl)(phenyl)methanone 3J = 7.4 Hz, 1H), 7.30–7.25 (m, 6H), 7.05 (d, J = 8.0 Hz, 2H),
3
3
(5ad). The synthesis was carried out according to the general 6.78 (s, 1H), 2.86 (t, J = 7.2 Hz, 2H), 2.52 (t, J = 7.4 Hz, 2H).
procedure, and compound 5ad was obtained in 81% yield as a 13C NMR (100 MHz, CDCl3) δ (ppm): 170.0, 140.7, 138.2,
yellow oil after purification by silica gel column chromato- 137.3, 135.0, 132.9, 132.1, 130.2, 129.2, 128.8, 128.3, 128.1,
1
3
graphy. H NMR (400 MHz, CDCl3) δ (ppm): 7.95 (d, J = 8.4 124.3, 123.1, 120.7, 118.8, 114.1, 109.6, 31.2, 19.2. HRMS (ESI)
Hz, 1H), 7.90 (d, 3J = 8.8 Hz, 1H), 7.80 (d, 3J = 7.2 Hz, 2H), 7.69 m/z: calcd for C24H18N2NaO [M + Na]+: 373.1311, found
(d, 4J = 2.0 Hz, 1H), 7.60 (dd, 3J = 10.8 Hz, 4J = 2.0 Hz, 1H), 7.51 373.1316.
1562 | Org. Biomol. Chem., 2021, 19, 1555–1564
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(5-Phenylthiophen-2-yl)(1H-pyrrol-1-yl)methanone (12). The
synthesis was carried out according to the general procedure,
and compound 12 was obtained in 63% yield as a pale
yellow solid after purification by silica gel column chromato-
Notes and references
1 For materials sciences, see: (a) A. Yokoyama, A. Kato,
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1
graphy. Mp 122–123 °C. H NMR (400 MHz, CDCl3) δ (ppm):
3
3
4
7.75 (d, J = 4.0 Hz, 1H), 7.68 (d, J = 7.2 Hz, 2H), 7.50 (t, J =
2.2 Hz, 2H), 7.46–7.39 (m, 3H), 7.37 (d, 3J = 4.4 Hz, 1H), 6.39 (t,
4J = 2.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm): 160.5,
152.6, 135.2, 134.3, 132.9, 129.2, 126.3, 123.6, 121.0, 113.1.
HRMS (ESI) m/z: calcd for C15H11NNaOS [M + Na]+: 276.0454,
found 276.0450.
(5-Phenylfuran-2-yl)(1H-pyrrol-1-yl)methanone (13). The syn-
thesis was carried out according to the general procedure, and
compound 13 was obtained in 69% yield as a yellow oil after
purification by silica gel column chromatography. 1H NMR
4
(400 MHz, CDCl3) δ (ppm): 7.57 (d, J = 0.8 Hz, 1H), 7.38 (dd,
3J = 3.2 Hz, 4J = 1.6 Hz, 1H), 7.32–7.28 (m, 5H), 7.21 (d, 3J = 3.6 Hz,
1H), 6.52 (dd, 3J = 3.2 Hz, 4J = 1.6 Hz, 1H), 6.44 (dd, 3J = 3.2 Hz, 4J =
1.6 Hz, 1H), 6.36 (t, 3J = 3.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ
(ppm): 157.4, 147.2, 146.6, 136.0, 133.1, 128.1, 127.8, 126.9, 123.7,
121.5, 114.8, 112.4, 111.5. HRMS (ESI) m/z: calcd for C15H11NNaO2
[M + Na]+: 260.0682, found 260.0687.
1-Benzyl-2-phenyl-1H-pyrrole (15). The synthesis was carried
out according to the general procedure, and compound 15 was
obtained in 54% yield as a colorless oil after purification by
1
silica gel column chromatography. H NMR (400 MHz, CDCl3)
δ (ppm): 7.33–7.26 (m, 8H), 7.04 (t, 3J = 7.2 Hz, 2H), 6.78 (t, 4J =
2.0 Hz, 1H), 6.31 (d, 3J = 2.4 Hz, 2H), 5.18 (s, 2H). 13C NMR
(100 MHz, CDCl3) δ (ppm): 138.8, 134.9, 133.2, 128.8, 128.6,
128.3, 127.3, 127.0, 126.4, 122.9, 108.8, 108.5, 50.6. These spec-
tral data correspond to previously reported data.25
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Author contributions
Weiqiang Chen: Investigation, writing-original draft. Hui-Jing
Li: Conceptualization, supervision. Yun-Fei Cheng: Data cura-
tion, methodology. Yan-Chao Wu: Writing-review and editing,
funding acquisition.
Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
We thank the Natural Science Foundation of Shandong
Province (ZR2020MB009 and ZR2019MB009), Key Research
and Development Program of Shandong Province
(2019GSF108089), National Natural Science Foundation of
China (21672046 and 21372054), and Fund from the Huancui
District of Weihai City.
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